Giovanni Marco Dall'Olio committed 556b6e3

FIX: giving up manually reviewing the data. I will filter out USA and merge Europe and latin

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File results/freqs_by_nationality_reviewed.csv

 "liability (from 0 to 3)"	"nationality"	"country"	"country_reviewed"	"withfreq"	"adverbs_freq"	"adjectives_freq"	"tot_words"	"mean_sentence_length"	"journal"	"authors"	"affiliation"	"abstract"	"url"
-3	"latin"	"Argentina"	"Argentina"	"0.0112359550562"	"0.0112359550562"	"0.0861423220974"	"267"	"10.68"	"BMC Bioinformatics"	"Gallo CA, Carballido JA, Ponzoni I"	"Laboratorio de Investigacion y Desarrollo en Computacion Cientifica (LIDeCC), Departamento de Ciencias e Ingenieria de la Computacion, Universidad Nacional del Sur, Av, Alem 1253, 8000, Bahia Blanca, Argentina."	"BACKGROUND: Gene regulatory networks have an essential role in every process of life. In this regard, the amount of genome-wide time series data is becoming increasingly available, providing the opportunity to discover the time-delayed gene regulatory networks that govern the majority of these molecular processes. RESULTS: This paper aims at reconstructing gene regulatory networks from multiple genome-wide microarray time series datasets. In this sense, a new model-free algorithm called GRNCOP2 (Gene Regulatory Network inference by Combinatorial OPtimization 2), which is a significant evolution of the GRNCOP algorithm, was developed using combinatorial optimization of gene profile classifiers. The method is capable of inferring potential time-delay relationships with any span of time between genes from various time series datasets given as input. The proposed algorithm was applied to time series data composed of twenty yeast genes that are highly relevant for the cell-cycle study, and the results were compared against several related approaches. The outcomes have shown that GRNCOP2 outperforms the contrasted methods in terms of the proposed metrics, and that the results are consistent with previous biological knowledge. Additionally, a genome-wide study on multiple publicly available time series data was performed. In this case, the experimentation has exhibited the soundness and scalability of the new method which inferred highly-related statistically-significant gene associations. CONCLUSIONS: A novel method for inferring time-delayed gene regulatory networks from genome-wide time series datasets is proposed in this paper. The method was carefully validated with several publicly available data sets. The results have demonstrated that the algorithm constitutes a usable model-free approach capable of predicting meaningful relationships between genes, revealing the time-trends of gene regulation."	""
-3	"latin"	"Argentina"	"Argentina"	"0.00478468899522"	"0.0143540669856"	"0.0574162679426"	"209"	"9.95238095238"	"PLoS One"	"Primo ME, Jakoncic J, Noguera ME, Risso VA, Sosa L, Sica MP, Solimena M, Poskus E, Ermacora MR"	"Consejo Nacional de Investigaciones Cientificas y Tecnicas (Conicet), Ciudad Autonoma de Buenos Aires, Argentina."	"ICA512 (or IA-2) is a transmembrane protein-tyrosine phosphatase located in secretory granules of neuroendocrine cells. Initially, it was identified as one of the main antigens of autoimmune diabetes. Later, it was found that during insulin secretion, the cytoplasmic domain of ICA512 is cleaved and relocated to the nucleus, where it stimulates the transcription of the insulin gene. The role of the other parts of the receptor in insulin secretion is yet to be unveiled. The structures of the intracellular pseudocatalytic and mature extracellular domains are known, but the transmembrane domain and several intracellular and extracellular parts of the receptor are poorly characterized. Moreover the overall structure of the receptor remains to be established. We started to address this issue studying by X-ray crystallography the structure of the mature ectodomain of ICA512 (ME ICA512) and variants thereof. The variants and crystallization conditions were chosen with the purpose of exploring putative association interfaces, metal binding sites and all other structural details that might help, in subsequent works, to build a model of the entire receptor. Several structural features were clarified and three main different association modes of ME ICA512 were identified. The results provide essential pieces of information for the design of new experiments aimed to assess the structure in vivo."	""
-3	"latin"	"Argentina"	"Argentina"	"0.00568181818182"	"0.0113636363636"	"0.0795454545455"	"176"	"10.3529411765"	"Glycobiology"	"Salinas SR, Bianco MI, Barreras M, Ielpi L"	"Laboratory of Bacterial Genetics, Fundacion Instituto Leloir, IIBBA-CONICET, C1405BWE Buenos Aires, Argentina."	"We describe the first biochemical characterization of the gumI gene product, an essential protein for xanthan polysaccharide synthesis. Cellular fractionation experiments reveal the presence of a protein associated with the membrane fraction, even in the absence of the other proteins responsible for the synthesis of glycolipid intermediates and the proteins involved in the polymerization and transport of the xanthan chains. By alkaline buffer extraction and detergent phase partitioning, GumI was categorized as a monotopic membrane protein. GumI was overexpressed in Escherichia coli, solubilized and purified in an active and stable form using a simple and reproducible two-step procedure. The purified recombinant GumI is a nonprocessive beta-mannosyltransferase that uses GDP-Man as a donor substrate and glucuronic acid-beta-1,2-mannose-alpha-1,3-glucose-beta-1,4-glucose-PP-polyisoprenyl as an acceptor. We also established the optimal biochemical conditions for GumI enzymatic activity. Sequence analysis revealed the presence of a conserved domain for glycosyltransferases (GTs) of the GT-B superfamily and homologous proteins in several prokaryote organisms. On the basis of this biochemical characterization, GumI may represent the founding member of a new GT family in the Carbohydrate-Active EnZymes classification."	""
-2	"english"	"Australia"	"Australia"	"0.0188679245283"	"0.00471698113208"	"0.0990566037736"	"212"	"6.96774193548"	"Bioinformatics"	"Bauer DC, Willadsen K, Buske FA, Le Cao KA, Bailey TL, Dellaire G, Boden M"	"Queensland Brain Institute, School of Chemistry and Molecular Biosciences, Queensland Facility for Advanced Bioinformatics, The University of Queensland, St Lucia, Australia."	"MOTIVATION: Quantitative experimental analyses of the nuclear interior reveal a morphologically structured yet dynamic mix of membraneless compartments. Major nuclear events depend on the functional integrity and timely assembly of these intra-nuclear compartments. Yet, unknown drivers of protein mobility ensure that they are in the right place at the time when they are needed. RESULTS: This study investigates determinants of associations between eight intra-nuclear compartments and their proteins in heterogeneous genome-wide data. We develop a model based on a range of candidate determinants, capable of mapping the intra-nuclear organization of proteins. The model integrates protein interactions, protein domains, post-translational modification sites and protein sequence data. The predictions of our model are accurate with a mean AUC (over all compartments) of 0.71. We present a complete map of the association of 3567 mouse nuclear proteins with intra-nuclear compartments. Each decision is explained in terms of essential interactions and domains, and qualified with a false discovery assessment. Using this resource, we uncover the collective role of transcription factors in each of the compartments. We create diagrams illustrating the outcomes of a Gene Ontology enrichment analysis. Associated with an extensive range of transcription factors, the analysis suggests that PML bodies coordinate regulatory immune responses. CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
-2	"english"	"Australia"	"Australia"	"0.0"	"0.00740740740741"	"0.0814814814815"	"135"	"10.3846153846"	"Immunity"	"Brennan AJ, Chia J, Browne KA, Ciccone A, Ellis S, Lopez JA, Susanto O, Verschoor S, Yagita H, Whisstock JC, Trapani JA, Voskoboinik I"	"Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, 3002, Australia."	"Cytotoxic lymphocyte-mediated apoptosis is dependent on the delivery of perforin to secretory granules and its ability to form calcium-dependent pores in the target cell after granule exocytosis. It is unclear how cytotoxic lymphocytes synthesize and store perforin without incurring damage or death. We discovered that the extreme C terminus of perforin was essential for rapid trafficking from the endoplasmic reticulum to the Golgi compartment. Substitution of the C-terminal tryptophan residue resulted in retention of perforin in the ER followed by calcium-dependent toxic activity that eliminated host cells. We also found that N-linked glycosylation of perforin was critical for transport from the Golgi to secretory granules. Overall, an intact C terminus and N-linked glycosylation provide accurate and efficient export of perforin from the endoplasmic reticulum to the secretory granules and are critical for cytotoxic lymphocyte survival."	""
-2	"english"	"Australia"	"Australia"	"0.0138888888889"	"0.00694444444444"	"0.0555555555556"	"144"	"20.5714285714"	"Nature Genetics"	"Burdon KP, Macgregor S, Hewitt AW, Sharma S, Chidlow G, Mills RA, Danoy P, Casson R, Viswanathan AC, Liu JZ, Landers J, Henders AK, Wood J, Souzeau E, Crawford A, Leo P, Wang JJ, Rochtchina E, Nyholt DR, Martin NG, Montgomery GW, Mitchell P, Brown MA, Mackey DA, Craig JE"	"Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia."	"We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 x 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 x 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 x 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 x 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma."	""
-2	"english"	"Australia"	"Australia"	"0.0"	"0.0261194029851"	"0.0261194029851"	"268"	"11.652173913"	"PLoS One"	"Cameron TL, Bell KM, Tatarczuch L, Mackie EJ, Rajpar MH, McDermott BT, Boot-Handford RP, Bateman JF"	"Murdoch Childrens Research Institute, Parkville, Victoria, Australia."	"Metaphyseal chondrodysplasia, Schmid type (MCDS) is characterized by mild short stature and growth plate hypertrophic zone expansion, and caused by collagen X mutations. We recently demonstrated the central importance of ER stress in the pathology of MCDS by recapitulating the disease phenotype by expressing misfolding forms of collagen X (Schmid) or thyroglobulin (Cog) in the hypertrophic zone. Here we characterize the Schmid and Cog ER stress signaling networks by transcriptional profiling of microdissected mutant and wildtype hypertrophic zones. Both models displayed similar unfolded protein responses (UPRs), involving activation of canonical ER stress sensors and upregulation of their downstream targets, including molecular chaperones, foldases, and ER-associated degradation machinery. Also upregulated were the emerging UPR regulators Wfs1 and Syvn1, recently identified UPR components including Armet and Creld2, and genes not previously implicated in ER stress such as Steap1 and Fgf21. Despite upregulation of the Chop/Cebpb pathway, apoptosis was not increased in mutant hypertrophic zones. Ultrastructural analysis of mutant growth plates revealed ER stress and disrupted chondrocyte maturation throughout mutant hypertrophic zones. This disruption was defined by profiling the expression of wildtype growth plate zone gene signatures in the mutant hypertrophic zones. Hypertrophic zone gene upregulation and proliferative zone gene downregulation were both inhibited in Schmid hypertrophic zones, resulting in the persistence of a proliferative chondrocyte-like expression profile in ER-stressed Schmid chondrocytes. Our findings provide a transcriptional map of two chondrocyte UPR gene networks in vivo, and define the consequences of UPR activation for the adaptation, differentiation, and survival of chondrocytes experiencing ER stress during hypertrophy. Thus they provide important insights into ER stress signaling and its impact on cartilage pathophysiology."	""
-2	"english"	"Australia"	"Australia"	"0.0141342756184"	"0.0530035335689"	"0.144876325088"	"283"	"10.5185185185"	"PLoS One"	"Charlton-Robb K, Gershwin LA, Thompson R, Austin J, Owen K, McKechnie S"	"Centre for Environmental Stress and Adaptation Research, School of Biological Sciences, Monash University, Clayton, Victoria, Australia."	"Small coastal dolphins endemic to south-eastern Australia have variously been assigned to described species Tursiops truncatus, T. aduncus or T. maugeanus; however the specific affinities of these animals is controversial and have recently been questioned. Historically the southern Australian Tursiops was identified as unique and was formally named Tursiops maugeanus but was later synonymised with T. truncatus. Morphologically, these coastal dolphins share some characters with both aforementioned recognised Tursiops species, but they also possess unique characters not found in either. Recent mtDNA and microsatellite genetic evidence indicates deep evolutionary divergence between this dolphin and the two currently recognised Tursiops species. However, in accordance with the recommendations of the Workshop on Cetacean Systematics, and the Unified Species Concept the use of molecular evidence alone is inadequate for describing new species. Here we describe the macro-morphological, colouration and cranial characters of these animals, assess the available and new genetic data, and conclude that multiple lines of evidence clearly indicate a new species of dolphin. We demonstrate that the syntype material of T. maugeanus comprises two different species, one of which is the historical southern form of Tursiops most similar to T. truncatus, and the other is representative of the new species and requires formal classification. These dolphins are here described as Tursiops australis sp. nov., with the common name of Burrunan Dolphin following Australian aboriginal narrative. The recognition of T. australis sp. nov. is particularly significant given the endemism of this new species to a small geographic region of southern and south-eastern Australia, where only two small resident populations in close proximity to a major urban and agricultural centre are known, giving them a high conservation value and making them susceptible to numerous anthropogenic threats."	""
-2	"english"	"Australia"	"Australia"	"0.00423728813559"	"0.0169491525424"	"0.0550847457627"	"236"	"21.4545454545"	"ANNUAL REVIEW OF PSYCHOLOGY"	"Coltheart M, Langdon R, McKay R"	"Macquarie Center for Cognitive Science, Macquarie University, Sydney NSW Australia 2109."	"Delusional beliefs are seen in association with a number of neuropathological conditions, including schizophrenia, dementia, and traumatic brain injury. A key distinction exists between polythematic delusion (here the patient exhibits delusional beliefs about a variety of topics that are unrelated to each other) and monothematic delusion (here the patient exhibits just a single delusional belief or else a small set of delusional beliefs that are all related to a single theme). A great deal of recent research has focused on identifying and investigating various different forms of monothematic delusion. We discuss a general theoretical approach to the understanding of monothematic delusions--a two-factor approach according to which understanding the nature and genesis of any kind of monothematic delusion involves seeking answers to two questions. The first question is, what brought the delusional idea to mind in the first place? The second question is, why is this idea accepted as true and adopted as a belief when the belief is typically bizarre and when so much evidence against its truth is available to the patient? We discuss in detail six different kinds of monothematic delusion, showing for each how neuropsychological considerations allow a first factor (responsible for the content of the belief) and a second factor (responsible for the failure to reject the belief) to be plausibly identified. Five difficulties confronting this two-factor account of monothematic delusion are then identified, and attempts are made to address each one."	""
-2	"english"	"Australia"	"Australia"	"0.00507614213198"	"0.0203045685279"	"0.0710659898477"	"197"	"10.3684210526"	"PLoS One"	"Costa MW, Lee S, Furtado MB, Xin L, Sparrow DB, Martinez CG, Dunwoodie SL, Kurtenbach E, Mohun T, Rosenthal N, Harvey RP"	"Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia."	"Reversible post-translational protein modifications such as SUMOylation add complexity to cardiac transcriptional regulation. The homeodomain transcription factor Nkx2-5/Csx is essential for heart specification and morphogenesis. It has been previously suggested that SUMOylation of lysine 51 (K51) of Nkx2-5 is essential for its DNA binding and transcriptional activation. Here, we confirm that SUMOylation strongly enhances Nkx2-5 transcriptional activity and that residue K51 of Nkx2-5 is a SUMOylation target. However, in a range of cultured cell lines we find that a point mutation of K51 to arginine (K51R) does not affect Nkx2-5 activity or DNA binding, suggesting the existence of additional Nkx2-5 SUMOylated residues. Using biochemical assays, we demonstrate that Nkx2-5 is SUMOylated on at least one additional site, and this is the predominant site in cardiac cells. The second site is either non-canonical or a shifting site, as mutation of predicted consensus sites and indeed every individual lysine in the context of the K51R mutation failed to impair Nkx2-5 transcriptional synergism with SUMO, or its nuclear localization and DNA binding. We also observe SUMOylation of Nkx2-5 cofactors, which may be critical to Nkx2-5 regulation. Our data reveal highly complex regulatory mechanisms driven by SUMOylation to modulate Nkx2-5 activity."	""
-3	"english"	"Australia"	"Australia"	"0.0059880239521"	"0.0538922155689"	"0.0359281437126"	"167"	"15.1818181818"	"Glycobiology"	"Cunneen MM, Pacinelli E, Song WC, Reeves PR"	"Division of Microbiology, School of Molecular Bioscience, University of Sydney, Sydney 2006, Australia."	"Among the 21 O-polysaccharide (OPS) O-antigen-based serotypes described for Yersinia pseudotuberculosis, those of O:6 and O:7 are unusual in that both contain colitose (4-keto-3,6-dideoxy-d-mannose or 4-keto-3,6-dideoxy-l-xylo-hexose), which has not otherwise been reported for this species, and the O:6 OPS also contains yersiniose A (4-C[(R)-1-hydroxyethyl]-3,6-dideoxy-d-xylo-hexose), another unusual dideoxyhexose sugar. In Y. pseudotuberculosis, the genes for OPS synthesis generally cluster together between the hemH and gsk loci. Here, we present the sequences of the OPS gene clusters of Y. pseudotuberculosis O:6 and O:7, and the location of the genes required for synthesis of these OPSs, except that there is still ambiguity regarding allocation of some of the glycosyltransferase functions. The O:6 and O:7 gene clusters have much in common with each other, but differ substantially from the group of 13 gene clusters already sequenced, which share several features and sequence similarities. We also present a possible sequence of events for the derivation of the O:6 and O:7 gene clusters from the most closely related set of 13 sequenced previously."	""
-2	"english"	"Australia"	"Australia"	"0.0"	"0.0142857142857"	"0.1"	"70"	"3.47826086957"	"Bioinformatics"	"Demaere MZ, Lauro FM, Thomas T, Yau S, Cavicchioli R"	"School of Biotechnology and Biomolecular Sciences and Centre for Marine Bio-Innovation, The University of New South Wales, Sydney, NSW 2052, Australia."	"SUMMARY: SHAP (simple high-throughput annotation pipeline) is a lightweight and scalable sequence annotation pipeline capable of supporting research efforts that generate or utilize large volumes of DNA sequence data. The software provides Grid capable analysis, relational storage and Web-based full-text searching of annotation results. Implemented in Java, SHAP recognizes the limited resources of many smaller research groups. AVAILABILITY: Source code is freely available under GPLv3 at CONTACT:;"	""
-2	"english"	"Australia"	"Australia"	"0.0119760479042"	"0.0119760479042"	"0.101796407186"	"167"	"12.8461538462"	"Annual Review of Immunology"	"Frazer IH, Leggatt GR, Mattarollo SR"	"The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Australia."	"Cervical and other anogenital cancers are initiated by infection with one of a small group of human papillomaviruses (HPV). Virus-like particle-based vaccines have recently been developed to prevent infection with two cancer-associated HPV genotypes (HPV16, HPV18) and have been  approximately 95% effective at preventing HPV-associated disease caused by these genotypes in virus-naive subjects. Although immunization induces virus-neutralizing antibody sufficient to prevent infection, persistence of antibody as measured by current assays does not appear necessary to maintain protection over time. Investigators have not identified a reliable surrogate immunological marker of protection against disease following immunization. The prophylactic vaccines are not therapeutic for existing infection. Trials of HPV-specific immunotherapy have shown some efficacy for existing disease, although animal modeling suggests that a combination of immunization and local enhancement of innate immunity may be necessary for optimal therapeutic outcome. HPV prophylactic vaccines are the first vaccines designed to prevent a human cancer and are the practical outcome of a global collaborative effort between basic and applied scientists, clinicians, and industry."	""
-2	"english"	"Australia"	"Australia"	"0.00529100529101"	"0.010582010582"	"0.031746031746"	"189"	"9.94736842105"	"Blood"	"Ganderton T, Wong JW, Schroeder C, Hogg PJ"	"Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Medical School, University of New South Wales, Sydney, NSW, Australia."	"von Willebrand Factor (VWF) is a plasma protein that binds platelets to an injured vascular wall during thrombosis. When exposed to the shear forces found in flowing blood, VWF molecules undergo lateral self-association that results in a meshwork of VWF fibres. Fibre formation has been shown to involve thiol/disulfide exchange between VWF molecules. A C-terminal fragment of VWF was expressed in mammalian cells and examined for unpaired cysteine thiols using tandem mass spectrometry. The VWF C2 domain Cys2431-Cys2453 disulfide bond was shown to be reduced in approximately 75% of the molecules. Fragments containing all three C domains or just the C2 domain formed monomers, dimers and higher-order oligomers when expressed in mammalian cells. From mutagenesis studies, both the Cys2431-Cys2453 and nearby Cys2451-Cys2468 disulfide bonds were found to be involved in oligomer formation. The findings imply that lateral VWF dimers form when a Cys2431 thiolate anion attacks the Cys2431 sulfur atom of the Cys2431-Cys2453 disulfide bond of another VWF molecule, while the Cys2451-Cys2468 disulfide/dithiol mediates formation of trimers and higher-order oligomers. These observations provide the basis for exploring defects in lateral VWF association in patients with unexplained hemorrhage or thrombosis."	""
-2	"english"	"Australia"	"Australia"	"0.00826446280992"	"0.0206611570248"	"0.0826446280992"	"242"	"12.7368421053"	"Nature"	"Gebhardt T, Whitney PG, Zaid A, Mackay LK, Brooks AG, Heath WR, Carbone FR, Mueller SN"	"Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria 3010, Australia."	"Infections localized to peripheral tissues such as the skin result in the priming of T-cell responses that act to control pathogens. Activated T cells undergo migrational imprinting within the draining lymph nodes, resulting in memory T cells that provide local and systemic protection. Combinations of migrating and resident memory T cells have been implicated in long-term peripheral immunity, especially at the surfaces that form pathogen entry points into the body. However, T-cell immunity consists of separate CD4(+) helper T cells and CD8(+) killer T cells, with distinct effector and memory programming requirements. Whether these subsets also differ in their ability to form a migrating pool involved in peripheral immunosurveillance or a separate resident population responsible for local infection control has not been explored. Here, using mice, we show key differences in the migration and tissue localization of memory CD4(+) and CD8(+) T cells following infection of the skin by herpes simplex virus. On resolution of infection, the skin contained two distinct virus-specific memory subsets; a slow-moving population of sequestered CD8(+) T cells that were resident in the epidermis and confined largely to the original site of infection, and a dynamic population of CD4(+) T cells that trafficked rapidly through the dermis as part of a wider recirculation pattern. Unique homing-molecule expression by recirculating CD4(+) T effector-memory cells mirrored their preferential skin-migratory capacity. Overall, these results identify a complexity in memory T-cell migration, illuminating previously unappreciated differences between the CD4(+) and CD8(+) subsets."	""
-3	"english"	"Australia"	"Australia"	"0.0"	"0.0143540669856"	"0.105263157895"	"209"	"13.9333333333"	"PLoS One"	"Goldshmit Y, Spanevello MD, Tajouri S, Li L, Rogers F, Pearse M, Galea M, Bartlett PF, Boyd AW, Turnley AM"	"Centre for Neuroscience, The University of Melbourne, Parkville, Victoria, Australia."	"Upregulation and activation of developmental axon guidance molecules, such as semaphorins and members of the Eph receptor tyrosine kinase family and their ligands, the ephrins, play a role in the inhibition of axonal regeneration following injury to the central nervous system. Previously we have demonstrated in a knockout model that axonal regeneration following spinal cord injury is promoted in the absence of the axon guidance protein EphA4. Antagonism of EphA4 was therefore proposed as a potential therapy to promote recovery from spinal cord injury. To further assess this potential, two soluble recombinant blockers of EphA4, unclustered ephrin-A5-Fc and EphA4-Fc, were examined for their ability to promote axonal regeneration and to improve functional outcome following spinal cord hemisection in wildtype mice. A 2-week administration of either of these blockers following spinal cord injury was sufficient to promote substantial axonal regeneration and functional recovery by 5 weeks following injury. Both inhibitors produced a moderate reduction in astrocytic gliosis, indicating that much of the effect of the blockers may be due to promotion of axon growth. These studies provide definitive evidence that soluble inhibitors of EphA4 function offer considerable therapeutic potential for the treatment of spinal cord injury and may have broader potential for the treatment of other central nervous system injuries."	""
-3	"english"	"Australia"	"Australia"	"0.0"	"0.0"	"0.0777777777778"	"90"	"10.0"	"Immunity"	"Good MF, Doolan DL"	"Division of Immunology, The Queensland Institute of Medical Research, Brisbane, QLD 4006, Australia."	"The concept of a malaria vaccine has sparked great interest for decades; however, the challenge is proving to be a difficult one. Immune dysregulation by Plasmodium and the ability of the parasite to mutate critical epitopes in surface antigens have proved to be strong defense weapons. This has led to reconsideration of polyvalent and whole parasite strategies and ways to enhance cellular immunity to malaria that may be more likely to target conserved antigens and an expanded repertoire of antigens. These and other concepts will be discussed in this review."	""
-3	"english"	"Australia"	"Australia"	"0.0136054421769"	"0.0272108843537"	"0.0680272108844"	"294"	"14.0"	"Molecular Biology and Evolution"	"Gould SB, Kraft LG, van Dooren GG, Goodman CD, Ford KL, Cassin AM, Bacic A, McFadden GI, Waller RF"	"School of Botany, University of Melbourne, Victoria, Australia."	"The pellicles of alveolates (ciliates, apicomplexans, and dinoflagellates) share a common organization, yet perform very divergent functions, including motility, host cell invasion, and armor. The alveolate pellicle consists of a system of flattened membrane sacs (alveoli, which are the defining feature of the group) below the plasma membrane that is supported by a membrane skeleton as well as a network of microtubules and other filamentous elements. We recently showed that a family of proteins, alveolins, are common and unique to this pellicular structure in alveolates. To identify additional proteins that contribute to this structure, a pellicle proteome study was conducted for the ciliate Tetrahymena thermophila. We found 1,173 proteins associated with this structure, 45% (529 proteins) of which represented novel proteins without matches to other functionally characterized proteins. Expression of four newly identified T. thermophila pellicular proteins as green fluorescent protein-fusion constructs confirmed pellicular location, and one new protein located in the oral apparatus. Bioinformatic analysis revealed that 21% of the putative pellicular proteins, predominantly the novel proteins, contained highly repetitive regions with strong amino acid biases for particular residues (K, E, Q, L, I, and V). When the T. thermophila novel proteins were compared with apicomplexan genomic data, 278 proteins with high sequence similarity were identified, suggesting that many of these putative pellicular components are shared between the alveolates. Of these shared proteins, 126 contained the distinctive repeat regions. Localization of two such proteins in Toxoplasma gondii confirmed their role in the pellicle and in doing so identified two new proteins of the apicomplexan invasive structure--the apical complex. Screening broadly for these repetitive domains in genomic data revealed large and actively evolving families of such proteins in alveolates, suggesting that these proteins might underpin the diversity and utility of their unique pellicular structure."	""
-2	"english"	"Australia"	"Australia"	"0.0242718446602"	"0.0145631067961"	"0.0388349514563"	"206"	"9.08695652174"	"Blood"	"Harrison SJ, Quach H, Link E, Seymour JF, Ritchie DS, Ruell S, Dean J, Januszewicz H, Johnstone R, Neeson P, Dickinson M, Nichols J, Prince HM"	"Haematology Department, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia;"	"We report results from a study exploring the combination of romidepsin, bortezomib, and dexamethasone for the treatment of patients with multiple myeloma (MM) previously treated with >1 prior therapy. The primary objective was to determine the maximum tolerated dose (MTD) of the combination using a novel accelerated dose-escalation schedule in patients with relapsed or refractory MM. The secondary objective was to determine overall response (OR), time to progression (TTP) and overall survival (OS). The MTD identified was bortezomib 1.3mg/m(2) (D1,4,8 and 11), dexamethasone 20mg (D1,2,4,5,8,9,11 and 12) and romidepsin 10mg/m(2) (day 1,8 and 15) every 28 days. Thrombocytopenia (64%) was the most common grade >/=3 hematological toxicity. Peripheral neuropathy occurred in 76% (n = 19) (grade >/= 3, 8% [95% confidence interval (CI) [1% - 26%]). Maintenance romidepsin 10mg/m(2) (D1 and 8 of a 28-day cycle) proved feasible, with 12 patients receiving a median of 7.5 (range: 1- 29) cycles. An OR (M-protein) of >MR was seen in 18/25 patients (72%); 2 (8%) CR, 13 (52%) PR including 7 (28%) VGPR. Median TTP was 7.2 (95% CI 5.5 - 19.6) months and median OS was over 36 months. This regimen shows activity with manageable toxicity and warrants further evaluation. This trial was registered at (NCT00431990)."	""
-3	"english"	"Australia"	"Australia"	"0.0175438596491"	"0.0233918128655"	"0.0643274853801"	"171"	"13.1538461538"	"Nature"	"Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F, Greenfield M, Durkan M, Leong YS, Dong Y, Cook H, Axford J, Callahan AG, Kenny N, Omodei C, McGraw EA, Ryan PA, Ritchie SA, Turelli M, ONeill SL"	"Bio21 Institute, Department of Genetics, The University of Melbourne, Victoria 3010, Australia."	"Genetic manipulations of insect populations for pest control have been advocated for some time, but there are few cases where manipulated individuals have been released in the field and no cases where they have successfully invaded target populations. Population transformation using the intracellular bacterium Wolbachia is particularly attractive because this maternally-inherited agent provides a powerful mechanism to invade natural populations through cytoplasmic incompatibility. When Wolbachia are introduced into mosquitoes, they interfere with pathogen transmission and influence key life history traits such as lifespan. Here we describe how the wMel Wolbachia infection, introduced into the dengue vector Aedes aegypti from Drosophila melanogaster, successfully invaded two natural A. aegypti populations in Australia, reaching near-fixation in a few months following releases of wMel-infected A. aegypti adults. Models with plausible parameter values indicate that Wolbachia-infected mosquitoes suffered relatively small fitness costs, leading to an unstable equilibrium frequency <30% that must be exceeded for invasion. These findings demonstrate that Wolbachia-based strategies can be deployed as a practical approach to dengue suppression with potential for area-wide implementation."	""
-2	"english"	"Australia"	"Australia"	"0.0"	"0.00561797752809"	"0.0842696629213"	"178"	"10.4705882353"	"PLoS One"	"Huston WM, Tyndall JD, Lott WB, Stansfield SH, Timms P"	"Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia."	"DegP, a member of the HtrA family of proteins, conducts critical bacterial protein quality control by both chaperone and proteolysis activities. The regulatory mechanisms controlling these two distinct activities, however, are unknown. DegP activation is known to involve a unique mechanism of allosteric binding, conformational changes and oligomer formation. We have uncovered a novel role for the residues at the PDZ1:protease interface in oligomer formation specifically for chaperone substrates of Chlamydia trachomatis HtrA (DegP homolog). We have demonstrated that CtHtrA proteolysis could be activated by allosteric binding and oligomer formation. The PDZ1 activator cleft was required for the activation and oligomer formation. However, unique to CtHtrA was the critical role for residues at the PDZ1:protease interface in oligomer formation when the activator was an in vitro chaperone substrate. Furthermore, a potential in vivo chaperone substrate, the major outer membrane protein (MOMP) from Chlamydia, was able to activate CtHtrA and induce oligomer formation. Therefore, we have revealed novel residues involved in the activation of CtHtrA which are likely to have important in vivo implications for outer membrane protein assembly."	""
-2	"english"	"Australia"	"Australia"	"0.0"	"0.0227272727273"	"0.128787878788"	"132"	"10.1538461538"	"Molecular Biology and Evolution"	"Jayaswal V, Ababneh F, Jermiin LS, Robinson J"	"School of Mathematics and Statistics, University of Sydney, NSW, Australia."	"The selection of an optimal model for data analysis is an important component of model-based molecular phylogenetic studies. Owing to the large number of Markov models that can be used for data analysis, model selection is a combinatorial problem that cannot be solved by performing an exhaustive search of all possible models. Currently, model selection is based on a small subset of the available Markov models, namely those that assume the evolutionary process to be globally stationary, reversible, and homogeneous. This forces the optimal model to be time reversible even though the actual data may not satisfy these assumptions. This problem can be alleviated by including more complex models during the model selection. We present a novel heuristic that evaluates a small fraction of these complex models and identifies the optimal model."	""
-3	"english"	"Australia"	"Australia"	"0.0206896551724"	"0.0206896551724"	"0.048275862069"	"145"	"9.66666666667"	"Glycobiology"	"Kenyon JJ, De Castro C, Cunneen MM, Reeves PR, Molinaro A, Holst O, Skurnik M"	"Division of Microbiology, School of Molecular Bioscience, University of Sydney, Sydney 2006, Australia."	"The O-specific polysaccharide (OPS) is a variable constituent of the lipopolysaccharide of Gram-negative bacteria. The polymorphic nature of OPSs within a species is usually first defined serologically, and the current serotyping scheme for Yersinia pseudotuberculosis consists of 21 O serotypes of which 15 have been characterized genetically and structurally. Here, we present the structure and DNA sequence of Y. pseudotuberculosis O:10 OPS. The O unit consists of one residue each of d-galactopyranose, N-acetyl-d-galactosamine (2-amino-2-deoxy-d-galactopyranose) and d-glucopyranose in the backbone, with two colitose (3,6-dideoxy-l-xylo-hexopyranose) side-branch residues. This structure is very similar to that shared by Escherichia coli O111 and Salmonella enterica O35. The gene cluster sequences of these serotypes, however, have only low levels of similarity to that of Y. pseudotuberculosis O:10, although there is significant conservation of gene order. Within Y. pseudotuberculosis, the O10 structure is most closely related to the O:6 and O:7 structures."	""
-1	"english"	"Australia"	"Australia"	"0.0106382978723"	"0.0106382978723"	"0.063829787234"	"188"	"7.76"	"BMC Bioinformatics"	"Kim SN, Martinez D, Cavedon L, Yencken L"	"NICTA VRL, The University of Melbourne, 3010, Australia."	"AIM: Given a set of pre-defined medical categories used in Evidence Based Medicine, we aim to automatically annotate sentences in medical abstracts with these labels. METHOD: We constructed a corpus of 1,000 medical abstracts annotated by hand with specified medical categories (e.g. Intervention, Outcome). We explored the use of various features based on lexical, semantic, structural, and sequential information in the data, using Conditional Random Fields (CRF) for classification. RESULTS: For the classification tasks over all labels, our systems achieved micro-averaged f-scores of 80.9% and 66.9% over datasets of structured and unstructured abstracts respectively, using sequential features. In labeling only the key sentences, our systems produced f-scores of 89.3% and 74.0% over structured and unstructured abstracts respectively, using the same sequential features. The results over an external dataset were lower (f-scores of 63.1% for all labels, and 83.8% for key sentences). CONCLUSIONS: Of the features we used, the best for classifying any given sentence in an abstract were based on unigrams, section headings, and sequential information from preceding sentences. These features resulted in improved performance over a simple bag-of-words approach, and outperformed feature sets used in previous work."	""
-3	"english"	"Australia"	"Australia"	"0.0"	"0.0"	"0.046511627907"	"43"	"4.18181818182"	"Immunity"	"King C"	"Department of Immunology, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia."	"T follicular helper (Tfh) cells help B cells to generate affinity-matured antibodies. Three papers in this issue of Immunity (Choi et al., 2011; Kerfoot et al., 2011; Kitano et al., 2011) provide information about the reciprocal relationship between B cells and Tfh cells."	""
-2	"english"	"Australia"	"Australia"	"0.00806451612903"	"0.0403225806452"	"0.153225806452"	"248"	"6.66666666667"	"Bioinformatics"	"Konagurthu AS, Allison L, Stuckey PJ, Lesk AM"	"Clayton School of Information Technology, Monash University, Clayton, VIC 3800, Australia."	"Simple and concise representations of protein-folding patterns provide powerful abstractions for visualizations, comparisons, classifications, searching and aligning structural data. Structures are often abstracted by replacing standard secondary structural features-that is, helices and strands of sheet-by vectors or linear segments. Relying solely on standard secondary structure may result in a significant loss of structural information. Further, traditional methods of simplification crucially depend on the consistency and accuracy of external methods to assign secondary structures to protein coordinate data. Although many methods exist automatically to identify secondary structure, the impreciseness of definitions, along with errors and inconsistencies in experimental structure data, drastically limit their applicability to generate reliable simplified representations, especially for structural comparison. This article introduces a mathematically rigorous algorithm to delineate protein structure using the elegant statistical and inductive inference framework of minimum message length (MML). Our method generates consistent and statistically robust piecewise linear explanations of protein coordinate data, resulting in a powerful and concise representation of the structure. The delineation is completely independent of the approaches of using hydrogen-bonding patterns or inspecting local substructural geometry that the current methods use. Indeed, as is common with applications of the MML criterion, this method is free of parameters and thresholds, in striking contrast to the existing programs which are often beset by them. The analysis of results over a large number of proteins suggests that the method produces consistent delineation of structures that encompasses, among others, the segments corresponding to standard secondary structure. AVAILABILITY: CONTACT:;"	""
-2	"english"	"Australia"	"Australia"	"0.0"	"0.0109289617486"	"0.174863387978"	"183"	"10.7647058824"	"BMC Bioinformatics"	"Le Cao KA, Boitard S, Besse P"	"Queensland Facility for Advanced Bioinformatics, University of Queensland, 4072 St Lucia, QLD, Australia."	"BACKGROUND: Variable selection on high throughput biological data, such as gene expression or single nucleotide polymorphisms (SNPs), becomes inevitable to select relevant information and, therefore, to better characterize diseases or assess genetic structure. There are different ways to perform variable selection in large data sets. Statistical tests are commonly used to identify differentially expressed features for explanatory purposes, whereas Machine Learning wrapper approaches can be used for predictive purposes. In the case of multiple highly correlated variables, another option is to use multivariate exploratory approaches to give more insight into cell biology, biological pathways or complex traits. RESULTS: A simple extension of a sparse PLS exploratory approach is proposed to perform variable selection in a multiclass classification framework. CONCLUSIONS: sPLS-DA has a classification performance similar to other wrapper or sparse discriminant analysis approaches on public microarray and SNP data sets. More importantly, sPLS-DA is clearly competitive in terms of computational efficiency and superior in terms of interpretability of the results via valuable graphical outputs. sPLS-DA is available in the R package mixOmics, which is dedicated to the analysis of large biological data sets."	""
-2	"english"	"Australia"	"Australia"	"0.0197044334975"	"0.0147783251232"	"0.0788177339901"	"203"	"9.66666666667"	"Molecular Biology and Evolution"	"Lee SF, Chen Y, Varan AK, Wee CW, Rako L, Axford JK, Good RT, Blacket MJ, Reuter C, Partridge L, Hoffmann AA"	"Centre for Environmental Stress and Adaptation Research, Department of Genetics, Bio21 Institute, The University of Melbourne, Australia."	"Latitudinal body size clines in animals conforming to Bergmanns rule occur on many continents but isolating their underlying genetic basis remains a challenge. In Drosophila melanogaster, the gene Dca accounts for approximately 5-10% of the natural wing size variation (McKechnie SW, Blacket MJ, Song SV, Rako L, Carroll X, Johnson TK, Jensen LT, Lee SF, Wee CW, Hoffmann AA. 2010. A clinally varying promoter polymorphism associated with adaptive variation in wing size in Drosophila. Mol Ecol. 19:775-784). We present here functional evidence that Dca is a negative regulator of wing size. A significant negative latitudinal cline of Dca gene expression was detected in synchronized third instar larvae. In addition, we clarified the evolutionary history of the three most common Dca promoter alleles (Dca237-1, Dca237-2, and Dca247) and showed that the insertion allele (Dca247), whose frequency increases with latitude, is associated with larger wing centroid size and higher average cell number in male flies. Finally, we showed that the overall linkage disequilibrium (LD) was low in the Dca promoter and that the insertion/deletion polymorphism that defines the Dca alleles was in strong LD with two other upstream sites. Our results provide strong support that Dca is a candidate for climatic adaptation in D. melanogaster."	""
-1	"english"	"Australia"	"Australia"	"0.00763358778626"	"0.0267175572519"	"0.087786259542"	"262"	"13.8421052632"	"BMC Bioinformatics"	"Lin FP, Anthony S, Polasek TM, Tsafnat G, Doogue MP"	"Centre for Health Informatics, The University of New South Wales, Sydney, Australia."	"BACKGROUND: The identification of drug characteristics is a clinically important task, but it requires much expert knowledge and consumes substantial resources. We have developed a statistical text-mining approach (BInary Characteristics Extractor and biomedical Properties Predictor: BICEPP) to help experts screen drugs that may have important clinical characteristics of interest. RESULTS: BICEPP first retrieves MEDLINE abstracts containing drug names, then selects tokens that best predict the list of drugs which represents the characteristic of interest. Machine learning is then used to classify drugs using a document frequency-based measure. Evaluation experiments were performed to validate BICEPPs performance on 484 characteristics of 857 drugs, identified from the Australian Medicines Handbook (AMH) and the PharmacoKinetic Interaction Screening (PKIS) database. Stratified cross-validations revealed that BICEPP was able to classify drugs into all 20 major therapeutic classes (100%) and 157 (of 197) minor drug classes (80%) with areas under the receiver operating characteristic curve (AUC) > 0.80. Similarly, AUC > 0.80 could be obtained in the classification of 173 (of 238) adverse events (73%), up to 12 (of 15) groups of clinically significant cytochrome P450 enzyme (CYP) inducers or inhibitors (80%), and up to 11 (of 14) groups of narrow therapeutic index drugs (79%). Interestingly, it was observed that the keywords used to describe a drug characteristic were not necessarily the most predictive ones for the classification task. CONCLUSIONS: BICEPP has sufficient classification power to automatically distinguish a wide range of clinical properties of drugs. This may be used in pharmacovigilance applications to assist with rapid screening of large drug databases to identify important characteristics for further evaluation."	""
-1	"english"	"Australia"	"Australia"	"0.00760456273764"	"0.0190114068441"	"0.0798479087452"	"263"	"7.02564102564"	"Bioinformatics"	"Liu Q, Hoi SC, Su CT, Li Z, Kwoh CK, Wong L, Li J"	"School of Computer Engineering, Nanyang Technological University, Singapore, School of Computing, National University of Singapore, Singapore and Advanced Analytics Institute, University of Technology Sydney, Australia."	"MOTIVATION: Worldwide and substantial mortality caused by the 2009 H1N1 influenza A has stimulated a new surge of research on H1N1 viruses. An epitope conservation has been learned in the HA1 protein that allows antibodies to cross-neutralize both 1918 and 2009 H1N1. However, few works have thoroughly studied the binding hot spots in those two antigen-antibody interfaces which are responsible for the antibody cross-neutralization. RESULTS: We apply predictive methods to identify binding hot spots at the epitope sites of the HA1 proteins and at the paratope sites of the 2D1 antibody. We find that the six mutations at the HA1s epitope from 1918 to 2009 should not harm its binding to 2D1. Instead, the change of binding free energy on the whole exhibits an increased tendency after these mutations, making the binding stronger. This is consistent with the observation that the 1918 H1N1 neutralizing antibody can cross-react with 2009 H1N1. We identified three distinguished hot spot residues, including Lys(166), common between the two epitopes. These common hot spots again can explain why 2D1 cross-reacted. We believe that these hot spot residues are mutation candidates which may help H1N1 viruses to evade the immune system. We also identified eight residues at the paratope site of 2D1, five from its heavy chain and three from its light chain, that are predicted to be energetically important in the HA1 recognition. The identification of these hot spot residues and their structural analysis are potentially useful to fight against H1N1 viruses. CONTACT: AVAILABILITY: Z-score is available at SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
-2	"english"	"Australia"	"Australia"	"0.00803212851406"	"0.0200803212851"	"0.0642570281124"	"249"	"13.1578947368"	"Glycobiology"	"Maksimovic J, Sharp JA, Nicholas KR, Cocks BG, Savin K"	"Centre for Reproduction and Development, Monash Institute of Medical Research, Clayton 3168, Australia."	"Milk sialoglycoconjugates can protect the gastrointestinal tract of the suckling neonate by competitively binding to invading pathogens and promoting growth of beneficial flora, and their potential role in postnatal brain development is of particular interest in human infant nutrition. Although the concentration and the distribution of sialoglycoconjugates have been extensively studied in the milk of various species, the investigation of sialyltransferase gene expression in the mammary gland, in the context of lactation, has been limited. The sialyltransferase enzyme ST6Gal I transfers sialic acid from CMP-sialic acid to type 2 (Galbeta1,4GlcNAc) free disaccharides or the termini of N- or O-linked oligosaccharides using an alpha2,6-linkage. Expression of the ST6Gal I gene is primarily regulated at the level of transcription through the use of several cell and development-specific promoters, producing transcripts with divergent 5 untranslated regions (UTR). In the mouse mammary gland, the novel 5UTR exon (L) appears to be associated with a drastic increase in ST6Gal I gene expression during lactation. We find that rats also possess an exon (L), suggesting conservation of this regulatory mechanism in rodents. In contrast, an exon (L)-containing transcript was not detected in the lactating bovine or human mammary gland. We also observed a trend of increasing ST6Gal I gene expression in the bovine mammary gland, culminating in involution. This is in contrast to species such as mice where the greatest change in ST6Gal I gene expression occurs between pregnancy and lactation, suggesting different roles in rodents vs. other mammals for alpha2,6-sialylated oligosaccharides present in milk."	""
-1	"english"	"Australia"	"Australia"	"0.0120481927711"	"0.0120481927711"	"0.0481927710843"	"83"	"11.8571428571"	"BMC Bioinformatics"	"Martinez D, Baldwin T"	"NICTA VRL, The University of Melbourne, VIC 3010, Australia."	"This paper describes a method for detecting event trigger words in biomedical text based on a word sense disambiguation (WSD) approach. We first investigate the applicability of existing WSD techniques to trigger word disambiguation in the BioNLP 2009 shared task data, and find that we are able to outperform a traditional CRF-based approach for certain word types. On the basis of this finding, we combine the WSD approach with the CRF, and obtain significant improvements over the standalone CRF, gaining particularly in recall."	""
-2	"english"	"Australia"	"Australia"	"0.0103092783505"	"0.0137457044674"	"0.085910652921"	"291"	"12.652173913"	"PLoS Computational Biology"	"McCaw JM, Arinaminpathy N, Hurt AC, McVernon J, McLean AR"	"Vaccine and Immunisation Research Group, Murdoch Childrens Research Institute, Royal Childrens Hospital, Parkville, Victoria, Australia."	"We present a method to measure the relative transmissibility (transmission fitness) of one strain of a pathogen compared to another. The model is applied to data from competitive mixtures experiments in which animals are co-infected with a mixture of two strains. We observe the mixture in each animal over time and over multiple generations of transmission. We use data from influenza experiments in ferrets to demonstrate the approach. Assessment of the relative transmissibility between two strains of influenza is important in at least three contexts: 1) Within the human population antigenically novel strains of influenza arise and compete for susceptible hosts. 2) During a pandemic event, a novel sub-type of influenza competes with the existing seasonal strain(s). The unfolding epidemiological dynamics are dependent upon both the populations susceptibility profile and the inherent transmissibility of the novel strain compared to the existing strain(s). 3) Neuraminidase inhibitors (NAIs), while providing significant potential to reduce transmission of influenza, exert selective pressure on the virus and so promote the emergence of drug-resistant strains. Any adverse outcome due to selection and subsequent spread of an NAI-resistant strain is exquisitely dependent upon the transmission fitness of that strain. Measurement of the transmission fitness of two competing strains of influenza is thus of critical importance in determining the likely time-course and epidemiology of an influenza outbreak, or the potential impact of an intervention measure such as NAI distribution. The mathematical framework introduced here also provides an estimate for the size of the transmitted inoculum. We demonstrate the frameworks behaviour using data from ferret transmission studies, and through simulation suggest how to optimise experimental design for assessment of transmissibility. The method introduced here for assessment of mixed transmission events has applicability beyond influenza, to other viral and bacterial pathogens."	""
-2	"english"	"Australia"	"Australia"	"0.0"	"0.0128205128205"	"0.0448717948718"	"156"	"14.1818181818"	"Immunity"	"McGuire HM, Vogelzang A, Ma CS, Hughes WE, Silveira PA, Tangye SG, Christ D, Fulcher D, Falcone M, King C"	"Department of Immunology, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia."	"This study describes a CD4+ T helper (Th) cell subset marked by coexpression of the cytokine interleukin 21 (IL-21) and the gut-homing chemokine receptor CCR9. Although CCR9+ Th cells were observed in healthy mice and humans, they were enriched in the inflamed pancreas and salivary glands of NOD mice and in the circulation of Sjogrens syndrome patients. CCR9+ Th cells expressed large amounts of IL-21, inducible T cell costimulator (ICOS), and the transcription factors Bcl6 and Maf, and also supported antibody production from B cells, thereby resembling T follicular B helper (Tfh) cells. However, in contrast to Tfh cells, CCR9+ Th cells displayed limited expression of CXCR5 and the targets of CCR9+ Th cells were CD8+ T cells whose responsiveness to IL-21 was necessary for the development of diabetes. Thus, CCR9+ Th cells are a subset of IL-21-producing T helper cells that influence regional specification of autoimmune diseases that affect accessory organs of the digestive system."	""
-3	"english"	"Australia"	"Australia"	"0.00778210116732"	"0.0233463035019"	"0.0661478599222"	"257"	"8.54838709677"	"Bioinformatics"	"McLeay RC, Leat CJ, Bailey TL"	"Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia."	"Direct binding by a transcription factor (TF) to the proximal promoter of a gene is a strong evidence that the TF regulates the gene. Assaying the genome-wide binding of every TF in every cell type and condition is currently impractical. Histone modifications correlate with tissue/cell/condition-specific (tissue specific) TF binding, so histone ChIP-seq data can be combined with traditional position weight matrix (PWM) methods to make tissue-specific predictions of TF-promoter interactions. RESULTS: We use supervised learning to train a naive Bayes predictor of TF-promoter binding. The predictors features are the histone modification levels and a PWM-based score for the promoter. Training and testing uses sets of promoters labeled using TF ChIP-seq data, and we use cross-validation on 23 such datasets to measure the accuracy. A PWM+histone naive Bayes predictor using a single histone modification (H3K4me3) is substantially more accurate than a PWM score or a conservation-based score (phylogenetic motif model). The naive Bayes predictor is more accurate (on average) at all sensitivity levels, and makes only half as many false positive predictions at sensitivity levels from 10% to 80%. On average, it correctly predicts 80% of bound promoters at a false positive rate of 20%. Accuracy does not diminish when we test the predictor in a different cell type (and species) from training. Accuracy is barely diminished even when we train the predictor without using TF ChIP-seq data. AVAILABILITY: Our tissue-specific predictor of promoters bound by a TF is called Dr Gene and is available at CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
-3	"english"	"Australia"	"Australia"	"0.00673400673401"	"0.020202020202"	"0.0909090909091"	"297"	"14.1428571429"	"Molecular Biology and Evolution"	"Murray SA, Mihali TK, Neilan BA"	"School of Biotechnology and Biomolecular Sciences, University of New South Wales, New South Wales, Australia."	"The recent determination of the genetic basis for the biosynthesis of the neurotoxin, saxitoxin, produced by cyanobacteria, has revealed a highly complex sequence of reactions, involving over 30 biosynthetic steps encoded by up to 26 genes clustered at one genomic locus, sxt. Insights into evolutionary-ecological processes have been found through the study of such secondary metabolites because they consist of a measurable phenotype with clear ecological consequences, synthesized by known genes in a small number of species. However, the processes involved in and timing of the divergence of prokaryotic secondary metabolites have been difficult to determine due to their antiquity and the possible frequency of horizontal gene transfer and homologous recombination. Through analyses of gene synteny, phylogenies of individual genes, and analyses of recombination and selection, we identified the evolutionary processes of this cluster in five species of cyanobacteria. Here, we provide evidence that the sxt cluster appears to have been largely vertically inherited and was therefore likely present early in the divergence of the Nostocales, at least 2,100 Ma, the earliest reliably dated appearance of a secondary metabolite. The sxt cluster has been extraordinarily conserved through stabilizing selection. Genes have been lost and rearranged, have undergone intra- and interspecific recombination, and have been subject to duplication followed by positive selection along the duplicated lineage, with likely consequences for the toxin analogues produced. Several hypotheses exist as to the ecophysiological role of saxitoxin: as a method of chemical defense, cellular nitrogen storage, DNA metabolism, or chemical signaling. The antiquity of this gene cluster indicates that potassium channels, not sodium channels, may have been the original targets of this compound. The extraordinary conservation of the machinery for saxitoxin synthesis, under radically changing environmental conditions, shows that it has continued to play an important adaptive role in some cyanobacteria."	""
-3	"english"	"Australia"	"Australia"	"0.00378787878788"	"0.00378787878788"	"0.030303030303"	"264"	"10.64"	"PLoS One"	"Naughton S, Parker D, Seemann T, Thomas T, Turnbull L, Rose B, Bye P, Cordwell S, Whitchurch C, Manos J"	"Department of Infectious Diseases and Immunology, University of Sydney, Sydney, Australia."	"Pseudomonas aeruginosa, the leading cause of morbidity and mortality in people with cystic fibrosis (CF), adapts for survival in the CF lung through both mutation and gene expression changes. Frequent clonal strains such as the Australian Epidemic Strain-1 (AES-1), have increased ability to establish infection in the CF lung and to superimpose and replace infrequent clonal strains. Little is known about the factors underpinning these properties. Analysis has been hampered by lack of expression array templates containing CF-strain specific genes. We sequenced the genome of an acute infection AES-1 isolate from a CF infant (AES-1R) and constructed a non-redundant micro-array (PANarray) comprising AES-1R and seven other sequenced P. aeruginosa genomes. The unclosed AES-1R genome comprised 6.254Mbp and contained 6957 putative genes, including 338 not found in the other seven genomes. The PANarray contained 12,543 gene probe spots; comprising 12,147 P. aeruginosa gene probes, 326 quality-control probes and 70 probes for non-P. aeruginosa genes, including phage and plant genes. We grew AES-1R and its isogenic pair AES-1M, taken from the same patient 10.5 years later and not eradicated in the intervening period, in our validated artificial sputum medium (ASMDM) and used the PANarray to compare gene expression of both in duplicate. 675 genes were differentially expressed between the isogenic pairs, including upregulation of alginate, biofilm, persistence genes and virulence-related genes such as dihydroorotase, uridylate kinase and cardiolipin synthase, in AES-1M. Non-PAO1 genes upregulated in AES-1M included pathogenesis-related (PAGI-5) genes present in strains PACS2 and PA7, and numerous phage genes. Elucidation of these genes roles could lead to targeted treatment strategies for chronically infected CF patients."	""
-3	"english"	"Australia"	"Australia"	"0.00840336134454"	"0.00840336134454"	"0.0714285714286"	"238"	"11.3333333333"	"Molecular Biology and Evolution"	"Octavia S, Maharjan RP, Sintchenko V, Stevenson G, Reeves PR, Gilbert GL, Lan R"	"School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia."	"Despite high vaccine coverage, pertussis incidence has increased substantially in recent years in many countries. A significant factor that may be contributing to this increase is adaptation to the vaccine by Bordetella pertussis, the causative agent of pertussis. In this study, we first assessed the genetic diversity of B. pertussis by microarray-based comparative genome sequencing of 10 isolates representing diverse genotypes and different years of isolation. We discovered 171 single nucleotide polymorphisms (SNPs) in a total of 1.4 Mb genome analyzed. The frequency of base changes was estimated as one per 32 kb per isolate, confirming that B. pertussis is one of the least variable bacterial pathogens. We then analyzed an international collection of 316 B. pertussis isolates using a subset of 65 of the SNPs and identified 42 distinct SNP profiles (SPs). Phylogenetic analysis grouped the SPs into six clusters. The majority of recent isolates belonged to clusters I-IV and were descendants of a single prevaccine lineage. Cluster I appeared to be a major clone with a worldwide distribution. Typing of genes encoding acellular vaccine (ACV) antigens, ptxA, prn, fhaB, fim2, and fim3 revealed the emergence and increasing incidence of non-ACV alleles occurring in clusters I and IV, which may have been driven by ACV immune selection. Our findings suggest that B. pertussis, despite its high population homogeneity, is evolving in response to vaccination pressure with recent expansion of clones carrying variants of genes encoding ACV antigens."	""
-2	"english"	"Australia"	"Australia"	"0.0176470588235"	"0.0117647058824"	"0.0705882352941"	"170"	"13.1538461538"	"Nature Genetics"	"Painter JN, Anderson CA, Nyholt DR, Macgregor S, Lin J, Lee SH, Lambert A, Zhao ZZ, Roseman F, Guo Q, Gordon SD, Wallace L, Henders AK, Visscher PM, Kraft P, Martin NG, Morris AP, Treloar SA, Kennedy SH, Missmer SA, Montgomery GW, Zondervan KT"	"Molecular Epidemiology, Queensland Institute of Medical Research, Herston, Queensland, Australia."	"Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for all endometriosis (P = 2.6 x 10, odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 x 10, OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 x 10(3), OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 x 10 (OR = 1.20, 95% CI 1.13-1.27) for all endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10."	""
-"unk"	"english"	"Australia"	"Australia"	"0.0082304526749"	"0.0123456790123"	"0.0658436213992"	"243"	"8.37931034483"	"PLoS Computational Biology"	"Payzan-LeNestour E, Bossaerts P"	"University of New South Wales, Sydney, Australia."	"Recently, evidence has emerged that humans approach learning using Bayesian updating rather than (model-free) reinforcement algorithms in a six-arm restless bandit problem. Here, we investigate what this implies for human appreciation of uncertainty. In our task, a Bayesian learner distinguishes three equally salient levels of uncertainty. First, the Bayesian perceives irreducible uncertainty or risk: even knowing the payoff probabilities of a given arm, the outcome remains uncertain. Second, there is (parameter) estimation uncertainty or ambiguity: payoff probabilities are unknown and need to be estimated. Third, the outcome probabilities of the arms change: the sudden jumps are referred to as unexpected uncertainty. We document how the three levels of uncertainty evolved during the course of our experiment and how it affected the learning rate. We then zoom in on estimation uncertainty, which has been suggested to be a driving force in exploration, in spite of evidence of widespread aversion to ambiguity. Our data corroborate the latter. We discuss neural evidence that foreshadowed the ability of humans to distinguish between the three levels of uncertainty. Finally, we investigate the boundaries of human capacity to implement Bayesian learning. We repeat the experiment with different instructions, reflecting varying levels of structural uncertainty. Under this fourth notion of uncertainty, choices were no better explained by Bayesian updating than by (model-free) reinforcement learning. Exit questionnaires revealed that participants remained unaware of the presence of unexpected uncertainty and failed to acquire the right model with which to implement Bayesian updating."	""
-"unk"	"english"	"Australia"	"Australia"	"0.012084592145"	"0.0181268882175"	"0.0302114803625"	"331"	"8.14634146341"	"PLoS One"	"Price CF, Tyssen D, Sonza S, Davie A, Evans S, Lewis GR, Xia S, Spelman T, Hodsman P, Moench TR, Humberstone A, Paull JR, Tachedjian G"	"Starpharma Pty Ltd, Melbourne, Victoria, Australia."	"SPL7013 Gel (VivaGel((R))) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3% SPL7013 Gel in healthy women. Participants received 5 single doses of product with >/=5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p</=0.003 was significant. Eleven participants completed the study. Inhibition of HIV-1 and HSV-2 by pre-dose CVF samples was negligible. CVF samples obtained immediately after dosing almost completely inhibited (median, interquartile range) HIV-1 [96% (95,97)] and HSV-2 [86% (85,94)], and activity was maintained in all women at 3 h (HIV-1 [96% (95,98), p = 0.9]; HSV-2 [94% (91,97), p = 0.005]). At 24 h, >90% of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46% of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70% inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus. TRIAL REGISTRATION: The study is registered at under identifier: NCT00740584."	""
-"unk"	"english"	"Australia"	"Australia"	"0.00990099009901"	"0.0247524752475"	"0.0891089108911"	"202"	"13.4666666667"	"PLoS Computational Biology"	"Ragan C, Zuker M, Ragan MA"	"ARC Centre of Excellence in Bioinformatics, and Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia."	"MicroRNAs (miRNAs) suppress gene expression by forming a duplex with a target messenger RNA (mRNA), blocking translation or initiating cleavage. Computational approaches have proven valuable for predicting which mRNAs can be targeted by a given miRNA, but currently available prediction methods do not address the extent of duplex formation under physiological conditions. Some miRNAs can at low concentrations bind to target mRNAs, whereas others are unlikely to bind within a physiologically relevant concentration range. Here we present a novel approach in which we find potential target sites on mRNA that minimize the calculated free energy of duplex formation, compute the free energy change involved in unfolding these sites, and use these energies to estimate the extent of duplex formation at specified initial concentrations of both species. We compare our predictions to experimentally confirmed miRNA-mRNA interactions (and non-interactions) in Drosophila melanogaster and in human. Although our method does not predict whether the targeted mRNA is degraded and/or its translation to protein inhibited, our quantitative estimates generally track experimentally supported results, indicating that this approach can be used to predict whether an interaction occurs at specified concentrations. Our approach offers a more-quantitative understanding of post-translational regulation in different cell types, tissues, and developmental conditions."	""
-"unk"	"english"	"Australia"	"Australia"	"0.00787401574803"	"0.0275590551181"	"0.133858267717"	"254"	"10.2"	"PLoS Computational Biology"	"Rubinov M, Sporns O, Thivierge JP, Breakspear M"	"Black Dog Institute and School of Psychiatry, University of New South Wales, Sydney, Australia."	"Self-organized criticality refers to the spontaneous emergence of self-similar dynamics in complex systems poised between order and randomness. The presence of self-organized critical dynamics in the brain is theoretically appealing and is supported by recent neurophysiological studies. Despite this, the neurobiological determinants of these dynamics have not been previously sought. Here, we systematically examined the influence of such determinants in hierarchically modular networks of leaky integrate-and-fire neurons with spike-timing-dependent synaptic plasticity and axonal conduction delays. We characterized emergent dynamics in our networks by distributions of active neuronal ensemble modules (neuronal avalanches) and rigorously assessed these distributions for power-law scaling. We found that spike-timing-dependent synaptic plasticity enabled a rapid phase transition from random subcritical dynamics to ordered supercritical dynamics. Importantly, modular connectivity and low wiring cost broadened this transition, and enabled a regime indicative of self-organized criticality. The regime only occurred when modular connectivity, low wiring cost and synaptic plasticity were simultaneously present, and the regime was most evident when between-module connection density scaled as a power-law. The regime was robust to variations in other neurobiologically relevant parameters and favored systems with low external drive and strong internal interactions. Increases in system size and connectivity facilitated internal interactions, permitting reductions in external drive and facilitating convergence of postsynaptic-response magnitude and synaptic-plasticity learning rate parameter values towards neurobiologically realistic levels. We hence infer a novel association between self-organized critical neuronal dynamics and several neurobiologically realistic features of structural connectivity. The central role of these features in our model may reflect their importance for neuronal information processing."	""
-2	"english"	"Australia"	"Australia"	"0.0406504065041"	"0.0243902439024"	"0.0243902439024"	"123"	"11.1818181818"	"Nature Genetics"	"Spurdle AB, Thompson DJ, Ahmed S, Ferguson K, Healey CS, OMara T, Walker LC, Montgomery SB, Dermitzakis ET, Fahey P, Montgomery GW, Webb PM, Fasching PA, Beckmann MW, Ekici AB, Hein A, Lambrechts D, Coenegrachts L, Vergote I, Amant F, Salvesen HB, Trovik J, Njolstad TS, Helland H, Scott RJ, Ashton K, Proietto T, Otton G, Tomlinson I, Gorman M, Howarth K, Hodgson S, Garcia-Closas M, Wentzensen N, Yang H, Chanock S, Hall P, Czene K, Liu J, Li J, Shu XO, Zheng W, Long J, Xiang YB, Shah M, Morrison J, Michailidou K, Pharoah PD, Dunning AM, Easton DF"	"Division of Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Queensland, Australia."	"Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 x 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes."	""
-"unk"	"english"	"Australia"	"Australia"	"0.0122950819672"	"0.0286885245902"	"0.0860655737705"	"244"	"12.8421052632"	"Molecular Biology and Evolution"	"Subramanian S"	"Griffith School of Environment, Griffith University, Nathan, Queensland, Australia."	"Deleterious mutations associated with human diseases are predominantly found in conserved positions and positions that are essential for the structure and/or function of proteins. However, these mutations are purged from the human population over time and prevented from being fixed. Contrary to this belief, here I show that high proportions of deleterious amino acid changing mutations are fixed at positions critical for the structure and/or function of proteins. Similarly, a high rate of fixation of deleterious mutations was observed in slow-evolving amino acid positions of human proteins. The fraction of deleterious substitutions was found to be two times higher in relatively conserved amino acid positions than in highly variable positions. This study also found fixation of a much higher proportion of radical amino acid changes in primates compared with rodents and artiodactyls in slow-evolving positions. Previous studies observed a higher proportion of nonsynonymous substitutions in humans compared with other mammals, which was taken as indirect evidence for the fixation of deleterious mutations in humans. However, the results of this investigation provide direct evidence for this prediction by suggesting that the excess nonsynonymous mutations fixed in humans are indeed deleterious in nature. Furthermore, these results suggest that studies on disease-associated mutations should consider that a significant fraction of such deleterious mutations has already been fixed in the human genome, and thus, the effects of new mutations at those amino acid positions may not necessarily be deleterious and might even result in reversion to benign phenotypes."	""
-"unk"	"english"	"Australia"	"Australia"	"0.0"	"0.0"	"0.075"	"40"	"5.71428571429"	"Immunity"	"Tangye SG"	"Immunology Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia."	"Immunoglobulin (Ig) A is critical for protective immune responses at mucosal surfaces. In this issue of Immunity, Tezuka et al. (2011) identify an important relay between stromal cells and plasmacytoid dendritic cells that regulates IgA production by murine B cells."	""
-"unk"	"english"	"Australia"	"Australia"	"0.0204081632653"	"0.030612244898"	"0.0663265306122"	"196"	"9.33333333333"	"Blood"	"To LB, Levesque JP, Herbert KE"	"Haematology, IMVS/SA Pathology and Royal Adelaide Hospital, Adelaide, SA, Australia;"	"Transplantation using 2-5 x 10(6) mobilized CD34(+)cells/kg body weight (BW) lowers transplant costs and mortality. Mobilization is most commonly performed with recombinant human granulocyte colony stimulating factor (G-CSF) with or without chemotherapy but a proportion of patients/donors fail to mobilize sufficient cells. Bone marrow (BM) disease, prior treatment and age are factors influencing mobilization but genetics also contributes. Mobilization may fail because of the changes affecting the hematopoietic stem/progenitor cell (HSC)/BM niche integrity and chemotaxis. Poor mobilization affects patient outcome and increases resource utilization. Until recently increasing G-CSF dose and adding stem cell factor (SCF) have been used in poor mobilizers with limited success. However plerixafor through its rapid direct blockage of the CXCR4/CXCL12 chemotaxis pathway and synergy with G-CSF and chemotherapy has become a new and important agent for mobilization. It efficacy in upfront and failed mobilizers are well established. To maximize HSC harvest in poor mobilizers the clinician needs to optimize current mobilization protocols and to integrate novel agents like plerixafor. These include when to mobilize in relation to chemotherapy, how to schedule and perform apheresis, how to identify poor mobilizers and what are the criteria for pre-emptive and immediate salvage use of plerixafor."	""
-"unk"	"english"	"Australia"	"Australia"	"0.0103626943005"	"0.00518134715026"	"0.0777202072539"	"193"	"12.8666666667"	"Molecular Biology and Evolution"	"Tong J, Dolezal P, Selkrig J, Crawford S, Simpson AG, Noinaj N, Buchanan SK, Gabriel K, Lithgow T"	"Department of Biochemistry & Molecular Biology, Monash University, Clayton, Australia."	"The evolution of mitochondria from ancestral bacteria required that new protein transport machinery be established. Recent controversy over the evolution of these new molecular machines hinges on the degree to which ancestral bacterial transporters contributed during the establishment of the new protein import pathway. Reclinomonas americana is a unicellular eukaryote with the most gene-rich mitochondrial genome known, and the large collection of membrane proteins encoded on the mitochondrial genome of R. americana includes a bacterial-type SecY protein transporter. Analysis of expressed sequence tags shows R. americana also has components of a mitochondrial protein translocase or translocase in the inner mitochondrial membrane complex. Along with several other membrane proteins encoded on the mitochondrial genome Cox11, an assembly factor for cytochrome c oxidase retains sequence features suggesting that it is assembled by the SecY complex in R. americana. Despite this, protein import studies show that the RaCox11 protein is suited for import into mitochondria and functional complementation if the gene is transferred into the nucleus of yeast. Reclinomonas americana provides direct evidence that bacterial protein transport pathways were retained, alongside the evolving mitochondrial protein import machinery, shedding new light on the process of mitochondrial evolution."	""
-"unk"	"english"	"Australia"	"Australia"	"0.0148698884758"	"0.0371747211896"	"0.0371747211896"	"269"	"11.9130434783"	"PLoS One"	"Tse BW, Russell PJ, Lochner M, Forster I, Power CA"	"Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia."	"Interleukin(IL)-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa) was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM)/B4H7-luc. RM1 and RM1(BM)/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (alphaIL-18, SK113AE4). IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-gamma) completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-gamma as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-gamma was neutralized contained significantly fewer CD4(+) and CD8(+) T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1(-/-) mice or in mice depleted of CD4(+) and/or CD8(+) cells than in normal mice. The tumors in RAG1(-/-) mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms."	""
-"unk"	"english"	"Australia"	"Australia"	"0.00819672131148"	"0.0491803278689"	"0.114754098361"	"122"	"5.73913043478"	"Bioinformatics"	"Vinh NX, Chetty M, Coppel R, Wangikar PP"	"Gippsland School of Information Technology, Monash University, Victoria, Australia."	"MOTIVATION: Dynamic Bayesian networks (DBN) are widely applied in modeling various biological networks including the gene regulatory network (GRN). Due to the NP-hard nature of learning static Bayesian network structure, most methods for learning DBN also employ either local search such as hill-climbing, or a meta stochastic global optimization framework such as genetic algorithm or simulated annealing. RESULTS: This paper presents GlobalMIT, a toolbox for learning the globally optimal DBN structure from gene expression data. We propose using a recently introduced information theoretic based scoring metric named mutual information test (MIT). With MIT, the task of learning the globally optimal DBN is efficiently achieved in polynomial time. AVAILABILITY: The toolbox, implemented in Matlab and C++, is available at CONTACT:,"	""
-"unk"	"english"	"Australia"	"Australia"	"0.0220588235294"	"0.0257352941176"	"0.0808823529412"	"272"	"11.8260869565"	"Nature"	"Walker T, Johnson PH, Moreira LA, Iturbe-Ormaetxe I, Frentiu FD, McMeniman CJ, Leong YS, Dong Y, Axford J, Kriesner P, Lloyd AL, Ritchie SA, ONeill SL, Hoffmann AA"	"School of Biological Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia."	"Dengue fever is the most important mosquito-borne viral disease of humans with more than 50 million cases estimated annually in more than 100 countries. Disturbingly, the geographic range of dengue is currently expanding and the severity of outbreaks is increasing. Control options for dengue are very limited and currently focus on reducing population abundance of the major mosquito vector, Aedes aegypti. These strategies are failing to reduce dengue incidence in tropical communities and there is an urgent need for effective alternatives. It has been proposed that endosymbiotic bacterial Wolbachia infections of insects might be used in novel strategies for dengue control. For example, the wMelPop-CLA Wolbachia strain reduces the lifespan of adult A. aegypti mosquitoes in stably transinfected lines. This life-shortening phenotype was predicted to reduce the potential for dengue transmission. The recent discovery that several Wolbachia infections, including wMelPop-CLA, can also directly influence the susceptibility of insects to infection with a range of insect and human pathogens has markedly changed the potential for Wolbachia infections to control human diseases. Here we describe the successful transinfection of A. aegypti with the avirulent wMel strain of Wolbachia, which induces the reproductive phenotype cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, providing optimal phenotypic effects for invasion. Under semi-field conditions, the wMel strain increased from an initial starting frequency of 0.65 to near fixation within a few generations, invading A. aegypti populations at an accelerated rate relative to trials with the wMelPop-CLA strain. We also show that wMel and wMelPop-CLA strains block transmission of dengue serotype 2 (DENV-2) in A. aegypti, forming the basis of a practical approach to dengue suppression."	""
-"unk"	"english"	"Australia"	"Australia"	"0.0241935483871"	"0.0362903225806"	"0.100806451613"	"248"	"8.03225806452"	"PLoS One"	"Watson GS, Cribb BW, Watson JA"	"School of Pharmacy and Molecular Sciences, James Cook University, Townsville, Australia."	"Many termite species typically fly during or shortly after rain periods. Local precipitation will ensure water will be present when establishing a new colony after the initial flight. Here we show how different species of termite utilise two distinct and contrasting strategies for optimising the success of the colonisation flight. Nasutitermes sp. and Microcerotermes sp. fly during rain periods and adopt hydrophobic structuring/technologies on their wings to contend with a moving canvas of droplets in daylight hours. Schedorhinotermes sp. fly after rain periods (typically at night) and thus do not come into contact with mobile droplets. These termites, in contrast, display hydrophilic structuring on their wings with a small scale roughness which is not dimensionally sufficient to introduce an increase in hydrophobicity. The lack of hydrophobicity allows the termite to be hydrophilicly captured at locations where water may be present in large quantities; sufficient for the initial colonization period. The high wettability of the termite cuticle (Schedorhinotermes sp.) indicates that the membrane has a high surface energy and thus will also have strong attractions with solid particles. To investigate this the termite wings were also interacted with both artificial and natural contaminants in the form of hydrophilic silicon beads of various sizes, 4 microm C(18) beads and three differently structured pollens. These were compared to the superhydrophobic surface of the planthopper (Desudaba psittacus) and a native Si wafer surface. The termite cuticle demonstrated higher adhesive interactions with all particles in comparison to those measured on the plant hopper."	""
-"unk"	"english"	"Australia"	"Australia"	"0.00740740740741"	"0.00740740740741"	"0.0555555555556"	"270"	"8.70967741935"	"Molecular Biology and Evolution"	"Wong ES, Papenfuss AT, Whittington CM, Warren WC, Belov K"	"Faculty of Veterinary Science, The University of Sydney, NSW 2006, Australia."	"Gene duplication followed by adaptive selection is believed to be the primary driver of venom evolution. However, to date, no studies have evaluated the importance of gene duplications for venom evolution using a genomic approach. The availability of a sequenced genome and a venom gland transcriptome for the enigmatic platypus provides a unique opportunity to explore the role that gene duplication plays in venom evolution. Here, we identify gene duplication events and correlate them with expressed transcripts in an in-season venom gland. 1,508 gene duplicates were identified. 421 of these duplicated pairs, including genes that have undergone multiple rounds of gene duplications, were expressed in the venom gland. The majority of these genes are involved in metabolism and protein synthesis not toxin functions. Twelve secretory genes including serine proteases, metalloproteinases and protease inhibitors likely to produce symptoms of envenomation such as vasodilation and pain were detected. Only 16 out of 107 platypus genes with high similarity to known toxins evolved through gene duplication. Platypus venom C-type natriuretic peptides and nerve growth factor do not possess lineage-specific gene duplicates. Extensive duplications, believed to increase the potency of toxic content and promote toxin diversification were not found. This is the first study to take a genome-wide approach in order to examine the impact of gene duplication on venom evolution. Our findings support the idea that adaptive selection acts on gene duplicates to drive the independent evolution and functional diversification of similar venom genes in venomous species. However, gene duplications alone do not explain the venome of the platypus. Other mechanisms, such as alternative splicing and mutation, may be important in venom innovation."	""
-"unk"	"english"	"Australia"	"Australia"	"0.0"	"0.0408163265306"	"0.0"	"49"	"7.0"	"Immunity"	"Wu L"	"Immunology Division, Walter and Eliza Hall Institute, Melbourne, Parkville Victoria 3052, Australia."	"The signaling pathway of the cytokine Flt3L in dendritic cells (DCs) is poorly defined. In this issue of Immunity, Sathaliyawala et al. (2010) report that the kinase mTOR functions as a mediator of Flt3L signaling in the development and homeostasis of DCs, particularly of the CD8(+) and CD103(+) DCs."	""
-"unk"	"english"	"Australia"	"Australia"	"0.00657894736842"	"0.0131578947368"	"0.0526315789474"	"152"	"10.1333333333"	"Immunity"	"Wun KS, Cameron G, Patel O, Pang SS, Pellicci DG, Sullivan LC, Keshipeddy S, Young MH, Uldrich AP, Thakur MS, Richardson SK, Howell AR, Illarionov PA, Brooks AG, Besra GS, McCluskey J, Gapin L, Porcelli SA, Godfrey DI, Rossjohn J"	"The Protein Crystallography Unit, ARC Centre of Excellence in Structural and Functional Microbial Genomics, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia."	"Natural killer T (NKT) cells respond to a variety of CD1d-restricted antigens (Ags), although the basis for Ag discrimination by the NKT cell receptor (TCR) is unclear. Here we have described NKT TCR fine specificity against several closely related Ags, termed altered glycolipid ligands (AGLs), which differentially stimulate NKT cells. The structures of five ternary complexes all revealed similar docking. Acyl chain modifications did not affect the interaction, but reduced NKT cell proliferation, indicating an affect on Ag processing or presentation. Conversely, truncation of the phytosphingosine chain caused an induced fit mode of TCR binding that affected TCR affinity. Modifications in the glycosyl head group had a direct impact on the TCR interaction and associated cellular response, with ligand potency reflecting the t(1/2) life of the interaction. Accordingly, we have provided a molecular basis for understanding how modifications in AGLs can result in striking alterations in the cellular response of NKT cells."	""
-2	"english"	"Australia"	"Australia"	"0.00613496932515"	"0.0490797546012"	"0.0552147239264"	"163"	"14.8181818182"	"Nature Genetics"	"Yang J, Manolio TA, Pasquale LR, Boerwinkle E, Caporaso N, Cunningham JM, de Andrade M, Feenstra B, Feingold E, Hayes MG, Hill WG, Landi MT, Alonso A, Lettre G, Lin P, Ling H, Lowe W, Mathias RA, Melbye M, Pugh E, Cornelis MC, Weir BS, Goddard ME, Visscher PM"	"Queensland Statistical Genetics Laboratory, Queensland Institute of Medical Research, Brisbane, Australia."	"We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that  approximately 45%,  approximately 17%,  approximately 25% and  approximately 21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further  approximately 0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein."	""
-"unk"	"english"	"Australia"	"Australia"	"0.010752688172"	"0.0250896057348"	"0.0931899641577"	"279"	"12.2173913043"	"PLoS Computational Biology"	"Yu R, Craik DJ, Kaas Q"	"Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia."	"alpha-Conotoxins potently inhibit isoforms of nicotinic acetylcholine receptors (nAChRs), which are essential for neuronal and neuromuscular transmission. They are also used as neurochemical tools to study nAChR physiology and are being evaluated as drug leads to treat various neuronal disorders. A number of experimental studies have been performed to investigate the structure-activity relationships of conotoxin/nAChR complexes. However, the structural determinants of their binding interactions are still ambiguous in the absence of experimental structures of conotoxin-receptor complexes. In this study, the binding modes of alpha-conotoxin ImI to the alpha7-nAChR, currently the best-studied system experimentally, were investigated using comparative modeling and molecular dynamics simulations. The structures of more than 30 single point mutants of either the conotoxin or the receptor were modeled and analyzed. The models were used to explain qualitatively the change of affinities measured experimentally, including some nAChR positions located outside the binding site. Mutational energies were calculated using different methods that combine a conformational refinement procedure (minimization with a distance dependent dielectric constant or explicit water, or molecular dynamics using five restraint strategies) and a binding energy function (MM-GB/SA or MM-PB/SA). The protocol using explicit water energy minimization and MM-GB/SA gave the best correlations with experimental binding affinities, with an R2 value of 0.74. The van der Waals and non-polar desolvation components were found to be the main driving force for binding of the conotoxin to the nAChR. The electrostatic component was responsible for the selectivity of the various ImI mutants. Overall, this study provides novel insights into the binding mechanism of alpha-conotoxins to nAChRs and the methodological developments reported here open avenues for computational scanning studies of a rapidly expanding range of wild-type and chemically modified alpha-conotoxins."	""
-2	"english"	"Australia, Australia"	"Australia"	"0.00454545454545"	"0.00909090909091"	"0.0727272727273"	"220"	"7.35483870968"	"Bioinformatics"	"Bedo J, Kowalczyk A"	"National ICT Australia, Victoria Research Laboratories, The University of Melbourne, VIC 3010, Australia."	"MOTIVATION: Many ChIP-Seq experiments are aimed at developing gold standards for determining the locations of various genomic features such as transcription start or transcription factor binding sites on the whole genome. Many such pioneering experiments lack rigorous testing methods and adequate gold standard annotations to compare against as they themselves are the most reliable source of empirical data available. To overcome this problem, we propose a self-consistency test whereby a dataset is tested against itself. It relies on a supervised machine learning style protocol for in silico annotation of a genome and accuracy estimation to guarantee, at least, self-consistency. RESULTS: The main results use a novel performance metric (a calibrated precision) in order to assess and compare the robustness of the proposed supervised learning method across different test sets. As a proof of principle, we applied the whole protocol to two recent ChIP-Seq ENCODE datasets of STAT1 and Pol-II binding sites. STAT1 is benchmarked against in silicodetection of binding sites using available position weight matrices. Pol-II, the main focus of this paper, is benchmarked against 17 algorithms for the closely related and well-studied problem of in silico transcription start site (TSS) prediction. Our results also demonstrate the feasibility of in silico genome annotation extension with encouraging results from a small portion of annotated genome to the remainder. AVAILABILITY: Available from"	""
-2	"english"	"Australia, Australia"	"Australia"	"0.011811023622"	"0.0275590551181"	"0.0826771653543"	"254"	"13.3684210526"	"Glycobiology"	"Cooper PD, Petrovsky N"	"Department of Endocrinology, Vaxine Pty Ltd, Flinders Medical Centre, Bedford Park, South Australia, Australia."	"We report a novel isoform of beta-D-[2 --> 1] poly(fructo-furanosyl) alpha-D-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37-48 degrees C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56 degrees C, whereas GI is converted from AI at 45 degrees C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DIs polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity."	""
-1	"english"	"Australia, Australia"	"Australia"	"0.00806451612903"	"0.0"	"0.0443548387097"	"248"	"14.5882352941"	"Glycobiology"	"Gandhi NS, Mancera RL"	"Curtin Health Innovation Research Institute, Western Australian Biomedical Research Institute, GPO Box U1987, Perth, WA 6845, Australia."	"Mammalian heparanase is an endo-beta-glucuronidase associated with cell invasion in cancer metastasis, angiogenesis, and inflammation. Heparanase cleaves heparan sulphate proteoglycans in the extracellular matrix and basement membrane, releasing heparin/heparan sulphate oligosaccharides of appreciable size. This in turn causes the release of growth factors, which accelerate tumour growth and metastasis. Heparanase has two glycosaminoglycan binding domains; however, no three-dimensional structure information is available for human heparanase that can provide insight into how the two domains interact to degrade heparin fragments. We have constructed a new homology model of heparanase that takes into account the most recent structural and bioinformatics data available. Heparin analogues and glycosaminoglycan mimetics were computationally docked into the active site with energetically-stable ring conformations and their interaction energies were compared. The resulting docked structures were used to propose a model for substrate and conformer selectivity based on the dimensions of the active site. The docking of substrates and inhibitors indicate the existence of a large binding site extending at least two saccharide units beyond the cleavage site (towards the non-reducing end) and at least three saccharides towards the reducing end (towards heparin-binding site 2). The docking of substrates suggests that heparanase recognises the N-sulphated and O-sulphated glucosamine at subsite +1 and glucuronic acid at the cleavage site, whereas in the absence of 6-O-sulphation in glucosamine, glucuronic acid is docked at subsite +2. These findings will help to focus the rational design of heparanase-inhibiting molecules for anti-cancer drug development by targeting the two heparin/heparan sulphate recognition domains."	""
-2	"english"	"Australia, Australia"	"Australia"	"0.00429184549356"	"0.0300429184549"	"0.12017167382"	"233"	"11.0952380952"	"Molecular Biology and Evolution"	"Lloyd AH, Timmis JN"	"School of Molecular and Biomedical Science, The University of Adelaide, South Australia 5005 Australia."	"Endosymbiotic transfer of DNA and functional genes from the cytoplasmic organelles (mitochondria and chloroplasts) to the nucleus has been a major factor driving the origin of new nuclear genes, a process central to eukaryote evolution. Although organelle DNA transfers very frequently to the nucleus, most is quickly deleted, decays, or is alternatively scrapped. However, a very small proportion of it gives rise, immediately or eventually, to functional genes. To simulate the process of functional transfer, we screened for nuclear activation of a chloroplast reporter gene aadA, which had been transferred from the chloroplast to independent nuclear loci in 16 different plant lines. Cryptic nuclear activity of the chloroplast promoter was revealed, which became conspicuous when present in multiple nuclear copies. We screened  approximately 50 million cells of each line and retrieved three plants in which aadA showed strong nuclear activation. Activation occurred by acquisition of the CaMV 35S nuclear promoter or by nuclear activation of the native chloroplast promoter. Two fortuitous sites within the 3 UTR of aadA mRNA both promoted polyadenylation without any sequence change. Complete characterization of one nuclear sequence before and after gene transfer demonstrated integration by nonhomologous end joining involving simultaneous insertion of multiple chloroplast DNA fragments. The real-time observation of three different means by which a chloroplast gene can become expressed in the nucleus suggests that the process, though rare, may be more readily achieved than previously envisaged."	""
-"unk"	"english"	"Australia, Australia"	"Australia"	"0.0"	"0.0"	"0.0857142857143"	"35"	"5.0"	"Immunity"	"Vinuesa CG, Cook MC"	"John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia."	"Expression of the chemokine receptor CXCR5 identifies B follicular helper T cells. In this issue of Immunity, Morita et al. (2011) describe a heterogeneous circulating CXCR5(+)CD4(+) B cell helper population overrepresented in juvenile dermatomyositis patients."	""
-3	"english"	"Australia, Australia, Australia"	"Australia"	"0.0113636363636"	"0.0227272727273"	"0.0795454545455"	"176"	"10.3529411765"	"Molecular Biology and Evolution"	"Delannoy E, Fujii S, Colas des Francs-Small C, Brundrett M, Small I"	"Australian Research Council Centre of Excellence in Plant Energy Biology, University of Western Australia, Perth, Australia."	"Since the endosymbiotic origin of chloroplasts from cyanobacteria 2 billion years ago, the evolution of plastids has been characterized by massive loss of genes. Most plants and algae depend on photosynthesis for energy and have retained  approximately 110 genes in their chloroplast genome that encode components of the gene expression machinery and subunits of the photosystems. However, nonphotosynthetic parasitic plants have retained a reduced plastid genome, showing that plastids have other essential functions besides photosynthesis. We sequenced the complete plastid genome of the underground orchid, Rhizanthella gardneri. This remarkable parasitic subterranean orchid possesses the smallest organelle genome yet described in land plants. With only 20 proteins, 4 rRNAs, and 9 tRNAs encoded in 59,190 bp, it is the least gene-rich plastid genome known to date apart from the fragmented plastid genome of some dinoflagellates. Despite numerous differences, striking similarities with plastid genomes from unrelated parasitic plants identify a minimal set of protein-encoding and tRNA genes required to reside in plant plastids. This prime example of convergent evolution implies shared selective constraints on gene loss or transfer."	""
-2	"english"	"Australia, Australia, Australia"	"Australia"	"0.0"	"0.0161943319838"	"0.0566801619433"	"247"	"13.0"	"PLoS One"	"Douglass LL, Possingham HP, Carwardine J, Klein CJ, Roxburgh SH, Russell-Smith J, Wilson KA"	"The Australian Government National Environmental Research Program, The Australian Research Council Centre of Excellence for Environmental Decisions and The University of Queensland School of Biological Sciences, St. Lucia, Queensland, Australia."	"Carbon finance offers the potential to change land management and conservation planning priorities. We develop a novel approach to planning for improved land management to conserve biodiversity while utilizing potential revenue from carbon biosequestration. We apply our approach in northern Australias tropical savanna, a region of global significance for biodiversity and carbon storage, both of which are threatened by current fire and grazing regimes. Our approach aims to identify priority locations for protecting species and vegetation communities by retaining existing vegetation and managing fire and grazing regimes at a minimum cost. We explore the impact of accounting for potential carbon revenue (using a carbon price of US$14 per tonne of carbon dioxide equivalent) on priority areas for conservation and the impact of explicitly protecting carbon stocks in addition to biodiversity. Our results show that improved management can potentially raise approximately US$5 per hectare per year in carbon revenue and prevent the release of 1-2 billion tonnes of carbon dioxide equivalent over approximately 90 years. This revenue could be used to reduce the costs of improved land management by three quarters or double the number of biodiversity targets achieved and meet carbon storage targets for the same cost. These results are based on generalised cost and carbon data; more comprehensive applications will rely on fine scale, site-specific data and a supportive policy environment. Our research illustrates that the duel objective of conserving biodiversity and reducing the release of greenhouse gases offers important opportunities for cost-effective land management investments."	""
-"unk"	"english"	"Australia, Australia, Australia"	"Australia"	"0.0"	"0.0103092783505"	"0.0824742268041"	"194"	"11.4117647059"	"PLoS One"	"Stern DI, Gething PW, Kabaria CW, Temperley WH, Noor AM, Okiro EA, Shanks GD, Snow RW, Hay SI"	"Crawford School of Economics and Government, Australian National University, Canberra, Australian Capital Territory, Australia."	"There has been considerable debate on the existence of trends in climate in the highlands of East Africa and hypotheses about their potential effect on the trends in malaria in the region. We apply a new robust trend test to mean temperature time series data from three editions of the University of East Anglias Climatic Research Unit database (CRU TS) for several relevant locations. We find significant trends in the data extracted from newer editions of the database but not in the older version for periods ending in 1996. The trends in the newer data are even more significant when post-1996 data are added to the samples. We also test for trends in the data from the Kericho meteorological station prepared by Omumbo et al. We find no significant trend in the 1979-1995 period but a highly significant trend in the full 1979-2009 sample. However, although the malaria cases observed at Kericho, Kenya rose during a period of resurgent epidemics (1994-2002) they have since returned to a low level. A large assembly of parasite rate surveys from the region, stratified by altitude, show that this decrease in malaria prevalence is not limited to Kericho."	""
-2	"english"	"Australia, Australia, Australia, Australia"	"Australia"	"0.015625"	"0.0078125"	"0.09375"	"128"	"11.6363636364"	"Nature Genetics"	"Hahn CN, Chong CE, Carmichael CL, Wilkins EJ, Brautigan PJ, Li XC, Babic M, Lin M, Carmagnac A, Lee YK, Kok CH, Gagliardi L, Friend KL, Ekert PG, Butcher CM, Brown AL, Lewis ID, To LB, Timms AE, Storek J, Moore S, Altree M, Escher R, Bardy PG, Suthers GK, DAndrea RJ, Horwitz MS, Scott HS"	"1] Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia. [2] School of Medicine, University of Adelaide, South Australia, Australia."	"We report the discovery of GATA2 as a new myelodysplastic syndrome (MDS)-acute myeloid leukemia (AML) predisposition gene. We found the same, previously unidentified heterozygous c.1061C>T (p.Thr354Met) missense mutation in the GATA2 transcription factor gene segregating with the multigenerational transmission of MDS-AML in three families and a GATA2 c.1063_1065delACA (p.Thr355del) mutation at an adjacent codon in a fourth MDS family. The resulting alterations reside within the second zinc finger of GATA2, which mediates DNA-binding and protein-protein interactions. We show differential effects of the mutations on the transactivation of target genes, cellular differentiation, apoptosis and global gene expression. Identification of such predisposing genes to familial forms of MDS and AML is critical for more effective diagnosis and prognosis, counseling, selection of related bone marrow transplant donors and development of therapies."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0"	"0.0220264317181"	"0.0881057268722"	"227"	"9.08"	"PLoS One"	"Ahammer H"	"Institute of Biophysics, Centre of Physiological Medicine, Medical University of Graz, Graz, Austria."	"There exist several methods for calculating the fractal dimension of objects represented as 2D digital images. For example, Box counting, Minkowski dilation or Fourier analysis can be employed. However, there appear to be some limitations. It is not possible to calculate only the fractal dimension of an irregular region of interest in an image or to perform the calculations in a particular direction along a line on an arbitrary angle through the image. The calculations must be made for the whole image. In this paper, a new method to overcome these limitations is proposed. 2D images are appropriately prepared in order to apply 1D signal analyses, originally developed to investigate nonlinear time series. The Higuchi dimension of these 1D signals is calculated using Higuchis algorithm, and it is shown that both regions of interests and directional dependencies can be evaluated independently of the whole picture. A thorough validation of the proposed technique and a comparison of the new method to the Fourier dimension, a common two dimensional method for digital images, are given. The main result is that Higuchis algorithm allows a direction dependent as well as direction independent analysis. Actual values for the fractal dimensions are reliable and an effective treatment of regions of interests is possible. Moreover, the proposed method is not restricted to Higuchis algorithm, as any 1D method of analysis, can be applied."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0201342281879"	"0.0268456375839"	"0.0671140939597"	"149"	"13.5454545455"	"Nature"	"Antoci V, Handler G, Campante TL, Thygesen AO, Moya A, Kallinger T, Stello D, Grigahcene A, Kjeldsen H, Bedding TR, Luftinger T, Christensen-Dalsgaard J, Catanzaro G, Frasca A, De Cat P, Uytterhoeven K, Bruntt H, Houdek G, Kurtz DW, Lenz P, Kaiser A, Van Cleve J, Allen C, Clarke BD"	"Institute of Astronomy, University of Vienna, Turkenschanzstrabetae 18, A-1180 Vienna, Austria."	"Delta Scuti (delta Sct) stars are opacity-driven pulsators with masses of 1.5-2.5M(middle dot in circle), their pulsations resulting from the varying ionization of helium. In less massive stars such as the Sun, convection transports mass and energy through the outer 30 per cent of the star and excites a rich spectrum of resonant acoustic modes. Based on the solar example, with no firm theoretical basis, models predict that the convective envelope in delta Sct stars extends only about 1 per cent of the radius, but with sufficient energy to excite solar-like oscillations. This was not observed before the Kepler mission, so the presence of a convective envelope in the models has been questioned. Here we report the detection of solar-like oscillations in the delta Sct star HD 187547, implying that surface convection operates efficiently in stars about twice as massive as the Sun, as the ad hoc models predicted."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0147058823529"	"0.00980392156863"	"0.0686274509804"	"204"	"8.91304347826"	"Glycobiology"	"Arming S, Wipfler D, Mayr J, Merling A, Vilas U, Schauer R, Schwartz-Albiez R, Vlasak R"	"Department of Molecular Biology, University Salzburg, Austria."	"Sialic acids are important sugars at the reducing end of glycoproteins and glycolipids. They are among many other functions involved in cell-cell interactions, host-pathogen recognition and the regulation of serum half-life of glycoproteins. An important modification of sialic acids is O-acetylation, which can alter or mask the biological properties of the parent sialic acid molecule. The nature of mammalian sialate-O-acetyltransferases (EC involved in their biosynthesis is still unknown. We have identified the human CasD1 (capsule structure1 domain containing 1) gene as a candidate to encode the elusive enzyme. The human CasD1 gene encodes a protein with a serine-glycine-asparagine-histidine hydrolase domain and a hydrophobic transmembrane domain. Expression of the Cas1 protein tagged with enhanced green fluorescent protein in mammalian and insect cells directed the protein to the medial and trans-cisternae of the Golgi. Overexpression of the Cas1 protein in combination with alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (GD3 synthase) resulted in an up to 40% increased biosynthesis of 7-O-acetylated ganglioside GD3. By quantitative real-time polymerase chain reaction, we found up to 5-fold increase in CasD1 mRNA in tumor cells overexpressing O-Ac-GD3. CasD1-specific small interfering RNA reduced O-acetylation in tumor cells. These results suggest that the human Cas1 protein is directly involved in O-acetylation of alpha2-8-linked sialic acids."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0"	"0.012987012987"	"0.0909090909091"	"77"	"3.78260869565"	"Bioinformatics"	"Bodenhofer U, Kothmeier A, Hochreiter S"	"Institute of Bioinformatics, Johannes Kepler University, Linz, Austria."	"SUMMARY: Affinity propagation (AP) clustering has recently gained increasing popularity in bioinformatics. AP clustering has the advantage that it allows for determining typical cluster members, the so-called exemplars. We provide an R implementation of this promising new clustering technique to account for the ubiquity of R in bioinformatics. This article introduces the package and presents an application from structural biology. AVAILABILITY: The R package apcluster is available via CRAN-The Comprehensive R Archive Network: CONTACT:;"	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0204081632653"	"0.0204081632653"	"0.0561224489796"	"196"	"13.2"	"Glycobiology"	"Castilho A, Gattinger P, Grass J, Jez J, Pabst M, Altmann F, Gorfer M, Strasser R, Steinkellner H"	"Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Austria."	"Glycoengineering is increasingly being recognized as a powerful tool to generate recombinant glycoproteins with a customized N-glycosylation pattern. Here, we demonstrate the modulation of the plant glycosylation pathway toward the formation of human-type bisected and branched complex N-glycans. Glycoengineered Nicotiana benthamiana lacking plant-specific N-glycosylation (i.e. beta1,2-xylose and core alpha1,3-fucose) was used to transiently express human erythropoietin (hEPO) and human transferrin (hTF) together with modified versions of human beta1,4-mannosyl-beta1,4-N-acetylglucosaminyltransferase (GnTIII), alpha1,3-mannosyl-beta1,4-N-acetylglucosaminyltransferase (GnTIV) and alpha1,6-mannosyl-beta1,6-N-acetylglucosaminyltransferase (GnTV). hEPO was expressed as a fusion to the IgG-Fc domain (EPO-Fc) and purified via protein A affinity chromatography. Recombinant hTF was isolated from the intracellular fluid of infiltrated plant leaves. Mass spectrometry-based N-glycan analysis of hEPO and hTF revealed the quantitative formation of bisected (GnGnbi) and tri- as well as tetraantennary complex N-glycans (Gn[GnGn], [GnGn]Gn and [GnGn][GnGn]). Co-expression of GnTIII together with GnTIV and GnTV resulted in the efficient generation of bisected tetraantennary complex N-glycans. Our results show the generation of recombinant proteins with human-type N-glycosylation at great uniformity. The strategy described here provides a robust and straightforward method for producing mammalian-type N-linked glycans of defined structures on recombinant glycoproteins, which can advance glycoprotein research and accelerate the development of protein-based therapeutics."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0106007067138"	"0.0388692579505"	"0.0706713780919"	"283"	"16.6470588235"	"Molecular Biology and Evolution"	"Collingro A, Tischler P, Weinmaier T, Penz T, Heinz E, Brunham RC, Read TD, Bavoil PM, Sachse K, Kahane S, Friedman MG, Rattei T, Myers GS, Horn M"	"Department of Microbial Ecology, University of Vienna, Vienna, Austria."	"Chlamydiae are evolutionarily well-separated bacteria that live exclusively within eukaryotic host cells. They include important human pathogens such as Chlamydia trachomatis as well as symbionts of protozoa. As these bacteria are experimentally challenging and genetically intractable, our knowledge about them is still limited. In this study, we obtained the genome sequences of Simkania negevensis Z, Waddlia chondrophila 2032/99 and Parachlamydia acanthamoebae UV-7. This enabled us to perform the first comprehensive comparative and phylogenomic analysis of representative members of four major families of the Chlamydiae, including the Chlamydiaceae. We identified a surprisingly large core gene set present in all genomes and a high number of diverse accessory genes in those Chlamydiae that do not primarily infect humans or animals, including a chemosensory system in P. acanthamoebae and a type IV secretion system. In S. negevensis, the type IV secretion system is encoded on a large conjugative plasmid (pSn, 132 kb). Phylogenetic analyses suggested that a plasmid similar to the S. negevensis plasmid was originally acquired by the last common ancestor of all four families and that it was subsequently reduced, integrated into the chromosome, or lost during diversification, ultimately giving rise to the extant virulence-associated plasmid of pathogenic chlamydiae. Other virulence factors, including a type III secretion system, are conserved among the Chlamydiae to variable degrees, and together with differences in the composition of the cell wall, reflect adaptation to different host cells including convergent evolution among the four chlamydial families. Phylogenomic analysis focusing on chlamydial proteins with homology to plant proteins provided evidence for the acquisition of 53 chlamydial genes by a plant progenitor, lending further support for the hypothesis of an early interaction between a chlamydial ancestor and the primary photosynthetic eukaryote."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0132450331126"	"0.0331125827815"	"0.0662251655629"	"151"	"13.7272727273"	"Immunity"	"Ebert A, McManus S, Tagoh H, Medvedovic J, Salvagiotto G, Novatchkova M, Tamir I, Sommer A, Jaritz M, Busslinger M"	"Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, Vienna, Austria."	"V(H)-DJ(H) recombination of the immunoglobulin heavy chain (Igh) locus is temporally and spatially controlled during early B cell development, and yet no regulatory elements other than the V(H) gene promoters have been identified throughout the entire V(H) gene cluster. Here, we discovered regulatory sequences that are interspersed in the distal V(H) gene region. These conserved repeat elements were characterized by the presence of Pax5 transcription factor-dependent active chromatin by binding of the regulators Pax5, E2A, CTCF, and Rad21, as well as by Pax5-dependent antisense transcription in pro-B cells. The Pax5-activated intergenic repeat (PAIR) elements were no longer bound by Pax5 in pre-B and B cells consistent with the loss of antisense transcription, whereas E2A and CTCF interacted with PAIR elements throughout early B cell development. The pro-B cell-specific and Pax5-dependent activity of the PAIR elements suggests that they are involved in the regulation of distal V(H)-DJ(H) recombination at the Igh locus."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0171428571429"	"0.0228571428571"	"0.08"	"175"	"9.21052631579"	"Molecular Biology and Evolution"	"Farlow A, Dolezal M, Hua L, Schlotterer C"	"Institut fur Populationsgenetik, Vetmeduni Vienna, Austria."	"Understanding the function of non-coding regions in the genome, such as introns, is of central importance to evolutionary biology. One approach is to assay for the targets of natural selection. On one hand, the sequence of introns, especially short introns, appears to evolve in an almost neutral manner. While on the other hand, a large proportion of intronic sequence is under selective constraint. This discrepancy is largely dependent on intron length and differences in the methods used to infer selection. We have used a method based on DNA strand asymmetery that does not require comparison to any putatively neutrally evolving sequence, nor sequence conservation between species, to detect selection within introns. The strongest signal we identify is associated with short introns. This signal comes from a family of motifs that could act as cryptic 5 splice sites during mRNA processing, suggesting a mechanistic justification underlying this signal of selection. Together with an analysis of intron length and splice site strength, we observe that the genomic signature of splicing-coupled selection differs between long and short introns."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0"	"0.0484581497797"	"0.0484581497797"	"227"	"11.9473684211"	"Glycobiology"	"Gruber S, Vaaje-Kolstad G, Matarese F, Lopez-Mondejar R, Kubicek CP, Seidl-Seiboth V"	"Research Area Gene Technology and Applied Biochemistry, Institute of Chemical Engineering, Vienna University of Technology, Gumpendorferstrasse 1a, Vienna, Austria."	"Fungi have a plethora of chitinases, which can be phylogenetically divided into three subgroups (A, B and C). Subgroup C (sgC) chitinases are especially interesting due to their multiple carbohydrate-binding modules, but they have not been investigated in detail yet. In this study, we analyzed sgC chitinases in the mycoparasites Trichoderma atroviride and Trichoderma virens. The expression of sgC chitinase genes in T. atroviride was induced during mycoparasitism of the fungal prey Botrytis cinerea, but not Rhizoctonia solani and correspondingly only by fungal cell walls of the former. Interestingly, only few sgC chitinase genes were inducible by chitin, suggesting that non-chitinous cell wall components can act as inducers. In contrast, the transcriptional profile of the most abundantly expressed sgC chitinase gene tac6 indicated a role of the protein in hyphal network formation. This shows that sgC chitinases have diverse functions and are not only involved in the mycoparasitic attack. However, sequence analysis and 3D modelling revealed that TAC6 and also its ortholog in T. virens have potentially detrimental deletions in the substrate-binding site and are thus probably not catalytically active enzymes. Genomic analysis showed that the genes neighboring sgC chitinases often encode proteins that are solely composed of multiple LysM modules, which were induced by similar stimuli as their neighboring sgC chitinase genes. This study provides first insights into fungal sgC chitinases and their associated LysM proteins."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0168776371308"	"0.0210970464135"	"0.0548523206751"	"237"	"11.2857142857"	"PLoS Computational Biology"	"Klepsch F, Chiba P, Ecker GF"	"Department of Medicinal Chemistry, University of Vienna, Vienna, Austria."	"Overexpression of the xenotoxin transporter P-glycoprotein (P-gp) represents one major reason for the development of multidrug resistance (MDR), leading to the failure of antibiotic and cancer therapies. Inhibitors of P-gp have thus been advocated as promising candidates for overcoming the problem of MDR. However, due to lack of a high-resolution structure the concrete mode of interaction of both substrates and inhibitors is still not known. Therefore, structure-based design studies have to rely on protein homology models. In order to identify binding hypotheses for propafenone-type P-gp inhibitors, five different propafenone derivatives with known structure-activity relationship (SAR) pattern were docked into homology models of the apo and the nucleotide-bound conformation of the transporter. To circumvent the uncertainty of scoring functions, we exhaustively sampled the pose space and analyzed the poses by combining information retrieved from SAR studies with common scaffold clustering. The results suggest propafenone binding at the transmembrane helices 5, 6, 7 and 8 in both models, with the amino acid residue Y307 playing a crucial role. The identified binding site in the non-energized state is overlapping with, but not identical to, known binding areas of cyclic P-gp inhibitors and verapamil. These findings support the idea of several small binding sites forming one large binding cavity. Furthermore, the binding hypotheses for both catalytic states were analyzed and showed only small differences in their protein-ligand interaction fingerprints, which indicates only small movements of the ligand during the catalytic cycle."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0"	"0.0132158590308"	"0.123348017621"	"227"	"10.8095238095"	"BMC Bioinformatics"	"Knapp B, Giczi V, Ribarics R, Schreiner W"	"Center for Medical Statistics, Informatics and Intelligent Systems, Department for Biosimulation and Bioinformatics, Medical University of Vienna, Austria."	"BACKGROUND: The binding between the major histocompatibility complex and the presented peptide is an indispensable prerequisite for the adaptive immune response. There is a plethora of different in silico techniques for the prediction of the peptide binding affinity to major histocompatibility complexes. Most studies screen a set of peptides for promising candidates to predict possible T cell epitopes. In this study we ask the question vice versa: Which peptides do have highest binding affinities to a given major histocompatibility complex according to certain in silico scoring functions? RESULTS: Since a full screening of all possible peptides is not feasible in reasonable runtime, we introduce a heuristic approach. We developed a framework for Genetic Algorithms to optimize peptides for the binding to major histocompatibility complexes. In an extensive benchmark we tested various operator combinations. We found that (1) selection operators have a strong influence on the convergence of the population while recombination operators have minor influence and (2) that five different binding prediction methods lead to five different sets of optimal peptides for the same major histocompatibility complex. The consensus peptides were experimentally verified as high affinity binders. CONCLUSION: We provide a generalized framework to calculate sets of high affinity binders based on different previously published scoring functions in reasonable runtime. Furthermore we give insight into the different behaviours of operators and scoring functions of the Genetic Algorithm."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0197628458498"	"0.0474308300395"	"0.0869565217391"	"253"	"11.1304347826"	"Bioinformatics"	"Labaj PP, Leparc GG, Linggi BE, Markillie LM, Wiley HS, Kreil DP"	"Boku University Vienna, 1190 Muthgasse 18, Vienna, Austria."	"MOTIVATION: Measurement precision determines the power of any analysis to reliably identify significant signals, such as in screens for differential expression, independent of whether the experimental design incorporates replicates or not. With the compilation of large-scale RNA-Seq datasets with technical replicate samples, however, we can now, for the first time, perform a systematic analysis of the precision of expression level estimates from massively parallel sequencing technology. This then allows considerations for its improvement by computational or experimental means. RESULTS: We report on a comprehensive study of target identification and measurement precision, including their dependence on transcript expression levels, read depth and other parameters. In particular, an impressive recall of 84% of the estimated true transcript population could be achieved with 331 million 50 bp reads, with diminishing returns from longer read lengths and even less gains from increased sequencing depths. Most of the measurement power (75%) is spent on only 7% of the known transcriptome, however, making less strongly expressed transcripts harder to measure. Consequently, <30% of all transcripts could be quantified reliably with a relative error<20%. Based on established tools, we then introduce a new approach for mapping and analysing sequencing reads that yields substantially improved performance in gene expression profiling, increasing the number of transcripts that can reliably be quantified to over 40%. Extrapolations to higher sequencing depths highlight the need for efficient complementary steps. In discussion we outline possible experimental and computational strategies for further improvements in quantification precision. CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0"	"0.04"	"0.0909090909091"	"275"	"10.2592592593"	"BMC Bioinformatics"	"Labaj PP, Sykacek P, Kreil DP"	"Chair of Bioinformatics, Boku University Vienna, Muthgasse 18, 1190 Vienna, Austria."	"BACKGROUND: Sequence analysis aims to identify biologically relevant signals against a backdrop of functionally meaningless variation. Increasingly, it is recognized that the quality of the background model directly affects the performance of analyses. State-of-the-art approaches rely on classical sequence models that are adapted to the studied dataset. Although performing well in the analysis of globular protein domains, these models break down in regions of stronger compositional bias or low complexity. While these regions are typically filtered, there is increasing anecdotal evidence of functional roles. This motivates an exploration of more complex sequence models and application-specific approaches for the investigation of biased regions. RESULTS: Traditional Markov-chains and application-specific regression models are compared using the example of predicting runs of single amino acids, a particularly simple class of biased regions. Cross-fold validation experiments reveal that the alternative regression models capture the multi-variate trends well, despite their low dimensionality and in contrast even to higher-order Markov-predictors. We show how the significance of unusual observations can be computed for such empirical models. The power of a dedicated model in the detection of biologically interesting signals is then demonstrated in an analysis identifying the unexpected enrichment of contiguous leucine-repeats in signal-peptides. Considering different reference sets, we show how the question examined actually defines what constitutes the background. Results can thus be highly sensitive to the choice of appropriate model training sets. Conversely, the choice of reference data determines the questions that can be investigated in an analysis. CONCLUSIONS: Using a specific case of studying biased regions as an example, we have demonstrated that the construction of application-specific background models is both necessary and feasible in a challenging sequence analysis situation."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0137931034483"	"0.0275862068966"	"0.0620689655172"	"145"	"9.66666666667"	"Immunity"	"Nairz M, Schroll A, Moschen AR, Sonnweber T, Theurl M, Theurl I, Taub N, Jamnig C, Neurauter D, Huber LA, Tilg H, Moser PL, Weiss G"	"Department of Internal Medicine I, Clinical Immunology and Infectious Diseases, Innsbruck Medical University, 6020 Innsbruck, Austria."	"Erythropoietin (EPO) is the principal cytokine regulating erythropoiesis through its receptor, EPOR. Interestingly, EPORs are also found on immune cells with incompletely understood functions. Here, we show that EPO inhibits the induction of proinflammatory genes including tumor necrosis factor (TNF)-alpha and inducible nitric oxide (NO) synthase in activated macrophages, which is mechanistically attributable to blockage of nuclear factor (NF)-kappaB p65 activation by EPO. Accordingly, in systemic Salmonella infection, treatment of mice with EPO results in reduced survival and impaired pathogen clearance because of diminished formation of anti-microbial effector molecules such as TNF-alpha and NO. However, neutralization of endogenous EPO or genetic ablation of Epor promotes Salmonella elimination. In contrast, in chemically induced colitis, EPO-EPOR interaction decreases the production of NF-kappaB-inducible immune mediators, thus limiting tissue damage and ameliorating disease severity. These immune-modulatory effects of EPO may be of therapeutic relevance in infectious and inflammatory diseases."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.00862068965517"	"0.0215517241379"	"0.0560344827586"	"232"	"12.3684210526"	"Glycobiology"	"Rendic D, Sharrow M, Katoh T, Overcarsh B, Nguyen K, Kapurch J, Aoki K, Wilson IB, Tiemeyer M"	"Department fur Chemie, Universitat fur Bodenkultur, A-1190 Wien, Austria."	"Addition of fucose (Fuc) to glycoprotein N-linked glycans or in O-linkage directly to Ser/Thr residues modulates specific cell-cell interactions and cell signaling events. Vertebrates and invertebrates add Fuc in alpha6-linkage to the reducing terminal N-acetylglucosamine residue of N-glycans. In Drosophila and other invertebrates, Fuc can also be added in alpha3-linkage to the same residue. These difucosylated N-glycans are recognized by anti-horseradish peroxidase (anti-HRP) antisera, providing a well-established marker for insect neural tissue. To understand the mechanisms and consequences of tissue-specific glycan expression, we identified a single alpha3-fucosyltransferase (FucTA) that produces the anti-HRP epitope in Drosophila embryos. FucTA transcripts are temporally and spatially restricted to cells that express the anti-HRP epitope and are missing in a mutant that lacks neural alpha3-fucosylation. Transgenic expression of FucTA, but not of any other candidate alpha3-fucosyltransferase, rescues the anti-HRP epitope in the embryonic nervous system of this mutant. Mass spectrometric characterization of the N-glycans of Drosophila embryos overexpressing FucTA confirms that this enzyme is indeed responsible for the biosynthesis of difucosylated glycans in vivo. Whereas ectopic expression of FucTA in the larval wing disc produces mild wing notching, the heterochronic, pan-neural expression of FucTA in early differentiating neurons generates neurogenic and cell migration phenotypes; this latter effect is associated with reduced GDP-Fuc levels in the embryo and indicates that the diversion of fucosylation resources towards fucosylation of N-glycans has an impact on developmental signaling associated with O-fucosylation."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0"	"0.0291262135922"	"0.0776699029126"	"206"	"15.8461538462"	"PLoS One"	"Schafer B, Holzer GW, Joachimsthaler A, Coulibaly S, Schwendinger M, Crowe BA, Kreil TR, Barrett PN, Falkner FG"	"Department of Virology, Baxter Bioscience, Biomedical Research Center, Orth/Donau, Austria."	"BACKGROUND: Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. METHODOLOGY/PRINCIPAL FINDINGS: A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced gamma-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5) TCID(50). Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. CONCLUSIONS/SIGNIFICANCE: The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.005"	"0.015"	"0.025"	"200"	"13.3333333333"	"Blood"	"Schuster C, Berger A, Hoelzl MA, Putz EM, Frenzel A, Simma O, Moritz N, Hoelbl A, Kovacic B, Freissmuth M, Muller M, Villunger A, Mullauer L, Schmatz AI, Porpaczy E, Jager U, Stoiber D, Sexl V"	"Institute of Pharmacology, Center for Pharmacology and Physiology, Medical University of Vienna, Vienna, Austria;"	"In Emu-myc transgenic animals lymphoma formation requires additional genetic alterations, which frequently comprise loss of p53 or over-expression of BCL-2. We describe that the nature of the second hit affects the ability of the immune system to contain lymphoma development. Tumors with disrupted p53 signaling killed the host more rapidly than BCL-2 over-expressing ones. Relaxing immunological control, by employing Tyk2(-/-) mice or by antibody-mediated depletion of CD8(+) T or NK cells accelerated formation of BCL-2 over-expressing lymphomas but not of those lacking p53. Most strikingly, enforced expression of BCL-2 prolonged disease latency in the absence of p53, while blocking p53 function in BCL-2 over-expressing tumors, failed to accelerate disease. This demonstrates that blocking apoptosis in p53-deficient cells by enforcing BCL-2 expression can mitigate disease progression increasing the immunological visibility. In vitro cytotoxicity assays confirmed that high expression of BCL-2 protein facilitates NK and T cell-mediated killing. Moreover, we found that high BCL-2 expression is accompanied by significantly increased levels of the NKG2D-ligand MULT1 which may account for the enhanced killing. Our findings provide first evidence that the nature of the second hit impacts on tumor immune surveillance in c-MYC-driven lymphomas and define a potential shortcoming of antitumor therapies targeting BCL-2."	""
-"unk"	"europe_not_latin"	"Austria"	"Austria"	"0.0315789473684"	"0.0"	"0.126315789474"	"95"	"4.16"	"Bioinformatics"	"zu Siederdissen CH, Bernhart SH, Stadler PF, Hofacker IL"	"Institute for Theoretical Chemistry, University of Vienna, A-1090 Vienna, Austria."	"MOTIVATION: RNA secondary structure contains many non-canonical base pairs of different pair families. Successful prediction of these structural features leads to improved secondary structures with applications in tertiary structure prediction and simultaneous folding and alignment. RESULTS: We present a theoretical model capturing both RNA pair families and extended secondary structure motifs with shared nucleotides using 2-diagrams. We accompany this model with a number of programs for parameter optimization and structure prediction. AVAILABILITY: All sources (optimization routines, RNA folding, RNA evaluation, extended secondary structure visualization) are published under the GPLv3 and available at CONTACT:"	""
-"unk"	"europe_not_latin"	"Austria, Austria"	"Austria"	"0.00806451612903"	"0.00806451612903"	"0.104838709677"	"124"	"9.53846153846"	"PLoS Computational Biology"	"Burkard TR, Rix U, Breitwieser FP, Superti-Furga G, Colinge J"	"Research Center for Molecular Medicine of the Austrian Academy of Science, Vienna, Austria."	"Prediction of drug action in human cells is a major challenge in biomedical research. Additionally, there is strong interest in finding new applications for approved drugs and identifying potential side effects. We present a computational strategy to predict mechanisms, risks and potential new domains of drug treatment on the basis of target profiles acquired through chemical proteomics. Functional protein-protein interaction networks that share one biological function are constructed and their crosstalk with the drug is scored regarding function disruption. We apply this procedure to the target profile of the second-generation BCR-ABL inhibitor bafetinib which is in development for the treatment of imatinib-resistant chronic myeloid leukemia. Beside the well known effect on apoptosis, we propose potential treatment of lung cancer and IGF1R expressing blast crisis."	""
-2	"europe_not_latin"	"Austria, Austria"	"Austria"	"0.0"	"0.0204081632653"	"0.0544217687075"	"147"	"11.3076923077"	"Nature Genetics"	"Schramek D, Kotsinas A, Meixner A, Wada T, Elling U, Pospisilik JA, Neely GG, Zwick RH, Sigl V, Forni G, Serrano M, Gorgoulis VG, Penninger JM"	"Institute of Molecular Biotechnology of Austrian Academy of Sciences, Vienna, Austria."	"Most preneoplastic lesions are quiescent and do not progress to form overt tumors. It has been proposed that oncogenic stress activates the DNA damage response and the key tumor suppressor p53, which prohibits tumor growth. However, the molecular pathways by which cells sense a premalignant state in vivo are largely unknown. Here we report that tissue-specific inactivation of the stress signaling kinase MKK7 in KRas(G12D)-driven lung carcinomas and NeuT-driven mammary tumors markedly accelerates tumor onset and reduces overall survival. Mechanistically, MKK7 acts through the kinases JNK1 and JNK2, and this signaling pathway directly couples oncogenic and genotoxic stress to the stability of p53, which is required for cell cycle arrest and suppression of epithelial cancers. These results show that MKK7 functions as a major tumor suppressor in lung and mammary cancer in mouse and identify MKK7 as a vital molecular sensor to set a cellular anti-cancer barrier."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.0"	"0.0233333333333"	"0.06"	"300"	"8.57142857143"	"PLoS One"	"Chaudhari A, Braem A, Vleugels J, Martens JA, Naert I, Cardoso MV, Duyck J"	"Department of Prosthetic Dentistry, BIOMAT Research Group, K. U. Leuven, Leuven, Belgium."	"BACKGROUND: Topography and presence of bio-mimetic coatings are known to improve osseointegration. The objective of this study was to evaluate the bone regeneration potential of porous and osteogenic coatings. METHODOLOGY: Six-implants [Control (CTR); porous titanium coatings (T1, T2); thickened titanium (Ti) dioxide layer (TiO(2)); Amorphous Microporous Silica (AMS) and Bio-active Glass (BAG)] were implanted randomly in tibiae of 20-New Zealand white rabbits. The animals were sacrificed after 2 or 4 weeks. The samples were analyzed histologically and histomorphometrically. In the initial bone-free areas (bone regeneration areas (BRAs)), the bone area fraction (BAF) was evaluated in the whole cavity (500 microm, BAF-500), in the implant vicinity (100 microm, BAF-100) and further away (100-500 microm, BAF-400) from the implant. Bone-to-implant contact (BIC-BAA) was measured in the areas where the implants were installed in contact to the host bone (bone adaptation areas (BAAs)) to understand and compare the bone adaptation. Mixed models were used for statistical analysis. PRINCIPAL FINDINGS: After 2 weeks, the differences in BAF-500 for different surfaces were not significant (p>0.05). After 4 weeks, a higher BAF-500 was observed for BAG than CTR. BAF-100 for AMS was higher than BAG and BAF-400 for BAG was higher than CTR and AMS. For T1 and AMS, the bone regeneration was faster in the 100-microm compared to the 400-microm zone. BIC-BAA for AMS and BAG was lower after 4 than 2 weeks. After 4 weeks, BIC-BAA for BAG was lower than AMS and CTR. CONCLUSIONS: BAG is highly osteogenic at a distance from the implant. The porous titanium coatings didnt stimulate bone regeneration but allowed bone growth into the pores. Although AMS didnt stimulate higher bone response, it has a potential of faster bone growth in the vicinity compared to further away from the surface. BIC-BAA data were inconclusive to understand the bone adaptation."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.0"	"0.0507246376812"	"0.0797101449275"	"138"	"12.5454545455"	"PLoS Computational Biology"	"De Baets G, Reumers J, Delgado Blanco J, Dopazo J, Schymkowitz J, Rousseau F"	"VIB Switch Laboratory, VIB, Brussels, Belgium."	"We previously showed the existence of selective pressure against protein aggregation by the enrichment of aggregation-opposing gatekeeper residues at strategic places along the sequence of proteins. Here we analyzed the relationship between protein lifetime and protein aggregation by combining experimentally determined turnover rates, expression data, structural data and chaperone interaction data on a set of more than 500 proteins. We find that selective pressure on protein sequences against aggregation is not homogeneous but that short-living proteins on average have a higher aggregation propensity and fewer chaperone interactions than long-living proteins. We also find that short-living proteins are more often associated to deposition diseases. These findings suggest that the efficient degradation of high-turnover proteins is sufficient to preclude aggregation, but also that factors that inhibit proteasomal activity, such as physiological ageing, will primarily affect the aggregation of short-living proteins."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.0234741784038"	"0.0328638497653"	"0.0610328638498"	"213"	"8.72"	"Bioinformatics"	"De Smet R, Marchal K"	"Department of Plant Systems Biology, VIB, Ghent University, Technologiepark 927, Ghent, Belgium."	"MOTIVATION: Query-based biclustering techniques allow interrogating a gene expression compendium with a given gene or gene list. They do so by searching for genes in the compendium that have a profile close to the average expression profile of the genes in this query-list. As it can often not be guaranteed that the genes in a long query-list will all be mutually coexpressed, it is advisable to use each gene separately as a query. This approach, however, leaves the user with a tedious post-processing of partially redundant biclustering results. The fact that for each query-gene multiple parameter settings need to be tested in order to detect the most optimal bicluster size adds to the redundancy problem. RESULTS: To aid with this post-processing, we developed an ensemble approach to be used in combination with query-based biclustering. The method relies on a specifically designed consensus matrix in which the biclustering outcomes for multiple query-genes and for different possible parameter settings are merged in a statistically robust way. Clustering of this matrix results in distinct, non-redundant consensus biclusters that maximally reflect the information contained within the original query-based biclustering results. The usefulness of the developed approach is illustrated on a biological case study in Escherichia coli. Availability and implementation: Compiled Matlab code is available from 011/."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.0116618075802"	"0.0437317784257"	"0.110787172012"	"343"	"14.9130434783"	"BMC Bioinformatics"	"Dehouck Y, Kwasigroch JM, Gilis D, Rooman M"	"Bioinformatique genomique et structurale, Universite Libre de Bruxelles, Av, Fr, Roosevelt 50, CP165/61, 1050 Brussels, Belgium."	"BACKGROUND: The rational design of modified proteins with controlled stability is of extreme importance in a whole range of applications, notably in the biotechnological and environmental areas, where proteins are used for their catalytic or other functional activities. Future breakthroughs in medical research may also be expected from an improved understanding of the effect of naturally occurring disease-causing mutations on the molecular level. RESULTS: PoPMuSiC-2.1 is a web server that predicts the thermodynamic stability changes caused by single site mutations in proteins, using a linear combination of statistical potentials whose coefficients depend on the solvent accessibility of the mutated residue. PoPMuSiC presents good prediction performances (correlation coefficient of 0.8 between predicted and measured stability changes, in cross validation, after exclusion of 10% outliers). It is moreover very fast, allowing the prediction of the stability changes resulting from all possible mutations in a medium size protein in less than a minute. This unique functionality is user-friendly implemented in PoPMuSiC and is particularly easy to exploit. Another new functionality of our server concerns the estimation of the optimality of each amino acid in the sequence, with respect to the stability of the structure. It may be used to detect structural weaknesses, i.e. clusters of non-optimal residues, which represent particularly interesting sites for introducing targeted mutations. This sequence optimality data is also expected to have significant implications in the prediction and the analysis of particular structural or functional protein regions. To illustrate the interest of this new functionality, we apply it to a dataset of known catalytic sites, and show that a much larger than average concentration of structural weaknesses is detected, quantifying how these sites have been optimized for function rather than stability. CONCLUSION: The freely available PoPMuSiC-2.1 web server is highly useful for identifying very rapidly a list of possibly relevant mutations with the desired stability properties, on which subsequent experimental studies can be focused. It can also be used to detect sequence regions corresponding to structural weaknesses, which could be functionally important or structurally delicate regions, with obvious applications in rational protein design."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.0124481327801"	"0.0331950207469"	"0.0871369294606"	"241"	"11.4761904762"	"PLoS Computational Biology"	"Drion G, Massotte L, Sepulchre R, Seutin V"	"Laboratory of Pharmacology and GIGA Neurosciences, University of Liege, Liege, Belgium."	"Midbrain dopaminergic neurons are endowed with endogenous slow pacemaking properties. In recent years, many different groups have studied the basis for this phenomenon, often with conflicting conclusions. In particular, the role of a slowly-inactivating L-type calcium channel in the depolarizing phase between spikes is controversial, and the analysis of slow oscillatory potential (SOP) recordings during the blockade of sodium channels has led to conflicting conclusions. Based on a minimal model of a dopaminergic neuron, our analysis suggests that the same experimental protocol may lead to drastically different observations in almost identical neurons. For example, complete L-type calcium channel blockade eliminates spontaneous firing or has almost no effect in two neurons differing by less than 1% in their maximal sodium conductance. The same prediction can be reproduced in a state of the art detailed model of a dopaminergic neuron. Some of these predictions are confirmed experimentally using single-cell recordings in brain slices. Our minimal model exhibits SOPs when sodium channels are blocked, these SOPs being uncorrelated with the spiking activity, as has been shown experimentally. We also show that block of a specific conductance (in this case, the SK conductance) can have a different effect on these two oscillatory behaviors (pacemaking and SOPs), despite the fact that they have the same initiating mechanism. These results highlight the fact that computational approaches, besides their well known confirmatory and predictive interests in neurophysiology, may also be useful to resolve apparent discrepancies between experimental results."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.0110497237569"	"0.0220994475138"	"0.0552486187845"	"181"	"12.0666666667"	"Nature"	"Hannedouche S, Zhang J, Yi T, Shen W, Nguyen D, Pereira JP, Guerini D, Baumgarten BU, Roggo S, Wen B, Knochenmuss R, Noel S, Gessier F, Kelly LM, Vanek M, Laurent S, Preuss I, Miault C, Christen I, Karuna R, Li W, Koo DI, Suply T, Schmedt C, Peters EC, Falchetto R, Katopodis A, Spanka C, Roy MO, Detheux M, Chen YA, Schultz PG, Cho CY, Seuwen K, Cyster JG, Sailer AW"	"Euroscreen S.A., 6041 Gosselies, Belgium."	"Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7alpha,25-dihydroxycholesterol (also called 7alpha,25-OHC or 5-cholesten-3beta,7alpha,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7alpha,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7alpha,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7alpha,25-OHC is cholesterol 25-hydroxylase (CH25H). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.00943396226415"	"0.0188679245283"	"0.0518867924528"	"212"	"9.26086956522"	"BMC Bioinformatics"	"Iacucci E, Ojeda F, De Moor B, Moreau Y"	"SCD-ESAT, Department of Electrical Engineering, Katholieke Universiteit Leuven, Kasteelpark Arenberg 10, Leuven, 3001, Belgium."	"ABSTRACT: BACKGROUND: Regulation of cellular events is, often, initiated via extracellular signaling. Extracellular signaling occurs when a circulating ligand interacts with one or more membrane-bound receptors. Identification of receptor-ligand pairs is thus an important and specific form of PPI prediction. RESULTS: Given a set of disparate data sources (expression data, domain content, and phylogenetic profile) we seek to predict new receptor-ligand pairs. We create a combined kernel classifier and assess its performance with respect to the Database of Ligand-Receptor Partners (DLRP) golden standard as well as the method proposed by Gertz et al. Among our findings, we discover that our predictions for the tgfbeta family accurately reconstruct over 76% of the supported edges (0.76 recall and 0.67 precision) of the receptor-ligand bipartite graph defined by the DLRP golden standard. In addition, for the tgfbeta family, the combined kernel classifier is able to relatively improve upon the Gertz et al. work by a factor of approximately 1.5 when considering that our method has an F-measure of 0.71 while that of Gertz et al. has a value of 0.48. CONCLUSIONS: The prediction of receptor-ligand pairings is a difficult and complex task. We have demonstrated that using kernel learning on multiple data sources provides a stronger alternative to the existing method in solving this task."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.0131578947368"	"0.0328947368421"	"0.0460526315789"	"152"	"11.6923076923"	"Nature Genetics"	"Karim L, Takeda H, Lin L, Druet T, Arias JA, Baurain D, Cambisano N, Davis SR, Farnir F, Grisart B, Harris BL, Keehan MD, Littlejohn MD, Spelman RJ, Georges M, Coppieters W"	"Unit of Animal Genomics, Interdisciplinary Institute of Applied Genomics (GIGA-R) and Faculty of Veterinary Medicine, University of Liege (B34), Liege, Belgium."	"We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a  approximately 780-kb interval using a Hidden Markov Model-based approach that simultaneously exploits linkage and linkage disequilibrium. We re-sequenced the interval in six sires with known QTL genotype and identified 13 clustered candidate quantitative trait nucleotides (QTNs) out of >9,572 discovered variants. We eliminated five candidate QTNs by studying the phenotypic effect of a recombinant haplotype identified in a breed diversity panel. We show that the QTL influences fetal expression of seven of the nine genes mapping to the  approximately 780-kb interval. We further show that two of the eight candidate QTNs, mapping to the PLAG1-CHCHD7 intergenic region, influence bidirectional promoter strength and affect binding of nuclear factors. By performing expression QTL analyses, we identified a splice site variant in CHCHD7 and exploited this naturally occurring null allele to exclude CHCHD7 as single causative gene."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.00684931506849"	"0.00684931506849"	"0.0616438356164"	"146"	"11.2307692308"	"Immunity"	"Kool M, van Loo G, Waelput W, De Prijck S, Muskens F, Sze M, van Praet J, Branco-Madeira F, Janssens S, Reizis B, Elewaut D, Beyaert R, Hammad H, Lambrecht BN"	"Laboratory of Immunoregulation, Department of Pulmonary Medicine, University Hospital Gent, 9000 Gent, Belgium."	"Dendritic cells (DCs) regulate both immunity and tolerance. Here we have shown that the ubiquitin editing enzyme A20 (Tnfaip3) determines the activation threshold of DCs, via control of canonical NF-kappaB activation. Tnfaip3(fl/fl)Cd11c-cre(+) mice lacking A20 in DCs demonstrated spontaneous proliferation of conventional and double-negative T cells, their conversion to interferon-gamma (IFN-gamma)-producing effector cells, and expansion of plasma cells. They developed ds-DNA antibodies, nephritis, the antiphospholipid syndrome, and lymphosplenomegaly-features of systemic lupus erythematosus-and extramedullary hematopoiesis. A20-deficient DCs were resistant to apoptosis, caused by increased sensitivity to CD40L and RANKL prosurvival signals and upregulation of antiapoptotic proteins Bcl-2 and Bcl-x. They captured injected apoptotic cells more efficiently, resisted the inhibitory effects of apoptotic cells, and induced self-reactive effector lymphocytes. Because genetic polymorphisms in TNFAIP3 are associated with human autoimmune disorders, these findings identify A20-mediated control of DC activation as a crucial checkpoint in the development of systemic autoimmunity."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.00671140939597"	"0.0268456375839"	"0.0604026845638"	"149"	"11.4615384615"	"Immunity"	"Kool M, Willart MA, van Nimwegen M, Bergen I, Pouliot P, Virchow JC, Rogers N, Osorio F, Reis E Sousa C, Hammad H, Lambrecht BN"	"Laboratory of Immunoregulation and Mucosal Immunology, Department of Respiratory Diseases, University Ghent, Ghent 9000, Belgium."	"Although deposition of uric acid (UA) crystals is known as the cause of gout, it is unclear whether UA plays a role in other inflammatory diseases. We here have shown that UA is released in the airways of allergen-challenged asthmatic patients and mice, where it was necessary for mounting T helper 2 (Th2) cell immunity, airway eosinophilia, and bronchial hyperreactivity to inhaled harmless proteins and clinically relevant house dust mite allergen. Conversely, administration of UA crystals together with protein antigen was sufficient to promote Th2 cell immunity and features of asthma. The adjuvant effects of UA did not require the inflammasome (Nlrp3, Pycard) or the interleukin-1 (Myd88, IL-1r) axis. UA crystals promoted Th2 cell immunity by activating dendritic cells through spleen tyrosine kinase and PI3-kinase delta signaling. These findings provide further molecular insight into Th2 cell development and identify UA as an essential initiator and amplifier of allergic inflammation."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.0"	"0.0271739130435"	"0.0923913043478"	"184"	"14.1538461538"	"PLoS One"	"Menchon SA, Gartner A, Roman P, Dotti CG"	"Department of Molecular and Developmental Genetics, VIB and Center for Human Genetics, Katholieke Universiteit Leuven (KULeuven), Leuven, Belgium."	"Early in vitro and recent in vivo studies demonstrated that neuronal polarization occurs by the sequential formation of two oppositely located neurites. This early bipolar phenotype is of crucial relevance in brain organization, determining neuronal migration and brain layering. It is currently considered that the place of formation of the first neurite is dictated by extrinsic cues, through the induction of localized changes in membrane and cytoskeleton dynamics leading to deformation of the cells curvature followed by the growth of a cylindrical extension (neurite). It is unknown if the appearance of the second neurite at the opposite pole, thus the formation of a bipolar cell axis and capacity to undergo migration, is defined by the growth at the first place, therefore intrinsic, or requires external determinants. We addressed this question by using a mathematical model based on the induction of dynamic changes in one pole of a round cell. The model anticipates that a second area of growth can spontaneously form at the opposite pole. Hence, through mathematical modeling we prove that neuronal bipolar axis of growth can be due to an intrinsic mechanism."	""
-2	"europe_not_latin"	"Belgium"	"Belgium"	"0.00609756097561"	"0.00609756097561"	"0.103658536585"	"164"	"14.9090909091"	"Nature Genetics"	"Merveille AC, Davis EE, Becker-Heck A, Legendre M, Amirav I, Bataille G, Belmont J, Beydon N, Billen F, Clement A, Clercx C, Coste A, Crosbie R, de Blic J, Deleuze S, Duquesnoy P, Escalier D, Escudier E, Fliegauf M, Horvath J, Hill K, Jorissen M, Just J, Kispert A, Lathrop M, Loges NT, Marthin JK, Momozawa Y, Montantin G, Nielsen KG, Olbrich H, Papon JF, Rayet I, Roger G, Schmidts M, Tenreiro H, Towbin JA, Zelenika D, Zentgraf H, Georges M, Lequarre AS, Katsanis N, Omran H, Amselem S"	"Unit of Animal Genomics, Groupe Interdisciplinaire de Genomique Appliquee-Recherche (GIGA-R) and Faculty of Veterinary Medicine, University of Liege (B34), Liege, Belgium."	"Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.00404858299595"	"0.0121457489879"	"0.0404858299595"	"247"	"14.5294117647"	"PLoS One"	"Meurs L, Labuda L, Amoah AS, Mbow M, Ngoa UA, Boakye DA, Mboup S, Dieye TN, Mountford AP, Turner JD, Kremsner PG, Polman K, Yazdanbakhsh M, Adegnika AA"	"Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium."	"BACKGROUND: Schistosoma infection is thought to lead to down-regulation of the hosts immune response. This has been shown for adaptive immune responses, but the effect on innate immunity, that initiates and shapes the adaptive response, has not been extensively studied. In a first study to characterize these responses, we investigated the effect of Schistosoma haematobium infection on cytokine responses of Gabonese schoolchildren to a number of Toll-like receptor (TLR) ligands. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) were collected from S. haematobium-infected and uninfected schoolchildren from the rural area of Zile in Gabon. PBMCs were incubated for 24 h and 72 h with various TLR ligands, as well as schistosomal egg antigen (SEA) and adult worm antigen (AWA). Pro-inflammatory TNF-alpha and anti-inflammatory/regulatory IL-10 cytokine concentrations were determined in culture supernatants. PRINCIPAL FINDINGS: Infected children produced higher adaptive IL-10 responses than uninfected children against schistosomal antigens (72 h incubation). On the other hand, infected children had higher TNF-alpha responses than uninfected children and significantly higher TNF-alpha to IL-10 ratios in response to FSL-1 and Pam3, ligands of TLR2/6 and TLR2/1 respectively. A similar trend was observed for the TLR4 ligand LPS while Poly(I:C) (Mda5/TLR3 ligand) did not induce substantial cytokine responses (24 h incubation). CONCLUSIONS: This pilot study shows that Schistosoma-infected children develop a more pro-inflammatory TLR2-mediated response in the face of a more anti-inflammatory adaptive immune response. This suggests that S. haematobium infection does not suppress the hosts innate immune system in the context of single TLR ligation."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.0"	"0.0387096774194"	"0.0645161290323"	"155"	"12.0"	"Nature Genetics"	"Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, Amininejad L, Cleynen I, Colombel JF, de Rijk P, Dewit O, Finkel Y, Gassull MA, Goossens D, Laukens D, Lemann M, Libioulle C, OMorain C, Reenaers C, Rutgeerts P, Tysk C, Zelenika D, Lathrop M, Del-Favero J, Hugot JP, de Vos M, Franchimont D, Vermeire S, Louis E, Georges M"	"Unit of Animal Genomics, Groupe Interdisciplinaire de Genoproteomique Appliquee (GIGA-R) and Faculty of Veterinary Medicine, University of Liege (B34), Liege, Belgium."	"Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohns disease. However, common disease-associated SNPs explain at most  approximately 20% of the genetic variance for Crohns disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohns disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohns disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohns disease."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.012987012987"	"0.025974025974"	"0.0822510822511"	"231"	"13.6470588235"	"Molecular Biology and Evolution"	"Nevado B, Fazalova V, Backeljau T, Hanssens M, Verheyen E"	"Royal Belgian Institute of Natural Sciences, Brussels, Belgium."	"With an increasing number of reported cases of hybridization and introgression, interspecific gene flow between animals has recently become a widely accepted and broadly studied phenomenon. In this study, we examine patterns of hybridization and introgression in Ophthalmotilapia spp., a genus of cichlid fish from Lake Tanganyika, using mitochondrial and nuclear DNA from all four species in the genus and including specimens from over 800 km of shoreline. These four species have very different, partially overlapping distribution ranges, thus allowing us to study in detail patterns of gene flow between sympatric and allopatric populations of the different species. We show that a significant proportion of individuals of the lake-wide distributed O. nasuta carry mitochondrial and/or nuclear DNA typical of other Ophthalmotilapia species. Strikingly, all such individuals were found in populations living in sympatry with each of the other Ophthalmotilapia species, strongly suggesting that this pattern originated by repeated and independent episodes of genetic exchange in different parts of the lake, with unidirectional introgression occurring into O. nasuta. Our analysis rejects the hypotheses that unidirectional introgression is caused by natural selection favoring heterospecific DNA, by skewed abundances of Ophthalmotilapia species or by hybridization events occurring during a putative spatial expansion in O. nasuta. Instead, cytonuclear incompatibilities or asymmetric behavioral reproductive isolation seem to have driven repeated, unidirectional introgression of nuclear and mitochondrial DNA into O. nasuta in different parts of the lake."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.0"	"0.030701754386"	"0.0745614035088"	"228"	"12.0526315789"	"Glycobiology"	"Reynders E, Foulquier F, Annaert W, Matthijs G"	"Laboratory for Membrane Trafficking, Center for Human Genetics, KULeuven, Department for Molecular and Developmental Genetics (VIB), Leuven, Belgium."	"Protein glycosylation is one of the major biosynthetic functions occurring in the endoplasmic reticulum and Golgi compartments. It requires an amazing number of enzymes, chaperones, lectins and transporters whose actions delicately secure the fidelity of glycan structures. Over the past 30 years, glycobiologists hammered that glycan structures are not mere decorative elements but serve crucial cellular functions. This becomes dramatically illustrated by a group of mostly severe, inherited human disorders named congenital disorders of glycosylation (CDG). To date, many types of CDG have been defined genetically and most of the time the defects impair the biosynthesis, transfer and remodeling of N-glycans. Recently, the identification of the several types of CDG caused by deficiencies in the conserved oligomeric Golgi (COG) complex, a complex involved in vesicular Golgi trafficking, expanded the field of CDG but also brought novel insights in glycosylation. The molecular mechanisms underlying the complex pathway of N-glycosylation in the Golgi are far from understood. The availability of COG-deficient CDG patients and patients cells offered a new way to study how COG, and its different subunits, could influence the Golgi N-glycosylation machinery and localization. This review summarizes the recent findings on the implication of COG in Golgi glycosylation. It highlights the need for a dynamic, finely tuned balance between anterograde and retrograde trafficking for the correct localization of Golgi enzymes to assure the stepwise maturation of N-glycan chains."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.00591715976331"	"0.0236686390533"	"0.0769230769231"	"169"	"6.92"	"Bioinformatics"	"Thilakarathne PJ, Clement L, Lin D, Shkedy Z, Kasim A, Talloen W, Versele M, Verbeke G"	"Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Katholieke Universiteit Leuven, Kapucijnenvoer 35, Block D, box 7001, B3000 Leuven, Belgium."	"MOTIVATION: Phosphorylation by protein kinases is a central theme in biological systems. Aberrant protein kinase activity has been implicated in a variety of human diseases (e.g. cancer). Therefore, modulation of kinase activity represents an attractive therapeutic approach for the treatment of human illnesses. Thus, identification of signature peptides is crucial for protein kinase-targeting and can be achieved by using PamChip(R) microarray technology. we propose a flexible semi-parametric mixed model for analyzing PamChip(R) data. This approach enables the estimation of the phosphorylation rate (Velocity) as a function of time together with pointwise confidence intervals. RESULTS: Using a publicly available dataset (Versele et al., 2009), we show that our model is capable of adequately fitting the kinase activity profiles and provides velocity estimates over time. Moreover, it allows to test for differences in the velocity of kinase inhibition between responding and non-responding cell lines. This can be done at individual time point as well as for the entire velocity profile. CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
-"unk"	"europe_not_latin"	"Belgium"	"Belgium"	"0.00487804878049"	"0.00975609756098"	"0.107317073171"	"205"	"12.0588235294"	"PLoS One"	"Vandersteegen K, Mattheus W, Ceyssens PJ, Bilocq F, De Vos D, Pirnay JP, Noben JP, Merabishvili M, Lipinska U, Hermans K, Lavigne R"	"Division of Gene Technology, Katholieke Universiteit Leuven, Heverlee, Belgium."	"The increasing antibiotic resistance in bacterial populations requires alternatives for classical treatment of infectious diseases and therefore drives the renewed interest in phage therapy. Methicillin resistant Staphylococcus aureus (MRSA) is a major problem in health care settings and live-stock breeding across the world. This research aims at a thorough microbiological, genomic, and proteomic characterization of S. aureus phage ISP, required for therapeutic applications. Host range screening of a large batch of S. aureus isolates and subsequent fingerprint and DNA microarray analysis of the isolates revealed a substantial activity of ISP against 86% of the isolates, including relevant MRSA strains. From a phage therapy perspective, the infection parameters and the frequency of bacterial mutations conferring ISP resistance were determined. Further, ISP was proven to be stable in relevant in vivo conditions and subcutaneous as well as nasal and oral ISP administration to rabbits appeared to cause no adverse effects. ISP encodes 215 gene products on its 138,339 bp genome, 22 of which were confirmed as structural proteins using tandem electrospray ionization-mass spectrometry (ESI-MS/MS), and shares strong sequence homology with the Twort-like viruses. No toxic or virulence-associated proteins were observed. The microbiological and molecular characterization of ISP supports its application in a phage cocktail for therapeutic purposes."	""
-2	"europe_not_latin"	"Belgium, Belgium"	"Belgium"	"0.0131578947368"	"0.00657894736842"	"0.0921052631579"	"152"	"11.6923076923"	"Nature Genetics"	"Matmati M, Jacques P, Maelfait J, Verheugen E, Kool M, Sze M, Geboes L, Louagie E, Guire CM, Vereecke L, Chu Y, Boon L, Staelens S, Matthys P, Lambrecht BN, Schmidt-Supprian M, Pasparakis M, Elewaut D, Beyaert R, van Loo G"	"1] Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium. [2] Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. [3]."	"A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-kappaB signaling in response to specific proinflammatory stimuli in different cell types and has been suggested as a susceptibility gene for rheumatoid arthritis. To define the contribution of A20 to rheumatoid arthritis pathology, we generated myeloid-specific A20-deficient mice and show that specific ablation of Tnfaip3 in myeloid cells results in spontaneous development of a severe destructive polyarthritis with many features of rheumatoid arthritis. Myeloid-A20-deficient mice have high levels of inflammatory cytokines in their serum, consistent with a sustained NF-kappaB activation and higher TNF production by macrophages. Destructive polyarthritis in myeloid A20 knockout mice was TLR4-MyD88 and IL-6 dependent but was TNF independent. Myeloid A20 deficiency also promoted osteoclastogenesis in mice. Together, these observations indicate a critical and cell-specific function for A20 in the etiology of rheumatoid arthritis, supporting the idea of developing A20 modulatory drugs as cell-targeted therapies."	""
-3	"latin"	"Brasil"	"Brasil"	"0.012"	"0.024"	"0.052"	"250"	"14.7058823529"	"Molecular Biology and Evolution"	"Castelli EC, Mendes-Junior CT, Veiga-Castelli LC, Roger M, Moreau P, Donadi EA"	"Laboratorio de Genetica Molecular e Citogenetica, Departamento de Biologia Geral, Instituto de Ciencias Biologicas, Universidade Federal de Goias, Goiania, Brasil."	"HLA-G molecule plays an important role on immune response regulation and has been implicated on the inhibition of T and natural killer cell cytolytic function and inhibition of allogeneic T-cell proliferation. Due to its immune-modulator properties, the HLA-G gene expression has been associated with the outcome of allograft and of autoimmune, infectious, and malignant disorders. Several lines of evidence indicate that HLA-G polymorphisms at the 5-upstream regulatory region (5 URR) and 3-untranslated region (3 UTR) may influence the HLA-G expression levels. Because Brazilians represent one of the most heterogeneous populations in the world with the widest HLA-G coding region variability already detected among the studied populations, a high level of variability and haplotype diversity would be expected in Brazilians. On this basis, the 5 URR, coding, and 3 UTR variability were evaluated in a Brazilian series consisting of 100 healthy bone marrow donors, as well as the linkage disequilibrium pattern along the gene and the extended haplotypes encompassing several gene segment variations. The HLA-G locus seems to present six different HLA-G lineages showing functional variations mainly in nucleotides of the regulatory regions. Differences were observed at the 5 URR in positions that either coincide with or are close to transcription factor-binding sites and at the 3 UTR mainly in positions that have already been reported to influence HLA-G mRNA availability. We report several lines of evidence for balancing selection acting on the regulatory regions, which may indicate that these HLA-G lineages may be related to the differential HLA-G expression profiles."	""
-2	"latin"	"Brazil"	"Brazil"	"0.00344827586207"	"0.0275862068966"	"0.0724137931034"	"290"	"15.2631578947"	"PLoS Computational Biology"	"Andrade RF, Rocha-Neto IC, Santos LB, de Santana CN, Diniz MV, Lobao TP, Goes-Neto A, Pinho ST, El-Hani CN"	"Institute of Physics, Federal University of Bahia, Campus Universitario de Ondina, Salvador, Bahia, Brazil."	"This paper proposes a new method to identify communities in generally weighted complex networks and apply it to phylogenetic analysis. In this case, weights correspond to the similarity indexes among protein sequences, which can be used for network construction so that the network structure can be analyzed to recover phylogenetically useful information from its properties. The analyses discussed here are mainly based on the modular character of protein similarity networks, explored through the Newman-Girvan algorithm, with the help of the neighborhood matrix . The most relevant networks are found when the network topology changes abruptly revealing distinct modules related to the sets of organisms to which the proteins belong. Sound biological information can be retrieved by the computational routines used in the network approach, without using biological assumptions other than those incorporated by BLAST. Usually, all the main bacterial phyla and, in some cases, also some bacterial classes corresponded totally (100%) or to a great extent (>70%) to the modules. We checked for internal consistency in the obtained results, and we scored close to 84% of matches for community pertinence when comparisons between the results were performed. To illustrate how to use the network-based method, we employed data for enzymes involved in the chitin metabolic pathway that are present in more than 100 organisms from an original data set containing 1,695 organisms, downloaded from GenBank on May 19, 2007. A preliminary comparison between the outcomes of the network-based method and the results of methods based on Bayesian, distance, likelihood, and parsimony criteria suggests that the former is as reliable as these commonly used methods. We conclude that the network-based method can be used as a powerful tool for retrieving modularity information from weighted networks, which is useful for phylogenetic analysis."	""
-3	"latin"	"Brazil"	"Brazil"	"0.0165975103734"	"0.0124481327801"	"0.0663900414938"	"241"	"10.4782608696"	"PLoS One"	"Eggers S, Parks M, Grupe G, Reinhard KJ"	"Laboratorio de Antropologia Biologica, Departamento de Genetica e Biologia Evolutiva, Universidade de Sao Paulo, Instituto de Biociencias da USP, Sao Paulo, SP, Brazil."	"DURING THE EARLY HOLOCENE TWO MAIN PALEOAMERICAN CULTURES THRIVED IN BRAZIL: the Tradicao Nordeste in the semi-desertic Sertao and the Tradicao Itaparica in the high plains of the Planalto Central. Here we report on paleodietary singals of a Paleoamerican found in a third Brazilian ecological setting - a riverine shellmound, or sambaqui, located in the Atlantic forest. Most sambaquis are found along the coast. The peoples associated with them subsisted on marine resources. We are reporting a different situation from the oldest recorded riverine sambaqui, called Capelinha. Capelinha is a relatively small sambaqui established along a river 60 km from the Atlantic Ocean coast. It contained the well-preserved remains of a Paleoamerican known as Luzio dated to 9,945+/-235 years ago; the oldest sambaqui dweller so far. Luzios bones were remarkably well preserved and allowed for stable isotopic analysis of diet. Although artifacts found at this riverine site show connections with the Atlantic coast, we show that he represents a population that was dependent on inland resources as opposed to marine coastal resources. After comparing Luzios paleodietary data with that of other extant and prehistoric groups, we discuss where his group could have come from, if terrestrial diet persisted in riverine sambaquis and how Luzio fits within the discussion of the replacement of paleamerican by amerindian morphology. This study adds to the evidence that shows a greater complexity in the prehistory of the colonization of and the adaptations to the New World."	""
-2	"latin"	"Brazil"	"Brazil"	"0.0"	"0.0170068027211"	"0.0952380952381"	"294"	"10.8888888889"	"PLoS One"	"Higuchi MK, Fornari J, Del Ben CM, Graeff FG, Leite JP"	"Department of Neurosciences and Behavior, University of Sao Paulo School of Medicine at Ribeirao Preto, Ribeirao Preto, Brazil."	"BACKGROUND: High level piano performance requires complex integration of perceptual, motor, cognitive and emotive skills. Observations in psychology and neuroscience studies have suggested reciprocal inhibitory modulation of the cognition by emotion and emotion by cognition. However, it is still unclear how cognitive states may influence the pianistic performance. The aim of the present study is to verify the influence of cognitive and affective attention in the piano performances. METHODS AND FINDINGS: Nine pianists were instructed to play the same piece of music, firstly focusing only on cognitive aspects of musical structure (cognitive performances), and secondly, paying attention solely on affective aspects (affective performances). Audio files from pianistic performances were examined using a computational model that retrieves nine specific musical features (descriptors) - loudness, articulation, brightness, harmonic complexity, event detection, key clarity, mode detection, pulse clarity and repetition. In addition, the number of volunteers errors in the recording sessions was counted. Comments from pianists about their thoughts during performances were also evaluated. The analyses of audio files throughout musical descriptors indicated that the affective performances have more: agogics, legatos, pianos phrasing, and less perception of event density when compared to the cognitive ones. Error analysis demonstrated that volunteers misplayed more left hand notes in the cognitive performances than in the affective ones. Volunteers also played more wrong notes in affective than in cognitive performances. These results correspond to the volunteers comments that in the affective performances, the cognitive aspects of piano execution are inhibited, whereas in the cognitive performances, the expressiveness is inhibited. CONCLUSIONS: Therefore, the present results indicate that attention to the emotional aspects of performance enhances expressiveness, but constrains cognitive and motor skills in the piano execution. In contrast, attention to the cognitive aspects may constrain the expressivity and automatism of piano performances."	""
-3	"latin"	"Brazil"	"Brazil"	"0.00704225352113"	"0.0"	"0.0774647887324"	"142"	"10.9230769231"	"PLoS One"	"Icimoto MY, Barros NM, Ferreira JC, Marcondes MF, Andrade D, Machado MF, Juliano MA, Judice WA, Juliano L, Oliveira V"	"Departamento de Biofisica, Universidade Federal de Sao Paulo, Sao Paulo, Brazil."	"The proprotein convertases (PCs) are calcium-dependent proteases responsible for processing precursor proteins into their active forms in eukariotes. The PC1/3 is a pivotal enzyme of this family that participates in the proteolytic maturation of prohormones and neuropeptides inside the regulated secretory pathway. In this paper we demonstrate that mouse proprotein convertase 1/3 (mPC1/3) has a lag phase of activation by substrates that can be interpreted as a hysteretic behavior of the enzyme for their hydrolysis. This is an unprecedented observation in peptidases, but is frequent in regulatory enzymes with physiological relevance. The lag phase of mPC1/3 is dependent on substrate, calcium concentration and pH. This hysteretic behavior may have implications in the physiological processes in which PC1/3 participates and could be considered an additional control step in the peptide hormone maturation processes as for instance in the transformation of proinsulin to insulin."	""
-1	"latin"	"Brazil"	"Brazil"	"0.00709219858156"	"0.0212765957447"	"0.0709219858156"	"141"	"12.8181818182"	"Molecular Biology and Evolution"	"Kuhn GC, Kuttler H, Moreira-Filho O, Heslop-Harrison JS"	"Universidade Federal de Sao Carlos, Departamento de Genetica e Evolucao, Sao Carlos, SP, Brazil."	"Concerted evolution leading to homogenization of tandemly repeated DNA arrays is widespread and important for genome evolution. We investigated the range and nature of the process at chromosomal and array levels using the 1.688 tandem repeats of Drosophila melanogaster where large arrays are present in the heterochromatin of chromosomes 2, 3 and X, and short arrays are found in the euchromatin of the same chromosomes. Analysis of 326 euchromatic and heterochromatic repeats from 52 arrays, showed that the homogenization of 1.688 repeats occurred differentially for distinct genomic regions, from euchromatin to heterochromatin and from local arrays to chromosomes. We further found that most euchromatic arrays are either close to, or are within introns of, genes. The short size of euchromatic arrays (1-5 repeats) could be selectively constrained by their role as gene regulators, a situation similar to the so-called tuning knobs."	""
-3	"latin"	"Brazil"	"Brazil"	"0.0"	"0.0106382978723"	"0.0691489361702"	"188"	"6.35483870968"	"Bioinformatics"	"Santana F, Schober D, Medeiros Z, Freitas F, Schulz S"	"Informatics Center, Federal University of Pernambuco (CIn/UFPE), Recife, Brazil."	"MOTIVATION: Ontology-like domain knowledge is frequently published in a tabular format embedded in scientific publications. We explore the re-use of such tabular content in the process of building NTDO, an ontology of neglected tropical diseases (NTDs), where the representation of the interdependencies between hosts, pathogens and vectors plays a crucial role. RESULTS: As a proof of concept we analyzed a tabular compilation of knowledge about pathogens, vectors and geographic locations involved in the transmission of NTDs. After a thorough ontological analysis of the domain of interest, we formulated a comprehensive design pattern, rooted in the biomedical domain upper level ontology BioTop. This pattern was implemented in a VBA script which takes cell contents of an Excel spreadsheet and transforms them into OWL-DL. After minor manual post-processing, the correctness and completeness of the ontology was tested using pre-formulated competence questions as description logics (DL) queries. The expected results could be reproduced by the ontology. The proposed approach is recommended for optimizing the acquisition of ontological domain knowledge from tabular representations. Availability and implementation: Domain examples, source code and ontology are freely available on the web at CONTACT:"	""
-3	"latin"	"Brazil"	"Brazil"	"0.0134228187919"	"0.00671140939597"	"0.0939597315436"	"149"	"9.93333333333"	"PLoS One"	"Silva Vde A, Cargnelutti MT, Giesel GM, Palmieri LC, Monteiro RQ, Verli H, Lima LM"	"School of Pharmacy, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil."	"Thrombin is a serine proteinase that plays a fundamental role in coagulation. In this study, we address the effects of ligand site recognition by alpha-thrombin on conformation and energetics in solution. Active site occupation induces large changes in secondary structure content in thrombin as shown by circular dichroism. Thrombin-D-Phe-Pro-Arg-chloromethyl ketone (PPACK) exhibits enhanced equilibrium and kinetic stability compared to free thrombin, whose difference is rooted in the unfolding step. Small-angle X-ray scattering (SAXS) measurements in solution reveal an overall similarity in the molecular envelope of thrombin and thrombin-PPACK, which differs from the crystal structure of thrombin. Molecular dynamics simulations performed with thrombin lead to different conformations than the one observed in the crystal structure. These data shed light on the diversity of thrombin conformers not previously observed in crystal structures with distinguished catalytic and conformational behaviors, which might have direct implications on novel strategies to design direct thrombin inhibitors."	""
-3	"latin"	"Brazil"	"Brazil"	"0.00649350649351"	"0.025974025974"	"0.0584415584416"	"154"	"11.9230769231"	"Nature Genetics"	"Zenatti PP, Ribeiro D, Li W, Zuurbier L, Silva MC, Paganin M, Tritapoe J, Hixon JA, Silveira AB, Cardoso BA, Sarmento LM, Correia N, Toribio ML, Kobarg J, Horstmann M, Pieters R, Brandalise SR, Ferrando AA, Meijerink JP, Durum SK, Yunes JA, Barata JT"	"1] Laboratorio de Biologia Molecular, Centro Infantil Boldrini, Campinas, Sao Paulo, Brazil. [2]."	"Interleukin 7 (IL-7) and its receptor, formed by IL-7Ralpha (encoded by IL7R) and gammac, are essential for normal T-cell development and homeostasis. Here we show that IL7R is an oncogene mutated in T-cell acute lymphoblastic leukemia (T-ALL). We find that 9% of individuals with T-ALL have somatic gain-of-function IL7R exon 6 mutations. In most cases, these IL7R mutations introduce an unpaired cysteine in the extracellular juxtamembrane-transmembrane region and promote de novo formation of intermolecular disulfide bonds between mutant IL-7Ralpha subunits, thereby driving constitutive signaling via JAK1 and independently of IL-7, gammac or JAK3. IL7R mutations induce a gene expression profile partially resembling that provoked by IL-7 and are enriched in the T-ALL subgroup comprising TLX3 rearranged and HOXA deregulated cases. Notably, IL7R mutations promote cell transformation and tumor formation. Overall, our findings indicate that IL7R mutational activation is involved in human T-cell leukemogenesis, paving the way for therapeutic targeting of IL-7R-mediated signaling in T-ALL."	""
-2	"asian"	"Canada"	"Canada"	"0.0"	"0.0352112676056"	"0.0985915492958"	"142"	"8.52941176471"	"Database(Oxford)"	"Zhang J, Haider S, Baran J, Cros A, Guberman JM, Hsu J, Liang Y, Yao L, Kasprzyk A"	"Ontario Institute for Cancer Research, Toronto, Informatics and Biocomputing, Ontario M5G 0A3, Canada."	"BioMart is a freely available, open source, federated database system that provides a unified access to disparate, geographically distributed data sources. It is designed to be data agnostic and platform independent, such that existing databases can easily be incorporated into the BioMart framework. BioMart allows databases hosted on different servers to be presented seamlessly to users, facilitating collaborative projects between different research groups. BioMart contains several levels of query optimization to efficiently manage large data sets and offers a diverse selection of graphical user interfaces and application programming interfaces to ensure that queries can be performed in whatever manner is most convenient for the user. The software has now been adopted by a large number of different biological databases spanning a wide range of data types and providing a rich source of annotation available to bioinformaticians and biologists alike. Database URL:"	""
-1	"english"	"Canada"	"Canada"	"0.0126582278481"	"0.0295358649789"	"0.0801687763713"	"237"	"10.3913043478"	"Molecular Biology and Evolution"	"Abeysundera M, Field C, Gu H"	"Dept. of Mathematics and Statistics, Dalhousie University, Halifax, Canada, B3H 3J5."	"Whole-genome or multiple gene phylogenetic analysis is of interest since single gene analysis often results in poorly resolved trees. Here the use of spectral techniques for analyzing multi-gene data sets is explored. The protein sequences are treated as categorical time series, and a measure of similarity between a pair of sequences, the spectral covariance, is based on the common periodicity between these two sequences. Unlike the other methods, the spectral covariance method focuses on the relationship between the sites of genetic sequences. By properly scaling the dissimilarity measures derived from different genes between a pair of species, we can use the mean of these scaled dissimilarity measures as a summary statistic to measure the taxonomic distances across multiple genes.The methods are applied to three different data sets, one non-controversial and two with some dispute over the correct placement of the taxa in the tree. Trees are constructed using two distance based methods, BIONJ and FITCH. A variation of block bootstrap sampling method is used for inference. The methods are able to recover all major clades in the corresponding reference trees with moderate to high bootstrap support.Through simulations we show that the covariance based methods effectively capture phylogenetic signal even when structural information is not fully retained. Comparisons of simulation results with the bootstrap permutation results indicate that the covariance based methods are fairly robust under perturbations in sequence similarity but more sensitive to perturbations in structural similarity."	""
-1	"english"	"Canada"	"Canada"	"0.0108303249097"	"0.0252707581227"	"0.0794223826715"	"277"	"10.4814814815"	"BMC Bioinformatics"	"Amos-Binks A, Patulea C, Pitre S, Schoenrock A, Gui Y, Green JR, Golshani A, Dehne F"	"School of Computer Science, Carleton University, Ottawa, ON K1S5B6, Canada."	"BACKGROUND: While there are many methods for predicting protein-protein interaction, very few can determine the specific site of interaction on each protein. Characterization of the specific sequence regions mediating interaction (binding sites) is crucial for an understanding of cellular pathways. Experimental methods often report false binding sites due to experimental limitations, while computational methods tend to require data which is not available at the proteome-scale. Here we present PIPE-Sites, a novel method of protein specific binding site prediction based on pairs of re-occurring polypeptide sequences, which have been previously shown to accurately predict protein-protein interactions. PIPE-Sites operates at high specificity and requires only the sequences of query proteins and a database of known binary interactions with no binding site data, making it applicable to binding site prediction at the proteome-scale. RESULTS: PIPE-Sites was evaluated using a dataset of 265 yeast and 423 human interacting proteins pairs with experimentally-determined binding sites. We found that PIPE-Sites predictions were closer to the confirmed binding site than those of two existing binding site prediction methods based on domain-domain interactions, when applied to the same dataset. Finally, we applied PIPE-Sites to two datasets of 2347 yeast and 14,438 human novel interacting protein pairs predicted to interact with high confidence. An analysis of the predicted interaction sites revealed a number of protein subsequences which are highly re-occurring in binding sites and which may represent novel binding motifs. CONCLUSIONS: PIPE-Sites is an accurate method for predicting protein binding sites and is applicable to the proteome-scale. Thus, PIPE-Sites could be useful for exhaustive analysis of protein binding patterns in whole proteomes as well as discovery of novel binding motifs. PIPE-Sites is available online at"	""
-1	"english"	"Canada"	"Canada"	"0.0149253731343"	"0.0186567164179"	"0.0858208955224"	"268"	"12.8095238095"	"BMC Bioinformatics"	"Baghdadi L, Zamyadi M, Sled JG, Schneider JE, Bhattacharya S, Henkelman RM, Lerch JP"	"Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Canada."	"BACKGROUND: The motivation behind this paper is to aid the automatic phenotyping of mouse embryos, wherein multiple embryos embedded within a single tube were scanned using Magnetic Resonance Imaging (MRI). RESULTS: Our algorithm, a modified version of the simplex deformable model of Delingette, addresses various issues with deformable models including initialization and inability to adapt to boundary concavities. In addition, it proposes a novel technique for automatic collision detection of multiple objects which are being segmented simultaneously, hence avoiding major leaks into adjacent neighbouring structures. We address the initialization problem by introducing balloon forces which expand the initial spherical models close to the true boundaries of the embryos. This results in models which are less sensitive to initial minimum of two fold after each stage of deformation. To determine collision during segmentation, our unique collision detection algorithm finds the intersection between binary masks created from the deformed models after every few iterations of the deformation and modifies the segmentation parameters accordingly hence avoiding collision.We have segmented six tubes of three dimensional MR images of multiple mouse embryos using our modified deformable model algorithm. We have then validated the results of the our semi-automatic segmentation versus manual segmentation of the same embryos. Our Validation shows that except paws and tails we have been able to segment the mouse embryos with minor error. CONCLUSIONS: This paper describes our novel multiple object segmentation technique with collision detection using a modified deformable model algorithm. Further, it presents the results of segmenting magnetic resonance images of up to 32 mouse embryos stacked in one gel filled test tube and creating 32 individual masks."	""
-2	"english"	"Canada"	"Canada"	"0.0152284263959"	"0.0253807106599"	"0.0456852791878"	"197"	"11.6470588235"	"Blood"	"Balce DR, Li B, Allan ER, Rybicka JM, Krohn RM, Yates RM"	"Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada;"	"Alternatively activated macrophages, generated in a T-helper 2 environment, have demonstrated roles in wound repair and tissue remodeling in addition to being charged with immune tasks. Since the hydrolytic chemistries of the phagosomal lumen are central to many of these functions, we investigated their modification following alternative activation with interleukin-4 (IL-4) and IL-13. Most significantly, we found striking upregulation of the proteolytic levels within the phagosome of IL-4-activated macrophages. Two synergistic mechanisms were determined to underlie this upregulation. Firstly, IL-4-activated macrophages displayed increased expression of cathepsin S and L, providing greater proteolytic machinery to the phagosome despite unchanged rates of lysosomal contribution. Secondly, decreased phagosomal NADPH oxidase (NOX2) activity, at least partially resulting from decreased expression of the NOX2 subunit gp91(phox), resulted in a more reductive lumenal microenvironment, which in turn, enhanced activities of local cysteine cathepsins. Decreased NOX2 activity additionally increased the phagosomes ability to reduce disulfides, further enhancing the efficiency of the macrophage to degrade proteins containing disulfide bonds. Together, these changes initiated by IL-4, act synergistically to rapidly and dramatically enhance the macrophages ability to degrade phagocytosed protein, which we reason, better equips this cell for its roles in wound repair and tissue remodeling."	""
-2	"english"	"Canada"	"Canada"	"0.00446428571429"	"0.0178571428571"	"0.0625"	"224"	"8.37037037037"	"BMC Bioinformatics"	"Barrett N, Weber-Jahnke J"	"Department of Computer Science, University of Victoria, Victoria, Canada."	"BACKGROUND: Tokenization is an important component of language processing yet there is no widely accepted tokenization method for English texts, including biomedical texts. Other than rule based techniques, tokenization in the biomedical domain has been regarded as a classification task. Biomedical classifier-based tokenizers either split or join textual objects through classification to form tokens. The idiosyncratic nature of each biomedical tokenizers output complicates adoption and reuse. Furthermore, biomedical tokenizers generally lack guidance on how to apply an existing tokenizer to a new domain (subdomain). We identify and complete a novel tokenizer design pattern and suggest a systematic approach to tokenizer creation. We implement a tokenizer based on our design pattern that combines regular expressions and machine learning. Our machine learning approach differs from the previous split-join classification approaches. We evaluate our approach against three other tokenizers on the task of tokenizing biomedical text. RESULTS: Medpost and our adapted Viterbi tokenizer performed best with a 92.9% and 92.4% accuracy respectively. CONCLUSIONS: Our evaluation of our design pattern and guidelines supports our claim that the design pattern and guidelines are a viable approach to tokenizer construction (producing tokenizers matching leading custom-built tokenizers in a particular domain). Our evaluation also demonstrates that ambiguous tokenizations can be disambiguated through POS tagging. In doing so, POS tag sequences and training data have a significant impact on proper text tokenization."	""
-2	"english"	"Canada"	"Canada"	"0.0257731958763"	"0.0"	"0.0257731958763"	"194"	"14.9230769231"	"Blood"	"Bisaillon R, Wilhelm BT, Krosl J, Sauvageau G"	"Laboratory of Molecular Genetics of Stem Cells, Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada."	"The three-amino-acid loop extension (TALE) class homeodomain proteins MEIS1 and PKNOX1 (PREP1) share the ability to interact with PBX and HOX family members and bind similar DNA sequences, but appear to play opposing roles in tumor development. Elevated levels of MEIS1 accelerate development of HOX- and MLL-induced leukemias, and this pro-tumorigenic property has been associated with transcriptional activity of MEIS1. In contrast, reduction of PKNOX1 levels has been linked with cancer development despite the absence of an identifiable transactivating domain. In this report we show that a chimeric protein generated by fusion of the MEIS1 C-terminal region encompassing the transactivating domain with the full length PKNOX1 (PKNOX1-MC) acquired the ability to accelerate the onset of Hoxa9-induced leukemia in mouse bone marrow transduction/transplantation model. Gene expression profiling of primary bone marrow cells transduced with Hoxa9 + Meis1, or Hoxa9 + Pknox1-MC revealed perturbations in overlapping functional gene subsets implicated in DNA packaging, chromosome organization and in cell cycle regulation. Together, results presented in this report suggest that the C-terminal domain of MEIS1 confers to PKNOX1 an ectopic transactivating function that promotes leukemogenesis by regulating expression of genes involved in chromatin accessibility and cell cycle progression."	""
-2	"english"	"Canada"	"Canada"	"0.00985221674877"	"0.0295566502463"	"0.0738916256158"	"203"	"8.95652173913"	"Database(Oxford)"	"Bouffard M, Phillips MS, Brown AM, Marsh S, Tardif JC, van Rooij T"	"Beaulieu-Saucier Universite de Montreal Pharmacogenomics Centre, Universite de Montreal, Quebec, Canada."	"Data generation, driven by rapid advances in genomic technologies, is fast outpacing our analysis capabilities. Faced with this flood of data, more hardware and software resources are added to accommodate data sets whose structure has not specifically been designed for analysis. This leads to unnecessarily lengthy processing times and excessive data handling and storage costs. Current efforts to address this have centered on developing new indexing schemas and analysis algorithms, whereas the root of the problem lies in the format of the data itself. We have developed a new data structure for storing and analyzing genotype and phenotype data. By leveraging data normalization techniques, database management system capabilities and the use of a novel multi-table, multidimensional database structure we have eliminated the following: (i) unnecessarily large data set size due to high levels of redundancy, (ii) sequential access to these data sets and (iii) common bottlenecks in analysis times. The resulting novel data structure horizontally divides the data to circumvent traditional problems associated with the use of databases for very large genomic data sets. The resulting data set required 86% less disk space and performed analytical calculations 6248 times faster compared to a standard approach without any loss of information. Database URL:"	""
-2	"english"	"Canada"	"Canada"	"0.0"	"0.0350877192982"	"0.0438596491228"	"228"	"12.1052631579"	"Nature"	"Bouvignies G, Vallurupalli P, Hansen DF, Correia BE, Lange O, Bah A, Vernon RM, Dahlquist FW, Baker D, Kay LE"	"Department of Molecular Genetics, The University of Toronto, Toronto, Ontario M5S 1A8, Canada."	"Proteins are inherently plastic molecules, whose function often critically depends on excursions between different molecular conformations (conformers). However, a rigorous understanding of the relation between a proteins structure, dynamics and function remains elusive. This is because many of the conformers on its energy landscape are only transiently formed and marginally populated (less than a few per cent of the total number of molecules), so that they cannot be individually characterized by most biophysical tools. Here we study a lysozyme mutant from phage T4 that binds hydrophobic molecules and populates an excited state transiently (about 1 ms) to about 3% at 25  degrees C (ref. 5). We show that such binding occurs only via the ground state, and present the atomic-level model of the invisible, excited state obtained using a combined strategy of relaxation-dispersion NMR (ref. 6) and CS-Rosetta model building that rationalizes this observation. The model was tested using structure-based design calculations identifying point mutants predicted to stabilize the excited state relative to the ground state. In this way a pair of mutations were introduced, inverting the relative populations of the ground and excited states and altering function. Our results suggest a mechanism for the evolution of a proteins function by changing the delicate balance between the states on its energy landscape. More generally, they show that our approach can generate and validate models of excited protein states."	""
-2	"english"	"Canada"	"Canada"	"0.00523560209424"	"0.020942408377"	"0.0628272251309"	"191"	"11.3529411765"	"Glycobiology"	"Chaytor JL, Tokarew JM, Wu LK, Leclere M, Tam RY, Capicciotti CJ, Guolla L, von Moos E, Findlay CS, Allan DS, Ben RN"	"Department of Chemistry, DIorio Hall, 10 Marie Curie, University of Ottawa, Ottawa, ON, Canada, K1N 6N5."	"The ice recrystallization inhibition (IRI) activity of various mono- and disaccharides has been correlated to their ability to cryopreserve human cell lines at various concentrations. Cell viabilities after cryopreservation were compared to control experiments where cells were cryopreserved with dimethylsulfoxide (DMSO). The most potent inhibitors of ice recrystallization were 220 mM solutions of disaccharides however, the best cell viability was obtained when a 200 mM D-galactose solution was utilized. This solution was minimally cytotoxic at physiological temperature and effectively preserved cells during freeze-thaw. In fact, this carbohydrate was just as effective as a 5% DMSO solution. Further studies indicated that the cryoprotective benefit of D-galactose was a result of its internalization and it ability to mitigate osmotic stress, prevent intrcellular ice formation and/or inhibit ice recrystallization. This study supports the hypothesis that the ability of a cryoprotectant to inhibit ice recrystallization is an important property to enhance cell viability post freeze-thaw. This cryoprotective benefit is observed in three different human cell lines. Furthermore, we demonstrated that the ability of a potential cryoprotectant to inhibit ice recrystallation may be used as a predictor of its ability to preserve cells at sub-zero temperatures."	""
-2	"english"	"Canada"	"Canada"	"0.011396011396"	"0.017094017094"	"0.0797720797721"	"351"	"11.3225806452"	"BMC Bioinformatics"	"Chepelev LL, Riazanov A, Kouznetsov A, Low HS, Dumontier M, Baker CJ"	"Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Canada."	"ABSTRACT: BACKGROUND: The development of high-throughput experimentation has led to astronomical growth in biologically relevant lipids and lipid derivatives identified, screened, and deposited in numerous online databases. Unfortunately, efforts to annotate, classify, and analyze these chemical entities have largely remained in the hands of human curators using manual or semi-automated protocols, leaving many novel entities unclassified. Since chemical function is often closely linked to structure, accurate structure-based classification and annotation of chemical entities is imperative to understanding their functionality. RESULTS: As part of an exploratory study, we have investigated the utility of semantic web technologies in automated chemical classification and annotation of lipids. Our prototype framework consists of two components: an ontology and a set of federated web services that operate upon it. The formal lipid ontology we use here extends a part of the LiPrO ontology and draws on the lipid hierarchy in the LIPID MAPS database, as well as literature-derived knowledge. The federated semantic web services that operate upon this ontology are deployed within the Semantic Annotation, Discovery, and Integration (SADI) framework. Structure-based lipid classification is enacted by two core services. Firstly, a structural annotation service detects and enumerates relevant functional groups for a specified chemical structure. A second service reasons over lipid ontology class descriptions using the attributes obtained from the annotation service and identifies the appropriate lipid classification. We extend the utility of these core services by combining them with additional SADI services that retrieve associations between lipids and proteins and identify publications related to specified lipid types. We analyze the performance of SADI-enabled eicosanoid classification relative to the LIPID MAPS classification and reflect on the contribution of our integrative methodology in the context of high-throughput lipidomics. CONCLUSIONS: Our prototype framework is capable of accurate automated classification of lipids and facile integration of lipid class information with additional data obtained with SADI web services. The potential of programming-free integration of external web services through the SADI framework offers an opportunity for development of powerful novel applications in lipidomics. We conclude that semantic web technologies can provide an accurate and versatile means of classification and annotation of lipids."	""
-3	"asian"	"Canada"	"Canada"	"0.0137457044674"	"0.00343642611684"	"0.0996563573883"	"291"	"9.0"	"PLoS One"	"Choi M, Kim H, Qian H, Palepu A"	"Department of Medicine, University of British Columbia, Vancouver BC, Canada."	"OBJECTIVE: We compared the readmission rates and the pattern of readmission among patients discharged against medical advice (AMA) to control patients discharged with approval over a one-year follow-up period. METHODS: A retrospective matched-cohort study of 656 patients(328 were discharged AMA) who were followed for one year after their initial hospitalization at an urban university-affiliated teaching hospital in Vancouver, Canada that serves a population with high prevalence of addiction and psychiatric disorders. Multivariate conditional logistic regression was used to examine the independent association of discharge AMA on 14-day related diagnosis hospital readmission. We fit a multivariate conditional negative binomial regression model to examine the readmission frequency ratio between the AMA and non-AMA group. PRINCIPAL FINDINGS: AMA patients were more likely to be homeless (32.3% vs. 11%) and have co-morbid conditions such as psychiatric illnesses, injection drug use, HIV, hepatitis C and previous gastrointestinal bleeding. Patients discharged AMA were more likely to be readmitted: 25.6% vs. 3.4%, p<0.001 by day 14. The AMA group were more likely to be readmitted within 14 days with a related diagnosis than the non-AMA group (Adjusted Odds Ratio 12.0; 95% Confidence Interval [CI]: 3.7-38.9). Patients who left AMA were more likely to be readmitted multiple times at one year compared to the non-AMA group (adjusted frequency ratio 1.6; 95% CI: 1.3-2.0). There was also higher all-cause in-hospital mortality during the 12-month follow-up in the AMA group compared to non-AMA group (6.7% vs. 2.4%, p = 0.01). CONCLUSIONS: Patients discharged AMA were more likely to be homeless and have multiple co-morbid conditions. At one year follow-up, the AMA group had higher readmission rates, were predisposed to multiple readmissions and had a higher in-hospital mortality. Interventions to reduce discharges AMA in high-risk groups need to be developed and tested."	""
-2	"english"	"Canada"	"Canada"	"0.015625"	"0.03125"	"0.0546875"	"128"	"14.2222222222"	"Nature"	"Connors M, Wiegert P, Veillet C"	"Athabasca University, 1 University Drive, Athabasca, Alberta T9S 3A3, Canada."	"It was realized in 1772 that small bodies can stably share the same orbit as a planet if they remain near triangular points 60 degrees  ahead of or behind it in the orbit. Such Trojan asteroids have been found co-orbiting with Jupiter, Mars and Neptune. They have not hitherto been found associated with Earth, where the viewing geometry poses difficulties for their detection, although other kinds of co-orbital asteroid (horseshoe orbiters and quasi-satellites) have been observed. Here we report an archival search of infrared data for possible Earth Trojans, producing the candidate 2010 TK(7). We subsequently made optical observations which established that 2010 TK(7) is a Trojan companion of Earth, librating around the leading Lagrange triangular point, L(4). Its orbit is stable over at least ten thousand years."	""
-2	"english"	"Canada"	"Canada"	"0.0"	"0.0163043478261"	"0.0815217391304"	"184"	"10.8823529412"	"PLoS Computational Biology"	"Conway JM, Coombs D"	"Department of Mathematics and Institute of Applied Mathematics, University of British Columbia, Vancouver, British Columbia, Canada."	"Motivated by viral persistence in HIV+ patients on long-term anti-retroviral treatment (ART), we present a stochastic model of HIV viral dynamics in the blood stream. We consider the hypothesis that the residual viremia in patients on ART can be explained principally by the activation of cells latently infected by HIV before the initiation of ART and that viral blips (clinically-observed short periods of detectable viral load) represent large deviations from the mean. We model the system as a continuous-time, multi-type branching process. Deriving equations for the probability generating function we use a novel numerical approach to extract the probability distributions for latent reservoir sizes and viral loads. We find that latent reservoir extinction-time distributions underscore the importance of considering reservoir dynamics beyond simply the half-life. We calculate blip amplitudes and frequencies by computing complete viral load probability distributions, and study the duration of viral blips via direct numerical simulation. We find that our model qualitatively reproduces short small-amplitude blips detected in clinical studies of treated HIV infection. Stochastic models of this type provide insight into treatment-outcome variability that cannot be found from deterministic models."	""
-2	"english"	"Canada"	"Canada"	"0.0215517241379"	"0.0172413793103"	"0.0646551724138"	"232"	"13.6470588235"	"PLoS Computational Biology"	"Csuros M, Rogozin IB, Koonin EV"	"Department of Computer Science and Operations Research, Universite de Montreal, Montreal, Quebec, Canada."	"Protein-coding genes in eukaryotes are interrupted by introns, but intron densities widely differ between eukaryotic lineages. Vertebrates, some invertebrates and green plants have intron-rich genes, with 6-7 introns per kilobase of coding sequence, whereas most of the other eukaryotes have intron-poor genes. We reconstructed the history of intron gain and loss using a probabilistic Markov model (Markov Chain Monte Carlo, MCMC) on 245 orthologous genes from 99 genomes representing the three of the five supergroups of eukaryotes for which multiple genome sequences are available. Intron-rich ancestors are confidently reconstructed for each major group, with 53 to 74% of the human intron density inferred with 95% confidence for the Last Eukaryotic Common Ancestor (LECA). The results of the MCMC reconstruction are compared with the reconstructions obtained using Maximum Likelihood (ML) and Dollo parsimony methods. An excellent agreement between the MCMC and ML inferences is demonstrated whereas Dollo parsimony introduces a noticeable bias in the estimations, typically yielding lower ancestral intron densities than MCMC and ML. Evolution of eukaryotic genes was dominated by intron loss, with substantial gain only at the bases of several major branches including plants and animals. The highest intron density, 120 to 130% of the human value, is inferred for the last common ancestor of animals. The reconstruction shows that the entire line of descent from LECA to mammals was intron-rich, a state conducive to the evolution of alternative splicing."	""
-3	"english"	"Canada"	"Canada"	"0.0108695652174"	"0.0163043478261"	"0.0869565217391"	"184"	"12.2666666667"	"Molecular Biology and Evolution"	"Cutter AD, Moses AM"	"Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, ON, Canada."	"A contentious issue in molecular evolution and population genetics concerns the roles of recombination as a facilitator of natural selection and as a potential source of mutational input into genomes. The budding yeast Saccharomyces cerevisiae, in particular, has injected both insights and confusion into this topic, as an early system subject to genomic analysis with subsequent conflicting reports. Here, we revisit the role of recombination in mutation and selection with recent genome-wide maps of population polymorphism and recombination for S. cerevisiae. We confirm that recombination-associated mutation does not leave a genomic signature in yeast and conclude that a previously observed, enigmatic, negative recombination-divergence correlation is largely a consequence of weak selection and other genomic covariates. We also corroborate the presence of biased gene conversion from patterns of polymorphism. Moreover, we identify significant positive relations between recombination and population polymorphism at putatively neutrally evolving sites, independent of other factors and the genomic scale of interrogation. We conclude that widespread natural selection across the yeast genome has left its imprint on segregating genetic variation, but that this signature is much weaker than in Drosophila and Caenorhabditis."	""
-3	"english"	"Canada"	"Canada"	"0.0"	"0.0272108843537"	"0.0884353741497"	"147"	"11.3076923077"	"Nature"	"DCosta VM, King CE, Kalan L, Morar M, Sung WW, Schwarz C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB, Poinar HN, Wright GD"	"Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5."	"The discovery of antibiotics more than 70 years ago initiated a period of drug innovation and implementation in human and animal health and agriculture. These discoveries were tempered in all cases by the emergence of resistant microbes. This history has been interpreted to mean that antibiotic resistance in pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact that collections of microbes that predate the antibiotic era are highly susceptible to antibiotics. Here we report targeted metagenomic analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments and the identification of a highly diverse collection of genes encoding resistance to beta-lactam, tetracycline and glycopeptide antibiotics. Structure and function studies on the complete vancomycin resistance element VanA confirmed its similarity to modern variants. These results show conclusively that antibiotic resistance is a natural phenomenon that predates the modern selective pressure of clinical antibiotic use."	""
-1	"english"	"Canada"	"Canada"	"0.0298507462687"	"0.0"	"0.0597014925373"	"67"	"9.71428571429"	"Glycobiology"	"Deutschmann R, Boncheff AG, Daraban L, MacInnes JI, Monteiro MA"	"Department of Chemistry, University of Guelph, Guelph, Ontario, Canada."	"A sialylated oligosaccharide was identified in four representative strains of the Gram-negative swine pathogen, Actinobacillus suis. As characterized, the glycan consists of a free oligosaccharide with a N-acetyl-lactosamine-like backbone decorated with sialic acid, phosphoethanolamine (PEA) and O-acetyl units: 9-O-Ac-Neu5Ac-(2-->6)-beta-d-Galp-(1-->4)-beta-d-6-O-Ac-GlcpNAc-(1-->3)-[P EA-->6]-beta-d-Galp-(1-->3)-beta-d-GlcpNAc-(1-->2)-[9-O-Ac-Neu5Ac-(2-->6)] -beta-d-Galp-(1-->4)-beta-d-6-O-Ac-GlcpNAc-(1-->3)-[PEA-->6]-beta-d-Galp-( 1-->3)-d-GlcpNAc. The ubiquitous expression of this sialylated glycan suggests that this carbohydrate may play an important role in the survival of A. suis in the host."	""
-2	"english"	"Canada"	"Canada"	"0.00403225806452"	"0.0322580645161"	"0.0564516129032"	"248"	"11.8095238095"	"PLoS Computational Biology"	"Doyon N, Prescott SA, Castonguay A, Godin AG, Kroger H, De Koninck Y"	"Division of Cellular and Molecular Neuroscience, Centre de recherche Universite Laval Robert-Giffard, Quebec, Quebec, Canada."	"Chloride homeostasis is a critical determinant of the strength and robustness of inhibition mediated by GABA(A) receptors (GABA(A)Rs). The impact of changes in steady state Cl(-) gradient is relatively straightforward to understand, but how dynamic interplay between Cl(-) influx, diffusion, extrusion and interaction with other ion species affects synaptic signaling remains uncertain. Here we used electrodiffusion modeling to investigate the nonlinear interactions between these processes. Results demonstrate that diffusion is crucial for redistributing intracellular Cl(-) load on a fast time scale, whereas Cl(-)extrusion controls steady state levels. Interaction between diffusion and extrusion can result in a somato-dendritic Cl(-) gradient even when KCC2 is distributed uniformly across the cell. Reducing KCC2 activity led to decreased efficacy of GABA(A)R-mediated inhibition, but increasing GABA(A)R input failed to fully compensate for this form of disinhibition because of activity-dependent accumulation of Cl(-). Furthermore, if spiking persisted despite the presence of GABA(A)R input, Cl(-) accumulation became accelerated because of the large Cl(-) driving force that occurs during spikes. The resulting positive feedback loop caused catastrophic failure of inhibition. Simulations also revealed other feedback loops, such as competition between Cl(-) and pH regulation. Several model predictions were tested and confirmed by [Cl(-)](i) imaging experiments. Our study has thus uncovered how Cl(-) regulation depends on a multiplicity of dynamically interacting mechanisms. Furthermore, the model revealed that enhancing KCC2 activity beyond normal levels did not negatively impact firing frequency or cause overt extracellular K(-) accumulation, demonstrating that enhancing KCC2 activity is a valid strategy for therapeutic intervention."	""
-2	"english"	"Canada"	"Canada"	"0.0102040816327"	"0.0255102040816"	"0.0510204081633"	"196"	"15.1538461538"	"Glycobiology"	"El-Hawiet A, Kitova EN, Kitov PI, Eugenio L, Ng KK, Mulvey GL, Dingle TC, Szpacenko A, Armstrong GD, Klassen JS"	"Department of Chemistry, University of Alberta, Edmonton, AB, Canada."	"The binding of recombinant fragments of the C-terminal cell-binding domains of the two large exotoxins, toxin A (TcdA) and toxin B (TcdB), expressed by Clostridium difficile and a library consisting of the most abundant neutral and acidic human milk oligosaccharides (HMOs) was examined quantitatively at 25 degrees C and pH 7 using the direct electrospray ionization mass spectrometry (ES-MS) assay. The results of the ES-MS measurements indicate that both toxin fragments investigated, TcdB-B1 and TcdA-A2, which possess one and two carbohydrate binding sites, respectively, bind specifically to HMOs ranging in size from tri- to heptasaccharides. Notably, five of the HMOs tested bind to both toxins: Fuc(alpha1-2)Gal(beta1-4)Glc, Gal(beta1-3)GlcNAc(beta1-3)Gal(beta1-4)Glc, Fuc(alpha1-2)Gal(beta1-3)GlcNAc(beta1-3)Gal(beta1-4)Glc, Gal(beta1-3)[Fuc(alpha1-4)]GlcNAc(beta1-3)Gal(beta1-4)Glc and Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc. However, the binding of the HMOs is uniformly weak, with apparent affinities </=10(3 )M(-1). The results of molecular docking simulations, taken together with the experimental binding data, suggest that a disaccharide moiety (lactose or lactosamine) represents the core HMO recognition element for both toxin fragments. The results of a Verocytotoxicity neutralization assay reveal that HMOs do not significantly inhibit the cytotoxic effects of TcdA or TcdB. The absence of protection is attributed to the very weak intrinsic affinities that the toxins exhibit towards the HMOs."	""
-2	"english"	"Canada"	"Canada"	"0.0"	"0.0"	"0.075"	"40"	"5.71428571429"	"Immunity"	"Erdman LK, Kain KC"	"McLaughlin-Rotman Centre for Global Health, University Health Network, University of Toronto, Toronto, Ontario M5G 1L7, Canada."	"The innate immune response to malaria is a major determinant of disease severity and outcome. In this issue of Immunity, Sharma et al. (2011) provide evidence of a unique DNA sensing pathway that may contribute to immunopathology in plasmodial infections."	""
-2	"english"	"Canada"	"Canada"	"0.0045871559633"	"0.0045871559633"	"0.0779816513761"	"218"	"24.2222222222"	"Glycobiology"	"Evans DW, Muller-Loennies S, Brooks CL, Brade L, Kosma P, Brade H, Evans SV"	"Department of Biochemistry and Microbiology, University of Victoria, PO Box 3055 STN CSC, Victoria, BC, Canada V8P 3P6."	"The structure of the antigen-binding fragment from the monoclonal antibody S64-4 in complex with a pentasaccharide bisphosphate fragment from chlamydial lipopolysaccharide has been determined by x-ray diffraction to 2.6 A resolution. Like the well-characterized antibody S25-2, S64-4 displays a pocket formed by the residues of germline sequence corresponding to the heavy and light chain V gene segments that binds the terminal Kdo residue of the antigen; however, although S64-4 shares the same heavy chain V gene segment as S25-2, it has a different light chain V gene segment. The new light chain V gene segment codes for a combining site that displays greater affinity, different specificity, and allows a novel antigen conformation that brings a greater number of antigen residues into the combining site than possible in S25-2. Further, while antibodies in the S25-2 family use complementarity determining region (CDR) H3 to discriminate among antigens, S64-4 achieves its specificity via the new light chain V gene segment and resulting change in antigen conformation. These structures reveal an intriguing parallel strategy where two different combinations of germline-coded V gene segments can act as starting points for the generation of germline antibodies against chlamydial antigens and show how anti-carbohydrate antibodies can exploit the conformational flexibility of this class of antigens to achieve high affinity and specificity independently of CDR H3."	""
-2	"english"	"Canada"	"Canada"	"0.00617283950617"	"0.0185185185185"	"0.0555555555556"	"162"	"9.58823529412"	"PLoS Computational Biology"	"Fieldhouse RJ, Turgeon Z, White D, Merrill AR"	"Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada."	"Chelt, a cholera-like toxin from Vibrio cholerae, and Certhrax, an anthrax-like toxin from Bacillus cereus, are among six new bacterial protein toxins we identified and characterized using in silico and cell-based techniques. We also uncovered medically relevant toxins from Mycobacterium avium and Enterococcus faecalis. We found agriculturally relevant toxins in Photorhabdus luminescens and Vibrio splendidus. These toxins belong to the ADP-ribosyltransferase family that has conserved structure despite low sequence identity. Therefore, our search for new toxins combined fold recognition with rules for filtering sequences--including a primary sequence pattern--to reduce reliance on sequence identity and identify toxins using structure. We used computers to build models and analyzed each new toxin to understand features including: structure, secretion, cell entry, activation, NAD+ substrate binding, intracellular target binding and the reaction mechanism. We confirmed activity using a yeast growth test. In this era where an expanding protein structure library complements abundant protein sequence data--and we need high-throughput validation--our approach provides insight into the newest toxin ADP-ribosyltransferases."	""
-1	"english"	"Canada"	"Canada"	"0.00995024875622"	"0.00497512437811"	"0.089552238806"	"201"	"8.24"	"PLoS Computational Biology"	"French L, Pavlidis P"	"Bioinformatics Graduate Program, University of British Columbia, Vancouver, British Columbia, Canada."	"We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain connectome from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at"	""
-2	"english"	"Canada"	"Canada"	"0.0441176470588"	"0.0294117647059"	"0.0441176470588"	"68"	"7.77777777778"	"Nature Genetics"	"Galarneau G, Palmer CD, Sankaran VG, Orkin SH, Hirschhorn JN, Lettre G"	"Montreal Heart Institute, Montreal, Quebec, Canada."	"We used resequencing and genotyping in African Americans with sickle cell anemia (SCA) to characterize associations with fetal hemoglobin (HbF) levels at the BCL11A, HBS1L-MYB and beta-globin loci. Fine-mapping of HbF association signals at these loci confirmed seven SNPs with independent effects and increased the explained heritable variation in HbF levels from 38.6% to 49.5%. We also identified rare missense variants that causally implicate MYB in HbF production."	""
-2	"english"	"Canada"	"Canada"	"0.015625"	"0.0390625"	"0.0390625"	"128"	"14.2222222222"	"Glycobiology"	"Garron ML, Cygler M"	"Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6."	"Polysaccharide lyases (PLs) have been assigned to 21 families based on their sequences, with ~ 50 singletons awaiting further classification. For 19 of these families, the structure of at least one protein is known. In this review, we have analyzed the available structural information and show that presently known PL families belong to six general folds. Only two general catalytic mechanisms have been observed among these PLs: (1) metal-assisted neutralization of the acidic group of the sugar next to the cleaved bond, with, rather unusually, arginine or lysine playing the role of Bronsted base and (2) neutralization of the acidic group on the sugar by a close approach of an amino or acidic group forcing its protonation and Tyr or Tyr-His acting as the Bronsted base and acid."	""
-2	"english"	"Canada"	"Canada"	"0.004"	"0.024"	"0.088"	"250"	"8.29032258065"	"Bioinformatics"	"Gaston D, Susko E, Roger AJ"	"Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax, Canada, B3H 1X5."	"MOTIVATION: To understand the evolution of molecular function within protein families it is important to identify those amino acid residues responsible for functional divergence; i.e. those sites in a protein family that affect co-factor, protein, or substrate binding preferences; affinity; catalysis; flexibility; or folding. Type I functional divergence (FD) results from changes in conservation (evolutionary rate) at a site between protein subfamilies whereas type II FD occurs when there has been a shift in preferences for different amino acid chemical properties. A variety of methods have been developed for identifying both site types in protein sub-families, both from phylogenetic and information theoretic angles. However, evaluation of the performance of these methods has typically relied upon a handful of reasonably well characterized biological datasets (Chakrabarti et al, 2007; Capra and Singh, 2008) or analyses of a single biological example. While experimental validation of many truly functionally divergent sites (true positives) can be relatively straightforward, determining that particular sites do not contribute to functional divergence (i.e. false positives and true negatives) is much more difficult, resulting in noisy gold standard examples. RESULTS: We describe a novel, phylogeny-based functional divergence classifier, FunDi. Unlike previous approaches, FunDi uses a unified mixture model based approach to detect type I and type II FD. To assess FunDis overall classification performance relative to other methods, we introduce two methods for simulating functionally divergent datasets. We find that the FunDi method performs better than several other predictors over a wide variety of simulation conditions. AVAILABILITY: CONTACT: Andrew.Roger@Dal.Ca."	""
-1	"english"	"Canada"	"Canada"	"0.0"	"0.030534351145"	"0.0381679389313"	"131"	"5.6"	"Bioinformatics"	"Gillis J, Pavlidis P"	"Centre for High-Throughput Biology and Department of Psychiatry, 177 Michael Smith Laboratories, 2185 East Mall, University of British Columbia, Vancouver, BC V6T1Z4, Canada."	"MOTIVATION: Gene networks have been used widely in gene function prediction algorithms, many based on complex extensions of the guilt by association principle. We sought to provide a unified explanation for the performance of gene function prediction algorithms in exploiting network structure and thereby simplify future analysis. RESULTS: We use co-expression networks to show that most exploited network structure simply reconstructs the original correlation matrices from which the co-expression network was obtained. We show the same principle works in predicting gene function in protein interaction networks and that these methods perform comparably to much more sophisticated gene function prediction algorithms. AVAILABILITY AND IMPLEMENTATION: Data and algorithm implementation are fully described and available at Programs are provided in Matlab m-code. CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
-1	"english"	"Canada"	"Canada"	"0.00662251655629"	"0.0529801324503"	"0.0794701986755"	"151"	"10.0666666667"	"Nature Genetics"	"Girard SL, Gauthier J, Noreau A, Xiong L, Zhou S, Jouan L, Dionne-Laporte A, Spiegelman D, Henrion E, Diallo O, Thibodeau P, Bachand I, Bao JY, Tong AH, Lin CH, Millet B, Jaafari N, Joober R, Dion PA, Lok S, Krebs MO, Rouleau GA"	"Centre of Excellence in Neuromics of Universite de Montreal, Centre Hospitalier de lUniversite de Montreal Research Center, Montreal, Quebec, Canada."	"Schizophrenia is a severe psychiatric disorder that profoundly affects cognitive, behavioral and emotional processes. The wide spectrum of symptoms and clinical variability in schizophrenia suggest a complex genetic etiology, which is consistent with the numerous loci thus far identified by linkage, copy number variation and association studies. Although schizophrenia heritability may be as high as  approximately 80%, the genes responsible for much of this heritability remain to be identified. Here we sequenced the exomes of 14 schizophrenia probands and their parents. We identified 15 de novo mutations (DNMs) in eight probands, which is significantly more than expected considering the previously reported DNM rate. In addition, 4 of the 15 identified DNMs are nonsense mutations, which is more than what is expected by chance. Our study supports the notion that DNMs may account for some of the heritability reported for schizophrenia while providing a list of genes possibly involved in disease pathogenesis."	""
-3	"english"	"Canada"	"Canada"	"0.0230769230769"	"0.00769230769231"	"0.0692307692308"	"130"	"6.52380952381"	"Bioinformatics"	"Grant JR, Arantes AS, Liao X, Stothard P"	"Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G2P5, Canada."	"SUMMARY: NGS-SNP is a collection of command-line scripts for providing rich annotations for SNPs identified by the sequencing of whole genomes from any organism with reference sequences in Ensembl. Included among the annotations, several of which are not available from any existing SNP annotation tools, are the results of detailed comparisons with orthologous sequences. These comparisons can, for example, identify SNPs that affect conserved residues, or alter residues or genes linked to phenotypes in another species. AVAILABILITY: NGS-SNP is available both as a set of scripts and as a virtual machine. The virtual machine consists of a Linux operating system with all the NGS-SNP dependencies pre-installed. The source code and virtual machine are freely available for download at CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
-1	"english"	"Canada"	"Canada"	"0.0"	"0.0"	"0.0958904109589"	"146"	"9.73333333333"	"ANNUAL REVIEW OF PSYCHOLOGY"	"Grusec JE"	"Department of Psychology, University of Toronto, Toronto, Ontario M5S 3G3 Canada."	"Children learn moral values and social conventions through a process of socialization, much of which involves parenting. The process is bidirectional and involves a complex interplay between evolutionary predispositions and genetic and socio-cultural factors. Childrens perception of, or assignment of meaning to, parenting interventions is central. Socialization occurs in different domains marked by different aspects of the parent-child relationship and different underlying mechanisms. Each domain requires different parenting actions that must be matched to the domain in which the child is operating and that result in different outcomes for the child. The domains include protection, mutual reciprocity, control, guided learning, and group participation, and are assumed to be operative in all cultures. The review concludes that children need to experience their parents as supportive and understanding, that they need structure, and that they need to feel they have some degree of control over their own actions."	""
-2	"english"	"Canada"	"Canada"	"0.0125"	"0.025"	"0.05"	"160"	"7.7619047619"	"Database(Oxford)"	"Guberman JM, Ai J, Arnaiz O, Baran J, Blake A, Baldock R, Chelala C, Croft D, Cros A, Cutts RJ, Di Genova A, Forbes S, Fujisawa T, Gadaleta E, Goodstein DM, Gundem G, Haggarty B, Haider S, Hall M, Harris T, Haw R, Hu S, Hubbard S, Hsu J, Iyer V, Jones P, Katayama T, Kinsella R, Kong L, Lawson D, Liang Y, Lopez-Bigas N, Luo J, Lush M, Mason J, Moreews F, Ndegwa N, Oakley D, Perez-Llamas C, Primig M, Rivkin E, Rosanoff S, Shepherd R, Simon R, Skarnes B, Smedley D, Sperling L, Spooner W, Stevenson P, Stone K, Teague J, Wang J, Wang J, Whitty B, Wong DT, Wong-Erasmus M, Yao L, Youens-Clark K, Yung C, Zhang J, Kasprzyk A"	"Ontario Institute for Cancer Research, Toronto, M5G 0A3, Canada."	"BioMart Central Portal is a first of its kind, community-driven effort to provide unified access to dozens of biological databases spanning genomics, proteomics, model organisms, cancer data, ontology information and more. Anybody can contribute an independently maintained resource to the Central Portal, allowing it to be exposed to and shared with the research community, and linking it with the other resources in the portal. Users can take advantage of the common interface to quickly utilize different sources without learning a new system for each. The system also simplifies cross-database searches that might otherwise require several complicated steps. Several integrated tools streamline common tasks, such as converting between ID formats and retrieving sequences. The combination of a wide variety of databases, an easy-to-use interface, robust programmatic access and the array of tools make Central Portal a one-stop shop for biological data querying. Here, we describe the structure of Central Portal and show example queries to demonstrate its capabilities. Database URL:"	""
-2	"english"	"Canada"	"Canada"	"0.00694444444444"	"0.00694444444444"	"0.138888888889"	"144"	"13.0909090909"	"Nature Genetics"	"Guernsey DL, Matsuoka M, Jiang H, Evans S, Macgillivray C, Nightingale M, Perry S, Ferguson M, LeBlanc M, Paquette J, Patry L, Rideout AL, Thomas A, Orr A, McMaster CR, Michaud JL, Deal C, Langlois S, Superneau DW, Parkash S, Ludman M, Skidmore DL, Samuels ME"	"Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada."	"Meier-Gorlin syndrome is a rare autosomal recessive genetic condition whose primary clinical hallmarks include small stature, small external ears and small or absent patellae. Using marker-assisted mapping in multiple families from a founder population and traditional coding exon sequencing of positional candidate genes, we identified three different mutations in the gene encoding ORC4, a component of the eukaryotic origin recognition complex, in five individuals with Meier-Gorlin syndrome. In two such individuals that were negative for mutations in ORC4, we found potential mutations in ORC1 and CDT1, two other genes involved in origin recognition. ORC4 is well conserved in eukaryotes, and the yeast equivalent of the human ORC4 missense mutation was shown to be pathogenic in functional assays of cell growth. This is the first report, to our knowledge, of a germline mutation in any gene of the origin recognition complex in a vertebrate organism."	""
-2	"english"	"Canada"	"Canada"	"0.00687285223368"	"0.0240549828179"	"0.0756013745704"	"291"	"8.65714285714"	"Database(Oxford)"	"Harbi D, Kumar M, Harrison PM"	"Department of Biology, McGill University, Stewart Biology Building, 1205 Dr. Penfield Ave., Montreal, QC, H3A 1B1, Canada."	"Compositional bias (i.e. a skew in the composition of a biological sequence towards a subset of residue types) can occur at a wide variety of scales, from compositional biases of whole genomes, down to short regions in individual protein and gene-DNA sequences that are compositionally biased (CB regions). Such CB regions are made from a subset of residue types that are strewn along the length of the region in an irregular way. Here, we have developed the database server LPS-annotate, for the analysis of such CB regions, and protein disorder in protein sequences. The algorithm defines compositional bias through a thorough search for lowest-probability subsequences (LPSs) (i.e., the least likely sequence regions in terms of composition). Users can (i) initially annotate CB regions in input protein or nucleotide sequences of interest, and then (ii) query a database of greater than 1,500,000 pre-calculated protein-CB regions, for investigation of further functional hypotheses and inferences, about the specific CB regions that were discovered, and their protein disorder propensities. We demonstrate how a user can search for CB regions of similar compositional bias and protein disorder, with a worked example. We show that our annotations substantially augment the CB-region annotations that already exist in the UniProt database, with more comprehensive annotation of more complex CB regions. Our analysis indicates tens of thousands of CB regions that do not comprise globular domains or transmembrane domains, and that do not have a propensity to protein disorder, indicating a large cohort of protein-CB regions of biophysically uncharacterized types. This server and database is a conceptually novel addition to the workbench of tools now available to molecular biologists to generate hypotheses and inferences about the proteins that they are investigating. It can be accessed at Database URL:"	""
-2	"english"	"Canada"	"Canada"	"0.00534759358289"	"0.0267379679144"	"0.0909090909091"	"187"	"14.3846153846"	"PLoS One"	"Hetu S, Mercier C, Eugene F, Michon PE, Jackson PL"	"Centre Interdisciplinaire de Recherche en Readaptation et Integration Sociale, Quebec City, Quebec, Canada."	"The coupling process between observed and performed actions is thought to be performed by a fronto-parietal perception-action system including regions of the inferior frontal gyrus and the inferior parietal lobule. When investigating the influence of the movements characteristics on this process, most research on action observation has focused on only one particular variable even though the type of movements we observe can vary on several levels. By manipulating the visual perspective, transitivity and meaningfulness of observed movements in a functional magnetic resonance imaging study we aimed at investigating how the type of movements and the visual perspective can modulate brain activity during action observation in healthy individuals. Importantly, we used an active observation task where participants had to subsequently execute or imagine the observed movements. Our results show that the fronto-parietal regions of the perception action system were mostly recruited during the observation of meaningless actions while visual perspective had little influence on the activity within the perception-action system. Simultaneous investigation of several sources of modulation during active action observation is probably an approach that could lead to a greater ecological comprehension of this important sensorimotor process."	""
-3	"english"	"Canada"	"Canada"	"0.0"	"0.0143369175627"	"0.0716845878136"	"279"	"10.3333333333"	"PLoS Computational Biology"	"Holloway DM, Lopes FJ, da Fontoura Costa L, Travencolo BA, Golyandina N, Usevich K, Spirov AV"	"Mathematics Department, British Columbia Institute of Technology, Burnaby, British Columbia, Canada."	"Positional information in developing embryos is specified by spatial gradients of transcriptional regulators. One of the classic systems for studying this is the activation of the hunchback (hb) gene in early fruit fly (Drosophila) segmentation by the maternally-derived gradient of the Bicoid (Bcd) protein. Gene regulation is subject to intrinsic noise which can produce variable expression. This variability must be constrained in the highly reproducible and coordinated events of development. We identify means by which noise is controlled during gene expression by characterizing the dependence of hb mRNA and protein output noise on hb promoter structure and transcriptional dynamics. We use a stochastic model of the hb promoter in which the number and strength of Bcd and Hb (self-regulatory) binding sites can be varied. Model parameters are fit to data from WT embryos, the self-regulation mutant hb(14F), and lacZ reporter constructs using different portions of the hb promoter. We have corroborated model noise predictions experimentally. The results indicate that WT (self-regulatory) Hb output noise is predominantly dependent on the transcription and translation dynamics of its own expression, rather than on Bcd fluctuations. The constructs and mutant, which lack self-regulation, indicate that the multiple Bcd binding sites in the hb promoter (and their strengths) also play a role in buffering noise. The model is robust to the variation in Bcd binding site number across a number of fly species. This study identifies particular ways in which promoter structure and regulatory dynamics reduce hb output noise. Insofar as many of these are common features of genes (e.g. multiple regulatory sites, cooperativity, self-feedback), the current results contribute to the general understanding of the reproducibility and determinacy of spatial patterning in early development."	""
-3	"english"	"Canada"	"Canada"	"0.00409836065574"	"0.0122950819672"	"0.0286885245902"	"244"	"11.6666666667"	"Glycobiology"	"Hug I, Feldman MF"	"Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada."	"Bacteria generate and attach countless glycan structures to diverse macromolecules. Despite this diversity, the mechanisms of glycoconjugate biosynthesis are often surprisingly similar. The focus of this review is on the commonalities between lipopolysaccharide (LPS) and glycoprotein assembly pathways and their evolutionary relationship. Three steps that are essential for both pathways are completed by membrane proteins. These include the initiation of glycan assembly through the attachment of a first sugar residue onto the lipid carrier undecaprenyl pyrophosphate, the translocation across the plasma membrane and the final transfer onto proteins or lipid A-core. Two families of initiating enzymes have been described: the polyprenyl-P N-acetylhexosamine-1-P transferases and the polyprenyl-P hexosamine-1-P transferases, represented by Escherichia coli WecA and Salmonella enterica WbaP, respectively. Translocases are either Wzx-like flippases or adenosine triphosphate (ATP)-binding cassette transporters (ABC transporters). The latter can consist either of two polypeptides, Wzt and Wzm, or of a single polypeptide homolog to the Campylobacter jejuni PglK. Finally, there are two families of conjugating enzymes, the N-oligosaccharyltransferases (N-OTase), best represented by C. jejuni PglB, and the O-OTases, including Neisseria meningitidis PglL and the O antigen ligases involved in LPS biosynthesis. With the exception of the N-OTases, probably restricted to glycoprotein synthesis, members of all these transmembrane protein families can be involved in the synthesis of both glycoproteins and LPS. Because many translocation and conjugation enzymes display relaxed substrate specificity, these bacterial enzymes could be exploited in engineered living bacteria for customized glycoconjugate production, generating potential vaccines and therapeutics."	""
-2	"english"	"Canada"	"Canada"	"0.0"	"0.012"	"0.036"	"250"	"13.3157894737"	"Glycobiology"	"Ielmini MV, Feldman MF"	"Alberta Ingenuity Centre for Carbohydrate Science, Department of Biological Sciences, University of Alberta, Edmonton, Alta, Canada."	"Oligosaccharyltransferases (OTases) are responsible for the transfer of carbohydrates from lipid carriers to acceptor proteins and are present in all domains of life. In bacteria, the most studied member of this family is PglB from Campylobacter jejuni (PglB(Cj)). This enzyme is functional in Escherichia coli and, contrary to its eukaryotic counterparts, has the ability to transfer a variety of oligo- and polysaccharides to protein carriers in vivo. Phylogenetic analysis revealed that in the delta proteobacteria Desulfovibrio sp., the PglB homolog is more closely related to eukaryotic and archaeal OTases than to its Campylobacter counterparts. Genetic analysis revealed the presence of a putative operon that might encode all enzymes required for N-glycosylation in Desulfovibrio desulfuricans. D. desulfuricans PglB (PglB(Dd)) was cloned and successfully expressed in E. coli, and its activity was confirmed by transferring the C. jejuni heptasaccharide onto the model protein acceptor AcrA. In contrast to PglB(Cj), which adds two glycan chains to AcrA, a single oligosaccharide was attached to the protein by PglB(Dd). Site-directed mutagenesis of the five putative N-X-S/T glycosylation sites in AcrA and mass spectrometry analysis showed that PglB(Dd) does not recognize the conventional bacterial glycosylation sequon consisting of the sequence D/E-X(1)-N-X(2)-S/T (where X(1) and X(2) are any amino acid except proline), and instead used a different site for the attachment of the oligosaccharide than PglB(Cj.). Furthermore, PglB(Dd) exhibited relaxed glycan specificity, being able to transfer mono- and polysaccharides to AcrA. Our analysis constitutes the first characterization of an OTase from delta-proteobacteria involved in N-linked protein glycosylation."	""
-2	"english"	"Canada"	"Canada"	"0.0125"	"0.0375"	"0.125"	"80"	"4.52631578947"	"Bioinformatics"	"Ilie L, Ilie S, Mansouri Bigvand A"	"Department of Computer Science, University of Western Ontario, London, ON N6A 5B7 and Department of Mathematics, Ryerson University, Toronto, ON M5B 2K3, Canada."	"SUMMARY: Multiple spaced seeds represent the current state-of-the-art for similarity search in bioinformatics, with applications in various areas such as sequence alignment, read mapping, oligonucleotide design, etc. We present SpEED, a software program that computes highly sensitive multiple spaced seeds. SpEED can be several orders of magnitude faster and computes better seeds than the existing leading software programs. AVAILABILITY: The source code of SpEED is freely available at CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
-2	"english"	"Canada"	"Canada"	"0.0042194092827"	"0.0295358649789"	"0.0717299578059"	"237"	"13.9411764706"	"Nature"	"Isbell F, Calcagno V, Hector A, Connolly J, Harpole WS, Reich PB, Scherer-Lorenzen M, Schmid B, Tilman D, van Ruijven J, Weigelt A, Wilsey BJ, Zavaleta ES, Loreau M"	"Department of Biology, McGill University, Montreal, Quebec, H3A 1B1, Canada."	"Biodiversity is rapidly declining worldwide, and there is consensus that this can decrease ecosystem functioning and services. It remains unclear, though, whether few or many of the species in an ecosystem are needed to sustain the provisioning of ecosystem services. It has been hypothesized that most species would promote ecosystem services if many times, places, functions and environmental changes were considered; however, no previous study has considered all of these factors together. Here we show that 84% of the 147 grassland plant species studied in 17 biodiversity experiments promoted ecosystem functioning at least once. Different species promoted ecosystem functioning during different years, at different places, for different functions and under different environmental change scenarios. Furthermore, the species needed to provide one function during multiple years were not the same as those needed to provide multiple functions within one year. Our results indicate that even more species will be needed to maintain ecosystem functioning and services than previously suggested by studies that have either (1) considered only the number of species needed to promote one function under one set of environmental conditions, or (2) separately considered the importance of biodiversity for providing ecosystem functioning across multiple years, places, functions or environmental change scenarios. Therefore, although species may appear functionally redundant when one function is considered under one set of environmental conditions, many species are needed to maintain multiple functions at multiple times and places in a changing world."	""
-2	"english"	"Canada"	"Canada"	"0.0"	"0.0236686390533"	"0.0650887573964"	"169"	"11.6666666667"	"Database(Oxford)"	"Isserlin R, El-Badrawi RA, Bader GD"	"The Donnelly Centre, University of Toronto, ON, Canada."	"The Biomolecular Interaction Network Database (BIND) is a major source of curated biomolecular interactions, which has been unmaintained for the last few years, a trend which will eventually result in the loss of a significant amount of unique biomolecular interaction information, mostly as database identifiers become out of date. To help reverse this trend, we converted BIND to a standard format, Proteomics Standard Initiative-Molecular Interaction 2.5, starting from the last curated data release (from 2005) available in a custom XML format and made the core components (interactions and complexes) plus additional valuable curated information available for download ( Major work during the conversion process was required to update out of date molecule identifiers resulting in a more comprehensive conversion of BIND, by measures including number of species and interactor types covered, than what is currently accessible elsewhere. This work also highlights issues of data modeling, controlled vocabulary adoption and data cleaning that can serve as a general case study on the future compatibility of interaction databases. Database URL:"	""
-2	"english"	"Canada"	"Canada"	"0.00408163265306"	"0.00816326530612"	"0.0857142857143"	"245"	"10.7826086957"	"Bioinformatics"	"Jiline M, Matwin S, Turcotte M"	"School of Information Technology and Engineering, University of Ottawa, 800 King Edward Avenue, Ottawa, Ontario, K1N 6N5 Canada and Institute of Computer Science, Polish Academy of Sciences, Warsaw, Poland."	"MOTIVATION: Annotation Enrichment Analysis (AEA) is a widely used analytical approach to process data generated by high-throughput genomic and proteomic experiments such as gene expression microarrays. The analysis uncovers and summarizes discriminating background information (e.g. GO annotations) for sets of genes identified by experiments (e.g. a set of differentially expressed genes, a cluster). The discovered information is utilized by human experts to find biological interpretations of the experiments. However, AEA isolates and tests for overrepresentation only individual annotation terms or groups of similar terms and is limited in its ability to uncover complex phenomena involving relationship between multiple annotation terms from various knowledge bases. Also, AEA assumes that annotations describe the whole object of interest, which makes it difficult to apply it to sets of compound objects (e.g. sets of protein-protein interactions) and to sets of objects having an internal structure (e.g. protein complexes). RESULTS: We propose a novel logic-based Annotation Concept Synthesis and Enrichment Analysis (ACSEA) approach. ACSEA fuses inductive logic reasoning with statistical inference to uncover more complex phenomena captured by the experiments. We evaluate our approach on large-scale datasets from several microarray experiments and on a clustered genome-wide genetic interaction network using different biological knowledge bases. The discovered interpretations have lower P-values than the interpretations found by AEA, are highly integrative in nature, and include analysis of quantitative and structured information present in the knowledge bases. The results suggest that ACSEA can boost effectiveness of the processing of high-throughput experiments. CONTACT:"	""
-3	"english"	"Canada"	"Canada"	"0.0142857142857"	"0.0"	"0.0857142857143"	"70"	"14.2"	"Nature Genetics"	"Kahr WH, Hinckley J, Li L, Schwertz H, Christensen H, Rowley JW, Pluthero FG, Urban D, Fabbro S, Nixon B, Gadzinski R, Storck M, Wang K, Ryu GY, Jobe SM, Schutte BC, Moseley J, Loughran NB, Parkinson J, Weyrich AS, Di Paola J"	"Department of Paediatrics, University of Toronto, Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada."	"Next-generation RNA sequence analysis of platelets from an individual with autosomal recessive gray platelet syndrome (GPS, MIM139090) detected abnormal transcript reads, including intron retention, mapping to NBEAL2 (encoding neurobeachin-like 2). Genomic DNA sequencing confirmed mutations in NBEAL2 as the genetic cause of GPS. NBEAL2 encodes a protein containing a BEACH domain that is predicted to be involved in vesicular trafficking and may be critical for the development of platelet alpha-granules."	""
-3	"english"	"Canada"	"Canada"	"0.00813008130081"	"0.0284552845528"	"0.0528455284553"	"246"	"11.7619047619"	"Molecular Biology and Evolution"	"Kiethega GN, Turcotte M, Burger G"	"Department of Biochemistry, Universite de Montreal, Montreal, Canada."	"In the protist Diplonema papillatum (Diplonemea, Euglenozoa), mitochondrial genes are systematically fragmented with each nonoverlapping piece (module) encoded individually on a distinct circular chromosome. Gene modules are transcribed separately, and precursor transcripts are assembled to mature mRNA by a trans-splicing process of yet unknown mechanism. Expression of the cox1 gene that consists of nine modules, also involves RNA editing by which six uridines are added between Modules 4 and 5. Here, we investigate whether the unusual features of cox1 are shared by all Diplonemea and what the mechanism of trans-splicing might be. We examine three additional species representing both Diplonemea genera, namely D. papillatum described before, and D. ambulator, Diplonema sp.2, and Rhynchopus euleeides and discover that in all Diplonemea, the cox1 gene is discontinuous and split up into nine modules that each reside on a distinct chromosome. Positions of gene breakpoints vary by up to two nucleotides. Further, all taxa have six nonencoded uridines inserted in cox1 mRNA at exactly the same position as D. papillatum. In silico searches do not detect signatures of introns known to engage in trans-splicing, in particular Group I, Group II, spliceosomal, and transfer RNA introns. Nor did we find statistically significant reverse-complementary motifs between adjacent modules and their flanking regions, or residues conserved within or across species. This provides compelling evidence that trans-splicing in Diplonemea mitochondria does not rely on sequence elements in cis but rather proceeds by a mechanism employing matchmaking trans factors, such as RNAs or proteins."	""
-3	"english"	"Canada"	"Canada"	"0.0243902439024"	"0.0162601626016"	"0.113821138211"	"123"	"9.53846153846"	"Blood"	"Kingdom JC, Drewlo S"	"Maternal-Fetal Medicine Division, Department of Obstetrics & Gynaecology, Mount Sinai Hospital, Toronto, ON, Canada;"	"Randomized control trials demonstrate beneficial effects of heparin in high-risk pregnancies to prevent pre-eclampsia and intrauterine growth restriction. However the lack of placental pathology data in these trials challenges the assumption that heparin is a placental anticoagulant. Recent data demonstrates that placental infarction is more likely to be associated with abnormalities in development of the placenta, characterized by poor maternal perfusion and an abnormal villous trophoblast compartment in contact with maternal blood, than with maternal thrombophilia. At-risk pregnancies may therefore be predicted by non-invasive prenatal testing of placental function in mid-pregnancy. Heparin has diverse cellular functions that include direct actions on trophoblast. Dissecting the non-anti-coagulant actions of heparin may reveal novel and safer therapeutic targets to prevent the major placental complications of pregnancy."	""
-2	"english"	"Canada"	"Canada"	"0.0"	"0.0268456375839"	"0.0402684563758"	"149"	"16.5555555556"	"Immunity"	"Kosan C, Saba I, Godmann M, Herold S, Herkert B, Eilers M, Moroy T"	"Institut de recherches cliniques de Montreal (IRCM), Montreal, Quebec H2W 1R7, Canada."	"B cell development requires the coordinated action of transcription factors and cytokines, in particular interleukin-7 (IL-7). We report that mice lacking the POZ (Poxvirus and zinc finger) domain of the transcription factor Miz-1 (Zbtb17(DeltaPOZ/DeltaPOZ)) almost entirely lacked follicular B cells, as shown by the fact that their progenitors failed to activate the Jak-Stat5 pathway and to upregulate the antiapoptotic gene Bcl2 upon IL-7 stimulation. We show that Miz-1 exerted a dual role in the interleukin-7 receptor (IL-7R) pathway by directly repressing the Janus kinase (Jak) inhibitor suppressor of cytokine signaling 1 (Socs1) and by activating Bcl2 expression. Zbtb17(DeltaPOZ/DeltaPOZ) (Miz-1-deficient) B cell progenitors had low expression of early B cell genes as transcription factor 3 (Tcf3) and early B cell factor 1 (Ebf1) and showed a propensity for apoptosis. Only the combined re-expression of Bcl2 and Ebf1 could reconstitute the ability of Miz-1-deficient precursors to develop into CD19(+) B cells."	""
-2	"english"	"Canada"	"Canada"	"0.00354609929078"	"0.0390070921986"	"0.0992907801418"	"282"	"12.2608695652"	"Molecular Biology and Evolution"	"Lartillot N, Poujol R"	"Departement de Biochimie, Centre Robert Cedergren, Universite de Montreal, Montreal, Quebec, Canada."	"The comparative approach is routinely used to test for possible correlations between phenotypic or life-history traits. To correct for phylogenetic inertia, the method of independent contrasts assumes that continuous characters evolve along the phylogeny according to a multivariate Brownian process. Brownian diffusion processes have also been used to describe time variations of the parameters of the substitution process, such as the rate of substitution or the ratio of synonymous to nonsynonymous substitutions. Here, we develop a probabilistic framework for testing the coupling between continuous characters and parameters of the molecular substitution process. Rates of substitution and continuous characters are jointly modeled as a multivariate Brownian diffusion process of unknown covariance matrix. The covariance matrix, the divergence times and the phylogenetic variations of substitution rates and continuous characters are all jointly estimated in a Bayesian Monte Carlo framework, imposing on the covariance matrix a prior conjugate to the Brownian process so as to achieve a greater computational efficiency. The coupling between rates and phenotypes is assessed by measuring the posterior probability of positive or negative covariances, whereas divergence dates and phenotypic variations are marginally reconstructed in the context of the joint analysis. As an illustration, we apply the model to a set of 410 mammalian cytochrome b sequences. We observe a negative correlation between the rate of substitution and mass and longevity, which was previously observed. We also find a positive correlation between omega = dN/dS and mass and longevity, which we interpret as an indirect effect of variations of effective population size, thus in partial agreement with the nearly neutral theory. The method can easily be extended to any parameter of the substitution process and to any continuous phenotypic or environmental character."	""
-2	"english"	"Canada"	"Canada"	"0.0151515151515"	"0.0151515151515"	"0.0656565656566"	"198"	"13.2"	"Blood"	"Madureira PA, Surette AP, Phipps KD, Taboski MA, Miller VA, Waisman DM"	"Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, NS, Canada."	"The vascular endothelial cells line the inner surface of blood vessels and function to maintain blood fluidity by producing the protease plasmin that removes blood clots from the vasculature, a process called fibrinolysis. Plasminogen receptors play a central role in the regulation of plasmin activity. The protein complex annexin A2 heterotetramer (AIIt) is an important plasminogen receptor at the surface of the endothelial cell. AIIt is composed of two molecules of annexin A2 (ANXA2) bound together by a dimer of the protein S100A10. Recent work performed by our laboratory allowed us to clarify the specific roles played by ANXA2 and S100A10 subunits within the AIIt complex, which has been the subject of debate for many years. The ANXA2 subunit of AIIt functions to stabilize and anchor S100A10 to the plasma membrane, whereas the S100A10 subunit initiates the fibrinolytic cascade by co-localizing with the urokinase type plasminogen activator and receptor (uPA/uPAR) complex and also providing a common binding site for both tissue-type plasminogen activator (tPA) and plasminogen via its C-terminal lysine residue. The AIIt mediated co-localization of the plasminogen activators with plasminogen results in the rapid and localized generation of plasmin to the endothelial cell surface thereby regulating fibrinolysis."	""
-2	"english"	"Canada"	"Canada"	"0.0133333333333"	"0.00666666666667"	"0.08"	"150"	"8.82352941176"	"ANNUAL REVIEW OF PSYCHOLOGY"	"Mar RA"	"Department of Psychology, York University, Toronto M3J 1P3 Canada."	"A great deal of research exists on the neural basis of theory-of-mind (ToM) or mentalizing. Qualitative reviews on this topic have identified a mentalizing network composed of the medial prefrontal cortex, posterior cingulate/precuneus, and bilateral temporal parietal junction. These conclusions, however, are not based on a quantitative and systematic approach. The current review presents a quantitative meta-analysis of neuroimaging studies pertaining to ToM, using the activation-likelihood estimation (ALE) approach. Separate ALE meta-analyses are presented for story-based and nonstory-based studies of ToM. The conjunction of these two meta-analyses reveals a core mentalizing network that includes areas not typically noted by previous reviews. A third ALE meta-analysis was conducted with respect to story comprehension in order to examine the relation between ToM and stories. Story processing overlapped with many regions of the core mentalizing network, and these shared regions bear some resemblance to a network implicated by a number of other processes."	""
-1	"english"	"Canada"	"Canada"	"0.0126582278481"	"0.0126582278481"	"0.0696202531646"	"158"	"12.1538461538"	"Molecular Biology and Evolution"	"Mayrose I, Otto SP"	"Department of Zoology, University of British Columbia, Vancouver, BC, Canada."	"Rate heterogeneity within groups of organisms is known to exist even when closely related taxa are examined. A wide variety of phylogenetic and dating methods have been developed that aim either to test for the existence of rate variation or to correct for its bias. However, none of the existing methods track the evolution of features that account for observed rate heterogeneity. Here, we present a likelihood model that assumes that rate variation is caused, in part, by species intrinsic characteristics, such as a particular life-history trait, morphological feature, or habitat association. The model combines models of sequence and character state evolution such that rates of sequence change depend on the character state of a lineage at each point in time. We test, using simulations, the power and accuracy of the model to determine whether rates of molecular evolution depend on a particular character state and demonstrate its utility using an empirical example with halophilic and freshwater daphniids."	""
-3	"english"	"Canada"	"Canada"	"0.00383141762452"	"0.0229885057471"	"0.0651340996169"	"261"	"11.347826087"	"PLoS Computational Biology"	"McPherson A, Hormozdiari F, Zayed A, Giuliany R, Ha G, Sun MG, Griffith M, Heravi Moussavi A, Senz J, Melnyk N, Pacheco M, Marra MA, Hirst M, Nielsen TO, Sahinalp SC, Huntsman D, Shah SP"	"Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada."	"Gene fusions created by somatic genomic rearrangements are known to play an important role in the onset and development of some cancers, such as lymphomas and sarcomas. RNA-Seq (whole transcriptome shotgun sequencing) is proving to be a useful tool for the discovery of novel gene fusions in cancer transcriptomes. However, algorithmic methods for the discovery of gene fusions using RNA-Seq data remain underdeveloped. We have developed deFuse, a novel computational method for fusion discovery in tumor RNA-Seq data. Unlike existing methods that use only unique best-hit alignments and consider only fusion boundaries at the ends of known exons, deFuse considers all alignments and all possible locations for fusion boundaries. As a result, deFuse is able to identify fusion sequences with demonstrably better sensitivity than previous approaches. To increase the specificity of our approach, we curated a list of 60 true positive and 61 true negative fusion sequences (as confirmed by RT-PCR), and have trained an adaboost classifier on 11 novel features of the sequence data. The resulting classifier has an estimated value of 0.91 for the area under the ROC curve. We have used deFuse to discover gene fusions in 40 ovarian tumor samples, one ovarian cancer cell line, and three sarcoma samples. We report herein the first gene fusions discovered in ovarian cancer. We conclude that gene fusions are not infrequent events in ovarian cancer and that these events have the potential to substantially alter the expression patterns of the genes involved; gene fusions should therefore be considered in efforts to comprehensively characterize the mutational profiles of ovarian cancer transcriptomes."	""
-1	"english"	"Canada"	"Canada"	"0.010101010101"	"0.020202020202"	"0.040404040404"	"198"	"13.2666666667"	"Blood"	"Merindol N, Champagne MA, Duval M, Soudeyns H"	"Unite dimmunopathologie virale, CHU Sainte-Justine, Montreal, QC, Canada;"	"Recipients of umbilical cord blood (UCB) transplantation (UCBT) face a high risk of morbidity and mortality related to opportunistic infections (OI) and leukemic relapse. To understand the molecular basis of these UCBT-related complications, the characteristics of UCB-derived antigen-specific CD8(+) T cells were examined in a group of pediatric UCBT recipients. As compared with the UCB graft inoculum and the late post-UCBT period (12-36 months), declining clonal diversity of UCB-derived CD8(+) T cells specific for the Melan-A(26-35) A27L peptide and high frequencies of PD-1-expressing CD8(+) T cells were observed in the first 3 months post-UCBT, a period during which OI are most frequent. The CD8(+) T cell compartment predominantly comprised CD45RA(+) CCR7(-) terminally-differentiated effector-memory T cells until 6 months post-UCBT, at which time the polyfunctionality of antigen-specific CD8(+) T cells was re-established. Finally, the frequency of PD-1(+) CD8(+) T cells was significantly higher in subjects who subsequently experienced leukemic relapse. This study informs the biological properties of UCB-derived CD8(+) T cells and provides a rationale for the characteristics of UCBT in terms of immune reconstitution and OI. These results also suggest that elevated frequency of PD-1(+) CD8(+) T cells could be associated with leukemic relapse in pediatric UCBT recipients."	""
-3	"english"	"Canada"	"Canada"	"0.0"	"0.0604982206406"	"0.113879003559"	"281"	"10.4074074074"	"PLoS Computational Biology"	"Michaut M, Baryshnikova A, Costanzo M, Myers CL, Andrews BJ, Boone C, Bader GD"	"The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada."	"If perturbing two genes together has a stronger or weaker effect than expected, they are said to genetically interact. Genetic interactions are important because they help map gene function, and functionally related genes have similar genetic interaction patterns. Mapping quantitative (positive and negative) genetic interactions on a global scale has recently become possible. This data clearly shows groups of genes connected by predominantly positive or negative interactions, termed monochromatic groups. These groups often correspond to functional modules, like biological processes or complexes, or connections between modules. However it is not yet known how these patterns globally relate to known functional modules. Here we systematically study the monochromatic nature of known biological processes using the largest quantitative genetic interaction data set available, which includes fitness measurements for  approximately 5.4 million gene pairs in the yeast Saccharomyces cerevisiae. We find that only 10% of biological processes, as defined by Gene Ontology annotations, and less than 1% of inter-process connections are monochromatic. Further, we show that protein complexes are responsible for a surprisingly large fraction of these patterns. This suggests that complexes play a central role in shaping the monochromatic landscape of biological processes. Altogether this work shows that both positive and negative monochromatic patterns are found in known biological processes and in their connections and that protein complexes play an important role in these patterns. The monochromatic processes, complexes and connections we find chart a hierarchical and modular map of sensitive and redundant biological systems in the yeast cell that will be useful for gene function prediction and comparison across phenotypes and organisms. Furthermore the analysis methods we develop are applicable to other species for which genetic interactions will progressively become more available."	""
-3	"english"	"Canada"	"Canada"	"0.0"	"0.0373134328358"	"0.0970149253731"	"268"	"12.7619047619"	"PLoS Computational Biology"	"Misic B, Vakorin VA, Kovacevic N, Paus T, McIntosh AR"	"Rotman Research Institute, Baycrest Centre, Toronto, Ontario, Canada."	"The complex connectivity of the cerebral cortex is a topic of much study, yet the link between structure and function is still unclear. The processing capacity and throughput of information at individual brain regions remains an open question and one that could potentially bridge these two aspects of neural organization. The rate at which information is emitted from different nodes in the network and how this output process changes under different external conditions are general questions that are not unique to neuroscience, but are of interest in multiple classes of telecommunication networks. In the present study we show how some of these questions may be addressed using tools from telecommunications research. An important system statistic for modeling and performance evaluation of distributed communication systems is the time between successive departures of units of information at each node in the network. We describe a method to extract and fully characterize the distribution of such inter-departure times from the resting-state electroencephalogram (EEG). We show that inter-departure times are well fitted by the two-parameter Gamma distribution. Moreover, they are not spatially or neurophysiologically trivial and instead are regionally specific and sensitive to the presence of sensory input. In both the eyes-closed and eyes-open conditions, inter-departure time distributions were more dispersed over posterior parietal channels, close to regions which are known to have the most dense structural connectivity. The biggest differences between the two conditions were observed at occipital sites, where inter-departure times were significantly more variable in the eyes-open condition. Together, these results suggest that message departure times are indicative of network traffic and capture a novel facet of neural activity."	""
-1	"english"	"Canada"	"Canada"	"0.0"	"0.0106761565836"	"0.085409252669"	"281"	"8.72727272727"	"Bioinformatics"	"Mizianty MJ, Kurgan L"	"Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Canada."	"MOTIVATION: X-ray crystallography-based protein structure determination, which accounts for majority of solved structures, is characterized by relatively low success rates. One solution is to build tools which support selection of targets that are more likely to crystallize. Several in silico methods that predict propensity of diffraction-quality crystallization from protein chains were developed. We show that the quality of their predictions drops when applied to more recent crystallization trails, which calls for new solutions. We propose a novel approach that alleviates drawbacks of the existing methods by using a recent dataset and improved protocol to annotate progress along the crystallization process, by predicting the success of the entire process and steps which result in the failed attempts, and by utilizing a compact and comprehensive set of sequence-derived inputs to generate accurate predictions. RESULTS: The proposed PPCpred (predictor of protein Production, Purification and Crystallization) predict propensity for production of diffraction-quality crystals, production of crystals, purification and production of the protein material. PPCpred utilizes comprehensive set of inputs based on energy and hydrophobicity indices, composition of certain amino acid types, predicted disorder, secondary structure and solvent accessibility, and content of certain buried and exposed residues. Our method significantly outperforms alignment-based predictions and several modern crystallization propensity predictors. Receiver operating characteristic (ROC) curves show that PPCpred is particularly useful for users who desire high true positive (TP) rates, i.e. low rate of mispredictions for solvable chains. Our model reveals several intuitive factors that influence the success of individual steps and the entire crystallization process, including the content of Cys, buried His and Ser, hydrophobic/hydrophilic segments and the number of predicted disordered segments. AVAILABILITY: CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
-1	"english"	"Canada"	"Canada"	"0.013468013468"	"0.010101010101"	"0.0740740740741"	"297"	"10.3793103448"	"BMC Bioinformatics"	"Mizianty MJ, Zhang T, Xue B, Zhou Y, Dunker AK, Uversky VN, Kurgan L"	"Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta T6G 2V4, Canada."	"BACKGROUND: Intrinsically disordered proteins play important roles in various cellular activities and their prevalence was implicated in a number of human diseases. The knowledge of the content of the intrinsic disorder in proteins is useful for a variety of studies including estimation of the abundance of disorder in protein families, classes, and complete proteomes, and for the analysis of disorder-related protein functions. The above investigations currently utilize the disorder content derived from the per-residue disorder predictions. We show that these predictions may over-or under-predict the overall amount of disorder, which motivates development of novel tools for direct and accurate sequence-based prediction of the disorder content. RESULTS: We hypothesize that sequence-level aggregation of input information may provide more accurate content prediction when compared with the content extracted from the local window-based residue-level disorder predictors. We propose a novel predictor, DisCon, that takes advantage of a small set of 29 custom-designed descriptors that aggregate and hybridize information concerning sequence, evolutionary profiles, and predicted secondary structure, solvent accessibility, flexibility, and annotation of globular domains. Using these descriptors and a ridge regression model, DisCon predicts the content with low, 0.05, mean squared error and high, 0.68, Pearson correlation. This is a statistically significant improvement over the content computed from outputs of ten modern disorder predictors on a test dataset with proteins that share low sequence identity with the training sequences. The proposed predictive model is analyzed to discuss factors related to the prediction of the disorder content. CONCLUSIONS: DisCon is a high-quality alternative for high-throughput annotation of the disorder content. We also empirically demonstrate that the DisCons predictions can be used to improve binary annotations of the disordered residues from the real-value disorder propensities generated by current residue-level disorder predictors. The web server that implements the DisCon is available at"	""
-2	"english"	"Canada"	"Canada"	"0.0"	"0.0182648401826"	"0.0776255707763"	"219"	"8.88"	"Database(Oxford)"	"Murphy C, Powlowski J, Wu M, Butler G, Tsang A"	"Centre for Structural and Functional Genomics, Concordia University, Montreal QC H4B 1R6, Canada."	"Fungi produce a wide range of extracellular enzymes to break down plant cell walls, which are composed mainly of cellulose, lignin and hemicellulose. Among them are the glycoside hydrolases (GH), the largest and most diverse family of enzymes active on these substrates. To facilitate research and development of enzymes for the conversion of cell-wall polysaccharides into fermentable sugars, we have manually curated a comprehensive set of characterized fungal glycoside hydrolases. Characterized glycoside hydrolases were retrieved from protein and enzyme databases, as well as literature repositories. A total of 453 characterized glycoside hydrolases have been cataloged. They come from 131 different fungal species, most of which belong to the phylum Ascomycota. These enzymes represent 46 different GH activities and cover 44 of the 115 CAZy GH families. In addition to enzyme source and enzyme family, available biochemical properties such as temperature and pH optima, specific activity, kinetic parameters and substrate specificities were recorded. To simplify comparative studies, enzyme and species abbreviations have been standardized, Gene Ontology terms assigned and reference to supporting evidence provided. The annotated genes have been organized in a searchable, online database called mycoCLAP (Characterized Lignocellulose-Active Proteins of fungal origin). It is anticipated that this manually curated collection of biochemically characterized fungal proteins will be used to enhance functional annotation of novel GH genes. Database URL:"	""
-2	"english"	"Canada"	"Canada"	"0.00546448087432"	"0.016393442623"	"0.0710382513661"	"183"	"12.2666666667"	"PLoS Computational Biology"	"Nasica-Labouze J, Meli M, Derreumaux P, Colombo G, Mousseau N"	"Departement de Physique and GEPROM, Universite de Montreal, Montreal, Quebec, Canada."	"The self-organization of peptides into amyloidogenic oligomers is one of the key events for a wide range of molecular and degenerative diseases. Atomic-resolution characterization of the mechanisms responsible for the aggregation process and the resulting structures is thus a necessary step to improve our understanding of the determinants of these pathologies. To address this issue, we combine the accelerated sampling properties of replica exchange molecular dynamics simulations based on the OPEP coarse-grained potential with the atomic resolution description of interactions provided by all-atom MD simulations, and investigate the oligomerization process of the GNNQQNY for three system sizes: 3-mers, 12-mers and 20-mers. Results for our integrated simulations show a rich variety of structural arrangements for aggregates of all sizes. Elongated fibril-like structures can form transiently in the 20-mer case, but they are not stable and easily interconvert in more globular and disordered forms. Our extensive characterization of the intermediate structures and their physico-chemical determinants points to a high degree of polymorphism for the GNNQQNY sequence that can be reflected at the macroscopic scale. Detailed mechanisms and structures that underlie amyloid aggregation are also provided."	""
-2	"english"	"Canada"	"Canada"	"0.0298507462687"	"0.0298507462687"	"0.0298507462687"	"201"	"13.4"	"Blood"	"Neri P, Ren L, Gratton K, Stebner E, Johnson J, Klimowicz A, Duggan P, Tassone P, Mansoor A, Stewart DA, Lonial S, Boise LH, Bahlis NJ"	"Division of Hematology and Bone Marrow Transplant, University of Calgary, Calgary, AB, Canada;"	"Chromosomal instability is a defining feature of clonal myeloma plasma cells resulting in the perpetual accumulation of genomic aberrations. In addition to its role in protein homeostasis the ubiquitin-proteasome system is also involved in the regulation of DNA damage repair proteins. Here we show that proteasome inhibition induces a BRCAness state in myeloma cells (MM) with depletion of their nuclear pool of ubiquitin and abrogation of H2AX polyubiquitylation, an essential step for the recruitment of BRCA1 and RAD51 to the sites of DNA double-stranded breaks (DSBs) and initiation of homology-mediated (HR) DNA repair. Inhibition of poly-ADP-ribose-polymerase (PARP) 1-2 with ABT-888 induced transient DNA-DSBs that were rapidly resolved and hence had no effect on MM cells viability. In contrast, co-treatment of MM cell lines and primary CD138+ cells with bortezomib and ABT-888 resulted in the sustained accumulation of unrepaired DNA-DSBs with persistence of unubiquitylated gammaH2AX foci, lack of recruitment of BRCA1 and RAD51 and ensuing MM cell death. The heightened cytotoxicity of ABT-888 in combination with bortezomib compared to either drug alone was also confirmed in MM xenografts in scid mice. Our studies indicate that bortezomib impairs HR in MM and results in a contextual synthetic lethality when combined with PARP inhibitors."	""
-2	"english"	"Canada"	"Canada"	"0.0106007067138"	"0.0318021201413"	"0.0636042402827"	"283"	"13.4761904762"	"Molecular Biology and Evolution"	"Ness RW, Graham SW, Barrett SC"	"Department of Ecology & Evolutionary Biology, University of Toronto, Toronto, Ontario, Canada."	"Most plant phylogenetic inference has used DNA sequence data from the plastid genome. This genome represents a single genealogical sample with no recombination among genes, potentially limiting the resolution of evolutionary relationships in some contexts. In contrast, nuclear DNA is inherently more difficult to employ for phylogeny reconstruction because major mutational events in the genome, including polyploidization, gene duplication, and gene extinction can result in homologous gene copies that are difficult to identify as orthologs or paralogs. Gene tree parsimony (GTP) can be used to infer the rooted species tree by fitting gene genealogies to species trees while simultaneously minimizing the estimated number of duplications needed to reconcile conflicts among them. Here, we use GTP for five nuclear gene families and a previously published plastid data set to reconstruct the phylogenetic backbone of the aquatic plant family Pontederiaceae. Plastid-based phylogenetic studies strongly supported extensive paraphyly of Eichhornia (one of the four major genera) but also depicted considerable ambiguity concerning the true root placement for the family. Our results indicate that species trees inferred from the nuclear genes (alone and in combination with the plastid data) are highly congruent with gene trees inferred from plastid data alone. Consideration of optimal and suboptimal gene tree reconciliations place the root of the family at (or near) a branch leading to the rare and locally restricted E. meyeri. We also explore methods to incorporate uncertainty in individual gene trees during reconciliation by considering their individual bootstrap profiles and relate inferred excesses of gene duplication events on individual branches to whole-genome duplication events inferred for the same branches. Our study improves understanding of the phylogenetic history of Pontederiaceae and also demonstrates the utility of GTP for phylogenetic analysis."	""
-2	"english"	"Canada"	"Canada"	"0.00593471810089"	"0.0178041543027"	"0.0593471810089"	"337"	"13.48"	"BMC Bioinformatics"	"Parks DH, Macdonald NJ, Beiko RG"	"Faculty of Computer Science, Dalhousie University, 6050 University Avenue, Halifax, Nova Scotia, Canada."	"ABSTRACT: BACKGROUND: The assignment of taxonomic attributions to DNA fragments recovered directly from the environment is a vital step in metagenomic data analysis. Assignments can be made using rank-specific classifiers, which assign reads to taxonomic labels from a predetermined level such as named species or strain, or rank-flexible classifiers, which choose an appropriate taxonomic rank for each sequence in a data set. The choice of rank typically depends on the optimal model for a given sequence and on the breadth of taxonomic groups seen in a set of close-to-optimal models. Homology-based (e.g., LCA) and composition-based (e.g., PhyloPythia, TACOA) rank-flexible classifiers have been proposed, but there is at present no hybrid approach that utilizes both homology and composition. RESULTS: We first develop a hybrid, rank-specific classifier based on BLAST and Naive Bayes (NB) that has comparable accuracy and a faster running time than the current best approach, PhymmBL. By substituting LCA for BLAST or allowing the inclusion of suboptimal NB models, we obtain a rank-flexible classifier. This hybrid classifier outperforms established rank-flexible approaches on simulated metagenomic fragments of length 200 bp to 1000 bp and is able to assign taxonomic attributions to a subset of sequences with few misclassifications. We then demonstrate the performance of different classifiers on an enhanced biological phosphorous removal metagenome, illustrating the advantages of rank-flexible classifiers when representative genomes are absent from the set of reference genomes. Application to a glacier ice metagenome demonstrates that similar taxonomic profiles are obtained across a set of classifiers which are increasingly conservative in their classification. CONCLUSIONS: Our NB-based classification scheme is faster than the current best composition-based algorithm, Phymm, while providing equally accurate predictions. The rank-flexible variant of NB, which we term epsilon-NB, is complementary to LCA and can be combined with it to yield conservative prediction sets of very high confidence. The simple parameterization of LCA and epsilon-NB allows for tuning of the balance between more predictions and increased precision, allowing the user to account for the sensitivity of downstream analyses to misclassified or unclassified sequences."	""
-2	"english"	"Canada"	"Canada"	"0.0"	"0.0"	"0.0694444444444"	"144"	"11.1538461538"	"Glycobiology"	"Patel KB, Furlong SE, Valvano MA"	"Department of Microbiology and Immunology, Infectious Diseases Research Group, Siebens-Drake Research Institute, University of Western Ontario, London, Ontario N6A5C1, Canada."	"WbaP catalyzes the transfer of galactose-1-phosphate onto undecaprenyl phosphate (Und-P). The enzyme belongs to a large family of bacterial membrane proteins required for initiation of the synthesis of O antigen lipopolysaccharide and polysaccharide capsules. Previous work in our laboratory demonstrated that the last transmembrane helix and C-terminal tail region of WbaP (WbaP(CT)) are sufficient for enzymatic activity. Here, we demonstrate the cytoplasmic location of the WbaP C-terminal tail and show that WbaP(CT) domain N-terminally fused to thioredoxin (TrxA-WbaP(CT)) exhibits improved protein folding and enhanced transferase activity. Alanine replacement of highly conserved charged or polar amino acids identified seven critical residues for enzyme activity in vivo and in vitro. Four of these residues are located in regions predicted to be alpha-helical. These regions and their secondary structure predictions are conserved in distinct WbaP family members, suggesting they may contribute to form a conserved catalytic center."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00892857142857"	"0.03125"	"0.0803571428571"	"224"	"24.8888888889"	"PLoS One"	"Petit A, Sanders AD, Kennedy TE, Tetzlaff W, Glattfelder KJ, Dalley RA, Puchalski RB, Jones AR, Roskams AJ"	"Department of Zoology, Life Sciences Institute and International Collaboration On Repair Discoveries (iCORD), University of British Columbia, Vancouver, British Columbia, Canada."	"Radial glia (RG) are primarily embryonic neuroglial progenitors that express Brain Lipid Binding Protein (Blbp a.k.a. Fabp7) and Glial Fibrillary Acidic Protein (Gfap). We used these transcripts to demarcate the distribution of spinal cord radial glia (SCRG) and screen for SCRG gene expression in the Allen Spinal Cord Atlas (ASCA). We reveal that neonatal and adult SCRG are anchored in a non-ventricular niche at the spinal cord (SC) pial boundary, and express a signature subset of 122 genes, many of which are shared with classic neural stem cells (NSCs) of the subventricular zone (SVZ) and SC central canal (CC). A core expressed gene set shared between SCRG and progenitors of the SVZ and CC is particularly enriched in genes associated with human disease. Visualizing SCRG in a Fabp7-EGFP reporter mouse reveals an extensive population of SCRG that extend processes around the SC boundary and inwardly (through) the SC white matter (WM), whose abundance increases in a gradient from cervical to lumbar SC. Confocal analysis of multiple NSC-enriched proteins reveals that postnatal SCRG are a discrete and heterogeneous potential progenitor population that become activated by multiple SC lesions, and that CC progenitors are also more heterogeneous than previously appreciated. Gene ontology analysis highlights potentially unique regulatory pathways that may be further manipulated in SCRG to enhance repair in the context of injury and SC disease."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0138248847926"	"0.0138248847926"	"0.115207373272"	"217"	"10.3333333333"	"PLoS Computational Biology"	"Phenix H, Morin K, Batenchuk C, Parker J, Abedi V, Yang L, Tepliakova L, Perkins TJ, Kaern M"	"Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada."	"Inferring regulatory and metabolic network models from quantitative genetic interaction data remains a major challenge in systems biology. Here, we present a novel quantitative model for interpreting epistasis within pathways responding to an external signal. The model provides the basis of an experimental method to determine the architecture of such pathways, and establishes a new set of rules to infer the order of genes within them. The method also allows the extraction of quantitative parameters enabling a new level of information to be added to genetic network models. It is applicable to any system where the impact of combinatorial loss-of-function mutations can be quantified with sufficient accuracy. We test the method by conducting a systematic analysis of a thoroughly characterized eukaryotic gene network, the galactose utilization pathway in Saccharomyces cerevisiae. For this purpose, we quantify the effects of single and double gene deletions on two phenotypic traits, fitness and reporter gene expression. We show that applying our method to fitness traits reveals the order of metabolic enzymes and the effects of accumulating metabolic intermediates. Conversely, the analysis of expression traits reveals the order of transcriptional regulatory genes, secondary regulatory signals and their relative strength. Strikingly, when the analyses of the two traits are combined, the method correctly infers ~80% of the known relationships without any false positives."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0093023255814"	"0.0325581395349"	"0.0325581395349"	"215"	"11.3157894737"	"Glycobiology"	"Picco G, Julien S, Brockhausen I, Beatson R, Antonopoulos A, Haslam S, Mandel U, Dell A, Pinder S, Taylor-Papadimitriou J, Burchell J"	"Departments of Medicine and Biochemistry, Queens University, Ontario, Canada."	"Changes in glycosylation are common in malignancy, and as almost all surface proteins are glycosylated, this can dramatically affect the behavior of tumor cells. In breast carcinomas, the O-linked glycans are frequently truncated, often as a result of premature sialylation. The sialyltransferase ST3Gal-I adds sialic acid to the galactose residue of core 1 (Galbeta1,3GalNAc) O-glycans and this enzyme is over-expressed in breast cancer resulting in the expression of sialylated core 1 glycans. In order to study the role of ST3Gal-I in mammary tumor development, we developed transgenic mice that over-express the sialyltransferase under the control of the human membrane-bound mucin 1 promoter. These mice were then crossed with PyMT mice that spontaneously develop mammary tumors. As expected, ST3Gal-I transgenic mice showed increased activity and expression of the enzyme in the pregnant and lactating mammary glands, the stomach, lungs and intestine. Although no obvious defects were observed in the fully developed mammary gland, when these mice were crossed with PyMT mice, a highly significant decrease in tumor latency was observed compared to the PyMT mice on an identical background. These results indicate that ST3Gal-I is acting as a tumor promoter in this model of breast cancer. This, we believe, is the first demonstration that over-expression of a glycosyltransferase involved in mucin-type O-linked glycosylation can promote tumorigenesis."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0140845070423"	"0.00704225352113"	"0.0422535211268"	"142"	"10.9230769231"	"Immunity"	"Reardon C, Lechmann M, Brustle A, Gareau MG, Shuman N, Philpott D, Ziegler SF, Mak TW"	"The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada."	"Thymic stromal lymphopoetin (TSLP) influences numerous immune functions, including those in the colonic mucosa. Here we report that TSLP-deficient (Tslp(-/-)) mice did not exhibit increased inflammation during dextran sodium sulfate (DSS)-induced colitis but failed to recover from disease, resulting in death. Increased localized neutrophil elastase (NE) activity during overt inflammation was observed in Tslp(-/-) mice and was paralleled by reduced expression of an endogenous inhibitor, secretory leukocyte peptidase inhibitor (SLPI). Pharmacological inhibition of NE or treatment with rSLPI reduced DSS-induced mortality in Tslp(-/-) mice. Signaling through TSLPR on nonhematopoietic cells was sufficient for recovery from DSS-induced colitis. Expression of the receptor occurred on intestinal epithelial cells (IEC), with stimulation inducing SLPI expression. Therefore, TSLP is critical in mediating mucosal healing after insult and functions in a nonredundant capacity that is independent of restraining T helper 1 (Th1) and Th17 cell cytokine production."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00877192982456"	"0.0350877192982"	"0.0701754385965"	"228"	"12.0"	"PLoS One"	"Rintoul JL, Wang J, Gammon DB, van Buuren NJ, Garson K, Jardine K, Barry M, Evans DH, Bell JC"	"Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada."	"BACKGROUND: Genetic manipulation of poxvirus genomes through attenuation, or insertion of therapeutic genes has led to a number of vector candidates for the treatment of a variety of human diseases. The development of recombinant poxviruses often involves the genomic insertion of a selectable marker for purification and selection purposes. The use of marker genes however inevitably results in a vector that contains unwanted genetic information of no therapeutic value. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe an improved strategy that allows for the creation of marker-free recombinant poxviruses of any species. The Selectable and Excisable Marker (SEM) system incorporates a unique fusion marker gene for the efficient selection of poxvirus recombinants and the Cre/loxP system to facilitate the subsequent removal of the marker. We have defined and characterized this new methodological tool by insertion of a foreign gene into vaccinia virus, with the subsequent removal of the selectable marker. We then analyzed the importance of loxP orientation during Cre recombination, and show that the SEM system can be used to introduce site-specific deletions or inversions into the viral genome. Finally, we demonstrate that the SEM strategy is amenable to other poxviruses, as demonstrated here with the creation of an ectromelia virus recombinant lacking the EVM002 gene. CONCLUSION/SIGNIFICANCE: The system described here thus provides a faster, simpler and more efficient means to create clinic-ready recombinant poxviruses for therapeutic gene therapy applications."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0110497237569"	"0.0331491712707"	"0.121546961326"	"181"	"13.9230769231"	"PLoS One"	"Ristic J, Giesbrecht B"	"Department of Psychology, McGill University, Montreal, Canada."	"Successful completion of many everyday tasks depends on interactions between voluntary attention, which acts to maintain current goals, and reflexive attention, which enables responding to unexpected events by interrupting the current focus of attention. Past studies, which have mostly examined each attentional mechanism in isolation, indicate that volitional and reflexive orienting depend on two functionally specialized cortical networks in the human brain. Here we investigated how the interplay between these two cortical networks affects sensory processing and the resulting overt behavior. By combining measurements of human performance and electrocortical recordings with a novel analytical technique for estimating spatiotemporal activity in the human cortex, we found that the subregions that comprise the reflexive ventrolateral attention network dissociate both spatially and temporally as a function of the nature of the sensory information and current task demands. Moreover, we found that together with the magnitude of the early sensory gain, the spatiotemporal neural dynamics accounted for the high amount of the variance in the behavioral data. Collectively these data support the conclusion that the ventrolateral attention network is recruited flexibly to support complex behaviors."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00862068965517"	"0.0258620689655"	"0.0862068965517"	"232"	"13.8235294118"	"BMC Bioinformatics"	"Rueda L, Rezaeian I"	"School of Computer Science, University of Windsor, Ontario, Canada."	"BACKGROUND: Processing cDNA microarray images is a crucial step in gene expression analysis, since any errors in early stages affect subsequent steps, leading to possibly erroneous biological conclusions. When processing the underlying images, accurately separating the sub-grids and spots is extremely important for subsequent steps that include segmentation, quantification, normalization and clustering. RESULTS: We propose a parameterless and fully automatic approach that first detects the sub-grids given the entire microarray image, and then detects the locations of the spots in each sub-grid. The approach, first, detects and corrects rotations in the images by applying an affine transformation, followed by a polynomial-time optimal multi-level thresholding algorithm used to find the positions of the sub-grids in the image and the positions of the spots in each sub-grid. Additionally, a new validity index is proposed in order to find the correct number of sub-grids in the image, and the correct number of spots in each sub-grid. Moreover, a refinement procedure is used to correct possible misalignments and increase the accuracy of the method. CONCLUSIONS: Extensive experiments on real-life microarray images and a comparison to other methods show that the proposed method performs these tasks fully automatically and with a very high degree of accuracy. Moreover, unlike previous methods, the proposed approach can be used in various type of microarray images with different resolutions and spot sizes and does not need any parameter to be adjusted."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00549450549451"	"0.032967032967"	"0.0769230769231"	"182"	"12.1333333333"	"PLoS Computational Biology"	"Saberi S, Emberly E"	"Physics, Simon Fraser University, Burnaby, British Columbia, Canada."	"The spatial patterning of proteins in bacteria plays an important role in many processes, from cell division to chemotaxis. In the asymmetrically dividing bacteria Caulobacter crescentus, a scaffolding protein, PopZ, localizes to both poles and aids the differential patterning of proteins between mother and daughter cells during division. Polar patterning of misfolded proteins in Escherichia coli has also been shown, and likely plays an important role in cellular ageing. Recent experiments on both of the above systems suggest that the presence of chromosome free regions along with protein multimerization may be a mechanism for driving the polar localization of proteins. We have developed a simple physical model for protein localization using only these two driving mechanisms. Our model reproduces all the observed patterns of PopZ and misfolded protein localization--from diffuse, unipolar, and bipolar patterns and can also account for the observed patterns in a variety of mutants. The model also suggests new experiments to further test the role of the chromosome in driving protein patterning, and whether such a mechanism is responsible for helping to drive the differentiation of the cell poles."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0341463414634"	"0.0390243902439"	"0.0487804878049"	"205"	"13.6666666667"	"PLoS One"	"Saberianfar R, Cunningham-Dunlop S, Karagiannis J"	"Department of Biology, University of Western Ontario, London, Ontario, Canada."	"In Schizosaccharomyces pombe the nuclear-localized Lsk1p-Lsc1p cyclin dependent kinase complex promotes Ser-2 phosphorylation of the heptad repeats found within the RNA pol II carboxy terminal domain (CTD). Here, we first provide evidence supporting the existence of a third previously uncharacterized Ser-2 CTD kinase subunit, Lsg1p. As expected for a component of the complex, Lsg1p localizes to the nucleus, promotes Ser-2 phosphorylation of the CTD, and physically interacts with both Lsk1p and Lsc1p in vivo. Interestingly, we also demonstrate that lsg1Delta mutants - just like lsk1Delta and lsc1Delta strains - are compromised in their ability to faithfully and reliably complete cytokinesis. Next, to address whether kinase mediated alterations in CTD phosphorylation might selectively alter the expression of genes with roles in cytokinesis and/or the cytoskeleton, global gene expression profiles were analyzed. Mutants impaired in Ser-2 phosphorylation display little change with respect to the level of transcription of most genes. However, genes affecting cytokinesis - including the actin interacting protein gene, aip1 - as well as genes with roles in meiosis, are included in a small subset that are differentially regulated. Significantly, genetic analysis of lsk1Delta aip1Delta double mutants is consistent with Lsk1p and Aip1p acting in a linear pathway with respect to the regulation of cytokinesis."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00881057268722"	"0.0220264317181"	"0.114537444934"	"227"	"7.58064516129"	"Bioinformatics"	"Sadri J, Diallo AB, Blanchette M"	"School of Computer Science, McGill University, 3630 University, Montreal, QC, Canada H3A 2B2."	"MOTIVATION: The identification of non-coding functional regions of the human genome remains one of the main challenges of genomics. By observing how a given region evolved over time, one can detect signs of negative or positive selection hinting that the region may be functional. With the quickly increasing number of vertebrate genomes to compare with our own, this type of approach is set to become extremely powerful, provided the right analytical tools are available. RESULTS: A large number of approaches have been proposed to measure signs of past selective pressure, usually in the form of reduced mutation rate. Here, we propose a radically different approach to the detection of non-coding functional region: instead of measuring past evolutionary rates, we build a machine learning classifier to predict current substitution rates in human based on the inferred evolutionary events that affected the region during vertebrate evolution. We show that different types of evolutionary events, occurring along different branches of the phylogenetic tree, bring very different amounts of information. We propose a number of simple machine learning classifiers and show that a Support-Vector Machine (SVM) predictor clearly outperforms existing tools at predicting human non-coding functional sites. Comparison to external evidences of selection and regulatory function confirms that these SVM predictions are more accurate than those of other approaches. AVAILABILITY: The predictor and predictions made are available at CONTACT:"	""
-"unk"	"english"	"Canada"	"Canada"	"0.0"	"0.0"	"0.111111111111"	"108"	"9.81818181818"	"Immunity"	"Saleh M, Elson CO"	"Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 0B1."	"Inflammatory bowel disease appears to result from an abnormal host immune response to the intestinal microbiota. Experimental models have allowed the dissection of the complex dialog between the host and its microbiota. Through genetic manipulation of the host genome the immune compartments, cells, molecules, and genes that are critical for maintenance of intestinal homeostasis are being identified. Genetic association studies in humans have identified over 100 susceptibility loci. Although there is remarkable coherence between the experimental model and the human genetic data, a full understanding of the mechanisms involved in genetic susceptibility to IBD and of gene-gene and gene-environmental interactions will require a next generation of experimental models."	""
-"unk"	"english"	"Canada"	"Canada"	"0.020618556701"	"0.020618556701"	"0.0360824742268"	"194"	"12.9333333333"	"Blood"	"Savage KJ, Skinnider B, Al-Mansour M, Sehn LH, Gascoyne RD, Connors JM"	"Centre for Lymphoid Cancer and Department of Medical Oncology, British Columbia Cancer Agency and the University of British Columbia, Vancouver, BC, Canada;"	"The appropriate therapy for limited stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is unclear. In contrast to classical Hodgkin lymphoma (CHL), chemotherapy is often omitted; however, it is unknown whether this impacts the risk of relapse. Herein, we compared the outcome of patients with limited stage NLPHL treated in an era in which ABVD chemotherapy was routinely incorporated into the primary therapy to an earlier era in which radiotherapy (RT) was used as a single modality. Using the BCCA Lymphoid Cancer Database 88 patients with limited stage NLPHL (stage 1A/1B or 2A, non-bulky disease < 10 cm) were identified. Patients were treated following era-specific guidelines: Before 1993 (n=32) RT alone; 1993-present (n=56) ABVD-like chemotherapy for 2 cycles followed by RT with the exception of 14 patients who received ABVD chemotherapy alone. Most patients were male (75%) with stage 1 disease (61%). In an era to era comparison, the 10 year TTP (98% vs 76% p=0.0074), PFS (91% vs 65% p=0.0024) and OS (93% vs 84%, p=0.074) favored the ABVD treatment era compared to the RT alone era. Treating limited stage NLPHL similarly to CHL may improve outcome compared to the use of radiation alone."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00653594771242"	"0.0294117647059"	"0.0751633986928"	"306"	"14.5714285714"	"PLoS Computational Biology"	"Schneider AD, Cullen KE, Chacron MJ"	"Department of Physics, McGill University, Montreal, Quebec, Canada."	"Previous studies have shown that neurons within the vestibular nuclei (VN) can faithfully encode the time course of sensory input through changes in firing rate in vivo. However, studies performed in vitro have shown that these same VN neurons often display nonlinear synchronization (i.e. phase locking) in their spiking activity to the local maxima of sensory input, thereby severely limiting their capacity for faithful encoding of said input through changes in firing rate. We investigated this apparent discrepancy by studying the effects of in vivo conditions on VN neuron activity in vitro using a simple, physiologically based, model of cellular dynamics. We found that membrane potential oscillations were evoked both in response to step and zap current injection for a wide range of channel conductance values. These oscillations gave rise to a resonance in the spiking activity that causes synchronization to sinusoidal current injection at frequencies below 25 Hz. We hypothesized that the apparent discrepancy between VN response dynamics measured in in vitro conditions (i.e., consistent with our modeling results) and the dynamics measured in vivo conditions could be explained by an increase in trial-to-trial variability under in vivo vs. in vitro conditions. Accordingly, we mimicked more physiologically realistic conditions in our model by introducing a noise current to match the levels of resting discharge variability seen in vivo as quantified by the coefficient of variation (CV). While low noise intensities corresponding to CV values in the range 0.04-0.24 only eliminated synchronization for low (<8 Hz) frequency stimulation but not high (>12 Hz) frequency stimulation, higher noise intensities corresponding to CV values in the range 0.5-0.7 almost completely eliminated synchronization for all frequencies. Our results thus predict that, under natural (i.e. in vivo) conditions, the vestibular system uses increased variability to promote fidelity of encoding by single neurons. This prediction can be tested experimentally in vitro."	""
-"unk"	"english"	"Canada"	"Canada"	"0.015"	"0.025"	"0.04"	"200"	"15.3846153846"	"Blood"	"Sekulovic S, Gasparetto M, Lecault V, Hoesli CA, Kent DG, Rosten P, Wan A, Brookes C, Hansen CL, Piret JM, Smith C, Eaves CJ, Humphries RK"	"Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada;"	"Achieving high-level expansion of hematopoietic stem cells (HSCs) in vitro will have an important clinical impact in addition to enabling elucidation of their regulation. Here we couple the ability of engineered NUP98-HOXA10hd expression to stimulate >1,000-fold net expansions of murine HSCs in 10-day cultures initiated with bulk lin(-)Sca-1(+)c-kit(+) cells, with strategies to purify fetal and adult HSCs and analyze their expansion clonally. We find that NUP98-HOXA10hd stimulates comparable expansions of HSCs from both sources at ~60-90% unit efficiency in cultures initiated with single cells. Clonally expanded HSCs consistently show balanced long-term contributions to the lymphoid and myeloid lineages without evidence of leukemogenic activity. Although effects on fetal and adult HSCs were indistinguishable, NUP98-HOXA10hd-transduced-adult HSCs did not thereby gain a competitive advantage in vivo over freshly isolated fetal HSCs. Live-cell image tracking of single transduced HSCs cultured in a microfluidic device indicates that NUP98-HOXA10hd does not affect their proliferation kinetics and flow cytometry confirmed the phenotype of normal proliferating HSCs and allowed re-isolation of large numbers of expanded HSCs at a purity of 25%. These findings point to the effects of NUP98-HOXA10hd on HSCs in vitro being mediated by promoting self-renewal and set the stage for further dissection of this process."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0105263157895"	"0.0105263157895"	"0.0736842105263"	"285"	"11.44"	"PLoS One"	"She K, Craig AM"	"Brain Research Centre and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada."	"BACKGROUND: Activity through NMDA type glutamate receptors sculpts connectivity in the developing nervous system. This topic is typically studied in the visual system in vivo, where activity of inputs can be differentially regulated, but in which individual synapses are difficult to visualize and mechanisms governing synaptic competition can be difficult to ascertain. Here, we develop a model of NMDA-receptor dependent synaptic competition in dissociated cultured hippocampal neurons. METHODOLOGY/PRINCIPAL FINDINGS: GluN1 -/- (KO) mouse hippocampal neurons lacking the essential NMDA receptor subunit were cultured alone or cultured in defined ratios with wild type (WT) neurons. The absence of functional NMDA receptors did not alter neuron survival. Synapse development was assessed by immunofluorescence for postsynaptic PSD-95 family scaffold and apposed presynaptic vesicular glutamate transporter VGlut1. Synapse density was specifically enhanced onto minority wild type neurons co-cultured with a majority of GluN1 -/- neighbour neurons, both relative to the GluN1 -/- neighbours and relative to sister pure wild type cultures. This form of synaptic competition was dependent on NMDA receptor activity and not conferred by the mere physical presence of GluN1. In contrast to these results in 10% WT and 90% KO co-cultures, synapse density did not differ by genotype in 50% WT and 50% KO co-cultures or in 90% WT and 10% KO co-cultures. CONCLUSIONS/SIGNIFICANCE: The enhanced synaptic density onto NMDA receptor-competent neurons in minority coculture with GluN1 -/- neurons represents a cell culture paradigm for studying synaptic competition. Mechanisms involved may include a retrograde reward signal generated by WT neurons, although in this paradigm there was no punishment signal against GluN1 -/- neurons. Cell culture assays involving such defined circuits may help uncover the rules and mechanisms of activity-dependent synaptic competition in the developing nervous system."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0116279069767"	"0.046511627907"	"0.046511627907"	"86"	"7.0"	"Bioinformatics"	"She R, Chu JS, Uyar B, Wang J, Wang K, Chen N"	"School of Computing Science, Simon Fraser University, Burnaby, British Columbia, Canada V5A 0A1."	"MOTIVATION: BLAST users frequently expect to obtain homologous genes with certain similarity to their query genes. But what they get from BLAST searches are often collections of local alignments called high-scoring segment pairs (HSPs). On the other hand, most homology-based gene finders have been built using computation-intensive algorithms, without taking full advantage of BLAST searches that have been perfected over the last decades. RESULTS: Here we report an efficient algorithm, genBlastG that directly uses the HSPs reported by BLAST to define high-quality gene models. AVAILABILITY:"	""
-"unk"	"english"	"Canada"	"Canada"	"0.0220588235294"	"0.0"	"0.0514705882353"	"136"	"10.4615384615"	"Glycobiology"	"Soya N, Fang Y, Palcic MM, Klassen JS"	"Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton, Alta, Canada."	"The enzymatic mechanism by which retaining glycosyltransferases (GTs) transfer monosaccharides with net retention of the anomeric configuration has, so far, resisted elucidation. Here, direct detection of covalent glycosyl-enzyme intermediates for mutants of two model retaining GTs, the human blood group synthesizing alpha-(1 --> 3)-N-acetylgalactosaminyltransferase (GTA) and alpha-(1 --> 3)-galactosyltransferase (GTB) mutants, by mass spectrometry (MS) is reported. Incubation of mutants of GTA or GTB, in which the putative catalytic nucleophile Glu(303) was replaced with Cys (i.e. GTA(E303C) and GTB(E303C)), with their respective donor substrate results in a covalent intermediate. Tandem MS analysis using collision-induced dissociation confirmed Cys(303) as the site of glycosylation. Exposure of the glycosyl-enzyme intermediates to a disaccharide acceptor results in the formation of the corresponding enzymatic trisaccharide products. These findings suggest that the GTA(E303C) and GTB(E303C) mutants may operate by a double-displacement mechanism."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00340136054422"	"0.0238095238095"	"0.0544217687075"	"294"	"15.4736842105"	"Molecular Biology and Evolution"	"Stairs CW, Roger AJ, Hampl V"	"Centre for Comparative Genomics and Evolutionary Bioinformatics, Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada."	"Most of the major groups of eukaryotes have microbial representatives that thrive in low oxygen conditions. Those that have been studied in detail generate ATP via pathways involving anaerobically functioning enzymes of pyruvate catabolism that are typically absent in aerobic eukaryotes and whose origins remain controversial. These enzymes include pyruvate:ferredoxin oxidoreductase, pyruvate:NADP(+) oxidoreductase, and pyruvate formate lyase (Pfl). Pfl catalyzes the nonoxidative generation of formate and acetyl-Coenzyme A (CoA) from pyruvate and CoA and is activated by Pfl activating enzyme (Pfla). Within eukaryotes, this extremely oxygen-sensitive pathway was first described in the hydrogenosomes of anaerobic chytrid fungi and has more recently been characterized in the mitochondria and chloroplasts of the chlorophyte alga Chlamydomonas reinhardtii. To clarify the origins of this pathway, we have comprehensively searched for homologs of Pfl and Pfla in publicly available large-scale eukaryotic genomic and cDNA sequencing data, including our own from the anaerobic amoebozoan Mastigamoeba balamuthi. Surprisingly, we find that these enzymes are widely distributed and are present in diverse facultative or obligate anaerobic eukaryotic representatives of the archaeplastidan, metazoan, amoebozoan, and haptophyte lineages. Using maximum likelihood and Bayesian phylogenetic methods, we show that the eukaryotic Pfl and Pfla sequences each form monophyletic groups that are most closely related to homologs in firmicute gram-positive bacteria. Topology tests exclude both alpha-proteobacterial and cyanobacterial affinities for these genes suggesting that neither originated from the endosymbiotic ancestors of mitochondria or chloroplasts. Furthermore, the topologies of the eukaryote portion of the Pfl and Pfla trees significantly differ from well-accepted eukaryote relationships. Collectively, these results indicate that the Pfl pathway was first acquired by lateral gene transfer into a eukaryotic lineage most probably from a firmicute bacterial lineage and that it has since been spread across diverse eukaryotic groups by more recent eukaryote-to-eukaryote transfer events."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00813008130081"	"0.0162601626016"	"0.0447154471545"	"246"	"9.88"	"PLoS One"	"Suliman S, Tan J, Xu K, Kousis PC, Kowalski PE, Chang G, Egan SE, Guidos C"	"Program in Stem Cell and Developmental Biology, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada."	"Notch1 (N1) signaling induced by intrathymic Delta-like (DL) ligands is required for T cell lineage commitment as well as self-renewal during beta-selection of TCRbeta(+) CD4(-)CD8(-) double negative 3 (DN3) T cell progenitors. However, over-expression of the N1 intracellular domain (ICN1) renders N1 activation ligand-independent and drives leukemic transformation during beta-selection. DN3 progenitors also express Notch3 (N3) mRNA, and over-expression of ligand-independent mutant N3 (ICN3) influences beta-selection and drives T cell leukemogenesis. However, the importance of ligand-activated N3 in promoting beta-selection and ICN1-induced T cell leukemogenesis has not been examined. To address these questions we generated mice lacking functional N3. We confirmed that DN3 progenitors express N3 protein using a N3-specific antibody. Surprisingly however, N3-deficient DN3 thymocytes were not defective in generating DP thymocytes under steady state conditions or in more stringent competition assays. To determine if N3 co-operates with N1 to regulate beta-selection, we generated N1;N3 compound mutants. However, N3 deficiency did not exacerbate the competitive defect of N1(+/-) DN3 progenitors, demonstrating that N3 does not compensate for limiting N1 during T cell development. Finally, N3 deficiency did not attenuate T cell leukemogenesis induced by conditional expression of ICN1 in DN3 thymocytes. Importantly, we showed that in contrast to N1, N3 has a low binding affinity for DL4, the most abundant intrathymic DL ligand. Thus, despite the profound effects of ectopic ligand-independent N3 activation on T cell development and leukemogenesis, physiologically activated N3 is dispensable for both processes, likely because N3 interacts poorly with intrathymic DL4."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00446428571429"	"0.00892857142857"	"0.125"	"224"	"13.1764705882"	"Molecular Biology and Evolution"	"Sun S, Evans BJ, Golding GB"	"Department of Biology, McMaster University, Hamilton, Ontario, Canada."	"Indirect tests have detected recombination in mitochondrial DNA (mtDNA) from many animal lineages, including mammals. However, it is possible that features of the molecular evolutionary process without recombination could be incorrectly inferred by indirect tests as being due to recombination. We have identified one such example, which we call patchy-tachy (PT), where different partitions of sequences evolve at different rates, that leads to an excess of false positives for recombination inferred by indirect tests. To explore this phenomena, we characterized the false positive rates of six widely used indirect tests for recombination using simulations of general models for mtDNA evolution with PT but without recombination. All tests produced 30-99% false positives for recombination, although the conditions that produced the maximal level of false positives differed between the tests. To evaluate the degree to which conditions that exacerbate false positives are found in published sequence data, we turned to 20 animal mtDNA data sets in which recombination is suggested by indirect tests. Using a model where different regions of the sequences were free to evolve at different rates in different lineages, we demonstrated that PT is prevalent in many data sets in which recombination was previously inferred using indirect tests. Taken together, our results argue that PT without recombination is a viable alternative explanation for detection of widespread recombination in animal mtDNA using indirect tests."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00555555555556"	"0.0277777777778"	"0.0722222222222"	"180"	"5.42857142857"	"Bioinformatics"	"Tan A, Tripp B, Daley D"	"James Hogg iCAPTURE Center, Department of Medicine, University of British Columbia (UBC), Vancouver, BC, Canada V6Z1Y6."	"MOTIVATION: In genetic science, large-scale international research collaborations represent a growing trend. These collaborations have demanding and challenging database, storage, retrieval and communication needs. These studies typically involve demographic and clinical data, in addition to the results from numerous genomic studies (omics studies) such as gene expression, eQTL, genome-wide association and methylation studies, which present numerous challenges, thus the need for data integration platforms that can handle these complex data structures. Inefficient methods of data transfer and access control still plague research collaboration. As science becomes more and more collaborative in nature, the need for a system that adequately manages data sharing becomes paramount. RESULTS: Biology-Related Information Storage Kit (BRISK) is a package of several web-based data management tools that provide a cohesive data integration and management platform. It was specifically designed to provide the architecture necessary to promote collaboration and expedite data sharing between scientists. Availability and Implementation: The software, documentation, Java source code and demo are available at BRISK was developed in Java, and tested on an Apache Tomcat 6 server with a MySQL database. CONTACT:"	""
-"unk"	"english"	"Canada"	"Canada"	"0.0"	"0.018779342723"	"0.037558685446"	"213"	"10.1428571429"	"PLoS One"	"Tremblay-Letourneau M, Despins S, Bougie I, Bisaillon M"	"RNA Group, Departement de Biochimie, Faculte de Medecine et des Sciences de la Sante, Universite de Sherbrooke, Sherbrooke, Quebec, Canada."	"The RNA guanylyltransferase (GTase) is involved in the synthesis of the (m7)Gppp-RNA cap structure found at the 5 end of eukaryotic mRNAs. GTases are members of the covalent nucleotidyl transferase superfamily, which also includes DNA and RNA ligases. GTases catalyze a two-step reaction in which they initially utilize GTP as a substrate to form a covalent enzyme-GMP intermediate. The GMP moiety is then transferred to the diphosphate end of the RNA transcript in the second step of the reaction to form the Gppp-RNA structure. In the current study, we used a combination of virtual database screening, homology modeling, and biochemical assays to search for novel GTase inhibitors. Using this approach, we demonstrate that mycophenolic acid (MPA) can inhibit the GTase reaction by preventing the catalytic transfer of the GMP moiety onto an acceptor RNA. As such, MPA represents a novel type of inhibitor against RNA guanylyltransferases that inhibits the second step of the catalytic reaction. Moreover, we show that the addition of MPA to S. cerevisiae cells leads to a reduction of capped mRNAs. Finally, biochemical assays also demonstrate that MPA can inhibit DNA ligases through inhibition of the second step of the reaction. The biological implications of these findings for the MPA-mediated inhibition of members of the covalent nucleotidyl superfamily are discussed."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00442477876106"	"0.0176991150442"	"0.0575221238938"	"226"	"9.24"	"Bioinformatics"	"Trost B, Kusalik A"	"Department of Computer Science, University of Saskatchewan, Saskatoon, Canada S7N 5C9."	"MOTIVATION: Kinase-mediated phosphorylation is the central mechanism of post-translational modification to regulate cellular responses and phenotypes. Signalling defects associated with protein phosphorylation are linked to many diseases, particularly cancer. Characterizing protein kinases and their substrates enhances our ability to understand and treat such diseases and broadens our knowledge of signaling networks in general.While most or all protein kinases have been identified in well-studied eukaryotes, the sites that they phosphorylate have been only partially elucidated. Experimental methods for identifying phosphorylation sites are resource-intensive, so the ability to computationally predict potential sites has considerable value. RESULTS: Many computational techniques for phosphorylation site prediction have been proposed, most of which are available on the web. These techniques differ in several ways, including the machine learning technique used; the amount of sequence information used; whether or not structural information is used in addition to sequence information; whether predictions are made for specific kinases or for kinases in general; and sources of training and testing data.This review summarizes, categorizes, and compares the available methods for phosphorylation site prediction, and provides an overview of the challenges that are faced when designing predictors and how they have been addressed. It should therefore be useful both for those wishing to choose a phosphorylation site predictor for their particular biological application, and for those attempting to improve upon established techniques in the future. CONTACT:"	""
-"unk"	"english"	"Canada"	"Canada"	"0.0"	"0.0281690140845"	"0.0845070422535"	"142"	"5.51851851852"	"BMC Bioinformatics"	"Truszkowski J, Brown DG"	"David R Cheriton School of Computer Science, University of Waterloo, Waterloo, ON, Canada."	"BACKGROUND: Identifying recombinations in HIV is important for studying the epidemiology of the virus and aids in the design of potential vaccines and treatments. The previous widely-used tool for this task uses the Viterbi algorithm in a hidden Markov model to model recombinant sequences. RESULTS: We apply a new decoding algorithm for this HMM that improves prediction accuracy. Exactly locating breakpoints is usually impossible, since different subtypes are highly conserved in some sequence regions. Our algorithm identifies these sites up to a certain error tolerance. Our new algorithm is more accurate in predicting the location of recombination breakpoints. Our implementation of the algorithm is available at CONCLUSIONS: By explicitly accounting for uncertainty in breakpoint positions, our algorithm offers more reliable predictions of recombination breakpoints in HIV-1. We also document a new domain of use for our new decoding approach in HMMs."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00510204081633"	"0.015306122449"	"0.0816326530612"	"196"	"10.3157894737"	"Molecular Biology and Evolution"	"Tsaousis AD, Gaston D, Stechmann A, Walker PB, Lithgow T, Roger AJ"	"Department of Biochemistry and Molecular Biology, Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax, Canada."	"Core proteins of mitochondrial protein import are found in all mitochondria, suggesting a common origin of this import machinery. Despite the presence of a universal core import mechanism, there are specific proteins found only in a few groups of organisms. One of these proteins is the translocase of outer membrane 70 (Tom70), a protein that is essential for the import of preproteins with internal targeting sequences into the mitochondrion. Until now, Tom70 has only been found in animals and Fungi. We have identified a tom70 gene in the human parasitic anaerobic stramenopile Blastocystis sp. that is neither an animal nor a fungus. Using a combination of bioinformatics, genetic complementation, and immunofluorescence microscopy analyses, we demonstrate that this protein functions as a typical Tom70 in Blastocystis mitochondrion-related organelles. Additionally, we identified putative tom70 genes in the genomes of other stramenopiles and a haptophyte, that, in phylogenies, form a monophyletic group distinct from the animal and the fungal homologues. The presence of Tom70 in these lineages significantly expands the evolutionary spectrum of eukaryotes that contain this protein and suggests that it may have been part of the core mitochondrial protein import apparatus of the last common ancestral eukaryote."	""
-1	"english"	"Canada"	"Canada"	"0.0"	"0.030303030303"	"0.0787878787879"	"165"	"8.84210526316"	"Database(Oxford)"	"Turinsky AL, Razick S, Turner B, Donaldson IM, Wodak SJ"	"Molecular Structure and Function Program, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada."	"Literature curation of protein interaction data faces a number of challenges. Although curators increasingly adhere to standard data representations, the data that various databases actually record from the same published information may differ significantly. Some of the reasons underlying these differences are well known, but their global impact on the interactions collectively curated by major public databases has not been evaluated. Here we quantify the agreement between curated interactions from 15 471 publications shared across nine major public databases. Results show that on average, two databases fully agree on 42% of the interactions and 62% of the proteins curated from the same publication. Furthermore, a sizable fraction of the measured differences can be attributed to divergent assignments of organism or splice isoforms, different organism focus and alternative representations of multi-protein complexes. Our findings highlight the impact of divergent curation policies across databases, and should be relevant to both curators and data consumers interested in analyzing protein-interaction data generated by the scientific community. Database URL:"	""
-2	"english"	"Canada"	"Canada"	"0.0"	"0.00657894736842"	"0.0723684210526"	"152"	"9.23529411765"	"Database(Oxford)"	"Turner B, Razick S, Turinsky AL, Vlasblom J, Crowdy EK, Cho E, Morrison K, Donaldson IM, Wodak SJ"	"Molecular Structure and Function Program, Hospital for Sick Children, Toronto, ON, Canada."	"We present iRefWeb, a web interface to protein interaction data consolidated from 10 public databases: BIND, BioGRID, CORUM, DIP, IntAct, HPRD, MINT, MPact, MPPI and OPHID. iRefWeb enables users to examine aggregated interactions for a protein of interest, and presents various statistical summaries of the data across databases, such as the number of organism-specific interactions, proteins and cited publications. Through links to source databases and supporting evidence, researchers may gauge the reliability of an interaction using simple criteria, such as the detection methods, the scale of the study (high- or low-throughput) or the number of cited publications. Furthermore, iRefWeb compares the information extracted from the same publication by different databases, and offers means to follow-up possible inconsistencies. We provide an overview of the consolidated protein-protein interaction landscape and show how it can be automatically cropped to aid the generation of meaningful organism-specific interactomes. iRefWeb can be accessed at: Database URL:"	""
-"unk"	"english"	"Canada"	"Canada"	"0.00529100529101"	"0.026455026455"	"0.0529100529101"	"189"	"12.6"	"Molecular Biology and Evolution"	"van Weringh A, Ragonnet-Cronin M, Pranckeviciene E, Pavon-Eternod M, Kleiman L, Xia X"	"Department of Biology, University of Ottawa, Ottawa, Ontario, Canada."	"Despite its poorly adapted codon usage, HIV-1 replicates and is expressed extremely well in human host cells. HIV-1 has recently been shown to package non-lysyl transfer RNAs (tRNAs) in addition to the tRNA(Lys) needed for priming reverse transcription and integration of the HIV-1 genome. By comparing the codon usage of HIV-1 genes with that of its human host, we found that tRNAs decoding codons that are highly used by HIV-1 but avoided by its host are overrepresented in HIV-1 virions. In particular, tRNAs decoding A-ending codons, required for the expression of HIVs A-rich genome, are highly enriched. Because the affinity of Gag-Pol for all tRNAs is nonspecific, HIV packaging is most likely passive and reflects the tRNA pool at the time of viral particle formation. Codon usage of HIV-1 early genes is similar to that of highly expressed host genes, but codon usage of HIV-1 late genes was better adapted to the selectively enriched tRNA pool, suggesting that alterations in the tRNA pool are induced late in viral infection. If HIV-1 genes are adapting to an altered tRNA pool, codon adaptation of HIV-1 may be better than previously thought."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0"	"0.0167224080268"	"0.0468227424749"	"299"	"10.3448275862"	"Molecular Biology and Evolution"	"Wang HC, Susko E, Roger AJ"	"Department of Mathematics and Statistics, Dalhousie University, Halifax, Nova Scotia, Canada."	"The w statistic introduced by Lockhart et al. (1998. A covariotide model explains apparent phylogenetic structure of oxygenic photosynthetic lineages. Mol Biol Evol. 15:1183-1188) is a simple and easily calculated statistic intended to detect heterotachy by comparing amino acid substitution patterns between two monophyletic groups of protein sequences. It is defined as the difference between the fraction of varied sites in both groups and the fraction of varied sites in each group. The w test has been used to distinguish a covarion process from equal rates and rates variation across sites processes. Using simulation we show that the w test is effective for small data sets and for data sets that have low substitution rates in the groups but can have difficulties when these conditions are not met. Using site entropy as a measure of variability of a sequence site, we modify the w statistic to a w statistic by assigning as varied in one group those sites that are actually varied in both groups but have a large entropy difference. We show that the w test has more power to detect two kinds of heterotachy processes (covarion and bivariate rate shifts) in large and variable data. We also show that a test of Pearsons correlation of the site entropies between two monophyletic groups can be used to detect heterotachy and has more power than the w test. Furthermore, we demonstrate that there are settings where the correlation test as well as w and w tests do not detect heterotachy signals in data simulated under a branch length mixture model. In such cases, it is sometimes possible to detect heterotachy through subselection of appropriate taxa. Finally, we discuss the abilities of the three statistical tests to detect a fourth mode of heterotachy: lineage-specific changes in proportion of variable sites."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00442477876106"	"0.0176991150442"	"0.0575221238938"	"226"	"13.2941176471"	"PLoS One"	"Wilson JJ"	"Department of Integrative Biology, University of Guelph, Guelph, Ontario, Canada."	"BACKGROUND: A common perception is that DNA barcode datamatrices have limited phylogenetic signal due to the small number of characters available per taxon. However, another school of thought suggests that the massively increased taxon sampling afforded through the use of DNA barcodes may considerably increase the phylogenetic signal present in a datamatrix. Here I test this hypothesis using a large dataset of macrolepidopteran DNA barcodes. METHODOLOGY/PRINCIPAL FINDINGS: Taxon sampling was systematically increased in datamatrices containing macrolepidopteran DNA barcodes. Sixteen family groups were designated as concordance groups and two quantitative measures; the taxon consistency index and the taxon retention index, were used to assess any changes in phylogenetic signal as a result of the increase in taxon sampling. DNA barcodes alone, even with maximal taxon sampling (500 species per family), were not sufficient to reconstruct monophyly of families and increased taxon sampling generally increased the number of clades formed per family. However, the scores indicated a similar level of taxon retention (species from a family clustering together) in the cladograms as the number of species included in the datamatrix was increased, suggesting substantial phylogenetic signal below the family branch. CONCLUSIONS/SIGNIFICANCE: The development of supermatrix, supertree or constrained tree approaches could enable the exploitation of the massive taxon sampling afforded through DNA barcodes for phylogenetics, connecting the twigs resolved by barcodes to the deep branches resolved through phylogenomics."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0272108843537"	"0.0340136054422"	"0.0612244897959"	"147"	"9.86666666667"	"Molecular Biology and Evolution"	"Wu J, Susko E"	"Department of Mathematics and Statistics, Dalhousie University, Halifax, Nova Scotia, Canada."	"Heterotachy is a general term to describe positions that evolve at different rates in different lineages. Heterotachy also can generally be viewed as multivariate rates-across-sites variation, which can be described as randomly drawing rates (or branch lengths) from a multivariate distribution for each branch at each site (Wu J, Susko E. 2009. General heterotachy and distance method adjustments. Mol Biol Evol. 26:2689-2697). Motivated by this result, we propose three new distance-based tests: a heterogeneity test, a heterotachy test, and a within-gene heterotachy test and demonstrate with simulations that they perform well under a wide range of conditions. We also applied the first two tests to two real data sets and found that although all these data sets showed significant evidence of heterotachy, there were subtrees for which the data were consistent with an equal rates or rates-across-sites model.heterogeneity, heterotachy, within-gene heterotachy, covarion model, distance method, hypothesis test."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00793650793651"	"0.015873015873"	"0.111111111111"	"126"	"6.2380952381"	"Bioinformatics"	"Xia J, Sinelnikov IV, Wishart DS"	"Department of Biological Sciences, Department of Computing Sciences and National Research Council, National Institute for Nanotechnology (NINT), University of Alberta, Edmonton, Alberta, Canada."	"SUMMARY: Time-series and multifactor studies have become increasingly common in metabolomic studies. Common tasks for analyzing data from these relatively complex experiments include identification of major variations associated with each experimental factor, comparison of temporal profiles across different biological conditions, as well as detection and validation of the presence of interactions. Here we introduce MetATT, a web-based tool for time-series and two-factor metabolomic data analysis. MetATT offers a number of complementary approaches including 3D interactive principal component analysis, two-way heatmap visualization, two-way ANOVA, ANOVA-simultaneous component analysis and multivariate empirical Bayes time-series analysis. These procedures are presented through an intuitive web interface. At the end of each session, a detailed analysis report is generated to facilitate understanding of the results. AVAILABILITY: Freely available at CONTACT:"	""
-"unk"	"english"	"Canada"	"Canada"	"0.00515463917526"	"0.0"	"0.0670103092784"	"194"	"8.69565217391"	"Bioinformatics"	"Xiong HY, Barash Y, Frey BJ"	"Department of Electrical and Computer Engineering, University of Toronto, Toronto, M5S3G4 and Banting and Best Department of Medical Research, Centre of Cellular and Biomolecular Research, University of Toronto, Toronto, M5S3E1, Canada."	"MOTIVATION: Alternative splicing is a major contributor to cellular diversity in mammalian tissues and relates to many human diseases. An important goal in understanding this phenomenon is to infer a splicing code that predicts how splicing is regulated in different cell types by features derived from RNA, DNA and epigenetic modifiers. METHODS: We formulate the assembly of a splicing code as a problem of statistical inference and introduce a Bayesian method that uses an adaptively selected number of hidden variables to combine subgroups of features into a network, allows different tissues to share feature subgroups and uses a Gibbs sampler to hedge predictions and ascertain the statistical significance of identified features. RESULTS: Using data for 3665 cassette exons, 1014 RNA features and 4 tissue types derived from 27 mouse tissues (, we benchmarked several methods. Our method outperforms all others, and achieves relative improvements of 52% in splicing code quality and up to 22% in classification error, compared with the state of the art. Novel combinations of regulatory features and novel combinations of tissues that share feature subgroups were identified using our method. CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0"	"0.0227272727273"	"0.0772727272727"	"220"	"6.4"	"Bioinformatics"	"Yan R, Boutros PC, Jurisica I"	"Department of Computer Science, University of Toronto, Toronto, Canada M5S 3G4."	"MOTIVATION: Pattern discovery algorithms are widely used for the analysis of DNA and protein sequences. Most algorithms have been designed to find overrepresented motifs in sparse datasets of long sequences, and ignore most positional information. We introduce an algorithm optimized to exploit spatial information in sparse-but-populous datasets. RESULTS: Our algorithm Tree-based Weighted-Position Pattern Discovery and Classification (T-WPPDC) supports both unsupervised pattern discovery and supervised sequence classification. It identifies positionally enriched patterns using the Kullback-Leibler distance between foreground and background sequences at each position. This spatial information is used to discover positionally important patterns. T-WPPDC then uses a scoring function to discriminate different biological classes. We validated T-WPPDC on an important biological problem: prediction of single nucleotide polymorphisms (SNPs) from flanking sequence. We evaluated 672 separate experiments on 120 datasets derived from multiple species. T-WPPDC outperformed other pattern discovery methods and was comparable to the supervised machine learning algorithms. The algorithm is computationally efficient and largely insensitive to dataset size. It allows arbitrary parameterization and is embarrassingly parallelizable. Conclusions: T-WPPDC is a minimally parameterized algorithm for both pattern discovery and sequence classification that directly incorporates positional information. We use it to confirm the predictability of SNPs from flanking sequence, and show that positional information is a key to this biological problem. AVAILABILITY: The algorithm, code and data are available at:"	""
-"unk"	"english"	"Canada"	"Canada"	"0.0"	"0.00769230769231"	"0.107692307692"	"130"	"14.4444444444"	"Molecular Biology and Evolution"	"Yotova V, Lefebvre JF, Moreau C, Gbeha E, Hovhannesyan K, Bourgeois S, Bedarida S, Azevedo L, Amorim A, Sarkisian T, Avogbe PH, Chabi N, Dicko MH, Kou Santa Amouzou ES, Sanni A, Roberts-Thomson J, Boettcher B, Scott RJ, Labuda D"	"Research Center, CHU Sainte-Justine, Universite de Montreal, Montreal, Quebec, Canada."	"Recent work on the Neandertal genome has raised the possibility of admixture between Neandertals and the expanding population of Homo sapiens who left Africa between 80 and 50 Kya (thousand years ago) to colonize the rest of the world. Here, we provide evidence of a notable presence (9% overall) of a Neandertal-derived X chromosome segment among all contemporary human populations outside Africa. Our analysis of 6,092 X-chromosomes from all inhabited continents supports earlier contentions that a mosaic of lineages of different time depths and different geographic provenance could have contributed to the genetic constitution of modern humans. It indicates a very early admixture between expanding African migrants and Neandertals prior to or very early on the route of the out-of-Africa expansion that led to the successful colonization of the planet."	""
-"unk"	"english"	"Canada"	"Canada"	"0.00956937799043"	"0.0239234449761"	"0.0430622009569"	"209"	"11.1052631579"	"Glycobiology"	"Zandberg WF, Benjannet S, Hamelin J, Pinto BM, Seidah NG"	"Department of Chemistry, Simon Fraser University, Burnaby, BC, Canada V5A 1S6."	"The limited proteolysis of proteins by the proprotein convertases (PCs) is a common means of producing bioactive proteins or peptides. The PCs are associated with numerous human pathologies and their activity can be reduced through the use of specific inhibitors. Here, we demonstrate an alternative approach to inhibiting PCs by altering their N-glycosylation. Through site-directed mutagenesis, we show that the convertase PC1/3 contains two N-glycans, only one of which is critical for its prosegment cleavage. The exact structure of PC1/3 N-glycans does not significantly affect its zymogen activation within endocrine cells, but glycosylation of Asn(146) is critical. Processing of the PC1/3s substrate proopiomelanocortin (POMC) was used in a cell-based assay to screen a collection of 45 compounds structurally related to known glycosidase inhibitors. Two 5-thiomannose-containing disaccharide derivatives were discovered to block PC1/3 and POMC processing into the analgesic peptide beta-endorphin. These compounds also reduced the zymogen activation of the convertase subtilisin kexin isozyme-1 (SKI-1), blocked the processing of its substrate the sterol regulatory element-binding protein SREBP-2 and altered its glycosylation. Thus, modification of PC glycosylation may also be a means of blocking their activity, an effect which, in the case of SKI-1, may be of possible therapeutic use since SREBP-2 regulates sterol levels including cholesterol biosynthesis and its metabolism."	""
-1	"english"	"Canada"	"Canada"	"0.0"	"0.0252525252525"	"0.0707070707071"	"198"	"6.93103448276"	"Database(Oxford)"	"Zhang J, Baran J, Cros A, Guberman JM, Haider S, Hsu J, Liang Y, Rivkin E, Wang J, Whitty B, Wong-Erasmus M, Yao L, Kasprzyk A"	"Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada."	"The International Cancer Genome Consortium (ICGC) is a collaborative effort to characterize genomic abnormalities in 50 different cancer types. To make this data available, the ICGC has created the ICGC Data Portal. Powered by the BioMart software, the Data Portal allows each ICGC member institution to manage and maintain its own databases locally, while seamlessly presenting all the data in a single access point for users. The Data Portal currently contains data from 24 cancer projects, including ICGC, The Cancer Genome Atlas (TCGA), Johns Hopkins University, and the Tumor Sequencing Project. It consists of 3478 genomes and 13 cancer types and subtypes. Available open access data types include simple somatic mutations, copy number alterations, structural rearrangements, gene expression, microRNAs, DNA methylation and exon junctions. Additionally, simple germline variations are available as controlled access data. The Data Portal uses a web-based graphical user interface (GUI) to offer researchers multiple ways to quickly and easily search and analyze the available data. The web interface can assist in constructing complicated queries across multiple data sets. Several application programming interfaces are also available for programmatic access. Here we describe the organization, functionality, and capabilities of the ICGC Data Portal. Database URL:"	""
-"unk"	"english"	"Canada"	"Canada"	"0.0102389078498"	"0.0238907849829"	"0.061433447099"	"293"	"8.9696969697"	"PLoS Computational Biology"	"Zhang KX, Ouellette BF"	"Graduate Program in Bioinformatics, University of British Columbia, Vancouver, British Columbia, Canada."	"Carcinogenesis is a complex process with multiple genetic and environmental factors contributing to the development of one or more tumors. Understanding the underlying mechanism of this process and identifying related markers to assess the outcome of this process would lead to more directed treatment and thus significantly reduce the mortality rate of cancers. Recently, molecular diagnostics and prognostics based on the identification of patterns within gene expression profiles in the context of protein interaction networks were reported. However, the predictive performances of these approaches were limited. In this study we propose a novel integrated approach, named CAERUS, for the identification of gene signatures to predict cancer outcomes based on the domain interaction network in human proteome. We first developed a model to score each protein by quantifying the domain connections to its interacting partners and the somatic mutations present in the domain. We then defined proteins as gene signatures if their scores were above a preset threshold. Next, for each gene signature, we quantified the correlation of the expression levels between this gene signature and its neighboring proteins. The results of the quantification in each patient were then used to predict cancer outcome by a modified naive Bayes classifier. In this study we achieved a favorable accuracy of 88.3%, sensitivity of 87.2%, and specificity of 88.9% on a set of well-documented gene expression profiles of 253 consecutive breast cancer patients with different outcomes. We also compiled a list of cancer-associated gene signatures and domains, which provided testable hypotheses for further experimental investigation. Our approach proved successful on different independent breast cancer data sets as well as an ovarian cancer data set. This study constitutes the first predictive method to classify cancer outcomes based on the relationship between the domain organization and protein network."	""
-"unk"	"english"	"Canada"	"Canada"	"0.011811023622"	"0.00787401574803"	"0.011811023622"	"254"	"10.16"	"PLoS One"	"Zhang T, Dayanandan B, Rouiller I, Lawrence EJ, Mandato CA"	"Department of Biology, McGill University, Montreal, Quebec, Canada."	"BACKGROUND: Growth-arrest-specific 2 gene was originally identified in murine fibroblasts under growth arrest conditions. Furthermore, serum stimulation of quiescent, non-dividing cells leads to the down-regulation of gas2 and results in re-entry into the cell cycle. Cytoskeleton rearrangements are critical for cell cycle progression and cell division and the Gas2 protein has been shown to co-localize with actin and microtubules in interphase mammalian cells. Despite these findings, direct evidence supporting a role for Gas2 in the mechanism of cell division has not been reported. METHODOLOGY AND PRINCIPAL FINDINGS: To determine whether the Gas2 protein plays a role in cell division, we over-expressed the full-length Gas2 protein and Gas2 truncations containing either the actin-binding CH domain or the tubulin-binding Gas2 domain in Xenopus laevis embryos. We found that both the full-length Gas2 protein and the Gas2 domain, but not the CH domain, inhibited cell division and resulted in multinucleated cells. The observation that Gas2 domain alone can arrest cell division suggests that Gas2 function is mediated by microtubule binding. Gas2 co-localized with microtubules at the cell cortex of Gas2-injected Xenopus embryos using cryo-confocal microscopy and co-sedimented with microtubules in cytoskeleton co-sedimentation assays. To investigate the mechanism of Gas2-induced cell division arrest, we showed, using a wound-induced contractile array assay, that Gas2 stabilized microtubules. Finally, electron microscopy studies demonstrated that Gas2 bundled microtubules into higher-order structures. CONCLUSION AND SIGNIFICANCE: Our experiments show that Gas2 inhibits cell division in Xenopus embryos. We propose that Gas2 function is mediated by binding and bundling microtubules, leading to cell division arrest."	""
-"unk"	"english"	"Canada"	"Canada"	"0.013986013986"	"0.027972027972"	"0.0769230769231"	"286"	"12.4347826087"	"PLoS Computational Biology"	"Zhang Y, Romanish MT, Mager DL"	"Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada."	"Comprising nearly half of the human and mouse genomes, transposable elements (TEs) are found within most genes. Although the vast majority of TEs in introns are fixed in the species and presumably exert no significant effects on the enclosing gene, some markedly perturb transcription and result in disease or a mutated phenotype. Factors determining the likelihood that an intronic TE will affect transcription are not clear. In this study, we examined intronic TE distributions in both human and mouse and found several factors that likely contribute to whether a particular TE can influence gene transcription. Specifically, we observed that TEs near exons are greatly underrepresented compared to random distributions, but the size of these underrepresentation zones differs between TE classes. Compared to elsewhere in introns, TEs within these zones are shorter on average and show stronger orientation biases. Moreover, TEs in extremely close proximity (<20 bp) to exons show a strong bias to be near splice-donor sites. Interestingly, disease-causing intronic TE insertions show the opposite distributional trends, and by examining expressed sequence tag (EST) databases, we found that the proportion of TEs contributing to chimeric TE-gene transcripts is significantly higher within their underrepresentation zones. In addition, an analysis of predicted splice sites within human long terminal repeat (LTR) elements showed a significantly lower total number and weaker strength for intronic LTRs near exons. Based on these factors, we selectively examined a list of polymorphic mouse LTR elements in introns and showed clear evidence of transcriptional disruption by LTR element insertions in the Trpc6 and Kcnh6 genes. Taken together, these studies lend insight into the potential selective forces that have shaped intronic TE distributions and enable identification of TEs most likely to exert transcriptional effects on genes."	""
-"unk"	"english"	"Canada"	"Canada"	"0.0120481927711"	"0.0401606425703"	"0.0803212851406"	"249"	"13.1052631579"	"BMC Bioinformatics"	"Zia A, Moses AM"	"Department of Cell & Systems Biology, University of Toronto, 25 Willcocks Street, Toronto, Ontario, M5S 3B2, Canada."	"ABSTRACT: BACKGROUND: Genetic variations contribute to normal phenotypic differences as well as diseases, and new sequencing technologies are greatly increasing the capacity to identify these variations. Given the large number of variations now being discovered, computational methods to prioritize the functional importance of genetic variations are of growing interest. Thus far, the focus of computational tools has been mainly on the prediction of the effects of amino acid changing single nucleotide polymorphisms (SNPs) and little attention has been paid to indels or nonsense SNPs that result in premature stop codons. RESULTS: We propose computational methods to rank insertion-deletion mutations in the coding as well as non-coding regions and nonsense mutations. We rank these variations by measuring the extent of their effect on biological function, based on the assumption that evolutionary conservation reflects function. Using sequence data from budding yeast and human, we show that variations which that we predict to have larger effects segregate at significantly lower allele frequencies, and occur less frequently than expected by chance, indicating stronger purifying selection. Furthermore, we find that insertions, deletions and premature stop codons associated with disease in the human have significantly larger predicted effects than those not associated with disease. Interestingly, the large-effect mutations associated with disease show a similar distribution of predicted effects to that expected for completely random mutations. CONCLUSIONS: This demonstrates that the evolutionary conservation context of the sequences that harbour insertions, deletions and nonsense mutations can be used to predict and rank the effects of the mutations."	""
-1	"english"	"Canada, Canada"	"Canada"	"0.0045871559633"	"0.00917431192661"	"0.0779816513761"	"218"	"11.4736842105"	"PLoS Computational Biology"	"Li YY, An J, Jones SJ"	"Canadas Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada."	"Repositioning existing drugs for new therapeutic uses is an efficient approach to drug discovery. We have developed a computational drug repositioning pipeline to perform large-scale molecular docking of small molecule drugs against protein drug targets, in order to map the drug-target interaction space and find novel interactions. Our method emphasizes removing false positive interaction predictions using criteria from known interaction docking, consensus scoring, and specificity. In all, our database contains 252 human protein drug targets that we classify as reliable-for-docking as well as 4621 approved and experimental small molecule drugs from DrugBank. These were cross-docked, then filtered through stringent scoring criteria to select top drug-target interactions. In particular, we used MAPK14 and the kinase inhibitor BIM-8 as examples where our stringent thresholds enriched the predicted drug-target interactions with known interactions up to 20 times compared to standard score thresholds. We validated nilotinib as a potent MAPK14 inhibitor in vitro (IC50 40 nM), suggesting a potential use for this drug in treating inflammatory diseases. The published literature indicated experimental evidence for 31 of the top predicted interactions, highlighting the promising nature of our approach. Novel interactions discovered may lead to the drug being repositioned as a therapeutic treatment for its off-targets associated disease, added insight into the drugs mechanism of action, and added insight into the drugs side effects."	""
-3	"english"	"Canada, Canada"	"Canada"	"0.00711743772242"	"0.0391459074733"	"0.0711743772242"	"281"	"8.78787878788"	"Bioinformatics"	"Naderi N, Kappler T, Baker CJ, Witte R"	"Department of Computer Science and Software Engineering, Concordia University, Montreal, Quebec, Canada. Swiss Institute of Bioinformatics, Geneva, Switzerland Department of Computer Science and Applied Statistics, University of New Brunswick, Saint John, Canada."	"MOTIVATION: Semantic tagging of organism mentions in full-text articles is an important part of literature mining and semantic enrichment solutions. Tagged organism mentions also play a pivotal role in disambiguating other entities in a text, such as proteins. A high-precision organism tagging system must be able to detect the numerous forms of organism mentions, including common names as well as the traditional taxonomic groups: genus, species, and strains. In addition, such a system must resolve abbreviations and acronyms, assign the scientific name, and if possible link the detected mention to the NCBI Taxonomy database for further semantic queries and literature navigation. RESULTS: We present the OrganismTagger, a hybrid rule-based/ machine learning system to extract organism mentions from the literature. It includes tools for automatically generating lexical and ontological resources from a copy of the NCBI Taxonomy database, thereby facilitating system updates by end-users. Its novel ontology-based resources can also be reused in other semantic mining and linked data tasks. Each detected organism mention is normalized to a canonical name through the resolution of acronyms and abbreviations and subsequently grounded with an NCBI Taxonomy database ID. In particular, our system combines a novel machine-learning approach with rule-based and lexical methods for detecting strain mentions in documents. On our manually annotated OT corpus, the OrganismTagger achieves a precision of 95%, a recall of 94% and a grounding accuracy of 97.5%. On the manually annotated corpus of Linnaeus-100, the results show a precision of 99%, recall of 97% and grounding accuracy of 97.4%. AVAILABILITY: The OrganismTagger, including supporting tools, resources, training data and manual annotations, as well as end-user and developer documentation, is freely available under an open source license at CONTACT:"	""
-"unk"	"english"	"Canada, Canada"	"Canada"	"0.0454545454545"	"0.0272727272727"	"0.0681818181818"	"220"	"13.0"	"Glycobiology"	"Watson DC, Leclerc S, Wakarchuk WW, Young NM"	"Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario, Canada."	"In addition to sialic acid, bacteria produce several other nonulosonic acids, including legionaminic acid (Leg). This has exactly the same stereochemistry as sialic acid, with the added features of 9-deoxy and 7-amino groups. In order to explore the biological effects of replacing sialic acid residues (Neu5Ac) in glycoconjugates with Leg in its diacetylated form, diacetyllegionaminic acid (Leg5Ac7Ac), we tested CMP-Leg5Ac7Ac as a donor substrate with a selection of bacterial and mammalian sialyltransferases. The CMP-Leg5Ac7Ac was synthesized in vitro by means of cloned enzymes from the bacillosamine portion of the Campylobacter jejuni N-glycan pathway and from the Leg pathway of Legionella pneumophila. Using fluorescent derivatives of lactose, Galbeta1,4GlcNAcbeta and T-antigen (Galbeta1,3GalNAcalpha) as acceptors, we tested eight different sialyltransferases and found that the Pasteurella multocida PM0188h and porcine ST3Gal1 sialyltransferases were significantly active with CMP-Leg5Ac7Ac, showing  approximately 60% activity when compared with CMP-Neu5Ac. The Photobacterium alpha2,6 sialyltransferase was weakly active, with  approximately 6% relative activity. The Leg5Ac7Ac-alpha-2,3-lactose product was then tested as a substrate with six sialidases of viral, bacterial and mammalian origin. All showed much lower activities than with the corresponding sialic acid substrate, with the influenza virus N1 being the most active and human NEU2 being the least active. These results show the feasibility of producing glycoconjugates with Leg5Ac7Ac residues as the terminal sugars, which should display novel biological properties."	""
-"unk"	"english"	"Canada, Canada"	"Canada"	"0.0140186915888"	"0.00934579439252"	"0.0607476635514"	"214"	"16.5384615385"	"Glycobiology"	"Young NM, Kreisman LS, Stupak J, Maclean LL, Cobb BA, Richards JC"	"Institute for Biological Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ont., Canada K1A 0R6."	"Morganella morganii is a commensal Gram-negative bacterium that has long been known to produce an antigen bearing phosphocholine groups. We determined the structure of this O-chain antigen and found that its repeating unit also contains a free amino group and a second phosphate: This alternating charge character places the M. morganii O-chain polysaccharide into a small family of zwitterionic polysaccharides (ZPSs) known to induce T-cell-dependent immune responses via presentation by class II major histocompatibility complex (MHCII) molecules. In vitro binding assays demonstrate that this O-chain interacts with MHCII in a manner that competes with binding of the prototypical ZPS antigen PSA from Bacteroides fragilis, despite its lack of a helical structure. Cellular studies also showed that the M. morganii polysaccharide induces activation of CD4(+) T-cells. Antibody binding experiments using acid hydrolyzed fragments representing the monomer and higher oligomers of the repeating unit showed that the phosphocholine group was the dominant element of the epitope with an overall affinity (K(D)) of about 5 x 10(-5) M, a typical value for an IgM anti-carbohydrate antibody but much lower than the affinity for phosphocholine itself. These data show that the structure of the M. morganii polysaccharide contains a unique zwitterionic repeating unit which allows for immune recognition by T-cells, making it the first identified T-cell-dependent O-chain antigen."	""
-2	"english"	"Canada, Canada, Canada"	"Canada"	"0.00657894736842"	"0.0"	"0.0526315789474"	"152"	"11.6923076923"	"Immunity"	"Omilusik K, Priatel JJ, Chen X, Wang YT, Xu H, Choi KB, Gopaul R, McIntyre-Smith A, Teh HS, Tan R, Bech-Hansen NT, Waterfield D, Fedida D, Hunt SV, Jefferies WA"	"The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; The Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada."	"The transport of calcium ions (Ca(2+)) to the cytosol is essential for immunoreceptor signaling, regulating lymphocyte differentiation, activation, and effector function. Increases in cytosolic-free Ca(2+) concentrations are thought to be mediated through two interconnected and complementary mechanisms: the release of endoplasmic reticulum Ca(2+) stores and store-operated Ca(2+) entry via plasma membrane channels. However, the identity of molecular components conducting Ca(2+) currents within developing and mature T cells is unclear. Here, we have demonstrated that the L-type voltage-dependent Ca(2+) channel Ca(V)1.4 plays a cell-intrinsic role in the function, development, and survival of naive T cells. Plasma membrane Ca(V)1.4 was found to be essential for modulation of intracellular Ca(2+) stores and T cell receptor (TCR)-induced rises in cytosolic-free Ca(2+), impacting activation of Ras-extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells (NFAT) pathways. Collectively, these studies revealed that Ca(V)1.4 functions in controlling naive T cell homeostasis and antigen-driven T cell immune responses."	""
-"unk"	"english"	"Canada, Canada, Canada, Canada, Canada"	"Canada"	"0.0202702702703"	"0.027027027027"	"0.0405405405405"	"148"	"13.4545454545"	"Nature Genetics"	"Zhang J, Zahir N, Jiang Q, Miliotis H, Heyraud S, Meng X, Dong B, Xie G, Qiu F, Hao Z, McCulloch CA, Keystone EC, Peterson AC, Siminovitch KA"	"1] Department of Medicine, University of Toronto, Toronto, Ontario, Canada. [2] Department of Immunology, University of Toronto, Toronto, Ontario, Canada. [3] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. [4] Mount Sinai Hospital Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada. [5] Toronto General Research Institute, Toronto, Ontario, Canada."	"A variant of the PTPN22-encoded Lyp phosphatase (Lyp620W) confers risk for autoimmune disease, but the mechanisms underlying this association remain unclear. We show here that mice expressing the Lyp variant homolog Pep619W manifest thymic and splenic enlargement accompanied by increases in T-cell number, activation and positive selection and in dendritic- and B-cell activation. Although Ptpn22 (Pep) transcript levels were comparable in Pep619W and wild-type Pep619R mice, Pep protein levels were dramatically reduced in the mutant mice, with Pep619W protein being more rapidly degraded and showing greater association with and in vitro cleavage by calpain 1 than Pep619R. Similarly, levels of the Lyp620W variant were decreased in human T and B cells, and its calpain binding and cleavage were increased relative to wild-type Lyp620R. Thus, calpain-mediated degradation with consequently reduced Lyp/Pep expression and lymphocyte and dendritic cell hyperresponsiveness represents a mechanism whereby Lyp620W may increase risk for autoimmune disease."	""
+3	"asian"	"Malaysia, Malaysia"	"Malaysia"	"0.0194805194805"	"0.0"	"0.0519480519481"	"154"	"10.3333333333"	"PLoS One"	"Abdi MM, Abdullah LC, Sadrolhosseini AR, Mat Yunus WM, Moksin MM, Tahir PM"	"Laboratory of Biopolymer and Derivatives, Institute of Tropical Forestry and Forest Products (INTROP), Universiti Putra Malaysia, Serdang, Selangor, Malaysia."	"A new sensing area for a sensor based on surface plasmon resonance (SPR) was fabricated to detect trace amounts of mercury and lead ions. The gold surface used for SPR measurements were modified with polypyrrole-chitosan (PPy-CHI) conducting polymer composite. The polymer layer was deposited on the gold surface by electrodeposition. This optical sensor was used for monitoring toxic metal ions with and without sensitivity enhancement by chitosan in water samples. The higher amounts of resonance angle unit (DeltaRU) were obtained for PPy-CHI film due to a specific binding of chitosan with Pb(2+) and Hg(2+) ions. The Pb(2+) ion bind to the polymer films most strongly, and the sensor was more sensitive to Pb(2+) compared to Hg(2+). The concentrations of ions in the parts per million range produced the changes in the SPR angle minimum in the region of 0.03 to 0.07. Data analysis was done by Matlab software using Fresnel formula for multilayer system."	""
+3	"asian"	"Korea"	"Korea"	"0.00485436893204"	"0.0291262135922"	"0.0485436893204"	"206"	"6.17142857143"	"Bioinformatics"	"Ahn J, Yoon Y, Park C, Shin E, Park S"	"Department of Computer Science, Yonsei University, Seoul, South Korea."	"MOTIVATION: Diagnosis and prognosis of cancer and understanding oncogenesis within the context of biological pathways is one of the most important research areas in bioinformatics. Recently, there have been several attempts to integrate interactome and transcriptome data to identify subnetworks that provide limited interpretations of known and candidate cancer genes, as well as increase classification accuracy. However, these studies provide little information about the detailed roles of identified cancer genes. RESULTS: To provide more information to the network, we constructed the network by incorporating genetic interactions and manually curated gene regulations to the protein interaction network. To make our newly constructed network cancer specific, we identified edges where two genes show different expression patterns between cancer and normal phenotypes. We showed that the integration of various datasets increased classification accuracy, which suggests that our network is more complete than a network based solely on protein interactions. We also showed that our network contains significantly more known cancer-related genes than other feature selection algorithms. Through observations of some examples of cancer-specific subnetworks, we were able to predict more detailed and interpretable roles of oncogenes and other cancer candidate genes in the prostate cancer cells. AVAILABILITY: CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
+3	"asian"	"Japan"	"Japan"	"0.0"	"0.0161290322581"	"0.0443548387097"	"248"	"13.0526315789"	"Glycobiology"	"Akatsu C, Mizumoto S, Kaneiwa T, Maccarana M, Malmstrom A, Yamada S, Sugahara K"	"Laboratory of Proteoglycan Signaling and Therapeutics, Hokkaido University Graduate School of Life Science, Sapporo, Japan."	"Chondroitin sulfate (CS) and dermatan sulfate (DS) are expressed in significant amounts in the brain and play important roles in the development of the central nervous system in mammals. CS and DS structures are often found in a single CS/DS hybrid chain. The l-iduronic acid (IdoA)-containing domain, which defines a DS-type domain, appears key to the biological functions of the CS/DS hybrid chain. In this study, to clarify the distribution of the DS-type structure in the brain during development, the expression patterns of DS epimerase 1 (DS-epi1) and DS-epi2, both of which convert d-glucuronic acid into IdoA, were investigated by in situ hybridization. DS-epi2 was ubiquitously expressed in the developing brain after birth, whereas the expression of DS-epi1 was faint and obscure at all developmental stages. Quantitative real-time polymerase chain reaction revealed the expression of DS-epi2 to be higher than that of DS-epi1 throughout development, suggesting that DS-epi2 but not DS-epi1 is mostly expressed in the brain and plays key roles in the epimerization of CS/DS during its biosynthesis. Moreover, an analysis of the disaccharides of CS/DS demonstrated significant amounts of IdoA-containing iD units [IdoA(2S)-GalNAc(6S)] and iB units [IdoA(2S)-GalNAc(4S)], where 2S, 4S and 6S stand for 2-O-, 4-O- and 6-O-sulfate, respectively, in every region of the brain examined. The proportion of these units in cerebellar CS/DS was greatly altered during postnatal development. These results suggest that the IdoA-containing structures in the developing brain are mainly produced by the actions of DS-epi2 and play crucial roles in postnatal development."	""
+3	"asian"	"United Arab Emirates, United Arab Emirates"	"United Arab Emirates"	"0.00921658986175"	"0.00921658986175"	"0.0875576036866"	"217"	"10.4285714286"	"PLoS One"	"Alkaabi JM, Al Neyadi M, Al Darei F, Al Mazrooei M, Al Yazedi J, Abdulle AM"	"Department of Internal Medicine, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates."	"BACKGROUND: To describe the characteristics, clinical presentations, management and complications of snakebites in the border region between Al-Ain, United Arab Emirates (UAE) and Buraimi, Sultanate of Oman. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a retrospective review of medical records to study snakebite cases over four-year duration at three tertiary hospitals. Overall, 64 snakebite cases were studied with median hospitalization of 2 (interquartile range [IQR] 1-4) days. The majority of cases were male (87.5%), and most (61%) of the incidents occurred during summer months. The bite sites were predominantly (95%) to the feet and hands. Main clinical features included pain, local swelling, and coagulopathy, blistering and skin peeling. Overall, there were no deaths, but few major complications occurred; extensive skin peeling (n = 5, 8%), multi-organ failure (n = 1, 1.5%), and compartment syndrome (n = 1, 1.5%). Polyvalent anti snake venom (ASV), analgesia, tetanus toxoid, intravenous fluids, and antibiotics such as ampicillin, cloxacillin, and cephalosporins were commonly instituted as part of treatment protocols in the three hospitals. CONCLUSION: The overwhelming majority of bites occurred during summer months, and envenomations were more common in, relatively, young male farmers, but with no serious clinical complications. Prevention and treatment strategies should include increasing public awareness, developing management guidelines, and manufacturing specific ASV for a wide spectrum of the local venomous snakes."	""
+3	"asian"	"Israel"	"Israel"	"0.0"	"0.0"	"0.0512820512821"	"39"	"7.8"	"Immunity"	"Alon R"	"Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel."	"In this issue of Immunity, Bao et al. (2010) provide in vivo evidence that heparan sulfate glycosaminoglycans (GAGs) are indispensable for immobilization and function of major chemokines required for leukocyte adhesion to and crossing through blood and lymphatic vessels."	""
+3	"asian"	"Singapore, Singapore"	"Singapore"	"0.00803212851406"	"0.0120481927711"	"0.0562248995984"	"249"	"11.8571428571"	"PLoS One"	"Ang SF, Moochhala SM, Macary PA, Bhatia M"	"Immunology Program and Department of Microbiology, Center for Life Sciences, National University of Singapore, Singapore."	"Hydrogen sulfide (H(2)S) has been shown to induce transient receptor potential vanilloid 1 (TRPV1)-mediated neurogenic inflammation in polymicrobial sepsis. However, endogenous neural factors that modulate this event and the molecular mechanism by which this occurs remain unclear. Therefore, this study tested the hypothesis that whether substance P (SP) is one important neural element that implicates in H(2)S-induced neurogenic inflammation in sepsis in a TRPV1-dependent manner, and if so, whether H(2)S regulates this response through activation of the extracellular signal-regulated kinase-nuclear factor-kappaB (ERK-NF-kappaB) pathway. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with TRPV1 antagonist capsazepine 30 minutes before CLP. DL-propargylglycine (PAG), an inhibitor of H(2)S formation, was administrated 1 hour before or 1 hour after sepsis, whereas sodium hydrosulfide (NaHS), an H(2)S donor, was given at the same time as CLP. Capsazepine significantly attenuated H(2)S-induced SP production, inflammatory cytokines, chemokines, and adhesion molecules levels, and protected against lung and liver dysfunction in sepsis. In the absence of H(2)S, capsazepine caused no significant changes to the PAG-mediated attenuation of lung and plasma SP levels, sepsis-associated systemic inflammatory response and multiple organ dysfunction. In addition, capsazepine greatly inhibited phosphorylation of ERK(1/2) and inhibitory kappaBalpha, concurrent with suppression of NF-kappaB activation even in the presence of NaHS. Furthermore, capsazepine had no effect on PAG-mediated abrogation of these levels in sepsis. Taken together, the present findings show that H(2)S regulates TRPV1-mediated neurogenic inflammation in polymicrobial sepsis through enhancement of SP production and activation of the ERK-NF-kappaB pathway."	""
+3	"asian"	"Japan, Japan"	"Japan"	"0.00653594771242"	"0.0"	"0.0653594771242"	"153"	"17.0"	"Nature Genetics"	"Arakawa S, Takahashi A, Ashikawa K, Hosono N, Aoi T, Yasuda M, Oshima Y, Yoshida S, Enaida H, Tsuchihashi T, Mori K, Honda S, Negi A, Arakawa A, Kadonosono K, Kiyohara Y, Kamatani N, Nakamura Y, Ishibashi T, Kubo M"	"1] Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan. [2] Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan."	"Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the world, is a complex disease caused by multiple environmental and genetic risk factors. To identify genetic factors that modify the risk of exudative AMD in the Japanese population, we conducted a genome-wide association study and a replication study using a total of 1,536 individuals with exudative AMD and 18,894 controls. In addition to CFH (rs800292, P = 4.23 x 10(-15)) and ARMS2 (rs3750847, P = 8.67 x 10(-29)) loci, we identified two new susceptibility loci for exudative AMD: TNFRSF10A-LOC389641 on chromosome 8p21 (rs13278062, combined P = 1.03 x 10(-12), odds ratio = 0.73) and REST-C4orf14-POLR2B-IGFBP7 on chromosome 4q12 (rs1713985, combined P = 2.34 x 10(-8), odds ratio = 1.30). Fine mapping revealed that rs13278062, which is known to alter TNFRSF10A transcriptional activity, had the most significant association in 8p21 region. Our results provide new insights into the pathophysiology of exudative AMD."	""
+3	"asian"	"Japan"	"Japan"	"0.0135135135135"	"0.027027027027"	"0.0608108108108"	"148"	"8.70588235294"	"Immunity"	"Asano K, Nabeyama A, Miyake Y, Qiu CH, Kurita A, Tomura M, Kanagawa O, Fujii S, Tanaka M"	"Laboratory for Innate Cellular Immunity, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan."	"The generation of tumor-directed cytotoxic T lymphocytes is considered crucial for the induction of antitumor immunity. To activate these CD8(+) T cells, antigen-presenting cells (APCs) must initially acquire tumor cell-associated antigens. The major source of tumor antigens is dead tumor cells, but little is known about how APCs in draining lymph nodes acquire and crosspresent these antigens. Here we show that CD169(+) macrophages phagocytose dead tumor cells transported via lymphatic flow and subsequently crosspresent tumor antigens to CD8(+) T cells. Subcutaneous immunization with irradiated tumor cells protects mice from syngenic tumor. However, tumor antigen-specific CD8(+) T cell activation and subsequent antitumor immunity are severely impaired in mice depleted with CD169(+) macrophages. Neither migratory dendritic cells (DCs) nor lymph node-resident conventional DCs are essential for the crosspresentation of tumor antigens. Thus, we have identified CD169(+) macrophages as lymph node-resident APCs dominating early activation of tumor antigen-specific CD8(+) T cells."	""
+3	"asian"	"Israel"	"Israel"	"0.00392156862745"	"0.0235294117647"	"0.113725490196"	"255"	"8.35483870968"	"Bioinformatics"	"Ashkenazy H, Unger R, Kliger Y"	"Compugen LTD, Tel Aviv 69512, Israel."	"MOTIVATION: Prediction of interactions between protein residues (contact map prediction) can facilitate various aspects of 3D structure modeling. However, the accuracy of ab initio contact prediction is still limited. As structural genomics initiatives move ahead, solved structures of homologous proteins can be used as multiple templates to improve contact prediction of the major conformation of an unsolved target protein. Furthermore, multiple templates may provide a wider view of the proteins conformational space. However, successful usage of multiple structural templates is not straightforward, due to their variable relevance to the target protein, and because of data redundancy issues. RESULTS: We present here an algorithm that addresses these two limitations in the use of multiple structure templates. First, the algorithm unites contact maps extracted from templates sharing high sequence similarity with each other in a fashion that acknowledges the possibility of multiple conformations. Next, it weights the resulting united maps in inverse proportion to their evolutionary distance from the target protein. Testing this algorithm against CASP8 targets resulted in high precision contact maps. Remarkably, based solely on structural data of remote homologues, our algorithm identified residue-residue interactions that account for all the known conformations of calmodulin, a multifaceted protein. Therefore, employing multiple templates, which improves prediction of contact maps, can also be used to reveal novel conformations. As multiple templates will soon be available for most proteins, our scheme suggests an effective procedure for their optimal consideration. AVAILABILITY: A Perl script implementing the WMC algorithm described in this article is freely available for academic use at"	""
+3	"asian"	"Iran"	"Iran"	"0.0238095238095"	"0.00793650793651"	"0.047619047619"	"252"	"10.9565217391"	"PLoS One"	"Assadi M, Salimipour H, Akbarzadeh S, Nemati R, Jafari SM, Bargahi A, Samani Z, Seyedabadi M, Sanjdideh Z, Nabipour I"	"The Persian Gulf Nuclear Medicine Research Centre, Bushehr University of Medical Sciences, Bushehr, Iran."	"BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of osteoporosis and fractures. Adipose tissue-derived adipokines may play important roles in the osteoimmunology of MS. In order to determine whether omentin-1 and vaspin may be related to bone health in MS patients, we compared circulating levels of these recently identified adipokines, between MS patients and healthy controls. METHODS: A total of 35 ambulatory MS patients with relapsing-remitting courses were compared with 38 age- and sex-matched healthy controls. Bone mineral density (BMD) was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy x-ray absorptiometry. Circulating omentin-1, vaspin, osteocalcin, osteopontin, osteoprotegerin, the receptor activator of nuclear factor-kappaB ligand, matrix metalloproteinase 9, C-reactive protein and 25-hydroxy vitamin D levels were evaluated by highly specific enzyme-linked immunosorbent assay methods. RESULTS: There was no significant difference between the two groups regarding bone-related cytokines, adipocytokines, and the BMD measurements of patients with MS and the healthy controls. However, in multiple regression analysis, serum omentin-1 levels were positively correlated with BMD at the femoral neck (beta = 0.49, p = 0.016), total hip (beta = 0.42, p = 0.035), osteopontin (beta = 0.42, p = 0.030) and osteocalcin (beta = 0.53, p = 0.004) in MS patients. No correlations were found between vaspin, biochemical, and BMD measures in both groups. CONCLUSIONS: Elevated omentin-1 serum levels are correlated with BMD at the femoral neck and the serum levels of osteocalcin and osteopontin in MS patients. Therefore, there is crosstalk between adipose tissue and bone in MS."	""
+3	"asian"	"India"	"India"	"0.00934579439252"	"0.00934579439252"	"0.0560747663551"	"107"	"8.23076923077"	"Bioinformatics"	"Athale CA, Chaudhari H"	"Division of Biology, IISER Pune, Central Tower, Sai Trinity, Pashan, Pune 411021, India."	"MOTIVATION: Cell sizes and shapes are a fundamental defining characteristic of all cellular life. In bacteria like E. coli, the machinery that determines cell length is complex and interconnected, spanning extracellular cues, biosynthesis and cell division. Few tools exist to study cell lengths in a population. We have developed and tested three automated image analysis routines on growing E. coli cultures to simultaneously measure cell lengths and nucleoid numbers in populations of bacteria. We find population profiles changing with culture density- higher density of culture leads to fewer long cells. Additionally, lab strains mutant for recA show a correlation between the number of nucleoids and cell length."	""
+3	"asian"	"Israel"	"Israel"	"0.00990099009901"	"0.039603960396"	"0.108910891089"	"303"	"8.82857142857"	"BMC Bioinformatics"	"Avihoo A, Churkin A, Barash D"	"Department of Computer Science, Ben-Gurion University, 84105 Beer Sheva, Israel."	"ABSTRACT: BACKGROUND: RNAexinv is an interactive java application that performs RNA sequence design, constrained to yield a specific RNA shape and physical attributes. It is an extended inverse RNA folding program with the rationale behind that the generated sequences should not only fold into a desired structure, but they should also exhibit favorable attributes such as thermodynamic stability and mutational robustness. RNAexinv considers not only the secondary structure in order to design sequences, but also the mutational robustness and the minimum free energy. The sequences that are generated may not fully conform with the given RNA secondary structure, but they will strictly conform with the RNA shape of the given secondary structure and thereby take into consideration the recommended values of thermodynamic stability and mutational robustness that are provided. RESULTS: The output consists of designed sequences that are generated by the proposed method. Selecting a sequence displays the secondary structure drawings of the target and the predicted fold of the sequence, including some basic information about the desired and achieved thermodynamic stability and mutational robustness. RNAexinv can be used successfully without prior experience, simply specifying an initial RNA secondary structure in dot-bracket notation and numerical values for the desired neutrality and minimum free energy. The package runs under LINUX operating system. Secondary structure predictions are performed using the Vienna RNA package. CONCLUSIONS: RNAexinv is a user friendly tool that can be used for RNA sequence design. It is especially useful in cases where a functional stem-loop structure of a natural sequence should be strictly kept in the designed sequences but a distant motif in the rest of the structure may contain one more or less nucleotide at the expense of another, as long as the global shape is preserved. This allows the insertion of physical observables as constraints. RNAexinv is available at"	""
+3	"asian"	"India"	"India"	"0.012"	"0.028"	"0.1"	"250"	"10.8695652174"	"PLoS One"	"B R, C GP"	"Medical Biotechnology Division, Center for Nanobiotechnology, School of Biosciences and Technology, Vellore Institute of Technology University, Vellore, Tamil Nadu, India."	"BACKGROUND: A major area of effort in current genomics is to distinguish mutations that are functionally neutral from those that contribute to disease. Single Nucleotide Polymorphisms (SNPs) are amino acid substitutions that currently account for approximately half of the known gene lesions responsible for human inherited diseases. As a result, the prediction of non-synonymous SNPs (nsSNPs) that affect protein functions and relate to disease is an important task. PRINCIPAL FINDINGS: In this study, we performed a comprehensive analysis of deleterious SNPs at both functional and structural level in the respective genes associated with red blood cell metabolism disorders using bioinformatics tools. We analyzed the variants in Glucose-6-phosphate dehydrogenase (G6PD) and isoforms of Pyruvate Kinase (PKLR & PKM2) genes responsible for major red blood cell disorders. Deleterious nsSNPs were categorized based on empirical rule and support vector machine based methods to predict the impact on protein functions. Furthermore, we modeled mutant proteins and compared them with the native protein for evaluation of protein structure stability. SIGNIFICANCE: We argue here that bioinformatics tools can play an important role in addressing the complexity of the underlying genetic basis of Red Blood Cell disorders. Based on our investigation, we report here the potential candidate SNPs, for future studies in human Red Blood Cell disorders. Current study also demonstrates the presence of other deleterious mutations and also endorses with in vivo experimental studies. Our approach will present the application of computational tools in understanding functional variation from the perspective of structure, expression, evolution and phenotype."	""
+3	"asian"	"Korea"	"Korea"	"0.01"	"0.025"	"0.08"	"200"	"11.7647058824"	"Blood"	"Bae JS, Rezaie AR"	"College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea, Republic of;"	"A pathogenic role for high mobility group box 1 (HMGB1) protein has been postulated in severe sepsis. Activated protein C (APC) is the only FDA-approved drug for severe sepsis, however, its effect on HMGB1 signaling has never been investigated. Here, we monitored the effect of APC on the LPS-mediated release of HMGB1 and the HMGB1-mediated modulation of pro-inflammatory responses in human umbilical vein endothelial cells. APC potently inhibited the release of HMGB1 and down-regulated the adhesion of the monocytic cell line, THP-1, to HMGB1-activated endothelial cells. HMGB1 up-regulated pro-inflammatory responses by interacting with three pathogen-related pattern recognition receptors: toll-like receptors 2, 4 and the receptor for advanced glycation end products. APC not only inhibited HMGB1 release, but also down-regulated the cell surface expression of all three HMGB1 receptors in endothelial cells. The protective effects of APC were mediated through EPCR and PAR-1. Interestingly, a thrombin derivative containing the Gla-domain of APC recapitulated all protective effects of APC with a 20-50-fold higher efficacy. These results suggest that the EPCR- and PAR-1-dependent protective effects of APC in severe sepsis may partially be mediated through the inhibition of HMGB1 signaling and that the chimeric thrombin mutant has potential therapeutic utility for severe sepsis."	""
+3	"asian"	"Korea"	"Korea"	"0.0"	"0.027397260274"	"0.0821917808219"	"219"	"10.4285714286"	"BMC Bioinformatics"	"Bae SE, Son HS"	"Laboratory of Computational Biology & Bioinformatics, Institute of Health and Environment, Graduate School of Public Health, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea."	"BACKGROUND: Viral zoonosis, the transmission of a virus from its primary vertebrate reservoir species to humans, requires ubiquitous cellular proteins known as receptor proteins. Zoonosis can occur not only through direct transmission from vertebrates to humans, but also through intermediate reservoirs or other environmental factors. Viruses can be categorized according to genotype (ssDNA, dsDNA, ssRNA and dsRNA viruses). Among them, the RNA viruses exhibit particularly high mutation rates and are especially problematic for this reason. Most zoonotic viruses are RNA viruses that change their envelope proteins to facilitate binding to various receptors of host species. In this study, we sought to predict zoonotic propensity through the analysis of receptor characteristics. We hypothesized that the major barrier to interspecies virus transmission is that receptor sequences vary among species--in other words, that the specific amino acid sequence of the receptor determines the ability of the viral envelope protein to attach to the cell. RESULTS: We analysed host-cell receptor sequences for their hydrophobicity/hydrophilicity characteristics. We then analysed these properties for similarities among receptors of different species and used a statistical discriminant analysis to predict the likelihood of transmission among species. CONCLUSIONS: This study is an attempt to predict zoonosis through simple computational analysis of receptor sequence differences. Our method may be useful in predicting the zoonotic potential of newly discovered viral strains."	""
 3	"asian"	"China"	"China"	"0.00497512437811"	"0.0149253731343"	"0.0597014925373"	"201"	"11.8235294118"	"PLoS One"	"Bai F, Watson DR, Shi Y, Wang Y, Yue C, Yuhuanteng, Wu D, Yuan Y, Zhang Z"	"Medical School of Southeast University, Nanjing, China."	"BACKGROUND: Deficits of the default mode network (DMN) have been demonstrated in subjects with amnestic type mild cognitive impairment (aMCI) who have a high risk of developing Alzheimers disease (AD). However, no longitudinal study of this network has been reported in aMCI. Identifying links between development of DMN and aMCI progression would be of considerable value in understanding brain changes underpinning aMCI and determining risk of conversion to AD. METHODOLOGY/PRINCIPAL FINDINGS: Resting-state fMRI was acquired in aMCI subjects (n = 26) and controls (n = 18) at baseline and after approximately 20 months follow up. Independent component analysis was used to isolate the DMN in each participant. Differences in DMN between aMCI and controls were examined at baseline, and subsequent changes between baseline and follow-up were also assessed in the groups. Posterior cingulate cortex/precuneus (PCC/PCu) hyper-functional connectivity was observed at baseline in aMCI subjects, while a substantial decrement of these connections was evident at follow-up in aMCI subjects, compared to matched controls. Specifically, PCC/PCu dysfunction was positively related to the impairments of episodic memory from baseline to follow up in aMCI group. CONCLUSIONS/SIGNIFICANCE: The patterns of longitudinal deficits of DMN may assist investigators to identify and monitor the development of aMCI."	""
+3	"asian"	"India"	"India"	"0.0103626943005"	"0.0259067357513"	"0.0518134715026"	"193"	"12.8666666667"	"Glycobiology"	"Bajaj M, Hinge A, Limaye LS, Gupta RK, Surolia A, Kale VP"	"National Center for Cell Science, NCCS Complex, University of Pune Campus, Pune 411007, India."	"We have recently demonstrated that the mannose-binding lectins, namely banana lectin (BL) and garlic lectin (GL), interacted with the insulin receptors on M210B4 cells--an established mesenchymal cell line of murine marrow origin--and initiate mitogen-activated protein kinase kinase (MEK)-dependent extracellular signal-regulated kinase (ERK) signaling in them. In this study, we show that this lectin-mediated active ERK signaling culminates into an adipogenic differentiation of these cells. Gene expression studies indicate that the effect takes place at the transcriptional level. Experiments carried out with pharmacological inhibitors show that MEK-dependent ERK and phosphatidylinositol 3-kinase-dependent AKT pathways are positive regulators of the lectin- and insulin-mediated adipogenic differentiation, while stress-activated kinase/c-jun N-terminal kinase pathway acts as a negative one. Since both lectins could efficiently substitute for insulin in the standard adipogenic induction medium, they may perhaps serve as molecular tools to study the mechanistic aspects of the adipogenic process that are independent of cell proliferation. Our study clearly demonstrates the ability of BL and GL to activate insulin-like signaling in the mesenchymal cells in vitro leading to their adipocytic differentiation. The dietary origin of these lectins underscores an urgent need to examine their in vivo effects on tissue homeostasis."	""
+3	"asian"	"Israel"	"Israel"	"0.00363636363636"	"0.00727272727273"	"0.0727272727273"	"275"	"13.1428571429"	"PLoS Computational Biology"	"Bar-On D, Nachliel E, Gutman M, Ashery U"	"Department of Neurobiology, Tel Aviv University, Tel Aviv, Israel."	"The Sec1/munc18 protein family is essential for vesicle fusion in eukaryotic cells via binding to SNARE proteins. Protein kinase C modulates these interactions by phosphorylating munc18a thereby reducing its affinity to one of the central SNARE members, syntaxin-1a. The established hypothesis is that the reduced affinity of the phosphorylated munc18a to syntaxin-1a is a result of local electrostatic repulsion between the two proteins, which interferes with their compatibility. The current study challenges this paradigm and offers a novel mechanistic explanation by revealing a syntaxin-non-binding conformation of munc18a that is induced by the phosphomimetic mutations. In the present study, using molecular dynamics simulations, we explored the dynamics of the wild-type munc18a versus phosphomimetic mutant munc18a. We focused on the structural changes that occur in the cavity between domains 3a and 1, which serves as the main syntaxin-binding site. The results of the simulations suggest that the free wild-type munc18a exhibits a dynamic equilibrium between several conformations differing in the size of its cavity (the main syntaxin-binding site). The flexibility of the cavitys size might facilitate the binding or unbinding of syntaxin. In silico insertion of phosphomimetic mutations into the munc18a structure induces the formation of a conformation where the syntaxin-binding area is rigid and blocked as a result of interactions between residues located on both sides of the cavity. Therefore, we suggest that the reduced affinity of the phosphomimetic mutant/phosphorylated munc18a is a result of the closed-cavity conformation, which makes syntaxin binding energetically and sterically unfavorable. The current study demonstrates the potential of phosphorylation, an essential biological process, to serve as a driving force for dramatic conformational changes of proteins modulating their affinity to target proteins."	""
+3	"asian"	"Kolkata, India"	"India"	"0.0106382978723"	"0.0248226950355"	"0.102836879433"	"282"	"11.28"	"BMC Bioinformatics"	"Basu S, Bhattacharyya D, Banerjee R"	"Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Bidhannagar, Kolkata, India."	"BACKGROUND: Mapping protein primary sequences to their three dimensional folds referred to as the second genetic code remains an unsolved scientific problem. A crucial part of the problem concerns the geometrical specificity in side chain association leading to densely packed protein cores, a hallmark of correctly folded native structures. Thus, any model of packing within proteins should constitute an indispensable component of protein folding and design. RESULTS: In this study an attempt has been made to find, characterize and classify recurring patterns in the packing of side chain atoms within a protein which sustains its native fold. The interaction of side chain atoms within the protein core has been represented as a contact network based on the surface complementarity and overlap between associating side chain surfaces. Some network topologies definitely appear to be preferred and they have been termed packing motifs, analogous to super secondary structures in proteins. Study of the distribution of these motifs reveals the ubiquitous presence of typical smaller graphs, which appear to get linked or coalesce to give larger graphs, reminiscent of the nucleation-condensation model in protein folding. One such frequently occurring motif, also envisaged as the unit of clustering, the three residue clique was invariably found in regions of dense packing. Finally, topological measures based on surface contact networks appeared to be effective in discriminating sequences native to a specific fold amongst a set of decoys. CONCLUSIONS: Out of innumerable topological possibilities, only a finite number of specific packing motifs are actually realized in proteins. This small number of motifs could serve as a basis set in the construction of larger networks. Of these, the triplet clique exhibits distinct preference both in terms of composition and geometry."	""
+3	"asian"	"Kolkata, India"	"India"	"0.00657894736842"	"0.00657894736842"	"0.0592105263158"	"304"	"17.8823529412"	"PLoS One"	"Bhattacharya P, Gupta G, Majumder S, Adhikari A, Banerjee S, Halder K, Bhattacharya Majumdar S, Ghosh M, Chaudhuri S, Roy S, Majumdar S"	"Division of Molecular Medicine, Bose Institute, Kolkata, India."	"The parasitic protozoan Leishmania donovani is the causative organism for visceral leishmaniasis (VL) which persists in the host macrophages by deactivating its signaling machinery resulting in a critical shift from proinflammatory (Th1) to an anti-inflammatory (Th2) response. The severity of this disease is mainly determined by the production of IL-12 and IL-10 which could be reversed by use of effective immunoprophylactics. In this study we have evaluated the potential of Arabinosylated Lipoarabinomannan (Ara-LAM), a cell wall glycolipid isolated from non pathogenic Mycobacterium smegmatis, in regulating the host effector response via effective regulation of mitogen-activated protein kinases (MAPK) signaling cascades in Leishmania donovani infected macrophages isolated from BALB/C mice. Ara-LAM, a Toll-like receptor 2 (TLR2) specific ligand, was found to activate p38 MAPK signaling along with subsequent abrogation of extracellular signal-regulated kinase (ERKs) signaling. The use of pharmacological inhibitors of p38MAPK and ERK signaling showed the importance of these signaling pathways in the regulation of IL-10 and IL-12 in Ara-LAM pretreated parasitized macrophages. Molecular characterization of this regulation of IL-10 and IL-12 was revealed by chromatin immunoprecipitation assay (CHIP) which showed that in Ara-LAM pretreated parasitized murine macrophages there was a significant induction of IL-12 by selective phosphorylation and acetylation of histone H3 residues at its promoter region. While, IL-10 production was attenuated by Ara-LAM pretreatment via abrogation of histone H3 phosphorylation and acetylation at its promoter region. This Ara-LAM mediated antagonistic regulations in the induction of IL-10 and IL-12 genes were further correlated to changes in the transcriptional regulators Signal transducer and activator of transcription 3 (STAT3) and Suppressor of cytokine signaling 3 (SOCS3). These results demonstrate the crucial role played by Ara-LAM in regulating the MAPK signaling pathway along with subsequent changes in host effector response during VL which might provide crucial clues in understanding the Ara-LAM mediated protection during Leishmania induced pathogenesis."	""
+1	"asian"	"New York, New York"	"USA"	"0.0"	"0.0263157894737"	"0.0592105263158"	"152"	"11.6923076923"	"Molecular Biology and Evolution"	"Cai X, Clapham DE"	"Molecular Pathogenesis Program, The Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, NY 10016."	"Animals and fungi diverged from a common unicellular ancestor of Opisthokonta, yet they exhibit significant differences in their components of Ca(2+) signaling pathways. Many Ca(2+) signaling molecules appear to be either animal-specific or fungal-specific, which is generally believed to result from lineage-specific adaptations to distinct physiological requirements. Here, by analyzing the genomic data from several close relatives of animals and fungi, we demonstrate that many components of animal and fungal Ca(2+) signaling machineries are present in the apusozoan protist Thecamonas trahens, which belongs to the putative unicellular sister group to Opisthokonta. We also identify the conserved portion of Ca(2+) signaling molecules in early evolution of animals and fungi following their divergence. Furthermore, our results reveal the lineage-specific expansion of Ca(2+) channels and transporters in the unicellular ancestors of animals and in basal fungi. These findings provide novel insights into the evolution and regulation of Ca(2+) signaling critical for animal and fungal biology."	""
+1	"asian"	"USA."	"USA"	"0.0177304964539"	"0.0283687943262"	"0.102836879433"	"282"	"13.4285714286"	"BMC Bioinformatics"	"Cai X, Huang A, Xu S"	"Department of Electrical and Computer Engineering, University of Miami, Coral Gables, FL 33146, USA."	"BACKGROUND: The Bayesian shrinkage technique has been applied to multiple quantitative trait loci (QTLs) mapping to estimate the genetic effects of QTLs on quantitative traits from a very large set of possible effects including the main and epistatic effects of QTLs. Although the recently developed empirical Bayes (EB) method significantly reduced computation comparing with the fully Bayesian approach, its speed and accuracy are limited by the fact that numerical optimization is required to estimate the variance components in the QTL model. RESULTS: We developed a fast empirical Bayesian LASSO (EBLASSO) method for multiple QTL mapping. The fact that the EBLASSO can estimate the variance components in a closed form along with other algorithmic techniques render the EBLASSO method more efficient and accurate. Comparing with the EB method, our simulation study demonstrated that the EBLASSO method could substantially improve the computational speed and detect more QTL effects without increasing the false positive rate. Particularly, the EBLASSO algorithm running on a personal computer could easily handle a linear QTL model with more than 100,000 variables in our simulation study. Real data analysis also demonstrated that the EBLASSO method detected more reasonable effects than the EB method. Comparing with the LASSO, our simulation showed that the current version of the EBLASSO implemented in Matlab had similar speed as the LASSO implemented in Fortran, and that the EBLASSO detected the same number of true effects as the LASSO but a much smaller number of false positive effects. CONCLUSIONS: The EBLASSO method can handle a large number of effects possibly including both the main and epistatic QTL effects, environmental effects and the effects of gene-environment interactions. It will be a very useful tool for multiple QTL mapping."	""
 3	"asian"	"China"	"China"	"0.0"	"0.0131578947368"	"0.0592105263158"	"152"	"11.6923076923"	"Immunity"	"Cao W, Yang Y, Wang Z, Liu A, Fang L, Wu F, Hong J, Shi Y, Leung S, Dong C, Zhang JZ"	"Institute of Health Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences and Shanghai JiaoTong University School of Medicine, Shanghai 200025, China."	"Neural progenitor cell (NPC) therapy is considered a promising treatment modality for multiple sclerosis (MS), potentially acting through neural repair. Here, we showed that intravenous administration of NPCs ameliorated experimental autoimmune encephalomyelitis (EAE) by selectively inhibiting pathogenic T helper 17 (Th17) cell differentiation. Leukemia inhibitory factor (LIF) produced by NPCs was responsible for the observed EAE suppression. Through the inducible LIF receptor expression, LIF inhibited the differentiation of Th17 cells in EAE mice and that from MS subjects. At the molecular level, LIF exerted an opposing effect on interleukin 6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation required for Th17 cell differentiation by triggering a signaling cascade that activated extracellular signal-regulated MAP kinase (ERK) and upregulated suppressor of cytokine signaling 3 (SOCS3) expression. This study reveals a critical role for LIF in regulating Th17 cell differentiation and provides insights into the mechanisms of action of NPC therapy in MS."	""
+3	"asian"	"Japan"	"Japan"	"0.0138888888889"	"0.0138888888889"	"0.0694444444444"	"144"	"7.0"	"Nature Genetics"	"Cha PC, Takahashi A, Hosono N, Low SK, Kamatani N, Kubo M, Nakamura Y"	"Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan."	"Uterine fibroids are a common benign tumor of the female genital tract. We conducted a genome-wide association study in which 457,044 SNPs were analyzed in 1,607 individuals with clinically diagnosed uterine fibroids and 1,428 female controls. SNPs showing suggestive associations (P < 5 x 10(-5)) were further genotyped in 3,466 additional cases and 3,245 female controls. Three loci on chromosomes 10q24.33, 22q13.1 and 11p15.5 revealed genome-wide significant associations with uterine fibroids. The SNPs showing the most significant association in a combination analysis at each of these loci were rs7913069 (P = 8.65 x 10(-14), odds ratio (OR) = 1.47), rs12484776 (P = 2.79 x 10(-12), OR = 1.23) and rs2280543 (P = 3.82 x 10(-12), OR = 1.39), respectively. Subsequent fine mapping of these regions will be necessary to pinpoint the causal variants. Our findings should shed light on the pathogenesis of uterine fibroids."	""
+3	"asian"	"Hong Kong, Hong Kong"	"Hong Kong"	"0.004329004329"	"0.017316017316"	"0.0952380952381"	"231"	"7.12121212121"	"Bioinformatics"	"Chan SH, Ji P"	"Department of Industrial and Systems Engineering, The Hong Kong Polytechnic University, Hung Hom, Hong Kong."	"MOTIVATION: Elementary flux mode (EFM) is a fundamental concept as well as a useful tool in metabolic pathway analysis. One important role of EFMs is that every flux distribution can be decomposed into a set of EFMs and a number of methods to study flux distributions originated from it. Yet finding such decompositions requires the complete set of EFMs, which is intractable in genome-scale metabolic networks due to combinatorial explosion. RESULTS: In this article, we proposed an algorithm to decompose flux distributions into EFMs in genome-scale networks. It is an iterative scheme of a mixed integer linear program. Unlike previous optimization models to find pathways, any feasible solutions can become EFMs in our algorithm. This advantage enables the algorithm to approximate the EFM of largest contribution to an objective reaction in a flux distribution. Our algorithm is able to find EFMs of flux distributions with complex structures, closer to the realistic case in which a cell is subject to various constraints. A case of Escherichia coli growth in the Lysogeny broth (LB) medium containing various carbon sources was studied. Essential metabolites and their syntheses were located. Information on the contribution of each carbon source not obvious from the apparent flux distribution was also revealed. Our work further confirms the utility of finding EFMs by optimization models in genome-scale metabolic networks. CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
+3	"asian"	"Taiwan, China"	"China"	"0.00571428571429"	"0.0342857142857"	"0.0857142857143"	"175"	"10.2941176471"	"Molecular Biology and Evolution"	"Chang AY, Liao BY"	"Division of Biostatistics & Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Taiwan, Republic of China."	"Although gene duplication plays a major role in organismal evolution, it may also lead to gene dosage imbalance, thereby having an immediate adverse effect on an organisms fitness. Investigating the evolution of the expression patterns of genes that duplicated after the divergence of rodents and primates, we confirm that adaptive evolution has been involved in dosage rebalance after gene duplication. To understand mechanisms underlying this process, we examined 1) microRNA (miRNA)-mediated gene regulation, 2) cis-regulatory sequence modifications, and 3) DNA methylation. Neither miRNA-mediated regulation nor cis-regulatory changes was found to be associated with expression reduction of duplicate genes. By contrast, duplicate genes, especially lowly expressed copies, were heavily methylated in the upstream region. However, for duplicate genes encoding proteins that are members of macromolecular complexes, heavy methylation in the genic region was not consistently observed. This result held after controlling potential confounding factors, such as enrichment in functional categories. Our results suggest that during mammalian evolution, DNA methylation plays a dominant role in dosage rebalance after gene duplication by inhibiting transcription initiation of duplicate genes."	""
+3	"asian"	"Taiwan"	"China"	"0.0229007633588"	"0.00763358778626"	"0.106870229008"	"131"	"10.0769230769"	"Glycobiology"	"Chang CF, Pan JF, Lin CN, Wu IL, Wong CH, Lin CH"	"Department of Medical Laboratory Science and Biotechnology, National Taiwan University, Taipei."	"Cell-surface carbohydrates are known to participate in many important physiological and pathological activities by interacting with their corresponding proteins or receptors. Although several methods have been developed for studying carbohydrate-protein interactions, one major problem originates from the weak bindings of carbohydrates/proteins that are often lost during repeating wash steps. Herein, we established a homogeneous solution carbohydrate array in which polyacrylamide-based glycans are used for offering a multivalent environment. The method requires no wash step and can be carried out in a high-throughput manner. We characterized the carbohydrate-binding specificities of 11 lectins and 7 antibodies, the majority of which displayed the binding patterns in consistence with previous reports. These results demonstrate that our developed solution carbohydrate array provides a useful alternative that is better than or comparable with the current available methods."	""
 3	"asian"	"China"	"China"	"0.0"	"0.030303030303"	"0.0519480519481"	"231"	"11.0"	"BMC Bioinformatics"	"Chang Q, Luan Y, Sun F"	"School of Mathematics, Shandong University, Jinan, Shandong, PR China."	"BACKGROUND: Beta diversity, which involves the assessment of differences between communities, is an important problem in ecological studies. Many statistical methods have been developed to quantify beta diversity, and among them, UniFrac and weighted-UniFrac (W-UniFrac) are widely used. The W-UniFrac is a weighted sum of branch lengths in a phylogenetic tree of the sequences from the communities. However, W-UniFrac does not consider the variation of the weights under random sampling resulting in less power detecting the differences between communities. RESULTS: We develop a new statistic termed variance adjusted weighted UniFrac (VAW-UniFrac) to compare two communities based on the phylogenetic relationships of the individuals. The VAW-UniFrac is used to test if the two communities are different. To test the power of VAW-UniFrac, we first ran a series of simulations which revealed that it always outperforms W-UniFrac, as well as UniFrac when the individuals are not uniformly distributed. Next, all three methods were applied to analyze three large 16S rRNA sequence collections, including human skin bacteria, mouse gut microbial communities, microbial communities from hypersaline soil and sediments, and a tropical forest census data. Both simulations and applications to real data show that VAW-UniFrac can satisfactorily measure differences between communities, considering not only the species composition but also abundance information. CONCLUSIONS: VAW-UniFrac can recover biological insights that cannot be revealed by other beta diversity measures, and it provides a novel alternative for comparing communities."	""
+3	"asian"	"Yale, USA."	"USA"	"0.0137931034483"	"0.0206896551724"	"0.0551724137931"	"145"	"11.1538461538"	"Immunity"	"Chang X, Liu F, Wang X, Lin A, Zhao H, Su B"	"Department of Immunobiology and Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06519, USA."	"Mitogen-activated protein kinases (MAPKs) are key mediators of the T cell receptor (TCR) signals but their roles in T helper (Th) cell differentiation are unclear. Here we showed that the MAPK kinase kinases MEKK2 (encoded by Map3k2) and MEKK3 (encoded by Map3k3) negatively regulated transforming growth factor-beta (TGF-beta)-mediated Th cell differentiation. Map3k2(-/-)Map3k3(Lck-Cre/-) mice showed an abnormal accumulation of regulatory T (Treg) and Th17 cells in the periphery, consistent with Map3k2(-/-)Map3k3(Lck-Cre/-) naive CD4(+) T cells differentiation into Treg and Th17 cells with a higher frequency than wild-type (WT) cells after TGF-beta stimulation in vitro. In addition, Map3k2(-/-)Map3k3(Lck-Cre/-) mice developed more severe experimental autoimmune encephalomyelitis. Map3k2(-/-)Map3k3(Lck-Cre/-) T cells exhibited impaired phosphorylation of SMAD2 and SMAD3 proteins at their linker regions, which negatively regulated the TGF-beta responses in T cells. Thus, the crosstalk between TCR-induced MAPK and the TGF-beta signaling pathways is important in regulating Th cell differentiation."	""
+3	"asian"	"California, United States of America"	"USA"	"0.0176056338028"	"0.0176056338028"	"0.056338028169"	"284"	"11.36"	"PLoS One"	"Chen F, Zhang X, Sun S, Zara JN, Zou X, Chiu R, Culiat CT, Ting K, Soo C"	"Dental and Craniofacial Research Institute, University of California Los Angeles, Los Angeles, United States of America."	"NELL-1 is a novel secreted protein associated with premature fusion of cranial sutures in craniosynostosis that has been found to promote osteoblast cell differentiation and mineralization. Our previous study showed that Runx2, the key transcription factor in osteoblast differentiation, transactivates the NELL-1 promoter. In this study, we evaluated the regulatory involvement and mechanisms of Osterix, an essential transcription factor of osteoblasts, in NELL-1 gene expression and function. Promoter analysis showed a cluster of potential Sp1 sites (Sp1/Osterix binding sites) within approximately 70 bp (from -71 to -142) of the 5 flanking region of the human NELL-1 transcriptional start site. Luciferase activity in our NELL-1 promoter reporter systems was significantly decreased in Saos-2 cells when Osterix was overexpressed. Mutagenesis study demonstrated that this suppression is mediated by the Sp1 sites. The binding specificity of Osterix to these Sp1 sites was confirmed in Saos-2 cells and primary human osteoblasts by EMSA in vitro and ChIP assay in vivo. ChIP assay also showed that Osterix downregulated NELL-1 by affecting binding of RNA polymerase II to the NELL-1 promoter, but not by competing with Runx2 binding to the OSE2 sites. Moreover, NELL-1 mRNA levels were significantly decreased when Osterix was overexpressed in Saos-2, U2OS, Hela and Glioma cells. Correspondingly, knockdown of Osterix increased NELL-1 transcription and osteoblastic differentiation in both Saos-2 cells and primary human osteoblasts. These results suggest that Osterix is a direct transcriptional regulator with repressive effect on NELL-1 gene expression, contributing to a delicate balance of regulatory effects on NELL-1 transcription with Runx2, and may play a crucial role in osteoblast differentiation and mineralization. These findings also extend our understanding of the molecular mechanism of Runx2, Osterix, and NELL-1 and demonstrate their crosstalk during osteogenesis."	""
+3	"asian"	"Taiwan, China"	"China"	"0.0114942528736"	"0.0459770114943"	"0.0689655172414"	"261"	"11.347826087"	"Molecular Biology and Evolution"	"Chen FC, Pan CL, Lin HY"	"Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan, Republic of China."	"Alternative splicing (AS) is known to significantly affect exon-level protein evolutionary rates in mammals. Particularly, alternatively spliced exons (ASEs) have a higher nonsynonymous-to-synonymous substitution rate (dN/dS) ratio than constitutively spliced exons (CSEs), possibly because the former are required only occasionally for normal biological functions. Meanwhile, intrinsically disordered regions (IDRs), the protein regions lacking fixed 3D structures, are also reported to have an increased evolutionary rate due to lack of structural constraint. Interestingly, IDRs tend to be located in alternative protein regions. Yet which of these two factors is the major determinant of the increased dN/dS in mammalian ASEs remains unclear. By comparing human-macaque and human-mouse one-to-one orthologous genes, we demonstrate that AS and protein structural disorder have independent effects on mammalian exon evolution. We performed analyses of covariance to demonstrate that the slopes of the (dN/dS-percentage of IDR) regression lines differ significantly between CSEs and ASEs. In other words, the dN/dS ratios of both ASEs and CSEs increase with the proportion of IDR (PIDR), whereas ASEs have higher dN/dS ratios than CSEs when they have similar PIDRs. Since ASEs and IDRs may less frequently overlap with protein domains (which also affect dN/dS), we also examined the correlations between dN/dS ratio and exon type/PIDR by controlling for the density of protein domain. We found that the effects of exon type and PIDR on dN/dS are both independent of domain density. Our results imply that nature can select for different biological features with regard to ASEs and IDRs, even though the two biological features tend to be localized in the same protein regions."	""
+3	"asian"	"California, United States of America"	"USA"	"0.00460829493088"	"0.0138248847926"	"0.10599078341"	"217"	"14.4666666667"	"PLoS Computational Biology"	"Chen H, Xing H, Zhang NR"	"Department of Statistics, Stanford University, Stanford, California, United States of America."	"Chromosomal gains and losses comprise an important type of genetic change in tumors, and can now be assayed using microarray hybridization-based experiments. Most current statistical models for DNA copy number estimate total copy number, which do not distinguish between the underlying quantities of the two inherited chromosomes. This latter information, sometimes called parent specific copy number, is important for identifying allele-specific amplifications and deletions, for quantifying normal cell contamination, and for giving a more complete molecular portrait of the tumor. We propose a stochastic segmentation model for parent-specific DNA copy number in tumor samples, and give an estimation procedure that is computationally efficient and can be applied to data from the current high density genotyping platforms. The proposed method does not require matched normal samples, and can estimate the unknown genotypes simultaneously with the parent specific copy number. The new method is used to analyze 223 glioblastoma samples from the Cancer Genome Atlas (TCGA) project, giving a more comprehensive summary of the copy number events in these samples. Detailed case studies on these samples reveal the additional insights that can be gained from an allele-specific copy number analysis, such as the quantification of fractional gains and losses, the identification of copy neutral loss of heterozygosity, and the characterization of regions of simultaneous changes of both inherited chromosomes."	""
+3	"asian"	"Hong Kong, Hong Kong"	"Hong Kong"	"0.0093023255814"	"0.0325581395349"	"0.0883720930233"	"215"	"11.3157894737"	"PLoS One"	"Chen J, Schooling CM, Johnston JM, Hedley AJ, McGhee SM"	"Department of Community Medicine and School of Public Health, The University of Hong Kong, Hong Kong."	"BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of death, particularly in developing countries. Little is known about the effects of economic development on COPD mortality, although economic development may potentially have positive and negative influences over the life course on COPD. We took advantage of a unique population whose rapid and recent economic development is marked by changes at clearly delineated and identifiable time points, and where few women smoke, to examine the effect of macro-level events on COPD mortality. METHODS: We used Poisson regression to decompose sex-specific COPD mortality rates in Hong Kong from 1981 to 2005 into the effects of age, period and cohort. RESULTS: COPD mortality declined strongly over generations for people born from the early to mid 20th century, which was particularly evident for the first generation to grow up in a more economically developed environment for both sexes. Population wide COPD mortality decreased when air quality improved and increased with increasing air pollution. COPD mortality increased with age, particularly after menopause among women. CONCLUSIONS: Economic development may reduce vulnerability to COPD by reducing long-lasting insults to the respiratory system, such as infections, poor nutrition and indoor air pollution. However, some of these gains may be offset if economic development results in increasing air pollution or increasing smoking."	""
 3	"asian"	"China"	"China"	"0.00869565217391"	"0.0130434782609"	"0.0391304347826"	"230"	"15.3333333333"	"PLoS One"	"Chen KJ, Lin SZ, Zhou L, Xie HY, Zhou WH, Taki-Eldin A, Zheng SS"	"Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China."	"BACKGROUND: Regulatory T cells (Tregs) are highly prevalent in tumor tissue and can suppress effective anti-tumor immune responses. However, the source of the increased tumor-infiltrating Tregs and their contribution to cancer progression remain poorly understood. METHODOLOGY/PRINCIPAL FINDING: We here investigated the frequency, phenotype and trafficking property of Tregs and their prognostic value in patients with hepatocellular carcinoma (HCC). Our results showed that FoxP3(+) Tregs highly aggregated and were in an activated phenotype (CD69(+)HLA-DR(high)) in the tumor site, where they can suppress the proliferation and INF-gamma secretion of CD4(+)CD25(-) T cells. These tumor-infiltrating Tregs could be selectively recruited though CCR6-CCL20 axis as illustrated by (a) high expression of CCR6 on circulating Tregs and their selective migration to CCR6 ligand CCL20, and (b) correlation of distribution and expression between tumor-infiltrating Tregs and intratumoral CCL20. In addition, we found that the number of tumor-infiltrating Tregs was associated with cirrhosis background (P = 0.011) and tumor differentiation (P = 0.003), and was an independent prognostic factor for overall survival (HR = 2.408, P = 0.013) and disease-free survival (HR = 2.204, P = 0.041). The increased tumor-infiltrating Tregs predicted poorer prognosis in HCC patients. CONCLUSIONS: The CCL20-CCR6 axis mediates the migration of circulating Tregs into tumor microenvironment, which in turn results in tumor progression and poor prognosis in HCC patients. Thus, blocking CCL20-CCR6 axis-mediated Treg migration may be a novel therapeutic target for HCC."	""
+3	"asian"	"New York, USA."	"USA"	"0.014598540146"	"0.029197080292"	"0.0656934306569"	"137"	"6.30434782609"	"Bioinformatics"	"Chen L, Chan TH, Choyke PL, Hillman EM, Chi CY, Bhujwalla ZM, Wang G, Wang SS, Szabo Z, Wang Y"	"Bradley Department of Electrical and Computer Engineering, Virginia Tech, Arlington, VA 22203, USA, Department of Electrical Engineering, National Tsing Hua University, Taiwan, ROC 30013, Molecular Imaging Program, National Cancer Institute, NIH, Bethesda, MD 20892, Department of Biomedical Engineering and Radiology, Columbia University, New York, NY 10027, Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA 24061 and Science, Mathematics, Computer Science House, Poolesville High School, Poolesville, MD 20837, USA."	"SUMMARY: In vivo dynamic contrast-enhanced imaging tools provide non-invasive methods for analyzing various functional changes associated with disease initiation, progression and responses to therapy. The quantitative application of these tools has been hindered by its inability to accurately resolve and characterize targeted tissues due to spatially mixed tissue heterogeneity. Convex Analysis of Mixtures - Compartment Modeling (CAM-CM) signal deconvolution tool has been developed to automatically identify pure-volume pixels located at the corners of the clustered pixel time series scatter simplex and subsequently estimate tissue-specific pharmacokinetic parameters. CAM-CM can dissect complex tissues into regions with differential tracer kinetics at pixel-wise resolution and provide a systems biology tool for defining imaging signatures predictive of phenotypes. AVAILABILITY: The MATLAB source code can be downloaded at the authors website CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
 3	"asian"	"China"	"China"	"0.0143369175627"	"0.010752688172"	"0.0573476702509"	"279"	"10.3703703704"	"PLoS One"	"Chen L, He Z, Qin L, Li Q, Shi X, Zhao S, Chen L, Zhong N, Chen X"	"Center for Infection and Immunity, State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China."	"BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-gamma and TNF-alpha and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer immune-based therapy."	""
 3	"asian"	"China"	"China"	"0.00903614457831"	"0.0271084337349"	"0.0963855421687"	"332"	"12.2962962963"	"BMC Bioinformatics"	"Chen R, Chen W, Yang S, Wu D, Wang Y, Tian Y, Shi Y"	"Research Center on Fictitious Economy and Data Science, Chinese Academy of Sciences, Beijing 100190, China."	"ABSTRACT: BACKGROUND: Systematic mutagenesis studies have shown that only a few interface residues termed hot spots contribute significantly to the binding free energy of protein-protein interactions. Therefore, hot spots prediction becomes increasingly important for well understanding the essence of proteins interactions and helping narrow down the search space for drug design. Currently many computational methods have been developed by proposing different features. However comparative assessment of these features and furthermore effective and accurate methods are still in pressing need. RESULTS: In this study, we first comprehensively collect the features to discriminate hot spots and non-hot spots and analyze their distributions. We find that hot spots have lower relASA and larger relative change in ASA, suggesting hot spots tend to be protected from bulk solvent. In addition, hot spots have more contacts including hydrogen bonds, salt bridges, and atomic contacts, which favor complexes formation. Interestingly, we find that conservation score and sequence entropy are not significantly different between hot spots and non-hot spots in Ab+ dataset (all complexes). While in Ab- dataset (antigen-antibody complexes are excluded), there are significant differences in two features between hot pots and non-hot spots. Secondly, we explore the predictive ability for each feature and the combinations of features by support vector machines (SVMs). The results indicate that sequence-based feature outperforms other combinations of features with reasonable accuracy, with a precision of 0.69, a recall of 0.68, an F1 score of 0.68, and an AUC of 0.68 on independent test set. Compared with other machine learning methods and two energy-based approaches, our approach achieves the best performance. Moreover, we demonstrate the applicability of our method to predict hot spots of two protein complexes. CONCLUSION: Experimental results show that support vector machine classifiers are quite effective in predicting hot spots based on sequence features. Hot spots cannot be fully predicted through simple analysis based on physicochemical characteristics, but there is reason to believe that integration of features and machine learning methods can remarkably improve the predictive performance for hot spots."	""
+3	"asian"	"Taiwan"	"China"	"0.0164835164835"	"0.0164835164835"	"0.0769230769231"	"182"	"5.78787878788"	"Bioinformatics"	"Chen SA, Ou YY, Lee TY, Gromiha MM"	"Department of Computer Science and Engineering, Yuan Ze University, Chung-Li, Taiwan."	"SUMMARY: Transporters are proteins that are involved in the movement of ions or molecules across biological membranes. Currently, our knowledge about the functions of transporters is limited due to the paucity of their 3D structures. Hence, computational techniques are necessary to annotate the functions of transporters. In this work, we focused on an important functional aspect of transporters, namely annotation of targets for transport proteins. We have systematically analyzed four major classes of transporters with different transporter targets: (i) electron, (ii) protein/mRNA, (iii) ion and (iv) others, using amino acid properties. We have developed a radial basis function network-based method for predicting transport targets with amino acid properties and position specific scoring matrix profiles. Our method showed a 10-fold cross-validation accuracy of 90.1, 80.1, 70.3 and 82.3% for electron transporters, protein/mRNA transporters, ion transporters and others, respectively, in a dataset of 543 transporters. We have also evaluated the performance of the method with an independent dataset of 108 proteins and we obtained similar accuracy. We suggest that our method could be an effective tool for functional annotation of transport proteins. AVAILABILITY:"	""
+3	"asian"	"Taiwan"	"China"	"0.00952380952381"	"0.0238095238095"	"0.0428571428571"	"210"	"12.4117647059"	"Molecular Biology and Evolution"	"Chen SC, Chuang TJ, Li WH"	"Institute of BioMedical Informatics, National Yang-Ming University, Taipei, Taiwan."	"Many indicators of protein evolutionary rate have been proposed, but some of them are interrelated. The purpose of this study is to disentangle their correlations. We assess the strength of each indicator by controlling for the other indicators under study. We find that the number of microRNA (miRNA) types that regulate a gene is the strongest rate indicator (a negative correlation), followed by disorder content (the percentage of disordered regions in a protein, a positive correlation); the strength of disorder content as a rate indicator is substantially increased after controlling for the number of miRNA types. By dividing proteins into lowly and highly intrinsically disordered proteins (L-IDPs and H-IDPs), we find that proteins interacting with more H-IDPs tend to evolve more slowly, which largely explains the previous observation of a negative correlation between the number of protein-protein interactions and evolutionary rate. Moreover, all of the indicators examined here, except for the number of miRNA types, have different strengths in L-IDPs and in H-IDPs. Finally, the number of phosphorylation sites is weakly correlated with the number of miRNA types, and its strength as a rate indicator is substantially reduced when other indicators are considered. Our study reveals the relative strength of each rate indicator and increases our understanding of protein evolution."	""
 3	"asian"	"China"	"China"	"0.00931677018634"	"0.027950310559"	"0.0714285714286"	"322"	"9.90909090909"	"BMC Bioinformatics"	"Chen WH, Sun PP, Lu Y, Guo WW, Huang YX, Ma ZQ"	"School of Computer Science and Information Technology, Northeast Normal University, Changchun 130024, P.R. China."	"BACKGROUND: A B-cell epitope is a group of residues on the surface of an antigen which stimulates humoral responses. Locating these epitopes on antigens is important for the purpose of effective vaccine design. In recent years, mapping affinity-selected peptides screened from a random phage display library to the native epitope has become popular in epitope prediction. These peptides, also known as mimotopes, share the similar structure and function with the corresponding native epitopes. Great effort has been made in using this similarity between such mimotopes and native epitopes in prediction, which has resulted in better outcomes than statistics-based methods can. However, it cannot maintain a high degree of satisfaction in various circumstances. RESULTS: In this study, we propose a new method that maps a group of mimotopes back to a source antigen so as to locate the interacting epitope on the antigen. The core of this method is a searching algorithm that is incorporated with both dynamic programming (DP) and branch and bound (BB) optimization and operated on a series of overlapping patches on the surface of a protein. These patches are then transformed to a number of graphs using an adaptable distance threshold (ADT) regulated by an appropriate compactness factor (CF), a novel parameter proposed in this study. Compared with both Pep-3D-Search and PepSurf, two leading graph-based search tools, on average from the results of 18 test cases, MimoPro, the Web-based implementation of our proposed method, performed better in sensitivity, precision, and Matthews correlation coefficient (MCC) than both did in epitope prediction. In addition, MimoPro is significantly faster than both Pep-3D-Search and PepSurf in processing. CONCLUSIONS: Our search algorithm designed for processing well constructed graphs using an ADT regulated by CF is more sensitive and significantly faster than other graph-based approaches in epitope prediction. MimoPro is a viable alternative to both PepSurf and Pep-3D-Search for epitope prediction in the same kind, and freely accessible through the MimoPro server located at"	""
 3	"asian"	"China"	"China"	"0.0127118644068"	"0.00847457627119"	"0.0423728813559"	"236"	"9.56"	"Bioinformatics"	"Chen Y, Jiang T, Jiang R"	"MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing 1000084, China."	"MOTIVATION: Pinpointing genes that underlie human inherited diseases among candidate genes in susceptibility genetic regions is the primary step towards the understanding of pathogenesis of diseases. Although several probabilistic models have been proposed to prioritize candidate genes using phenotype similarities and protein-protein interactions, no combinatorial approaches have been proposed in the literature. RESULTS: We propose the first combinatorial approach for prioritizing candidate genes. We first construct a phenome-interactome network by integrating the given phenotype similarity profile, protein-protein interaction network and associations between diseases and genes. Then, we introduce a computational method called MAXIF to maximize the information flow in this network for uncovering genes that underlie diseases. We demonstrate the effectiveness of this method in prioritizing candidate genes through a series of cross-validation experiments, and we show the possibility of using this method to identify diseases with which a query gene may be associated. We demonstrate the competitive performance of our method through a comparison with two existing state-of-the-art methods, and we analyze the robustness of our method with respect to the parameters involved. As an example application, we apply our method to predict driver genes in 50 copy number aberration regions of melanoma. Our method is not only able to identify several driver genes that have been reported in the literature, it also shed some new biological insights on the understanding of the modular property and transcriptional regulation scheme of these driver genes. CONTACT:"	""
 3	"asian"	"China"	"China"	"0.0"	"0.0"	"0.0846153846154"	"130"	"10.1538461538"	"Nature Genetics"	"Chen ZJ, Zhao H, He L, Shi Y, Qin Y, Shi Y, Li Z, You L, Zhao J, Liu J, Liang X, Zhao X, Zhao J, Sun Y, Zhang B, Jiang H, Zhao D, Bian Y, Gao X, Geng L, Li Y, Zhu D, Sun X, Xu JE, Hao C, Ren CE, Zhang Y, Chen S, Zhang W, Yang A, Yan J, Li Y, Ma J, Zhao Y"	"Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China."	"Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P(meta) = 7.55 x 10(2)(1), odds ratio (OR) 0.71); 2p21 (rs13429458, P(meta) = 1.73 x 10(2)(3), OR 0.67); and 9q33.3 (rs2479106, P(meta) = 8.12 x 10(1), OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended."	""
 3	"asian"	"China"	"China"	"0.00613496932515"	"0.0368098159509"	"0.0981595092025"	"163"	"12.5384615385"	"Molecular Biology and Evolution"	"Chen ZX, Zhang YE, Vibranovski M, Luo J, Gao G, Long M"	"Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, PR China."	"Inverted duplicates (IDs) are pervasive in genomes and have been reported to play functional roles in various biological processes. However, the general underlying evolutionary forces that maintain IDs in genomes remain largely elusive. Through a systematic screening of the Drosophila melanogaster genome, 20,223 IDs were detected in nonrepetitive intergenic regions, far more than expectation under the neutrality model. 3,846 of these IDs were identified to have stable hairpin structure (i.e., the structural IDs). Based on whole-genome transcriptome profiling data, we found 628 unannotated expressed structural IDs, which had significantly different genomic distributions and structural properties from the unexpressed IDs. Among the expressed structural IDs, 130 exhibited higher expression in males than in females (i.e., male-biased expression). Compared with sex-unbiased ones, these male-biased IDs were significantly underrepresented on the X chromosome, similar to previously reported pattern of male-biased protein-coding genes. These analyses suggest that a selection-driven process, rather than a purely neutral mutation-driven mechanism, contributes to the maintenance of IDs in the Drosophila genome."	""
+3	"asian"	"California, United States of America"	"USA"	"0.00357142857143"	"0.0178571428571"	"0.0821428571429"	"280"	"6.67441860465"	"PLoS One"	"Cho HJ, Joo NS, Wine JJ"	"Cystic Fibrosis Research Laboratory, Psychology Department, Stanford University, Stanford, California, United States of America."	"BACKGROUND: Cystic fibrosis (CF), caused by reduced CFTR function, includes severe sinonasal disease which may predispose to lung disease. Newly developed CF pigs provide models to study the onset of CF pathophysiology. We asked if glands from pig nasal turbinates have secretory responses similar to those of tracheal glands and if CF nasal glands show reduced fluid secretion. METHODOLOGY/PRINCIPAL FINDINGS: Unexpectedly, we found that nasal glands differed from tracheal glands in five ways, being smaller, more numerous (density per airway surface area), more sensitive to carbachol, more sensitive to forskolin, and nonresponsive to Substance P (a potent agonist for pig tracheal glands). Nasal gland fluid secretion from newborn piglets (12 CF and 12 controls) in response to agonists was measured using digital imaging of mucus bubbles formed under oil. Secretion rates were significantly reduced in all conditions tested. Fluid secretory rates (Controls vs. CF, in pl/min/gland) were as follows: 3 microM forskolin: 9.2+/-2.2 vs. 0.6+/-0.3; 1 microM carbachol: 143.5+/-35.5 vs. 52.2+/-10.3; 3 microM forskolin + 0.1 microM carbachol: 25.8+/-5.8 vs. CF 4.5+/-0.9. We also compared CF(DeltaF508/DeltaF508) with CFTR(-/-) piglets and found significantly greater forskolin-stimulated secretion rates in the DeltaF508 vs. the null piglets (1.4+/-0.8, n = 4 vs. 0.2+/-0.1, n = 7). An unexpected age effect was also discovered: the ratio of secretion to 3 microM forskolin vs. 1 microM carbachol was  approximately 4 times greater in adult than in neonatal nasal glands. CONCLUSIONS/SIGNIFICANCE: These findings reveal differences between nasal and tracheal glands, show defective fluid secretion in nasal glands of CF pigs, reveal some spared function in the DeltaF508 vs. null piglets, and show unexpected age-dependent differences. Reduced nasal gland fluid secretion may predispose to sinonasal and lung infections."	""
+3	"asian"	"Canada"	"Canada"	"0.0137457044674"	"0.00343642611684"	"0.0996563573883"	"291"	"9.0"	"PLoS One"	"Choi M, Kim H, Qian H, Palepu A"	"Department of Medicine, University of British Columbia, Vancouver BC, Canada."	"OBJECTIVE: We compared the readmission rates and the pattern of readmission among patients discharged against medical advice (AMA) to control patients discharged with approval over a one-year follow-up period. METHODS: A retrospective matched-cohort study of 656 patients(328 were discharged AMA) who were followed for one year after their initial hospitalization at an urban university-affiliated teaching hospital in Vancouver, Canada that serves a population with high prevalence of addiction and psychiatric disorders. Multivariate conditional logistic regression was used to examine the independent association of discharge AMA on 14-day related diagnosis hospital readmission. We fit a multivariate conditional negative binomial regression model to examine the readmission frequency ratio between the AMA and non-AMA group. PRINCIPAL FINDINGS: AMA patients were more likely to be homeless (32.3% vs. 11%) and have co-morbid conditions such as psychiatric illnesses, injection drug use, HIV, hepatitis C and previous gastrointestinal bleeding. Patients discharged AMA were more likely to be readmitted: 25.6% vs. 3.4%, p<0.001 by day 14. The AMA group were more likely to be readmitted within 14 days with a related diagnosis than the non-AMA group (Adjusted Odds Ratio 12.0; 95% Confidence Interval [CI]: 3.7-38.9). Patients who left AMA were more likely to be readmitted multiple times at one year compared to the non-AMA group (adjusted frequency ratio 1.6; 95% CI: 1.3-2.0). There was also higher all-cause in-hospital mortality during the 12-month follow-up in the AMA group compared to non-AMA group (6.7% vs. 2.4%, p = 0.01). CONCLUSIONS: Patients discharged AMA were more likely to be homeless and have multiple co-morbid conditions. At one year follow-up, the AMA group had higher readmission rates, were predisposed to multiple readmissions and had a higher in-hospital mortality. Interventions to reduce discharges AMA in high-risk groups need to be developed and tested."	""
+3	"asian"	"Taiwan, Taiwan"	"China"	"0.0597014925373"	"0.0298507462687"	"0.0995024875622"	"201"	"13.4666666667"	"Blood"	"Chou WC, Chou SC, Liu CY, Chen CY, Hou HA, Kuo YY, Lee MC, Ko BS, Tang JL, Yao M, Tsay W, Wu SJ, Huang SY, Hsu SC, Chen YC, Chang YC, Kuo YY, Kuo KT, Lee FY, Liu MC, Liu CW, Tseng MH, Huang CF, Tien HF"	"Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan;"	"The studies concerning clinical implications of TET2 mutation in patients with primary acute myeloid leukemia (AML) are scarce. We analyzed TET2 mutation in a cohort of 486 adult patients with primary AML. TET2 mutation occurred in 13.2% of our patients, and was closely associated with older age, higher white blood cell and blast counts, lower platelet numbers, normal karyotype, intermediate-risk cytogenetics, isolated trisomy 8, NPM1 mutation, and ASXL1 mutation but mutually exclusive with IDH mutation. TET2 mutation is an unfavorable prognostic factor in patients with intermediate-risk cytogenetics, and its negative impact was further enhanced when the mutation was combined with FLT3-ITD, NPM1-wild, or unfavorable genotypes (other than [NPM1(+)/FLT3-ITD(-) or CEBPA(+)]). A scoring system integrating TET2 mutation with FLT3-ITD, NPM1 and CEBPA mutations could well separate AML patients with intermediate-risk cytogenetics into four groups with different prognosis (P < 0.0001). Sequential analysis revealed that TET2 mutation detected at diagnosis was frequently lost at relapse; rarely, the mutation was acquired at relapse in those without TET2 mutation at diagnosis. In conclusion, TET2 mutation is associated with poor prognosis in AML patients with intermediate-risk cytogenetics, especially when it is combined with other adverse molecular markers. TET2 mutation appeared to be unstable during disease evolution."	""
+3	"asian"	"China, China"	"China"	"0.0201342281879"	"0.0335570469799"	"0.0536912751678"	"149"	"13.5454545455"	"Nature Genetics"	"Chu X, Pan CM, Zhao SX, Liang J, Gao GQ, Zhang XM, Yuan GY, Li CG, Xue LQ, Shen M, Liu W, Xie F, Yang SY, Wang HF, Shi JY, Sun WW, Du WH, Zuo CL, Shi JX, Liu BL, Guo CC, Zhan M, Gu ZH, Zhang XN, Sun F, Wang ZQ, Song ZY, Zou CY, Sun WH, Guo T, Cao HM, Ma JH, Han B, Li P, Jiang H, Huang QH, Liang L, Liu LB, Chen G, Su Q, Peng YD, Zhao JJ, Ning G, Chen Z, Chen JL, Chen SJ, Huang W, Song HD"	"1] State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China. [2] Department of Genetics, Shanghai-Ministry of Science and Technology (MOST) Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai, China. [3]."	"Graves disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves disease, we conducted a genome-wide association study in 1,536 individuals with Graves disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls. We confirmed four previously reported loci (in the major histocompatibility complex, TSHR, CTLA4 and FCRL3) and identified two new susceptibility loci (the RNASET2-FGFR1OP-CCR6 region at 6q27 (P(combined) = 6.85 x 10(-10) for rs9355610) and an intergenic region at 4p14 (P(combined) = 1.08 x 10(-13) for rs6832151)). These newly associated SNPs were correlated with the expression levels of RNASET2 at 6q27, of CHRNA9 and of a previously uncharacterized gene at 4p14, respectively. Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves disease."	""
+3	"asian"	"Israel"	"Israel"	"0.0"	"0.0216718266254"	"0.0526315789474"	"323"	"11.1379310345"	"Molecular Biology and Evolution"	"Cohen NE, Shen R, Carmel L"	"Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, Jerusalem, Israel."	"Intron density is highly variable across eukaryotic species. It seems that different lineages have experienced considerably different levels of intron gain and loss events, but the reasons for this are not well known. A large number of mechanisms for intron loss and gain have been suggested, and most of them have at least some level of indirect support. We therefore figured out that the variability in intron density can be a reflection of the fact that different mechanisms are active in different lineages. Quite a number of these putative mechanisms, both for intron loss and for intron gain, postulate that the enzyme reverse transcriptase (RT) has a key role in the process. In this paper, we lay out three predictions whose approval or falsification gives indication for the involvement of RT in intron gain and loss processes. Testing these predictions requires data on the intron gain and loss rates of individual genes along different branches of the eukaryotic phylogenetic tree. So far, such rates could not be computed, and hence, these predictions could not be rigorously evaluated. Here, we use a maximum likelihood algorithm that we have devised in the past, Evolutionary Reconstruction by Expectation Maximization, which allows the estimation of such rates. Using this algorithm, we computed the intron loss and gain rates of more than 300 genes in each branch of the phylogenetic tree of 19 eukaryotic species. Based on that we found only little support for RT activity in intron gain. In contrast, we suggest that RT-mediated intron loss is a mechanism that is very efficient in removing introns, and thus, its levels of activity may be a major determinant of intron number. Moreover, we found that intron gain and loss rates are negatively correlated in intron-poor species but are positively correlated for intron-rich species. One explanation to this is that intron gain and loss mechanisms in intron-rich species (like metazoans) share a common mechanistic component, albeit not a RT."	""
+3	"asian"	"Israel"	"Israel"	"0.00749063670412"	"0.0149812734082"	"0.0786516853933"	"267"	"12.7142857143"	"Molecular Biology and Evolution"	"Cohen O, Gophna U, Pupko T"	"Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel."	"Horizontal gene transfer (HGT) is a prevalent and a highly important phenomenon in microbial species evolution. One of the important challenges in HGT research is to better understand the factors that determine the tendency of genes to be successfully transferred and retained in evolution (i.e., transferability). It was previously observed that transferability of genes depends on the cellular process in which they are involved where genes involved in transcription or translation are less likely to be transferred than metabolic genes. It was further shown that gene connectivity in the protein-protein interaction network affects HGT. These two factors were shown to be correlated, and their influence on HGT is collectively termed the Complexity Hypothesis. In this study, we used a stochastic mapping method utilizing advanced likelihood-based evolutionary models to quantify gene family acquisition events by HGT. We applied our methodology to an extensive across-species genome-wide dataset that enabled us to estimate the overall extent of transfer events in evolution and to study the trends and barriers to gene transferability. Focusing on the biological function and the connectivity of genes, we obtained novel insights regarding the complexity hypothesis. Specifically, we aimed to disentangle the relationships between protein connectivity, cellular function, and transferability and to quantify the relative contribution of each of these factors in determining transferability. We show that the biological function of a gene family is an insignificant factor in the determination of transferability when proteins with similar levels of connectivity are compared. In contrast, we found that connectivity is an important and a statistically significant factor in determining transferability when proteins with a similar function are compared."	""
+3	"asian"	"China, China"	"China"	"0.00956937799043"	"0.0191387559809"	"0.0478468899522"	"209"	"11.0526315789"	"Molecular Biology and Evolution"	"Cui J, Pan YH, Zhang Y, Jones G, Zhang S"	"Institute of Molecular Ecology and Evolution, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, China."	"For the past 50 years, it was believed that all bats, like humans and guinea pigs, did not synthesize vitamin C (Vc) because they lacked activity of L-gulonolactone oxidase (GULO) in their livers. Humans and guinea pigs lack the activity due to pseudogenization of GULO in their genomes, but there is no genetic evidence to show whether such loss in bats is caused by pseudogenization. Unexpectedly, our successful molecular cloning in one frugivorous bat (Rousettus leschenaultii) and one insectivorous bat (Hipposideros armiger) ascertains that no pseudogenization occurs in these species. Furthermore, we find normal GULO protein expression using bat-specific anti-GULO polyclonal antibodies in bats, evaluated by Western blotting. Most surprisingly, GULO activity assays reveal that these two bat species have retained the ability to synthesize Vc, but at low levels compared with the mouse. It is known that bats in the genus Pteropus have lost GULO activity. We then found that functional constraints acting on the GULO of Pteropus vampyrus (which lost its function) are relaxed. These results imply that the ability to synthesize Vc in bats has not been lost completely in species as previously thought. We also suggest that the evolution of bat GULO genes can be a good model to study genetic processes associated with loss-of-function."	""
+3	"asian"	"Israel"	"Israel"	"0.0"	"0.020202020202"	"0.0909090909091"	"99"	"9.0"	"Molecular Biology and Evolution"	"Dahary D, Shalgi R, Pilpel Y"	"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel."	"MicroRNAs (miRs) are considered major contributors to the evolution of animal morphological complexity. Multiple bursts of novel miR families were documented throughout animal evolution, yet, their evolutionary origins are not understood. Here, we discuss two alternative genomic sources for novel miR families, namely, transposable elements, which were previously described, and a newly proposed origin: CpG islands. We show that these two origins are evolutionarily distinct and that they correspond to marked differences in several functional and genomic characteristics. Together, our results shed light on the intriguing origin of one of the major constituents of regulatory networks in animals, miRs."	""
+3	"asian"	"Taiwan"	"China"	"0.0"	"0.0151515151515"	"0.0555555555556"	"198"	"7.48148148148"	"Bioinformatics"	"Dai HJ, Chang YC, Tsai RT, Hsu WL"	"Department of Computer Science, National Tsing-Hua University, Hsinchu, Intelligent Agent Systems Lab., Institute of Information Science, Academia Sinica, Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei and Department of Computer Science and Engineering, Yuan Ze University, Chung-Li, Taiwan, R.O.C."	"MOTIVATION: Gene normalization (GN) is the task of normalizing a textual gene mention to a unique gene database ID. Traditional top performing GN systems usually need to consider several constraints to make decisions in the normalization process, including filtering out false positives, or disambiguating an ambiguous gene mention, to improve system performance. However, these constraints are usually executed in several separate stages and cannot use each others input/output interactively. In this article, we propose a novel approach that employs a Markov logic network (MLN) to model the constraints used in the GN task. Firstly, we show how various constraints can be formulated and combined in an MLN. Secondly, we are the first to apply the two main concepts of co-reference resolution-discourse salience in centering theory and transitivity-to GN models. Furthermore, to make our results more relevant to developers of information extraction applications, we adopt the instance-based precision/recall/F-measure (PRF) in addition to the article-wide PRF to assess system performance. RESULTS: Experimental results show that our system outperforms baseline and state-of-the-art systems under two evaluation schemes. Through further analysis, we have found several unexplored challenges in the GN task. CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
 3	"asian"	"China"	"China"	"0.0"	"0.0204081632653"	"0.0680272108844"	"147"	"5.66666666667"	"Bioinformatics"	"Dai Z, Dai X, Xiang Q"	"Department of Electronic, School of Information Science and Technology, Sun Yat-Sen University, Guangzhou 510006, China."	"MOTIVATION: The intrinsic DNA sequence is an important determinant of nucleosome positioning. Some DNA sequence patterns can facilitate nucleosome formation, while others can inhibit nucleosome formation. Nucleosome positioning influences the overall rate of sequence evolution. However, its impacts on specific patterns of sequence evolution are still poorly understood. RESULTS: Here, we examined whether nucleosomal DNA and nucleosome-depleted DNA show distinct polymorphism patterns to maintain adequate nucleosome architecture on a genome scale in yeast. We found that sequence polymorphisms in nucleosomal DNA tend to facilitate nucleosome formation, whereas polymorphisms in nucleosome-depleted DNA tend to inhibit nucleosome formation, which is especially evident at nucleosome-disfavored sequences in nucleosome-free regions at both ends of genes. Sequence polymorphisms facilitating nucleosome positioning correspond to stable nucleosome positioning. These results reveal that sequence polymorphisms are under selective constraints to maintain nucleosome positioning. CONTACT:; SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
+3	"asian"	"Vietnam"	"Vietnam"	"0.0110497237569"	"0.0165745856354"	"0.060773480663"	"181"	"7.52"	"Bioinformatics"	"Dang CC, Lefort V, Le VS, Le QS, Gascuel O"	"College of Technology and Information Technology Institute, National University of Hanoi, Vietnam."	"SUMMARY: Amino acid replacement rate matrices are an essential basis of protein studies (e.g. in phylogenetics and alignment). A number of general-purpose matrices have been proposed (e.g. JTT, WAG, LG) since the seminal work of Margaret Dayhoff and coworkers. However, it has been shown that matrices specific to certain protein groups (e.g. mitochondrial) or life domains (e.g. viruses) differ significantly from general average matrices, and thus perform better when applied to the data to which they are dedicated. This Web server implements the maximum-likelihood estimation procedure of Le and Gascuel (2008) and provides a number of tools and facilities. Users upload a set of multiple protein alignments from their domain of interest and receive the resulting matrix by email, along with statistics and comparisons with other matrices. A non-parametric bootstrap is performed optionally to assess the variability of replacement rate estimates. Maximum-likelihood trees, inferred using the estimated rate matrix, are also computed optionally for each input alignment. Finely-tuned procedures and up-to-date ML software (PhyML 3.0, XRATE) are combined to perform all these heavy calculations on our clusters. AVAILABILITY: CONTACT:"	""
+2	"asian"	"USA."	"USA"	"0.00595238095238"	"0.0119047619048"	"0.077380952381"	"168"	"9.0"	"BMC Bioinformatics"	"Deng X"	"Bioinformatics Core Facility, Department of Molecular Medicine, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA."	"BACKGROUND: The popularity of massively parallel exome and transcriptome sequencing projects demands new data mining tools with a comprehensive set of features to support a wide range of analysis tasks. RESULTS: SeqGene, a new data mining tool, supports mutation detection and annotation, dbSNP and 1000 Genome data integration, RNA-Seq expression quantification, mutation and coverage visualization, allele specific expression (ASE), differentially expressed genes (DEGs) identification, copy number variation (CNV) analysis, and gene expression quantitative trait loci (eQTLs) detection. We also developed novel methods for testing the association between SNP and expression and identifying genotype-controlled DEGs. We showed that the results generated from SeqGene compares favourably to other existing methods in our case studies. CONCLUSION: SeqGene is designed as a general-purpose software package. It supports both paired-end reads and single reads generated on most sequencing platforms; it runs on all major types of computers; it supports arbitrary genome assemblies for arbitrary organisms; and it scales well to support both large and small scale sequencing projects. The software homepage is"	""
 3	"asian"	"China"	"China"	"0.00696864111498"	"0.0452961672474"	"0.0801393728223"	"287"	"10.8518518519"	"BMC Bioinformatics"	"Ding J, Zhou S, Guan J"	"School of Computer Science, Fudan University, Shanghai 200433, China."	"BACKGROUND: MicroRNAs (miRNAs) are ~22 nt long integral elements responsible for post-transcriptional control of gene expressions. After the identification of thousands of miRNAs, the challenge is now to explore their specific biological functions. To this end, it will be greatly helpful to construct a reasonable organization of these miRNAs according to their homologous relationships. Given an established miRNA family system (e.g. the miRBase family organization), this paper addresses the problem of automatically and accurately classifying newly found miRNAs to their corresponding families by supervised learning techniques. Concretely, we propose an effective method, miRFam, which uses only primary information of pre-miRNAs or mature miRNAs and a multiclass SVM, to automatically classify miRNA genes. RESULTS: An existing miRNA family system prepared by miRBase was downloaded online. We first employed n-grams to extract features from known precursor sequences, and then trained a multiclass SVM classifier to classify new miRNAs (i.e. their families are unknown). Comparing with miRBases sequence alignment and manual modification, our study shows that the application of machine learning techniques to miRNA family classification is a general and more effective approach. When the testing dataset contains more than 300 families (each of which holds no less than 5 members), the classification accuracy is around 98%. Even with the entire miRBase15 (1056 families and more than 650 of them hold less than 5 samples), the accuracy surprisingly reaches 90%. CONCLUSIONS: Based on experimental results, we argue that miRFam is suitable for application as an automated method of family classification, and it is an important supplementary tool to the existing alignment-based small non-coding RNA (sncRNA) classification methods, since it only requires primary sequence information. AVAILABILITY: The source code of miRFam, written in C++, is freely and publicly available at:"	""
+3	"asian"	"Israel"	"Israel"	"0.0102040816327"	"0.030612244898"	"0.0765306122449"	"196"	"5.64864864865"	"Bioinformatics"	"Donsky E, Wolfson HJ"	"Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel."	"MOTIVATION: Design of protein-protein interaction (PPI) inhibitors is a key challenge in Structural Bioinformatics and Computer Aided Drug Design. Peptides, which partially mimic the interface area of one of the interacting proteins, are natural candidates to form protein-peptide complexes competing with the original PPI. The prediction of such complexes is especially challenging due to the high flexibility of peptide conformations. RESULTS: In this article we present PepCrawler, a new tool for deriving binding peptides from protein-protein complexes and prediction of peptide-protein complexes, by performing high-resolution docking refinement and estimation of binding-affinity. By using a fast path planning approach, PepCrawler rapidly generates large amounts of flexible peptide conformations, allowing backbone and side-chain flexibility. A newly introduced binding energy funnel steepness score was applied for the evaluation of the protein-peptide complexes binding-affinity. PepCrawler simulations predicted high binding- affinity for native protein-peptide complexes benchmark and low affinity for low-energy decoy complexes. In three cases, where wetlab data is available, the PepCrawler predictions were consistent with the data. Comparing to other state of the art flexible peptide-protein structure prediction algorithms, our algorithm is very fast, and takes only minutes to run on a single PC. AVAILABILITY: CONTACT:,"	""
+1	"asian"	"Israel"	"Israel"	"0.0"	"0.0291262135922"	"0.121359223301"	"206"	"13.7333333333"	"PLoS Computational Biology"	"Druckmann S, Berger TK, Schurmann F, Hill S, Markram H, Segev I"	"Interdisciplinary Center for Neural Computation, Hebrew University of Jerusalem, Jerusalem, Israel."	"The rich dynamical nature of neurons poses major conceptual and technical challenges for unraveling their nonlinear membrane properties. Traditionally, various current waveforms have been injected at the soma to probe neuron dynamics, but the rationale for selecting specific stimuli has never been rigorously justified. The present experimental and theoretical study proposes a novel framework, inspired by learning theory, for objectively selecting the stimuli that best unravel the neurons dynamics. The efficacy of stimuli is assessed in terms of their ability to constrain the parameter space of biophysically detailed conductance-based models that faithfully replicate the neurons dynamics as attested by their ability to generalize well to the neurons response to novel experimental stimuli. We used this framework to evaluate a variety of stimuli in different types of cortical neurons, ages and animals. Despite their simplicity, a set of stimuli consisting of step and ramp current pulses outperforms synaptic-like noisy stimuli in revealing the dynamics of these neurons. The general framework that we propose paves a new way for defining, evaluating and standardizing effective electrical probing of neurons and will thus lay the foundation for a much deeper understanding of the electrical nature of these highly sophisticated and non-linear devices and of the neuronal networks that they compose."	""
 3	"asian"	"China"	"China"	"0.00636942675159"	"0.031847133758"	"0.0891719745223"	"157"	"14.2727272727"	"Glycobiology"	"Duan J, Kasper DL"	"College of Science, Northwest A&F University, Yangling, Shaanxi 712100, Peoples Republic of China."	"Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are constantly produced and are tightly regulated to maintain a redox balance (or homeostasis) together with antioxidants (e.g. superoxide dismutase and glutathione) under normal physiological circumstances. These ROS/RNS have been shown to be critical for various biological events including signal transduction, aging, apoptosis, and development. Despite the known beneficial effects, an overproduction of ROS/RNS in the cases of receptor-mediated stimulation and disease-induced oxidative stress can inflict severe tissue damage. In particular, these ROS/RNS are capable of degrading macromolecules including proteins, lipids and nucleic acids as well as polysaccharides, and presumably lead to their dysfunction. The purpose of this review is to highlight (1) chemical mechanisms related to cell-free and cell-based depolymerization of polysaccharides initiated by individual oxidative species; (2) the effect of ROS/RNS-mediated depolymerization on the successive cleavage of the glycosidic linkage of polysaccharides by glycoside hydrolases; and (3) the potential biological outcome of ROS/RNS-mediated depolymerization of polysaccharides."	""
+3	"asian"	"Japan"	"Japan"	"0.013986013986"	"0.020979020979"	"0.0909090909091"	"143"	"11.0"	"Nature Genetics"	"Fujimoto A, Nakagawa H, Hosono N, Nakano K, Abe T, Boroevich KA, Nagasaki M, Yamaguchi R, Shibuya T, Kubo M, Miyano S, Nakamura Y, Tsunoda T"	"Center for Genomic Medicine, RIKEN, Tsurumi, Yokohama, Japan."	"We report the analysis of a Japanese male using high-throughput sequencing to x 40 coverage. More than 99% of the sequence reads were mapped to the reference human genome. Using a Bayesian decision method, we identified 3,132,608 single nucleotide variations (SNVs). Comparison with six previously reported genomes revealed an excess of singleton nonsense and nonsynonymous SNVs, as well as singleton SNVs in conserved non-coding regions. We also identified 5,319 deletions smaller than 10 kb with high accuracy, in addition to copy number variations and rearrangements. De novo assembly of the unmapped sequence reads generated around 3 Mb of novel sequence, which showed high similarity to non-reference human genomes and the human herpesvirus 4 genome. Our analysis suggests that considerable variation remains undiscovered in the human genome and that whole-genome sequencing is an invaluable tool for obtaining a complete understanding of human genetic variation."	""
+3	"asian"	"Japan"	"Japan"	"0.00735294117647"	"0.0147058823529"	"0.0514705882353"	"136"	"7.15789473684"	"Immunity"	"Fukui R, Saitoh S, Kanno A, Onji M, Shibata T, Ito A, Onji M, Matsumoto M, Akira S, Yoshida N, Miyake K"	"Division of Infectious Genetics, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minatoku, Tokyo 108-8639, Japan."	"Toll-like receptor-7 (TLR7) and 9, innate immune sensors for microbial RNA or DNA, have been implicated in autoimmunity. Upon activation, TLR7 and 9 are transported from the endoplasmic reticulum (ER) to endolysosomes for nucleic acid sensing by an ER-resident protein, Unc93B1. Little is known, however, about a role for sensor transportation in controlling autoimmunity. TLR9 competes with TLR7 for Unc93B1-dependent trafficking and predominates over TLR7. TLR9 skewing is actively maintained by Unc93B1 and reversed to TLR7 if Unc93B1 loses preferential binding via a D34A mutation. We here demonstrate that mice harboring a D34A mutation showed TLR7-dependent, systemic lethal inflammation. CD4(+) T cells showed marked differentiation toward T helper 1 (Th1) or Th17 cell subsets. B cell depletion abolished T cell differentiation and systemic inflammation. Thus, Unc93B1 controls homeostatic TLR7 activation by balancing TLR9 to TLR7 trafficking."	""
+3	"asian"	"Japan"	"Japan"	"0.00413223140496"	"0.0247933884298"	"0.0537190082645"	"242"	"12.7368421053"	"Nature"	"Furumoto T, Yamaguchi T, Ohshima-Ichie Y, Nakamura M, Tsuchida-Iwata Y, Shimamura M, Ohnishi J, Hata S, Gowik U, Westhoff P, Brautigam A, Weber AP, Izui K"	"Graduate School of Science, Hiroshima University, 1-3-1, Kagamiyama, Higashi-Hiroshima, 739-8526, Japan."	"Pyruvate serves as a metabolic precursor for many plastid-localized biosynthetic pathways, such as those for fatty acids, terpenoids and branched-chain amino acids. In spite of the importance of pyruvate uptake into plastids (organelles within cells of plants and algae), the molecular mechanisms of this uptake have not yet been explored. This is mainly because pyruvate is a relatively small compound that is able to passively permeate lipid bilayers, which precludes accurate measurement of pyruvate transport activity in reconstituted liposomes. Using differential transcriptome analyses of C(3) and C(4) plants of the genera Flaveria and Cleome, here we have identified a novel gene that is abundant in C(4) species, named BASS2 (BILE ACID:SODIUM SYMPORTER FAMILY PROTEIN 2). The BASS2 protein is localized at the chloroplast envelope membrane, and is highly abundant in C(4) plants that have the sodium-dependent pyruvate transporter. Recombinant BASS2 shows sodium-dependent pyruvate uptake activity. Sodium influx is balanced by a sodium:proton antiporter (NHD1), which was mimicked in recombinant Escherichia coli cells expressing both BASS2 and NHD1. Arabidopsis thaliana bass2 mutants lack pyruvate uptake into chloroplasts, which affects plastid-localized isopentenyl diphosphate synthesis, as evidenced by increased sensitivity of such mutants to mevastatin, an inhibitor of cytosolic isopentenyl diphosphate biosynthesis. We thus provide molecular evidence for a sodium-coupled metabolite transporter in plastid envelopes. Orthologues of BASS2 can be detected in all the genomes of land plants that have been characterized so far, thus indicating the widespread importance of sodium-coupled pyruvate import into plastids."	""
+3	"asian"	"Kyoto, Kyoto, Japan"	"Japan"	"0.0126582278481"	"0.0126582278481"	"0.0189873417722"	"158"	"10.5333333333"	"Nature Genetics"	"Furuyama K, Kawaguchi Y, Akiyama H, Horiguchi M, Kodama S, Kuhara T, Hosokawa S, Elbahrawy A, Soeda T, Koizumi M, Masui T, Kawaguchi M, Takaori K, Doi R, Nishi E, Kakinoki R, Deng JM, Behringer RR, Nakamura T, Uemoto S"	"Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan."	"The liver and exocrine pancreas share a common structure, with functioning units (hepatic plates and pancreatic acini) connected to the ductal tree. Here we show that Sox9 is expressed throughout the biliary and pancreatic ductal epithelia, which are connected to the intestinal stem-cell zone. Cre-based lineage tracing showed that adult intestinal cells, hepatocytes and pancreatic acinar cells are supplied physiologically from Sox9-expressing progenitors. Combination of lineage analysis and hepatic injury experiments showed involvement of Sox9-positive precursors in liver regeneration. Embryonic pancreatic Sox9-expressing cells differentiate into all types of mature cells, but their capacity for endocrine differentiation diminishes shortly after birth, when endocrine cells detach from the epithelial lining of the ducts and form the islets of Langerhans. We observed a developmental switch in the hepatic progenitor cell type from Sox9-negative to Sox9-positive progenitors as the biliary tree develops. These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status."	""
+3	"asian"	"Yale, Yale, USA."	"USA"	"0.0"	"0.0197368421053"	"0.0789473684211"	"152"	"10.1333333333"	"Nature Genetics"	"Gangaraju VK, Yin H, Weiner MM, Wang J, Huang XA, Lin H"	"Yale Stem Cell Center and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, USA."	"Canalization, also known as developmental robustness, describes an organisms ability to produce the same phenotype despite genotypic variations and environmental influences. In Drosophila, Hsp90, the trithorax-group proteins and transposon silencing have been previously implicated in canalization. Despite this, the molecular mechanism underlying canalization remains elusive. Here using a Drosophila eye-outgrowth assay sensitized by the dominant Kr(irregular facets-1)(Kr(If-1)) allele, we show that the Piwi-interacting RNA (piRNA) pathway, but not the short interfering RNA or micro RNA pathway, is involved in canalization. Furthermore, we isolated a protein complex composed of Hsp90, Piwi and Hop, the Hsp70/Hsp90 organizing protein homolog, and we demonstrated the function of this complex in canalization. Our data indicate that Hsp90 and Hop regulate the piRNA pathway through Piwi to mediate canalization. Moreover, they point to epigenetic silencing of the expression of existing genetic variants and the suppression of transposon-induced new genetic variation as two major mechanisms underlying piRNA pathway-mediated canalization."	""
 3	"asian"	"China"	"China"	"0.0045045045045"	"0.0135135135135"	"0.0585585585586"	"222"	"9.65217391304"	"BMC Bioinformatics"	"Gao H, Dou Y, Yang J, Wang J"	"School of Mathematical Sciences, Dalian University of Technology, Dalian, Peoples Republic of China."	"BACKGROUND: The covariation of two sites in a protein is often used as the degree of their coevolution. To quantify the covariation many methods have been developed and most of them are based on residues position-specific frequencies by using the mutual information (MI) model. RESULTS: In the paper, we proposed several new measures to incorporate new biological constraints in quantifying the covariation. The first measure is the mutual information with the amino acid background distribution (MIB), which incorporates the amino acid background distribution into the marginal distribution of the MI model. The modification is made to remove the effect of amino acid evolutionary pressure in measuring covariation. The second measure is the mutual information of residues physicochemical properties (MIP), which is used to measure the covariation of physicochemical properties of two sites. The third measure called MIBP is proposed by applying residues physicochemical properties into the MIB model. Moreover, scores of our new measures are applied to a robust indicator conn(k) in finding the covariation signal of each site. CONCLUSIONS: We find that incorporating amino acid background distribution is effective in removing the effect of evolutionary pressure of amino acids. Thus the MIB measure describes more biological background information for the coevolution of residues. Besides, our analysis also reveals that the covariation of physicochemical properties is a new aspect of coevolution information."	""
+3	"asian"	"Israel"	"Israel"	"0.00847457627119"	"0.0127118644068"	"0.0635593220339"	"236"	"11.2380952381"	"BMC Bioinformatics"	"Geifman N, Rubin E"	"Shraga Segal Department of Microbiology and Immunology, The National Institute for Biotechnology in the Negev, Ben Gurion University, Israel."	"BACKGROUND: Currently, data about age-phenotype associations are not systematically organized and cannot be studied methodically. Searching for scientific articles describing phenotypic changes reported as occurring at a given age is not possible for most ages. RESULTS: Here we present the Age-Phenome Knowledge-base (APK), in which knowledge about age-related phenotypic patterns and events can be modeled and stored for retrieval. The APK contains evidence connecting specific ages or age groups with phenotypes, such as disease and clinical traits. Using a simple text mining tool developed for this purpose, we extracted instances of age-phenotype associations from journal abstracts related to non-insulin-dependent Diabetes Mellitus. In addition, links between age and phenotype were extracted from clinical data obtained from the NHANES III survey. The knowledge stored in the APK is made available for the relevant research community in the form of Age-Cards, each card holds the collection of all the information stored in the APK about a particular age. These Age-Cards are presented in a wiki, allowing community review, amendment and contribution of additional information. In addition to the wiki interaction, complex searches can also be conducted which require the user to have some knowledge of database query construction. CONCLUSIONS: The combination of a knowledge model based repository with community participation in the evolution and refinement of the knowledge-base makes the APK a useful and valuable environment for collecting and curating existing knowledge of the connections between age and phenotypes."	""
+2	"asian"	"New York, New York, USA."	"USA"	"0.00645161290323"	"0.0193548387097"	"0.0903225806452"	"155"	"17.2222222222"	"Nature Genetics"	"Gharavi AG, Kiryluk K, Choi M, Li Y, Hou P, Xie J, Sanna-Cherchi S, Men CJ, Julian BA, Wyatt RJ, Novak J, He JC, Wang H, Lv J, Zhu L, Wang W, Wang Z, Yasuno K, Gunel M, Mane S, Umlauf S, Tikhonova I, Beerman I, Savoldi S, Magistroni R, Ghiggeri GM, Bodria M, Lugani F, Ravani P, Ponticelli C, Allegri L, Boscutti G, Frasca G, Amore A, Peruzzi L, Coppo R, Izzi C, Viola BF, Prati E, Salvadori M, Mignani R, Gesualdo L, Bertinetto F, Mesiano P, Amoroso A, Scolari F, Chen N, Zhang H, Lifton RP"	"Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA."	"We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance (P values for association between 1.59 x 10(2) and 4.84 x 10 and minor allele odds ratios of 0.63-0.80). These five loci explain 4-7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures."	""
+3	"asian"	"Singapore, Singapore, Singapore"	"Singapore"	"0.01"	"0.055"	"0.11"	"200"	"11.7647058824"	"Nature"	"Gibson L, Lee TM, Koh LP, Brook BW, Gardner TA, Barlow J, Peres CA, Bradshaw CJ, Laurance WF, Lovejoy TE, Sodhi NS"	"1] Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore [2]."	"Human-driven land-use changes increasingly threaten biodiversity, particularly in tropical forests where both species diversity and human pressures on natural environments are high. The rapid conversion of tropical forests for agriculture, timber production and other uses has generated vast, human-dominated landscapes with potentially dire consequences for tropical biodiversity. Today, few truly undisturbed tropical forests exist, whereas those degraded by repeated logging and fires, as well as secondary and plantation forests, are rapidly expanding. Here we provide a global assessment of the impact of disturbance and land conversion on biodiversity in tropical forests using a meta-analysis of 138 studies. We analysed 2,220 pairwise comparisons of biodiversity values in primary forests (with little or no human disturbance) and disturbed forests. We found that biodiversity values were substantially lower in degraded forests, but that this varied considerably by geographic region, taxonomic group, ecological metric and disturbance type. Even after partly accounting for confounding colonization and succession effects due to the composition of surrounding habitats, isolation and time since disturbance, we find that most forms of forest degradation have an overwhelmingly detrimental effect on tropical biodiversity. Our results clearly indicate that when it comes to maintaining tropical biodiversity, there is no substitute for primary forests."	""
+3	"asian"	"Israel"	"Israel"	"0.0054347826087"	"0.0163043478261"	"0.0652173913043"	"184"	"6.12903225806"	"Bioinformatics"	"Golan D, Rosset S"	"School of Mathematical Sciences, Tel Aviv University, Tel Aviv, Israel."	"MOTIVATION: Random effects models have recently been introduced as an approach for analyzing genome wide association studies (GWASs), which allows estimation of overall heritability of traits without explicitly identifying the genetic loci responsible. Using this approach, Yang et al. (2010) have demonstrated that the heritability of height is much higher than the ~10% associated with identified genetic factors. However, Yang et al. (2010) relied on a heuristic for performing estimation in this model. RESULTS: We adopt the model framework of Yang et al. (2010) and develop a method for maximum-likelihood (ML) estimation in this framework. Our method is based on Monte-Carlo expectation-maximization (MCEM; Wei et al., 1990), an expectation-maximization algorithm wherein a Markov chain Monte Carlo approach is used in the E-step. We demonstrate that this method leads to more stable and accurate heritability estimation compared to the approach of Yang et al. (2010), and it also allows us to find ML estimates of the portion of markers which are causal, indicating whether the heritability stems from a small number of powerful genetic factors or a large number of less powerful ones. CONTACT:"	""
+1	"asian"	"Lebanon"	"Lebanon"	"0.00865800865801"	"0.017316017316"	"0.0822510822511"	"231"	"12.2105263158"	"Glycobiology"	"Gomathinayagam S, Mitchell T, Zartler ER, Heiss C, Azadi P, Zha D, Houston-Cummings NR, Jiang Y, Li F, Giaccone E, Porambo RJ, Anderson CL, Sethuraman N, Li H, Stadheim TA"	"GlycoFi Inc., A wholly-owned subsidiary of Merck & Co Inc., 21 Lafayette Street, Suite 200, Lebanon, NH, 03766."	"The N-glycosylation pathway in Pichia pastoris has been humanized by the deletion of genes responsible for fungal-type glycosylation (high mannose) as well as the introduction of heterologous genes capable of forming human like N-glycosylation. This results in a yeast host that is capable of expressing therapeutic glycoproteins. A thorough investigation was performed to examine whether glycoproteins expressed in glycoengineered P. pastoris strains may contain residual fungal-type high mannose structures. In a pool of N-linked glycans enzymatically released by protein N-glycosidase from a reporter glycoprotein expressed in a developmental glycoengineered P. pastoris strain, an oligosaccharide with a mass consistent with a Hexose(9)GlcNAc(2) oligosaccharide was identified. When this structure was analyzed by normal phase HPLC, its retention time was identical to a Man(9)GlcNAc(2) standard. However, this Hexose(9)GlcNAc(2) oligosaccharide was found to be resistant to alpha-1,2 mannosidase as well as endomannosidase, which preferentially catabolizes endoplasmic reticulum oligosaccharides containing terminal alpha-linked glucose. To further characterize this oligosaccharide, we purified the Hexose(9)GlcNAc(2) oligosaccharide by HPLC and analyzed the structure by high field one and two dimensional (1)H NMR spectroscopy followed by structural elucidation by homonuclear and heteronuclear 1-dimensional (1D) and 2-dimensional (2D) (1)H and (13)C NMR spectroscopy. The results of these experiments lead to the identification of an oligosaccharide alpha-Man-(1-->2)-beta-Man-(1-->2)-beta-Man-(1-->2)-alpha-Man-(1-->2) moiety as part of a tri-antennary structure. The difference in enzymatic reactivity can be attributed to multiple beta-linkages on the alpha-1,3 arm of the Man(9)GlcNAc(2) oligosaccharide."	""
 3	"asian"	"China"	"China"	"0.0108695652174"	"0.036231884058"	"0.0615942028986"	"276"	"9.03225806452"	"BMC Bioinformatics"	"Gu H, Zhu P, Jiao Y, Meng Y, Chen M"	"Department of Bioinformatics, State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058, China."	"BACKGROUND: Protein-protein interactions play a fundamental role in elucidating the molecular mechanisms of biomolecular function, signal transductions and metabolic pathways of living organisms. Although high-throughput technologies such as yeast two-hybrid system and affinity purification followed by mass spectrometry are widely used in model organisms, the progress of protein-protein interactions detection in plants is rather slow. With this motivation, our work presents a computational approach to predict protein-protein interactions in Oryza sativa. RESULTS: To better understand the interactions of proteins in Oryza sativa, we have developed PRIN, a Predicted Rice Interactome Network. Protein-protein interaction data of PRIN are based on the interologs of six model organisms where large-scale protein-protein interaction experiments have been applied: yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans), fruit fly (Drosophila melanogaster), human (Homo sapiens), Escherichia coli K12 and Arabidopsis thaliana. With certain quality controls, altogether we obtained 76,585 non-redundant rice protein interaction pairs among 5,049 rice proteins. Further analysis showed that the topology properties of predicted rice protein interaction network are more similar to yeast than to the other 5 organisms. This may not be surprising as the interologs based on yeast contribute nearly 74% of total interactions. In addition, GO annotation, subcellular localization information and gene expression data are also mapped to our network for validation. Finally, a user-friendly web interface was developed to offer convenient database search and network visualization. CONCLUSIONS: PRIN is the first well annotated protein interaction database for the important model plant Oryza sativa. It has greatly extended the current available protein-protein interaction data of rice with a computational approach, which will certainly provide further insights into rice functional genomics and systems biology. PRIN is available online at"	""
 3	"asian"	"China"	"China"	"0.00487804878049"	"0.0341463414634"	"0.0780487804878"	"205"	"9.80952380952"	"Nature"	"Gu TP, Guo F, Yang H, Wu HP, Xu GF, Liu W, Xie ZG, Shi L, He X, Jin SG, Iqbal K, Shi YG, Deng Z, Szabo PE, Pfeifer GP, Li J, Xu GL"	"1] Group of DNA Metabolism, The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2]."	"Sperm and eggs carry distinctive epigenetic modifications that are adjusted by reprogramming after fertilization. The paternal genome in a zygote undergoes active DNA demethylation before the first mitosis. The biological significance and mechanisms of this paternal epigenome remodelling have remained unclear. Here we report that, within mouse zygotes, oxidation of 5-methylcytosine (5mC) occurs on the paternal genome, changing 5mC into 5-hydroxymethylcytosine (5hmC). Furthermore, we demonstrate that the dioxygenase Tet3 (ref. 5) is enriched specifically in the male pronucleus. In Tet3-deficient zygotes from conditional knockout mice, paternal-genome conversion of 5mC into 5hmC fails to occur and the level of 5mC remains constant. Deficiency of Tet3 also impedes the demethylation process of the paternal Oct4 and Nanog genes and delays the subsequent activation of a paternally derived Oct4 transgene in early embryos. Female mice depleted of Tet3 in the germ line show severely reduced fecundity and their heterozygous mutant offspring lacking maternal Tet3 suffer an increased incidence of developmental failure. Oocytes lacking Tet3 also seem to have a reduced ability to reprogram the injected nuclei from somatic cells. Therefore, Tet3-mediated DNA hydroxylation is involved in epigenetic reprogramming of the zygotic paternal DNA following natural fertilization and may also contribute to somatic cell nuclear reprogramming during animal cloning."	""
 3	"asian"	"China"	"China"	"0.0281690140845"	"0.0281690140845"	"0.056338028169"	"142"	"10.9230769231"	"Nature Genetics"	"Gui Y, Guo G, Huang Y, Hu X, Tang A, Gao S, Wu R, Chen C, Li X, Zhou L, He M, Li Z, Sun X, Jia W, Chen J, Yang S, Zhou F, Zhao X, Wan S, Ye R, Liang C, Liu Z, Huang P, Liu C, Jiang H, Wang Y, Zheng H, Sun L, Liu X, Jiang Z, Feng D, Chen J, Wu S, Zou J, Zhang Z, Yang R, Zhao J, Xu C, Yin W, Guan Z, Ye J, Zhang H, Li J, Kristiansen K, Nickerson ML, Theodorescu D, Li Y, Zhang X, Li S, Wang J, Yang H, Wang J, Cai Z"	"1] Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, China. [2]."	"Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer."	""
+3	"asian"	"West Point, USA."	"USA"	"0.00892857142857"	"0.0401785714286"	"0.0491071428571"	"224"	"14.9333333333"	"Glycobiology"	"Ha S, Ou Y, Vlasak J, Li Y, Wang S, Vo K, Du Y, Mach A, Fang Y, Zhang N"	"Merck Research Laboratories, West Point, PA 19486, USA."	"N-glycosylation of immunoglobulin G (IgG) at asparigine residue 297 plays a critical role in antibody stability and immune cell-mediated Fc effector function. Current understanding pertaining to Fc glycosylation is based on studies with IgGs that are either fully glycosylated [both heavy chain (HC) glycosylated] or aglycosylated (neither HC glycosylated). No study has been reported on the properties of hemi-glycosylated IgGs, antibodies with asymmetrical glycosylation in the Fc region such that one HC is glycosylated and the other is aglycosylated. We report here for the first time a detailed study of how hemi-glycosylation affects the stability and functional activities of an IgG1 antibody, mAb-X, in comparison to its fully glycosylated counterpart. Our results show that hemi-glycosylation does not impact Fab-mediated antigen binding, nor does it impact neonatal Fc receptor binding. Hemi-glycosylated mAb-X has slightly decreased thermal stability in the CH2 domain and a moderate decrease ( approximately 20%) in C1q binding. More importantly, the hemi-glycosylated form shows significantly decreased binding affinities toward all Fc gamma receptors (FcgammaRs) including the high-affinity FcgammaRI, and the low-affinity FcgammaRIIA, FcgammaRIIB, FcgammaRIIIA and FcgammaRIIIB. The decreased binding affinities to FcgammaRs result in a 3.5-fold decrease in antibody-dependent cell cytotoxicity (ADCC). As ADCC often plays an important role in therapeutic antibody efficacy, glycosylation status will not only affect the antibody quality but also may impact the biological function of the product."	""
+3	"asian"	"Japan"	"Japan"	"0.00502512562814"	"0.0150753768844"	"0.0854271356784"	"199"	"15.3076923077"	"Nature"	"Hada K, Doi A, Kino M, Nagai H, Hagiwara Y, Kawaguchi N"	"Department of Astronomical Science, The Graduate University for Advanced Studies (SOKENDAI), 2-21-1 Osawa, Mitaka, Tokyo 181-8588, Japan."	"Powerful radio jets from active galactic nuclei are thought to be powered by the accretion of material onto the supermassive black hole (the central engine). M87 is one of the closest examples of this phenomenon, and the structure of its jet has been probed on a scale of about 100 Schwarzschild radii (R(s), the radius of the event horizon). However, the location of the central black hole relative to the jet base (a bright compact radio core) remains elusive. Observations of other jets indicate that the central engines are located about 10(4)-10(6)R(s) upstream from the radio core. Here we report radio observations of M87 at six frequencies that allow us to achieve a positional accuracy of about 20 microarcseconds. As the jet base becomes more transparent at higher frequencies, the multifrequency position measurements of the radio core enable us to determine the upstream end of the jet. The data reveal that the central engine of M87 is located within 14-23R(s) of the radio core at 43 GHz. This implies that the site of material infall onto the black hole and the eventual origin of the jet reside in the bright compact region seen on the image at 43 GHz."	""
+3	"asian"	"Japan"	"Japan"	"0.0150753768844"	"0.00502512562814"	"0.0854271356784"	"199"	"15.3076923077"	"Blood"	"Hamada Y, Gonda K, Takeda M, Sato A, Watanabe M, Yambe T, Satomi S, Ohuchi N"	"Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Sendai, Japan;"	"Vascular endothelial growth factor (VEGF) plays a critical role in angiogenesis and has been applied to medical therapy. However, as vascular imaging at the molecular level is impossible, the detailed in vivo dynamics of VEGF and its receptor (VEGF-R) remain unknown. In this study, to understand the molecular distribution of VEGF and the VEGF-R, we prepared ischemic mice with a new surgical method and induced angiogenesis in the gastrocnemius muscle. Then, we made a VEGF-conjugated fluorescence nano-particle and performed staining of VEGF-R-expressing cells with the fluorescent probe, demonstrating the high-affinity of the probe for VEGF-R. To observe the physiological molecular distribution of VEGF-R, we performed in vivo single particle imaging of gastrocnemius in the ischemic leg with the fluorescent probe. The results suggested that only a 3-fold difference of VEGF-receptor distribution is involved in the formation of branched vasculature in angiogenesis, although previous ex vivo data showed a 13-fold difference in its distribution, indicating that a method inducing a several-fold local increase of VEGF-R concentration may be effective in generating site-specific angiogenesis in ischemic disease. This new in vivo imaging of ischemic mice could make useful contributions to understanding the mechanisms of angiogenesis and to developing a VEGF-R-related drug."	""
+3	"asian"	"Singapore, Singapore"	"Singapore"	"0.0132450331126"	"0.00662251655629"	"0.0993377483444"	"151"	"8.88235294118"	"Nature Genetics"	"Handoko L, Xu H, Li G, Ngan CY, Chew E, Schnapp M, Lee CW, Ye C, Ping JL, Mulawadi F, Wong E, Sheng J, Zhang Y, Poh T, Chan CS, Kunarso G, Shahab A, Bourque G, Cacheux-Rataboul V, Sung WK, Ruan Y, Wei CL"	"Genome Institute of Singapore, Singapore."	"Mammalian genomes are viewed as functional organizations that orchestrate spatial and temporal gene regulation. CTCF, the most characterized insulator-binding protein, has been implicated as a key genome organizer. However, little is known about CTCF-associated higher-order chromatin structures at a global scale. Here we applied chromatin interaction analysis by paired-end tag (ChIA-PET) sequencing to elucidate the CTCF-chromatin interactome in pluripotent cells. From this analysis, we identified 1,480 cis- and 336 trans-interacting loci with high reproducibility and precision. Associating these chromatin interaction loci with their underlying epigenetic states, promoter activities, enhancer binding and nuclear lamina occupancy, we uncovered five distinct chromatin domains that suggest potential new models of CTCF function in chromatin organization and transcriptional control. Specifically, CTCF interactions demarcate chromatin-nuclear membrane attachments and influence proper gene expression through extensive cross-talk between promoters and regulatory elements. This highly complex nuclear organization offers insights toward the unifying principles that govern genome plasticity and function."	""
+3	"asian"	"China, China"	"China"	"0.0105633802817"	"0.0140845070423"	"0.0528169014085"	"284"	"14.9473684211"	"PLoS One"	"Hao C, Hao J, Wang W, Han Z, Li G, Zhang L, Zhao X, Yu G"	"Key Laboratory of Marine Drugs, Chinese Ministry of Education, Ocean University of China, Qingdao, Peoples Republic of China."	"BACKGROUND: It was known that the insulin resistance in skeletal muscle is a major pathogenic factor in diabetes mellitus. Therefore prevention of metabolic disorder caused by insulin resistance and improvement of insulin sensitivity are very important for the therapy of type 2 diabetes. In the present study, we investigated the ability of marine oligosaccharides oligomannuronate and its chromium (III) complexes from brown alga to enhance insulin sensitivity in C2C12 skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that oligomannuronate, especially its chromium (III) complexes, enhanced insulin-stimulated glucose uptake and increased the mRNA expression of glucose transporter 4 (GLUT4) and insulin receptor (IR) after their internalization into C2C12 skeletal muscle cells. Additionally, oligosaccharides treatment also significantly enhanced the phosphorylation of proteins involved in both AMP activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways in C2C12 cells, indicating that the oligosaccharides activated both the insulin signal pathway and AMPK pathways as their mode of action. Moreover, oligosaccharides distributed to the mitochondria after internalization into C2C12 cells and increased the expression of transcriptional regulator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), carnitine palmitoyl transferase-1 (CPT-1), and phosphorylated acetyl-CoA carboxylase (p-ACC), which suggested that the actions of these oligosaccharides might be associated with mitochondria through increasing energy expenditure. All of these effects of marine oligosaccharides were comparable to that of the established anti-diabetic drug, metformin. In addition, the treatment with oligosaccharides showed less toxicity than that of metformin. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that oligomannuonate and its chromium (III) complexes improved insulin sensitivity in C2C12 skeletal muscle cells, and acted as a novel glucose uptake stimulator with low toxicity, and could be used as dietary supplementary or potential drug for type 2 diabetes mellitus."	""
+3	"asian"	"Japan"	"Japan"	"0.0131578947368"	"0.00657894736842"	"0.0328947368421"	"152"	"11.6923076923"	"Immunity"	"Hashimoto-Tane A, Yokosuka T, Sakata-Sogawa K, Sakuma M, Ishihara C, Tokunaga M, Saito T"	"Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan."	"When T cells recognize a peptide-major histocompatibility complex on antigen-presenting cells (APCs), T cell receptor microclusters (TCR-MCs) are generated and move to the center of the T cell-APC interface to form the central supramolecular activation cluster (cSMAC). cSMAC formation depends on stimulation strength and regulates T cell activation. We demonstrate that the dynein motor complex colocalized and coimmunoprecipitated with the TCR complex and that TCR-MCs moved along microtubules (MTs) toward the center of the immune synapse in a dynein-dependent manner to form cSMAC. MTs are located in close proximity to the plasma membrane at the activation site. TCR-MC velocity and cSMAC formation were impaired by dynein or MT inhibitors or by ablation of dynein expression. T cells with impaired cSMAC formation exhibited enhanced cellular activation including protein phosphorylation and interleukin-2 production. These results indicate that cSMAC formation by TCR-MC movement depends on dynein and MTs, and the movement regulates T cell activation."	""
+3	"asian"	"Israel"	"Israel"	"0.00763358778626"	"0.030534351145"	"0.103053435115"	"262"	"17.4666666667"	"PLoS Computational Biology"	"Hay E, Hill S, Schurmann F, Markram H, Segev I"	"Interdisciplinary Center for Neural Computation and Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel."	"The thick-tufted layer 5b pyramidal cell extends its dendritic tree to all six layers of the mammalian neocortex and serves as a major building block for the cortical column. L5b pyramidal cells have been the subject of extensive experimental and modeling studies, yet conductance-based models of these cells that faithfully reproduce both their perisomatic Na(+)-spiking behavior as well as key dendritic active properties, including Ca(2+) spikes and back-propagating action potentials, are still lacking. Based on a large body of experimental recordings from both the soma and dendrites of L5b pyramidal cells in adult rats, we characterized key features of the somatic and dendritic firing and quantified their statistics. We used these features to constrain the density of a set of ion channels over the soma and dendritic surface via multi-objective optimization with an evolutionary algorithm, thus generating a set of detailed conductance-based models that faithfully replicate the back-propagating action potential activated Ca(2+) spike firing and the perisomatic firing response to current steps, as well as the experimental variability of the properties. Furthermore, we show a useful way to analyze model parameters with our sets of models, which enabled us to identify some of the mechanisms responsible for the dynamic properties of L5b pyramidal cells as well as mechanisms that are sensitive to morphological changes. This automated framework can be used to develop a database of faithful models for other neuron types. The models we present provide several experimentally-testable predictions and can serve as a powerful tool for theoretical investigations of the contribution of single-cell dynamics to network activity and its computational capabilities."	""
+3	"asian"	"Israel"	"Israel"	"0.00602409638554"	"0.0180722891566"	"0.0542168674699"	"332"	"12.2962962963"	"Molecular Biology and Evolution"	"Hilman D, Gat U"	"Department of Cell and Developmental Biology, The Alexander Silberman Institute of Life Sciences, Edmond Safra Campus at Givat Ram, The Hebrew University, Jerusalem, Israel."	"The Hippo/YAP pathway plays an important role in animal organ size control, which it exerts by regulating tissue proliferation and apoptosis rates as a response to developmental cues, cell contact, and density. With the ever increasing advance in genome sequencing and analysis tools, our understanding of the animal world and its evolution has greatly increased in the recent years. We used bioinformatic tools to study the evolution of the Hippo/YAP pathway focusing on the transcriptional coactivator YAP, which is a pivotal effector of the pathway. The aim was to establish the origin and mode of development of YAP and its pathway in the animal world. Some pathway members can be already identified in single-celled eukaryotes like the yeast that have preceded multicellular animals. Interestingly, we can find most of the components that are present in human in the sea-anemone Nematostella, which belongs to a very basal group of metazoans, the cnidarians. All the major domains of YAP have been conserved between cnidarians and mammals, and YAP can be identified even in the more basal placozoan clade. We show a very high degree of conservation in regions such as the WW and the TEAD-binding domains, TEAD being the major DNA-binding partner of YAP. Remarkably, we found that the location of an intron in the WW1 genomic region has been invariant along an evolutionary span of over 700 My. We have followed the evolutionary changes in YAP and in other main components of the pathway from the first metazoans such as sponges, described the phylogenetic relationships between the YAP genes and indicated where YAP and other components have been secondarily lost. Evidence is provided that YAP and its binding partner TEAD demonstrate strong coevolution. This gives further support for the importance of the TEAD-YAP association. Beyond contributing to an understanding of the evolutionary history of this pathway, we have provided insights into the birth of this pathway, its functions and its mode of operation in animals with different body plans, development, and life styles."	""
+3	"asian"	"Kyoto, Kyoto, Japan"	"Japan"	"0.0147783251232"	"0.00985221674877"	"0.0886699507389"	"203"	"13.5333333333"	"Glycobiology"	"Hirano M, Ma BY, Kawasaki N, Oka S, Kawasaki T"	"Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan."	"Ischemia/reperfusion (I/R) is an important cause of acute renal failure. Recent studies have shown that the complement system mediated by the mannan-binding protein (MBP), which is a C-type serum lectin recognizing mannose, fucose, and N-acetylglucosamine residues, plays a critical role in pathogenesis of ischemic acute renal failure. MBP causes complement activation through the MBP-lectin pathway and a resulting complement component, C3b, is accumulated on the brush borders of kidney proximal tubules in renal I/R-operated mouse. However, the initial step of the complement activation has not been studied extensively. We previously identified both meprin alpha and beta (meprins), highly glycosylated zinc-metalloproteases, localized on kidney proximal tubules as endogenous MBP ligands. In the present study, we demonstrated that serum type MBP (S-MBP) and C3b were co-localized with meprins on both the cortex and medulla in renal I/R-operated mouse kidney, S-MBP was indicated to interact with meprins in vivo in I/R-operated mouse kidney, and S-MBP was shown to initiate complement activation through the interaction with meprins in vitro. Taken together, the present study strongly suggested that the binding of S-MBP to meprins triggers the complement activation through the lectin pathway and may cause the acute renal failure due to I/R on kidney transplantation and hemorrhagic shock."	""
+3	"asian"	"Japan"	"Japan"	"0.00507614213198"	"0.0203045685279"	"0.0609137055838"	"197"	"8.5652173913"	"Glycobiology"	"Hirayama H, Suzuki T"	"Glycometabolome Team, Systems Glycobiology Research Group, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako Saitama 351-0198, Japan."	"In eukaryotic cells, it is known that N-glycans play a pivotal role in quality control of carrier proteins. Although free forms of oligosaccharides (fOSs) are known to be accumulated in the cytosol, the precise mechanism of their formation, degradation and biological relevance remains poorly understood. It has been shown that, in budding yeast, almost all fOSs are formed from misfolded glycoproteins. Precise structural analysis of fOSs revealed that several yeast fOSs bear a yeast-specific modification by Golgi-resident alpha-1,6-mannosyltransferase, Och1. In this study, structural diversity of fOSs in och1Delta cells was analyzed. To our surprise, several fOSs in och1Delta cells have unusual alpha-1,3-linked mannose residues at their non-reducing termini. These mannose residues were not observed in wild-type cells, suggesting that the addition of these unique mannoses occurred as a compensation of Och1 defect. A significant increase in the amount of fOSs modified by Golgi-localized mannosyltransferases was also observed in och1Delta cells. Moreover, the amount of processed fOSs and intracellular alpha-mannosidase (Ams1) both increased in this mutant. Up-regulation of Ams1 activity was also apparent for cells treated with cell wall perturbation reagent. These results provide an insight into a possible link between catabolism of fOSs and cell wall stress."	""
+3	"asian"	"Japan"	"Japan"	"0.0251572327044"	"0.0188679245283"	"0.0754716981132"	"159"	"17.6666666667"	"Nature Genetics"	"Hirota T, Takahashi A, Kubo M, Tsunoda T, Tomita K, Doi S, Fujita K, Miyatake A, Enomoto T, Miyagawa T, Adachi M, Tanaka H, Niimi A, Matsumoto H, Ito I, Masuko H, Sakamoto T, Hizawa N, Taniguchi M, Lima JJ, Irvin CG, Peters SP, Himes BE, Litonjua AA, Tantisira KG, Weiss ST, Kamatani N, Nakamura Y, Tamari M"	"Laboratory for Respiratory Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa, Japan."	"Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 x 10(-12)), a locus on chromosome 10p14 (P = 1.79 x 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 x 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 x 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility."	""
+3	"asian"	"Japan"	"Japan"	"0.0119047619048"	"0.0238095238095"	"0.0892857142857"	"168"	"9.10526315789"	"Database(Oxford)"	"Hishigaki H, Kuhara S"	"Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan."	"Drug-induced QT interval prolongation is one of the most common reasons for the withdrawal of drugs from the market. In the past decade, at least nine drugs, i.e. terfenadine, astemizole, grepafloxacin, terodiline, droperidol, lidoflazine, sertindole, levomethadyl and cisapride, have been removed from the market or their use has been severely restricted because of drug-induced QT interval prolongation. Therefore, this irregularity is a major safety concern in the case of drugs submitted for regulatory approval. The most common mechanism of drug-induced QT interval prolongation may be drug-related inhibition of the human ether-a-go-go-related gene (hERG) channel, which subsequently results in prolongation of the cardiac action potential duration (APD). hERGAPDbase is a database of electrophysiological experimental data documenting potential hERG channel inhibitory actions and the APD-prolongation activities of chemical compounds. All data entries are manually collected from scientific papers and curated by a person. With hERGAPDbase, we aim to provide useful information for chemical and pharmacological scientists and enable easy access to electrophysiological experimental data on chemical compounds. Database URL:"	""
+3	"asian"	"Taiwan"	"China"	"0.014598540146"	"0.029197080292"	"0.0802919708029"	"274"	"10.1851851852"	"BMC Bioinformatics"	"Ho SY, Chao CY, Huang HL, Chiu TW, Charoenkwan P, Hwang E"	"Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan."	"BACKGROUND: Automatic quantification of neuronal morphology from images of fluorescence microscopy plays an increasingly important role in high-content screenings. However, there exist very few freeware tools and methods which provide automatic neuronal morphology quantification for pharmacological discovery. RESULTS: This study proposes an effective quantification method, called NeurphologyJ, capable of automatically quantifying neuronal morphologies such as soma number and size, neurite length, and neurite branching complexity (which is highly related to the numbers of attachment points and ending points). NeurphologyJ is implemented as a plugin to ImageJ, an open-source Java-based image processing and analysis platform. The high performance of NeurphologyJ arises mainly from an elegant image enhancement method. Consequently, some morphology operations of image processing can be efficiently applied. We evaluated NeurphologyJ by comparing it with both the computer-aided manual tracing method NeuronJ and an existing ImageJ-based plugin method NeuriteTracer. Our results reveal that NeurphologyJ is comparable to NeuronJ, that the coefficient correlation between the estimated neurite lengths is as high as 0.992. NeurphologyJ can accurately measure neurite length, soma number, neurite attachment points, and neurite ending points from a single image. Furthermore, the quantification result of nocodazole perturbation is consistent with its known inhibitory effect on neurite outgrowth. We were also able to calculate the IC50 of nocodazole using NeurphologyJ. This reveals that NeurphologyJ is effective enough to be utilized in applications of pharmacological discoveries. CONCLUSIONS: This study proposes an automatic and fast neuronal quantification method NeurphologyJ. The ImageJ plugin with supports of batch processing is easily customized for dealing with high-content screening applications. The source codes of NeurphologyJ (interactive and high-throughput versions) and the images used for testing are freely available (see Availability)."	""
+2	"asian"	"California, California, USA."	"USA"	"0.0215517241379"	"0.0215517241379"	"0.137931034483"	"232"	"13.6470588235"	"ANNUAL REVIEW OF PSYCHOLOGY"	"Holyoak KJ, Cheng PW"	"Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095-1563, USA."	"Over the past decade, an active line of research within the field of human causal learning and inference has converged on a general representational framework: causal models integrated with bayesian probabilistic inference. We describe this new synthesis, which views causal learning and inference as a fundamentally rational process, and review a sample of the empirical findings that support the causal framework over associative alternatives. Causal events, like all events in the distal world as opposed to our proximal perceptual input, are inherently unobservable. A central assumption of the causal approach is that humans (and potentially nonhuman animals) have been designed in such a way as to infer the most invariant causal relations for achieving their goals based on observed events. In contrast, the associative approach assumes that learners only acquire associations among important observed events, omitting the representation of the distal relations. By incorporating bayesian inference over distributions of causal strength and causal structures, along with noisy-logical (i.e., causal) functions for integrating the influences of multiple causes on a single effect, human judgments about causal strength and structure can be predicted accurately for relatively simple causal structures. Dynamic models of learning based on the causal framework can explain patterns of acquisition observed with serial presentation of contingency data and are consistent with available neuroimaging data. The approach has been extended to a diverse range of inductive tasks, including category-based and analogical inferences."	""
+3	"asian"	"Japan"	"Japan"	"0.00396825396825"	"0.00396825396825"	"0.107142857143"	"252"	"16.8"	"PLoS Computational Biology"	"Honda T, Yamazaki T, Tanaka S, Nagao S, Nishino T"	"Department of Information and Communication Engineering, Graduate School of Electro-Communications, The University of Electro-Communications, Chofu-shi, Tokyo, Japan."	"Information processing of the cerebellar granular layer composed of granule and Golgi cells is regarded as an important first step toward the cerebellar computation. Our previous theoretical studies have shown that granule cells can exhibit random alternation between burst and silent modes, which provides a basis of population representation of the passage-of-time (POT) from the onset of external input stimuli. On the other hand, another computational study has reported that granule cells can exhibit synchronized oscillation of activity, as consistent with observed oscillation in local field potential recorded from the granular layer while animals keep still. Here we have a question of whether an identical network model can explain these distinct dynamics. In the present study, we carried out computer simulations based on a spiking network model of the granular layer varying two parameters: the strength of a current injected to granule cells and the concentration of Mg(2) which controls the conductance of NMDA channels assumed on the Golgi cell dendrites. The simulations showed that cells in the granular layer can switch activity states between synchronized oscillation and random burst-silent alternation depending on the two parameters. For higher Mg(2) concentration and a weaker injected current, granule and Golgi cells elicited spikes synchronously (synchronized oscillation state). In contrast, for lower Mg(2) concentration and a stronger injected current, those cells showed the random burst-silent alternation (POT-representing state). It is suggested that NMDA channels on the Golgi cell dendrites play an important role for determining how the granular layer works in response to external input."	""
+3	"asian"	"Japan"	"Japan"	"0.00584795321637"	"0.0116959064327"	"0.0292397660819"	"171"	"11.4"	"Glycobiology"	"Honda Y, Shimaya N, Ishisaki K, Ebihara M, Taniguchi H"	"Department of Food Science, Ishikawa Prefectural University, 1-308 Suematsu, Nonoichi, Ishikawa 921-8836, Japan."	"A glycoside hydrolase (GH) gene from Photobacterium profundum SS9 (PBPRA0520) belonging to GH family 9 was expressed in Escherichia coli. The protein was expressed with the intact N-terminal sequence, suggesting that it is an intracellular enzyme. The recombinant protein showed hydrolytic activity toward chitobiose [(GlcN)(2)] and cellobiose (CG(2)) in various disaccharides. This protein also released 4-nitrophenol (PNP) from both 4-nitrophenyl-beta-D-glucosaminide (GlcN-PNP) and 4-nitrophenyl-beta-D-glucoside (Glc-PNP). The hydrolytic pattern observed in chitooligosaccharides and cellooligosaccharides suggested that the reaction proceeded from the nonreducing end in an exo-type manner. Time-dependent (1)H-nuclear magnetic resonance (NMR) analysis of the anomeric form of the enzymatic reaction products indicated that the protein is an inverting enzyme. k(cat)/K(m) of (GlcN)(2) hydrolysis was 14 times greater than that of CG(2) hydrolysis. These results suggested that the protein is an exo-beta-D-glucosaminidase (EC rather than a glucan 1,4-beta-D-glucosidase (EC Based on the results, we suggest that the function of conserved GH9 proteins in the chitin catabolic operon is to cleave a (GlcN)(2)-phosphate derivative by hydrolysis during intracellular chitooligosaccharide catabolism in Vibrionaceae."	""
+3	"asian"	"Lebanon"	"Lebanon"	"0.0132158590308"	"0.0132158590308"	"0.0704845814978"	"227"	"13.3529411765"	"Glycobiology"	"Hopkins D, Gomathinayagam S, Rittenhour AM, Du M, Hoyt E, Karaveg K, Mitchell T, Nett JH, Sharkey NJ, Stadheim TA, Li H, Hamilton SR"	"GlycoFi Inc., A wholly-owned subsidiary of Merck & Co Inc., 21 Lafayette street, Suite 200 Lebanon, NH, 03766."	"The methylotrophic yeast, Pichia pastoris, is an important organism used for the production of therapeutic proteins. However, the presence of fungal-like glycans such as those containing beta-mannose linkages can elicit an immune response or bind to mannose receptors, thus reducing their efficacy. Recent studies have confirmed that Pichia pastoris has four genes from the beta-mannosyl transferase (BMT) family and that Bmt2p is responsible for the majority of beta-mannose linkages on glycans. While expressing recombinant human erythropoietin (rhEPO) in a developmental glycoengineered strain devoid of BMT2 gene expression, cross-reactivity was observed with an antibody raised against host cell antigens (HCA). Treatment of the rhEPO with protein N-glycosidase F (PNGase F) eliminated cross-reactivity, indicating that the antigen was associated with the glycan. Thorough analysis of the glycan profile of rhEPO demonstrated the presence of low amounts of alpha-1,2-mannosidase resistant high mannose glycoforms. In an attempt to eliminate the alpha-mannosidase resistant glycoforms, we used a systemic approach to genetically knock-out the remaining members of the beta-mannosyl transferase family culminating in a quadruple bmt2,4,1,3 knock-out strain. Data presented here concludes that the additive elimination of Bmt2p, Bmt3p and Bmt1p activities are required for total abolition of beta-mannose associated glycans and their related antigenicity. Taken together, the elimination of beta-mannose containing glycoforms represents an important step forward for the Pichia production platform as a suitable system for the production of therapeutic glycoproteins."	""
 3	"asian"	"China"	"China"	"0.0"	"0.0188679245283"	"0.125786163522"	"159"	"7.21739130435"	"Bioinformatics"	"Hou T, Li Y, Wang W"	"Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, PR China."	"MOTIVATION: Favorable interaction between the regulatory subunit of the cAMP-dependent protein kinase (PKA) and a peptide in A-kinase anchoring proteins (AKAPs) is critical for translocating PKA to the subcellular sites where the enzyme phosphorylates its substrates. It is very hard to identify AKAPs peptides binding to PKA due to the high sequence diversity of AKAPs. RESULTS: We propose a hierarchical and efficient approach, which combines molecular dynamics (MD) simulations, free energy calculations, virtual mutagenesis (VM) and bioinformatics analyses, to predict peptides binding to the PKA RIIalpha regulatory subunit in the human proteome systematically. Our approach successfully retrieved 15 out of 18 documented RIIalpha-binding peptides. Literature curation supported that many newly predicted peptides might be true AKAPs. Here, we present the first systematic search for AKAP peptides in the human proteome, which is useful to further experimental identification of AKAPs and functional analysis of their biological roles. CONTACT:;; SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
 3	"asian"	"China"	"China"	"0.0196078431373"	"0.0313725490196"	"0.043137254902"	"255"	"11.1739130435"	"PLoS One"	"Hou X, Sun L, Li Z, Mou H, Yu Z, Li H, Jiang P, Yu D, Wu H, Ye X, Lin X, Le Y"	"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China."	"BACKGROUND: Cellular and animal studies implicate multiple roles of amylin in regulating insulin action, glucose and lipid metabolisms. However, the role of amylin in obesity related metabolic disorders has not been thoroughly investigated in humans. Therefore, we aimed to evaluate the distribution of circulating amylin and its association with metabolic syndrome (MetS) and explore if this association is influenced by obesity, inflammatory markers or insulin resistance in apparently healthy Chinese. METHODS: A population-based sample of 1,011 Chinese men and women aged 35-54 years was employed to measure plasma amylin, inflammatory markers (C-reactive protein [CRP] and interleukin-6 [IL-6]), insulin, glucose and lipid profiles. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. RESULTS: Plasma amylin concentrations were higher in overweight/obese participants than normal-weight counterparts (P<0.001) without sex difference. Circulating amylin was positively associated with CRP, IL-6, BMI, waist circumference, blood pressure, fasting glucose, insulin, amylin/insulin ratio, HOMA-IR, LDL cholesterol and triglycerides, while negatively associated with HDL cholesterol (all P<0.001). After multiple adjustments, the risk of MetS was significantly higher (odds ratio 3.71; 95% confidence interval: 2.53 to 5.46) comparing the highest with the lowest amylin quartile. The association remained significant even further controlling for BMI, inflammatory markers, insulin or HOMA-IR. CONCLUSIONS: Our study suggests that amylin is strongly associated with inflammatory markers and MetS. The amylin-MetS association is independent of established risk factors of MetS, including obesity, inflammatory markers and insulin resistance. The causal role of hyperamylinemia in the development of MetS needs to be confirmed prospectively."	""
+3	"asian"	"China, Taiwan"	"China"	"0.013468013468"	"0.010101010101"	"0.047138047138"	"297"	"11.88"	"PLoS One"	"Hsieh CH, Shyu WC, Chiang CY, Kuo JW, Shen WC, Liu RS"	"Graduate Institute of Basic Medical Science, China Medical University and Hospital, Taichung, Taiwan."	"BACKGROUND: Cycling and chronic tumor hypoxia are involved in tumor development and growth. However, the impact of cycling hypoxia and its molecular mechanism on glioblastoma multiforme (GBM) progression remain unclear. METHODOLOGY: Glioblastoma cell lines, GBM8401 and U87, and their xenografts were exposed to cycling hypoxic stress in vitro and in vivo. Reactive oxygen species (ROS) production in glioblastoma cells and xenografts was assayed by in vitro ROS analysis and in vivo molecular imaging studies. NADPH oxidase subunit 4 (Nox4) RNAi-knockdown technology was utilized to study the role of Nox4 in cycling hypoxia-mediated ROS production and tumor progression. Furthermore, glioblastoma cells were stably transfected with a retroviral vector bearing a dual reporter gene cassette that allowed for dynamic monitoring of HIF-1 signal transduction and tumor cell growth in vitro and in vivo, using optical and nuclear imaging. Tempol, an antioxidant compound, was used to investigate the impact of ROS on cycling hypoxia-mediated HIF-1 activation and tumor progression. PRINCIPAL FINDINGS: Glioblastoma cells and xenografts were compared under cycling hypoxic and normoxic conditions; upregulation of NOX4 expression and ROS levels were observed under cycling hypoxia in glioblastoma cells and xenografts, concomitant with increased tumor cell growth in vitro and in vivo. However, knockdown of Nox4 inhibited these effects. Moreover, in vivo molecular imaging studies demonstrated that Tempol is a good antioxidant compound for inhibiting cycling hypoxia-mediated ROS production, HIF-1 activation, and tumor growth. Immunofluorescence imaging and flow cytometric analysis for NOX4, HIF-1 activation, and Hoechst 3342 in glioblastoma also revealed high localized NOX4 expression predominantly in potentially cycling hypoxic areas with HIF-1 activation and blood perfusion within the endogenous solid tumor microenvironment. CONCLUSIONS: Cycling hypoxia-induced ROS via Nox4 is a critical aspect of cancer biology to consider for therapeutic targeting of cycling hypoxia-promoted HIF-1 activation and tumor progression in GBM."	""
+3	"asian"	"Taiwan"	"China"	"0.0139534883721"	"0.0139534883721"	"0.0697674418605"	"215"	"11.3157894737"	"BMC Bioinformatics"	"Hsieh WP, Chu TM, Lin YM, Wolfinger RD"	"Institute of Statistics, National Tsing Hua University, Hsin-Chu City, 300, Taiwan."	"BACKGROUND: Normalization of gene expression data has been studied for many years and various strategies have been formulated to deal with various types of data. Most normalization algorithms rely on the assumption that the number of up-regulated genes and the number of down-regulated genes are roughly the same. However, the well-known Golden Spike experiment presents a unique situation in which differentially regulated genes are biased toward one direction, thereby challenging the conclusions of previous bench mark studies. RESULTS: This study proposes two novel approaches, KDL and KDQ, based on kernel density estimation to improve upon the basic idea of invariant set selection. The key concept is to provide various importance scores to data points on the MA plot according to their proximity to the cluster of the null genes under the assumption that null genes are more densely distributed than those that are differentially regulated. The comparison is demonstrated in the Golden Spike experiment as well as with simulation data using the ROC curves and compression rates. KDL and KDQ in combination with GCRMA provided the best performance among all approaches. CONCLUSIONS: This study determined that methods based on invariant sets are better able to resolve the problem of asymmetry. Normalization, either before or after expression summary for probesets, improves performance to a similar degree."	""
+3	"asian"	"Taiwan"	"China"	"0.0"	"0.0197628458498"	"0.0830039525692"	"253"	"9.55555555556"	"BMC Bioinformatics"	"Hsu JB, Chiu CM, Hsu SD, Huang WY, Chien CH, Lee TY, Huang HD"	"Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsin-Chu 300, Taiwan."	"ABSTRACT: BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules that are ~22-nt-long sequences capable of suppressing protein synthesis. Previous research has suggested that miRNAs regulate 30% or more of the human protein-coding genes. The aim of this work is to consider various analyzing scenarios in the identification of miRNA-target interactions, as well as to provide an integrated system that will aid in facilitating investigation on the influence of miRNA targets by alternative splicing and the biological function of miRNAs in biological pathways. RESULTS: This work presents an integrated system, miRTar, which adopts various analyzing scenarios to identify putative miRNA target sites of the gene transcripts and elucidates the biological functions of miRNAs toward their targets in biological pathways. The system has three major features. First, the prediction system is able to consider various analyzing scenarios (1 miRNA:1 gene, 1:N, N:1, N:M, all miRNAs:N genes, and N miRNAs: genes involved in a pathway) to easily identify the regulatory relationships between interesting miRNAs and their targets, in 3UTR, 5UTR and coding regions. Second, miRTar can analyze and highlight a group of miRNA-regulated genes that participate in particular KEGG pathways to elucidate the biological roles of miRNAs in biological pathways. Third, miRTar can provide further information for elucidating the miRNA regulation, i.e., miRNA-target interactions, affected by alternative splicing. CONCLUSIONS: In this work, we developed an integrated resource, miRTar, to enable biologists to easily identify the biological functions and regulatory relationships between a group of known/putative miRNAs and protein coding genes. miRTar is now available at"	""
+3	"asian"	"Taiwan"	"China"	"0.013468013468"	"0.020202020202"	"0.131313131313"	"297"	"11.0"	"BMC Bioinformatics"	"Hsu JT, Peng CH, Hsieh WP, Lan CY, Tang CY"	"Department of Computer Science, National Tsing Hua University, Hsinchu 30013, Taiwan."	"BACKGROUND: Identifying key components in biological processes and their associations is critical for deciphering cellular functions. Recently, numerous gene expression and molecular interaction experiments have been reported in Saccharomyces cerevisiae, and these have enabled systematic studies. Although a number of approaches have been used to predict gene functions and interactions, tools that analyze the essential coordination of functional components in cellular processes still need to be developed. RESULTS: In this work, we present a new approach to study the cooperation of functional modules (sets of functionally related genes) in a specific cellular process. A cooperative module pair is defined as two modules that significantly cooperate with certain functional genes in a cellular process. This method identifies cooperative module pairs that significantly influence a cellular process and the correlated genes and interactions that are essential to that process. Using the yeast cell cycle as an example, we identified 101 cooperative module associations among 82 modules, and importantly, we established a cell cycle-specific cooperative module network. Most of the identified module pairs cover cooperative pathways and components essential to the cell cycle. We found that 14, 36, 18, 15, and 20 cooperative module pairs significantly cooperate with genes regulated in early G1, late G1, S, G2, and M phase, respectively. Fifty-nine module pairs that correlate with Cdc28 and other essential regulators were also identified. These results are consistent with previous studies and demonstrate that our methodology is effective for studying cooperative mechanisms in the cell cycle. CONCLUSIONS: In this work, we propose a new approach to identifying condition-related cooperative interactions, and importantly, we establish a cell cycle-specific cooperation module network. These results provide a global view of the cell cycle and the method can be used to discover the dynamic coordination properties of functional components in other cellular processes."	""
 3	"asian"	"China"	"China"	"0.0"	"0.0169491525424"	"0.0847457627119"	"59"	"3.19047619048"	"Bioinformatics"	"Hu QN, Deng Z, Hu H, Cao DS, Liang YZ"	"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, School of Psychology, Southwest University, Chongqing 400715, Normal School, Tibet University, Lhasa 850000 and Research Center of Modernization of Traditional Chinese Medicines, Central South University, Changsha 410083, P. R. China."	"SUMMARY: Biochemical reactions play a key role to help sustain life and allow cells to grow. RxnFinder was developed to search biochemical reactions from KEGG reaction database using three search criteria: molecular structures, molecular fragments and reaction similarity. RxnFinder is helpful to get reference reactions for biosynthesis and xenobiotics metabolism. AVAILABILITY: RxnFinder is freely available via: CONTACT:"	""
+3	"asian"	"China, China"	"China"	"0.0157894736842"	"0.0157894736842"	"0.131578947368"	"190"	"11.1764705882"	"Blood"	"Hu Z, Van Rooijen N, Yang YG"	"Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, China;"	"An animal model supporting human erythropoiesis will be highly valuable for assessing the biological function of human RBCs under physiological and disease settings, and for evaluating protocols of in vitro RBC differentiation. Herein, we analyzed human RBC reconstitution in NOD/SCID or NOD/SCID/gammac(-/-) mice that were transplanted with human CD34(+) fetal liver cells and fetal thymic tissue. Although a large number of human CD45(-)CD71(+) nucleated immature erythroid cells were detected in the bone marrow, human RBCs were undetectable in the blood of these mice. Human RBCs became detectable in blood following macrophage depletion, but disappeared again after withdrawal of treatment. Furthermore, treatment with human erythropoietin and IL-3 significantly increased human RBC reconstitution in macrophage-depleted, but not control, humanized mice. Significantly more rapid rejection of human RBCs than CD47-deficient mouse RBCs indicates that mechanisms other than insufficient CD47-SIRPalpha signaling are involved in human RBC xenorejection in mice. All considered, our data demonstrate that human RBCs are highly susceptible to rejection by macrophages in immunodeficient mice. Thus, strategies for preventing human RBC rejection by macrophages are required for using immunodeficient mice as an in vivo model to study human erythropoiesis and RBC function."	""
 3	"asian"	"China"	"China"	"0.0116959064327"	"0.00584795321637"	"0.0350877192982"	"171"	"7.82608695652"	"Nature Genetics"	"Hu Z, Wu C, Shi Y, Guo H, Zhao X, Yin Z, Yang L, Dai J, Hu L, Tan W, Li Z, Deng Q, Wang J, Wu W, Jin G, Jiang Y, Yu D, Zhou G, Chen H, Guan P, Chen Y, Shu Y, Xu L, Liu X, Liu L, Xu P, Han B, Bai C, Zhao Y, Zhang H, Yan Y, Ma H, Chen J, Chu M, Lu F, Zhang Z, Chen F, Wang X, Jin L, Lu J, Zhou B, Lu D, Wu T, Lin D, Shen H"	"Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China."	"Lung cancer is the leading cause of cancer-related deaths worldwide. To identify genetic factors that modify the risk of lung cancer in individuals of Chinese ancestry, we performed a genome-wide association scan in 5,408 subjects (2,331 individuals with lung cancer (cases) and 3,077 controls) followed by a two-stage validation among 12,722 subjects (6,313 cases and 6,409 controls). The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 x 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 x 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 x 10(-20) and P = 1.0 x 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 x 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 x 10(-11) and P = 6.2 x 10(-13), respectively). Two of these loci (13q12.12 and 22q12.2) were newly identified in the Chinese population. These results suggest that genetic variants in 3q28, 5p15.33, 13q12.12 and 22q12.2 may contribute to the susceptibility of lung cancer in Han Chinese."	""
 3	"asian"	"China"	"China"	"0.00806451612903"	"0.0241935483871"	"0.108870967742"	"248"	"13.1578947368"	"PLoS One"	"Huang D, Haack RA, Zhang R"	"CAS Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China."	"BACKGROUND: The establishment rate of invasive alien insect species has been increasing worldwide during the past century. This trend has been widely attributed to increased rates of international trade and associated species introductions, but rarely linked to environmental change. To better understand and manage the bioinvasion process, it is crucial to understand the relationship between global warming and establishment rate of invasive alien species, especially for poikilothermic invaders such as insects. METHODOLOGY/PRINCIPAL FINDINGS: We present data that demonstrate a significant positive relationship between the change in average annual surface air temperature and the establishment rate of invasive alien insects in mainland China during 1900-2005. This relationship was modeled by regression analysis, and indicated that a 1 degrees C increase in average annual surface temperature in mainland China was associated with an increase in the establishment rate of invasive alien insects of about 0.5 species year(-1). The relationship between rising surface air temperature and increasing establishment rate remained significant even after accounting for increases in international trade during the period 1950-2005. Moreover, similar relationships were detected using additional data from the United Kingdom and the contiguous United States. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the perceived increase in establishments of invasive alien insects can be explained only in part by an increase in introduction rate or propagule pressure. Besides increasing propagule pressure, global warming is another driver that could favor worldwide bioinvasions. Our study highlights the need to consider global warming when designing strategies and policies to deal with bioinvasions."	""
 3	"asian"	"China"	"China"	"0.00909090909091"	"0.0181818181818"	"0.1"	"110"	"5.13043478261"	"Bioinformatics"	"Huang J, Liu Y, Zhang W, Yu H, Han JD"	"Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China."	"MOTIVATION: Although genome-wide association studies (GWAS) have found many common genetic variants associated with human diseases, it remains a challenge to elucidate the functional links between associated variants and complex traits. RESULTS: We developed a package called eResponseNet by implementing and extending the existing ResponseNet algorithm for prioritizing candidate disease genes through cellular pathways. Using type II diabetes (T2D) as a study case, we demonstrate that eResponseNet outperforms currently available approaches in prioritizing candidate disease genes. More importantly, the package is instrumental in revealing cellular pathways underlying disease-associated genetic variations. AVAILABILITY: The eResponseNet package is freely downloadable at CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
+3	"asian"	"USA."	"USA"	"0.0276243093923"	"0.0331491712707"	"0.0331491712707"	"181"	"10.7058823529"	"Glycobiology"	"Huang J, Xu Z, Wang D, Ogata CM, Palczewski K, Lee X, Young NM"	"Department of Pharmacology, School of Medicine, Case Western Reserve University, 2109 Adelbert Rd, Cleveland, OH 44106, USA."	"The Maclura pomifera agglutinin (MPA) recognizes the T-antigen disaccharide Galbeta1,3GalNAc mainly through interaction of the alpha-GalNAc moiety with its primary site, but the interactions of the two flanking subsites A and B with aglycones and substituents other than Gal, respectively, are not well understood. We therefore characterized the specificity of MPA in more detail by glycan microarray analysis and determined the crystal structures of MPA without ligand and in complexes with Galbeta1,3GalNAc and p-nitrophenyl alpha-GalNAc. In both sugar complexes, pairs of ligands created inter-tetramer hydrogen-bond bridging networks. While subsite A showed increased affinity for hydrophobic aglycones, it also accommodated several sugar substituents. Notably, a GalNAc-O-tripeptide, a Tn-antigen mimic, showed lower affinity than these compounds in surface plasmon resonance (SPR) experiments. The glycan array data that showed subsite B accepted compounds in which the O3 position of the GalNAc was substituted with various sugars other than Gal, but substitutions at O6 led to inactivity. Additions to the Gal moiety of the disaccharide also had only small effects on reactivity. These results are all compatible with the features seen in the crystal structures."	""
 3	"asian"	"China"	"China"	"0.0047619047619"	"0.0285714285714"	"0.114285714286"	"210"	"8.03703703704"	"Bioinformatics"	"Huang Q, Wu LY, Zhang XS"	"National Center for Mathematics and Interdisciplinary Sciences, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China."	"MOTIVATION: A large amount of biomolecular network data for multiple species have been generated by high-throughput experimental techniques, including undirected and directed networks such as protein-protein interaction networks, gene regulatory networks and metabolic networks. There are many conserved functionally similar modules and pathways among multiple biomolecular networks in different species, therefore, it is important to analyze the similarity between the biomolecular networks. Network querying approaches aim at efficiently discovering the similar subnetworks among different species. However, many existing methods only partially solve this problem. RESULTS: In this paper, a novel approach for network querying problem based on conditional random fields (CRF) model is presented, which can handle both undirected and directed networks, acyclic and cyclic networks, and any number of insertions/deletions. The CRF method is fast and can query pathways in a large network in seconds using a PC. To evaluate the CRF method, extensive computational experiments are conducted on the simulated and real data, and the results are compared with the existing network querying methods. All results show that the CRF method is very useful and efficient to find the conserved functionally similar modules and pathways in multiple biomolecular networks. AVAILABILITY: Code and data are available at CONTACT: SUPPLEMENTARY INFORMATION: Supplementary materials are available at Bioinformatics online."	""
 3	"asian"	"China"	"China"	"0.0"	"0.018779342723"	"0.0657276995305"	"213"	"8.52"	"Glycobiology"	"Huang QS, Xie XL, Liang G, Gong F, Wang Y, Wei XQ, Wang Q, Ji ZL, Chen QX"	"State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, P.R. China."	"The glycoside hydrolase 18 (GH18) family of chitinases are multi-gene family that play various roles, such as ecdysis, embryonic development, allergic inflammation and so on. Efforts are still expected to reveal their functional diversification in an evolutionary and systematic manner. We collected 85 GH18 genes from eukaryotic representatives. The domain architectures of GH18 proteins were analyzed, several conserved patterns were identified. It was observed that some (11 proteins) GH18 members in Ecdysozoa or fungi possess repeats of catalytic domains and/or chitin-binding domains (ChtBs). The domain repeats are likely to meet requirements for higher efficiency of chitin degradation in chitin-containing species. On the contrary, all vertebrate GH18 proteins contain no more than one catalytic domain or ChtB. The results from homologous analysis, domain architectures, exon arrangements and synteny loci supported the two evolutionary paths of GH18 family. One experienced gene expansion and contraction several times during evolution, covering most of GH18 members except CHID1 and its homologs. Proteins in the path undergo frequent domain gain and loss, as well as domain recombination, thus could achieve versatility in function. The other path is comparatively conserved that CHID1 gene evolved without gene duplication except in D. rerio. Domain architectures of CHID1 orthologs are all identical. The diverse phylogeny of GH18 family in arthropod was also presented."	""
+3	"asian"	"Singapore"	"Singapore"	"0.0235294117647"	"0.0235294117647"	"0.0764705882353"	"170"	"8.94736842105"	"Blood"	"Huang RL, Teo Z, Chong HC, Zhu P, Tan MJ, Tan CK, Lam CR, Sng MK, Leong DT, Tan SM, Kersten S, Ding JL, Li HY, Tan NS"	"School of Biological Sciences, Nanyang Technological University, Singapore;"	"Vascular disruption induced by interactions between tumor-secreted permeability factors and adhesive proteins on endothelial cells facilitates metastasis. The role of tumor-secreted angiopoietin-like 4 (cANGPTL4) in vascular leakiness and metastasis is controversial due to the lack of understanding of how cANGPTL4 modulates vascular integrity. Here, we show that cANGPTL4 instigated the disruption of endothelial continuity by directly interacting with three novel binding partners, integrin alpha5beta1, VE-cadherin and claudin-5, in a temporally sequential manner, thus facilitating metastasis. We showed that cANGPTL4 binds and activates integrin alpha5beta1-mediated Rac1/PAK signaling to weaken cell-cell contacts. cANGPTL4 subsequently associated with and declustered VE-cadherin and claudin-5, leading to endothelial disruption. Interfering with the formation of these cANGPTL4 complexes delayed vascular disruption. In vivo vascular permeability and metastatic assays performed using ANGPTL4-knockout and wild-type mice injected with either control or ANGPTL4-knockdown tumors confirmed that cANGPTL4 induced vascular leakiness and facilitated lung metastasis in mice. Thus, our findings elucidate how cANGPTL4 induces endothelial disruption. Our findings have direct implications for targeting cANGPTL4 to treat cancer and other vascular pathologies."	""
 3	"asian"	"China"	"China"	"0.0"	"0.036496350365"	"0.0583941605839"	"137"	"10.5384615385"	"Nature Genetics"	"Huang X, Wei X, Sang T, Zhao Q, Feng Q, Zhao Y, Li C, Zhu C, Lu T, Zhang Z, Li M, Fan D, Guo Y, Wang A, Wang L, Deng L, Li W, Lu Y, Weng Q, Liu K, Huang T, Zhou T, Jing Y, Li W, Lin Z, Buckler ES, Qian Q, Zhang QF, Li J, Han B"	"National Center for Gene Research, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China."	"Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified  approximately  3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained  approximately  36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice."	""
+3	"asian"	"Taiwan"	"China"	"0.00943396226415"	"0.0188679245283"	"0.0518867924528"	"212"	"10.0952380952"	"BMC Bioinformatics"	"Huang YT, Wu MH"	"Department of Computer Science and Information Engineering, National Chung Cheng University, Chia-Yi, Taiwan."	"BACKGROUND: Using microarray and sequencing platforms, a large number of copy number variations (CNVs) have been identified in humans. In practice, because our human genome is a diploid, these platforms are limited to or more accurate for detecting total copy numbers rather than chromosome-specific copy numbers at each of the two homologous chromosomes. Nevertheless, the analysis of linkage disequilibrium (LD) between CNVs and SNPs indicates that distinct copy numbers often sit on their own background haplotypes. RESULTS: We propose new computational models for inferring chromosome-specific copy numbers by distinguishing background haplotypes of each copy number. The formulated problems are shown to be NP-hard and approximation/heuristic algorithms are developed. Simulation indicates that our method is accurate and outperforms the existing approach. By testing the program in 60 parent-offspring trios, the inferred chromosome-specific copy numbers are highly consistent with the law of Mendelian inheritance. The distributions of copy numbers at chromosomal level are provided for 270 individuals in three HapMap panels. CONCLUSIONS: The estimation of chromosome-specific copy numbers using microarray or sequencing platforms was often confounded by a number of factors. This study showed that the integration of background haplotypes is able to improve the accuracies of copy number estimation at chromosome level, especially for the CNVs having strong LD with SNPs in proximity."	""
+1	"asian"	"Minneapolis, USA."	"USA"	"0.0127659574468"	"0.0170212765957"	"0.0425531914894"	"235"	"7.8064516129"	"Bioinformatics"	"Hwang T, Zhang W, Xie M, Liu J, Kuang R"	"Department of Computer Science and Engineering, University of Minnesota Twin Cities, Minneapolis, MN, USA."	"MOTIVATION: To validate the candidate disease genes identified from high-throughput genomic studies, a necessary step is to elucidate the associations between the set of candidate genes and disease phenotypes. The conventional gene set enrichment analysis often fails to reveal associations between disease phenotypes and the gene sets with a short list of poorly annotated genes, because the existing annotations of disease causative genes are incomplete. This paper introduces a network-based computational approach called rcNet to discover the associations between gene sets and disease phenotypes. A learning framework is proposed to maximize the coherence between the predicted phenotype-gene set relations and the known disease phenotype-gene associations. An efficient algorithm coupling ridge regression with label propagation, and two variants are designed to find the optimal solution to the objective functions of the learning framework. RESULTS: We evaluated the rcNet algorithms with leave-one-out cross-validation on OMIM data and an independent test set of recently discovered disease-gene associations. In the experiments, the rcNet algorithms achieved best overall rankings compared to the baselines. To further validate the reproducibility of the performance, we applied the algorithms to identify the target diseases of novel candidate disease genes obtained from recent studies of GWAS, DNA copy number variation analysis, and gene expression profiling. The algorithms ranked the target disease of the candidate genes at the top of the rank list in many cases across all the three case studies. AVAILABILITY: CONTACT:"	""
+3	"asian"	"Japan"	"Japan"	"0.0"	"0.0266666666667"	"0.0266666666667"	"150"	"10.0"	"Immunity"	"Ichiyama K, Sekiya T, Inoue N, Tamiya T, Kashiwagi I, Kimura A, Morita R, Muto G, Shichita T, Takahashi R, Yoshimura A"	"Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan."	"Transforming growth factor-beta (TGF-beta) has been shown to be required for Th17 cell differentiation via Smad-independent mechanisms. The molecular mechanism underlying this pathway remains to be clarified, however. We searched for genes regulated by TGF-beta through the Smad-independent pathway by using Smad2 and Smad3 double-deficient T cells and identified the transcription factor Eomesodermin (Eomes), whose expression was suppressed by TGF-beta via the c-Jun N-terminal kinase (JNK)-c-Jun signaling pathway. Inhibition of JNK strongly suppressed disease in an in vivo EAE model as well as in vitro Th17 cell induction. Overexpression of Eomes substantially suppressed Th17 cell differentiation, whereas ablation of Eomes expression could substitute for TGF-beta in Th17 cell induction in primary T cells. Eomes suppressed Rorc and Il17a promoters by directly binding to the proximal region of these promoters. In conclusion, the suppression of Eomes by TGF-beta via the JNK pathway is an important mechanism for Smad-independent Th17 cell differentiation."	""
+3	"asian"	"Japan"	"Japan"	"0.0179372197309"	"0.00896860986547"	"0.0448430493274"	"223"	"11.7368421053"	"Glycobiology"	"Igura M, Kohda D"	"Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan."	"Oligosaccharyltransferase (OST) catalyzes the transfer of an oligosaccharide to an asparagine residue in polypeptide chains. Using positional scanning peptide libraries, we assessed the effects of amino acid variations on the in vitro glycosylation efficiency within and adjacent to an N-glycosylation consensus, Asn-X-Ser/Thr, with an archaeal OST from Pyrococcus furiosus. The amino acid variations at the X(-2), X(-1) and X(+1) positions in the sequence X(-2)-X(-1)-Asn-X-Ser/Thr-X(+1) strongly influenced the glycosylation efficiency to a similar extent at position X. The rank orders of the amino acid preferences were unique at each site. We experimentally confirmed that the archaeal OST does not require an acidic residue at the -2 position, unlike the eubacterial OSTs. Pro was disfavored at the -1 and +1 positions, although the exclusion was not as strict as that at X, whereas Pro was the most favored amino acid residue among those studied at the -2 position. The overall amino acid preferences are correlated with a conformational propensity to extend around the sequon. The results of the library experiments revealed that the optimal acceptor sequence was PYNVTK, with a K(m) of 10 microM. The heat-stable, single-subunit OST of P. furiosus is a potential candidate enzyme for the production of recombinant glycoproteins in bacterial cells. Quantitative assessment of the amino acid preferences of the OST enzyme will facilitate the proper design of a production system."	""
+3	"asian"	"Japan"	"Japan"	"0.0102040816327"	"0.015306122449"	"0.0357142857143"	"196"	"9.61904761905"	"Glycobiology"	"Ihara Y, Manabe S, Ikezaki M, Inai Y, Matsui IS, Ohta Y, Muroi E, Ito Y"	"Department of Biochemistry, Wakayama Medical University, Wakayama, Japan."	"The thrombospondin type 1 repeat (TSR) is a functional module of proteins called TSR superfamily proteins (e.g., thrombospondin, F-spondin, mindin, etc.) and includes a conserved Trp-x-x-Trp (W-x-x-W) motif, in which the first Trp residue is preferably modified by C-mannosylation. We previously reported that synthesized C-mannosylated TSR-derived peptides (e.g., C-Man-WSPW) specifically enhanced lipopolysaccharide-induced signaling in macrophage-like RAW264.7 cells. In this study, we searched for the proteins that bind to C-mannosylated TSR-derived peptides in RAW264.7 cells and identified heat shock cognate protein 70 (Hsc70). The binding affinity of Hsc70 for C-mannosylated peptides in solution was higher than that for the peptides without C-mannose. The binding was influenced by a nucleotide-induced conformational change of Hsc70, and C-mannosylated peptides preferred the substrate-binding domain of Hsc70. Furthermore, in RAW264.7 cells, addition of Hsc70 stimulated cellular signaling to produce tumor necrosis factor-alpha, via transforming growth factor-beta-activated kinase 1, and the Hsc70-induced signaling was enhanced more in the presence of the peptides with C-mannose than that without C-mannose, suggesting functional interaction between Hsc70 and the C-mannosylated peptides in the cells. Together, these results demonstrate a novel function of the C-mannosylation of TSR-derived peptides in terms of interaction with Hsc70 to regulate cellular signaling."	""
+3	"asian"	"Japan"	"Japan"	"0.0077519379845"	"0.0116279069767"	"0.0426356589147"	"258"	"19.8461538462"	"Glycobiology"	"Ikarashi K, Fujiwara H, Yamazaki Y, Goto J, Kaneko K, Kato H, Fujii S, Sasaki H, Fukumoto S, Furukawa K, Waki H, Furukawa K"	"Department of Physiology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan."	"Gangliosides (sialic acid-containing glycosphingolipids) play important roles in many physiological functions, including synaptic plasticity in the hippocampus, which is considered as a cellular mechanism of learning and memory. In the present study, three types of synaptic plasticity, long-term potentiation (LTP), long-term depression (LTD) and reversal of LTP (depotentiation, DP), in the field excitatory post-synaptic potential in CA1 hippocampal neurons and learning behavior were examined in beta1,4-N-acetylgalactosaminyltransferase (beta1,4 GalNAc-T; GM2/GD2 synthase) gene transgenic (TG) mice, which showed a marked decrease in b-pathway gangliosides (GQ1b, GT1b and GD1b) in the brain and isolated hippocampus compared with wild-type (WT) mice. The magnitude of the LTP induced by tetanus (100 pulses at 100 Hz) in TG mice was significantly smaller than that in control WT mice, whereas there was no difference in the magnitude of the LTD induced by three short trains of low-frequency stimulation (LFS) (200 pulses at 1 Hz) at 20 min intervals between the two groups of mice. The reduction in the LTP produced by delivering three trains of LFS (200 pulses at 1 Hz, 20 min intervals) was significantly greater in the TG mice than in the WT mice. Learning was impaired in the four-pellet taking test (4PTT) in TG mice, with no significant difference in daily activity or activity during the 4PTT between TG and WT mice. These results suggest that the overexpression of beta1,4 GalNAc-T resulted in altered synaptic plasticity of LTP and DP in hippocampal CA1 neurons and learning in the 4PTT, and this is attributable to the shift from b-pathway gangliosides to a-pathway gangliosides."	""
+3	"asian"	"Thailand"	"Thailand"	"0.00819672131148"	"0.00819672131148"	"0.0655737704918"	"122"	"11.4545454545"	"Bioinformatics"	"Ingsriswang S, Yokwai S, Wichadakul D"	"Information Systems Laboratory, Bioresources Technology Unit, National Center for Genetic Engineering and Biotechnology, Klong Luang, Pathumthani 12120, Thailand."	"SUMMARY: LinkinPath is a pathway mapping and analysis tool that enables users to explore and visualize the list of gene/protein sequences through various Flash-driven interactive web interfaces including KEGG pathway maps, functional composition maps (TreeMaps), molecular interaction/reaction networks and pathway-to-pathway networks. Users can submit single or multiple datasets of gene/protein sequences to LinkinPath to (i) determine the co-occurrence and co-absence of genes/proteins on animated KEGG pathway maps; (ii) compare functional compositions within and among the datasets using TreeMaps; (iii) analyze the statistically enriched pathways across the datasets; (iv) build the pathway-to-pathway networks for each dataset; (v) explore potential interaction/reaction paths between pathways; and (vi) identify common pathway-to-pathway networks across the datasets. AVAILABILITY: LinkinPath is freely available to all interested users at"	""
+3	"asian"	"Israel"	"Israel"	"0.0"	"0.044776119403"	"0.119402985075"	"67"	"9.57142857143"	"Bioinformatics"	"Isakov O, Modai S, Shomron N"	"Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel."	"MOTIVATION: Early and accurate detection of human pathogen infection is critical for treatment and therapeutics. Here we describe pathogen identification using short RNA subtraction and assembly (SRSA), a detection method that overcomes the requirement of prior knowledge and culturing of pathogens, by using degraded small RNA and deep sequencing technology. We prove our approachs efficiency through identification of a combined viral and bacterial infection in human cells."	""
+3	"asian"	"Japan"	"Japan"	"0.00694444444444"	"0.00694444444444"	"0.0555555555556"	"144"	"16.0"	"Glycobiology"	"Ishisaki K, Honda Y, Taniguchi H, Hatano N, Hamada T"	"Department of Food Science, Ishikawa Prefectural University, 1-308, Suematsu, Nonoichi, Ishikawa 921-8836, Japan."	"A class IV chitinase belonging to the GH19 family from Nepenthes alata (NaCHIT1) was expressed in Escherichia coli. The enzyme exhibited weak activity toward polymeric substrates and significant activity toward (GlcNAc)(n) (n=4-6). The enzyme hydrolyzed the third and fourth glycosidic linkages from the non-reducing end of (GlcNAc)(6). The pH optimum of the enzymatic reaction was 5.5 at 37 degrees C. The optimal temperature for activity was 60 degrees C in 50 mM sodium acetate buffer (pH 5.5). The anomeric form of the products indicated it was an inverting enzyme. The k(cat)/K(m) of the (GlcNAc)(n) hydrolysis increased with an increase in the degree of polymerization. Amino acid sequence alignment analysis between NaCHIT1 and a class IV chitinase from a Picea abies (Norway spruce) suggested that deletion of four loops likely led the enzyme to optimize the (GlcNAc)(n) hydrolytic reaction rather than hydrolysis of polymeric substrates."	""
+3	"asian"	"Japan"	"Japan"	"0.0"	"0.0344827586207"	"0.051724137931"	"116"	"10.5454545455"	"Immunity"	"Iwakura Y, Ishigame H, Saijo S, Nakae S"	"Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan."	"Interleukin-17A (IL-17A) is the signature cytokine of the recently identified T helper 17 (Th17) cell subset. IL-17 has six family members (IL-17A to IL-17F). Although IL-17A and IL-17F share the highest amino acid sequence homology, they perform distinct functions; IL-17A is involved in the development of autoimmunity, inflammation, and tumors, and also plays important roles in the host defenses against bacterial and fungal infections, whereas IL-17F is mainly involved in mucosal host defense mechanisms. IL-17E (IL-25) is an amplifier of Th2 immune responses. The functions of IL-17B, IL-17C, and IL-17D remain largely elusive. In this review, we describe the identified functions of each IL-17 family member and discuss the potential of these molecules as therapeutic targets."	""
+3	"asian"	"Korea"	"Korea"	"0.0"	"0.0"	"0.0846560846561"	"189"	"9.94736842105"	"PLoS Computational Biology"	"Jeon J, Jeong JH, Baek JH, Koo HJ, Park WH, Yang JS, Yu MH, Kim S, Pak YK"	"Division of Molecular and Life Science, School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea."	"The mitochondrial protein repertoire varies depending on the cellular state. Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states. In this study, we investigated the systemic alterations of mtDNA-depleted (rho(0)) mitochondria by using network analysis of gene expression data. By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed. We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes. The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport. Furthermore, comparisons of proteome and transcriptome data revealed that rho(0) cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins. Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states. Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions."	""
+3	"asian"	"Korea"	"Korea"	"0.00709219858156"	"0.0212765957447"	"0.0851063829787"	"141"	"10.8461538462"	"Molecular Biology and Evolution"	"Jeon J, Nam HJ, Choi YS, Yang JS, Hwang J, Kim S"	"Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea."	"An improved understanding of protein conformational changes has broad implications for elucidating the mechanisms of various biological processes and for the design of protein engineering experiments. Understanding rearrangements of residue interactions is a key component in the challenge of describing structural transitions. Evolutionary properties of protein sequences and structures are extensively studied; however, evolution of protein motions, especially with respect to interaction rearrangements, has yet to be explored. Here, we investigated the relationship between sequence evolution and protein conformational changes and discovered that structural transitions are encoded in amino acid sequences as coevolving residue pairs. Furthermore, we found that highly coevolving residues are clustered in the flexible regions of proteins and facilitate structural transitions by forming and disrupting their interactions cooperatively. Our results provide insight into the evolution of protein conformational changes and help to identify residues important for structural transitions."	""
+3	"asian"	"Japan"	"Japan"	"0.0"	"0.0114942528736"	"0.0919540229885"	"87"	"4.84210526316"	"Bioinformatics"	"Jeong E, Nagasaki M, Ikeda E, Sekiya Y, Saito A, Miyano S"	"Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan."	"SUMMARY: Manual curation and validation of large-scale biological pathways are required to obtain high-quality pathway databases. In a typical curation process, model validation and model update based on appropriate feedback are repeated and requires considerable cooperation of scientists. We have developed a CSO (Cell System Ontology) validator to reduce the repetition and time during the curation process. This tool assists in quickly obtaining agreement among curators and domain experts and in providing a consistent and accurate pathway database. AVAILABILITY: The tool is available on CONTACT:"	""
+3	"asian"	"Singapore, Singapore"	"Singapore"	"0.00505050505051"	"0.010101010101"	"0.0959595959596"	"198"	"13.2"	"Bioinformatics"	"Jia G, Stephanopoulos GN, Gunawan R"	"Chemical and Pharmaceutical Engineering, Singapore-MIT Alliance, Singapore 117576."	"MOTIVATION: Time-series measurements of metabolite concentration have become increasingly more common, providing data for building kinetic models of metabolic networks using ordinary differential equations (ODEs). In practice, however, such time-course data are usually incomplete and noisy, and the estimation of kinetic parameters from these data is challenging. Practical limitations due to data and computational aspects, such as solving stiff ODEs and finding global optimal solution to the estimation problem, give motivations to develop a new estimation procedure that can circumvent some of these constraints. RESULTS: In this work, an incremental and iterative parameter estimation method is proposed that combines and iterates between two estimation phases. One phase involves a decoupling method, in which a subset of model parameters that are associated with measured metabolites, are estimated using the minimization of slope errors. Another phase follows, in which the ODE model is solved one equation at a time and the remaining model parameters are obtained by minimizing concentration errors. The performance of this two-phase method was tested on a generic branched metabolic pathway and the glycolytic pathway of Lactococcus lactis. The results showed that the method is efficient in getting accurate parameter estimates, even when some information is missing."	""
 3	"asian"	"China"	"China"	"0.00990099009901"	"0.0148514851485"	"0.0841584158416"	"202"	"10.6315789474"	"PLoS One"	"Jian W, Ying-Ying F, Shu-Juan W, Peng-Fei L, Jin-Ling W, Jian-Hua Q"	"Deafness Gene Diagnosis, PLA Otolaryngology-Head and Neck Surgery Center, Xijing Hospital, Fourth Military Medical University, Xian, Shannxi, China."	"BACKGROUND: Mutations in OTOF and PJVK genes cause DFNB9 and DFNB59 types of hearing loss, respectively. The patients carrying pathogenic mutations in either of these genes may show the typical phenotype of auditory neuropathy spectrum disorder (ANSD). The aim of the present study was to identify OTOF and PJVK mutations in sporadic ANSD patients. METHODS AND FINDINGS: A total of 76 unrelated Chinese non-syndromic ANSD patients were sequenced on the gene OTOF and PJVK exon by exon. Variants were valued in 105 controls with normal hearing to verify the carrying rate. We identified one pathogenic mutation (c.1194T>A) and three novel, possibly pathogenic, variants (c.3570+2T>C, c.4023+1 G>A, and c.1102G>A) in the OTOF gene, and one novel, possibly pathogenic, variant (c.548G>A) in PJVK. Moreover, we found three novel missense mutations within the exons of OTOF. CONCLUSIONS: As we identified 4 and 1 possible pathogenic variants of the OTOF gene and the PJVK gene, respectively, we believe that screening in these genes are important in sporadic ANSD patients. The pathogenicity of these novel mutations needs further study because of their single heterozygous nature. Knowledge on the mutation spectra of these genes in Chinese would be beneficial in understanding the genetic character of this worldwide disease."	""
+2	"asian"	"USA."	"USA"	"0.0"	"0.0151515151515"	"0.030303030303"	"132"	"8.8"	"Immunity"	"Jiang N, Huang J, Edwards LJ, Liu B, Zhang Y, Beal CD, Evavold BD, Zhu C"	"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA."	"The T cell receptor (TCR) and CD8 bind peptide-major histocompatibility complex (pMHC) glycoproteins to initiate adaptive immune responses, yet the trimolecular binding kinetics at the T cell membrane is unknown. By using a micropipette adhesion frequency assay, we show that this kinetics has two stages. The first consists of TCR-dominant binding to agonist pMHC. This triggers a second stage consisting of a step increase in adhesion after a one second delay. The second-stage binding requires Src family kinase activity to initiate CD8 binding to the same pMHC engaged by the TCR. This induced trimeric-cooperative interaction enhances adhesion synergistically to favor potent ligands, which further amplifies discrimination. Our data reveal a TCR-CD8 positive-feedback loop involved in initial signaling steps that is sensitive to a single pMHC is rapid, reversible, synergistic, and peptide discriminative."	""
+3	"asian"	"Texas, USA."	"USA"	"0.0"	"0.0263157894737"	"0.0263157894737"	"38"	"5.42857142857"	"Immunity"	"Jiang X, Chen ZJ"	"Department of Molecular Biology, University of Texas Southwestern Medical Center Dallas, TX 75390-9148, USA."	"Viperin is an interferon-stimulated gene that exerts antiviral effects. In this issue of Immunity, Saitoh et al. (2011) uncovered an unexpected function of Viperin and lipid bodies in interferon induction by Toll-like receptors, specifically in plasmacytoid dendritic cells."	""
+3	"asian"	"USA."	"USA"	"0.00787401574803"	"0.011811023622"	"0.0590551181102"	"254"	"8.8275862069"	"Bioinformatics"	"Jin G, Zhao H, Zhou X, Wong ST"	"Systems Medicine and Bioengineering Department, The Methodist Hospital Research Institute, Weill Medical College, Cornell University, Houston, TX 77030, USA."	"MOTIVATION: Prediction of synergistic effects of drug combinations has traditionally been relied on phenotypic response data. However, such methods cannot be used to identify molecular signaling mechanisms of synergistic drug combinations. In this article, we propose an enhanced Petri-Net (EPN) model to recognize the synergistic effects of drug combinations from the molecular response profiles, i.e. drug-treated microarray data. METHODS: We addressed the downstream signaling network of the targets for the two individual drugs used in the pairwise combinations and applied EPN to the identified targeted signaling network. In EPN, drugs and signaling molecules are assigned to different types of places, while drug doses and molecular expressions are denoted by color tokens. The changes of molecular expressions caused by treatments of drugs are simulated by two actions of EPN: firing and blasting. Firing is to transit the drug and molecule tokens from one node or place to another, and blasting is to reduce the number of molecule tokens by drug tokens in a molecule node. The goal of EPN is to mediate the state characterized by control condition without any treatment to that of treatment and to depict the drug effects on molecules by the drug tokens. RESULTS: We applied EPN to our generated pairwise drug combination microarray data. The synergistic predictions using EPN are consistent with those predicted using phenotypic response data. The molecules responsible for the synergistic effects with their associated feedback loops display the mechanisms of synergism. AVAILABILITY: The software implemented in Python 2.7 programming language is available from request. CONTACT:"	""
+3	"asian"	"India"	"India"	"0.00529100529101"	"0.015873015873"	"0.0793650793651"	"189"	"9.94736842105"	"Glycobiology"	"Joladarashi D, Salimath PV, Chilkunda ND"	"Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, Karnataka, India."	"Chondroitin sulfate (CS)/dermatan sulfate (DS) is a group of sulfated polymers, which play an essential role in various biological phenomena. In the kidney, they are present in small but significant amounts. Studies on their structure-function relationship in the kidney and their changes during diabetic conditions have not been rigorously looked into, which is the focus of this paper. The CS/DS content decreased significantly (14%) during diabetic conditions. This was accompanied by a decrease in the CS/heparan sulfate ratio. Disaccharide composition analysis revealed fine structural changes especially with respect to the E unit [glucuronic acid beta1-3 N-acetyl d-galactosamine (4,6-O-sulfate)] and the degree of sulfation. The mRNA expression levels of major enzymes involved in the synthesis of the E-disaccharide unit showed a decrease during diabetes. The changes in CS/DS had implications on ligand-binding properties when tested in vitro for binding to major extracellular matrix (ECM) components such as type IV collagen, laminin and fibronectin. Thus, this study provides insights into the structure-function relationship of CS/DS in the kidney during diabetes and alterations of which could aggravate conditions such as diabetic nephropathy by virtue of them being a part of ECM components."	""
+3	"asian"	"Korea"	"Korea"	"0.0"	"0.034965034965"	"0.104895104895"	"143"	"8.47058823529"	"Nature Genetics"	"Ju YS, Kim JI, Kim S, Hong D, Park H, Shin JY, Lee S, Lee WC, Kim S, Yu SB, Park SS, Seo SH, Yun JY, Kim HJ, Lee DS, Yavartanoo M, Kang HP, Gokcumen O, Govindaraju DR, Jung JH, Chong H, Yang KS, Kim H, Lee C, Seo JS"	"Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea."	"Massively parallel sequencing technologies have identified a broad spectrum of human genome diversity. Here we deep sequenced and correlated 18 genomes and 17 transcriptomes of unrelated Korean individuals. This has allowed us to construct a genome-wide map of common and rare variants and also identify variants formed during DNA-RNA transcription. We identified 9.56 million genomic variants, 23.2% of which appear to be previously unidentified. From transcriptome sequencing, we discovered 4,414 transcripts not previously annotated. Finally, we revealed 1,809 sites of transcriptional base modification, where the transcriptional landscape is different from the corresponding genomic sequences, and 580 sites of allele-specific expression. Our findings suggest that a considerable number of unexplored genomic variants still remain to be identified in the human genome, and that the integrated analysis of genome and transcriptome sequencing is powerful for understanding the diversity and functional aspects of human genomic variants."	""
+1	"asian"	"Israel"	"Israel"	"0.00564971751412"	"0.0112994350282"	"0.112994350282"	"177"	"10.4117647059"	"PLoS Computational Biology"	"Kabaso D, Shlomovitz R, Schloen K, Stradal T, Gov NS"	"Department of Chemical Physics, The Weizmann Institute of Science, Rehovot, Israel."	"The forces that arise from the actin cytoskeleton play a crucial role in determining the cell shape. These include protrusive forces due to actin polymerization and adhesion to the external matrix. We present here a theoretical model for the cellular shapes resulting from the feedback between the membrane shape and the forces acting on the membrane, mediated by curvature-sensitive membrane complexes of a convex shape. In previous theoretical studies we have investigated the regimes of linear instability where spontaneous formation of cellular protrusions is initiated. Here we calculate the evolution of a two dimensional cell contour beyond the linear regime and determine the final steady-state shapes arising within the model. We find that shapes driven by adhesion or by actin polymerization (lamellipodia) have very different morphologies, as observed in cells. Furthermore, we find that as the strength of the protrusive forces diminish, the system approaches a stabilization of a periodic pattern of protrusions. This result can provide an explanation for a number of puzzling experimental observations regarding cellular shape dependence on the properties of the extra-cellular matrix."	""
+3	"asian"	"Japan"	"Japan"	"0.020325203252"	"0.00813008130081"	"0.0731707317073"	"246"	"10.7391304348"	"PLoS One"	"Kadokura M, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, Uetake T, Inoue T, Sakamoto M, Nakagawa M, Sakamoto N, Watanabe M, Enomoto N"	"First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan."	"BACKGROUND AND AIMS: Patients infected with genotype 2b hepatitis C virus (HCV) generally can achieve favorable responses to pegylated-interferon plus ribavirin therapy (PEG-IFN/RBV). However, a proportion of patients show poorer responses and the correlation between viral sequence variation and treatment outcome remains unclear. METHODS: The pretreatment complete open reading frame (ORF) sequences of genotype 2b HCV determined by direct sequencing were investigated for correlation with the final outcome in a total of 60 patients. RESULTS: In this study group, 87.5% (14/16) of non-sustained virological response (non-SVR) patients (n = 16) were relapsers. Compared to sustained virological response (SVR) patients (n = 44), non-SVR patients were older and could not achieve prompt viral clearance after the therapy induction. Comparing each viral protein between the two groups, viral sequences were more diverse in SVR patients and that diversity was found primarily in the E1, p7, and NS5A proteins. In searching for specific viral regions associated with the final outcome, several regions in E2, p7, NS2, NS5A, and NS5B were extracted. Among these regions, part of the interferon sensitivity determining region (ISDR) was included. In these regions, amino acid substitutions were associated with the final outcome in an incremental manner, depending upon the number of substitutions. CONCLUSIONS: Viral sequences are more diverse in SVR patients than non-SVR patients receiving PEG-IFN/RBV therapy for genotype-2b HCV infection. Through systematic comparison of viral sequences, several specific regions, including part of the ISDR, were extracted as having significant correlation with the final outcome."	""
+3	"asian"	"Japan"	"Japan"	"0.0122448979592"	"0.0204081632653"	"0.0775510204082"	"245"	"11.6666666667"	"BMC Bioinformatics"	"Kadota K, Shimizu K"	"Agricultural Bioinformatics Research Unit, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo-ku, Japan."	"BACKGROUND: Statistical methods for ranking differentially expressed genes (DEGs) from gene expression data should be evaluated with regard to high sensitivity, specificity, and reproducibility. In our previous studies, we evaluated eight gene ranking methods applied to only Affymetrix GeneChip data. A more general evaluation that also includes other microarray platforms, such as the Agilent or Illumina systems, is desirable for determining which methods are suitable for each platform and which method has better inter-platform reproducibility. RESULTS: We compared the eight gene ranking methods using the MicroArray Quality Control (MAQC) datasets produced by five manufacturers: Affymetrix, Applied Biosystems, Agilent, GE Healthcare, and Illumina. The area under the curve (AUC) was used as a measure for both sensitivity and specificity. Although the highest AUC values can vary with the definition of true DEGs, the best methods were, in most cases, either the weighted average difference (WAD), rank products (RP), or intensity-based moderated t statistic (ibmT). The percentages of overlapping genes (POGs) across different test sites were mainly evaluated as a measure for both intra- and inter-platform reproducibility. The POG values for WAD were the highest overall, irrespective of the choice of microarray platform. The high intra- and inter-platform reproducibility of WAD was also observed at a higher biological function level. CONCLUSION: These results for the five microarray platforms were consistent with our previous ones based on 36 real experimental datasets measured using the Affymetrix platform. Thus, recommendations made using the MAQC benchmark data might be universally applicable."	""
+3	"asian"	"Japan"	"Japan"	"0.0170212765957"	"0.0127659574468"	"0.0340425531915"	"235"	"11.1904761905"	"Glycobiology"	"Kakutani R, Adachi Y, Takata H, Kuriki T, Ohno N"	"Institute of Health Sciences, Ezaki Glico Co., Ltd., Nishiyodogawa-ku, Osaka 555-8502, Japan."	"We prepared enzymatically synthesized glycogen (ESG) with the same characteristics as natural glycogen, and investigated whether the macrophage-stimulating activity of glycogen was related to Toll-like receptors (TLRs), which are important receptors for innate immunity. ESG induced no NF-kappaB activity in TLR4/MD-2/CD14-expressed HEK293 reporter cells, while this polysaccharide did activate peritoneal exude cells (PECs) derived from TLR4-deficient mice at the same level as those from wild-type mice. Similarly, ESG did not activate HEK293 cells expressing TLR3, 5, 7, 8, or 9, suggesting that these TLRs were irrelevant to the activity of ESG. In contrast, ESG enhanced the NF-kappaB activity of TLR2-expressed HEK293 reporter cells in a concentration-dependent manner. Furthermore, the cell-stimulating activity of ESG was remarkably lower for PECs from TLR2-deficient mice compared with those from wild-type mice. The activity of ESG completely disappeared after treatment with a glycogen-degrading enzyme, indicating that the activity derived from ESG itself and not from contamination with canonical TLR2 ligands such as bacterial lipopeptides. Moreover, it was clarified by ELISA that ESG was directly bound to TLR2. Taken together, these results demonstrated that TLR2 directly recognizes glycogen, and that the recognition activates immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines. In addition, it was suggested that TLR2 could be involved in the glycogen activity in vivo. We propose that glycogen act as an activator to potentiate the host defense through TLR2 on the macrophage."	""
+3	"asian"	"Japan"	"Japan"	"0.0"	"0.0"	"0.051724137931"	"174"	"10.2352941176"	"Glycobiology"	"Kamiyama S, Ichimiya T, Ikehara Y, Takase T, Fujimoto I, Suda T, Nakamori S, Nakamura M, Nakayama F, Irimura T, Nakanishi H, Watanabe M, Narimatsu H, Nishihara S"	"Department of Bioinformatics, Soka University, Tokyo, Japan."	"Sulfation represents an essential modification for various molecules and regulates many biological processes. The sulfation of glycans requires a specific transporter for 3-phosphoadenosine 5-phosphosulfate (PAPS) on the Golgi apparatus. This study investigated the expression of PAPS transporter genes in colorectal carcinomas and the significance of Golgi-specific sulfation in the proliferation of colorectal carcinoma cells. The relative amount of PAPST1 transcripts was found to be higher than those of PAPST2 in colorectal cancerous tissues. Immunohistochemically, the enhanced expression of PAPST1 was observed in fibroblasts in the vicinity of invasive cancer cells, whereas the expression of PAPST2 was decreased in the epithelial cells. RNA interference of either of the two PAPS transporter genes reduced the extent of sulfation of cellular proteins and cellular proliferation of DLD-1 human colorectal carcinoma cells. Silencing the PAPS transporter genes reduced fibroblast growth factor signaling in DLD-1 cells. These findings indicate that PAPS transporters play a role in the proliferation of colorectal carcinoma cells themselves and take part in a desmoplastic reaction to support cancer growth by controlling their sulfation status."	""
+3	"asian"	"India, India"	"India"	"0.0"	"0.0190476190476"	"0.119047619048"	"210"	"12.3529411765"	"Molecular Biology and Evolution"	"Kane NC, Barker MS, Zhan SH, Rieseberg LH"	"Department of Biology, Indiana University, Bloomington, Indiana 47405."	"The Asteraceae (Compositae) is a large family of over 20,000 wild, weedy and domesticated species that comprise approximately 10% of all angiosperms, including annual and perennial herbs, shrubs and trees, and species on every continent except Antarctica. As a result, the Asteraceae provide a unique opportunity to understand the evolutionary genomics of lineage radiation and diversification at numerous phylogenetic scales. Using publicly available ESTs from 22 species representing four of the major Asteraceae lineages, we assessed neutral and non-neutral evolutionary processes across this diverse plant family. We used bioinformatic tools to identify candidate genes under selection in each species. Evolution at silent and coding sites were assessed for different Gene Ontology functional categories to compare rates of evolution over both short and long evolutionary time scales. Our results indicate that patterns of molecular change across the family are surprisingly consistent on a macroevolutionary timescale and much more so more than would be predicted from the analysis of one (or many) examples of microevolution. These analyses also point to particular classes of genes that may be crucial in shaping the radiation of this diverse plant family. Similar analyses of nuclear and chloroplast genes in six other plant families confirms that many of these patterns are common features of the plant kingdom."	""
+3	"asian"	"Japan"	"Japan"	"0.0"	"0.0492957746479"	"0.0845070422535"	"142"	"10.9230769231"	"Annual Review of Immunology"	"Karasuyama H, Mukai K, Obata K, Tsujimura Y, Wada T"	"Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Japan."	"Basophils are the rarest granulocytes and represent less than 1% of peripheral blood leukocytes. They are evolutionarily conserved in many animal species, but their functional significance remained an enigma long after their discovery by Paul Ehrlich in 1879. Studies of basophils were hindered by their rarity, by difficulties in identifying them, and by the paucity of useful analytical tools. Because basophils display several characteristics shared by tissue-resident mast cells, they were often considered minor and possibly redundant relatives of mast cells or even blood-circulating precursors of mast cells. However, newly developed tools for their functional analysis, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, have fueled basophil research and defined previously unrecognized functions of basophils. We now appreciate that basophils play nonredundant roles in acquired immunity regulation, protective immunity to pathogens, and immunological disorders such as allergy and autoimmunity."	""
+3	"asian"	"Japan"	"Japan"	"0.00653594771242"	"0.0196078431373"	"0.0261437908497"	"153"	"11.7692307692"	"Immunity"	"Katagiri K, Ueda Y, Tomiyama T, Yasuda K, Toda Y, Ikehara S, Nakayama KI, Kinashi T"	"Department of Life Science, School of Science and Technology, Kwanseigakuen University, and JST, CREST, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan."	"RAPL (an alternative spliced form of Rassf5) is a critical Ras-related protein1 (Rap1) effector that regulates lymphocyte adhesion. Here, we have shown that in addition to this previously described function, RAPL also negatively controls lymphocyte proliferation and prevents autoimmunity and lymphoma. RAPL-deficient mice experienced age-related lupus-like glomerulonephritis and developed B cell lymphomas. RAPL-deficient lymphocytes showed hyperproliferation by enhanced S phase entry after antigen receptor ligation. Compared to wild-type cells, RAPL-deficient naive lymphocytes had a 2- to 3-fold increase in Cdk2 kinase activity with a cytoplasmic mislocalization of the cyclin-dependent kinase inhibitor p27(kip1). RAPL was found to suppress the phosphorylation of p27(kip1) on serine 10 (S10) and promoted p27(kip1) nuclear translocation. An S10A mutation in p27(kip1) corrected its cytoplasmic accumulation, reduced hyperproliferation in RAPL-deficient lymphocytes, and suppressed glomerulonephritis and development of B cell lymphoma. Thus, RAPL serves as a checkpoint for S phase entry to prevent lymphoproliferative disorders through the spatial regulation of p27(kip1)."	""
+3	"asian"	"Japan"	"Japan"	"0.00502512562814"	"0.0402010050251"	"0.0854271356784"	"199"	"8.65217391304"	"Blood"	"Kataoka H, Hayashi M, Nakagawa R, Tanaka Y, Izumi N, Nishikawa S, Jakt ML, Tarui H, Nishikawa SI"	"Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe, Japan;"	"Etv2 (Ets Variant 2) was shown to be an indispensable gene for the development of hematopoietic/endothelial cells. However, how Etv2 specifies the mesoderm generating hematopoietic/endothelial cells remains incompletely understood. In ES differentiation culture and Etv2-null embryos Etv2 is dispensable for the generation of primitive Flk-1(+)/PDGFRalpha(+) mesoderm but required for the progression of Flk-1(+)/PDGFRalpha(+) cells into vascular/hematopoietic mesoderm. Etv2 null ES and embryonic cells were arrested as Flk-1(+)/PDGFRalpha(+) and failed to generate Flk-1(+)/PDGFRalpha(-) mesoderm. Flk-1(+)/Etv2(+) early embryonic cells showed significantly higher hemato-endothelial potential than Flk-1(+)/Etv2(-) population, suggesting that Etv2 specifies a hemato-endothelial subset of Flk-1(+) mesoderm. Critical hemato-endothelial genes were severely downregulated in Etv2 null Flk-1(+) cells. Among those genes Scl, Fli1, and GATA2 were expressed simultaneously with Etv2 in early embryos and indicated to be critical targets. Etv2 re-expression in Etv2 null cells restored development of CD41(+), CD45(+), and VE-cadherin(+) cells. Expression of Scl or Fli1 alone could also restore hematopoietic/endothelial cells in Etv2 null background indicating that these two genes are critical downstream targets. Furthermore, VEGF induced Etv2 potently and rapidly in Flk-1(+) mesoderm. We propose that Flk-1(+)/PDGFRalpha(+) primitive mesoderm is committed into Flk-1(+)/PDGFRalpha(-) vascular mesoderm through Etv2 and that upregulation of Etv2 by VEGF promotes this commitment."	""
+3	"asian"	"Korea, Korea"	"Korea"	"0.00704225352113"	"0.0211267605634"	"0.0492957746479"	"142"	"11.0"	"Immunity"	"Kataru RP, Kim H, Jang C, Choi DK, Koh BI, Kim M, Gollamudi S, Kim YK, Lee SH, Koh GY"	"National Research Laboratory of Vascular Biology, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea."	"Lymph node lymphatic vessels (LNLVs) serve as a conduit to drain antigens from peripheral tissues to within the lymph nodes. LNLV density is known to be positively regulated by vascular endothelial growth factors secreted by B cells, macrophages, and dendritic cells (DCs). Here, we show that LNLV formation was negatively regulated by T cells. In both steady and inflammatory states, the density of LNLVs was increased in the absence of T cells but decreased when T cells were restored. Interferon-gamma secretion by T cells suppressed lymphatic-specific genes in lymphatic endothelial cells and consequently caused marked reduction in LNLV formation. When T cells were depleted, recruitment of antigen-carrying DCs to LNs was augmented, reflecting a compensatory mechanism for antigen presentation to T cells through increased LNLVs. Thus, T cells maintain the homeostatic balance of LNLV density through a negative paracrine action of interferon-gamma."	""
+3	"asian"	"Japan"	"Japan"	"0.0193548387097"	"0.0322580645161"	"0.0709677419355"	"155"	"10.4"	"Nature Genetics"	"Kato N, Takeuchi F, Tabara Y, Kelly TN, Go MJ, Sim X, Tay WT, Chen CH, Zhang Y, Yamamoto K, Katsuya T, Yokota M, Kim YJ, Ong RT, Nabika T, Gu D, Chang LC, Kokubo Y, Huang W, Ohnaka K, Yamori Y, Nakashima E, Jaquish CE, Lee JY, Seielstad M, Isono M, Hixson JE, Chen YT, Miki T, Zhou X, Sugiyama T, Jeon JP, Liu JJ, Takayanagi R, Kim SS, Aung T, Sung YJ, Zhang X, Wong TY, Han BG, Kobayashi S, Ogihara T, Zhu D, Iwai N, Wu JY, Teo YY, Tai ES, Cho YS, He J"	"Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan."	"We conducted a meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of east Asian ancestry from the AGEN-BP consortium followed up with de novo genotyping (n = 10,518) and further replication (n = 20,247) in east Asian samples. We identified genome-wide significant (P < 5 x 10(-8)) associations with SBP or DBP, which included variants at four new loci (ST7L-CAPZA1, FIGN-GRB14, ENPEP and NPR3) and a newly discovered variant near TBX3. Among the five newly discovered variants, we obtained significant replication in the independent samples for all of these loci except NPR3. We also confirmed seven loci previously identified in populations of European descent. Moreover, at 12q24.13 near ALDH2, we observed strong association signals (P = 7.9 x 10(-31) and P = 1.3 x 10(-35) for SBP and DBP, respectively) with ethnic specificity. These findings provide new insights into blood pressure regulation and potential targets for intervention."	""
+3	"asian"	"Japan"	"Japan"	"0.0202702702703"	"0.0202702702703"	"0.0472972972973"	"296"	"10.2068965517"	"PLoS One"	"Kawabe-Yako R, Masaaki I, Masuo O, Asahara T, Itakura T"	"Group of Vascular Regeneration Research, Institute of Biomedical Research and Innovation, RIKEN Center for Developmental Biology, Kobe, Japan."	"BACKGROUND: Cilostazol(CLZ) has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM)-derived endothelial progenitor cell (EPC) contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. METHODOLOGY/PRINCIPAL FINDINGS: Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin alphavbeta3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1alpha that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. CONCLUSIONS/SIGNIFICANCE: CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for endothelial regeneration, which is a key event for preventing atherosclerosis or restenosis after vascular intervention."	""
+3	"asian"	"Japan"	"Japan"	"0.018691588785"	"0.00934579439252"	"0.0934579439252"	"107"	"15.2857142857"	"Immunity"	"Kawai T, Akira S"	"Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan."	"Toll-like receptors (TLRs) are germline-encoded pattern recognition receptors (PRRs) that play a central role in host cell recognition and responses to microbial pathogens. TLR-mediated recognition of components derived from a wide range of pathogens and their role in the subsequent initiation of innate immune responses is widely accepted; however, the recent discovery of non-TLR PRRs, such as C-type lectin receptors, NOD-like receptors, and RIG-I-like receptors, suggests that many aspects of innate immunity are more sophisticated and complex. In this review, we will focus on the role played by TLRs in mounting protective immune responses against infection and their crosstalk with other PRRs with respect to pathogen recognition."	""
+3	"asian"	"Japan"	"Japan"	"0.0199203187251"	"0.0199203187251"	"0.0677290836653"	"251"	"13.2105263158"	"Glycobiology"	"Kawasaki Y, Ito A, Withers DA, Taima T, Kakoi N, Saito S, Arai Y"	"Department of Urology, Tohoku University School of Medicine, Sendai 980-8574, Japan."	"In renal cell carcinoma (RCC), the presence of higher gangliosides correlates with systematic metastasis. Disialosyl globopentaosylceramide (DSGb5) was identified previously as one of the major gangliosides from RCC tissues. Siglec-7 (sialic acid-binding Ig-like lectin-7), expressed on natural killer (NK) cells as an inhibitory receptor, has a striking preference for internally branched alpha2,6-linked disialic gangliosides such as DSGb5. To clarify the functional role of DSGb5 in RCC metastases, we have investigated whether DSGb5 expressed on RCC cells can modulate NK cell cytotoxicity in a Siglec-7-dependent manner. The binding activity of RCC cells to Siglec-7-Fc fusion protein was specifically inhibited by anti-DSGb5 monoclonal antibody and transfection of siRNA for ST6GalNAcVI (synthetase of DSGb5). These observations showed that Siglec-7-Fc fusion protein specifically bound to DSGb5 expressed on RCC cells. In contrast, the sialic acid-binding site of Siglec-7 on NK cells was masked by cis interactions with endogenous sialoconjugates at the cell surface, but it could be unmasked by sialidase treatment of the NK cells. Following sialidase treatment of NK cells, NK cell cytotoxicity against RCC cells with high DSGb5 expression was significantly decreased relative to cells with low DSGb5 expression. These findings indicate that such NK cell cytotoxicity against RCC cells could be inhibited by the interaction between Siglec-7 on effecter cells and DSGb5 on target cells. The results of the present study suggest that DSGb5 expressed on RCC cells can downregulate NK cell cytotoxicity in a DSGb5-Siglec-7-dependent manner and that RCC cells with DSGb5 create favorable circumstance for their own survival and metastases."	""
+3	"asian"	"Israel"	"Israel"	"0.00649350649351"	"0.0584415584416"	"0.0909090909091"	"154"	"10.2666666667"	"PLoS Computational Biology"	"Kenigsberg E, Bar A, Segal E, Tanay A"	"Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel."	"Evolution maintains organismal fitness by preserving genomic information. This is widely assumed to involve conservation of specific genomic loci among species. Many genomic encodings are now recognized to integrate small contributions from multiple genomic positions into quantitative dispersed codes, but the evolutionary dynamics of such codes are still poorly understood. Here we show that in yeast, sequences that quantitatively affect nucleosome occupancy evolve under compensatory dynamics that maintain heterogeneous levels of A+T content through spatially coupled A/T-losing and A/T-gaining substitutions. Evolutionary modeling combined with data on yeast polymorphisms supports the idea that these substitution dynamics are a consequence of weak selection. This shows that compensatory evolution, so far believed to affect specific groups of epistatically linked loci like paired RNA bases, is a widespread phenomenon in the yeast genome, affecting the majority of intergenic sequences in it. The model thus derived suggests that compensation is inevitable when evolution conserves quantitative and dispersed genomic functions."	""
+3	"asian"	"Iran"	"Iran"	"0.00381679389313"	"0.0343511450382"	"0.0725190839695"	"262"	"13.7894736842"	"PLoS Computational Biology"	"Keramati M, Dezfouli A, Piray P"	"School of Management and Economics, Sharif University of Technology, Tehran, Iran."	"Instrumental responses are hypothesized to be of two kinds: habitual and goal-directed, mediated by the sensorimotor and the associative cortico-basal ganglia circuits, respectively. The existence of the two heterogeneous associative learning mechanisms can be hypothesized to arise from the comparative advantages that they have at different stages of learning. In this paper, we assume that the goal-directed system is behaviourally flexible, but slow in choice selection. The habitual system, in contrast, is fast in responding, but inflexible in adapting its behavioural strategy to new conditions. Based on these assumptions and using the computational theory of reinforcement learning, we propose a normative model for arbitration between the two processes that makes an approximately optimal balance between search-time and accuracy in decision making. Behaviourally, the model can explain experimental evidence on behavioural sensitivity to outcome at the early stages of learning, but insensitivity at the later stages. It also explains that when two choices with equal incentive values are available concurrently, the behaviour remains outcome-sensitive, even after extensive training. Moreover, the model can explain choice reaction time variations during the course of learning, as well as the experimental observation that as the number of choices increases, the reaction time also increases. Neurobiologically, by assuming that phasic and tonic activities of midbrain dopamine neurons carry the reward prediction error and the average reward signals used by the model, respectively, the model predicts that whereas phasic dopamine indirectly affects behaviour through reinforcing stimulus-response associations, tonic dopamine can directly affect behaviour through manipulating the competition between the habitual and the goal-directed systems and thus, affect reaction time."	""
+3	"asian"	"Israel, Israel"	"Israel"	"0.0100502512563"	"0.0251256281407"	"0.0502512562814"	"199"	"13.2666666667"	"Blood"	"Kigel B, Rabinowicz N, Varshavsky A, Kessler O, Neufeld G"	"Cancer and Vascular Biology Research Center, Rappaport Research Institute in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel."	"Plexin-A4 is a receptor for sema6A and sema6B and associates with neuropilins to transduce signals of class-3 semaphorins. We observed that plexin-A1 and plexin-A4 are required simultaneously for transduction of inhibitory sema3A signals and that they form complexes. Unexpectedly, inhibition of plexin-A1 or plexin-A4 expression in endothelial cells using specific shRNAs resulted in prominent plexin type specific rearrangements of the actin cytoskeleton that were accompanied by inhibition of bFGF and VEGF induced cell proliferation. The two responses were not interdependent since silencing plexin-A4 in U87MG glioblastoma cells inhibited cell proliferation and strongly inhibited the formation of tumors from these cells without affecting cytoskeletal organization. Plexin-A4 formed stable complexes with the FGFR1 and VEGFR2 tyrosine-kinase receptors and enhanced VEGF induced VEGFR-2 phosphorylation in endothelial cells as well as bFGF induced cell proliferation. We also obtained evidence suggesting that some of the pro-proliferative effects of plexin-A4 are due to transduction of autocrine sema6B induced pro-proliferative signals, since silencing sema6B expression in endothelial cells and in U87MG cells mimicked the effects of plexin-A4 silencing and also inhibited tumor formation from the U87MG cells. Our results suggest that plexin-A4 may represent a target for the development of novel anti-angiogenic and anti- tumorigenic drugs."	""
+3	"asian"	"Korea"	"Korea"	"0.0049504950495"	"0.0049504950495"	"0.0841584158416"	"202"	"9.7619047619"	"Bioinformatics"	"Kim DS, Hahn Y"	"School of Biological Sciences (BK21 Program) and Research Center for Biomolecules and Biosystems, Chung-Ang University, Seoul 156-756, Korea."	"MOTIVATION: Phosphorylation modifications of specific protein residues are involved in a wide range of biological processes such as modulation of intracellular signal networks. Here, we present the development and application of a bioinformatics procedure for systematic identification of human-specific phosphorylation sites in proteins that may have occurred after the human-chimpanzee divergence. RESULTS: We collected annotated human phosphorylation sites and compared each site to orthologous mammalian proteins across taxa including chimpanzee, orangutan, rhesus macaque, marmoset, mouse, dog, cow, elephant, opossum and platypus. We identified 37 human-specific gains of annotated phosphorylation sites in 35 proteins: 22 serines, 12 threonines and 3 tyrosines. The novel phosphorylation sites are situated in highly conserved segments of the protein. Proteins with novel phosphorylation sites are involved in crucial biological processes such as cell division (AURKB, CASC5, MKI67 and PDCD4) and chromatin remodeling (HIRA, HIRIP3, HIST1H1T, NAP1L4 and LRWD1). Modified phosphorylatable residues produce novel target sites for protein kinases such as cyclin-dependent kinases and casein kinases, possibly resulting in rewiring and fine-tuning of phosphorylation regulatory networks. The potential human-specific phosphorylation sites identified in this study are useful as candidates for functional analysis to identify novel phenotypes in humans. CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
+3	"asian"	"Korea"	"Korea"	"0.0210526315789"	"0.0105263157895"	"0.0736842105263"	"285"	"10.5555555556"	"PLoS One"	"Kim H, Lee S, Jang Y"	"Division of EcoScience and Research Institute of EcoScience, Ewha Womans University, Seoul, Republic of Korea."	"BACKGROUND: Due to its biogeographic origins and rapid diversification, understanding the tribe Aphidini is key to understanding aphid evolution. Major questions about aphid evolution include origins of host alternation as well as age and patterns of diversification in relation to host plants. To address these questions, we reconstructed the phylogeny of the Aphidini which contains Aphis, the most diverse genus in the family. We used a combined dataset of one nuclear and four mitochondrial DNA regions. A molecular dating approach, calibrated with fossil records, was used to estimate divergence times of these taxa. PRINCIPAL FINDINGS: Most generic divergences in Aphidini occurred in the Middle Tertiary, and species-level divergences occurred between the Middle and Late Tertiary. The ancestral state of host use for Aphidini was equivocal with respect to three states: monoecy on trees, heteroecy, and monoecy on grasses. The ancestral state of Rhopalosiphina likely included both heteroecy and monoecy, whereas that of Aphidina was most likely monoecy. The divergence times of aphid lineages at the generic or subgeneric levels are close to those of their primary hosts. The species-level divergences in aphids are consistent with the diversification of the secondary hosts, as a few examples suggest. The biogeographic origin of Aphidini as a whole was equivocal, but the major lineages within Aphidina likely separated into Nearctic, Western Palearctic, and Eastern Palearctic regions. CONCLUSIONS: Most generic divergences in Aphidini occurred in the Middle Tertiary when primary hosts, mainly in the Rosaceae, were diverging, whereas species-level divergences were contemporaneous with diversification of the secondary hosts such as Poaceae in the Middle to Late Tertiary. Our results suggest that evolution of host alternation within Aphidini may have occurred during the Middle Tertiary (Oligocene) when the secondary hosts emerged."	""
+3	"asian"	"Korea"	"Korea"	"0.00657894736842"	"0.0131578947368"	"0.0592105263158"	"152"	"7.0"	"Nature Genetics"	"Kim YJ, Go MJ, Hu C, Hong CB, Kim YK, Lee JY, Hwang JY, Oh JH, Kim DJ, Kim NH, Kim S, Hong EJ, Kim JH, Min H, Kim Y, Zhang R, Jia W, Okada Y, Takahashi A, Kubo M, Tanaka T, Kamatani N, Matsuda K, Park T, Oh B, Kimm K, Kang D, Shin C, Cho NH, Kim HL, Han BG, Lee JY, Cho YS"	"1] Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea. [2]."	"To identify the genetic bases for nine metabolic traits, we conducted a meta-analysis combining Korean genome-wide association results from the KARE project (n = 8,842) and the HEXA shared control study (n = 3,703). We verified the associations of the loci selected from the discovery meta-analysis in the replication stage (30,395 individuals from the BioBank Japan genome-wide association study and individuals comprising the Health2 and Shanghai Jiao Tong University Diabetes cohorts). We identified ten genome-wide significant signals newly associated with traits from an overall meta-analysis. The most compelling associations involved 12q24.11 (near MYL2) and 12q24.13 (in C12orf51) for high-density lipoprotein cholesterol, 2p21 (near SIX2-SIX3) for fasting plasma glucose, 19q13.33 (in RPS11) and 6q22.33 (in RSPO3) for renal traits, and 12q24.11 (near MYL2), 12q24.13 (in C12orf51 and near OAS1), 4q31.22 (in ZNF827) and 7q11.23 (near TBL2-BCL7B) for hepatic traits. These findings highlight previously unknown biological pathways for metabolic traits investigated in this study."	""
+3	"asian"	"Japan"	"Japan"	"0.0"	"0.0140845070423"	"0.0892018779343"	"213"	"8.11111111111"	"Bioinformatics"	"Kiryu H"	"Department of Computational Biology, Faculty of Frontier Science, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan."	"MOTIVATION: Measuring evolutionary conservation is a routine step in the identification of functional elements in genome sequences. Although a number of studies have proposed methods that use the continuous time Markov models (CTMMs) to find evolutionarily constrained elements, their probabilistic structures have been less frequently investigated. RESULTS: In this article, we investigate a sufficient statistic for CTMMs. The statistic is composed of the fractional duration of nucleotide characters over evolutionary time, F(d), and the number of substitutions occurring in phylogenetic trees, N(s). We first derive basic properties of the sufficient statistic. Then, we derive an expectation maximization (EM) algorithm for estimating the parameters of a phylogenetic model, which iteratively computes the expectation values of the sufficient statistic. We show that the EM algorithm exhibits much faster convergence than other optimization methods that use numerical gradient descent algorithms. Finally, we investigate the genome-wide distribution of fractional duration time F(d) which, unlike the number of substitutions N(s), has rarely been investigated. We show that F(d) has evolutionary information that is distinct from that in N(s), which may be useful for detecting novel types of evolutionary constraints existing in the human genome. AVAILABILITY: The C++ source code of the Fdur software is available at CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
+3	"asian"	"Japan"	"Japan"	"0.0093896713615"	"0.018779342723"	"0.0469483568075"	"213"	"10.1428571429"	"Glycobiology"	"Kitamoto S, Yamada N, Yokoyama S, Houjou I, Higashi M, Goto M, Batra SK, Yonezawa S"	"Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan."	"MUC17 glycoprotein is a membrane-associated mucin that is mainly expressed in the digestive tract. It has been suggested that MUC17 expression is correlated with the malignancy potential of pancreatic ductal adenocarcinomas (PDACs). In the present study, we provided the first report of the MUC17 gene expression through epigenetic regulation such as promoter methylation, histone modification and microRNA (miRNA) expression. Near the transcriptional start site, the DNA methylation level of MUC17-negative cancer cell lines (e.g. PANC1) was high, whereas that of MUC17-positive cells (e.g. AsPC-1) was low. Histone H3-K9 (H3-K9) modification status was also closely related to MUC17 expression. Our results indicate that DNA methylation and histone H3-K9 modification in the 5 flanking region play a critical role in MUC17 expression. Furthermore, the hypomethylation status was observed in patients with PDAC. This indicates that the hypomethylation status in the MUC17 promoter could be a novel epigenetic marker for the diagnosis of PDAC. In addition, the result of miRNA microarray analysis showed that five potential miRNA candidates existed. It is also possible that the MUC17 might be post-transcriptionally regulated by miRNA targeting to the 3-untranslated region of its mRNA. These understandings of the epigenetic changes of MUC17 may be of importance for the diagnosis of carcinogenic risk and the prediction of outcomes for cancer patients."	""
+3	"asian"	"Japan"	"Japan"	"0.00684931506849"	"0.0205479452055"	"0.0342465753425"	"146"	"9.73333333333"	"Immunity"	"Kitano M, Moriyama S, Ando Y, Hikida M, Mori Y, Kurosaki T, Okada T"	"Research Unit for Immunodynamics, RIKEN, Research Center for Allergy and Immunology, Yokohama, 230-0045, Japan."	"The transcription factor Bcl6 is essential for the development of germinal center (GC) B cells and follicular helper T (Tfh) cells. However, little is known about in vivo dynamics of Bcl6 protein expression during and after development of these cells. By using a Bcl6 reporter mouse strain, we found that antigen-engaged B cells upregulated Bcl6 before clustering in GCs. Two-photon microscopic analysis indicated that Bcl6 upregulation in pre-GC B cells contributed to sustaining their interactions with helper T cells and was required for their entry to GC clusters. Our data also suggested that Tfh cells gradually downmodulated Bcl6 protein over weeks after development. The Bcl6-low Tfh cells rapidly terminated proliferation and upregulated IL-7 receptor. These results clarify the role of Bcl6 in pre-GC B cell dynamics and highlight the modulation of Bcl6 expression in Tfh cells that persist in the late phase of the antibody response."	""
+3	"asian"	"Kyoto, Kyoto, Japan"	"Japan"	"0.00403225806452"	"0.0201612903226"	"0.0362903225806"	"248"	"11.8571428571"	"Glycobiology"	"Kiyohara M, Tanigawa K, Chaiwangsri T, Katayama T, Ashida H, Yamamoto K"	"Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan."	"Bifidobacteria are health-promoting enteric commensals that are assumed to proliferate predominantly in the intestines of breast-fed infants by assimilating human milk oligosaccharides (HMOs) that are frequently fucosylated and/or sialylated. We previously identified two different alpha-l-fucosidases in Bifidobacterium bifidum and showed that the strain furnishes an extracellular degradation pathway for fucosylated HMOs. However, the catabolism of sialylated HMOs by bifidobacteria has remained unresolved. Here we describe the identification and characterization of an exo-alpha-sialidase in bifidobacteria. By expression cloning, we isolated a novel exo-alpha-sialidase gene (siabb2) from B. bifidum JCM1254, which encodes a protein (SiaBb2) consisting of 835-amino-acid residues with a predicted molecular mass of 87 kDa. SiaBb2 possesses an N-terminal signal sequence, a sialidase catalytic domain classified into the glycoside hydrolase family 33 (GH33) and a C-terminal transmembrane region, indicating that the mature SiaBb2 is an extracellular membrane-anchored enzyme. The recombinant enzyme expressed in Escherichia coli showed the highest activity in an acidic pH range from 4.0 to 5.0, and at 50  degrees C. Notably, 80% activity remained after 30 min incubation at 80  degrees C, indicating that the enzyme is highly thermostable. SiaBb2 liberated sialic acids from sialyloligosaccharides, gangliosides, glycoproteins and colominic acid; however, the linkage preference of the enzyme was remarkably biased toward the alpha2,3-linkage rather than alpha2,6- and alpha2,8-linkages. Expression of siabb2 in B. longum 105-A, which has no endogenous exo-alpha-sialidase, enabled this strain to degrade sialyloligosaccharides present in human milk. Our results suggest that SiaBb2 plays a crucial role in bifidobacterial catabolism of sialylated HMOs."	""
+3	"asian"	"Japan"	"Japan"	"0.0125523012552"	"0.0125523012552"	"0.0962343096234"	"239"	"15.9333333333"	"PLoS One"	"Kohara K, Ochi M, Tabara Y, Nagai T, Igase M, Miki T"	"Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan."	"The combination of sarcopenia, age-related loss of muscle strength and mass, and obesity has been recognized as a new category of obesity among the elderly. Given that leptin has been hypothesized to be involved in the pathogenesis of sarcopenic obesity, we investigated the relationship between plasma leptin levels and thigh muscle sarcopenia and visceral obesity. Thigh muscle cross-sectional area (CSA) and visceral fat area were measured using computed tomography as indices for muscle mass and visceral fat, respectively, in 782 middle-aged to elderly subjects (303 men and 479 women), participating in a medical check-up program. Visceral obesity was defined as visceral fat area >100 cm(2), and sarcopenia was defined as < (one standard deviation - mean of thigh muscle CSA/body weight of young subjects [aged <50 years]).Thigh muscle CSA was significantly and negatively associated with plasma levels of leptin in both men (beta = -0.28, p<0.0001) and women (beta = -0.20, p<0.0001), even after correcting for other confounding parameters, including age, body weight, body height, visceral fat area, blood pressure, homeostatic model assessment index, and high sensitive C reactive protein. Subjects were divided into four groups based on presence or absence of sarcopenia or visceral obesity. Plasma levels of leptin were higher in subjects with sarcopenic visceral obesity than in those with either sarcopenia or visceral obesity alone. These findings indicate that sarcopenic visceral obesity is a more advanced, and suggest that leptin may link visceral obesity and sarcopenia."	""
 3	"asian"	"China"	"China"	"0.0143884892086"	"0.0143884892086"	"0.0719424460432"	"278"	"18.6"	"PLoS One"	"Kong Y, Wang D, Shang Y, Liang W, Ling X, Guo Z, He X"	"Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China."	"BACKGROUND: Introduction of calcineurin-inhibitor (CNI) has made transplantation a miracle in the past century. However, the side effects of long-term use of CNI turn out to be one of the major challenges in the current century. Among these, renal dysfunction attracts more and more attention. Herein, we undertook a meta-analysis to evaluate the efficacy and safety of calcineurin-inhibitor (CNI) minimization protocols in liver transplant recipients with CNI-related renal dysfunction. METHODS: We included randomized trials with no year and language restriction. All data were analyzed using random effect model by Review Manager 5.0. The primary endpoints were glomerular filtration rate (GFR), serum creatinine level (sCr) and creatinine clearance rate (CrCl), and the secondary endpoints were acute rejection episodes, incidence of infection and patient survival at the end of follow-up. RESULTS: GFR was significantly improved in CNI minimization group than in routine CNI regimen group (Z = 5.45, P<0.00001; I(2) = 0%). Likely, sCr level was significantly lower in the CNI minimization group (Z = 2.84, P = 0.005; I(2) = 39%). However, CrCl was not significantly higher in the CNI minimization group (Z = 1.59, P = 0.11; I(2) = 0%). Both acute rejection episodes and patient survival were comparable between two groups (rejection: Z = 0.01, P = 0.99; I(2) = 0%; survival: Z = 0.28, P = 0.78; I(2) = 0%, respectively). However, current CNI minimization protocols may be related to a higher incidence of infections (Z = 3.06, P = 0.002; I(2) = 0%). CONCLUSION: CNI minimization can preserve or even improve renal function in liver transplant patients with renal impairment, while sharing similar short term acute rejection rate and patient survival with routine CNI regimen."	""
+3	"asian"	"India, India"	"India"	"0.0"	"0.0252100840336"	"0.0882352941176"	"238"	"8.37931034483"	"BMC Bioinformatics"	"Krishnadev O, Srinivasan N"	"Molecular Biophysics Unit Indian Institute of Science, Bangalore 560012, India."	"BACKGROUND: Sensitive remote homology detection and accurate alignments especially in the midnight zone of sequence similarity are needed for better function annotation and structural modeling of proteins. An algorithm, AlignHUSH for HMM-HMM alignment has been developed which is capable of recognizing distantly related domain families The method uses structural information, in the form of predicted secondary structure probabilities, and hydrophobicity of amino acids to align HMMs of two sets of aligned sequences. The effect of using adjoining column(s) information has also been investigated and is found to increase the sensitivity of HMM-HMM alignments and remote homology detection. RESULTS: We have assessed the performance of AlignHUSH using known evolutionary relationships available in SCOP. AlignHUSH performs better than the best HMM-HMM alignment methods and is observed to be even more sensitive at higher error rates. Accuracy of the alignments obtained using AlignHUSH has been assessed using the structure-based alignments available in BaliBASE. The alignment length and the alignment quality are found to be appropriate for homology modeling and function annotation. The alignment accuracy is found to be comparable to existing methods for profile-profile alignments. CONCLUSIONS: A new method to align HMMs has been developed and is shown to have better sensitivity at error rates of 10% and above when compared to other available programs. The proposed method could effectively aid obtaining clues to functions of proteins of yet unknown function. A web-server incorporating the AlignHUSH method is available at"	""
+3	"asian"	"India, India"	"India"	"0.00711743772242"	"0.0355871886121"	"0.0569395017794"	"281"	"12.2173913043"	"PLoS Computational Biology"	"Krishnan SM, Dixit NM"	"Department of Chemical Engineering, Indian Institute of Science, Bangalore, India."	"The current standard of care for hepatitis C virus (HCV) infection - combination therapy with pegylated interferon and ribavirin - elicits sustained responses in only  approximately 50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation of therapy, suggesting that increasing ribavirin exposure may further improve treatment response. A key limitation, however, is the toxic side-effect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan during therapy, and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones, such as erythropoietin, that stimulate erythrocyte production and avert the reduction of ribavirin dosage, thereby improving treatment response. Our model thus facilitates, in conjunction with models of viral kinetics, the rational identification of treatment protocols that maximize treatment response while curtailing side effects."	""
+3	"asian"	"Singapore"	"Singapore"	"0.00595238095238"	"0.0119047619048"	"0.077380952381"	"168"	"6.96"	"BMC Bioinformatics"	"Kriston-Vizi J, Thong NW, Poh CL, Yee KC, Ling JS, Kraut R, Wasser M"	"Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 138671, Singapore."	"BACKGROUND: Image segmentation is a crucial step in quantitative microscopy that helps to define regions of tissues, cells or subcellular compartments. Depending on the degree of user interactions, segmentation methods can be divided into manual, automated or semi-automated approaches. 3D image stacks usually require automated methods due to their large number of optical sections. However, certain applications benefit from manual or semi-automated approaches. Scenarios include the quantification of 3D images with poor signal-to-noise ratios or the generation of so-called ground truth segmentations that are used to evaluate the accuracy of automated segmentation methods. RESULTS: We have developed Gebiss; an ImageJ plugin for the interactive segmentation, visualisation and quantification of 3D microscopic image stacks. We integrated a variety of existing plugins for threshold-based segmentation and volume visualisation. CONCLUSIONS: We demonstrate the application of Gebiss to the segmentation of nuclei in live Drosophila embryos and the quantification of neurodegeneration in Drosophila larval brains. Gebiss was developed as a cross-platform ImageJ plugin and is freely available on the web at"	""
+3	"asian"	"India, India"	"India"	"0.0"	"0.00704225352113"	"0.056338028169"	"284"	"11.48"	"PLoS One"	"Kumar D, Patro S, Ranjan R, Sahoo DK, Maiti IB, Dey N"	"Department of Gene Function and Regulation, Institute of Life Sciences, Department of Biotechnology, Government of India, Nalco Square, Chandrasekherpur, Bhubaneswar, Orissa, India."	"BACKGROUND: Designing functionally efficient recombinant promoters having reduced sequence homology and enhanced promoter activity will be an important step toward successful stacking or pyramiding of genes in a plant cell for developing transgenic plants expressing desired traits(s). Also basic knowledge regarding plant cell specific expression of a transgene under control of a promoter is crucial to assess the promoters efficacy. METHODOLOGY/PRINCIPAL FINDINGS: We have constructed a set of 10 recombinant promoters incorporating different up-stream activation sequences (UAS) of Mirabilis mosaic virus sub-genomic transcript (MS8, -306 to +27) and TATA containing core domains of Figwort mosaic virus sub-genomic transcript promoter (FS3, -271 to +31). Efficacies of recombinant promoters coupled to GUS and GFP reporter genes were tested in tobacco protoplasts. Among these, a 369-bp long hybrid sub-genomic transcript promoter (MSgt-FSgt) showed the highest activity in both transient and transgenic systems. In a transient system, MSgt-FSgt was 10.31, 2.86 and 2.18 times more active compared to the CaMV35S, MS8 and FS3 promoters, respectively. In transgenic tobacco (Nicotiana tabaccum, var. Samsun NN) and Arabidopsis plants, the MSgt-FSgt hybrid promoter showed 14.22 and 7.16 times stronger activity compared to CaMV35S promoter respectively. The correlation between GUS activity and uidA-mRNA levels in transgenic tobacco plants were identified by qRT-PCR. Both CaMV35S and MSgt-FSgt promoters caused gene silencing but the degree of silencing are less in the case of the MSgt-FSgt promoter compared to CaMV35S. Quantification of GUS activity in individual plant cells driven by the MSgt-FSgt and the CaMV35S promoter were estimated using confocal laser scanning microscopy and compared. CONCLUSION AND SIGNIFICANCE: We propose strong recombinant promoter MSgt-FSgt, developed in this study, could be very useful for high-level constitutive expression of transgenes in a wide variety of plant cells."	""
+3	"asian"	"Japan"	"Japan"	"0.0440251572327"	"0.0314465408805"	"0.0503144654088"	"159"	"17.7777777778"	"Nature Genetics"	"Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, Otsuka M, Tateishi R, Omata M, Nakagawa H, Koike K, Kamatani N, Kubo M, Nakamura Y, Matsuda K"	"Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan."	"To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide association study using 432,703 autosomal SNPs in 721 individuals with HCV-induced HCC (cases) and 2,890 HCV-negative controls of Japanese origin. Eight SNPs that showed possible association (P < 1 x 10(-5)) in the genome-wide association study were further genotyped in 673 cases and 2,596 controls. We found a previously unidentified locus in the 5 flanking region of MICA on 6p21.33 (rs2596542, P(combined) = 4.21 x 10(-13), odds ratio = 1.39) to be strongly associated with HCV-induced HCC. Subsequent analyses using individuals with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61) but is significantly associated with progression from CHC to HCC (P = 3.13 x 10(-8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 x 10(-13))."	""
+3	"asian"	"Japan, Japan"	"Japan"	"0.00680272108844"	"0.00680272108844"	"0.0204081632653"	"147"	"11.3076923077"	"Immunity"	"Kuroda E, Ishii KJ, Uematsu S, Ohata K, Coban C, Akira S, Aritake K, Urade Y, Morimoto Y"	"Department of Immunology and Parasitology, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka 807-8555, Japan."	"Particulates such as silica crystal (silica) and aluminum salts (alum) activate the inflammasome and induce the secretion of proinflammatory cytokines in macrophages. These particulates also induce the production of immunoglobulin E via a T helper 2 (Th2) cell-associated mechanism. However, the mechanism involved in the induction of type 2 immunity has not been elucidated. Here, we showed that silica and alum induced lipopolysaccharide-primed macrophages to produce the lipid mediator prostaglandin E (PGE) and interleukin-1beta (IL-1beta). Macrophages deficient in the inflammasome components caspase 1, NALP3, and ASC revealed that PGE production was independent of the NALP3 inflammasome. PGE expression was markedly reduced in PGE synthase-deficient (Ptges/) macrophages, and Ptges/ mice displayed reduced antigen-specific serum IgE concentrations after immunization with alum or silica. Our results indicate that silica and alum regulate the production of PGE and that the induction of PGE by particulates controls the immune response in vivo."	""
+3	"asian"	"Japan"	"Japan"	"0.0237154150198"	"0.0197628458498"	"0.106719367589"	"253"	"11.0"	"PLoS One"	"Kuwano Y, Kamio Y, Kawai T, Katsuura S, Inada N, Takaki A, Rokutan K"	"Department of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan."	"Autism spectrum disorder (ASD) is a severe neuropsychiatric disorder which has complex pathobiology with profound influences of genetic factors in its development. Although the numerous autism susceptible genes were identified, the etiology of autism is not fully explained. Using DNA microarray, we examined gene expression profiling in peripheral blood from 21 individuals in each of the four groups; young adults with ASD, age- and gender-matched healthy subjects (ASD control), healthy mothers having children with ASD (asdMO), and asdMO control. There was no blood relationship between ASD and asdMO. Comparing the ASD group with control, 19 genes were found to be significantly changed. These genes were mainly involved in cell morphology, cellular assembly and organization, and nerve system development and function. In addition, the asdMO group possessed a unique gene expression signature shown as significant alterations of protein synthesis despite of their nonautistic diagnostic status. Moreover, an ASD-associated gene expression signature was commonly observed in both individuals with ASD and asdMO. This unique gene expression profiling detected in peripheral leukocytes from affected subjects with ASD and unaffected mothers having ASD children suggest that a genetic predisposition to ASD may be detectable even in peripheral cells. Altered expression of several autism candidate genes such as FMR-1 and MECP2, could be detected in leukocytes. Taken together, these findings suggest that the ASD-associated genes identified in leukocytes are informative to explore the genetic, epigenetic, and environmental background of ASD and might become potential tools to assess the crucial factors related to the clinical onset of the disorder."	""
+3	"asian"	"China, China"	"China"	"0.0"	"0.019801980198"	"0.0792079207921"	"101"	"9.18181818182"	"Nature Genetics"	"Lai J, Li R, Xu X, Jin W, Xu M, Zhao H, Xiang Z, Song W, Ying K, Zhang M, Jiao Y, Ni P, Zhang J, Li D, Guo X, Ye K, Jian M, Wang B, Zheng H, Liang H, Zhang X, Wang S, Chen S, Li J, Fu Y, Springer NM, Yang H, Wang J, Dai J, Schnable PS, Wang J"	"State Key Lab of Agrobiotechnology, China Agricultural University, Beijing, China."	"We have resequenced a group of six elite maize inbred lines, including the parents of the most productive commercial hybrid in China. This effort uncovered more than 1,000,000 SNPs, 30,000 indel polymorphisms and 101 low-sequence-diversity chromosomal intervals in the maize genome. We also identified several hundred complete genes that show presence/absence variation among these resequenced lines. We discuss the potential roles of complementation of presence/absence variations and other deleterious mutations in contributing to heterosis. High-density SNP and indel polymorphism markers reported here are expected to be a valuable resource for future genetic studies and the molecular breeding of this important crop."	""
+3	"asian"	"Hong Kong, Hong Kong"	"Hong Kong"	"0.0"	"0.014598540146"	"0.0948905109489"	"137"	"10.5384615385"	"Nature Genetics"	"Lam HM, Xu X, Liu X, Chen W, Yang G, Wong FL, Li MW, He W, Qin N, Wang B, Li J, Jian M, Wang J, Shao G, Wang J, Sun SS, Zhang G"	"State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong."	"We report a large-scale analysis of the patterns of genome-wide genetic variation in soybeans. We re-sequenced a total of 17 wild and 14 cultivated soybean genomes to an average of approximately x5 depth and >90% coverage using the Illumina Genome Analyzer II platform. We compared the patterns of genetic variation between wild and cultivated soybeans and identified higher allelic diversity in wild soybeans. We identified a high level of linkage disequilibrium in the soybean genome, suggesting that marker-assisted breeding of soybean will be less challenging than map-based cloning. We report linkage disequilibrium block location and distribution, and we identified a set of 205,614 tag SNPs that may be useful for QTL mapping and association studies. The data here provide a valuable resource for the analysis of wild soybeans and to facilitate future breeding and quantitative trait analysis."	""
+3	"asian"	"China, China"	"China"	"0.0133333333333"	"0.0166666666667"	"0.05"	"300"	"9.83870967742"	"Bioinformatics"	"Lao YM, Xiao L, Ye ZW, Jiang JG, Zhou SS"	"College of Food and Bioengineering, South China University of Technology, Guangzhou, 510640, China."	"MOTIVATION: Previous researches showed that phytoene synthase (Psy) from Dunaliella bardawil is the first regulatory point in carotenogenesis. We hypothesize certain interactions between the environmental stress factors and the regulatory sequences of Psy in D.bardawil (DbPsy). Consequently, LA PCR-based genomic walking approach was performed for isolation of psy promoter and terminator, respectively. The obtained nucleic acid sequences and the corresponding protein structure of DbPsy were analyzed and predicted using various bioinformatics tools. Finally, we presented some hints for the regulation mechanisms of DbPsy at the molecular level according to the computed results. RESULTS: LA PCR-based genomic walking results showed that the isolated sequences are the promoter and terminator of psy, correspondingly. Computational analysis demonstrated several candidate motifs of the promoter exhibiting hypothetic UV-B-, norglurzon- and salt-induced characteristics, as well as some typical domains universally discovered in promoter sequences, such as TATA-box, CCAAT-box and GATA-box, etc. Furthermore, the structure of Psy was also predicted and aligned along with many counterparts at the protein level. Low homology of N-terminus was found in D.bardawil, while a relatively conserved C-terminus was predicted to be involved in the catalytic activity and substrate recognization/binding. Phylogenic analysis classified the DbPsy into a cluster with other algae. These results implied that Psy may share similar regulation mechanisms among algae with respect to their C-termini; while the diversity in N-terminus among Psys, along with the predicted inducible motifs in psy promoter from D.bardawil, may confer the fine tuning differences between D.bardawil and other algae. CONCLUSION: By means of computer techniques, we found in D.barawali that two interesting conserved motifs of psy promoter may involve in UV-B, norglurzon and salt regulation correspondingly; and that the diversity of Psy protein mainly lies in the N-termini among algae. These results indicate some hints for regulation mechanisms of carotenogenesis in D.bradawil. CONTACT:"	""
+3	"asian"	"Ulsan, Ulsan"	"Korea"	"0.00925925925926"	"0.037037037037"	"0.0648148148148"	"108"	"6.0"	"Bioinformatics"	"Le DH, Kwon YK"	"School of Electrical Engineering, University of Ulsan, 93, Daehak-ro, Nam-gu, Ulsan 680-749."	"SUMMARY: NetDS is a novel Cytoscape plugin that conveniently simulates dynamics related to robustness, and examine structural properties with respect to feedforward/feedback loops. It can evaluate how robustly a network sustains a stable state against mutations by employing a Boolean network model. In addition, the plugin can examine all feedforward/feedback loops appearing in a network and determine whether or not a pair of loops is coupled. Random networks can also be generated to evaluate whether or not an interesting finding in real biological networks is significantly random. AVAILABILITY: NetDS is freely available for non-commercial purposes at CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
+3	"asian"	"Singapore"	"Singapore"	"0.0"	"0.0169491525424"	"0.0635593220339"	"236"	"11.2380952381"	"Molecular Biology and Evolution"	"Lee AP, Kerk SY, Tan YY, Brenner S, Venkatesh B"	"Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore."	"Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. In this study, we have identified CNEs in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu) using elephant shark, a cartilaginous vertebrate, as the base genome and investigated the evolution of these ancient vertebrate CNEs (aCNEs) in bony vertebrate lineages. Our analysis shows that aCNEs have been evolving at different rates in different bony vertebrate lineages. Although 78-83% of CNEs have diverged beyond recognition (lost) in different teleost fishes, only 24% and 40% have been lost in the chicken and mammalian lineages, respectively. Relative rate tests of substitution rates in CNEs revealed that the teleost fish CNEs have been evolving at a significantly higher rate than those in other bony vertebrates. In the ray-finned fish lineage, 68% of aCNEs were lost before the divergence of the four teleosts. This implicates the fish-specific whole-genome duplication in the accelerated evolution and the loss of a large number of both copies of duplicated CNEs in teleost fishes. The aCNEs are rich in tissue-specific enhancers and thus many of them are likely to be evolutionarily constrained cis-regulatory elements. The rapid evolution of aCNEs might have affected the expression patterns driven by them. Transgenic zebrafish assay of some human CNE enhancers that have been lost in teleosts has indicated instances of conservation or changes in trans-acting factors between mammals and fishes."	""
+3	"asian"	"Korea"	"Korea"	"0.0150943396226"	"0.0188679245283"	"0.0528301886792"	"265"	"10.037037037"	"BMC Bioinformatics"	"Lee J, Pham MD, Lee J, Han WS, Cho H, Yu H, Lee JH"	"Department of Computer Engineering, Kyungpook National University, Daegu, Korea."	"BACKGROUND: As the Resource Description Framework (RDF) data model is widely used for modeling and sharing a lot of online bioinformatics resources such as Uniprot ( or Bio2RDF (, SPARQL - a W3C recommendation query for RDF databases - has become an important query language for querying the bioinformatics knowledge bases. Moreover, due to the diversity of users requests for extracting information from the RDF data as well as the lack of users knowledge about the exact value of each fact in the RDF databases, it is desirable to use the SPARQL query with regular expression patterns for querying the RDF data. To the best of our knowledge, there is currently no work that efficiently supports regular expression processing in SPARQL over RDF databases. Most of the existing techniques for processing regular expressions are designed for querying a text corpus, or only for supporting the matching over the paths in an RDF graph. RESULTS: In this paper, we propose a novel framework for supporting regular expression processing in SPARQL query. Our contributions can be summarized as follows. 1) We propose an efficient framework for processing SPARQL queries with regular expression patterns in RDF databases. 2) We propose a cost model in order to adapt the proposed framework in the existing query optimizers. 3) We build a prototype for the proposed framework in C++ and conduct extensive experiments demonstrating the efficiency and effectiveness of our technique. CONCLUSIONS: Experiments with a full-blown RDF engine show that our framework outperforms the existing ones by up to two orders of magnitude in processing SPARQL queries with regular expression patterns."	""
+3	"asian"	"Ulsan, Korea"	"Korea"	"0.0150753768844"	"0.00502512562814"	"0.0603015075377"	"199"	"6.74193548387"	"Blood"	"Lee JH, Joo YD, Kim H, Bae SH, Kim MK, Zang DY, Lee JL, Lee GW, Lee JH, Park JH, Kim DY, Lee WS, Ryoo HM, Hyun MS, Kim HJ, Min YJ, Jang YE, Lee KH"	"Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of;"	"We conducted a Phase 3 randomized trial comparing two different doses of daunorubicin as induction chemotherapy in young adults (60 years or younger) with acute myeloid leukemia (AML). Of 383 patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m(2)/d x 3 d) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m(2)/d x 3 d) in addition to cytarabine (200 mg/m(2)/d x 7 d) to induce complete remission (CR). The CR rates were 72.0% in SD-DN arm and 82.5% in HD-DN arm (P=0.014). At a median follow-up time of 52.6 months, overall (OS) and event-free (EFS) survival were higher in HD-DN arm than in SD-DN arm (OS, 46.8% vs. 34.6%, P=0.030; EFS, 40.8% vs. 28.4%, P=0.030). Differences in CR rate and both OS and EFS remained significant after adjustment for other variables (CR, hazard ratio [HR], 1.802, P=0.024; OS, HR, 0.739, P=0.032; EFS, HR, 0.774, P=0.048). The survival benefits of HD-DN therapy were evident principally in patients with intermediate-risk cytogenetic features. The toxicity profiles were similar in the two arms. In conclusion, high-dose daunorubicin improved both the CR rate and survival duration compared to standard-dose daunorubicin in young adults with AML. This study is registered at as #NCT00474006."	""
+3	"asian"	"Korea"	"Korea"	"0.00607902735562"	"0.0121580547112"	"0.0729483282675"	"329"	"12.1851851852"	"BMC Bioinformatics"	"Lee S, Lee KH, Song M, Lee D"	"Bio and Brain Engineering Department, KAIST, Daejeon 305-701, South Korea."	"BACKGROUND: Side effects are unwanted responses to drug treatment and are important resources for human phenotype information. The recent development of a database on side effects, the side effect resource (SIDER), is a first step in documenting the relationship between drugs and their side effects. It is, however, insufficient to simply find the association of drugs with biological processes; that relationship is crucial because drugs that influence biological processes can have an impact on phenotype. Therefore, knowing which processes respond to drugs that influence the phenotype will enable more effective and systematic study of the effect of drugs on phenotype. To the best of our knowledge, the relationship between biological processes and side effects of drugs has not yet been systematically researched. METHODS: We propose 3 steps for systematically searching relationships between drugs and biological processes: enrichment scores (ES) calculations, t-score calculation, and threshold-based filtering. Subsequently, the side effect-related biological processes are found by merging the drug-biological process network and the drug-side effect network. Evaluation is conducted in 2 ways: first, by discerning the number of biological processes discovered by our method that co-occur with Gene Ontology (GO) terms in relation to effects extracted from PubMed records using a text-mining technique and second, determining whether there is improvement in performance by limiting response processes by drugs sharing the same side effect to frequent ones alone. RESULTS: The multi-level network (the process-drug-side effect network) was built by merging the drug-biological process network and the drug-side effect network. We generated a network of 74 drugs-168 side effects-2209 biological process relation resources. The preliminary results showed that the process-drug-side effect network was able to find meaningful relationships between biological processes and side effects in an efficient manner. CONCLUSIONS: We propose a novel process-drug-side effect network for discovering the relationship between biological processes and side effects. By exploring the relationship between drugs and phenotypes through a multi-level network, the mechanisms underlying the effect of specific drugs on the human body may be understood."	""
+3	"asian"	"Taiwan"	"China"	"0.00706713780919"	"0.017667844523"	"0.0636042402827"	"283"	"6.02040816327"	"BMC Bioinformatics"	"Lee TY, Bretana NA, Lu CT"	"Department of Computer Science and Engineering, Yuan Ze University, Chungli 320, Taiwan."	"BACKGROUND: Protein phosphorylation catalyzed by kinases plays crucial regulatory roles in intracellular signal transduction. Due to the difficulty in performing high-throughput mass spectrometry-based experiment, there is a desire to predict phosphorylation sites using computational methods. However, previous studies regarding in silico prediction of plant phosphorylation sites lack the consideration of kinase-specific phosphorylation data. Thus, we are motivated to propose a new method that investigates different substrate specificities in plant phosphorylation sites. RESULTS: Experimentally verified phosphorylation data were extracted from TAIR9-a protein database containing 3006 phosphorylation data from the plant species Arabidopsis thaliana. In an attempt to investigate the various substrate motifs in plant phosphorylation, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. Profile hidden Markov model (HMM) is then applied to learn a predictive model for each subgroup. Cross-validation evaluation on the MDD-clustered HMMs yields an average accuracy of 82.4% for serine, 78.6% for threonine, and 89.0% for tyrosine models. Moreover, independent test results using Arabidopsis thaliana phosphorylation data from UniProtKB/Swiss-Prot show that the proposed models are able to correctly predict 81.4% phosphoserine, 77.1% phosphothreonine, and 83.7% phosphotyrosine sites. Interestingly, several MDD-clustered subgroups are observed to have similar amino acid conservation with the substrate motifs of well-known kinases from Phospho.ELM-a database containing kinase-specific phosphorylation data from multiple organisms. CONCLUSIONS: This work presents a novel method for identifying plant phosphorylation sites with various substrate motifs. Based on cross-validation and independent testing, results show that the MDD-clustered models outperform models trained without using MDD. The proposed method has been implemented as a web-based plant phosphorylation prediction tool, PlantPhos Additionally, two case studies have been demonstrated to further evaluate the effectiveness of PlantPhos."	""
+3	"asian"	"Taiwan"	"China"	"0.0251256281407"	"0.0201005025126"	"0.0804020100503"	"199"	"9.71428571429"	"Bioinformatics"	"Lee TY, Lin ZQ, Hsieh SJ, Bretana NA, Lu CT"	"Department of Computer Science and Engineering, Yuan Ze University, Taoyuan 320, Taiwan."	"Bioinformatics research often requires conservative analyses of a group of sequences associated with a specific biological function (e.g. transcription factor binding sites, micro RNA target sites or protein post-translational modification sites). Due to the difficulty in exploring conserved motifs on a large-scale sequence data involved with various signals, a new method, MDDLogo, is developed. MDDLogo applies maximal dependence decomposition (MDD) to cluster a group of aligned signal sequences into subgroups containing statistically significant motifs. In order to extract motifs that contain a conserved biochemical property of amino acids in protein sequences, the set of 20 amino acids is further categorized according to their physicochemical properties, e.g. hydrophobicity, charge or molecular size. MDDLogo has been demonstrated to accurately identify the kinase-specific substrate motifs in 1221 human phosphorylation sites associated with seven well-known kinase families from Phospho.ELM. Moreover, in a set of plant phosphorylation data-lacking kinase information, MDDLogo has been applied to help in the investigation of substrate motifs of potential kinases and in the improvement of the identification of plant phosphorylation sites with various substrate specificities. In this study, MDDLogo is comparable with another well-known motif discover tool, Motif-X. CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
 3	"asian"	"China"	"China"	"0.00671140939597"	"0.0134228187919"	"0.0604026845638"	"149"	"11.4615384615"	"Immunity"	"Lei CQ, Zhong B, Zhang Y, Zhang J, Wang S, Shu HB"	"College of Life Sciences, Wuhan University, Wuhan 430072, China."	"Viral infection activates transcription factors IRF3 and NF-kappaB, which collaborate to induce type I interferons (IFNs). Here, we identified glycogen synthase kinase 3beta (GSK3beta) as an important regulator for virus-triggered IRF3 and NF-kappaB activation, IFN-beta induction, and cellular antiviral response. Overexpression of GSK3beta potentiated virus-induced activation of IRF3 and transcription of the IFNB1 gene, whereas reduced expression or deletion of GSK3beta impaired virus-induced IRF3 and NF-kappaB activation, transcription of the IFNB1 gene, as well as cellular antiviral response. GSK3beta physically associated with the kinase TBK1 in a viral infection-dependent manner. GSK3beta promoted TBK1 self-association and autophosphorylation at Ser172, which is critical for virus-induced IRF3 activation and IFN-beta induction. The effect of GSK3beta on virus-induced signaling is independent of its kinase activity. Our findings suggest that GSK3beta plays important roles in virus-triggered IRF3 activation by promoting TBK1 activation and provide new insights to the molecular mechanisms of cellular antiviral response."	""
+3	"asian"	"China, China"	"China"	"0.0125786163522"	"0.0314465408805"	"0.0691823899371"	"159"	"12.2307692308"	"Glycobiology"	"Li J, Dai G, Cheng YB, Qi X, Geng MY"	"Department of Pharmacology and Glycobiology, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, PR China."	"Polysialic acid (PSA), a carbohydrate polymer mainly present in the neural cell adhesion molecule (NCAM), promotes neural plasticity; however, its mode of action in tumor malignancy remains largely unknown. In this study, we investigated the influence of polysialylation on cell migration. PSA consistently promoted cell migration on different extracellular matrices (ECMs) but differentially affected cell adhesion. All of these actions were reversed by endo-N-acetylneuraminidase treatment, and PSA-driven migration was inhibited by the specific fibroblast growth factor receptor (FGFR) inhibitor Su5402. Consistent with this latter observation, PSA-stimulated migration on different ECMs was paralleled by activation of the FGFR and its downstream signaling components, PLC-gamma, focal adhesion kinase and extracellular signal-regulated kinase 1/2. In contrast, the pattern of p59(fyn) activation correlated with differential adhesion to different ECMs. Collectively, these results indicate that PSA-conjugated NCAM potentiates signal transduction by the FGFR pathway and thereby enhances cell migration independent of adhesion capability, providing additional insights into the role of PSA in cancer development."	""
 3	"asian"	"China"	"China"	"0.00302114803625"	"0.0181268882175"	"0.0634441087613"	"331"	"8.19512195122"	"BMC Bioinformatics"	"Li J, Gong B, Chen X, Liu T, Wu C, Zhang F, Li C, Li X, Rao S, Li X"	"College of Bioinformatics Science and Technology, Harbin Medical University, 194 Xuefu Road, Harbin 150081, China."	"BACKGROUND: The construction of the Disease Ontology (DO) has helped promote the investigation of diseases and disease risk factors. DO enables researchers to analyse disease similarity by adopting semantic similarity measures, and has expanded our understanding of the relationships between different diseases and to classify them. Simultaneously, similarities between genes can also be analysed by their associations with similar diseases. As a result, disease heterogeneity is better understood and insights into the molecular pathogenesis of similar diseases have been gained. However, bioinformatics tools that provide easy and straight forward ways to use DO to study disease and gene similarity simultaneously are required. RESULTS: We have developed an R-based software package (DOSim) to compute the similarity between diseases and to measure the similarity between human genes in terms of diseases. DOSim incorporates a DO-based enrichment analysis function that can be used to explore the disease feature of an independent gene set. A multilayered enrichment analysis (GO and KEGG annotation) annotation function that helps users explore the biological meaning implied in a newly detected gene module is also part of the DOSim package. We used the disease similarity application to demonstrate the relationship between 128 different DO cancer terms. The hierarchical clustering of these 128 different cancers showed modular characteristics. In another case study, we used the gene similarity application on 361 obesity-related genes. The results revealed the complex pathogenesis of obesity. In addition, the gene module detection and gene module multilayered annotation functions in DOSim when applied on these 361 obesity-related genes helped extend our understanding of the complex pathogenesis of obesity risk phenotypes and the heterogeneity of obesity-related diseases. CONCLUSIONS: DOSim can be used to detect disease-driven gene modules, and to annotate the modules for functions and pathways. The DOSim package can also be used to visualise DO structure. DOSim can reflect the modular characteristic of disease related genes and promote our understanding of the complex pathogenesis of diseases. DOSim is available on the Comprehensive R Archive Network (CRAN) or"	""
+3	"asian"	"China, China, China"	"China"	"0.0"	"0.0122448979592"	"0.110204081633"	"245"	"12.8947368421"	"PLoS One"	"Li L, Li H, Li Q, Yang X, Zheng D, Warburton M, Chai Y, Zhang P, Guo Y, Yan J, Li J"	"National Maize Improvement Center of China, China Agricultural University, Beijing, China."	"The ratio of saturated to unsaturated fatty acids in maize kernels strongly impacts human and livestock health, but is a complex trait that is difficult to select based on phenotype. Map-based cloning of quantitative trait loci (QTL) is a powerful but time-consuming method for the dissection of complex traits. Here, we combine linkage and association analyses to fine map QTL-Pal9, a QTL influencing levels of palmitic acid, an important class of saturated fatty acid. QTL-Pal9 was mapped to a 90-kb region, in which we identified a candidate gene, Zea mays fatb (Zmfatb), which encodes acyl-ACP thioesterase. An 11-bp insertion in the last exon of Zmfatb decreases palmitic acid content and concentration, leading to an optimization of the ratio of saturated to unsaturated fatty acids while having no effect on total oil content. We used three-dimensional structure analysis to explain the functional mechanism of the ZmFATB protein and confirmed the proposed model in vitro and in vivo. We measured the genetic effect of the functional site in 15 different genetic backgrounds and found a maximum change of 4.57 mg/g palmitic acid content, which accounts for  approximately 20-60% of the variation in the ratio of saturated to unsaturated fatty acids. A PCR-based marker for QTL-Pal9 was developed for marker-assisted selection of nutritionally healthier maize lines. The method presented here provides a new, efficient way to clone QTL, and the cloned palmitic acid QTL sheds lights on the genetic mechanism of oil biosynthesis and targeted maize molecular breeding."	""
+3	"asian"	"Taiwan"	"China"	"0.00854700854701"	"0.0"	"0.106837606838"	"234"	"10.2173913043"	"PLoS One"	"Li LF, Chen BX, Tsai YH, Kao WW, Yang CT, Chu PH"	"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan."	"BACKGROUND: Diaphragmatic dysfunction found in the patients with acute lung injury required prolonged mechanical ventilation. Mechanical ventilation can induce production of inflammatory cytokines and excess deposition of extracellular matrix proteins via up-regulation of transforming growth factor (TGF)-beta1. Lumican is known to participate in TGF-beta1 signaling during wound healing. The mechanisms regulating interactions between mechanical ventilation and diaphragmatic injury are unclear. We hypothesized that diaphragmatic damage by short duration of mechanical stretch caused up-regulation of lumican that modulated TGF-beta1 signaling. METHODS: Male C57BL/6 mice, either wild-type or lumican-null, aged 3 months, weighing between 25 and 30 g, were exposed to normal tidal volume (10 ml/kg) or high tidal volume (30 ml/kg) mechanical ventilation with room air for 2 to 8 hours. Nonventilated mice served as control groups. RESULTS: High tidal volume mechanical ventilation induced interfibrillar disassembly of diaphragmatic collagen fiber, lumican activation, type I and III procollagen, fibronectin, and alpha-smooth muscle actin (alpha-SMA) mRNA, production of free radical and TGF-beta1 protein, and positive staining of lumican in diaphragmatic fiber. Mechanical ventilation of lumican deficient mice attenuated diaphragmatic injury, type I and III procollagen, fibronectin, and alpha-SMA mRNA, and production of free radical and TGF-beta1 protein. No significant diaphragmatic injury was found in mice subjected to normal tidal volume mechanical ventilation. CONCLUSION: Our data showed that high tidal volume mechanical ventilation induced TGF-beta1 production, TGF-beta1-inducible genes, e.g., collagen, and diaphragmatic dysfunction through activation of the lumican."	""
+3	"asian"	"USA."	"USA"	"0.0246913580247"	"0.0123456790123"	"0.037037037037"	"81"	"16.4"	"Nature Genetics"	"Li M, Zhao H, Zhang X, Wood LD, Anders RA, Choti MA, Pawlik TM, Daniel HD, Kannangai R, Offerhaus GJ, Velculescu VE, Wang L, Zhou S, Vogelstein B, Hruban RH, Papadopoulos N, Cai J, Torbenson MS, Kinzler KW"	"1] Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2]."	"Through exomic sequencing of ten hepatitis C virus (HCV)-associated hepatocellular carcinomas (HCC) and subsequent evaluation of additional affected individuals, we discovered novel inactivating mutations of ARID2 in four major subtypes of HCC (HCV-associated HCC, hepatitis B virus (HBV)-associated HCC, alcohol-associated HCC and HCC with no known etiology). Notably, 18.2% of individuals with HCV-associated HCC in the United States and Europe harbored ARID2 inactivation mutations, suggesting that ARID2 is a tumor suppressor gene that is relatively commonly mutated in this tumor subtype."	""
+3	"asian"	"Hong Kong, Hong Kong"	"Hong Kong"	"0.0062893081761"	"0.0251572327044"	"0.125786163522"	"159"	"5.12121212121"	"Bioinformatics"	"Li Q, Fan X, Liang T, Li SY"	"Department of Statistics, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong."	"MOTIVATION: Repeats detection problems are traditionally formulated as string matching or signal processing problems. They cannot readily handle gaps between repeat units and are incapable of detecting repeat patterns shared by multiple sequences. This study detects short adjacent repeats with interunit insertions from multiple sequences. For biological sequences, such studies can shed light on molecular structure, biological function and evolution. RESULTS: The task of detecting short adjacent repeats is formulated as a statistical inference problem by using a probabilistic generative model. An Markov chain Monte Carlo algorithm is proposed to infer the parameters in a de novo fashion. Its applications on synthetic and real biological data show that the new method not only has a competitive edge over existing methods, but also can provide a way to study the structure and the evolution of repeat-containing genes. AVAILABILITY: The related C++ source code and datasets are available at CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
+2	"asian"	"Chicago, United States"	"USA"	"0.005"	"0.01"	"0.045"	"200"	"15.4615384615"	"Blood"	"Li S, Choi HJ, Felio K, Wang CR"	"Department of Microbiology and Immunology, Northwestern University, Chicago, IL, United States."	"Group 1 CD1 (CD1a, -b, and -c) presents self and foreign lipid antigens to multiple T cell subsets in humans. However, in the absence of a suitable animal model, the specific functions and developmental requirements of these T cells remain unknown. To study group 1 CD1-restricted T cells in vivo, we generated double transgenic mice (HJ1Tg/hCD1Tg) that express group 1 CD1 molecules in a similar pattern to that observed in humans (hCD1Tg) as well as a TCR derived from an autoreactive CD1b-restricted T cell line (HJ1Tg). Using this model, we found that similar to CD1d-restricted NKT cells, HJ1 T cells exhibit an activated phenotype (CD44(hi)CD69(+)CD122(+)) and a subset of HJ1 T cells expresses NK1.1 and is selected by CD1b-expressing hematopoietic cells. HJ1 T cells secrete proinflammatory cytokines in response to stimulation with CD1b-expressing dendritic cells derived from humans as well as hCD1Tg mice, suggesting that they recognize species conserved self-lipid antigen(s). Importantly, this basal autoreactivity is enhanced by TLR-mediated signaling and HJ1 T cells can be activated and confer protection against Listeria infection. Taken together, our data indicate that CD1b-autoreactive T cells, unlike mycobacterial lipid antigen-specific T cells, are innate-like T cells that may contribute to early anti-microbial host defense."	""
+3	"asian"	"USA."	"USA"	"0.0"	"0.0077519379845"	"0.077519379845"	"129"	"7.76470588235"	"Database(Oxford)"	"Li X, Wu F, Qi F, Beard DA"	"Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA."	"A database of thermodynamic properties is developed, which extends a previous database of glycolysis and tricarboxylic acid cycle by adding the reactions of the pentose phosphate pathway. The raw data and documented estimations of solution properties are made electronically available. The database is determined by estimation of a set of parameters representing species-level free energies of formation. The resulting calculations provide thermodynamic and network-based estimates of thermodynamic properties for six reactions of the pentose phosphate pathway for which estimates are not available in the preexisting literature. Optimized results are made available in ThermoML format. Because calculations depend on estimated hydrogen and metal cation dissociation constants, an uncertainty and sensitivity analysis is performed, revealing 23 critical dissociation constants to which the computed thermodynamic properties are particularly sensitive. DATABASE URL:"	""
 3	"asian"	"China"	"China"	"0.0"	"0.0153846153846"	"0.0923076923077"	"195"	"11.4705882353"	"PLoS One"	"Li XC, Wei L, Zhang GQ, Bai ZL, Hu YY, Zhou P, Bai SH, Chai Z, Lakatta EG, Hao XM, Wang SQ"	"State Key Lab of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, China."	"Heart tissues from hibernating mammals, such as ground squirrels, are able to endure hypothermia, hypoxia and other extreme insulting factors that are fatal for human and nonhibernating mammals. This study was designed to understand adaptive mechanisms involved in intracellular Ca(2+) homeostasis in cardiomyocytes from the mammalian hibernator, ground squirrel, compared to rat. Electrophysiological and confocal imaging experiments showed that the voltage-dependence of L-type Ca(2+) current (I(Ca)) was shifted to higher potentials in ventricular myocytes from ground squirrels vs. rats. The elevated threshold of I(Ca) did not compromise the Ca(2+)-induced Ca(2+) release, because a higher depolarization rate and a longer duration of action potential compensated the voltage shift of I(Ca). Both the caffeine-sensitive and caffeine-resistant components of cytosolic Ca(2+) removal were more rapid in ground squirrels. Ca(2+) sparks in ground squirrels exhibited larger amplitude/size and much lower frequency than in rats. Due to the high I(Ca) threshold, low SR Ca(2+) leak and rapid cytosolic Ca(2+) clearance, heart cells from ground squirrels exhibited better capability in maintaining intracellular Ca(2+) homeostasis than those from rats and other nonhibernating mammals. These findings not only reveal adaptive mechanisms of hibernation, but also provide novel strategies against Ca(2+) overload-related heart diseases."	""
 3	"asian"	"China"	"China"	"0.0201342281879"	"0.00671140939597"	"0.0671140939597"	"149"	"13.7272727273"	"Nature Genetics"	"Li Y, Vinckenbosch N, Tian G, Huerta-Sanchez E, Jiang T, Jiang H, Albrechtsen A, Andersen G, Cao H, Korneliussen T, Grarup N, Guo Y, Hellman I, Jin X, Li Q, Liu J, Liu X, Sparso T, Tang M, Wu H, Wu R, Yu C, Zheng H, Astrup A, Bolund L, Holmkvist J, Jorgensen T, Kristiansen K, Schmitz O, Schwartz TW, Zhang X, Li R, Yang H, Wang J, Hansen T, Pedersen O, Nielsen R, Wang J"	"BGI-Shenzhen, Shenzhen, China."	"Targeted capture combined with massively parallel exome sequencing is a promising approach to identify genetic variants implicated in human traits. We report exome sequencing of 200 individuals from Denmark with targeted capture of 18,654 coding genes and sequence coverage of each individual exome at an average depth of 12-fold. On average, about 95% of the target regions were covered by at least one read. We identified 121,870 SNPs in the sample population, including 53,081 coding SNPs (cSNPs). Using a statistical method for SNP calling and an estimation of allelic frequencies based on our population data, we derived the allele frequency spectrum of cSNPs with a minor allele frequency greater than 0.02. We identified a 1.8-fold excess of deleterious, non-syonomyous cSNPs over synonymous cSNPs in the low-frequency range (minor allele frequencies between 2% and 5%). This excess was more pronounced for X-linked SNPs, suggesting that deleterious substitutions are primarily recessive."	""
+3	"asian"	"Japan"	"Japan"	"0.00943396226415"	"0.0188679245283"	"0.103773584906"	"106"	"6.05263157895"	"Bioinformatics"	"Liang S, Zheng D, Zhang C, Standley DM"	"Systems Immunology Lab, Immunology Frontier Research Center, Osaka University, Suita, Osaka, 565-0871, Japan."	"SUMMARY: We developed a fast and accurate side-chain modeling program (OSCAR-star) based on orientation dependent energy functions and a rigid rotamer model. The average computing time was 18 seconds per protein for 218 test proteins with higher prediction accuracy (1.1% increase for chi(1) and 0.8% increase for chi(1+2)) than the best performing program developed by other groups. We show that the energy functions, which were calibrated to tolerate the discrete errors of rigid rotamers, are appropriate for protein loop selection, especially for decoys without extensive structural refinement. AVAILABILITY: OSCAR-star and the 218 test proteins are available for download at CONTACT: Information: Supplementary Data Available."	""
+3	"asian"	"Thailand"	"Thailand"	"0.00578034682081"	"0.0260115606936"	"0.0924855491329"	"346"	"7.46808510638"	"BMC Bioinformatics"	"Limpiti T, Intarapanich A, Assawamakin A, Shaw PJ, Wangkumhang P, Piriyapongsa J, Ngamphiw C, Tongsima S"	"Faculty of Engineering, King Mongkuts Institute of Technology Ladkrabang, Bangkok, Thailand."	"BACKGROUND: The ever increasing sizes of population genetic datasets pose great challenges for population structure analysis. The Tracy-Widom (TW) statistical test is widely used for detecting structure. However, it has not been adequately investigated whether the TW statistic is susceptible to type I error, especially in large, complex datasets. Non-parametric, Principal Component Analysis (PCA) based methods for resolving structure have been developed which rely on the TW test. Although PCA-based methods can resolve structure, they cannot infer ancestry. Model-based methods are still needed for ancestry analysis, but they are not suitable for large datasets. We propose a new structure analysis framework for large datasets. This includes a new heuristic for detecting structure and incorporation of the structure patterns inferred by a PCA method to complement STRUCTURE analysis. RESULTS: A new heuristic called EigenDev for detecting population structure is presented. When tested on simulated data, this heuristic is robust to sample size. In contrast, the TW statistic was found to be susceptible to type I error, especially for large population samples. EigenDev is thus better-suited for analysis of large datasets containing many individuals, in which spurious patterns are likely to exist and could be incorrectly interpreted as population stratification. EigenDev was applied to the iterative pruning PCA (ipPCA) method, which resolves the underlying subpopulations. This subpopulation information was used to supervise STRUCTURE analysis to infer patterns of ancestry at an unprecedented level of resolution. To validate the new approach, a bovine and a large human genetic dataset (3945 individuals) were analyzed. We found new ancestry patterns consistent with the subpopulations resolved by ipPCA. CONCLUSIONS: The EigenDev heuristic is robust to sampling and is thus superior for detecting structure in large datasets. The application of EigenDev to the ipPCA algorithm improves the estimation of the number of subpopulations and the individual assignment accuracy, especially for very large and complex datasets. Furthermore, we have demonstrated that the structure resolved by this approach complements parametric analysis, allowing a much more comprehensive account of population structure. The new version of the ipPCA software with EigenDev incorporated can be downloaded from"	""
+3	"asian"	"Taiwan, Taiwan"	"China"	"0.0162601626016"	"0.0487804878049"	"0.0894308943089"	"246"	"14.4705882353"	"Glycobiology"	"Lin CW, Chen JM, Wang YM, Wu SW, Tsai IH, Khoo KH"	"Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan."	"Glycosylation analysis of nonmammalian sources often springs surprises and conjures up intriguing views of evolutionary adaptation. Many of the constituents of snake venoms are known to be glycosylated and yet very few were fully characterized and accorded specific functions. In the process of glycomic screening through the venoms from Asian pit vipers, a partially O-acetylated NeuAcalpha2-8NeuAcalpha2-3Galbeta1-4GlcNAcbeta1-terminal epitope was found to be the predominant glycosylation characteristic of the snake venom produced by the monotypic Deinagkistrodon acutus, with acutobin, a highly specific fibrinogenase, being identified as a primary protein carrier. Full structural definition and glycosylation site mapping were completed through advanced mass spectrometry analyses at both the glycan and glycopeptide levels in conjunction with chemical and enzymatic cleavages. Although similar occurrence of such terminal disialyl cap on the N-glycans of several mammalian glycoproteins has been implicated, most of these correspond to only minor constituents of the full glycomic heterogeneity and remain poorly characterized. In contrast, each antennae of the hybrid- and complex-type N-glycans derived from acutobin was found to be rather homogeneously disialylated. With up to eight sialic acids evenly distributed on nonextended tetraantennary core structure, these unusual N-glycans are among those of highest sialic acid density ever identified without actually carrying polysialic acid chains. It remains to be tested whether they may serve as multivalent disialyl ligands for several of the human Siglecs and thus meddle with the natural immuno-recognition systems of snakebite victims, apart from affecting the general efficacy of acutobin as anticoagulant in biomedical applications."	""
 3	"asian"	"China"	"China"	"0.00429184549356"	"0.0257510729614"	"0.0944206008584"	"233"	"7.90322580645"	"PLoS One"	"Lin WZ, Fang JA, Xiao X, Chou KC"	"Information Science and Technology School, Donghua University, Shanghai, China."	"DNA-binding proteins play crucial roles in various cellular processes. Developing high throughput tools for rapidly and effectively identifying DNA-binding proteins is one of the major challenges in the field of genome annotation. Although many efforts have been made in this regard, further effort is needed to enhance the prediction power.By incorporating the features into the general form of pseudo amino acid composition that were extracted from protein sequences via the grey model and by adopting the random forest operation engine, we proposed a new predictor, called iDNA-Prot, for identifying uncharacterized proteins as DNA-binding proteins or non-DNA binding proteins based on their amino acid sequences information alone. The overall success rate by iDNA-Prot was 83.96% that was obtained via jackknife tests on a newly constructed stringent benchmark dataset in which none of the proteins included has [Formula: see text] pairwise sequence identity to any other in a same subset. In addition to achieving high success rate, the computational time for iDNA-Prot is remarkably shorter in comparison with the relevant existing predictors. Hence it is anticipated that iDNA-Prot may become a useful high throughput tool for large-scale analysis of DNA-binding proteins.As a user-friendly web-server, iDNA-Prot is freely accessible to the public at the web-site on or Moreover, for the convenience of the vast majority of experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results."	""
 3	"asian"	"China"	"China"	"0.0"	"0.0326086956522"	"0.0815217391304"	"184"	"12.2666666667"	"Bioinformatics"	"Lin Y, Li J, Shen H, Zhang L, Papasian CJ, Deng HW"	"Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai 200093, P R China."	"MOTIVATION: Several new de novo assembly tools have been developed recently to assemble short sequencing reads generated by next-generation sequencing platforms. However, the performance of these tools under various conditions has not been fully investigated, and sufficient information is not currently available for informed decisions to be made regarding the tool that would be most likely to produce the best performance under a specific set of conditions. RESULTS: We studied and compared the performance of commonly used de novo assembly tools specifically designed for next-generation sequencing data, including SSAKE, VCAKE, Euler-sr, Edena, Velvet, ABySS and SOAPdenovo. Tools were compared using several performance criteria, including N50 length, sequence coverage and assembly accuracy. Various properties of read data, including single-end/paired-end, sequence GC content, depth of coverage and base calling error rates, were investigated for their effects on the performance of different assembly tools. We also compared the computation time and memory usage of these seven tools. Based on the results of our comparison, the relative performance of individual tools are summarized and tentative guidelines for optimal selection of different assembly tools, under different conditions, are provided."	""
+3	"asian"	"Singapore, Singapore"	"Singapore"	"0.0"	"0.0207468879668"	"0.0871369294606"	"241"	"9.68"	"PLoS Computational Biology"	"Liu B, Zhang J, Tan PY, Hsu D, Blom AM, Leong B, Sethi S, Ho B, Ding JL, Thiagarajan PS"	"School of Computing, National University of Singapore, Singapore."	"The complement system is key to innate immunity and its activation is necessary for the clearance of bacteria and apoptotic cells. However, insufficient or excessive complement activation will lead to immune-related diseases. It is so far unknown how the complement activity is up- or down- regulated and what the associated pathophysiological mechanisms are. To quantitatively understand the modulatory mechanisms of the complement system, we built a computational model involving the enhancement and suppression mechanisms that regulate complement activity. Our model consists of a large system of Ordinary Differential Equations (ODEs) accompanied by a dynamic Bayesian network as a probabilistic approximation of the ODE dynamics. Applying Bayesian inference techniques, this approximation was used to perform parameter estimation and sensitivity analysis. Our combined computational and experimental study showed that the antimicrobial response is sensitive to changes in pH and calcium levels, which determines the strength of the crosstalk between CRP and L-ficolin. Our study also revealed differential regulatory effects of C4BP. While C4BP delays but does not decrease the classical complement activation, it attenuates but does not significantly delay the lectin pathway activation. We also found that the major inhibitory role of C4BP is to facilitate the decay of C3 convertase. In summary, the present work elucidates the regulatory mechanisms of the complement system and demonstrates how the bio-pathway machinery maintains the balance between activation and inhibition. The insights we have gained could contribute to the development of therapies targeting the complement system."	""
 3	"asian"	"China"	"China"	"0.0155279503106"	"0.0310559006211"	"0.0590062111801"	"322"	"17.0"	"BMC Bioinformatics"	"Liu Q, Zhou H, Liu L, Chen X, Zhu R, Cao Z"	"College of Life Science and Biotechnology, Tongji University, 200092, China."	"ABSTRACT: BACKGROUND: HIV and HCV infections have become the leading global public-health threats. Even more remarkable, HIV-HCV co-infection is rapidly emerging as a major cause of morbidity and mortality throughout the world, due to the common rapid mutation characteristics of the two viruses as well as their similar complex influence to immunology system. Although considerable progresses have been made on the study of the infection of HIV and HCV respectively, few researches have been conducted on the investigation of the molecular mechanism of their co-infection and designing of the multi-target co-inhibitors for the two viruses simultaneously. RESULTS: In our study, a multi-target Quantitative Structure-Activity Relationship (QSAR) study of the inhibitors for HIV-HCV co-infection were addressed with an in-silico machine learning technique, i.e. multi-task learning, to help to guide the co-inhibitor design. Firstly, an integrated dataset with 3 HIV inhibitor subsets targeted on protease, integrase and reverse transcriptase respectively, together with another 6 subsets of 2 HCV inhibitors targeted on NS3 serine protease and NS5B polymerase respectively were compiled. Secondly, an efficient multi-target QSAR modelling of HIV-HCV co-inhibitors was performed by applying an accelerated gradient method based multi-task learning on the whole 9 datasets. Furthermore, by solving the L-1-infinity regularized optimization, the Drug-like index features for compound description were ranked according to their joint importance in multi-target QSAR modelling of HIV and HCV. Finally, a drug structure-activity simulation for investigating the relationships between compound structures and binding affinities was presented based on our multiple target analysis, which is then providing several novel clues for the design of multi-target HIV-HCV co-inhibitors with increasing likelihood of successful therapies on HIV, HCV and HIV-HCV co-infection. CONCLUSIONS: The framework presented in our study provided an efficient way to identify and design inhibitors that simultaneously and selectively bind to multiple targets from multiple viruses with high affinity, and will definitely shed new lights on the future work of inhibitor synthesis for multi-target HIV, HCV, and HIV-HCV co-infection treatments."	""
 3	"asian"	"China"	"China"	"0.0"	"0.0187969924812"	"0.0601503759398"	"266"	"9.85185185185"	"BMC Bioinformatics"	"Liu S, Vakser IA"	"Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China."	"BACKGROUND: Computational approaches to protein-protein docking typically include scoring aimed at improving the rank of the near-native structure relative to the false-positive matches. Knowledge-based potentials improve modeling of protein complexes by taking advantage of the rapidly increasing amount of experimentally derived information on protein-protein association. An essential element of knowledge-based potentials is defining the reference state for an optimal description of the residue-residue (or atom-atom) pairs in the non-interaction state. RESULTS: The study presents a new Distance- and Environment-dependent, Coarse-grained, Knowledge-based (DECK) potential for scoring of protein-protein docking predictions. Training sets of protein-protein matches were generated based on bound and unbound forms of proteins taken from the DOCKGROUND resource. Each residue was represented by a pseudo-atom in the geometric center of the side chain. To capture the long-range and the multi-body interactions, residues in different secondary structure elements at protein-protein interfaces were considered as different residue types. Five reference states for the potentials were defined and tested. The optimal reference state was selected and the cutoff effect on the distance-dependent potentials investigated. The potentials were validated on the docking decoys sets, showing better performance than the existing potentials used in scoring of protein-protein docking results. CONCLUSIONS: A novel residue-based statistical potential for protein-protein docking was developed and validated on docking decoy sets. The results show that the scoring function DECK can successfully identify near-native protein-protein matches and thus is useful in protein docking. In addition to the practical application of the potentials, the study provides insights into the relative utility of the reference states, the scope of the distance dependence, and the coarse-graining of the potentials."	""
+3	"asian"	"Japan"	"Japan"	"0.00574712643678"	"0.0172413793103"	"0.0632183908046"	"174"	"13.3846153846"	"Glycobiology"	"Liu TW, Ito H, Chiba Y, Kubota T, Sato T, Narimatsu H"	"Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Central-2 OSL, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan."	"The biosynthesis of glycoconjugates requires the relevant glycosyltransferases and nucleotide sugars that can act as donors. Given the biological importance of posttranslational glycosylation, a facile, robust and cost-effective strategy for the synthesis of nucleotide sugars is highly desirable. In this study, we demonstrate the synthesis of nucleotide sugars from corresponding monosaccharides in a highly efficient manner via metabolic engineering, using an enzymatic approach. This method exploits l-fucokinase/guanosine 5-diphosphate (GDP)-l-fucose (L-Fuc) pyrophosphorylase (FKP), a bifunctional enzyme isolated from Bacteroides fragilis 9343, which converts l-Fuc into GDP-L-Fuc via an L-Fuc-1-phosphate intermediate. Because L-Fuc and d-arabinose (D-Ara) are structurally similar, it is assumed that the biosynthesis of GDP-D-Ara in a recombinant Saccharomyces cerevisiae strain harboring the FKP gene can occur through a mechanism akin to that of GDP-L-Fuc via the salvage pathway. Thus, we reasoned that by exogenously supplying different monosaccharides structurally related to L-Fuc, it should be possible to produce the corresponding nucleotide sugars with this recombinant yeast strain, regardless of internal acquisition of nucleotide sugars through expression of additive enzymes in the de novo pathway."	""
 3	"asian"	"China"	"China"	"0.0"	"0.015625"	"0.0859375"	"128"	"5.44"	"Bioinformatics"	"Liu X, Su X, Wang F, Huang Z, Wang Q, Li Z, Zhang R, Wu L, Pan Y, Chen Y, Zhuang H, Chen G, Shi T, Zhang J"	"Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China."	"SUMMARY: ODORactor is an open access web server aimed at providing a platform for identifying odorant receptors (ORs) for small molecules and for browsing existing OR-ligand pairs. It enables the prediction of ORs from the molecular structures of arbitrary chemicals by integrating two individual functionalities: odorant verification and OR recognition. The prediction of the ORs for several odorants was experimentally validated in the study. In addition, ODORactor features a comprehensive repertoire of olfactory information that has been manually curated from literature. Therefore, ODORactor may provide an effective way to decipher olfactory coding and could be a useful server tool for both basic olfaction research in academia and for odorant discovery in industry. AVAILABILITY: Freely available at CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	""
 3	"asian"	"China"	"China"	"0.00420168067227"	"0.0126050420168"	"0.0378151260504"	"238"	"11.3333333333"	"PLoS One"	"Liu X, Wang JM"	"College of Pharmaceutical Sciences,Zhejiang University, Hangzhou, China."	"BACKGROUND AND AIMS: Iridoid glycosides (IG), the major active fraction of F. syringae leaves has been demonstrated to have strong anti-inflammatory properties to ulcerative colitis (UC) in our previous study. The aim of this study was to investigate whether IG modulates the inflammatory response in experimental colitis at the level of NF-kappaB signal pathway and epithelial cell apoptosis. METHODS: UC in rats was induced by administration with dextran sulfate sodium (DSS) in drinking water. The inflammatory damage was assessed by disease activity index (DAI), macroscopic findings, histology and myeloperoxidase (MPO) activity. The effect of IG on pro-inflammatory cytokines TNF-alpha, IL-8, COX-2 and regulatory peptide TGF-beta1 was measured. Epithelial cell apoptosis and the protein and mRNA expressions of Fas/FasL, Bcl-2/Bax, caspase-3, NF-kappaB p65, IkappaBalpha, p-IkappaBalpha and IKKbeta were detected by TUNEL method, immunohistochemistry, Western blotting and real-time quantitative PCR, respectively. RESULTS: IG significantly ameliorated macroscopic damage and histological changes, reduced the activity of MPO, and strongly inhibited epithelial cell apoptosis. Moreover, IG markedly depressed TNF-alpha, IL-8, COX-2 and TGF-beta1 levels in the colon tissues in a dose-dependent manner. Furthermore, IG significantly blocked of NF-kappaB signaling by inhibiting IkappaBalpha phosphorylation/degradation and IKKbeta activity, down-regulated the protein and mRNA expressions of Fas/FasL, Bax and caspase-3, and activated Bcl-2 in intestinal epithelial cells. CONCLUSIONS: These results demonstrated for the first time that IG possessed marked protective effects on experimental colitis through inhibition of epithelial cell apoptosis and blockade of NF-kappaB signal pathway."	""
+3	"asian"	"Singapore"	"Singapore"	"0.0207468879668"	"0.00829875518672"	"0.124481327801"	"241"	"12.7368421053"	"BMC Bioinformatics"	"Liu Y, Schmidt B, Maskell DL"	"School of Computer Engineering, Nanyang Technological University, Singapore."	"ABSTRACT: BACKGROUND: Next-generation sequencing technologies have given rise to the explosive increase in DNA sequencing throughput, and have promoted the recent development of de novo short read assemblers. However, existing assemblers require high execution times and a large amount of compute resources to assemble large genomes from quantities of short reads. RESULTS: We present PASHA, a parallelized short read assembler using de Bruijn graphs, which takes advantage of hybrid computing architectures consisting of both shared-memory multi-core CPUs and distributed-memory compute clusters to gain efficiency and scalability. Evaluation using three small-scale real paired-end datasets shows that PASHA is able to produce more contiguous high-quality assemblies in shorter time compared to three leading assemblers: Velvet, ABySS and SOAPdenovo. PASHAs scalability for large genome datasets is demonstrated with human genome assembly. Compared to ABySS, PASHA achieves competitive assembly quality with faster execution speed on the same compute resources, yielding an NG50 contig size of 503 with the longest correct contig size of 18,252, and an NG50 scaffold size of 2,294. Moreover, the human assembly is completed in about 21 hours with only modest compute resources. CONCLUSIONS: Developing parallel assemblers for large genomes has been garnering significant research efforts due to the explosive size growth of high-throughput short read datasets. By employing hybrid parallelism consisting of multi-threading on multi-core CPUs and message passing on compute clusters, PASHA is able to assemble the human genome with high quality and in reasonable time using modest compute resources."	""
+3	"asian"	"Taiwan"	"China"	"0.0082304526749"	"0.0082304526749"	"0.0905349794239"	"243"	"6.86486486486"	"Bioinformatics"	"Liu YC, Cheng CP, Tseng VS"	"Department of Computer Science and Information Engineering, and Institute of Medical Informatics, National Cheng Kung University, No.1, University Road, Tainan City 701, Taiwan, R.O.C."	"MOTIVATION: Association rule analysis methods are important techniques applied to gene expression data for finding expression relationships between genes. However, previous methods implicitly assume that all genes have similar importance, or they ignore the individual importance of each gene. The relation intensity between any two items has never been taken in to consideration. Therefore, we proposed a technique named REMMAR (RElational-based Multiple Minimum supports Association Rules) algorithm to tackle this problem. This method adjusts the minimum relation support (MRS) for each gene pair depending on the regulatory relation intensity to discover more important association rules with stronger biological meaning. RESULTS: In the actual case study of this research, REMMAR utilized the shortest distance between any two genes in the Saccharomyces cerevisiae gene regulatory network (GRN) as the relation intensity to discover the association rules from two Saccharomyces cerevisiae gene expression datasets. Under experimental evaluation, REMMAR can generate more rules with stronger relation intensity, and filter out rules without biological meaning in the protein-protein interaction network (PPIN). Furthermore, the proposed method has a higher precision (100%) than the precision of reference Apriori method (86%) for the discovered rules use a literature survey. Therefore, the proposed REMMAR algorithm can discover stronger association rules in biological relationships dissimilated by traditional methods to assist biologists in complicated genetic exploration. AVAILABILITY: The source code in Java and other materials used in this study as available under CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available online from Bioinformatics."	""