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Giovanni Marco Dall'Olio  committed 62a8d77

DATA: removed a few "unknown" nationalities

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File results/freqs_by_nationality_reviewed.csv

 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21935394"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21106560"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21390273"
+"unk"	"asian"	"unknown"	"unknown"	"0.0234899328859"	"0.00335570469799"	"0.0536912751678"	"298"	"14.2380952381"	"PLoS One"	"Barakat A, Ihazmad H, Benkaroum S, Cherkaoui I, Benmamoun A, Youbi M, El Aouad R"	"Centre National de Reference de la Grippe, Institut National dHygiene, Ministere de la Sante, Rabat, Morocco."	"BACKGROUND: There is limited information about the epidemiology of influenza in Africa. We describe the epidemiology and seasonality of influenza in Morocco from 1996 to 2009 with particular emphasis on the 2007-2008 and 2008-2009 influenza seasons. Successes and challenges of the enhanced surveillance system introduced in 2007 are also discussed. METHODS: Virologic sentinel surveillance for influenza virus was initiated in Morocco in 1996 using a network of private practitioners that collected oro-pharyngeal and naso-pharyngeal swabs from outpatients presenting with influenza-like-illness (ILI). The surveillance network expanded over the years to include inpatients presenting with severe acute respiratory illness (SARI) at hospitals and syndromic surveillance for ILI and acute respiratory infection (ARI). Respiratory samples and structured questionnaires were collected from eligible patients, and samples were tested by immunofluorescence assays and by viral isolation for influenza viruses. RESULTS: We obtained a total of 6465 respiratory specimens during 1996 to 2009, of which, 3102 were collected during 2007-2009. Of those, 2249 (72%) were from patients with ILI, and 853 (27%) were from patients with SARI. Among the 3,102 patients, 98 (3%) had laboratory-confirmed influenza, of whom, 85 (87%) had ILI and 13 (13%) had SARI. Among ILI patients, the highest proportion of laboratory-confirmed influenza occurred in children less than 5 years of age (3/169; 2% during 2007-2008 and 23/271; 9% during 2008-2009) and patients 25-59 years of age (8/440; 2% during 2007-2009 and 21/483; 4% during 2008-2009). All SARI patients with influenza were less than 14 years of age. During all surveillance years, influenza virus circulation was seasonal with peak circulation during the winter months of October through April. CONCLUSION: Influenza results in both mild and severe respiratory infections in Morocco, and accounted for a large proportion of all hospitalizations for severe respiratory illness among children 5 years of age and younger."	"http://www.ncbi.nlm.nih.gov/pubmed/21931764"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21605466"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21935379"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21680871"
 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: ruijiang@tsinghua.edu.cn."	"http://www.ncbi.nlm.nih.gov/pubmed/21685067"
 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. zjchen59@yahoo.com"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21151128"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21546357"
+"unk"	"asian"	"unknown"	"unknown"	"0.0137614678899"	"0.045871559633"	"0.0596330275229"	"218"	"6.78787878788"	"BMC Bioinformatics"	"Cheng F, Zhang X, Zhang Y, Li C, Zeng C"		"ABSTRACT: BACKGROUND: Generally, SNPs are abundant in the genome; however, they display low power in linkage analysis because of their limited heterozygosity. Haplotype markers, on the other hand, which are composed of many SNPs, greatly increase heterozygosity and have superiority in linkage statistics. RESULTS: Here we developed Haplo2Ped to automatically transform SNP data into haplotype markers and then to compute the logarithm (base 10) of odds (LOD) scores of regional haplotypes that are homozygous within the disease co-segregation haploid group. The results are reported as a hypertext file and a 3D figure to help users to obtain the candidate linkage regions. The hypertext file contains parameters of the disease linked regions, candidate genes, and their links to public databases. The 3D figure clearly displays the linkage signals in each chromosome. We tested Haplo2Ped in a simulated SNP dataset and also applied it to data from a real study. It successfully and accurately located the causative genomic regions. Comparison of Haplo2Ped with other existing software for linkage analysis further indicated the high effectiveness of this software. CONCLUSIONS: Haplo2Ped uses haplotype fragments as mapping markers in whole genome linkage analysis. The advantages of Haplo2Ped over other existing software include straightforward output files, increased accuracy and superior ability to deal with pedigrees showing incomplete penetrance. Haplo2Ped is freely available at: http://bighapmap.big.ac.cn/software.html."	"http://www.ncbi.nlm.nih.gov/pubmed/21854652"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21935358"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21931723"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21828143"
 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: hongjie@iis.sinica.edu.tw SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21685052"
 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. zhimdai@gmail.com"	"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: zhimdai@gmail.com; issdxh@mail.sysu.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21551148"
 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: http://www.atgc-montpellier.fr/ReplacementMatrix/ CONTACT: olivier.gascuel@lirmm.fr."	"http://www.ncbi.nlm.nih.gov/pubmed/21791535"
+"unk"	"asian"	"unknown"	"unknown"	"0.0253807106599"	"0.0304568527919"	"0.0558375634518"	"197"	"6.0"	"Bioinformatics"	"Dao P, Wang K, Collins C, Ester M, Lapuk A, Sahinalp SC"	"School of Computing Science, Simon Fraser University."	"MOTIVATION: Molecular profiles of tumour samples have been widely and successfully used for classification problems. A number of algorithms have been proposed to predict classes of tumor samples based on expression profiles with relatively high performance. However, prediction of response to cancer treatment has proved to be more challenging and novel approaches with improved generalizability are still highly needed. Recent studies have clearly demonstrated the advantages of integrating protein-protein interaction (PPI) data with gene expression profiles for the development of subnetwork markers in classification problems. RESULTS: We describe a novel network-based classification algorithm (OptDis) using color coding technique to identify optimally discriminative subnetwork markers. Focusing on PPI networks, we apply our algorithm to drug response studies: we evaluate our algorithm using published cohorts of breast cancer patients treated with combination chemotherapy. We show that our OptDis method improves over previously published subnetwork methods and provides better and more stable performance compared with other subnetwork and single gene methods. We also show that our subnetwork method produces predictive markers that are more reproducible across independent cohorts and offer valuable insight into biological processes underlying response to therapy. AVAILABILITY: The implementation is available at: http://www.cs.sfu.ca/~pdao/personal/OptDis.html CONTACT: cenk@cs.sfu.ca; alapuk@prostatecentre.com; ccollins@prostatecentre.com."	"http://www.ncbi.nlm.nih.gov/pubmed/21685072"
 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. xutaodeng@gmail.com"	"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 http://seqgene.sourceforge.net."	"http://www.ncbi.nlm.nih.gov/pubmed/21714929"
 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: http://admis.fudan.edu.cn/projects/miRFam.htm."	"http://www.ncbi.nlm.nih.gov/pubmed/21619662"
 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: http://bioinfo3d.cs.tau.ac.il/PepCrawler/ CONTACT: eladdons@tau.ac.il, wolfson@tau.ac.il."	"http://www.ncbi.nlm.nih.gov/pubmed/21880702"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21113154"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21186352"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21612664"
+"unk"	"asian"	"unknown"	"unknown"	"0.0034965034965"	"0.0384615384615"	"0.101398601399"	"286"	"10.5925925926"	"BMC Bioinformatics"	"Gao S, Wang X"		"ABSTRACT: BACKGROUND: Bayesian Network (BN) is a powerful approach to reconstructing genetic regulatory networks from gene expression data. However, expression data by itself suffers from high noise and lack of power. Incorporating prior biological knowledge can improve the performance. As each type of prior knowledge on its own may be incomplete or limited by quality issues, integrating multiple sources of prior knowledge to utilize their consensus is desirable. RESULTS: We introduce a new method to incorporate the quantitative information from multiple sources of prior knowledge. It first uses the Naive Bayesian classifier to assess the likelihood of functional linkage between gene pairs based on prior knowledge. In this study we included co-citation in PubMed and schematic similarity in Gene Ontology annotation. A candidate network edge reservoir is then created in which the copy number of each edge is proportional to the estimated likelihood of linkage between the two corresponding genes. In network simulation the Markov Chain Monte Carlo sampling algorithm is adopted, and samples from this reservoir at each iteration to generate new candidate networks. We evaluated the new algorithm using both simulated and real gene expression data including that from a yeast cell cycle and a mouse pancreas development/growth study. Incorporating prior knowledge led to a ~2 fold increase in the number of known transcription regulations recovered, without significant change in false positive rate. In contrast, without the prior knowledge BN modeling is not always better than a random selection, demonstrating the necessity in network modeling to supplement the gene expression data with additional information. CONCLUSION: our new development provides a statistical means to utilize the quantitative information in prior biological knowledge in the BN modeling of gene expression data, which significantly improves the performance."	"http://www.ncbi.nlm.nih.gov/pubmed/21884587"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21651792"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21399633"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21918513"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21841165"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/20972439"
 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. ythuang@cs.ccu.edu.tw"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21605463"
+"unk"	"asian"	"unknown"	"unknown"	"0.00970873786408"	"0.0242718446602"	"0.0436893203883"	"206"	"22.8888888889"	"PLoS One"	"Hussain AR, Uddin S, Bu R, Khan OS, Ahmed SO, Ahmed M, Al-Kuraya KS"	"Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia."	"BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4, 5-trihydroxystilbene), a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL) cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS). Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway."	"http://www.ncbi.nlm.nih.gov/pubmed/21931821"
 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: http://compbio.cs.umn.edu/dgsa_rcNet CONTACT: kuang@cs.umn.edu."	"http://www.ncbi.nlm.nih.gov/pubmed/21824970"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21600798"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21115605"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21738461"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21470969"
 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 http://csovalidator.csml.org. CONTACT: masao@hgc.jp."	"http://www.ncbi.nlm.nih.gov/pubmed/21743062"
+"unk"	"asian"	"unknown"	"unknown"	"0.01953125"	"0.0078125"	"0.0703125"	"256"	"7.87878787879"	"PLoS One"	"Jewkes R, Sikweyiya Y, Morrell R, Dunkle K"	"School of Public Health, University of the Witwatersrand, Johannesburg, South Africa."	"OBJECTIVE: To investigate the associations between intimate partner violence, rape and HIV among South African men. DESIGN: Cross-sectional study involving a randomly-selected sample of men. METHODS: We tested hypotheses that perpetration of physical intimate partner violence and rape were associated with prevalent HIV infections in a cross-sectional household study of 1229 South African men aged 18-49. Violence perpetration was elicited in response to a questionnaire administered using an Audio-enhanced Personal Digital Assistant and blood samples were tested for HIV. A multivariable logistic regression model was built to identify factors associated with HIV. RESULTS: 18.3% of men had HIV. 29.6% (358/1211) of men disclosed rape perpetration, 5.2% (63/1208) rape in the past year and 30.7% (362/1180) of had been physically violent towards an intimate partner more than once. Overall rape perpetration was not associated with HIV. The model of factors associated with having HIV showed men under 25 years who had been physically violent towards partners were more likely to have HIV than men under 25 who had not (aOR 2.08 95% CI 1.07-4.06, p = 0.03). We failed to detect any association in older men. CONCLUSIONS: Perpetration of physical IPV is associated with HIV sero-prevalence in young men, after adjusting for other risk factors. This contributes to our understanding of why women who experience violence have a higher HIV prevalence. Rape perpetration was not associated, but the HIV prevalence among men who had raped was very high. HIV prevention in young men must seek to change ideals of masculinity in which male partner violence is rooted."	"http://www.ncbi.nlm.nih.gov/pubmed/21935392"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21558155"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21935370"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21256056"
 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. mohammadmahdi.keramati@ens.fr"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21637741"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21832283"
 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: hahny@cau.ac.kr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21775310"
+"unk"	"asian"	"unknown"	"unknown"	"0.0297619047619"	"0.0238095238095"	"0.0654761904762"	"168"	"8.2380952381"	"BMC Bioinformatics"	"Kim H, Bi Y, Pal S, Gupta R, Davuluri RV"		"ABSTRACT: BACKGROUND: mRNA-Seq technology has revolutionized the field of transcriptomics for identification and quantification of gene transcripts not only at gene level but also at isoform level. Estimating the expression levels of transcript isoforms from mRNA-Seq data is a challenging problem due to the presence of constitutive exons. RESULTS: We propose a novel algorithm (IsoformEx) that employs weighted non-negative least squares estimation method to estimate the expression levels of transcript isoforms. Validations based on in silico simulation of mRNA-Seq and qRT-PCR experiments with real mRNA-Seq data showed that IsoformEx could accurately estimate transcript expression levels. In comparisons with published methods, the transcript expression levels estimated by IsoformEx showed higher correlation with known transcript expression levels from simulated mRNA-Seq data, and higher agreement with qRT-PCR measurements of specific transcripts for real mRNA-Seq data. CONCLUSIONS: IsoformEx is a fast and accurate algorithm to estimate transcript expression levels and gene expression levels, which takes into account short exons and alternative exons with a weighting scheme. The software is available at http://bioinformatics.wistar.upenn.edu/isoformex."	"http://www.ncbi.nlm.nih.gov/pubmed/21794104"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21935453"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21909109"
 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 http://www.ncrna.org/software/fdur/ CONTACT: kiryu-h@k.u-tokyo.ac.jp SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21757463"
 3	"asian"	"Japan"	"Japan"	"0.00357142857143"	"0.0142857142857"	"0.0678571428571"	"280"	"12.1739130435"	"PLoS One"	"Sakai D, Kii I, Nakagawa K, Matsumoto HN, Takahashi M, Yoshida S, Hosoya T, Takakuda K, Kudo A"	"Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan."	"BACKGROUND: The adaptive nature of bone formation under mechanical loading is well known; however, the molecular and cellular mechanisms in vivo of mechanical loading in bone formation are not fully understood. To investigate both mechanisms at the early response against mechanotransduction in vivo, we employed a noninvasive 3-point bone bending method for mouse tibiae. It is important to investigate periosteal woven bone formation to elucidate the adaptive nature against mechanical stress. We hypothesize that cell morphological alteration at the early stage of mechanical loading is essential for bone formation in vivo. PRINCIPAL FINDINGS: We found the significant bone formation on the bone surface subjected to change of the stress toward compression by this method. The histological analysis revealed the proliferation of periosteal cells, and we successively observed the appearance of ALP-positive osteoblasts and increase of mature BMP-2, resulting in woven bone formation in the hypertrophic area. To investigate the mechanism underlying the response to mechanical loading at the molecular level, we established an in-situ immunofluorescence imaging method to visualize molecules in these periosteal cells, and with it examined their cytoskeletal actin and nuclei and the extracellular matrix proteins produced by them. The results demonstrated that the actin cytoskeleton of the periosteal cells was disorganized, and the shapes of their nuclei were drastically changed, under the mechanical loading. Moreover, the disorganized actin cytoskeleton was reorganized after release from the load. Further, inhibition of onset of the actin remodeling blocked the proliferation of the periosteal cells. CONCLUSIONS: These results suggest that the structural change in cell shape via disorganization and remodeling of the actin cytoskeleton played an important role in the mechanical loading-dependent proliferation of cells in the periosteum during bone formation."	"http://www.ncbi.nlm.nih.gov/pubmed/21935480"
 3	"asian"	"Japan"	"Japan"	"0.020202020202"	"0.020202020202"	"0.0707070707071"	"198"	"8.60869565217"	"Blood"	"Sakakibara K, Saito N, Sato T, Suzuki A, Hasegawa Y, Friedman JM, Kufe DW, Vonhoff DD, Iwami T, Kawabe T"	"CanBas Co., Ltd., Numazu, Japan;"	"CRM1 plays an important role in the nuclear export of cargo proteins bearing nuclear exporting signal (NES) sequences. Leptomycin B (LMB), a well-known CRM1 inhibitor, possesses strong anti-tumor properties. However, its toxicity prevents it from being clinically useful. In this study, we demonstrate that a novel compound, CBS9106, inhibits CRM1-dependent nuclear export, causing arrest of the cell cycle and inducing apoptosis in a time- and dose-dependent manner for a broad-spectrum of cancer cells, including multiple myeloma (MM) cells. CBS9106 reduces CRM1 protein levels significantly without affecting CRM1 mRNA expression. This effect could be reversed by adding bortezomib or LMB. Moreover, CBS9106-biotin allows capture of CRM1 protein by streptavidin beads in competitive manner with LMB and vice versa. Mass spectrometric analysis demonstrates that CBS9106 reacts with a synthetic CRM1 peptide that contains Cys528, but not with a Cys528 mutant peptide. Oral administration of CBS9106 significantly suppresses tumor growth and prolongs survival in mice bearing tumor xenograft without a significant loss in body weight. A reduced level of CRM1 protein is also observed in tumor xenografts isolated from mice treated with CBS9106. Taken together, these results indicate that CBS9106 is a novel reversible CRM1 inhibitor and a promising clinical candidate."	"http://www.ncbi.nlm.nih.gov/pubmed/21841164"
 1	"asian"	"Israel"	"Israel"	"0.0080971659919"	"0.00404858299595"	"0.0323886639676"	"247"	"13.0526315789"	"PLoS One"	"Sarfstein R, Bruchim I, Fishman A, Werner H"	"Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel."	"A correlation between components of the insulin-like growth factor (IGF) system and endometrial cancer risk has been shown in recent studies. The antitumor action of vorinostat, a histone deacetylase inhibitor, involves changes in the expression of specific genes via acetylation of histones and transcription factors. The aim of this study was to establish whether vorinostat can modify the expression of specific genes related to the IGF-I receptor (IGF-IR) signaling pathway and revert the transformed phenotype. Human endometrioid (Type I, Ishikawa) and uterine serous papillary (Type II, USPC-2) endometrial cancer cell lines were treated with vorinostat in the presence or absence of IGF-I. Vorinostat increased IGF-IR phosphorylation, produced acetylation of histone H3, up-regulated pTEN and p21 expression, and reduced p53 and cyclin D1 levels in Ishikawa cells. Vorinostat up-regulated IGF-IR and p21 expression, produced acetylation of histone H3, and down-regulated the expression of total AKT, pTEN and cyclin D1 in USPC-2 cells. Of interest, IGF-IR activation was associated with a major elevation in IGF-IR promoter activity. In addition, vorinostat treatment induced apoptosis in both cell lines and abolished the anti-apoptotic activity of IGF-I both in the absence or presence of a humanized monoclonal IGF-IR antibody, MK-0646. Finally, vorinostat treatment led to a significant decrease in proliferation and colony forming capability in both cell lines. In summary, our studies demonstrate that vorinostat exhibits a potent apoptotic and anti-proliferative effect in both Type I and II endometrial cancer cells, thus suggesting that endometrial cancer may be therapeutically targeted by vorinostat."	"http://www.ncbi.nlm.nih.gov/pubmed/21931726"
+2	"asian"	"Yale, USA."	"USA"	"0.0"	"0.0"	"0.027027027027"	"37"	"5.28571428571"	"Immunity"	"Sasai M, Iwasaki A"	"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA."	"Unc93B1, a multitransmembrane ER-resident protein, controls intracellular trafficking of endosomal Toll-like receptors. In this issue of Immunity, Fukui et al. (2011) revealed that Unc93B1 regulates differential transport of TLR7 and TLR9 into signaling endosomes to prevent autoimmunity."	"http://www.ncbi.nlm.nih.gov/pubmed/21777792"
 3	"asian"	"Japan"	"Japan"	"0.00294985250737"	"0.0294985250737"	"0.0678466076696"	"339"	"12.5555555556"	"Molecular Biology and Evolution"	"Sato A, Tichy H, Grant PR, Grant BR, Sato T, OhUigin C"	"Department of Anatomy, School of Dental Medicine, Tsurumi University, Yokohama, Japan. sato-ake@tsurumi-u.ac.jp"	"The study describes >400 major histocompatibility complex (MHC) class II B exon 2 and 114 intron 2 sequences of 36 passerine bird species, 13 of which belong to the group of Darwins finches (DFs) and the remaining 23 to close or more distant relatives of DFs in Central and South America. The data set is analyzed by a combination of judiciously selected statistical methods. The analysis reveals that reliable information concerning MHC organization, including the assignment of sequences to loci, and evolution, as well as the process of species divergence, can be obtained in the absence of genomic sequence data, if the analysis is taken several steps beyond the standard phylogenetic tree construction approach. The main findings of the present study are these: The MHC class II B region of the passerine birds is as elaborate in its organization, divergence, and genetic diversity as the MHC of the eutherian mammals, specifically the primates. Hence, the reported simplicity of the fowl MHC is an oddity. With the help of appropriate markers, the divergence of the MHC genes can be traced deep in the phylogeny of the bird taxa. Transspecies polymorphism is rampant at many of the bird MHC loci. In this respect, the DFs behave as if they were a single, genetically undifferentiated population. There is thus far no indication of alleles that could be considered species, genus, or even DF group specific. The implication of these findings is that DFs are in the midst of adaptive radiations, in which morphological differentiation into species is running ahead of genetic differentiation in genetic systems such as the MHC or the mitochondrial DNA. The radiations are so young that there has not been enough time to sort out polymorphisms at most of the loci among the morphologically differentiating species. These findings parallel those on Lake Victoria haplochromine fishes. Several of the DF MHC allelic lineages can be traced back to the MHC genes of the species Tiaris obscura, which we identified previously as the closest extant relative of DFs in continental America."	"http://www.ncbi.nlm.nih.gov/pubmed/21273633"
 3	"asian"	"Japan"	"Japan"	"0.0182648401826"	"0.0182648401826"	"0.0867579908676"	"219"	"6.6"	"Bioinformatics"	"Sato K, Kato Y, Hamada M, Akutsu T, Asai K"	"Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan. satoken@k.u-tokyo.ac.jp"	"MOTIVATION: Pseudoknots found in secondary structures of a number of functional RNAs play various roles in biological processes. Recent methods for predicting RNA secondary structures cover certain classes of pseudoknotted structures, but only a few of them achieve satisfying predictions in terms of both speed and accuracy. RESULTS: We propose IPknot, a novel computational method for predicting RNA secondary structures with pseudoknots based on maximizing expected accuracy of a predicted structure. IPknot decomposes a pseudoknotted structure into a set of pseudoknot-free substructures and approximates a base-pairing probability distribution that considers pseudoknots, leading to the capability of modeling a wide class of pseudoknots and running quite fast. In addition, we propose a heuristic algorithm for refining base-paring probabilities to improve the prediction accuracy of IPknot. The problem of maximizing expected accuracy is solved by using integer programming with threshold cut. We also extend IPknot so that it can predict the consensus secondary structure with pseudoknots when a multiple sequence alignment is given. IPknot is validated through extensive experiments on various datasets, showing that IPknot achieves better prediction accuracy and faster running time as compared with several competitive prediction methods. AVAILABILITY: The program of IPknot is available at http://www.ncrna.org/software/ipknot/. IPknot is also available as a web server at http://rna.naist.jp/ipknot/. CONTACT: satoken@k.u-tokyo.ac.jp; ykato@is.naist.jp SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21685106"
 3	"asian"	"Israel"	"Israel"	"0.00711743772242"	"0.0320284697509"	"0.0747330960854"	"281"	"6.02040816327"	"Bioinformatics"	"Schweiger R, Linial M, Linial N"	"School of Computer Science and Engineering, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences and The Sudarsky Center for Computational Biology, The Hebrew University, Jerusalem, 91904 Israel. regevs01@cs.huji.ac.il"	"MOTIVATION: Much of the large-scale molecular data from living cells can be represented in terms of networks. Such networks occupy a central position in cellular systems biology. In the protein-protein interaction (PPI) network, nodes represent proteins and edges represent connections between them, based on experimental evidence. As PPI networks are rich and complex, a mathematical model is sought to capture their properties and shed light on PPI evolution. The mathematical literature contains various generative models of random graphs. It is a major, still largely open question, which of these models (if any) can properly reproduce various biologically interesting networks. Here, we consider this problem where the graph at hand is the PPI network of Saccharomyces cerevisiae. We are trying to distinguishing between a model family which performs a process of copying neighbors, represented by the duplication-divergence (DD) model, and models which do not copy neighbors, with the Barabasi-Albert (BA) preferential attachment model as a leading example. RESULTS: The observed property of the network is the distribution of maximal bicliques in the graph. This is a novel criterion to distinguish between models in this area. It is particularly appropriate for this purpose, since it reflects the graphs growth pattern under either model. This test clearly favors the DD model. In particular, for the BA model, the vast majority (92.9%) of the bicliques with both sides >/=4 must be already embedded in the models seed graph, whereas the corresponding figure for the DD model is only 5.1%. Our results, based on the biclique perspective, conclusively show that a naive unmodified DD model can capture a key aspect of PPI networks. CONTACT: regevs01@cs.huji.ac.il; michall@cc.huji.ac.il; nati@cs.huji.ac.il SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21685063"
 3	"asian"	"China"	"China"	"0.00546448087432"	"0.0437158469945"	"0.0874316939891"	"183"	"9.68421052632"	"BMC Bioinformatics"	"Stacklies W, Seifert C, Graeter F"	"CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China."	"BACKGROUND: The way mechanical stress is distributed inside and propagated by proteins and other biopolymers largely defines their function. Yet, determining the network of interactions propagating internal strain remains a challenge for both, experiment and theory. Based on molecular dynamics simulations, we developed force distribution analysis (FDA), a method that allows visualizing strain propagation in macromolecules. RESULTS: To be immediately applicable to a wide range of systems, FDA was implemented as an extension to Gromacs, a commonly used package for molecular simulations. The FDA code comes with an easy-to-use command line interface and can directly be applied to every system built using Gromacs. We provide an additional R-package providing functions for advanced statistical analysis and presentation of the FDA data. CONCLUSIONS: Using FDA, we were able to explain the origin of mechanical robustness in immunoglobulin domains and silk fibers. By elucidating propagation of internal strain upon ligand binding, we previously also successfully revealed the functionality of a stiff allosteric protein. FDA thus has the potential to be a valuable tool in the investigation and rational design of mechanical properties in proteins and nano-materials."	"http://www.ncbi.nlm.nih.gov/pubmed/21501475"
 3	"asian"	"Taiwan"	"China"	"0.0117647058824"	"0.0117647058824"	"0.0823529411765"	"85"	"3.37931034483"	"Bioinformatics"	"Su CH, Hsu MT, Wang TY, Chiang S, Cheng JH, Weng FC, Kao CY, Wang D, Tsai HK"	"Institute of Information Science, Academia Sinica, Taipei 115, Taiwan."	"SUMMARY: MetaABC is a metagenomic platform that integrates several binning tools coupled with methods for removing artifacts, analyzing unassigned reads and controlling sampling biases. It allows users to arrive at a better interpretation via series of distinct combinations of analysis tools. After execution, MetaABC provides outputs in various visual formats such as tables, pie and bar charts as well as clustering result diagrams. AVAILABILITY: MetaABC source code and documentation are available at http://bits2.iis.sinica.edu.tw/MetaABC/ CONTACT: dywang@gate.sinica.edu.tw; hktsai@iis.sinica.edu.tw SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21697124"
 3	"asian"	"China"	"China"	"0.00334448160535"	"0.0234113712375"	"0.0535117056856"	"299"	"13.0"	"PLoS One"	"Su X, Chu Y, Li H, Hou Y, Zhang B, Huang Q, Hu Z, Huang R, Tian Y"	"Key Laboratory of Tree Breeding and Cultivation, State Forestry Administration, Research Institute of Forestry, Chinese Academy of Forestry, Beijing, China."	"Commercial and non-commercial plants face a variety of environmental stressors that often cannot be controlled. In this study, transgenic hybrid poplar (Populus x euramericana Guariento) harboring five effector genes (vgb, SacB, JERF36, BtCry3A and OC-I) were subjected to drought, salinity, waterlogging and insect stressors in greenhouse or laboratory conditions. Field trials were also conducted to investigate long-term effects of transgenic trees on insects and salt tolerance in the transformants. In greenhouse studies, two transgenic lines D5-20 and D5-21 showed improved growth, as evidenced by greater height and basal diameter increments and total biomass relative to the control plants after drought or salt stress treatments. The improved tolerance to drought and salt was primarily attributed to greater instantaneous water use efficiency (WUEi) in the transgenic trees. The chlorophyll concentrations tended to be higher in the transgenic lines under drought or saline conditions. Transformed trees in drought conditions accumulated more fructan and proline and had increased Fv/Fm ratios (maximum quantum yield of photosystem II) under waterlogging stress. Insect-feeding assays in the laboratory revealed a higher total mortality rate and lower exuviation index of leaf beetle [Plagiodera versicolora (Laicharting)] larvae fed with D5-21 leaves, suggesting enhanced insect resistance in the transgenic poplar. In field trials, the dominance of targeted insects on 2-year-old D5-21 transgenic trees was substantially lower than that of the controls, indicating enhanced resistance to Coleoptera. The average height and DBH (diameter at breast height) of 2.5-year-old transgenic trees growing in naturally saline soil were 3.80% and 4.12% greater than those of the control trees, but these increases were not significant. These results suggested that multiple stress-resistance properties in important crop tree species could be simultaneously improved, although additional research is needed to fully understand the relationships between the altered phenotypes and the function of each transgene in multigene transformants."	"http://www.ncbi.nlm.nih.gov/pubmed/21931776"
+"unk"	"asian"	"unknown"	"unknown"	"0.00657894736842"	"0.0197368421053"	"0.0855263157895"	"152"	"13.8181818182"	"Molecular Biology and Evolution"	"Subramanian S"		"Previous studies on human mitochondrial genomes showed that the ratio of intra-specific diversities at nonsynonymous-to-synonymous positions was two to ten times higher than the ratio of interspecific divergences at these positions, suggesting an excess of slightly deleterious nonsynonymous polymorphisms. However, such an overabundance of nonsynonymous single nucleotide polymorphisms (SNPs) was not found in human nuclear genomes. Here, genome-wide estimates using >14,000 human-chimp nuclear genes and 1 million SNPs from four human genomes showed a significant proportion of deleterious nonsynonymous SNPs ( approximately  15%). Importantly, this study reveals a negative correlation between the magnitude of selection pressure and the proportion of deleterious SNPs on human genes. The proportion of deleterious amino acid replacement polymorphisms is 3.5 times higher in genes under high purifying selection compared with that in less constrained genes (28% vs. 8%). These results are explained by differences in the extent of contribution of mildly deleterious mutations to diversity and substitution."	"http://www.ncbi.nlm.nih.gov/pubmed/20974690"
 3	"asian"	"Kyoto, Japan, kyoto"	"Japan"	"0.0225225225225"	"0.0225225225225"	"0.117117117117"	"222"	"17.0769230769"	"Molecular Biology and Evolution"	"Sugawara T, Go Y, Udono T, Morimura N, Tomonaga M, Hirai H, Imai H"	"Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan. sugawarat@pri.kyoto-u.ac.jp"	"In mammals, bitter taste is mediated by T2R genes, which belong to the large family of seven transmembrane G protein-coupled receptors. Because T2Rs are directly involved in the interaction between mammals and their dietary sources, it is likely that these genes evolved to reflect species specific diets during mammalian evolution. Here, we investigated the sequences of all 28 putative functional chimpanzee T2R genes (cT2Rs) in 46 western chimpanzees to compare the intraspecies variations in chimpanzees to those already known for all 25 human functional T2R genes (hT2Rs). The numbers of functional genes varied among individuals in western chimpanzees, and most chimpanzees had two or three more functional genes than humans. Similarly to hT2Rs, cT2Rs showed high nucleotide diversity along with a large number of amino acid substitutions. Comparison of the nucleotide substitution patterns in cT2Rs with those in five cT2R pseudogenes and 14 autosomal intergenic noncoding regions among the same individuals revealed that the evolution of cT2R genes was almost identical to that of putative neutral regions with slight but significantly positive Tajimas D values, suggesting that selective constraint on these genes was relaxed with weak balancing selection. These trends have resulted in the occurrence of various divergent alleles of T2Rs within the western chimpanzee populations and in heterozygous individuals who might have the ability to taste a broader range of substances."	"http://www.ncbi.nlm.nih.gov/pubmed/20961961"
 3	"asian"	"Japan"	"Japan"	"0.00529100529101"	"0.047619047619"	"0.116402116402"	"189"	"12.6666666667"	"Molecular Biology and Evolution"	"Sugino RP, Innan H"	"Graduate University for Advanced Studies, Hayama, Kanagawa 240-0193, Japan."	"A genome must locate its coding genes on the chromosomes in a meaningful manner with help of natural selection, but the mechanism of gene order evolution is poorly understood. To explore the role of selection in shaping the current order of coding genes and their cis-regulatory elements, a comparative genomic approach was applied to the bakers yeast Saccharomyces cerevisiae and its close relatives. S. cerevisiae have experienced a whole genome duplication followed by an extensive re-organization process of gene order, during which a number of new adjacent gene pairs appeared. We found that the proportion of new adjacent gene pairs in divergent orientation is significantly reduced, suggesting that such new divergent gene pairs may be disfavored most likely because their co-regulation may be deleterious. It is also found such new divergent gene pairs have particularly long intergenic regions. These observations suggest that selection specifically worked against deletions in intergenic regions of new divergent gene pairs, perhaps because they should be physically kept away so that they are not co-regulated. It is indicated that gene regulation would be one of the major factors to determine the order of coding genes."	"http://www.ncbi.nlm.nih.gov/pubmed/21546358"
 3	"asian"	"Kyoto, Kyoto, Japan"	"Japan"	"0.0"	"0.0"	"0.0"	"42"	"6.0"	"Immunity"	"Sugiyama T, Nagasawa T"	"Department of Immunobiology and Hematology, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan."	"The roles of hematopoietic stem and/or progenitor cell niches during infection remain unclear. In this issue of Immunity, Shi et al. (2011) reveal that these niches upregulate MCP1 chemokine expression, inducing emigration of bone marrow monocytes into the circulation via the endothelium."	"http://www.ncbi.nlm.nih.gov/pubmed/21511181"
 3	"asian"	"China"	"China"	"0.00444444444444"	"0.0177777777778"	"0.08"	"225"	"15.0"	"PLoS One"	"Sun J, Fu F, Gu W, Yan R, Zhang G, Shen Z, Zhou Y, Wang H, Shen B, Zhang X"	"Suzhou Health Technology College, Suzhou, China."	"B7-H3, a recently identified B7 family member, has different isoforms in human and mouse. Mouse B7-H3 gene has only one isoform (2IgB7-H3) with two Ig-like domains, whereas human B7-H3 has two isoforms (2IgB7-H3 and 4IgB7-H3). In this study a systematic genomic survey across various species from teleost fishes to mammals revealed that 4IgB7-H3 isoform also appeared in pigs, guinea pigs, cows, dogs, African elephants, pandas, megabats and higher primate animals, which resulted from tandem exon duplication. Further sequence analysis indicated that this duplication generated a new conserved region in the first IgC domain, which might disable 4IgB7-H3 from releasing soluble form, while 2IgB7-H3 presented both membrane and soluble forms. Through three-dimensional (3D) structure modeling and fusion-protein binding assays, we discovered that the duplicated isoform had a different structure and might bind to another potential receptor on activated T cells. In T cell proliferation assay, human 2IgB7-H3 (h2IgB7-H3) and mouse B7-H3 (mB7-H3) both increased T cell proliferation and IL-2, IFN-gamma production, whereas human 4IgB7-H3 (h4IgB7-H3) reduced cytokine production and T cell proliferation compared to control. Furthermore, both h2IgB7-H3 and mB7-H3 upregulated the function of lipopolysacharide (LPS)-activated monocyte in vitro. Taken together, our data implied that during the evolution of vertebrates, B7-H3 exon duplication contributed to the generation of a new 4IgB7-H3 isoform in many mammalian species, which have carried out distinct functions in the immune responses."	"http://www.ncbi.nlm.nih.gov/pubmed/21931843"
 3	"asian"	"China"	"China"	"0.0315789473684"	"0.0105263157895"	"0.0736842105263"	"190"	"14.6923076923"	"Nature Genetics"	"Sun LD, Cheng H, Wang ZX, Zhang AP, Wang PG, Xu JH, Zhu QX, Zhou HS, Ellinghaus E, Zhang FR, Pu XM, Yang XQ, Zhang JZ, Xu AE, Wu RN, Xu LM, Peng L, Helms CA, Ren YQ, Zhang C, Zhang SM, Nair RP, Wang HY, Lin GS, Stuart PE, Fan X, Chen G, Tejasvi T, Li P, Zhu J, Li ZM, Ge HM, Weichenthal M, Ye WZ, Zhang C, Shen SK, Yang BQ, Sun YY, Li SS, Lin Y, Jiang JH, Li CT, Chen RX, Cheng J, Jiang X, Zhang P, Song WM, Tang J, Zhang HQ, Sun L, Cui J, Zhang LJ, Tang B, Huang F, Qin Q, Pei XP, Zhou AM, Shao LM, Liu JL, Zhang FY, Du WD, Franke A, Bowcock AM, Elder JT, Liu JJ, Yang S, Zhang XJ"	"Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China."	"We extended our previous genome-wide association study for psoriasis with a multistage replication study including 8,312 individuals with psoriasis (cases) and 12,919 controls from China as well as 3,293 cases and 4,188 controls from Germany and the United States and 254 nuclear families from the United States. We identified six new susceptibility loci associated with psoriasis in the Chinese study containing the candidate genes ERAP1, PTTG1, CSMD1, GJB2, SERPINB8 and ZNF816A (combined P < 5 x 10) and replicated one locus, 5q33.1 (TNIP1-ANXA6), previously reported (combined P = 3.8 x 10(2)(1)) in the European studies. Two of these loci showed evidence for association in the German study at ZNF816A and GJB2 with P = 3.6 x 10(3) and P = 7.9 x 10(3), respectively. ERAP1 and ZNF816A were associated with type 1 (early onset) psoriasis in the Chinese Han population (test for heterogeneity P = 6.5 x 10(3) and P = 1.5 x 10(3), respectively). Comparisons with the results of previous GWAS of psoriasis highlight the heterogeneity of disease susceptibility between the Chinese and European populations. Our study identifies new genetic susceptibility factors and suggests new biological pathways in psoriasis."	"http://www.ncbi.nlm.nih.gov/pubmed/20953187"
 3	"asian"	"China"	"China"	"0.0"	"0.0306748466258"	"0.0674846625767"	"163"	"9.82352941176"	"Nature Genetics"	"Sun LD, Xiao FL, Li Y, Zhou WM, Tang HY, Tang XF, Zhang H, Schaarschmidt H, Zuo XB, Foelster-Holst R, He SM, Shi M, Liu Q, Lv YM, Chen XL, Zhu KJ, Guo YF, Hu DY, Li M, Li M, Zhang YH, Zhang X, Tang JP, Guo BR, Wang H, Liu Y, Zou XY, Zhou FS, Liu XY, Chen G, Ma L, Zhang SM, Jiang AP, Zheng XD, Gao XH, Li P, Tu CX, Yin XY, Han XP, Ren YQ, Song SP, Lu ZY, Zhang XL, Cui Y, Chang J, Gao M, Luo XY, Wang PG, Dai X, Su W, Li H, Shen CP, Liu SX, Feng XB, Yang CJ, Lin GS, Wang ZX, Huang JQ, Fan X, Wang Y, Bao YX, Yang S, Liu JJ, Franke A, Weidinger S, Yao ZR, Zhang XJ"	"Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, Anhui, China."	"Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 x 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 x 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 x 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 x 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis."	"http://www.ncbi.nlm.nih.gov/pubmed/21666691"
+"unk"	"asian"	"unknown"	"unknown"	"0.0"	"0.0493827160494"	"0.0987654320988"	"162"	"10.8"	"Molecular Biology and Evolution"	"Sun YB, Shen YY, Irwin DM, Zhang YP"		"Mitochondria are the power plant of cells, which play critical roles not only in energy metabolism but also in thermoregulation. These two roles have been individually suggested to influence mitochondrial DNA (mtDNA) evolution, however their relative importance is still rarely considered. Here, we conduct a comparative genomic analysis of 401 teleost complete mitochondrial genomes and test the roles of these dual functional constraints on mitochondria to provide a more complete view of mtDNA evolution. We found that mitochondrial protein-coding genes of migratory fishes have significantly smaller Ka/Ks than nonmigratory fishes. The same data set showed that the genes of fishes living in cold climates have significantly smaller Ka/Ks than tropical fishes. In contrast, these trends were not observed for two nuclear genes that are not involved in energy metabolism. The differences in selection patterns observed between mitochondrial and nuclear genes suggest that the functional constraints acting on mitochondria, due to energy metabolism and/or thermoregulation, influence the evolution of mitochondrial-encoded proteins in teleosts."	"http://www.ncbi.nlm.nih.gov/pubmed/20924083"
 3	"asian"	"Japan"	"Japan"	"0.0"	"0.0138888888889"	"0.0555555555556"	"216"	"12.7058823529"	"Glycobiology"	"Suzuki N, Nawa D, Yamamoto K"	"Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba 277-8562, Japan. nrsuzuki@k.u-tokyo.ac.jp"	"We previously identified two novel enzymes in pigeon, alpha1,4- and beta1,4-galactosyltransferases (GalTs), which are responsible for the biosynthesis of the Galalpha1-4Gal and Galbeta1-4Gal sequences on glycoproteins, respectively. No such glycan structures and/or enzymes have been found in mammals, suggesting that the expression of these enzymes diverged during the course of vertebrate evolution. To compare their expression profiles among avian species, we first established a method for detecting the activities of these two GalTs based on the two-dimensional high pressure liquid chromatography mapping technique, using 2-aminopyridine-derivatized asialo-biantennary N-glycans as an acceptor substrate. When we analyzed the activities of GalTs in pigeon liver extracts in the presence of UDP-Gal, 13 different products containing Galalpha1-4Galbeta1-4GlcNAc, Galbeta1-4Galbeta1-4GlcNAc and/or Galalpha1-4Galbeta1-4Galbeta1-4GlcNAc branches were identified. The newly formed glycosidic linkages of the enzymatic products were determined by nuclear magnetic resonance and methylation analysis, as well as by galactosidase digestions. The activities of both alpha1,4- and beta1,4-GalTs were detected in various tissues in pigeon, although their relative activities were different in each tissue. In contrast, ostrich expressed beta1,4-GalT, but not alpha1,4-GalT, in all tissues analyzed, whereas neither alpha1,4- nor beta1,4-GalT activity was detected in chicken. These results indicate that alpha1,4- and beta1,4-GalTs are expressed in a species-specific manner and are distributed throughout the entire body of pigeon or ostrich when the enzymes are present."	"http://www.ncbi.nlm.nih.gov/pubmed/20959391"
 3	"asian"	"Japan"	"Japan"	"0.0"	"0.0"	"0.0693069306931"	"202"	"10.6842105263"	"Glycobiology"	"Taira T, Mahoe Y, Kawamoto N, Onaga S, Iwasaki H, Ohnuma T, Fukamizo T"	"Department of Bioscience and Biotechnology, Faculty of Agriculture, University of the Ryukyus, Okinawa, Japan. tokey@agr.u-ryukyu.ac.jp"	"Chitinase-A (BcChi-A) was purified from a moss, Bryum coronatum, by several steps of column chromatography. The purified BcChi-A was found to be a molecular mass of 25 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an isoelectric point of 3.5. A cDNA encoding BcChi-A was cloned by rapid amplification of cDNA ends and polymerase chain reaction. It consisted of 1012 nucleotides and encoded an open reading frame of 228 amino acid residues. The predicted mature BcChi-A consists of 205 amino acid residues and has a molecular weight of 22,654. Sequence analysis indicated that BcChi-A is glycoside hydrolase family-19 (GH19) chitinase lacking loops I, II, IV and V, and a C-terminal loop, which are present in the catalytic domain of plant class I and II chitinases. BcChi-A is a compact chitinase that has the fewest loop regions of the GH19 chitinases. Enzymatic experiments using chitooligosaccharides showed that BcChi-A has higher activity toward shorter substrates than class II enzymes. This characteristic is likely due to the loss of the loop regions that are located at the end of the substrate-binding cleft and would be involved in substrate binding of class II enzymes. This is the first report of a chitinase from mosses, nonvascular plants."	"http://www.ncbi.nlm.nih.gov/pubmed/21367878"
 3	"asian"	"Japan"	"Japan"	"0.0104712041885"	"0.0104712041885"	"0.125654450262"	"191"	"7.84"	"BMC Bioinformatics"	"Takahashi H, Morimoto T, Ogasawara N, Kanaya S"	"Graduate School of Information Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan."	"BACKGROUND: Liquid chromatography-mass spectrometry (LC-MS) utilizing the high-resolution power of an orbitrap is an important analytical technique for both metabolomics and proteomics. Most important feature of the orbitrap is excellent mass accuracy. Thus, it is necessary to convert raw data to accurate and reliable m/z values for metabolic fingerprinting by high-resolution LC-MS. RESULTS: In the present study, we developed a novel, easy-to-use and straightforward m/z detection method, AMDORAP. For assessing the performance, we used real biological samples, Bacillus subtilis strains 168 and MGB874, in the positive mode by LC-orbitrap. For 14 identified compounds by measuring the authentic compounds, we compared obtained m/z values with other LC-MS processing tools. The errors by AMDORAP were distributed within +/-3 ppm and showed the best performance in m/z value accuracy. CONCLUSIONS: Our method can detect m/z values of biological samples much more accurately than other LC-MS analysis tools. AMDORAP allows us to address the relationships between biological effects and cellular metabolites based on accurate m/z values. Obtaining the accurate m/z values from raw data should be indispensable as a starting point for comparative LC-orbitrap analysis. AMDORAP is freely available under an open-source license at http://amdorap.sourceforge.net/."	"http://www.ncbi.nlm.nih.gov/pubmed/21702951"
 3	"asian"	"Japan"	"Japan"	"0.00699300699301"	"0.034965034965"	"0.0909090909091"	"143"	"9.53333333333"	"BMC Bioinformatics"	"Tsugawa H, Tsujimoto Y, Arita M, Bamba T, Fukusaki E"	"Department of Bioengineering, Graduate School of Engineering, Osaka University, Suita, Japan."	"BACKGROUND: The goal of metabolomics analyses is a comprehensive and systematic understanding of all metabolites in biological samples. Many useful platforms have been developed to achieve this goal. Gas chromatography coupled to mass spectrometry (GC/MS) is a well-established analytical method in metabolomics study, and 200 to 500 peaks are routinely observed with one biological sample. However, only ~100 metabolites can be identified, and the remaining peaks are left as unknowns. RESULT: We present an algorithm that acquires more extensive metabolite information. Pearsons product-moment correlation coefficient and the Soft Independent Modeling of Class Analogy (SIMCA) method were combined to automatically identify and annotate unknown peaks, which tend to be missed in routine studies that employ manual processing. CONCLUSIONS: Our data mining system can offer a wealth of metabolite information quickly and easily, and it provides new insights, particularly into food quality evaluation and prediction."	"http://www.ncbi.nlm.nih.gov/pubmed/21542920"
 3	"asian"	"Japan, Japan"	"Japan"	"0.00970873786408"	"0.0"	"0.0679611650485"	"206"	"6.25714285714"	"Bioinformatics"	"Tsuruoka Y, Miwa M, Hamamoto K, Tsujii J, Ananiadou S"	"School of Information Science, Japan Advanced Institute of Science and Technology (JAIST), Nomi, Japan. tsuruoka@jaist.ac.jp"	"MOTIVATION: Discovering useful associations between biomedical concepts has been one of the main goals in biomedical text-mining, and understanding their biomedical contexts is crucial in the discovery process. Hence, we need a text-mining system that helps users explore various types of (possibly hidden) associations in an easy and comprehensible manner. RESULTS: This article describes FACTA+, a real-time text-mining system for finding and visualizing indirect associations between biomedical concepts from MEDLINE abstracts. The system can be used as a text search engine like PubMed with additional features to help users discover and visualize indirect associations between important biomedical concepts such as genes, diseases and chemical compounds. FACTA+ inherits all functionality from its predecessor, FACTA, and extends it by incorporating three new features: (i) detecting biomolecular events in text using a machine learning model, (ii) discovering hidden associations using co-occurrence statistics between concepts, and (iii) visualizing associations to improve the interpretability of the output. To the best of our knowledge, FACTA+ is the first real-time web application that offers the functionality of finding concepts involving biomolecular events and visualizing indirect associations of concepts with both their categories and importance. AVAILABILITY: FACTA+ is available as a web application at http://refine1-nactem.mc.man.ac.uk/facta/, and its visualizer is available at http://refine1-nactem.mc.man.ac.uk/facta-visualizer/. CONTACT: tsuruoka@jaist.ac.jp."	"http://www.ncbi.nlm.nih.gov/pubmed/21685059"
 3	"asian"	"Japan"	"Japan"	"0.00471698113208"	"0.0377358490566"	"0.0330188679245"	"212"	"12.4705882353"	"Glycobiology"	"Tsutsui S, Okamoto M, Ono M, Suetake H, Kikuchi K, Nakamura O, Suzuki Y, Watanabe T"	"School of Marine Biosciences, Kitasato University, Okirai, Sanriku, Ofunato, Iwate 022-0101, Japan;"	"A skin mucus lectin exhibiting a homodimeric structure and a S-S bond between subunits of approximately 40 kDa was purified from flathead Platycephalus indicus (Scorpaeniformes). This lectin, named FHL, exhibited mannose-specific activity in a Ca(2+) dependent manner. Although FHL showed no homology to any previously reported lectins, it did exhibit ~20% identity to previously discovered plasma kallikreins and coagulation factor XIs of mammals and Xenopus laevis. These known proteins are serine proteases and play pivotal roles in the kinin-generating system or the blood coagulation pathway. However, alignment analysis revealed that whilst FHL lacked a serine-protease domain it was homologous to the heavy chain domain of plasma kallikreins and coagulation factor XI therefore suggesting that FHL is not an enzyme but rather, a novel animal lectin. On the basis of this finding, we investigated the lectin-activity of human plasma kallikrein, and revealed that it could indeed act as lectin. Other genes homologous to FHL were also found in the genome databases of some fish species, but not in mammals. In contrast, plasma kallikreins and coagulation factor XI have yet to be identified in fish. The present findings suggest that these mammalian enzymes may have originally emerged as a lectin and may have evolved into molecules with protease activity after separation from common ancestors."	"http://www.ncbi.nlm.nih.gov/pubmed/21613239"
+"unk"	"asian"	"unknown"	"unknown"	"0.0157068062827"	"0.0104712041885"	"0.0890052356021"	"191"	"9.2380952381"	"BMC Bioinformatics"	"Tuszynska I, Bujnicki JM"		"ABSTRACT: BACKGROUND: Protein-RNA interactions play fundamental roles in many biological processes. Understanding the molecular mechanism of protein-RNA recognition and formation of protein-RNA complexes is a major challenge in structural biology. Unfortunately, the experimental determination of protein-RNA complexes is tedious and difficult, both by X-ray crystallography and NMR. For many interacting proteins and RNAs the individual structures are available, enabling computational prediction of complex structures by computational docking. However, methods for protein-RNA docking remain scarce, in particular in comparison to the numerous methods for protein-protein docking. RESULTS: We developed two medium-resolution, knowledge-based potentials for scoring protein-RNA models obtained by docking: the quasichemical potential (QUASI-RNP) and the Decoys As the Reference State potential (DARS-RNP). Both potentials use a coarse-grained representation for both RNA and protein molecules and are capable of dealing with RNA structures with posttranscriptionally modified residues. We compared the discriminative power of DARS-RNP and QUASI-RNP for selecting rigid-body docking poses with the potentials previously developed by the Varani and Fernandez groups. CONCLUSIONS: In both bound and unbound docking tests, DARS-RNP showed the highest ability to identify native-like structures. Python implementations of DARS-RNP and QUASI-RNP are freely available for download at http://iimcb.genesilico.pl/RNP/"	"http://www.ncbi.nlm.nih.gov/pubmed/21851628"
 3	"asian"	"Japan"	"Japan"	"0.0"	"0.0107142857143"	"0.0535714285714"	"280"	"9.65517241379"	"PLoS One"	"Ueno K, Matsumoto Y, Uno J, Sasamoto K, Sekimizu K, Kinjo Y, Chibana H"	"Medical Mycology Research Center (MMRC), Chiba University, Chiba, Japan."	"The intestinal resident Candida glabrata opportunistically infects humans. However few genetic factors for adaptation in the intestine are identified in this fungus. Here we describe the C. glabrata CYB2 gene encoding lactate dehydrogenase as an adaptation factor for survival in the intestine. CYB2 was identified as a virulence factor by a silkworm infection study. To determine the function of CYB2, we analysed in vitro phenotypes of the mutant Deltacyb2. The Deltacyb2 mutant grew well in glucose medium under aerobic and anaerobic conditions, was not supersensitive to nitric oxide which has fungicidal-effect in phagocytes, and had normal levels of general virulence factors protease, lipase and adherence activities. A previous report suggested that Cyb2p is responsible for lactate assimilation. Additionally, it was speculated that lactate assimilation was required for Candida virulence because Candida must synthesize glucose via gluconeogenesis under glucose-limited conditions such as in the host. Indeed, the Deltacyb2 mutant could not grow on lactate medium in which lactate is the sole carbon source in the absence of glucose, indicating that Cyb2p plays a role in lactate assimilation. We hypothesized that Cyb2p-mediated lactate assimilation is necessary for proliferation in the intestinal tract, as the intestine is rich in lactate produced by bacteria flora, but not glucose. The Deltacyb2 mutant showed 100-fold decreased adaptation and few cells of Saccharomyces cerevisiae can adapt in mouse ceca. Interestingly, C. glabrata could assimilate lactate under hypoxic conditions, dependent on CYB2, but not yeast S. cerevisiae. Because accessible oxygen is limited in the intestine, the ability for lactate assimilation in hypoxic conditions may provide an advantage for a pathogenic yeast. From those results, we conclude that Cyb2p-mediated lactate assimilation is an intestinal adaptation factor of C. glabrata."	"http://www.ncbi.nlm.nih.gov/pubmed/21931845"
 1	"asian"	"unknown"	"unknown"	"0.0115384615385"	"0.0153846153846"	"0.0653846153846"	"260"	"12.380952381"	"PLoS One"	"Ulucan O, Keskin O, Erman B, Gursoy A"	"Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Istanbul, Turkey."	"Histone modifications have great importance in epigenetic regulation. JMJD2A is a histone demethylase which is selective for di- and trimethyl forms of residues Lys9 and Lys36 of Histone 3 tail (H3K9 and H3K36). We present a molecular dynamics simulations of mono-, di- and trimethylated histone tails in complex with JMJD2A catalytic domain to gain insight into how JMJD2A discriminates between the methylation states of H3K9. The methyl groups are located at specific distances and orientations with respect to Fe(II) in methylammonium binding pocket. For the trimethyllysine the mechanism which provides the effectual orientation of methyl groups is the symmetry, whereas for the dimethyllysine case the determining factors are the interactions between methyllysine head and its environment and subsequently the restriction on angular motion. The occurrence frequency of methyl groups in a certain proximity of Fe(II) comes out as the explanation of the enzyme activity difference on di- and tri-methylated peptides. Energy analysis suggests that recognition is mostly driven by van der Waals and followed by Coulombic interactions in the enzyme-substrate interface. The number (mono, di or tri) and orientations of methyl groups and water molecules significantly affect the extent of van der Waals interaction strengths. Hydrogen bonding analysis suggests that the interaction between JMJD2A and its substrates mainly comes from main chain-side chain interactions. Binding free energy analysis points out Arg8 as an important residue forming an intra-substrate hydrogen bond with tri and dimethylated Lys9 of the H3 chain. Our study provides new insights into how JMJD2A discriminates between its substrates from both a structural and dynamical point of view."	"http://www.ncbi.nlm.nih.gov/pubmed/21931800"
 3	"asian"	"India"	"India"	"0.0281690140845"	"0.0140845070423"	"0.0798122065728"	"213"	"10.1904761905"	"PLoS One"	"Vadwai V, Daver G, Udwadia Z, Sadani M, Shetty A, Rodrigues C"	"P. D. Hinduja National Hospital and Medical Research Centre, Mahim, Mumbai, India."	"BACKGROUND: Unsuccessful treatment outcomes among patients with multi-/extensively- drug resistant tuberculosis (TB) have hampered efforts involved in eradicating this disease. In order to better understand the etiology of this disease, we aimed to determine whether single or multiple strains of Mycobacterium tuberculosis (MTB) are localized within lung cavities of patients suffering from chronic progressive TB. METHODOLOGY/FINDINGS: Multiple cavity isolates from lung of 5 patients who had undergone pulmonary resection surgery were analyzed on the basis of their drug susceptibility profile, and genotyped by spoligotyping and 24-loci MIRU-VNTR. The patients past history including treatment was studied. Three of the 5 patients had extensive drug resistant TB. Heteroresistance was also reported within different cavity isolates of the lung. Both genotyping methods reported the presence of clonal population of MTB strain within different cavities of the each patient, even those reporting heteroresistance. Four of the 5 patients were infected with a population of the Beijing genotype. Post-surgery they were prescribed a drug regimen consisting of cycloserine, a fluoroquinolone and an injectable drug. A 6 month post-surgery follow-up reported only 2 patients with positive clinical outcome, showing sputum conversion. CONCLUSION: Identical spoligotype patterns and MIRU-VNTR profiles between multiple cavities of each patient, characterize the presence of clonal population of MTB strains (and absence of multiple MTB infection)."	"http://www.ncbi.nlm.nih.gov/pubmed/21935462"
 3	"asian"	"Japan"	"Japan"	"0.0127659574468"	"0.0170212765957"	"0.0425531914894"	"235"	"9.48"	"Glycobiology"	"Yokoe S, Asahi M, Takeda T, Otsu K, Taniguchi N, Miyoshi E, Suzuki K"	"Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan."	"Cardiac-type sarco(endo)plasmic reticulum Ca(2)-ATPase (SERCA2a) plays a major role in cardiac muscle contractility. Phospholamban (PLN) regulates the function of SERCA2a via its Ser(16)-phosphorylation. Since it has been proposed that the Ser/Thr residues on cytoplasmic and nuclear proteins are modified by O-linked N-acetylglucosamine (O-GlcNAc), we examined the effect of O-GlcNAcylation on PLN function in rat adult cardiomyocytes. Studies using enzymatic labeling and co-immunoprecipitation of wild type and a series of mutants of PLN showed that PLN was O-GlcNAcylated and Ser(16) of PLN might be the site for O-GlcNAcylation. In cardiomyocytes treated with O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), the O-GlcNAcylation was significantly increased compared to non-treated cells. Simultaneously, Ser(16)-phosphorylation of PLN was reduced. In Chinese hamster ovary cells where PLN cDNA and O-GlcNAc transferase siRNA were co-transfected, the Ser(16)-phosphorylation of PLN was significantly increased compared to controls. The same results were observed in heart homogenates from diabetic rats. In a co-immunoprecipitation of PLN with SERCA2a, the physical interaction between the two proteins was increased in PUGNAc-treated cardiomyocytes. Unlike non-treated cells, the activity of SERCA2a and the profiles of calcium transients in PUGNAc-treated cardiomyocytes were not significantly changed even after treatment with catecholamine. These data suggest that PLN is O-GlcNAcylated to induce the inhibition of its phosphorylation, which correlates to the deterioration of cardiac function. This might define a novel mechanism by which PLN regulation of SERCA2a is altered under conditions where O-GlcNAcylation is increased, such as those occurring in diabetes."	"http://www.ncbi.nlm.nih.gov/pubmed/20484118"
 3	"asian"	"Japan"	"Japan"	"0.00671140939597"	"0.0268456375839"	"0.0402684563758"	"149"	"11.4615384615"	"Immunity"	"Yokosuka T, Kobayashi W, Takamatsu M, Sakata-Sogawa K, Zeng H, Hashimoto-Tane A, Yagita H, Tokunaga M, Saito T"	"Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan. yokosuka@rcai.riken.jp"	"T cell activation is positively and negatively regulated by a pair of costimulatory receptors, CD28 and CTLA-4, respectively. Because these receptors share common ligands, CD80 and CD86, the expression and behavior of CTLA-4 is critical for T cell costimulation regulation. However, in vivo blocking of CD28-mediated costimulation by CTLA-4 and its mechanisms still remain elusive. Here, we demonstrate the dynamic behavior of CTLA-4 in its real-time competition with CD28 at the central-supramolecular activation cluster (cSMAC), resulting in the dislocalization of protein kinase C-theta and CARMA1 scaffolding protein. CTLA-4 translocation to the T cell receptor microclusters and the cSMAC is tightly regulated by its ectodomain size, and its accumulation at the cSMAC is required for its inhibitory function. The CTLA-4-mediated suppression was demonstrated by the in vitro anergy induction in regulatory T cells constitutively expressing CTLA-4. These results show the dynamic mechanism of CTLA-4-mediated T cell suppression at the cSMAC."	"http://www.ncbi.nlm.nih.gov/pubmed/20870175"
 3	"asian"	"Korea, Korea, korea"	"Korea"	"0.0"	"0.0230769230769"	"0.0807692307692"	"260"	"8.64516129032"	"Bioinformatics"	"Yoon S, Kim J, Hum J, Kim H, Park S, Kladwang W, Das R"	"School of Electrical Engineering, Korea University, Seoul 136-713, Republic of Korea. sryoon@korea.ac.kr"	"MOTIVATION: Capillary electrophoresis (CE) of nucleic acids is a workhorse technology underlying high-throughput genome analysis and large-scale chemical mapping for nucleic acid structural inference. Despite the wide availability of CE-based instruments, there remain challenges in leveraging their full power for quantitative analysis of RNA and DNA structure, thermodynamics and kinetics. In particular, the slow rate and poor automation of available analysis tools have bottlenecked a new generation of studies involving hundreds of CE profiles per experiment. RESULTS: We propose a computational method called high-throughput robust analysis for capillary electrophoresis (HiTRACE) to automate the key tasks in large-scale nucleic acid CE analysis, including the profile alignment that has heretofore been a rate-limiting step in the highest throughput experiments. We illustrate the application of HiTRACE on 13 datasets representing 4 different RNAs, 3 chemical modification strategies and up to 480 single mutant variants; the largest datasets each include 87 360 bands. By applying a series of robust dynamic programming algorithms, HiTRACE outperforms prior tools in terms of alignment and fitting quality, as assessed by measures including the correlation between quantified band intensities between replicate datasets. Furthermore, while the smallest of these datasets required 7-10 h of manual intervention using prior approaches, HiTRACE quantitation of even the largest datasets herein was achieved in 3-12 min. The HiTRACE method, therefore, resolves a critical barrier to the efficient and accurate analysis of nucleic acid structure in experiments involving tens of thousands of electrophoretic bands. AVAILABILITY: HiTRACE is freely available for download at http://hitrace.stanford.edu. CONTACT: sryoon@korea.ac.kr; rhiju@stanford.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21561922"
+1	"asian"	"unknown"	"unknown"	"0.0121951219512"	"0.0243902439024"	"0.0569105691057"	"246"	"9.14814814815"	"Glycobiology"	"Yoshida E, Sakurama H, Kiyohara M, Nakajima M, Kitaoka M, Ashida H, Hirose J, Katayama T, Yamamoto K, Kumagai H"	"Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi, Ishikawa 921-8836."	"The breast-fed infant intestine is often colonized by particular bifidobacteria, and human milk oligosaccharides (HMOs) are considered to be bifidogenic. Recent studies showed that Bifidobacterium longum subsp. infantis can grow on HMOs as the sole carbon source. This ability has been ascribed to the presence of a gene cluster (HMO cluster-1) contained in its genome. However, the metabolism of HMOs by the organism remains unresolved because no enzymatic studies have been completed. In the present study, we characterized beta-galactosidases of this subspecies to understand how the organism degrades type-1 (Galbeta1-3GlcNAc) and type-2 (Galbeta1-4GlcNAc) isomers of HMOs. The results revealed that the locus tag Blon_2016 gene, which is distantly located from the HMO culster-1, encodes a novel beta-galactosidase (Bga42A) with a significantly higher specificity for LNT (Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc) than for lacto-N-biose I (Galbeta1-3GlcNAc), lactose and type-2 HMOs. The proposed name of Bga42A is lacto-N-tetraose beta-1,3-galactosidase. The Blon_2334 gene (Bga2A) located within the HMO cluster-1 encodes a beta-galactosidase specific for lactose and type-2 HMOs. Real-time quantitative reverse transcription PCR analysis revealed the physiological significance of Bga42A and Bga2A in HMO metabolism. The organism therefore uses two different beta-galactosidases to selectively degrade type-1 and type-2 HMOs. Despite the quite rare occurrence in nature of beta-galactosidases acting on type-1 chains, the close homologues of Bga42A were present in the genomes of infant-gut associated bifidobacteria that are known to consume LNT. The predominance of type-1 chains in HMOs and the conservation of Bga42A homologues suggest the coevolution of these bifidobacteria with humans."	"http://www.ncbi.nlm.nih.gov/pubmed/21926104"
 3	"asian"	"Japan"	"Japan"	"0.00657894736842"	"0.0526315789474"	"0.105263157895"	"152"	"13.8181818182"	"Nature"	"Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, Shih LY, Haferlach T, Chiba S, Nakauchi H, Miyano S, Ogawa S"	"1] Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan [2]."	"Myelodysplastic syndromes and related disorders (myelodysplasia) are a heterogeneous group of myeloid neoplasms showing deregulated blood cell production with evidence of myeloid dysplasia and a predisposition to acute myeloid leukaemia, whose pathogenesis is only incompletely understood. Here we report whole-exome sequencing of 29 myelodysplasia specimens, which unexpectedly revealed novel pathway mutations involving multiple components of the RNA splicing machinery, including U2AF35, ZRSR2, SRSF2 and SF3B1. In a large series analysis, these splicing pathway mutations were frequent ( approximately 45 to  approximately 85%) in, and highly specific to, myeloid neoplasms showing features of myelodysplasia. Conspicuously, most of the mutations, which occurred in a mutually exclusive manner, affected genes involved in the 3-splice site recognition during pre-mRNA processing, inducing abnormal RNA splicing and compromised haematopoiesis. Our results provide the first evidence indicating that genetic alterations of the major splicing components could be involved in human pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia."	"http://www.ncbi.nlm.nih.gov/pubmed/21909114"
 3	"asian"	"China"	"China"	"0.00934579439252"	"0.00467289719626"	"0.0794392523364"	"214"	"11.2631578947"	"PLoS One"	"Yu B, Zhou S, Wang Y, Ding G, Ding F, Gu X"	"Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China."	"Unlike the central nervous system, peripheral nerves can regenerate when damaged. MicroRNA (miRNA) is a novel class of small, non-coding RNA that regulates gene expression at the post-transcriptional level. Here, we report regular alterations of miRNA expression following rat sciatic nerve injury using deep sequencing. We harvested dorsal root ganglia tissues and the proximal stumps of the nerve, and identified 201 and 225 known miRNAs with significant expression variance at five time points in these tissues after sciatic nerve transaction, respectively. Subsequently, hierarchical clustering, miRNA expression pattern and co-expression network were performed. We screened out specific miRNAs and further obtained the intersection genes through target analysis software (Targetscan and miRanda). Moreover, GO and KEGG enrichment analyses of these intersection genes were performed. The bioinformatics analysis indicated that the potential targets for these miRNAs were involved in nerve regeneration, including neurogenesis, neuron differentiation, vesicle-mediated transport, homophilic cell adhesion and negative regulation of programmed cell death that were known to play important roles in regulating nerve repair. Finally, we combined differentially expressed mRNA with the predicted targets for selecting inverse miRNA-target pairs. Our results show that the abnormal expression of miRNA may contribute to illustrate the molecular mechanisms of nerve regeneration and that miRNAs are potential targets for therapeutic interventions and may enhance intrinsic regenerative ability."	"http://www.ncbi.nlm.nih.gov/pubmed/21931774"
 3	"asian"	"China"	"China"	"0.0"	"0.0248756218905"	"0.114427860697"	"201"	"13.4"	"BMC Bioinformatics"	"Yu H, Liu BH, Ye ZQ, Li C, Li YX, Li YY"	"Bioinformatics Center, Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, P, R, China. yxli@scbit.org."	"ABSTRACT: BACKGROUND: Differential coexpression analysis (DCEA) is increasingly used for investigating the global transcriptional mechanisms underlying phenotypic changes. Current DCEA methods mostly adopt a gene connectivity-based strategy to estimate differential coexpression, which is characterized by comparing the numbers of gene neighbors in different coexpression networks. Although it simplifies the calculation, this strategy mixes up the identities of different coexpression neighbors of a gene, and fails to differentiate significant differential coexpression changes from those trivial ones. Especially, the correlation-reversal is easily missed although it probably indicates remarkable biological significance. RESULTS: We developed two link-based quantitative methods, DCp and DCe, to identify differentially coexpressed genes and gene pairs (links). Bearing the uniqueness of exploiting the quantitative coexpression change of each gene pair in the coexpression networks, both methods proved to be superior to currently popular methods in simulation studies. Re-mining of a publicly available type 2 diabetes (T2D) expression dataset from the perspective of differential coexpression analysis led to additional discoveries than those from differential expression analysis. CONCLUSIONS: This work pointed out the critical weakness of current popular DCEA methods, and proposed two link-based DCEA algorithms that will make contribution to the development of DCEA and help extend it to a broader spectrum."	"http://www.ncbi.nlm.nih.gov/pubmed/21806838"
 2	"english"	"Boston, USA."	"USA"	"0.0"	"0.0510204081633"	"0.0408163265306"	"98"	"10.8888888889"	"Nature"	"Berger AH, Knudson AG, Pandolfi PP"	"Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts 02115, USA."	"This year, 2011, marks the forty-year anniversary of the statistical analysis of retinoblastoma that provided the first evidence that tumorigenesis can be initiated by as few as two mutations. This work provided the foundation for the two-hit hypothesis that explained the role of recessive tumour suppressor genes (TSGs) in dominantly inherited cancer susceptibility syndromes. However, four decades later, it is now known that even partial inactivation of tumour suppressors can critically contribute to tumorigenesis. Here we analyse this evidence and propose a continuum model of TSG function to explain the full range of TSG mutations found in cancer."	"http://www.ncbi.nlm.nih.gov/pubmed/21833082"
 2	"english"	"New York, New York"	"USA"	"0.0"	"0.0277777777778"	"0.0416666666667"	"72"	"4.58823529412"	"Bioinformatics"	"Bergey CM"	"Department of Anthropology, New York University. 25 Waverly Pl. New York, NY 10003. U.S.A."	"SUMMARY: AluHunter is a database of taxon-specific primate Alu elements for use in phylogeny and population genetics. The software automatically isolates potentially polymorphic Alu insertions in sequences submitted to GenBank by screening the elements against reference genomes. The resultant database of variable markers is a valuable resource for researchers interested in characterizing Alu elements in their primate taxon of interest.Availability and Implementation: The AluHunter database can be accessed at http://www.aluhunter.com. CONTACT: cmb433@nyu.edu."	"http://www.ncbi.nlm.nih.gov/pubmed/21880703"
 2	"english"	"UK."	"UK"	"0.0157068062827"	"0.020942408377"	"0.0890052356021"	"191"	"7.88"	"Bioinformatics"	"Berk M, Ebbels T, Montana G"	"Statistics Section, Department of Mathematics, Imperial College London, Huxley Building, South Kensington, London SW7 2AZ, UK."	"MOTIVATION: Metabolomics is the study of the complement of small molecule metabolites in cells, biofluids and tissues. Many metabolomic experiments are designed to compare changes observed over time under two experimental conditions or groups (e.g. a control and drug-treated group) with the goal of identifying discriminatory metabolites or biomarkers that characterize each condition. A common study design consists of repeated measurements taken on each experimental unit thus producing time courses of all metabolites. We describe a statistical framework for estimating time-varying metabolic profiles and their within-group variability and for detecting between-group differences. Specifically, we propose (i) a smoothing splines mixed effects (SME) model that treats each longitudinal measurement as a smooth function of time and (ii) an associated functional test statistic. Statistical significance is assessed by a non-parametric bootstrap procedure. RESULTS: The methodology has been extensively evaluated using simulated data and has been applied to real nuclear magnetic resonance spectroscopy data collected in a preclinical toxicology study as part of a larger project lead by the COMET (Consortium for Metabonomic Toxicology). Our findings are compatible with the previously published studies. AVAILABILITY: An R script is freely available for download at http://www2.imperial.ac.uk/~gmontana/sme.htm."	"http://www.ncbi.nlm.nih.gov/pubmed/21729866"
+"unk"	"english"	"unknown"	"unknown"	"0.0267558528428"	"0.0133779264214"	"0.0602006688963"	"299"	"9.21212121212"	"PLoS One"	"Bernabe-Ortiz A, Carcamo CP, Scott JD, Hughes JP, Garcia PJ, Holmes KK"	"School of Public Health and Administration, Universidad Peruana Cayetano Heredia, Lima, Peru."	"BACKGROUND: Data on hepatitis B virus (HBV) prevalence are limited in developing countries. There is also limited information of consistent condom use efficacy for reducing HBV transmission at the population level. The study goal was to evaluate the prevalence and factors associated with HBV infection in Peru, and the relationship between anti-HBc positivity and consistent condom use. METHODS AND FINDINGS: Data from two different surveys performed in 28 mid-sized Peruvian cities were analyzed. Participants aged 18-29 years were selected using a multistage cluster sampling. Information was collected through a validated two-part questionnaire. The first part (face-to-face) concerned demographic data, while the second part (self-administered using handheld computers) concerned sexual behavior. Hepatitis B core antibody (anti-HBc) was tested in 7,000 blood samples. Prevalences and associations were adjusted for sample strata, primary sampling units and population weights. Anti-HBc prevalence was 5.0% (95%CI 4.1%-5.9%), with the highest prevalence among jungle cities: 16.3% (95%CI 13.8%-19.1%). In the multivariable analysis, Anti-HBc positivity was directly associated with geographic region (highlands OR = 2.05; 95%CI 1.28-3.27, and jungle OR = 4.86; 95%CI 3.05-7.74; compared to coastal region); and inversely associated with age at sexual debut (OR = 0.90; 95%CI 0.85-0.97). Consistent condom use, evaluated in about 40% of participants, was associated with reduced prevalence (OR = 0.34; 95%CI 0.15-0.79) after adjusting for gender, geographic region, education level, lifetime number of sex partners, age at sexual debut and year of survey. CONCLUSION: Residence in highlands or jungle cities is associated with higher anti-HBc prevalences, whereas increasing age at sexual debut were associated with lower prevalences. Consistent condom use was associated with decreased risk of anti-HBc. Findings from this study emphasize the need of primary prevention programs (vaccination) especially in the jungle population, and imply that condom use promotion might be a potential strategy to prevent HBV infection."	"http://www.ncbi.nlm.nih.gov/pubmed/21931828"
 2	"english"	"Iowa, Iowa, United States"	"USA"	"0.0"	"0.0268817204301"	"0.10752688172"	"186"	"12.4666666667"	"Blood"	"Berquam-Vrieze KE, Nannanpaneni K, Brett BT, Holmfeldt L, Ma J, Zagorodna O, Jenkins NA, Copeland NG, Meyerholz DK, Knudson CM, Mullighan CG, Scheetz TE, Dupuy AJ"	"Department of Anatomy & Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, United States;"	"Identifying the normal cell from which a tumor originates is crucial to understanding the etiology of that cancer. However, retrospective identification of the cell of origin in cancer is challenging due to the accumulation of genetic and epigenetic changes in tumor cells. The biological state of the cell of origin likely influences the genetic events that drive transformation. We directly tested this hypothesis by performing a Sleeping Beauty transposon mutagenesis screen in which common insertion sites were identified in tumors that were produced by mutagenesis of cells at varying time points throughout the T-lineage. Mutation and gene expression data derived from these tumors was then compared to data obtained from a panel of 84 human T-cell acute lymphoblastic leukemia samples, including copy number alterations and gene expression profiles. This revealed that altering the cell of origin produces tumors that model distinct subtypes of human T-cell acute lymphoblastic leukemia, suggesting that even subtle changes in the cell of origin dramatically affect genetic selection in tumors. These findings have broad implications for the genetic analysis of human cancers as well as the production of mouse models of cancer."	"http://www.ncbi.nlm.nih.gov/pubmed/21828136"
 2	"english"	"New York, United States"	"USA"	"0.0"	"0.0298507462687"	"0.0597014925373"	"201"	"13.4"	"Blood"	"Betts BC, Abdel-Wahab O, Curran SA, St Angelo ET, Koppikar P, Heller G, Levine RL, Young JW"	"Laboratory of Cellular Immunobiology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States;"	"Janus kinase-2 (JAK2) conveys receptor binding signals by several inflammatory cytokines, including IL-6, via phosphorylation of signal transducer and activator of transcription 3 (STAT3). We demonstrate that selective JAK2 inhibition by TG101348, during initial encounters between human T-cells and allogeneic monocyte-derived dendritic cells (moDCs), induces durable, profound, and specific T-cell tolerance on reexposure to the same alloantigens. Subsequent responses by non-alloreactive T-cells to stimulation de novo by a pathogenic nominal antigen remain intact. TG101348 additionally suppresses primed T-cell responses when present only during alloantigen restimulation. TG101348 ablates IL-6/JAK2-mediated phosphorylation of STAT3 but has no off-target effects on IL-2 or IL-15/JAK3/pSTAT5-dependent signaling, which sustain Treg and other effector T-cell responses. JAK2 inhibition preserves Treg numbers and thereby enhances the ratio of CD4(+) Tregs to CD8(+)CD25(+) effector T-cells in favor of Tregs. JAK2 inhibition also reduces the production of IL-6 and TNF-alpha in allogeneic MLRs, impairing the activation of central and effector memory T-cells as well as the expansion of responder T helper 1 (Th1) and Th17 cells. While we have reported the limitations of isolated IL-6R-alpha inhibition in DC-stimulated alloreactivity, we demonstrate here that JAK2 represents a relevant biologic target for controlling graft-versus-host disease (GvHD) or allograft rejection, without broader immune impairment."	"http://www.ncbi.nlm.nih.gov/pubmed/21917753"
 2	"english"	"United Kingdom"	"UK"	"0.00473933649289"	"0.0473933649289"	"0.0995260663507"	"211"	"14.0666666667"	"Molecular Biology and Evolution"	"Bhatt S, Holmes EC, Pybus OG"	"Department of Zoology, University of Oxford, Oxford, United Kingdom."	"Quantifying adaptive evolution at the genomic scale is an essential yet challenging aspect of evolutionary biology. Here, we develop a method that extends and generalizes previous approaches to estimate the rate of genomic adaptation in rapidly evolving populations and apply it to a large data set of complete human influenza A virus genome sequences. In accord with previous studies, we observe particularly high rates of adaptive evolution in domain 1 of the viral hemagglutinin (HA1). However, our novel approach also reveals previously unseen adaptation in other viral genes. Notably, we find that the rate of adaptation (per codon per year) is higher in surface residues of the viral neuraminidase than in HA1, indicating strong antibody-mediated selection on the former. We also observed high rates of adaptive evolution in several nonstructural proteins, which may relate to viral evasion of T-cell and innate immune responses. Furthermore, our analysis provides strong quantitative support for the hypothesis that human H1N1 influenza experiences weaker antigenic selection than H3N2. As well as shedding new light on the dynamics and determinants of positive Darwinian selection in influenza viruses, the approach introduced here is applicable to other pathogens for which densely sampled genome sequences are available, and hence is ideally suited to the interpretation of next-generation genome sequencing data."	"http://www.ncbi.nlm.nih.gov/pubmed/21415025"
 2	"english"	"USA."	"USA"	"0.0"	"0.0571428571429"	"0.0571428571429"	"35"	"5.0"	"Immunity"	"Broxmeyer HE"	"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. hbroxmey@iupui.edu"	"Erythropoietin (EPO) an erythropoietic stimulating agent also exerts effects on other cell systems. Nairz et al. (2011) now link EPO and intracellular signaling through the EPO receptor (EPOR) to innate immune cell activity via macrophages."	"http://www.ncbi.nlm.nih.gov/pubmed/21272782"
 2	"english"	"United States of America"	"USA"	"0.0"	"0.0325203252033"	"0.0772357723577"	"246"	"8.55172413793"	"PLoS One"	"Brunskill EW, Georgas K, Rumballe B, Little MH, Potter SS"	"Division of Developmental Biology, Cincinnati Childrens Hospital Medical Center and the University of Cincinnati School of Medicine, Cincinnati, Ohio, United States of America."	"BACKGROUND: The podocyte is a remarkable cell type, which encases the capillaries of the kidney glomerulus. Although mesodermal in origin it sends out axonal like projections that wrap around the capillaries. These extend yet finer projections, the foot processes, which interdigitate, leaving between them the slit diaphragms, through which the glomerular filtrate must pass. The podocytes are a subject of keen interest because of their key roles in kidney development and disease. METHODOLOGY/PRINCIPAL FINDINGS: In this report we identified and characterized a novel transgenic mouse line, MafB-GFP, which specifically marked the kidney podocytes from a very early stage of development. These mice were then used to facilitate the fluorescent activated cell sorting based purification of podocytes from embryos at E13.5 and E15.5, as well as adults. Microarrays were then used to globally define the gene expression states of podocytes at these different developmental stages. A remarkable picture emerged, identifying the multiple sets of genes that establish the neuronal, muscle, and phagocytic properties of podocytes. The complete combinatorial code of transcription factors that create the podocyte was characterized, and the global lists of growth factors and receptors they express were defined. CONCLUSIONS/SIGNIFICANCE: The complete molecular character of the in vivo podocyte is established for the first time. The active molecular functions and biological processes further define their unique combination of features. The results provide a resource atlas of gene expression patterns of developing and adult podocytes that will help to guide further research of these incredible cells."	"http://www.ncbi.nlm.nih.gov/pubmed/21931791"
 2	"english"	"California, California, USA."	"USA"	"0.00398406374502"	"0.0318725099602"	"0.103585657371"	"251"	"13.2105263158"	"PLoS Computational Biology"	"Bucher D, Grant BJ, Markwick PR, McCammon JA"	"Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, California, USA. bucher.denis@gmail.com"	"Periplasmic binding proteins (PBPs) are a large family of molecular transporters that play a key role in nutrient uptake and chemotaxis in Gram-negative bacteria. All PBPs have characteristic two-domain architecture with a central interdomain ligand-binding cleft. Upon binding to their respective ligands, PBPs undergo a large conformational change that effectively closes the binding cleft. This conformational change is traditionally viewed as a ligand induced-fit process; however, the intrinsic dynamics of the protein may also be crucial for ligand recognition. Recent NMR paramagnetic relaxation enhancement (PRE) experiments have shown that the maltose binding protein (MBP) - a prototypical member of the PBP superfamily - exists in a rapidly exchanging (ns to micros regime) mixture comprising an open state (approx 95%), and a minor partially closed state (approx 5%). Here we describe accelerated MD simulations that provide a detailed picture of the transition between the open and partially closed states, and confirm the existence of a dynamical equilibrium between these two states in apo MBP. We find that a flexible part of the protein called the balancing interface motif (residues 175-184) is displaced during the transformation. Continuum electrostatic calculations indicate that the repacking of non-polar residues near the hinge region plays an important role in driving the conformational change. Oscillations between open and partially closed states create variations in the shape and size of the binding site. The study provides a detailed description of the conformational space available to ligand-free MBP, and has implications for understanding ligand recognition and allostery in related proteins."	"http://www.ncbi.nlm.nih.gov/pubmed/21533070"
+"unk"	"english"	"unknown"	"unknown"	"0.0152284263959"	"0.0152284263959"	"0.0609137055838"	"197"	"10.5263157895"	"BMC Bioinformatics"	"Bult CJ, Drabkin HJ, Evsikov A, Natale D, Arighi C, Roberts N, Ruttenberg A, DEustachio P, Smith B, Blake JA, Wu C"		"ABSTRACT: BACKGROUND: Representing species-specific proteins and protein complexes in ontologies that are both human- and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protein-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. Description: We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. Conclusion: PRO is a unique database resource for species-specific protein complexes. PRO facilitates robust annotation of variations in composition and function contexts for protein complexes within and between species."	"http://www.ncbi.nlm.nih.gov/pubmed/21929785"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21532571"
 2	"english"	"United States of America"	"USA"	"0.0042735042735"	"0.0128205128205"	"0.0555555555556"	"234"	"18.0769230769"	"PLoS One"	"Burks SR, Ziadloo A, Hancock HA, Chaudhry A, Dean DD, Lewis BK, Frenkel V, Frank JA"	"Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America."	"Continuous focused ultrasound (cFUS) has been widely used for thermal ablation of tissues, relying on continuous exposures to generate temperatures necessary to induce coagulative necrosis. Pulsed FUS (pFUS) employs non-continuous exposures that lower the rate of energy deposition and allow cooling to occur between pulses, thereby minimizing thermal effects and emphasizing effects created by non-thermal mechanisms of FUS (i.e., acoustic radiation forces and acoustic cavitation). pFUS has shown promise for a variety of applications including drug and nanoparticle delivery; however, little is understood about the effects these exposures have on tissue, especially with regard to cellular pro-homing factors (growth factors, cytokines, and cell adhesion molecules). We examined changes in murine hamstring muscle following pFUS or cFUS and demonstrate that pFUS, unlike cFUS, has little effect on the histological integrity of muscle and does not induce cell death. Infiltration of macrophages was observed 3 and 8 days following pFUS or cFUS exposures. pFUS increased expression of several cytokines (e.g., IL-1alpha, IL-1beta, TNFalpha, INFgamma, MIP-1alpha, MCP-1, and GMCSF) creating a local cytokine gradient on days 0 and 1 post-pFUS that returns to baseline levels by day 3 post-pFUS. pFUS exposures induced upregulation of other signaling molecules (e.g., VEGF, FGF, PlGF, HGF, and SDF-1alpha) and cell adhesion molecules (e.g., ICAM-1 and VCAM-1) on muscle vasculature. The observed molecular changes in muscle following pFUS may be utilized to target cellular therapies by increasing homing to areas of pathology."	"http://www.ncbi.nlm.nih.gov/pubmed/21931834"
 2	"english"	"United Kingdom"	"UK"	"0.00851063829787"	"0.0127659574468"	"0.0851063829787"	"235"	"13.8235294118"	"PLoS Computational Biology"	"Burroughs NJ, Kohler K, Miloserdov V, Dustin ML, van der Merwe PA, Davis DM"	"Systems Biology Centre, University of Warwick, Coventry, United Kingdom. N.J.Burroughs@warwick.ac.uk"	"Immune synapses formed by T and NK cells both show segregation of the integrin ICAM1 from other proteins such as CD2 (T cell) or KIR (NK cell). However, the mechanism by which these proteins segregate remains unclear; one key hypothesis is a redistribution based on protein size. Simulations of this mechanism qualitatively reproduce observed segregation patterns, but only in certain parameter regimes. Verifying that these parameter constraints in fact hold has not been possible to date, this requiring a quantitative coupling of theory to experimental data. Here, we address this challenge, developing a new methodology for analysing and quantifying image data and its integration with biophysical models. Specifically we fit a binding kinetics model to 2 colour fluorescence data for cytoskeleton independent synapses (2 and 3D) and test whether the observed inverse correlation between fluorophores conforms to size dependent exclusion, and further, whether patterned states are predicted when model parameters are estimated on individual synapses. All synapses analysed satisfy these conditions demonstrating that the mechanisms of protein redistribution have identifiable signatures in their spatial patterns. We conclude that energy processes implicit in protein size based segregation can drive the patternation observed in individual synapses, at least for the specific examples tested, such that no additional processes need to be invoked. This implies that biophysical processes within the membrane interface have a crucial impact on cell:cell communication and cell signalling, governing protein interactions and protein aggregation."	"http://www.ncbi.nlm.nih.gov/pubmed/21829338"
 2	"english"	"New York, USA."	"USA"	"0.00746268656716"	"0.0"	"0.089552238806"	"134"	"10.3076923077"	"Immunity"	"Chaudhry A, Samstein RM, Treuting P, Liang Y, Pils MC, Heinrich JM, Jack RS, Wunderlich FT, Bruning JC, Muller W, Rudensky AY"	"Howard Hughes Medical Institute and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA."	"Effector CD4+ T cell subsets, whose differentiation is facilitated by distinct cytokine cues, amplify the corresponding type of inflammatory response. Regulatory T (Treg) cells integrate environmental cues to suppress particular types of inflammation. In this regard, STAT3, a transcription factor essential for T helper 17 (Th17) cell differentiation, is necessary for Treg cell-mediated control of Th17 cell responses. Here, we showed that anti-inflammatory interleukin-10 (IL-10), and not proinflammatory IL-6 and IL-23 cytokine signaling, endowed Treg cells with the ability to suppress pathogenic Th17 cell responses. Ablation of the IL-10 receptor in Treg cells resulted in selective dysregulation of Th17 cell responses and colitis similar to that observed in mice harboring STAT3-deficient Treg cells. Thus, Treg cells limit Th17 cell inflammation by serving as principal amplifiers of negative regulatory circuits operating in immune effector cells."	"http://www.ncbi.nlm.nih.gov/pubmed/21511185"
 1	"english"	"Boston, United States"	"USA"	"0.0"	"0.0141843971631"	"0.0496453900709"	"141"	"10.8461538462"	"Blood"	"Chauhan SK, Jin Y, Goyal S, Lee HS, Fuchsluger TA, Lee HK, Dana R"	"Schepens Eye Research Institute, and Department of Ophthalmology, Harvard Medical School, Boston, MA, United States;"	"Th17 cells, in addition to their proinflammatory functions, have been recognized as potent inducers of angiogenesis in autoimmune diseases and malignancies. In the present study, we demonstrate distinct mechanisms by which IL17 induces lymphangiogenesis. Using the mouse cornea micropocket and cell culture assays, our data demonstrate that IL17 directly promotes growth of lymphatic vessels by inducing increased expression of prolymphangiogenic VEGF-D and proliferation of lymphatic endothelial cells. However, IL17-induced growth of blood vessels is primarily mediated through IL1beta secretion by IL17-responsive cells. Furthermore, in vivo blockade of IL17 in a preclinical model of Th17-dominant autoimmune ocular disease demonstrates a significant reduction in the corneal lymphangiogenesis and in the progression of clinical disease. Taken together, our findings demonstrate a novel prolymphangiogenic function for Th17/IL17, indicating that IL17 can promote the progression and amplification of immunity in part through its induction of lymphangiogenesis."	"http://www.ncbi.nlm.nih.gov/pubmed/21908425"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21852258"
+"unk"	"english"	"unknown"	"unknown"	"0.0100334448161"	"0.0167224080268"	"0.0535117056856"	"299"	"9.87096774194"	"PLoS One"	"Chelimo K, Embury PB, Odada Sumba P, Vulule J, Ofulla AV, Long C, Kazura JW, Moormann AM"	"Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya."	"Naturally acquired immunity to Plasmodium falciparum malaria in malaria holoendemic areas is characterized by the gradual, age-related development of protection against high-density parasitemia and clinical malaria. Animal studies, and less commonly, observations of humans with malaria, suggest that T-cell responses are important in the development and maintenance of this immunity, which is mediated primarily by antibodies that slow repeated cycles of merozoites through erythrocytes. To advance our rather limited knowledge on human T-cell immunity to blood stage malaria infection, we evaluated CD4 and CD8 T-cell effector memory subset responses to the 42 kDa C-terminal fragment of Merozoite Surface Protein 1 (MSP1(42)), a malaria vaccine candidate, by 49 healthy 0.5 to >/=18 year old residents of a holoendemic area in western Kenya. The proportion of individuals with peripheral blood mononuclear cell MSP1(42) driven IFN-gamma ELISPOT responses increased from 20% (2/20) among 0.5-1 year old children to 90% (9/10) of adults >/=18 years (P = 0.01); parallel increases in the magnitude of IFN-gamma responses were observed across all age groups (0.5, 1, 2, 5 and >/=18 years, P = 0.001). Less than 1% of total CD4 and CD8 T-cells from both children and adults produced IFN-gamma in response to MSP1(42). However, adults had higher proportions of MSP1(42) driven IFN-gamma secreting CD4 and CD8 effector memory (CD45RA(-) CD62L(-)) T-cells than children (CD4: 50.9% vs. 28.8%, P = 0.036; CD8: 52.1% vs. 18.3%, respectively P = 0.009). In contrast, MSP1(42) driven IFN-gamma secreting naive-like, transitional (CD45RA(+) CD62L(+)) CD4 and CD8 cells were the predominant T-cell subset among children with significantly fewer of these cells in adults (CD4: 34.9% vs. 5.1%, P = 0.002; CD8: 47.0% vs. 20.5%, respectively, P = 0.030). These data support the concept that meaningful age-related differences exist in the quality of T-cell immunity to malaria antigens such as MSP1."	"http://www.ncbi.nlm.nih.gov/pubmed/21935482"
 2	"english"	"USA."	"USA"	"0.0135135135135"	"0.027027027027"	"0.0675675675676"	"148"	"8.10526315789"	"Bioinformatics"	"Chen B, McConnell KJ, Wale N, Wild DJ, Gifford EM"	"School of Informatics and Computing, Indiana University at Bloomington, USA."	"MOTIVATION: Networks to predict protein pharmacology can be created using ligand similarity or using known bioassay response profiles of ligands. Recent publications indicate that similarity methods can be highly accurate, but it has been unclear how similarity methods compare to methods that use bioassay response data directly. RESULTS: We created protein networks based on ligand similarity (SEA) and ligand bioassay response-data (BARD) using 155 Pfizer internal BioPrint assays. Both SEA and BARD successfully cluster together proteins with known relationships, and predict some non-obvious relationships. Although the approaches assess target relations from different perspectives, their networks overlap considerably (40% overlap of the top 2% of correlated edges). They can thus be considered as comparable methods, with a distinct advantage of the similarity methods that they only require simple computations (similarity of compound) as opposed to extensive experimental data.Contacts: djwild@indiana.edu, eric.gifford@pfizer.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21903625"
 1	"english"	"United States"	"USA"	"0.0268817204301"	"0.00537634408602"	"0.0752688172043"	"186"	"7.6"	"Blood"	"Chen GL, Arai S, Flowers ME, Otani JM, Qiu J, Cheng EC, McMillan A, Johnston LJ, Shizuru JA, Miklos DB"	"Department of Medicine, Division of Blood and Marrow Transplant, Stanford University School of Medicine, Stanford, CA, United States;"	"Stimulatory anti-platelet derived growth factor receptor alpha (PDGFRA) antibodies have been associated with extensive chronic graft-versus-host disease (cGvHD). We performed a phase 1 dose escalation trial of imatinib in corticosteroid dependent / refractory cGvHD to assess the safety of imatinib and test the hypothesis that abrogation of PDGFRA signaling can ameliorate the manifestations of cGvHD. Fifteen patients were enrolled. Mean follow-up time was 56.6 (18-82.4) weeks. Imatinib 400 mg daily was associated with more frequent moderate to life threatening adverse events than 200 mg daily. The main adverse events were nausea, edema, confusion, diarrhea, liver function test elevation, fatigue, and myalgia. The overall response rate was 40% (6/15). The treatment failure rate was 40% (6/15). 20% (3/15) of subjects had stable disease. Of four subjects with phospho-PDGFRA and phospho-PDGFRB immunohistochemistry studies before and after treatment, inhibition of phosphorylation was observed in three but correlated with response in one. Anti-PDGFRA antibodies were observed in 7/11 evaluable subjects but correlated with clinical activity in four. We conclude that cGvHD responds to imatinib through multiple pathways that may include PDGFRA signal transduction. This study is registered at ClinicalTrials.gov (NCT00760981)."	"http://www.ncbi.nlm.nih.gov/pubmed/21828142"
 1	"english"	"New York, USA."	"USA"	"0.0"	"0.00900900900901"	"0.126126126126"	"111"	"10.0909090909"	"Immunity"	"Chen K, Cerutti A"	"Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. acerutti@imim.es"	"There are great interest and demand for the development of vaccines to prevent and treat diverse microbial infections. Mucosal vaccines elicit immune protection by stimulating the production of antibodies at mucosal surfaces and systemic districts. Being positioned in close proximity to a large community of commensal microbes, the mucosal immune system deploys a heterogeneous population of cells and a complex regulatory network to maintain the balance between surveillance and tolerance. A successful mucosal vaccine relies on leveraging the functions of these immune cells and regulatory components. We review the important cellular interactions and molecular pathways underlying the induction and regulation of mucosal antibody responses and discuss their implications on mucosal vaccination."	"http://www.ncbi.nlm.nih.gov/pubmed/21029959"
 1	"english"	"United States"	"USA"	"0.00480769230769"	"0.00961538461538"	"0.0480769230769"	"208"	"9.26086956522"	"Blood"	"Cuellar-Rodriguez J, Gea-Banacloche J, Freeman AF, Hsu AP, Zerbe CS, Calvo KR, Wilder J, Kurlander R, Olivier KN, Holland SM, Hickstein DD"	"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United States;"	"We performed nonmyeloablative hematopoietic stem cell transplantation in 6 patients with a newly described genetic immunodeficiency syndrome caused by mutations in GATA2- a disease characterized by nontuberculous mycobacterial infection, severe monocytopenia, B and NK cell deficiency, and the propensity to transform to myelodysplastic syndrome/acute myelogenous leukemia. Two patients received peripheral blood stem cells (PBSC) from matched-related donors, 2 patients received PBSC from matched-unrelated donors, and 2 patients received stem cells from umbilical cord blood (UCB) donors. Recipients of matched-related and -unrelated donors received fludarabine and 200 cGy of total body irradiation (TBI), while UCB recipients received cyclophosphamide in addition to fludarabine and TBI as conditioning. All patients received tacrolimus and sirolimus post-transplant. Five patients were alive at a median follow-up of 17.4 months (range, 10 to 25). All patients achieved high levels of donor engraftment in the hematopoietic compartments that were deficient pre-transplant. Adverse events consisted of delayed engraftment in the recipient of a single UCB, GVHD in 4 patients, and immune mediated pancytopenia and nephrotic syndrome in the recipient of a double UCB transplant. Nonmyeloablative allogeneic HSCT in GATA2 deficiency results in reconstitution of the severely deficient monocyte, B-cell, and NK cell populations and reversal of the clinical phenotype. This study was registered at www.clinicaltrials.gov as NCT00923364."	"http://www.ncbi.nlm.nih.gov/pubmed/21816832"
 1	"english"	"Boston"	"USA"	"0.0108695652174"	"0.0"	"0.054347826087"	"92"	"4.4347826087"	"Bioinformatics"	"Cui J, Deluca TF, Jung JY, Wall DP"	"Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115."	"SUMMARY: We developed a package TripletSearch to compute relationships within triplets of genes based on Roundup, an orthologous gene database containing more than 1500 genomes. These relationships, derived from the coevolution of genes, provide valuable information in the detection of biological network organization from the local to the system level, in the inference of protein functions, and in the identification of functional orthologs. To run the computation, users need to provide the GI IDs of the genes of interests. AVAILABILITY: http://wall.hms.harvard.edu/sites/default/files/tripletSearch.tar.gz CONTACT: dpwall@hms.harvard.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21856738"
 2	"english"	"United States of America"	"USA"	"0.0"	"0.008"	"0.048"	"250"	"13.1578947368"	"PLoS One"	"Culbertson MD, Lewis ZR, Nechiporuk AV"	"Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, Oregon, United States of America."	"In vertebrates, the sensory neurons of the epibranchial (EB) ganglia transmit somatosensory signals from the periphery to the CNS. These ganglia are formed during embryogenesis by the convergence and condensation of two distinct populations of precursors: placode-derived neuroblasts and neural crest- (NC) derived glial precursors. In addition to the gliogenic crest, chondrogenic NC migrates into the pharyngeal arches, which lie in close proximity to the EB placodes and ganglia. Here, we examine the respective roles of these two distinct NC-derived populations during development of the EB ganglia using zebrafish morphant and mutants that lack one or both of these NC populations. Our analyses of mutant and morphant zebrafish that exhibit deficiencies in chondrogenic NC at early stages reveal a distinct requirement for this NC subpopulation during early EB ganglion assembly and segmentation. Furthermore, restoration of wildtype chondrogenic NC in one of these mutants, prdm1a, is sufficient to restore ganglion formation, indicating a specific requirement of the chondrogenic NC for EB ganglia assembly. By contrast, analysis of the sox10 mutant, which lacks gliogenic NC, reveals that the initial assembly of ganglia is not affected. However, during later stages of development, EB ganglia are dispersed in the sox10 mutant, suggesting that glia are required to maintain normal EB ganglion morphology. These results highlight novel roles for two subpopulations of NC cells in the formation and maintenance of EB ganglia: chondrogenic NC promotes the early-stage formation of the developing EB ganglia while glial NC is required for the late-stage maintenance of ganglion morphology."	"http://www.ncbi.nlm.nih.gov/pubmed/21931719"
+"unk"	"english"	"unknown"	"unknown"	"0.0143369175627"	"0.00716845878136"	"0.0752688172043"	"279"	"11.16"	"BMC Bioinformatics"	"Cule E, Vineis P, De Iorio M"		"ABSTRACT: BACKGROUND: Technological developments have increased the feasibility of large scale genetic association studies. Densely typed genetic markers are obtained using SNP arrays, next-generation sequencing technologies and imputation. However, SNPs typed using these methods can be highly correlated due to linkage disequilibrium among them, and standard multiple regression techniques fail with these data sets due to their high dimensionality and correlation structure. There has been increasing interest in using penalised regression in the analysis of high dimensional data. Ridge regression is one such penalised regression technique which does not perform variable selection, instead estimating a regression coefficient for each predictor variable. It is therefore desirable to obtain an estimate of the significance of each ridge regression coefficient. RESULTS: We develop and evaluate a test of significance for ridge regression coefficients. Using simulation studies, we demonstrate that the performance of the test is comparable to that of a permutation test, with the advantage of a much-reduced computational cost. We introduce the p-value trace, a plot of the negative logarithm of the p-values of ridge regression coefficients with increasing shrinkage parameter, which enables the visualisation of the change in p-value of the regression coefficients with increasing penalisation. We apply the proposed method to a lung cancer case-control data set from EPIC, the European Prospective Investigation into Cancer and Nutrition. CONCLUSIONS: The proposed test is a useful alternative to a permutation test for the estimation of the significance of ridge regression coefficients, at a much-reduced computational cost. The p-value trace is an informative graphical tool for evaluating the results of a test of significance of ridge regression coefficients as the shrinkage parameter increases, and the proposed test makes its production computationally feasible."	"http://www.ncbi.nlm.nih.gov/pubmed/21929786"
 3	"english"	"United States of America"	"USA"	"0.0266666666667"	"0.00666666666667"	"0.0533333333333"	"150"	"13.6363636364"	"PLoS One"	"Cummins NW, Klicpera A, Sainski AM, Bren GD, Khosla S, Westendorf JJ, Badley AD"	"Division of Infectious Disease, Mayo Clinic, Rochester, Minnesota, United States of America."	"Patients with HIV infection have decreased numbers of osteoblasts, decreased bone mineral density and increased risk of fracture compared to uninfected patients; however, the molecular mechanisms behind these associations remain unclear. We questioned whether Gp120, a component of the envelope protein of HIV capable of inducing apoptosis in many cell types, is able to induce cell death in bone-forming osteoblasts. We show that treatment of immortalized osteoblast-like cells and primary human osteoblasts with exogenous Gp120 in vitro at physiologic concentrations does not result in apoptosis. Instead, in the osteoblast-like U2OS cell line, cells expressing CXCR4, a receptor for Gp120, had increased proliferation when treated with Gp120 compared to control (P<0.05), which was inhibited by pretreatment with a CXCR4 inhibitor and a G-protein inhibitor. This suggests that Gp120 is not an inducer of apoptosis in human osteoblasts and likely does not directly contribute to osteoporosis in infected patients by this mechanism."	"http://www.ncbi.nlm.nih.gov/pubmed/21931863"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21325338"
 2	"english"	"Carolina, Carolina, USA."	"USA"	"0.0164835164835"	"0.010989010989"	"0.0989010989011"	"182"	"12.1333333333"	"ANNUAL REVIEW OF PSYCHOLOGY"	"Curran PJ, Bauer DJ"	"Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. curran@unc.edu"	"Longitudinal models are becoming increasingly prevalent in the behavioral sciences, with key advantages including increased power, more comprehensive measurement, and establishment of temporal precedence. One particularly salient strength offered by longitudinal data is the ability to disaggregate between-person and within-person effects in the regression of an outcome on a time-varying covariate. However, the ability to disaggregate these effects has not been fully capitalized upon in many social science research applications. Two likely reasons for this omission are the general lack of discussion of disaggregating effects in the substantive literature and the need to overcome several remaining analytic challenges that limit existing quantitative methods used to isolate these effects in practice. This review explores both substantive and quantitative issues related to the disaggregation of effects over time, with a particular emphasis placed on the multilevel model. Existing analytic methods are reviewed, a general approach to the problem is proposed, and both the existing and proposed methods are demonstrated using several artificial data sets. Potential limitations and directions for future research are discussed, and recommendations for the disaggregation of effects in practice are offered."	"http://www.ncbi.nlm.nih.gov/pubmed/19575624"
 1	"english"	"California, United States of America"	"USA"	"0.0164835164835"	"0.0274725274725"	"0.120879120879"	"182"	"12.1333333333"	"PLoS Computational Biology"	"Davydov EV, Goode DL, Sirota M, Cooper GM, Sidow A, Batzoglou S"	"Department of Computer Science, Stanford University, Stanford, California, United States of America."	"Computational efforts to identify functional elements within genomes leverage comparative sequence information by looking for regions that exhibit evidence of selective constraint. One way of detecting constrained elements is to follow a bottom-up approach by computing constraint scores for individual positions of a multiple alignment and then defining constrained elements as segments of contiguous, highly scoring nucleotide positions. Here we present GERP++, a new tool that uses maximum likelihood evolutionary rate estimation for position-specific scoring and, in contrast to previous bottom-up methods, a novel dynamic programming approach to subsequently define constrained elements. GERP++ evaluates a richer set of candidate element breakpoints and ranks them based on statistical significance, eliminating the need for biased heuristic extension techniques. Using GERP++ we identify over 1.3 million constrained elements spanning over 7% of the human genome. We predict a higher fraction than earlier estimates largely due to the annotation of longer constrained elements, which improves one to one correspondence between predicted elements with known functional sequences. GERP++ is an efficient and effective tool to provide both nucleotide- and element-level constraint scores within deep multiple sequence alignments."	"http://www.ncbi.nlm.nih.gov/pubmed/21152010"
 2	"english"	"USA."	"USA"	"0.00746268656716"	"0.0261194029851"	"0.0522388059701"	"268"	"9.24137931034"	"BMC Bioinformatics"	"Day RS, McDade KK, Chandran UR, Lisovich A, Conrads TP, Hood BL, Kolli VS, Kirchner D, Litzi T, Maxwell GL"	"Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. day01@pitt.edu"	"BACKGROUND: Studies integrating transcriptomic data with proteomic data can illuminate the proteome more clearly than either separately. Integromic studies can deepen understanding of the dynamic complex regulatory relationship between the transcriptome and the proteome. Integrating these data dictates a reliable mapping between the identifier nomenclature resultant from the two high-throughput platforms. However, this kind of analysis is well known to be hampered by lack of standardization of identifier nomenclature among proteins, genes, and microarray probe sets. Therefore data integration may also play a role in critiquing the fallible gene identifications that both platforms emit. RESULTS: We compared three freely available internet-based identifier mapping resources for mapping UniProt accessions (ACCs) to Affymetrix probesets identifications (IDs): DAVID, EnVision, and NetAffx. Liquid chromatography-tandem mass spectrometry analyses of 91 endometrial cancer and 7 noncancer samples generated 11,879 distinct ACCs. For each ACC, we compared the retrieval sets of probeset IDs from each mapping resource. We confirmed a high level of discrepancy among the mapping resources. On the same samples, mRNA expression was available. Therefore, to evaluate the quality of each ACC-to-probeset match, we calculated proteome-transcriptome correlations, and compared the resources presuming that better mapping of identifiers should generate a higher proportion of mapped pairs with strong inter-platform correlations. A mixture model for the correlations fitted well and supported regression analysis, providing a window into the performance of the mapping resources. The resources have added and dropped matches over two years, but their overall performance has not changed. CONCLUSIONS: The methods presented here serve to achieve concrete context-specific insight, to support well-informed decisions in choosing an ID mapping strategy for omic data merging."	"http://www.ncbi.nlm.nih.gov/pubmed/21619611"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21881561"
+"unk"	"english"	"unknown"	"unknown"	"0.0219298245614"	"0.00877192982456"	"0.0614035087719"	"228"	"12.0"	"Molecular Biology and Evolution"	"Debarry JD, Kissinger JC"	"Center for Tropical and Emerging Global Diseases, University of Georgia."	"Whole-genome comparisons provide insight into genome evolution by informing on gene repertoires, gene gains/losses, and genome organization. Most of our knowledge about eukaryotic genome evolution is derived from studies of multicellular model organisms. The eukaryotic phylum Apicomplexa contains obligate intracellular protist parasites responsible for a wide range of human and veterinary diseases (e.g., malaria, toxoplasmosis, and theileriosis). We have developed an in silico protein-encoding gene based pipeline to investigate synteny across 12 apicomplexan species from six genera. Genome rearrangement between lineages is extensive. Syntenic regions (conserved gene content and order) are rare between lineages and appear to be totally absent across the phylum, with no group of three genes found on the same chromosome and in the same order within 25 kb up- and downstream of any orthologous genes. Conserved synteny between major lineages is limited to small regions in Plasmodium and Theileria/Babesia species, and within these conserved regions, there are a number of proteins putatively targeted to organelles. The observed overall lack of synteny is surprising considering the divergence times and the apparent absence of transposable elements (TEs) within any of the species examined. TEs are ubiquitous in all other groups of eukaryotes studied to date and have been shown to be involved in genomic rearrangements. It appears that there are different criteria governing genome evolution within the Apicomplexa relative to other well-studied unicellular and multicellular eukaryotes."	"http://www.ncbi.nlm.nih.gov/pubmed/21504890"
 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. delannoy@evry.inra.fr"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21289370"
 2	"english"	"Texas, USA."	"USA"	"0.0157480314961"	"0.0236220472441"	"0.0708661417323"	"254"	"13.3684210526"	"Nature"	"Dellomonaco C, Clomburg JM, Miller EN, Gonzalez R"	"Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005, USA."	"Advanced (long-chain) fuels and chemicals are generated from short-chain metabolic intermediates through pathways that require carbon-chain elongation. The condensation reactions mediating this carbon-carbon bond formation can be catalysed by enzymes from the thiolase superfamily, including beta-ketoacyl-acyl-carrier protein (ACP) synthases, polyketide synthases, 3-hydroxy-3-methylglutaryl-CoA synthases, and biosynthetic thiolases. Pathways involving these enzymes have been exploited for fuel and chemical production, with fatty-acid biosynthesis (beta-ketoacyl-ACP synthases) attracting the most attention in recent years. Degradative thiolases, which are part of the thiolase superfamily and naturally function in the beta-oxidation of fatty acids, can also operate in the synthetic direction and thus enable carbon-chain elongation. Here we demonstrate that a functional reversal of the beta-oxidation cycle can be used as a metabolic platform for the synthesis of alcohols and carboxylic acids with various chain lengths and functionalities. This pathway operates with coenzyme A (CoA) thioester intermediates and directly uses acetyl-CoA for acyl-chain elongation (rather than first requiring ATP-dependent activation to malonyl-CoA), characteristics that enable product synthesis at maximum carbon and energy efficiency. The reversal of the beta-oxidation cycle was engineered in Escherichia coli and used in combination with endogenous dehydrogenases and thioesterases to synthesize n-alcohols, fatty acids and 3-hydroxy-, 3-keto- and trans-Delta(2)-carboxylic acids. The superior nature of the engineered pathway was demonstrated by producing higher-chain linear n-alcohols (C >/= 4) and extracellular long-chain fatty acids (C > 10) at higher efficiency than previously reported. The ubiquitous nature of beta-oxidation, aldehyde/alcohol dehydrogenase and thioesterase enzymes has the potential to enable the efficient synthesis of these products in other industrial organisms."	"http://www.ncbi.nlm.nih.gov/pubmed/21832992"
 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 https://sourceforge.net/projects/shap. CONTACT: matt.demaere@unsw.edu.au; r.cavicchioli@unsw.edu.au."	"http://www.ncbi.nlm.nih.gov/pubmed/21775307"
 3	"english"	"United Kingdom"	"UK"	"0.003367003367"	"0.020202020202"	"0.0606060606061"	"297"	"14.1428571429"	"PLoS Computational Biology"	"Hollingsworth TD, Klinkenberg D, Heesterbeek H, Anderson RM"	"MRC Centre for Outbreak Control and Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom. d.hollingsworth@imperial.ac.uk"	"Mitigation of a severe influenza pandemic can be achieved using a range of interventions to reduce transmission. Interventions can reduce the impact of an outbreak and buy time until vaccines are developed, but they may have high social and economic costs. The non-linear effect on the epidemic dynamics means that suitable strategies crucially depend on the precise aim of the intervention. National pandemic influenza plans rarely contain clear statements of policy objectives or prioritization of potentially conflicting aims, such as minimizing mortality (depending on the severity of a pandemic) or peak prevalence or limiting the socio-economic burden of contact-reducing interventions. We use epidemiological models of influenza A to investigate how contact-reducing interventions and availability of antiviral drugs or pre-pandemic vaccines contribute to achieving particular policy objectives. Our analyses show that the ideal strategy depends on the aim of an intervention and that the achievement of one policy objective may preclude success with others, e.g., constraining peak demand for public health resources may lengthen the duration of the epidemic and hence its economic and social impact. Constraining total case numbers can be achieved by a range of strategies, whereas strategies which additionally constrain peak demand for services require a more sophisticated intervention. If, for example, there are multiple objectives which must be achieved prior to the availability of a pandemic vaccine (i.e., a time-limited intervention), our analysis shows that interventions should be implemented several weeks into the epidemic, not at the very start. This observation is shown to be robust across a range of constraints and for uncertainty in estimates of both R(0) and the timing of vaccine availability. These analyses highlight the need for more precise statements of policy objectives and their assumed consequences when planning and implementing strategies to mitigate the impact of an influenza pandemic."	"http://www.ncbi.nlm.nih.gov/pubmed/21347316"
 3	"english"	"UK."	"UK"	"0.0048309178744"	"0.0144927536232"	"0.0289855072464"	"207"	"41.4"	"Nature Genetics"	"Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, Abraham R, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Jones N, Stretton A, Thomas C, Richards A, Ivanov D, Widdowson C, Chapman J, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Beaumont H, Warden D, Wilcock G, Love S, Kehoe PG, Hooper NM, Vardy ER, Hardy J, Mead S, Fox NC, Rossor M, Collinge J, Maier W, Jessen F, Ruther E, Schurmann B, Heun R, Kolsch H, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Frolich L, Hampel H, Gallacher J, Hull M, Rujescu D, Giegling I, Goate AM, Kauwe JS, Cruchaga C, Nowotny P, Morris JC, Mayo K, Sleegers K, Bettens K, Engelborghs S, De Deyn PP, Van Broeckhoven C, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Tsolaki M, Singleton AB, Guerreiro R, Muhleisen TW, Nothen MM, Moebus S, Jockel KH, Klopp N, Wichmann HE, Pankratz VS, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Dickson DW, Graff-Radford NR, Petersen RC, van Duijn CM, Breteler MM, Ikram MA, DeStefano AL, Fitzpatrick AL, Lopez O, Launer LJ, Seshadri S, Berr C, Campion D, Epelbaum J, Dartigues JF, Tzourio C, Alperovitch A, Lathrop M, Feulner TM, Friedrich P, Riehle C, Krawczak M, Schreiber S, Mayhaus M, Nicolhaus S, Wagenpfeil S, Steinberg S, Stefansson H, Stefansson K, Snaedal J, Bjornsson S, Jonsson PV, Chouraki V, Genier-Boley B, Hiltunen M, Soininen H, Combarros O, Zelenika D, Delepine M, Bullido MJ, Pasquier F, Mateo I, Frank-Garcia A, Porcellini E, Hanon O, Coto E, Alvarez V, Bosco P, Siciliano G, Mancuso M, Panza F, Solfrizzi V, Nacmias B, Sorbi S, Bossu P, Piccardi P, Arosio B, Annoni G, Seripa D, Pilotto A, Scarpini E, Galimberti D, Brice A, Hannequin D, Licastro F, Jones L, Holmans PA, Jonsson T, Riemenschneider M, Morgan K, Younkin SG, Owen MJ, ODonovan M, Amouyel P, Williams J"	"Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK."	"We sought to identify new susceptibility loci for Alzheimers disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimers Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P </= 1 x 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 x 10(-17); including ADGC data, meta P = 5.0 x 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 x 10(-14); including ADGC data, meta P = 1.2 x 10(-16)) are new Alzheimers disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 x 10(-4); including ADGC data, meta P = 8.6 x 10(-9)), CD33 (GERAD+, P = 2.2 x 10(-4); including ADGC data, meta P = 1.6 x 10(-9)) and EPHA1 (GERAD+, P = 3.4 x 10(-4); including ADGC data, meta P = 6.0 x 10(-10))."	"http://www.ncbi.nlm.nih.gov/pubmed/21460840"
 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. David_Holloway@bcit.ca"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21304932"
+"unk"	"english"	"unknown"	"unknown"	"0.0285714285714"	"0.0190476190476"	"0.0761904761905"	"105"	"15.1428571429"	"Nature Genetics"	"Holm H, Gudbjartsson DF, Sulem P, Masson G, Helgadottir HT, Zanon C, Magnusson OT, Helgason A, Saemundsdottir J, Gylfason A, Stefansdottir H, Gretarsdottir S, Matthiasson SE, Thorgeirsson GM, Jonasdottir A, Sigurdsson A, Stefansson H, Werge T, Rafnar T, Kiemeney LA, Parvez B, Muhammad R, Roden DM, Darbar D, Thorleifsson G, Walters GB, Kong A, Thorsteinsdottir U, Arnar DO, Stefansson K"	"deCODE Genetics, Sturlugata 8, Reykjavik, Iceland. hilma.holm@decode.is"	"Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5 x 10(2). We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C>T but is approximately 50% for carriers of the c.2161C>T variant."	"http://www.ncbi.nlm.nih.gov/pubmed/21378987"
 1	"english"	"United States of America"	"USA"	"0.0140350877193"	"0.0140350877193"	"0.101754385965"	"285"	"16.7647058824"	"PLoS Computational Biology"	"Hong T, Xing J, Li L, Tyson JJ"	"Genetics, Bioinformatics, and Computational Biology Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America."	"The reciprocal differentiation of T helper 17 (T(H)17) cells and induced regulatory T (iT(reg)) cells plays a critical role in both the pathogenesis and resolution of diverse human inflammatory diseases. Although initial studies suggested a stable commitment to either the T(H)17 or the iT(reg) lineage, recent results reveal remarkable plasticity and heterogeneity, reflected in the capacity of differentiated effectors cells to be reprogrammed among T(H)17 and iT(reg) lineages and the intriguing phenomenon that a group of naive precursor CD4(+) T cells can be programmed into phenotypically diverse populations by the same differentiation signal, transforming growth factor beta. To reconcile these observations, we have built a mathematical model of T(H)17/iT(reg) differentiation that exhibits four different stable steady states, governed by pitchfork bifurcations with certain degrees of broken symmetry. According to the model, a group of precursor cells with some small cell-to-cell variability can differentiate into phenotypically distinct subsets of cells, which exhibit distinct levels of the master transcription-factor regulators for the two T cell lineages. A dynamical control system with these properties is flexible enough to be steered down alternative pathways by polarizing signals, such as interleukin-6 and retinoic acid and it may be used by the immune system to generate functionally distinct effector cells in desired fractions in response to a range of differentiation signals. Additionally, the model suggests a quantitative explanation for the phenotype with high expression levels of both master regulators. This phenotype corresponds to a re-stabilized co-expressing state, appearing at a late stage of differentiation, rather than a bipotent precursor state observed under some other circumstances. Our simulations reconcile most published experimental observations and predict novel differentiation states as well as transitions among different phenotypes that have not yet been observed experimentally."	"http://www.ncbi.nlm.nih.gov/pubmed/21829337"
 3	"english"	"Seattle, USA."	"USA"	"0.0136054421769"	"0.0340136054422"	"0.108843537415"	"147"	"8.82352941176"	"Bioinformatics"	"Hormozdiari F, Hach F, Sahinalp SC, Eichler EE, Alkan C"	"Department of Genome Sciences, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195-5065, USA."	"MOTIVATION: Discovering variation among high-throughput sequenced genomes relies on efficient and effective mapping of sequence reads. The speed, sensitivity and accuracy of read mapping are crucial to determining the full spectrum of single nucleotide variants (SNVs) as well as structural variants (SVs) in the donor genomes analyzed. RESULTS: We present drFAST, a read mapper designed for di-base encoded color-space sequences generated with the AB SOLiD platform. drFAST is specially designed for better delineation of structural variants, including segmental duplications, and is able to return all possible map locations and underlying sequence variation of short reads within a user-specified distance threshold. We show that drFAST is more sensitive in comparison to all commonly used aligners such as Bowtie, BFAST and SHRiMP. drFAST is also faster than both BFAST and SHRiMP and achieves a mapping speed comparable to Bowtie. AVAILABILITY: The source code for drFAST is available at http://drfast.sourceforge.net"	"http://www.ncbi.nlm.nih.gov/pubmed/21586516"
 2	"english"	"California, USA."	"USA"	"0.00833333333333"	"0.025"	"0.05"	"120"	"13.3333333333"	"Immunity"	"Hou B, Saudan P, Ott G, Wheeler ML, Ji M, Kuzmich L, Lee LM, Coffman RL, Bachmann MF, DeFranco AL"	"Department of Microbiology & Immunology, University of California, San Francisco, CA 94143, USA. baidong_hou@ibp.ac.cn"	"The contribution of Toll-like receptor (TLR) signaling to T cell-dependent (TD) antibody responses was assessed by using mice lacking the TLR signaling adaptor MyD88 in individual cell types. When a soluble TLR9 ligand was used as adjuvant for a protein antigen, MyD88 was required in dendritic cells but not in B cells to enhance the TD antibody response, regardless of the inherent immunogenicity of the antigen. In contrast, a TLR9 ligand contained within a virus-like particle substantially augmented the TD germinal center IgG antibody response, and this augmentation required B cell MyD88. The ability of B cells to discriminate between antigens based on the physical form of a TLR ligand probably reflects an adaptation to facilitate strong antiviral antibody responses."	"http://www.ncbi.nlm.nih.gov/pubmed/21353603"
 2	"english"	"United Kingdom"	"UK"	"0.0133333333333"	"0.0433333333333"	"0.0366666666667"	"300"	"12.0"	"PLoS One"	"Jordan TR, Fuggetta G, Paterson KB, Kurtev S, Xu M"	"Faculty of Medicine and Biological Sciences, University of Leicester, Leicester, United Kingdom."	"BACKGROUND: The existence and function of unilateral hemispheric projections within foveal vision may substantially affect foveal word recognition. The purpose of this research was to reveal these projections and determine their functionality. METHODOLOGY: Single words (and pseudowords) were presented to the left or right of fixation, entirely within either foveal or extrafoveal vision. To maximize the likelihood of unilateral projections for foveal displays, stimuli in foveal vision were presented away from the midline. The processing of stimuli in each location was assessed by combining behavioural measures (reaction times, accuracy) with on-line monitoring of hemispheric activity using event-related potentials recorded over each hemisphere, and carefully-controlled presentation procedures using an eye-tracker linked to a fixation-contingent display. PRINCIPAL FINDINGS: Event-related potentials 100-150 ms and 150-200 ms after stimulus onset indicated that stimuli in extrafoveal and foveal locations were projected unilaterally to the hemisphere contralateral to the presentation hemifield with no concurrent projection to the ipsilateral hemisphere. These effects were similar for words and pseudowords, suggesting this early division occurred before word recognition. Indeed, event-related potentials revealed differences between words and pseudowords 300-350 ms after stimulus onset, for foveal and extrafoveal locations, indicating that word recognition had now occurred. However, these later event-related potentials also revealed that the hemispheric division observed previously was no longer present for foveal locations but remained for extrafoveal locations. These findings closely matched the behavioural finding that foveal locations produced similar performance each side of fixation but extrafoveal locations produced left-right asymmetries. CONCLUSIONS: These findings indicate that an initial division in unilateral hemispheric projections occurs in foveal vision away from the midline but is not apparent, or functional, when foveal word recognition actually occurs. In contrast, the division in unilateral hemispheric projections that occurs in extrafoveal locations is still apparent, and is functional, when extrafoveal word recognition takes place."	"http://www.ncbi.nlm.nih.gov/pubmed/21935368"
 2	"english"	"United States of America"	"USA"	"0.00442477876106"	"0.0265486725664"	"0.0840707964602"	"226"	"15.0666666667"	"PLoS Computational Biology"	"Jovic A, Howell B, Cote M, Wade SM, Mehta K, Miyawaki A, Neubig RR, Linderman JJ, Takayama S"	"Biomedical Engineering Department, University of Michigan, Ann Arbor, Michigan, United States of America."	"This paper introduces the concept of phase-locking analysis of oscillatory cellular signaling systems to elucidate biochemical circuit architecture. Phase-locking is a physical phenomenon that refers to a response mode in which system output is synchronized to a periodic stimulus; in some instances, the number of responses can be fewer than the number of inputs, indicative of skipped beats. While the observation of phase-locking alone is largely independent of detailed mechanism, we find that the properties of phase-locking are useful for discriminating circuit architectures because they reflect not only the activation but also the recovery characteristics of biochemical circuits. Here, this principle is demonstrated for analysis of a G-protein coupled receptor system, the M3 muscarinic receptor-calcium signaling pathway, using microfluidic-mediated periodic chemical stimulation of the M3 receptor with carbachol and real-time imaging of resulting calcium transients. Using this approach we uncovered the potential importance of basal IP3 production, a finding that has important implications on calcium response fidelity to periodic stimulation. Based upon our analysis, we also negated the notion that the Gq-PLC interaction is switch-like, which has a strong influence upon how extracellular signals are filtered and interpreted downstream. Phase-locking analysis is a new and useful tool for model revision and mechanism elucidation; the method complements conventional genetic and chemical tools for analysis of cellular signaling circuitry and should be broadly applicable to other oscillatory pathways."	"http://www.ncbi.nlm.nih.gov/pubmed/21203481"
 1	"english"	"USA."	"USA"	"0.00877192982456"	"0.00877192982456"	"0.0701754385965"	"114"	"12.7777777778"	"Glycobiology"	"Ju T, Xia B, Aryal RP, Wang W, Wang Y, Ding X, Mi R, He M, Cummings RD"	"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA. tju@emory.edu"	"Loss of T-synthase (uridine diphosphate galactose:N-acetylgalactosaminyl-alpha1-Ser/Thr beta3galactosyltransferase), a key enzyme required for the formation of mucin-type core 1 O-glycans, is observed in several human diseases, including cancer, Tn syndrome and IgA nephropathy, but current methods to assay the enzyme use radioactive substrates and complicated isolation of the product. Here we report the development of a novel fluorescent assay to measure its activity in a variety of tumor cell lines. Deficiencies in T-synthase activity correlate with mutations in the gene encoding the molecular chaperone Cosmc that is required for folding the T-synthase. This new high-throughput assay allows for facile screening of tumor specimens and other biological material for T-synthase activity and could be used diagnostically."	"http://www.ncbi.nlm.nih.gov/pubmed/20959392"
+"unk"	"english"	"unknown"	"unknown"	"0.00961538461538"	"0.0144230769231"	"0.100961538462"	"208"	"8.44"	"BMC Bioinformatics"	"Jung SK, McDonald K"		"ABSTRACT: BACKGROUND: Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. RESULTS: The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. CONCLUSION: Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net."	"http://www.ncbi.nlm.nih.gov/pubmed/21846353"
 1	"english"	"Yale, USA."	"USA"	"0.0"	"0.0294117647059"	"0.0588235294118"	"34"	"6.8"	"Immunity"	"Jung YW, Kaech SM"	"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA."	"Beuneu et al. (2010) report that the amount of antigenic stimulation initially sensed by naive CD8(+) T cells can establish differentiation set points that are stably maintained in clonal progeny to promote functional diversity."	"http://www.ncbi.nlm.nih.gov/pubmed/20870171"
 1	"english"	"California, California, USA."	"USA"	"0.0193548387097"	"0.0322580645161"	"0.0903225806452"	"310"	"18.2352941176"	"Nature"	"Jutzi M, Asphaug E"	"Earth and Planetary Sciences Department, University of California, Santa Cruz, 1156 Highstreet, Santa Cruz, California 95060, USA. martin.jutzi@space.unibe.ch"	"The most striking geological feature of the Moon is the terrain and elevation dichotomy between the hemispheres: the nearside is low and flat, dominated by volcanic maria, whereas the farside is mountainous and deeply cratered. Associated with this geological dichotomy is a compositional and thermal variation, with the nearside Procellarum KREEP (potassium/rare-earth element/phosphorus) Terrane and environs interpreted as having thin, compositionally evolved crust in comparison with the massive feldspathic highlands. The lunar dichotomy may have been caused by internal effects (for example spatial variations in tidal heating, asymmetric convective processes or asymmetric crystallization of the magma ocean) or external effects (such as the event that formed the South Pole/Aitken basin or asymmetric cratering). Here we consider its origin as a late carapace added by the accretion of a companion moon. Companion moons are a common outcome of simulations of Moon formation from a protolunar disk resulting from a giant impact, and although most coplanar configurations are unstable, a  approximately 1,200-km-diameter moon located at one of the Trojan points could be dynamically stable for tens of millions of years after the giant impact. Most of the Moons magma ocean would solidify on this timescale, whereas the companion moon would evolve more quickly into a crust and a solid mantle derived from similar disk material, and would presumably have little or no core. Its likely fate would be to collide with the Moon at  approximately 2-3 km s(-1), well below the speed of sound in silicates. According to our simulations, a large moon/Moon size ratio ( approximately 0.3) and a subsonic impact velocity lead to an accretionary pile rather than a crater, contributing a hemispheric layer of extent and thickness consistent with the dimensions of the farside highlands and in agreement with the degree-two crustal thickness profile. The collision furthermore displaces the KREEP-rich layer to the opposite hemisphere, explaining the observed concentration."	"http://www.ncbi.nlm.nih.gov/pubmed/21814278"
 2	"english"	"USA."	"USA"	"0.0201005025126"	"0.0251256281407"	"0.0904522613065"	"199"	"13.3333333333"	"Glycobiology"	"Kadirvelraj R, Grant OC, Goldstein IJ, Winter HC, Tateno H, Fadda E, Woods RJ"	"Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA."	"Glycan chains that terminate in sialic acid (Neu5Ac) are frequently the receptors targeted by pathogens for initial adhesion. Carbohydrate-binding proteins (lectins) with specificity for Neu5Ac are particularly useful in the detection and isolation of sialylated glycoconjugates, such as those associated with pathogen adhesion as well as those characteristic of several diseases including cancer. Structural studies of lectins are essential in order to understand the origin of their specificity, which is particularly important when employing such reagents as diagnostic tools. Here, we report a crystallographic and molecular dynamics (MD) analysis of a lectin from Polyporus squamosus (PSL) that is specific for glycans terminating with the sequence Neu5Acalpha2-6Galbeta. Because of its importance as a histological reagent, the PSL structure was solved (to 1.7 A) in complex with a trisaccharide, whose sequence (Neu5Acalpha2-6Galbeta1-4GlcNAc) is exploited by influenza A hemagglutinin for viral adhesion to human tissue. The structural data illuminate the origin of the high specificity of PSL for the Neu5Acalpha2-6Gal sequence. Theoretical binding free energies derived from the MD data confirm the key interactions identified crystallographically and provide additional insight into the relative contributions from each amino acid, as well as estimates of the importance of entropic and enthalpic contributions to binding."	"http://www.ncbi.nlm.nih.gov/pubmed/21436237"
 2	"english"	"USA."	"USA"	"0.0"	"0.0"	"0.0526315789474"	"38"	"7.6"	"Immunity"	"Kang Z, Gulen MF, Li X"	"Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA."	"In this issue of Immunity, Shaw et al. (2011) report that the NOD-RICK signaling axis is required for the activation of dendritic cells infiltrating the central nervous system, leading to reactivation of antigen-specific T cells and autoimmune inflammation."	"http://www.ncbi.nlm.nih.gov/pubmed/21272781"
 2	"english"	"United Kingdom"	"UK"	"0.011673151751"	"0.0194552529183"	"0.0972762645914"	"257"	"13.5263157895"	"Molecular Biology and Evolution"	"Kapralov MV, Kubien DS, Andersson I, Filatov DA"	"Department of Plant Sciences, University of Oxford, Oxford, United Kingdom."	"Rubisco, the primary photosynthetic carboxylase, evolved 3-4 billion years ago in an anaerobic, high CO(2) atmosphere. The combined effect of low CO(2) and high O(2) levels in the modern atmosphere, and the inability of Rubisco to distinguish completely between CO(2) and O(2), leads to the occurrence of an oxygenation reaction that reduces the efficiency of photosynthesis. Among land plants, C(4) photosynthesis largely solves this problem by facilitating a high CO(2)/O(2) ratio at the site of Rubisco that resembles the atmosphere in which the ancestral enzyme evolved. The prediction that such conditions favor Rubiscos with higher kcat(CO2) and lower CO(2)/O(2) specificity (S(C/O)) is well supported, but the structural basis for the differences between C(3) and C(4) Rubiscos is not clear. Flaveria (Asteraceae) includes C(3), C(3)-C(4) intermediate, and C(4) species with kinetically distinct Rubiscos, providing a powerful system in which to study the biochemical transition of Rubisco during the evolution from C(3) to C(4) photosynthesis. We analyzed the molecular evolution of chloroplast rbcL and nuclear rbcS genes encoding the large subunit (LSu) and small subunit (SSu) of Rubisco from 15 Flaveria species. We demonstrate positive selection on both subunits, although selection is much stronger on the LSu. In Flaveria, two positively selected LSu amino acid substitutions, M309I and D149A, distinguish C(4) Rubiscos from the ancestral C(3) species and statistically account for much of the kinetic difference between the two groups. However, although Flaveria lacks a characteristic C(4) SSu, our data suggest that specific residue substitutions in the SSu are correlated with the kinetic properties of Rubisco in this genus."	"http://www.ncbi.nlm.nih.gov/pubmed/21172830"
 2	"english"	"California, California, United States of America"	"USA"	"0.0131004366812"	"0.0393013100437"	"0.131004366812"	"229"	"13.4705882353"	"PLoS One"	"Kashani AH, Kirkman E, Martin G, Humayun MS"	"Doheny Eye Institute, University of Southern California, Los Angeles, California, United States of America."	"Diagnosis of retinal vascular diseases depends on ophthalmoscopic findings that most often occur after severe visual loss (as in vein occlusions) or chronic changes that are irreversible (as in diabetic retinopathy). Despite recent advances, diagnostic imaging currently reveals very little about the vascular function and local oxygen delivery. One potentially useful measure of vascular function is measurement of hemoglobin oxygen content. In this paper, we demonstrate a novel method of accurately, rapidly and easily measuring oxygen saturation within retinal vessels using in vivo imaging spectroscopy. This method uses a commercially available fundus camera coupled to two-dimensional diffracting optics that scatter the incident light onto a focal plane array in a calibrated pattern. Computed tomographic algorithms are used to reconstruct the diffracted spectral patterns into wavelength components of the original image. In this paper the spectral components of oxy- and deoxyhemoglobin are analyzed from the vessels within the image. Up to 76 spectral measurements can be made in only a few milliseconds and used to quantify the oxygen saturation within the retinal vessels over a 10-15 degree field. The method described here can acquire 10-fold more spectral data in much less time than conventional oximetry systems (while utilizing the commonly accepted fundus camera platform). Application of this method to animal models of retinal vascular disease and clinical subjects will provide useful and novel information about retinal vascular disease and physiology."	"http://www.ncbi.nlm.nih.gov/pubmed/21931729"
+1	"english"	"unknown"	"unknown"	"0.0159362549801"	"0.0159362549801"	"0.0557768924303"	"251"	"8.22580645161"	"Database(Oxford)"	"Katz LS, Humphrey JC, Conley AB, Nelakuditi V, Kislyuk AO, Agrawal S, Jayaraman P, Harcourt BH, Olsen-Rasmussen MA, Frace M, Sharma NV, Mayer LW, Jordan IK"	"School of Biology, Georgia Institute of Technology."	"Neisseria meningitidis is an important pathogen, causing life-threatening diseases including meningitis, septicemia and in some cases pneumonia. Genomic studies hold great promise for N. meningitidis research, but substantial database resources are needed to deal with the wealth of information that comes with completely sequenced and annotated genomes. To address this need, we developed Neisseria Base (NBase), a comparative genomics database and genome browser that houses and displays publicly available N. meningitidis genomes. In addition to existing N. meningitidis genome sequences, we sequenced and annotated 19 new genomes using 454 pyrosequencing and the CG-Pipeline genome analysis tool. In total, NBase hosts 27 complete N. meningitidis genome sequences along with their associated annotations. The NBase platform is designed to be scalable, via the underlying database schema and modular code architecture, such that it can readily incorporate new genomes and their associated annotations. The front page of NBase provides user access to these genomes through searching, browsing and downloading. NBase search utility includes BLAST-based sequence similarity searches along with a variety of semantic search options. All genomes can be browsed using a modified version of the GBrowse platform, and a plethora of information on each gene can be viewed using a customized details page. NBase also has a whole-genome comparison tool that yields single-nucleotide polymorphism differences between two user-defined groups of genomes. Using the virulent ST-11 lineage as an example, we demonstrate how this comparative genomics utility can be used to identify novel genomic markers for molecular profiling of N. meningitidis. Database URL: http://nbase.biology.gatech.edu."	"http://www.ncbi.nlm.nih.gov/pubmed/21930505"
 2	"english"	"Boston, United States"	"USA"	"0.0257731958763"	"0.0154639175258"	"0.0618556701031"	"194"	"14.9230769231"	"Blood"	"Kawano Y, Kim HT, Matsuoka KI, Bascug G, McDonough S, Ho VT, Cutler C, Koreth J, Alyea EP, Antin JH, Soiffer RJ, Ritz J"	"Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States;"	"CD4+CD25+Foxp3+ regulatory T cells (Treg) play an important role in the control of chronic graft-versus-host disease (cGVHD). In this study, we examined telomere length and telomerase activity of Treg and conventional CD4+ T cells (Tcon) in 61 patients who survived more than 2 years after allogeneic hematopoietic stem cell transplantation (HSCT). Cell proliferation and expression of Bcl-2 were also measured in each subset. Treg telomere length was shorter and Treg telomerase activity was increased compared to Tcon (p <0.0001). Post transplant Treg were also more highly proliferative than Tcon (p <0.0001). Treg number, telomerase activity and expression of Bcl-2 were each inversely associated with severity of cGVHD. These data indicate that activation of telomerase is not sufficient to prevent telomere shortening in highly proliferative Treg. However, telomerase activation is associated with increased Bcl-2 expression and higher Treg numbers in patients with no or mild cGVHD. In contrast, patients with moderate or severe cGVHD have fewer Treg with lower levels of telomerase activity and Bcl-2 expression. These results suggest that failure to activate Treg telomerase may restrict proliferative capacity and increase apoptotic susceptibility, resulting in the loss of peripheral tolerance and the development of cGVHD."	"http://www.ncbi.nlm.nih.gov/pubmed/21900196"
 2	"english"	"USA."	"USA"	"0.00291545189504"	"0.0233236151603"	"0.0758017492711"	"343"	"10.3939393939"	"Molecular Biology and Evolution"	"Kawasaki K, Lafont AG, Sire JY"	"Department of Anthropology, Pennsylvania State University, USA. kuk2@psu.edu"	"Caseins are among cardinal proteins that evolved in the lineage leading to mammals. In milk, caseins and calcium phosphate (CaP) form a huge complex called casein micelle. By forming the micelle, milk maintains high CaP concentrations, which help altricial mammalian neonates to grow bone and teeth. Two types of caseins are known. Ca-sensitive caseins (alpha(s)- and beta-caseins) bind Ca but precipitate at high Ca concentrations, whereas Ca-insensitive casein (kappa-casein) does not usually interact with Ca but instead stabilizes the micelle. Thus, it is thought that these two types of caseins are both necessary for stable micelle formation. Both types of caseins show high substitution rates, which make it difficult to elucidate the evolution of caseins. Yet, recent studies have revealed that all casein genes belong to the secretory calcium-binding phosphoprotein (SCPP) gene family that arose by gene duplication. In the present study, we investigated exon-intron structures and phylogenetic distributions of casein and other SCPP genes, particularly the odontogenic ameloblast-associated (ODAM) gene, the SCPP-Pro-Gln-rich 1 (SCPPPQ1) gene, and the follicular dendritic cell secreted peptide (FDCSP) gene. The results suggest that contemporary Ca-sensitive casein genes arose from a putative common ancestor, which we refer to as CSN1/2. The six putative exons comprising CSN1/2 are all found in SCPPPQ1, although ODAM also shares four of these exons. By contrast, the five exons of the Ca-insensitive casein gene are all reminiscent of FDCSP. The phylogenetic distribution of these genes suggests that both SCPPPQ1 and FDCSP arose from ODAM. We thus argue that all casein genes evolved from ODAM via two different pathways; Ca-sensitive casein genes likely originated directly from SCPPPQ1, whereas the Ca-insensitive casein genes directly differentiated from FDCSP. Further, expression of ODAM, SCPPPQ1, and FDCSP was detected in dental tissues, supporting the idea that both types of caseins evolved as Ca-binding proteins. Based on these findings, we propose two alternative hypotheses for micelle formation in primitive milk. The conserved biochemical characteristics in caseins and their immediate ancestors also suggest that many slight genetic modifications have created modern caseins, proteins vital to the sustained success of mammals."	"http://www.ncbi.nlm.nih.gov/pubmed/21245413"
 2	"english"	"Cambridge, UK."	"USA"	"0.0"	"0.0178571428571"	"0.0803571428571"	"112"	"12.4444444444"	"Nature"	"Keane TM, Goodstadt L, Danecek P, White MA, Wong K, Yalcin B, Heger A, Agam A, Slater G, Goodson M, Furlotte NA, Eskin E, Nellaker C, Whitley H, Cleak J, Janowitz D, Hernandez-Pliego P, Edwards A, Belgard TG, Oliver PL, McIntyre RE, Bhomra A, Nicod J, Gan X, Yuan W, van der Weyden L, Steward CA, Bala S, Stalker J, Mott R, Durbin R, Jackson IJ, Czechanski A, Guerra-Assuncao JA, Donahue LR, Reinholdt LG, Payseur BA, Ponting CP, Birney E, Flint J, Adams DJ"	"The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK."	"We report genome sequences of 17 inbred strains of laboratory mice and identify almost ten times more variants than previously known. We use these genomes to explore the phylogenetic history of the laboratory mouse and to examine the functional consequences of allele-specific variation on transcript abundance, revealing that at least 12% of transcripts show a significant tissue-specific expression bias. By identifying candidate functional variants at 718 quantitative trait loci we show that the molecular nature of functional variants and their position relative to genes vary according to the effect size of the locus. These sequences provide a starting point for a new era in the functional analysis of a key model organism."	"http://www.ncbi.nlm.nih.gov/pubmed/21921910"
 2	"english"	"Ireland"	"Ireland"	"0.00425531914894"	"0.00425531914894"	"0.131914893617"	"235"	"12.6842105263"	"Glycobiology"	"Marino K, Lane JA, Abrahams JL, Struwe WB, Harvey DJ, Marotta M, Hickey RM, Rudd PM"	"National Institute for Bioprocessing Research and Training, Dublin-Oxford Glycobiology Laboratory, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland."	"Although the properties of milk oligosaccharides have been of scientific interest for many years, their structural diversity presents a challenging analytical task. In the quest for a simple and robust technology to characterize the different oligosaccharides present in milk, we developed an analytical scheme based on their fluorescent labeling, pre-fractionation by weak anionic exchange chromatography and separation by hydrophilic interaction liquid chromatography (HILIC)-high performance liquid chromatography (HPLC). HILIC relies on the hydrophilic potential of the molecule, which accounts for differences in properties such as molecular volume, lipophilic surface area, charge, composition, structure, linkage and oligosaccharide branching. The robustness of the methodology has been demonstrated using bovine colostrum oligosaccharides as a case study. Structural assignments for 37 free glycans, including 20 sialylated species, were obtained by a combination of HILIC-HPLC, exoglycosidase digestion and offline negative-ion mode mass spectrometry (MS)/MS. Parameters obtained for each glycan, including linkages, enzymatic digestion products and glucose unit values, will be added to GlycoBase, a public access database (http://glycobase.nibrt.ie/glycobase.html). This approach provides a basis for the analysis of free milk oligosaccharides in a fast and sensitive manner and could be adapted for an automated technology platform amenable to diverse environments. Indeed, our approach, in conjunction with bacterial-binding assays, can provide a better understanding of the structural elements required for biological activity of free milk oligosaccharides and could serve as a scientific basis for the selection of such bioactives from various food sources."	"http://www.ncbi.nlm.nih.gov/pubmed/21566017"
 2	"english"	"Cambridge, Cambridge, United Kingdom"	"USA"	"0.00381679389313"	"0.0229007633588"	"0.0572519083969"	"262"	"12.4761904762"	"PLoS Computational Biology"	"Markowetz F, Mulder KW, Airoldi EM, Lemischka IR, Troyanskaya OG"	"Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom. florian.markowetz@cancer.org.uk"	"Embryonic stem cells (ESC) have the potential to self-renew indefinitely and to differentiate into any of the three germ layers. The molecular mechanisms for self-renewal, maintenance of pluripotency and lineage specification are poorly understood, but recent results point to a key role for epigenetic mechanisms. In this study, we focus on quantifying the impact of histone 3 acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We analyze genome-wide histone acetylation patterns and gene expression profiles measured over the first five days of cell differentiation triggered by silencing Nanog, a key transcription factor in ESC regulation. We explore the temporal and spatial dynamics of histone acetylation data and its correlation with gene expression using supervised and unsupervised statistical models. On a genome-wide scale, changes in acetylation are significantly correlated to changes in mRNA expression and, surprisingly, this coherence increases over time. We quantify the predictive power of histone acetylation for gene expression changes in a balanced cross-validation procedure. In an in-depth study we focus on genes central to the regulatory network of Mouse ESC, including those identified in a recent genome-wide RNAi screen and in the PluriNet, a computationally derived stem cell signature. We find that compared to the rest of the genome, ESC-specific genes show significantly more acetylation signal and a much stronger decrease in acetylation over time, which is often not reflected in a concordant expression change. These results shed light on the complexity of the relationship between histone acetylation and gene expression and are a step forward to dissect the multilayer regulatory mechanisms that determine stem cell fate."	"http://www.ncbi.nlm.nih.gov/pubmed/21187909"
 2	"english"	"California, USA."	"USA"	"0.0"	"0.0"	"0.15625"	"64"	"12.8"	"Nature Genetics"	"Martin F, Dixit VM"	"Department of Immunology, Genentech, South San Francisco, California, USA."	"Complex autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, multiple sclerosis, psoriasis and inflammatory bowel disease have different pathological presentations but have overlapping genetic susceptibility variants. A new study using mice lacking Tnfaip3, whose ortholog is linked to autoimmune disease in humans, leads to insights in the role of one molecular driver of varied clinical symptomatology in disparate autoimmune disorders."	"http://www.ncbi.nlm.nih.gov/pubmed/21874034"
+"unk"	"english"	"unknown"	"unknown"	"0.0127118644068"	"0.021186440678"	"0.0550847457627"	"236"	"8.74074074074"	"Molecular Biology and Evolution"	"Martin SH, Wingfield BD, Wingfield MJ, Steenkamp ET"	"Department of Genetics, Forestry and Agricultural Biotechnology Institute, University of Pretoria, South Africa."	"The reproductive genes of fungi, like those of many other organisms, are thought to diversify rapidly. This phenomenon could be associated with the formation of reproductive barriers and speciation. Ascomycetes produce two classes of mating type-specific peptide pheromones. These are required for recognition between the mating types of heterothallic species. Little is known regarding the diversity or the extent of species specificity in pheromone peptides among these fungi. We compared the putative protein-coding DNA sequences of the 2 pheromone classes from 70 species of Ascomycetes. The data set included previously described pheromones and putative pheromones identified from genomic sequences. In addition, pheromone genes from 12 Fusarium species in the Gibberella fujikuroi complex were amplified and sequenced. Pheromones were largely conserved among species in this complex and, therefore, cannot alone account for the reproductive barriers observed between these species. In contrast, pheromone peptides were highly diverse among many other Ascomycetes, with evidence for both positive diversifying selection and relaxed selective constraint. Repeats of the alpha-factor-like pheromone, which occur in tandem arrays of variable copy number, were found to be conserved through purifying selection and not concerted evolution. This implies that sequence specificity may be important for pheromone reception and that interspecific differences may indeed be associated with functional divergence. Our findings also suggest that frequent duplication and loss causes the tandem repeats to experience birth-and-death evolution, which could in fact facilitate interspecific divergence of pheromone peptide sequences."	"http://www.ncbi.nlm.nih.gov/pubmed/21252281"
 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. david.martinez@nicta.com.au"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21489223"
 2	"english"	"USA."	"USA"	"0.00680272108844"	"0.0204081632653"	"0.0408163265306"	"147"	"11.3846153846"	"Immunity"	"Mashayekhi M, Sandau MM, Dunay IR, Frickel EM, Khan A, Goldszmid RS, Sher A, Ploegh HL, Murphy TL, Sibley LD, Murphy KM"	"Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA."	"CD8alpha(+) dendritic cells (DCs) are important in vivo for cross-presentation of antigens derived from intracellular pathogens and tumors. Additionally, secretion of interleukin-12 (IL-12) by CD8alpha(+) DCs suggests a role for these cells in response to Toxoplasma gondii antigens, although it remains unclear whether these cells are required for protection against T. gondii infection. Toward this goal, we examined T. gondii infection of Batf3(-/-) mice, which selectively lack only lymphoid-resident CD8alpha(+) DCs and related peripheral CD103(+) DCs. Batf3(-/-) mice were extremely susceptible to T. gondii infection, with decreased production of IL-12 and interferon-gamma. IL-12 administration restored resistance in Batf3(-/-) mice, and mice in which IL-12 production was ablated only from CD8alpha(+) DCs failed to control infection. These results reveal that the function of CD8alpha(+) DCs extends beyond a role in cross-presentation and includes a critical role for activation of innate immunity through IL-12 production during T. gondii infection."	"http://www.ncbi.nlm.nih.gov/pubmed/21867928"
 1	"english"	"USA."	"USA"	"0.0"	"0.0135135135135"	"0.0878378378378"	"148"	"8.70588235294"	"ANNUAL REVIEW OF PSYCHOLOGY"	"Matthews KA, Gallo LC"	"Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. matthewska@upmc.edu"	"Low socioeconomic status (SES) is a reliable correlate of poor physical health. Rather than treat SES as a covariate, health psychology has increasingly focused on the psychobiological pathways that inform understanding why SES is related to physical health. This review assesses the status of research that has examined stress and its associated distress, and social and personal resources as pathways. It highlights work on biomarkers and biological pathways related to SES that can serve as intermediate outcomes in future studies. Recent emphasis on the accumulation of psychobiological risks across the life course is summarized and represents an important direction for future research. Studies that test pathways from SES to candidate psychosocial pathways to health outcomes are few in number but promising. Future research should test integrated models rather than taking piecemeal approaches to evidence. Much work remains to be done, but the questions are of great health significance."	"http://www.ncbi.nlm.nih.gov/pubmed/20636127"
 2	"english"	"Duke, USA., duke"	"USA"	"0.00790513833992"	"0.0118577075099"	"0.0830039525692"	"253"	"6.74358974359"	"Bioinformatics"	"Mayhew MB, Robinson JW, Jung B, Haase SB, Hartemink AJ"	"Program in Computational Biology and Bioinformatics, Department of Computer Science, Center for Systems Biology, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA. michael.mayhew@duke.edu"	"MOTIVATION: To advance understanding of eukaryotic cell division, it is important to observe the process precisely. To this end, researchers monitor changes in dividing cells as they traverse the cell cycle, with the presence or absence of morphological or genetic markers indicating a cells position in a particular interval of the cell cycle. A wide variety of marker data is available, including information-rich cellular imaging data. However, few formal statistical methods have been developed to use these valuable data sources in estimating how a population of cells progresses through the cell cycle. Furthermore, existing methods are designed to handle only a single binary marker of cell cycle progression at a time. Consequently, they cannot facilitate comparison of experiments involving different sets of markers. RESULTS: Here, we develop a new sampling model to accommodate an arbitrary number of different binary markers that characterize the progression of a population of dividing cells along a branching process. We engineer a strain of Saccharomyces cerevisiae with fluorescently labeled markers of cell cycle progression, and apply our new model to two image datasets we collected from the strain, as well as an independent dataset of different markers. We use our model to estimate the duration of post-cytokinetic attachment between a S.cerevisiae mother and daughter cell. The Java implementation is fast and extensible, and includes a graphical user interface. Our model provides a powerful and flexible cell cycle analysis tool, suitable to any type or combination of binary markers. AVAILABILITY: The software is available from: http://www.cs.duke.edu/~amink/software/cloccs/. CONTACT: michael.mayhew@duke.edu; amink@cs.duke.edu."	"http://www.ncbi.nlm.nih.gov/pubmed/21685084"
 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. mayrose@zoology.ubc.ca"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/20961959"
 1	"english"	"United States of America"	"USA"	"0.0059880239521"	"0.0419161676647"	"0.119760479042"	"167"	"9.82352941176"	"PLoS One"	"Mazzocco MM, Feigenson L, Halberda J"	"Kennedy Krieger Institute, Baltimore, Maryland, United States of America."	"The Approximate Number System (ANS) is a primitive mental system of nonverbal representations that supports an intuitive sense of number in human adults, children, infants, and other animal species. The numerical approximations produced by the ANS are characteristically imprecise and, in humans, this precision gradually improves from infancy to adulthood. Throughout development, wide ranging individual differences in ANS precision are evident within age groups. These individual differences have been linked to formal mathematics outcomes, based on concurrent, retrospective, or short-term longitudinal correlations observed during the school age years. However, it remains unknown whether this approximate number sense actually serves as a foundation for these school mathematics abilities. Here we show that ANS precision measured at preschool, prior to formal instruction in mathematics, selectively predicts performance on school mathematics at 6 years of age. In contrast, ANS precision does not predict non-numerical cognitive abilities. To our knowledge, these results provide the first evidence for early ANS precision, measured before the onset of formal education, predicting later mathematical abilities."	"http://www.ncbi.nlm.nih.gov/pubmed/21935362"
+"unk"	"english"	"unknown"	"unknown"	"0.0"	"0.0536585365854"	"0.0585365853659"	"205"	"9.7619047619"	"BMC Bioinformatics"	"McCall MN, Irizarry RA"		"ABSTRACT: BACKGROUND: A novel method of microarray preprocessing - Frozen Robust Multi-array Analysis (fRMA) - has recently been developed. This algorithm allows the user to preprocess arrays individually while retaining the advantages of multi-array preprocessing methods. The frozen parameter estimates required by this algorithm are generated using a large database of publicly available arrays. Curation of such a database and creation of the frozen parameter estimates is time-consuming; therefore, fRMA has only been implemented on the most widely used Affymetrix platforms. RESULTS: We present an R package, frmaTools, that allows the user to quickly create his or her own frozen parameter vectors. We describe how this package fits into a preprocessing workflow and explore the size of the training data set needed to generate reliable frozen parameter estimates. This is followed by a discussion of specific situations in which one might wish to create ones own fRMA implementation. For a few specific scenarios, we demonstrate that fRMA performs well even when a large database of arrays in unavailable. CONCLUSIONS: By allowing the user to easily create his or her own fRMA implementation, the frmaTools package greatly increases the applicability of the fRMA algorithm. The frmaTools package is freely available as part of the Bioconductor project."	"http://www.ncbi.nlm.nih.gov/pubmed/21923903"
 2	"english"	"USA."	"USA"	"0.00719424460432"	"0.0323741007194"	"0.0647482014388"	"278"	"11.12"	"BMC Bioinformatics"	"McCall MN, Murakami PN, Lukk M, Huber W, Irizarry RA"	"Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 N, Wolfe St,, Baltimore, MD, USA."	"BACKGROUND: Microarray technology has become a widely used tool in the biological sciences. Over the past decade, the number of users has grown exponentially, and with the number of applications and secondary data analyses rapidly increasing, we expect this rate to continue. Various initiatives such as the External RNA Control Consortium (ERCC) and the MicroArray Quality Control (MAQC) project have explored ways to provide standards for the technology. For microarrays to become generally accepted as a reliable technology, statistical methods for assessing quality will be an indispensable component; however, there remains a lack of consensus in both defining and measuring microarray quality. RESULTS: We begin by providing a precise definition of microarray quality and reviewing existing Affymetrix GeneChip quality metrics in light of this definition. We show that the best-performing metrics require multiple arrays to be assessed simultaneously. While such multi-array quality metrics are adequate for bench science, as microarrays begin to be used in clinical settings, single-array quality metrics will be indispensable. To this end, we define a single-array version of one of the best multi-array quality metrics and show that this metric performs as well as the best multi-array metrics. We then use this new quality metric to assess the quality of microarry data available via the Gene Expression Omnibus (GEO) using more than 22,000 Affymetrix HGU133a and HGU133plus2 arrays from 809 studies. CONCLUSIONS: We find that approximately 10 percent of these publicly available arrays are of poor quality. Moreover, the quality of microarray measurements varies greatly from hybridization to hybridization, study to study, and lab to lab, with some experiments producing unusable data. Many of the concepts described here are applicable to other high-throughput technologies."	"http://www.ncbi.nlm.nih.gov/pubmed/21548974"
 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. jamesm@unimelb.edu.au"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21552544"
 2	"english"	"United States"	"USA"	"0.0165745856354"	"0.00552486187845"	"0.060773480663"	"181"	"8.7619047619"	"Blood"	"McDermott DH, Liu Q, Ulrick J, Kwatemaa N, Anaya-OBrien S, Penzak SR, Oliveira Filho J, Long Priel DA, Kelly C, Garofalo M, Littel P, Marquesen MM, Hilligoss D, Decastro R, Fleisher TA, Kuhns DB, Malech HL, Murphy PM"	"Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States;"	"WHIM syndrome is a rare congenital immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis (neutropenia due to impaired egress from the bone marrow); most patients also have severe panleukopenia. Since WHIM syndrome is caused by mutations in the chemokine receptor CXCR4 that result in increased agonist-dependent signaling, we hypothesized that the CXCR4 antagonist Plerixafor (Mozobil, AMD3100), might be an effective treatment. To test this, we enrolled three unrelated adult patients with the most common WHIM mutation, CXCR4(R334X), in a Phase I dose-escalation study. Plerixafor increased absolute lymphocyte, monocyte and neutrophil counts (ALC, AMC and ANC) in blood to normal without significant side effects in all three patients. Peak responses occurred at 3-12 hours post-injection and troughs at 24 hours post-injection, tracking with the drugs pharmacokinetics. All three cell types increased in a dose-dependent manner with the rank order of responsiveness ALC>AMC>ANC. These data provide the first pharmacological evidence that panleukopenia in WHIM syndrome is caused by CXCL12-CXCR4 signaling-dependent leukocyte sequestration, and support continued study of Plerixafor as mechanism-based therapy in this disease. The www.ClinicalTrials.gov Identifier for this study is NCT00967785."	"http://www.ncbi.nlm.nih.gov/pubmed/21890643"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21390331"
 3	"english"	"United Kingdom"	"UK"	"0.0104895104895"	"0.013986013986"	"0.048951048951"	"286"	"12.4347826087"	"PLoS Computational Biology"	"Mill R, Coath M, Wennekers T, Denham SL"	"School of Psychology/Centre for Robotics and Neural Systems, University of Plymouth, Plymouth, United Kingdom."	"Stimulus-specific adaptation (SSA) occurs when the spike rate of a neuron decreases with repetitions of the same stimulus, but recovers when a different stimulus is presented. It has been suggested that SSA in single auditory neurons may provide information to change detection mechanisms evident at other scales (e.g., mismatch negativity in the event related potential), and participate in the control of attention and the formation of auditory streams. This article presents a spiking-neuron model that accounts for SSA in terms of the convergence of depressing synapses that convey feature-specific inputs. The model is anatomically plausible, comprising just a few homogeneously connected populations, and does not require organised feature maps. The model is calibrated to match the SSA measured in the cortex of the awake rat, as reported in one study. The effect of frequency separation, deviant probability, repetition rate and duration upon SSA are investigated. With the same parameter set, the model generates responses consistent with a wide range of published data obtained in other auditory regions using other stimulus configurations, such as block, sequential and random stimuli. A new stimulus paradigm is introduced, which generalises the oddball concept to Markov chains, allowing the experimenter to vary the tone probabilities and the rate of switching independently. The model predicts greater SSA for higher rates of switching. Finally, the issue of whether rarity or novelty elicits SSA is addressed by comparing the responses of the model to deviants in the context of a sequence of a single standard or many standards. The results support the view that synaptic adaptation alone can explain almost all aspects of SSA reported to date, including its purported novelty component, and that non-trivial networks of depressing synapses can intensify this novelty response."	"http://www.ncbi.nlm.nih.gov/pubmed/21876661"
 3	"english"	"California, USA."	"USA"	"0.00291545189504"	"0.0233236151603"	"0.064139941691"	"343"	"10.3939393939"	"BMC Bioinformatics"	"Miller JA, Cai C, Langfelder P, Geschwind DH, Kurian SM, Salomon DR, Horvath S"	"Human Genetics Department, UCLA, Los Angeles, California, USA. shorvath@mednet.ucla.edu."	"ABSTRACT: BACKGROUND: Genomic and other high dimensional analyses often require one to summarize multiple related variables by a single representative. This task is also variously referred to as collapsing, combining, reducing, or aggregating variables. Examples include summarizing several probe measurements corresponding to a single gene, representing the expression profiles of a co-expression module by a single expression profile, and aggregating cell-type marker information to de-convolute expression data. Several standard statistical summary techniques can be used, but network methods also provide useful alternative methods to find representatives. Currently few collapsing functions are developed and widely applied. RESULTS: We introduce the R function collapseRows that implements several collapsing methods and evaluate its performance in three applications. First, we study a crucial step of the meta-analysis of microarray data: the merging of independent gene expression data sets, which may have been measured on different platforms. Toward this end, we collapse multiple microarray probes for a single gene and then merge the data by gene identifier. We find that choosing the probe with the highest average expression leads to best between-study consistency. Second, we study methods for summarizing the gene expression profiles of a co-expression module. Several gene co-expression network analysis applications show that the optimal collapsing strategy depends on the analysis goal. Third, we study aggregating the information of cell type marker genes when the aim is to predict the abundance of cell types in a tissue sample based on gene expression data (expression deconvolution). We apply different collapsing methods to predict cell type abundances in peripheral human blood and in mixtures of blood cell lines. Interestingly, the most accurate prediction method involves choosing the most highly connected hub marker gene. Finally, to facilitate biological interpretation of collapsed gene lists, we introduce the function userListEnrichment, which assesses the enrichment of gene lists for known brain and blood cell type markers, and for other published biological pathways. CONCLUSIONS: The R function collapseRows implements several standard and network-based collapsing methods. In various genomic applications we provide evidence that both types of methods are robust and biologically relevant tools."	"http://www.ncbi.nlm.nih.gov/pubmed/21816037"
+"unk"	"english"	"unknown"	"unknown"	"0.0232558139535"	"0.0232558139535"	"0.0891472868217"	"258"	"17.2"	"Molecular Biology and Evolution"	"Miller JS, Kamath A, Damashek J, Levin RA"	"Department of Biology, Amherst College. jsmiller@amherst.edu"	"The plant genus Lycium (Solanaceae) originated in the Americas and includes approximately 85 species that are distributed worldwide. The vast majority of Old World species occur in southern Africa and eastern Asia. In this study, we examine biogeographic relationships among Old World species using a phylogenetic approach coupled with molecular evolutionary analyses of the S-RNase self-incompatibility gene. The phylogeny inferred from nuclear granule-bound starch synthase I (GBSSI), nuclear conserved ortholog set II (COSII) marker C2_At1g24360, and plastid spacer data (trnH-pbsA, trnD(GUC)-trnT(GGU), rpl32-trnL(UAG), and ndhF-rpl32) includes a clade of eastern Asian Lycium nested within the African species, suggesting initial dispersal from the Americas to Africa, with subsequent dispersal to eastern Asia. Molecular dating estimates suggest that these dispersal events occurred relatively recently, with dispersal from the Americas to Africa approximately 3.64 Ma (95% highest posterior density [HPD]: 1.58-6.27), followed by subsequent dispersal to eastern Asia approximately 1.21 Ma (95% HPD: 0.32-2.42). In accordance, the S-RNase genealogy shows that S-RNases isolated from Old World species are restricted to four lineages, a subset of the 14 lineages including S-RNases isolated from New World Lycium species, supporting a bottleneck of S-RNase alleles concomitant with a single dispersal event from the Americas to the Old World. Furthermore, the S-RNase genealogy is also consistent with dispersal of Lycium from Africa to Asia, as eastern Asian alleles are restricted to a subset of the lineages that also include African alleles. Such a multilocus approach, including complementary data from GBSSI, COSII, plastid spacer regions, and S-RNase, is powerful for understanding dispersal histories of closely related species."	"http://www.ncbi.nlm.nih.gov/pubmed/20855430"
 3	"english"	"Minneapolis"	"USA"	"0.027027027027"	"0.027027027027"	"0.0486486486486"	"185"	"12.3333333333"	"Glycobiology"	"Miller MC, Ribeiro JP, Roldos V, Martin-Santamaria S, Canada FJ, Nesmelova I, Andre S, Pang M, Klyosov A, Baum LG, Jimenez-Barbero J, Gabius HJ, Mayo KH"	"Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota Health Sciences Center, 6-155 Jackson Hall, 321 Church Street, Minneapolis, MN 55455."	"By definition, adhesion/growth-regulatory galectins are known for their ability to bind beta-galactosides such as Galbeta(1-->4)Glc (lactose). Indications for affinity of human galectin-1 to alpha-linked digalactosides pose questions on the interaction profile with such bound ligands and selection of the galactose moiety for CH-pi stacking. These issues are resolved by a combination of (15)N(1)H HSQC chemical shift and STD NMR epitope mappings with docking analysis, using the alpha(1-->3/4)-linked digalactosides and also Galalpha(1-->6)Glc (melibiose) as test compounds. The experimental part revealed interaction with the canonical lectin site, and this preferentially via the non-reducing-end galactose moiety. Low-energy conformers appear to be selected without notable distortion, as shown by molecular dynamics simulations. With the alpha(1-->4) disaccharide, however, the typical CH-pi interaction is significantly diminished, yet binding appears to be partially compensated for by hydrogen bonding. Overall, these findings reveal that the type of alpha-linkage in digalactosides has an impact on maintaining CH-pi interactions and the pattern of hydrogen bonding, explaining preference for the alpha(1-->3) linkage. Thus, this lectin is able to accommodate both alpha- and beta-linked galactosides at the same site, with major contacts to the non-reducing-end sugar unit."	"http://www.ncbi.nlm.nih.gov/pubmed/21712397"
 3	"english"	"UK."	"UK"	"0.011583011583"	"0.03861003861"	"0.0694980694981"	"259"	"13.6315789474"	"BMC Bioinformatics"	"Milnthorpe AT, Soloviev M"	"School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK. A.T.Milnthorpe@rhul.ac.uk"	"BACKGROUND: The Cancer Genome Anatomy Project (CGAP) xProfiler and cDNA Digital Gene Expression Displayer (DGED) have been made available to the scientific community over a decade ago and since then were used widely to find genes which are differentially expressed between cancer and normal tissues. The tissue types are usually chosen according to the ontology hierarchy developed by NCBI. The xProfiler uses an internally available flat file database to determine the presence or absence of genes in the chosen libraries, while cDNA DGED uses the publicly available UniGene Expression and Gene relational databases to count the sequences found for each gene in the presented libraries. RESULTS: We discovered that the CGAP approach often includes libraries from dependent or irrelevant tissues (one third of libraries were incorrect on average, with some tissue searches no correct libraries being selected at all). We also discovered that the CGAP approach reported genes from outside the selected libraries and may omit genes found within the libraries. Other errors include the incorrect estimation of the significance values and inaccurate settings for the library size cut-off values. We advocated a revised approach to finding libraries associated with tissues. In doing so, libraries from dependent or irrelevant tissues do not get included in the final library pool. We also revised the method for determining the presence or absence of a gene by searching the UniGene relational database, revised calculation of statistical significance and sorted the library cut-off filter. CONCLUSION: Our results justify re-evaluation of all previously reported results where NCBI CGAP expression data and tools were used."	"http://www.ncbi.nlm.nih.gov/pubmed/21496233"
 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. bmisic@rotman-baycrest.on.ca"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21673866"
 1	"english"	"USA."	"USA"	"0.00507614213198"	"0.0152284263959"	"0.0761421319797"	"197"	"9.38095238095"	"Nature"	"Park D, Han CZ, Elliott MR, Kinchen JM, Trampont PC, Das S, Collins S, Lysiak JJ, Hoehn KL, Ravichandran KS"	"Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22908, USA."	"Rapid and efficient removal of apoptotic cells by phagocytes is important during development, tissue homeostasis and in immune responses. Efficient clearance depends on the capacity of a single phagocyte to ingest multiple apoptotic cells successively, and to process the corpse-derived cellular material. However, the factors that influence continued clearance by phagocytes are not known. Here we show that the mitochondrial membrane potential of the phagocyte critically controls engulfment capacity, with lower potential enhancing engulfment and vice versa. The mitochondrial membrane protein Ucp2, which acts to lower the mitochondrial membrane potential, was upregulated in phagocytes engulfing apoptotic cells. Loss of Ucp2 reduced phagocytic capacity, whereas Ucp2 overexpression enhanced engulfment. Mutational and pharmacological studies indicated a direct role for Ucp2-mediated mitochondrial function in phagocytosis. Macrophages from Ucp2-deficient mice were impaired in phagocytosis in vitro, and Ucp2-deficient mice showed profound in vivo defects in clearing dying cells in the thymus and testes. Collectively, these data indicate that mitochondrial membrane potential and Ucp2 are key molecular determinants of apoptotic cell clearance. As Ucp2 is linked to metabolic diseases and atherosclerosis, this newly discovered role for Ucp2 in apoptotic cell clearance has implications for the complex aetiology and pathogenesis of these diseases."	"http://www.ncbi.nlm.nih.gov/pubmed/21857682"
 2	"english"	"New York, USA."	"USA"	"0.0"	"0.0"	"0.0592105263158"	"152"	"10.1333333333"	"Immunity"	"Park SG, Mathur R, Long M, Hosh N, Hao L, Hayden MS, Ghosh S"	"Department of Microbiology & Immunology, Columbia University, College of Physicians & Surgeons, New York, NY 10032, USA."	"Immune tolerance against enteric commensal bacteria is important for preventing intestinal inflammation. Deletion of phosphoinositide-dependent protein kinase 1 (Pdk1) in T cells via Cd4-Cre induced chronic inflammation of the intestine despite the importance of PDK1 in T cell activation. Analysis of colonic intraepithelial lymphocytes of PDK1-deficient mice revealed markedly increased CD8alpha(+) T cell receptor (TCR)gammadelta(+) T cells, including an interleukin-17 (IL-17)-expressing population. TCRgammadelta(+) T cells were responsible for the inflammatory colitis as shown by the fact that deletion of Tcrd abolished spontaneous colitis in the PDK1-deficient mice. This dysregulation of intestinal TCRgammadelta(+) T cells was attributable to a reduction in the number and functional capacity of PDK1-deficient T regulatory (Treg) cells. Adoptive transfer of wild-type Treg cells abrogated the spontaneous activation and proliferation of intestinal TCRgammadelta(+) T cells observed in PDK1-deficient mice and prevented the development of colitis. Therefore, suppression of intestinal TCRgammadelta(+) T cells by Treg cells maintains enteric immune tolerance."	"http://www.ncbi.nlm.nih.gov/pubmed/21074460"
 2	"english"	"Texas, Texas, USA."	"USA"	"0.00452488687783"	"0.027149321267"	"0.0904977375566"	"221"	"6.6"	"Bioinformatics"	"Park Y, Marcotte EM"	"Center for Systems and Synthetic Biology, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA."	"MOTIVATION: A number of computational methods have been proposed that predict protein-protein interactions (PPIs) based on protein sequence features. Since the number of potential non-interacting protein pairs (negative PPIs) is very high both in absolute terms and in comparison to that of interacting protein pairs (positive PPIs), computational prediction methods rely upon subsets of negative PPIs for training and validation. Hence, the need arises for subset sampling for negative PPIs. RESULTS: We clarify that there are two fundamentally different types of subset sampling for negative PPIs. One is subset sampling for cross-validated testing, where one desires unbiased subsets so that predictive performance estimated with them can be safely assumed to generalize to the population level. The other is subset sampling for training, where one desires the subsets that best train predictive algorithms, even if these subsets are biased. We show that confusion between these two fundamentally different types of subset sampling led one study recently published in Bioinformatics to the erroneous conclusion that predictive algorithms based on protein sequence features are hardly better than random in predicting PPIs. Rather, both protein sequence features and the hubbiness of interacting proteins contribute to effective prediction of PPIs. We provide guidance for appropriate use of random versus balanced sampling. AVAILABILITY: The data sets used for this study are available at http://www.marcottelab.org/PPINegativeDataSampling. CONTACT: yungki@mail.utexas.edu, marcotte@icmb.utexas.edu."	"http://www.ncbi.nlm.nih.gov/pubmed/21908540"
+"unk"	"english"	"unknown"	"unknown"	"0.0150753768844"	"0.0201005025126"	"0.0301507537688"	"199"	"8.65217391304"	"Blood"	"Park YP, Choi SC, Kiesler P, Gil-Krzewska A, Borrego F, Weck J, Krzewski K, Coligan JE"	"Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD; and."	"Natural killer (NK) cells help protect the host against viral infections and tumors. NKG2D is a vital activating receptor, also expressed on subsets of T cells, whose ligands are up-regulated by cells in stress. Ligation of NKG2D leads to phosphorylation of the associated DAP10 adaptor protein, thereby activating immune cells. Understanding how the expression of NKG2D-DAP10 is regulated has implications for immunotherapy. We show that IL-2 and TGF-beta1 oppositely regulate NKG2D-DAP10 expression by NK cells. IL-2 stimulation increases NKG2D surface expression despite a decrease in NKG2D mRNA levels. Stimulation with IL-2 results in a small increase of DAP10 mRNA and a large up-regulation of DAP10 protein synthesis, indicating that IL-2-mediated effects are mostly posttranscriptional. Newly synthesized DAP10 undergoes glycosylation that is required for DAP10 association with NKG2D and stabilization of NKG2D expression. TGF-beta1 has an opposite and dominant effect to IL-2. TGF-beta1 treatment decreases DAP10, as its presence inhibits the association of RNA polymerase II with the DAP10 promoter, but not NKG2D mRNA levels. This leads to the down-regulation of DAP10 expression and, as a consequence, NKG2D protein as well. Finally, we show that other gamma(c) cytokines act similarly to IL-2 in up-regulating DAP10 expression and NKG2D-DAP10 surface expression."	"http://www.ncbi.nlm.nih.gov/pubmed/21816829"
 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. beiko@cs.dal.ca."	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21827705"
 2	"english"	"Jersey, USA."	"USA"	"0.0208333333333"	"0.0260416666667"	"0.0989583333333"	"192"	"12.8"	"Molecular Biology and Evolution"	"Parry BR, Shain DH"	"Biology Department, Rutgers The State University of New Jersey, USA."	"Diverse organisms have adapted to thrive at low temperatures (i.e., <20  degrees C, termed psychrophiles), colonizing the majority of earths biosphere. In contrast with mesophiles (20-40  degrees C thermal range), all observed psychrophiles increase intracellular adenosine 5-triphosphate concentrations as temperatures decline; this phenomenon has been described as an important compensatory mechanism to deal with decreases in thermal energy and molecular motion. We considered purine metabolic pathways in class gammaproteobacteria (n = 115) to investigate metabolic and evolutionary bases of this process. A survey of the KEGG database indicated that psychrophilic purine metabolic pathways tend to be enriched with de novo adenosine 5-monophosphate (AMP) synthetic enzymes, whereas mesophiles tend to be enriched with AMP degradative enzymes. Function of the observed psychrophilic pathway structure was tested by engineering the mesophilic gammaproteobacterium Escherichia coli to reflect psychrophilic purine metabolism, specifically by expressing adenylosuccinate synthetase (purA) from the psychrophilic gammaproteobacterium, Psychrobacter cryohalolentis, in an AMP nucleosidase (amn)-deficient background. Modified E. coli was capable of growing up to  approximately 70% faster at low temperatures and became up to  approximately 10-fold more cold tolerant relative to wild type. These findings highlight potentially important transitional steps in psychrophilic evolution."	"http://www.ncbi.nlm.nih.gov/pubmed/21300985"
 2	"english"	"Frederick, Frederick"	"USA"	"0.0129032258065"	"0.0387096774194"	"0.0451612903226"	"155"	"12.0769230769"	"Glycobiology"	"Pasek M, Ramakrishnan B, Boeggeman E, Mercer N, Dulcey AE, Griffiths GL, Qasba PK"	"Structural Glycobiology Section, Center for Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD 21702."	"In recent years, sugars with a unique chemical handle have been used to detect and elucidate the function of glycoconjugates. Such chemical handles have generally been part of an N-acetyl-moiety of a sugar. We have previously developed several applications using the single mutant Y289L-beta1, 4-galctosyltransferase (Y289L-beta4Gal-T1) and the wild-type polypeptide-alpha-GalNAc-T enzymes with UDP-C2-keto-Gal. Here we describe for the first time that the GlcNAc transferring enzymes-R228K-Y289L-beta4Gal-T1 mutant enzyme, the wild-type human beta1, 3-N-acetylglucosaminyltransferase-2 (beta3GN-T2), and human Maniac Fringe (MFng)-can also transfer the GlcNAc analog C2-keto-Glc molecule from UDP-C2-keto-Glc to their respective acceptor substrates. Although the R228K-Y289L-beta4Gal-T1 mutant enzyme transfers the donor sugar substrate GlcNAc or its analogue C2-keto-Glc only to its natural acceptor substrate, GlcNAc, it does not transfer to its analogue C2-keto-Glc. Thus, these observations suggest that the GlcNAc-transferring glycosyltransferases can generally accommodate a chemical handle in the N-acetyl binding-cavity of the donor sugar substrate, but not in the N-acetyl binding-cavity of the acceptor sugar."	"http://www.ncbi.nlm.nih.gov/pubmed/21868414"
 3	"english"	"Yale, yale"	"USA"	"0.0096463022508"	"0.0225080385852"	"0.0546623794212"	"311"	"12.44"	"Molecular Biology and Evolution"	"Powell JR, Dion K, Papaceit M, Aguade M, Vicario S, Garrick RC"	"Department of Ecology and Evolutionary Biology, Yale University. jeffrey.powell@yale.edu"	"Rate of recombination is a powerful variable affecting several aspects of molecular variation and evolution. A nonrecombining portion of the genome of most Drosophila species, the dot chromosome or F element, exhibits very low levels of variation and unusual codon usage. One lineage of Drosophila, the willistoni/saltans groups, has the F element fused to a normally recombining E element. Here, we present polymorphism data for genes on the F element in two Drosophila willistoni and one D. insularis populations, genes previously studied in D. melanogaster. The D. willistoni populations were known to be very low in inversion polymorphism, thus minimizing the recombination suppression effect of inversions. We first confirmed, by in situ hybridization, that D. insularis has the same E + F fusion as D. willistoni, implying this was a monophyletic event. A clear gradient in codon usage exists along the willistoni F element, from the centromere distally to the fusion with E; estimates of recombination rates parallel this gradient and also indicate D. insularis has greater recombination than D. willistoni. In contrast to D. melanogaster, genes on the F element exhibit moderate levels of nucleotide polymorphism not distinguishable from two genes elsewhere in the genome. Although some linkage disequilibrium (LD) was detected between polymorphic sites within genes (generally <500 bp apart), no long-range LD between F element loci exists in the two willistoni group species. In general, the distribution of allele frequencies of F element genes display the typical pattern of expectations of neutral variation at equilibrium. These results are consistent with the hypothesis that recombination allows the accumulation of nucleotide variation as well as allows selection to act on synonymous codon usage. It is estimated that the fusion occurred  approximately 20 Mya and while the F element in the willistoni lineage has evolved normal levels and patterns of nucleotide variation, equilibrium may not have been reached for codon usage."	"http://www.ncbi.nlm.nih.gov/pubmed/20940345"
 1	"english"	"USA."	"USA"	"0.0170454545455"	"0.0113636363636"	"0.0738636363636"	"352"	"10.2"	"BMC Bioinformatics"	"Prasad R, McRoy S, Frid N, Joshi A, Yu H"	"Institute for Research in Cognitive Science, University of Pennsylvania, 3401 Walnut Street, Philadelphia, PA 19104, USA."	"BACKGROUND: Identification of discourse relations, such as causal and contrastive relations, between situations mentioned in text is an important task for biomedical text-mining. A biomedical text corpus annotated with discourse relations would be very useful for developing and evaluating methods for biomedical discourse processing. However, little effort has been made to develop such an annotated resource. RESULTS: We have developed the Biomedical Discourse Relation Bank (BioDRB), in which we have annotated explicit and implicit discourse relations in 24 open-access full-text biomedical articles from the GENIA corpus. Guidelines for the annotation were adapted from the Penn Discourse TreeBank (PDTB), which has discourse relations annotated over open-domain news articles. We introduced new conventions and modifications to the sense classification. We report reliable inter-annotator agreement of over 80% for all sub-tasks. Experiments for identifying the sense of explicit discourse connectives show the connective itself as a highly reliable indicator for coarse sense classification (accuracy 90.9% and F1 score 0.89). These results are comparable to results obtained with the same classifier on the PDTB data. With more refined sense classification, there is degradation in performance (accuracy 69.2% and F1 score 0.28), mainly due to sparsity in the data. The size of the corpus was found to be sufficient for identifying the sense of explicit connectives, with classifier performance stabilizing at about 1900 training instances. Finally, the classifier performs poorly when trained on PDTB and tested on BioDRB (accuracy 54.5% and F1 score 0.57). CONCLUSION: Our work shows that discourse relations can be reliably annotated in biomedical text. Coarse sense disambiguation of explicit connectives can be done with high reliability by using just the connective as a feature, but more refined sense classification requires either richer features or more annotated data. The poor performance of a classifier trained in the open domain and tested in the biomedical domain suggests significant differences in the semantic usage of connectives across these domains, and provides robust evidence for a biomedical sublanguage for discourse and the need to develop a specialized biomedical discourse annotated corpus. The results of our cross-domain experiments are consistent with related work on identifying connectives in BioDRB."	"http://www.ncbi.nlm.nih.gov/pubmed/21605399"
 2	"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 ClinicalTrials.gov under identifier: NCT00740584."	"http://www.ncbi.nlm.nih.gov/pubmed/21935377"
+"unk"	"english"	"unknown"	"unknown"	"0.0148367952522"	"0.0148367952522"	"0.0563798219585"	"337"	"17.7368421053"	"Molecular Biology and Evolution"	"Price DR, Duncan RP, Shigenobu S, Wilson AC"	"Department of Biology, University of Miami, Coral Gables, Florida."	"In insects, some of the most ecologically important symbioses are nutritional symbioses that provide hosts with novel traits and thereby facilitate exploitation of otherwise inaccessible niches. One such symbiosis is the ancient obligate intracellular symbiosis of aphids with the gamma-proteobacteria, Buchnera aphidicola. Although the nutritional basis of the aphid/Buchnera symbiosis is well understood, the processes and structures that mediate the intimate interactions of symbiotic partners remain uncharacterized. Here, using a de novo approach, we characterize the complement of 40 amino acid polyamine organocation (APC) superfamily member amino acid transporters (AATs) encoded in the genome of the pea aphid, Acyrthosiphon pisum. We find that the A. pisum APC superfamily is characterized by extensive gene duplications such that A. pisum has more APC superfamily transporters than other fully sequenced insects, including a ten paralog aphid-specific expansion of the APC transporter slimfast. Detailed expression analysis of 17 transporters selected on the basis of their phylogenetic relationship to five AATs identified in an earlier bacteriocyte expressed sequence tag study distinguished a subset of eight transporters that have been recruited for amino acid transport in bacteriocyte cells at the symbiotic interface. These eight transporters include transporters that are highly expressed and/or highly enriched in bacteriocytes and intriguingly, the four AATs that show bacteriocyte-enriched expression are all members of gene family expansions, whereas three of the four that are highly expressed but not enriched in bacteriocytes retain one-to-one orthology with transporters in other genomes. Finally, analysis of evolutionary rates within the large A. pisum slimfast expansion demonstrated increased rates of molecular evolution coinciding with two major shifts in expression: 1) a loss of gut expression and possibly a gain of bacteriocyte expression and 2) loss of expression in all surveyed tissues in asexual females. Taken together, our characterization of nutrient AATs at the aphid/Buchnera symbiotic interface provides the first examination of the processes and structures operating at the interface of an obligate intracellular insect nutritional symbiosis, offering unique insight into the types of genomic change that likely facilitated evolutionary maintenance of the symbiosis."	"http://www.ncbi.nlm.nih.gov/pubmed/21613235"
 3	"english"	"USA."	"USA"	"0.00947867298578"	"0.0142180094787"	"0.123222748815"	"211"	"11.1052631579"	"Molecular Biology and Evolution"	"Price N, Cartwright RA, Sabath N, Graur D, Azevedo RB"	"Department of Biology and Biochemistry, University of Houston, USA. nprice2@uh.edu"	"Mutational robustness describes the extent to which a phenotype remains unchanged in the face of mutations. Theory predicts that the strength of direct selection for mutational robustness is at most the magnitude of the rate of deleterious mutation. As far as nucleic acid sequences are concerned, only long sequences in organisms with high deleterious mutation rates and large population sizes are expected to evolve mutational robustness. Surprisingly, recent studies have concluded that molecules that meet none of these conditions--the microRNA precursors (pre-miRNAs) of multicellular eukaryotes--show signs of selection for mutational and/or environmental robustness. To resolve the apparent disagreement between theory and these studies, we have reconstructed the evolutionary history of Drosophila pre-miRNAs and compared the robustness of each sequence to that of its reconstructed ancestor. In addition, we replayed the tape of pre-miRNA evolution via simulation under different evolutionary assumptions and compared these alternative histories with the actual one. We found that Drosophila pre-miRNAs have evolved under strong purifying selection against changes in secondary structure. Contrary to earlier claims, there is no evidence that these RNAs have been shaped by either direct or congruent selection for any kind of robustness. Instead, the high robustness of Drosophila pre-miRNAs appears to be mostly intrinsic and likely a consequence of selection for functional structures."	"http://www.ncbi.nlm.nih.gov/pubmed/21285032"
 3	"english"	"Duke, Carolina, United States of America"	"USA"	"0.00448430493274"	"0.0224215246637"	"0.112107623318"	"223"	"13.1764705882"	"PLoS Computational Biology"	"Pruteanu-Malinici I, Mace DL, Ohler U"	"Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America."	"Advances in reporters for gene expression have made it possible to document and quantify expression patterns in 2D-4D. In contrast to microarrays, which provide data for many genes but averaged and/or at low resolution, images reveal the high spatial dynamics of gene expression. Developing computational methods to compare, annotate, and model gene expression based on images is imperative, considering that available data are rapidly increasing. We have developed a sparse Bayesian factor analysis model in which the observed expression diversity of among a large set of high-dimensional images is modeled by a small number of hidden common factors. We apply this approach on embryonic expression patterns from a Drosophila RNA in situ image database, and show that the automatically inferred factors provide for a meaningful decomposition and represent common co-regulation or biological functions. The low-dimensional set of factor mixing weights is further used as features by a classifier to annotate expression patterns with functional categories. On human-curated annotations, our sparse approach reaches similar or better classification of expression patterns at different developmental stages, when compared to other automatic image annotation methods using thousands of hard-to-interpret features. Our study therefore outlines a general framework for large microscopy data sets, in which both the generative model itself, as well as its application for analysis tasks such as automated annotation, can provide insight into biological questions."	"http://www.ncbi.nlm.nih.gov/pubmed/21814502"
 3	"english"	"USA."	"USA"	"0.0"	"0.0333333333333"	"0.116666666667"	"120"	"10.9090909091"	"Immunity"	"Pulendran B, Li S, Nakaya HI"	"Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA. bpulend@emory.edu"	"Vaccination is one of the greatest triumphs of modern medicine, yet we remain largely ignorant of the mechanisms by which successful vaccines stimulate protective immunity. Two recent advances are beginning to illuminate such mechanisms: realization of the pivotal role of the innate immune system in sensing microbes and stimulating adaptive immunity, and advances in systems biology. Recent studies have used systems biology approaches to obtain a global picture of the immune responses to vaccination in humans. This has enabled the identification of early innate signatures that predict the immunogenicity of vaccines, and identification of potentially novel mechanisms of immune regulation. Here, we review these advances and critically examine the potential opportunities and challenges posed by systems biology in vaccine development."	"http://www.ncbi.nlm.nih.gov/pubmed/21029962"
 2	"english"	"USA."	"USA"	"0.0233918128655"	"0.00584795321637"	"0.0350877192982"	"171"	"8.47619047619"	"Nature Genetics"	"Rothman N, Garcia-Closas M, Chatterjee N, Malats N, Wu X, Figueroa JD, Real FX, Van Den Berg D, Matullo G, Baris D, Thun M, Kiemeney LA, Vineis P, De Vivo I, Albanes D, Purdue MP, Rafnar T, Hildebrandt MA, Kiltie AE, Cussenot O, Golka K, Kumar R, Taylor JA, Mayordomo JI, Jacobs KB, Kogevinas M, Hutchinson A, Wang Z, Fu YP, Prokunina-Olsson L, Burdett L, Yeager M, Wheeler W, Tardon A, Serra C, Carrato A, Garcia-Closas R, Lloreta J, Johnson A, Schwenn M, Karagas MR, Schned A, Andriole G Jr, Grubb R 3rd, Black A, Jacobs EJ, Diver WR, Gapstur SM, Weinstein SJ, Virtamo J, Cortessis VK, Gago-Dominguez M, Pike MC, Stern MC, Yuan JM, Hunter DJ, McGrath M, Dinney CP, Czerniak B, Chen M, Yang H, Vermeulen SH, Aben KK, Witjes JA, Makkinje RR, Sulem P, Besenbacher S, Stefansson K, Riboli E, Brennan P, Panico S, Navarro C, Allen NE, Bueno-de-Mesquita HB, Trichopoulos D, Caporaso N, Landi MT, Canzian F, Ljungberg B, Tjonneland A, Clavel-Chapelon F, Bishop DT, Teo MT, Knowles MA, Guarrera S, Polidoro S, Ricceri F, Sacerdote C, Allione A, Cancel-Tassin G, Selinski S, Hengstler JG, Dietrich H, Fletcher T, Rudnai P, Gurzau E, Koppova K, Bolick SC, Godfrey A, Xu Z, Sanz-Velez JI, D Garcia-Prats M, Sanchez M, Valdivia G, Porru S, Benhamou S, Hoover RN, Fraumeni JF Jr, Silverman DT, Chanock SJ"	"Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA."	"We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 x 10(1)(2)) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 x 10(1)(1)) on 19q12 maps to CCNE1 and rs11892031 (P = 1 x 10) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 x 10(1)(1)) and a tag SNP for NAT2 acetylation status (P = 4 x 10(1)(1)), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis."	"http://www.ncbi.nlm.nih.gov/pubmed/20972438"
 1	"english"	"Cambridge, USA."	"USA"	"0.0"	"0.0223463687151"	"0.072625698324"	"179"	"13.7692307692"	"Glycobiology"	"Roy S, Lai H, Zouaoui R, Duffner J, Zhou H, P Jayaraman L, Zhao G, Ganguly T, Kishimoto TK, Venkataraman G"	"Momenta Pharmaceuticals, Cambridge, MA 02142, USA."	"A series of size-defined low-molecular-weight heparins were generated by regioselective chemical modifications and profiled for their in vitro and in vivo activities. The compounds displayed reduced anti-coagulant activity, demonstrated varying affinities toward angiogenic growth factors (fibroblast growth factor-2, vascular endothelial growth factor and stromal cell-derived factor-1alpha), inhibited the P-selectin/P-selectin glycoprotein ligand-1 interaction and, notably, exhibited anti-tumor efficacy in a murine melanoma experimental metastasis model. Our results demonstrate that modulating specific sequences, especially the N-domains (-NS or -NH(2) or -NHCOCH(3)) in these polysaccharide sequences, has a major impact on the participation in a diverse range of biological activities. These results also suggest that the 6-O-sulfates, but not the 2-O-sulfates, critically affect the binding of a desulfated derivative to certain angiogenic proteins as well as its ability to inhibit P-selectin-mediated B16F10 melanoma metastases. Furthermore, N-desulfation followed by N-acetylation regenerates the affinity/inhibition properties to different extents in all the compounds tested in the in vitro assays. This systematic study lays a conceptual foundation for detailed structure function elucidation and will facilitate the rational design of targeted heparan sulfate proteoglycan-based anti-metastatic therapeutic candidates."	"http://www.ncbi.nlm.nih.gov/pubmed/21515908"
 2	"english"	"USA."	"USA"	"0.00429184549356"	"0.0429184549356"	"0.0515021459227"	"233"	"8.20689655172"	"Bioinformatics"	"Roy S, Werner-Washburne M, Lane T"	"Department of Computer Science, University of New Mexico, Albuquerque, NM 87131, USA. sroy@broadinstitute.org"	"MOTIVATION: Condition-specific networks capture system-wide behavior under varying conditions such as environmental stresses, cell types or tissues. These networks frequently comprise parts that are unique to each condition, and parts that are shared among related conditions. Existing approaches for learning condition-specific networks typically identify either only differences or only similarities across conditions. Most of these approaches first learn networks per condition independently, and then identify similarities and differences in a post-learning step. Such approaches do not exploit the shared information across conditions during network learning. RESULTS: We describe an approach for learning condition-specific networks that identifies the shared and unique subgraphs during network learning simultaneously, rather than as a post-processing step. Our approach learns networks across condition sets, shares data from different conditions and produces high-quality networks that capture biologically meaningful information. On simulated data, our approach outperformed an existing approach that learns networks independently for each condition, especially for small training datasets. On microarray data of hundreds of deletion mutants in two, yeast stationary-phase cell populations, the inferred network structure identified several common and population-specific effects of these deletion mutants and several high-confidence cases of double-deletion pairs, which can be experimentally tested. Our results are consistent with and extend the existing knowledge base of differentiated cell populations in yeast stationary phase. AVAILABILITY AND IMPLEMENTATION: C++ code can be accessed from http://www.broadinstitute.org/~sroy/condspec/ CONTACT: sroy@broadinstitute.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21551143"
+"unk"	"english"	"unknown"	"unknown"	"0.0142857142857"	"0.0238095238095"	"0.109523809524"	"210"	"10.0"	"Molecular Biology and Evolution"	"Roy SW, Hudson AJ, Joseph J, Yee J, Russell AG"	"Department of Biology, Stanford University, 371 Serra Mall, Stanford, CA 94305."	"Spliceosomal introns are hallmarks of eukaryotic genomes, dividing coding regions into separate exons which are joined during mRNA intron removal catalyzed by the spliceosome. With few known exceptions, spliceosomal introns are cis-spliced, that is, removed from one contiguous pre-mRNA transcript. The protistan intestinal parasite Giardia lamblia exhibits one of the most reduced eukaryotic genomes known, with short intergenic regions and only four known spliceosomal introns. Our genome-wide search for additional introns revealed four unusual cases of spliceosomal intron fragmentation, with consecutive exons of conserved protein-coding genes being dispersed to distant genomic sites. Independent transcripts are trans-spliced to yield contiguous mature mRNAs. Most strikingly, a dynein heavy chain subunit is both interrupted by two fragmented introns, and also predicted to be assembled as two separately translated polypeptides, a remarkably complex expression pathway for a nuclear-encoded sequence. For each case, we observe extensive base-pairing potential between intron halves. This basepairing provides both a rationale for the in vivo association of independently transcribed mRNAs transcripts and the apparent specificity of splicing. Similar base-pairing potential in two cis-spliced G. lamblia introns suggests an evolutionary pathway whereby intron fragmentation of cis-spliced introns is permissible and a preliminary evolutionary step to complete gene fission. These results reveal remarkably complex genome dynamics in a severely genomically-reduced parasite."	"http://www.ncbi.nlm.nih.gov/pubmed/21482665"
 3	"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. m.rubinov@student.unsw.edu.au"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21673863"
 1	"english"	"New York, USA."	"USA"	"0.0"	"0.0222222222222"	"0.0444444444444"	"45"	"6.42857142857"	"Immunity"	"Rudensky AY, Chervonsky AV"	"Howard Hughes Medical Institute and Immunology Program, Sloan Kettering Institute, New York, NY 10021, USA. rudenska@mskcc.org"	"Commensal microbiota confers a goldilocks state of alertness to pathogens, yet restrains deleterious inflammation. In this issue of Immunity, Geuking et al. (2011) demonstrate that a minimal bacterial community of the Schaedler flora establishes a balance between pro- and anti-inflammatory T cells in the gut."	"http://www.ncbi.nlm.nih.gov/pubmed/21616440"
 3	"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. lrueda@uwindsor.ca"	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21510903"
 3	"english"	"USA."	"USA"	"0.0180995475113"	"0.0588235294118"	"0.0678733031674"	"221"	"14.7333333333"	"BMC Bioinformatics"	"Sanders WS, Wang N, Bridges SM, Malone BM, Dandass YS, McCarthy FM, Nanduri B, Lawrence ML, Burgess SC"	"Department of Computer Science & Engineering, Mississippi State University, MS, USA."	"BACKGROUND: High-throughput mass spectrometry (MS) proteomics data is increasingly being used to complement traditional structural genome annotation methods. To keep pace with the high speed of experimental data generation and to aid in structural genome annotation, experimentally observed peptides need to be mapped back to their source genome location quickly and exactly. Previously, the tools to do this have been limited to custom scripts designed by individual research groups to analyze their own data, are generally not widely available, and do not scale well with large eukaryotic genomes. RESULTS: The Proteogenomic Mapping Tool includes a Java implementation of the Aho-Corasick string searching algorithm which takes as input standardized file types and rapidly searches experimentally observed peptides against a given genome translated in all 6 reading frames for exact matches. The Java implementation allows the application to scale well with larger eukaryotic genomes while providing cross-platform functionality. CONCLUSIONS: The Proteogenomic Mapping Tool provides a standalone application for mapping peptides back to their source genome on a number of operating system platforms with standard desktop computer hardware and executes very rapidly for a variety of datasets. Allowing the selection of different genetic codes for different organisms allows researchers to easily customize the tool to their own research interests and is recommended for anyone working to structurally annotate genomes using MS derived proteomics data."	"http://www.ncbi.nlm.nih.gov/pubmed/21513508"
 3	"english"	"USA."	"USA"	"0.00714285714286"	"0.0"	"0.0428571428571"	"140"	"15.5555555556"	"ANNUAL REVIEW OF PSYCHOLOGY"	"Sandler IN, Schoenfelder EN, Wolchik SA, MacKinnon DP"	"Prevention Research Center, Arizona State University, Tempe, Arizona 85287-6005, USA. irwin.sandler@asu.edu"	"This article reviews findings from 46 randomized experimental trials of preventive parenting interventions. The findings of these trials provide evidence of effects to prevent a wide range of problem outcomes and to promote competencies from one to 20 years later. However, there is a paucity of evidence concerning the processes that account for program effects. Three alternative pathways are proposed as a framework for future research on the long-term effects of preventive parenting programs: (a) through program effects on parenting skills, perceptions of parental efficacy, and reduction in barriers to effective parenting; (b) through program-induced reductions in short-term problems of youth that persist over time, improvements in youth adaptation to stress, and improvements in youth belief systems concerning the self and their relationships with others; and (c) through effects on contexts in which youth become involved and on youth-environment transactions."	"http://www.ncbi.nlm.nih.gov/pubmed/20822438"
 3	"english"	"California, USA."	"USA"	"0.00970873786408"	"0.0194174757282"	"0.106796116505"	"103"	"5.68421052632"	"Bioinformatics"	"Sanft KR, Wu S, Roh M, Fu J, Lim RK, Petzold LR"	"Department of Computer Science, University of California Santa Barbara, Santa Barbara, CA 93106, USA."	"SUMMARY: StochKit2 is the first major upgrade of the popular StochKit stochastic simulation software package. StochKit2 provides highly efficient implementations of several variants of Gillespies stochastic simulation algorithm (SSA), and tau-leaping with automatic step size selection. StochKit2 features include automatic selection of the optimal SSA method based on model properties, event handling, and automatic parallelism on multicore architectures. The underlying structure of the code has been completely updated to provide a flexible framework for extending its functionality. AVAILABILITY: StochKit2 runs on Linux/Unix, Mac OS X and Windows. It is freely available under GPL version 3 and can be downloaded from http://sourceforge.net/projects/stochkit/. CONTACT: petzold@engineering.ucsb.edu."	"http://www.ncbi.nlm.nih.gov/pubmed/21727139"
-2	"asian"	"Yale, USA."	"USA"	"0.0"	"0.0"	"0.027027027027"	"37"	"5.28571428571"	"Immunity"	"Sasai M, Iwasaki A"	"Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA."	"Unc93B1, a multitransmembrane ER-resident protein, controls intracellular trafficking of endosomal Toll-like receptors. In this issue of Immunity, Fukui et al. (2011) revealed that Unc93B1 regulates differential transport of TLR7 and TLR9 into signaling endosomes to prevent autoimmunity."	"http://www.ncbi.nlm.nih.gov/pubmed/21777792"
 2	"english"	"New York, USA."	"USA"	"0.0138888888889"	"0.0208333333333"	"0.0555555555556"	"144"	"11.0769230769"	"Immunity"	"Sathaliyawala T, OGorman WE, Greter M, Bogunovic M, Konjufca V, Hou ZE, Nolan GP, Miller MJ, Merad M, Reizis B"	"Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA."	"Dendritic cells (DCs) comprise distinct functional subsets including CD8 and CD8(+) classical DCs (cDCs) and interferon-secreting plasmacytoid DCs (pDCs). The cytokine Flt3 ligand (Flt3L) controls the development of DCs and is particularly important for the pDC and CD8(+) cDC and their CD103(+) tissue counterparts. We report that mammalian target of rapamycin (mTOR) inhibitor rapamycin impaired Flt3L-driven DC development in vitro, with the pDCs and CD8(+)-like cDCs most profoundly affected. Conversely, deletion of the phosphoinositide 3-kinase (PI3K)-mTOR negative regulator Pten facilitated Flt3L-driven DC development in culture. DC-specific Pten targeting in vivo caused the expansion of CD8(+) and CD103(+) cDC numbers, which was reversible by rapamycin. The increased CD8(+) cDC numbers caused by Pten deletion correlated with increased susceptibility to the intracellular pathogen Listeria. Thus, PI3K-mTOR signaling downstream of Flt3L controls DC development, and its restriction by Pten ensures optimal DC pool size and subset composition."	"http://www.ncbi.nlm.nih.gov/pubmed/20933441"
 2	"english"	"Boston"	"USA"	"0.0"	"0.00943396226415"	"0.0660377358491"	"106"	"9.63636363636"	"Bioinformatics"	"Sathirapongsasuti JF, Lee H, Horst BA, Brunner G, Cochran AJ, Binder S, Quackenbush J, Nelson SF"	"Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115."	"MOTIVATION: The ability to detect copy-number variation (CNV) and loss of heterozygosity (LOH) from exome sequencing data extends the utility of this powerful approach that has mainly been used for point or small insertion/deletion detection. RESULTS: We present ExomeCNV, a statistical method to detect CNV and LOH using depth-of-coverage and B-allele frequencies, from mapped short sequence reads, and we assess both the methods power and the effects of confounding variables. We apply our method to a cancer exome resequencing dataset. As expected, accuracy and resolution are dependent on depth-of-coverage and capture probe design. AVAILABILITY: CRAN package ExomeCNV SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21828086"
 3	"english"	"UK."	"UK"	"0.016"	"0.016"	"0.072"	"250"	"13.2105263158"	"Glycobiology"	"Sattelle BM, Almond A"	"Manchester Interdisciplinary Biocentre, 131 Princess Street, Manchester, M1 7DN, UK."	"Understanding microsecond-timescale dynamics is crucial to establish 3D-structure-activity relationships in sugars but has been intractable to experiments and simulations. As a consequence, whether arguably the most important chemical scaffold in glycobiology, N-acetyl-d-glucosamine (GlcNAc), deviates from a rigid (4)C(1)-chair is unknown. Here, conformer populations and exchange kinetics were quantified from the longest aqueous carbohydrate simulations to date (0.2 ms total) of GlcNAc, four derivatives from heparan sulfate and their methyl glycosides. Unmodified GlcNAc took 3-5 mus to reach a conformational equilibrium, which comprised a metastable (4)C(1)-chair that underwent (4)C(1)<-->(1)C(4) transitions at a predicted forward rate of 0.8 mus(-1) with an average (1)C(4)-chair lifetime of 3 ns. These predictions agree with high-resolution crystallography and NMR but not with the hypothesis that GlcNAc is a rigid (4)C(1)-chair, concluded from previous experimental analyses and non-aqueous modeling. The methyl glycoside was calculated to have a slower forward rate (0.3 mus(-1)) and a more stable (4)C(1)-conformer (0.2 kcal mol(-1)), suggesting that pivotal 3D-intermediates (particularly (2)S(O), (1)S(5) and B(2,5)) increased in energy, and water was implicated as a major cause. Sulfonation (N-, 3-O and 6-O) significantly augmented this effect by blocking pseudorotation, but did not alter the rotational preferences of hydroyxl or hydroxmethyl groups. We therefore propose that GlcNAc undergoes puckering exchange that is dependent on polymerization and sulfo-substituents. Our analyses, and 3D-model of the equilibrium GlcNAc conformer in water, can be used as dictionary data and present new opportunities to rationally modify puckering and carbohydrate bioactivity, with diverse applications from improving crop yields to disease amelioration."	"http://www.ncbi.nlm.nih.gov/pubmed/21807769"
 2	"english"	"Cambridge, USA."	"USA"	"0.010752688172"	"0.0215053763441"	"0.139784946237"	"186"	"14.3076923077"	"Nature"	"Savin T, Kurpios NA, Shyer AE, Florescu P, Liang H, Mahadevan L, Tabin CJ"	"School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA."	"The developing vertebrate gut tube forms a reproducible looped pattern as it grows into the body cavity. Here we use developmental experiments to eliminate alternative models and show that gut looping morphogenesis is driven by the homogeneous and isotropic forces that arise from the relative growth between the gut tube and the anchoring dorsal mesenteric sheet, tissues that grow at different rates. A simple physical mimic, using a differentially strained composite of a pliable rubber tube and a soft latex sheet is consistent with this mechanism and produces similar patterns. We devise a mathematical theory and a computational model for the number, size and shape of intestinal loops based solely on the measurable geometry, elasticity and relative growth of the tissues. The predictions of our theory are quantitatively consistent with observations of intestinal loops at different stages of development in the chick embryo. Our model also accounts for the qualitative and quantitative variation in the distinct gut looping patterns seen in a variety of species including quail, finch and mouse, illuminating how the simple macroscopic mechanics of differential growth drives the morphology of the developing gut."	"http://www.ncbi.nlm.nih.gov/pubmed/21814276"
 3	"english"	"USA."	"USA"	"0.0229357798165"	"0.0321100917431"	"0.0917431192661"	"218"	"8.88"	"Bioinformatics"	"Savol AJ, Burger VM, Agarwal PK, Ramanathan A, Chennubhotla CS"	"Joint Carnegie Mellon University-University of Pittsburgh Ph.D. Program in Computational Biology, Department of Computational and Systems Biology, University of Pittsburgh, PA 15260, USA."	"MOTIVATION: Molecular dynamics (MD) simulations have dramatically improved the atomistic understanding of protein motions, energetics and function. These growing datasets have necessitated a corresponding emphasis on trajectory analysis methods for characterizing simulation data, particularly since functional protein motions and transitions are often rare and/or intricate events. Observing that such events give rise to long-tailed spatial distributions, we recently developed a higher-order statistics based dimensionality reduction method, called quasi-anharmonic analysis (QAA), for identifying biophysically-relevant reaction coordinates and substates within MD simulations. Further characterization of conformation space should consider the temporal dynamics specific to each identified substate. RESULTS: Our model uses hierarchical clustering to learn energetically coherent substates and dynamic modes of motion from a 0.5 mus ubiqutin simulation. Autoregressive (AR) modeling within and between states enables a compact and generative description of the conformational landscape as it relates to functional transitions between binding poses. Lacking a predictive component, QAA is extended here within a general AR model appreciative of the trajectorys temporal dependencies and the specific, local dynamics accessible to a protein within identified energy wells. These metastable states and their transition rates are extracted within a QAA-derived subspace using hierarchical Markov clustering to provide parameter sets for the second-order AR model. We show the learned model can be extrapolated to synthesize trajectories of arbitrary length. CONTACT: ramanathana@ornl.gov; chakracs@pitt.edu."	"http://www.ncbi.nlm.nih.gov/pubmed/21685101"
 3	"english"	"United Kingdom"	"UK"	"0.0"	"0.0258620689655"	"0.129310344828"	"232"	"13.7058823529"	"PLoS One"	"Savory FR, Sait SM, Hope IA"	"Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, The University of Leeds, Leeds, United Kingdom."	"In Caenorhabditis elegans, mutants of the conserved insulin/IGF-1 signalling (IIS) pathway are long-lived and stress resistant due to the altered expression of DAF-16 target genes such as those involved in cellular defence and metabolism. The three Delta(9) desaturase genes, fat-5, fat-6 and fat-7, are included amongst these DAF-16 targets, and it is well established that Delta(9) desaturase enzymes play an important role in survival at low temperatures. However, no assessment of cold tolerance has previously been reported for IIS mutants. We demonstrate that long-lived age-1(hx546) mutants are remarkably resilient to low temperature stress relative to wild type worms, and that this is dependent upon daf-16. We also show that cold tolerance following direct transfer to low temperatures is increased in wild type worms during the facultative, daf-16 dependent, dauer stage. Although the cold tolerant phenotype of age-1(hx546) mutants is predominantly due to the Delta(9) desaturase genes, additional transcriptional targets of DAF-16 are also involved. Surprisingly, survival of wild type adults following a rapid temperature decline is not dependent upon functional daf-16, and cellular distributions of a DAF-16::GFP fusion protein indicate that DAF-16 is not activated during low temperature stress. This suggests that cold-induced physiological defences are not specifically regulated by the IIS pathway and DAF-16, but expression of DAF-16 target genes in IIS mutants and dauers is sufficient to promote cross tolerance to low temperatures in addition to other forms of stress."	"http://www.ncbi.nlm.nih.gov/pubmed/21931751"
+"unk"	"english"	"unknown"	"unknown"	"0.00803212851406"	"0.0401606425703"	"0.10843373494"	"249"	"16.6"	"Nature"	"Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, Dilthey A, Su Z, Freeman C, Hunt SE, Edkins S, Gray E, Booth DR, Potter SC, Goris A, Band G, Oturai AB, Strange A, Saarela J, Bellenguez C, Fontaine B, Gillman M, Hemmer B, Gwilliam R, Zipp F, Jayakumar A, Martin R, Leslie S, Hawkins S, Giannoulatou E, Dalfonso S, Blackburn H, Boneschi FM, Liddle J, Harbo HF, Perez ML, Spurkland A, Waller MJ, Mycko MP, Ricketts M, Comabella M, Hammond N, Kockum I, McCann OT, Ban M, Whittaker P, Kemppinen A, Weston P, Hawkins C, Widaa S, Zajicek J, Dronov S, Robertson N, Bumpstead SJ, Barcellos LF, Ravindrarajah R, Abraham R, Alfredsson L, Ardlie K, Aubin C, Baker A, Baker K, Baranzini SE, Bergamaschi L, Bergamaschi R, Bernstein A, Berthele A, Boggild M, Bradfield JP, Brassat D, Broadley SA, Buck D, Butzkueven H, Capra R, Carroll WM, Cavalla P, Celius EG, Cepok S, Chiavacci R, Clerget-Darpoux F, Clysters K, Comi G, Cossburn M, Cournu-Rebeix I, Cox MB, Cozen W, Cree BA, Cross AH, Cusi D, Daly MJ, Davis E, de Bakker PI, Debouverie M, Dhooghe MB, Dixon K, Dobosi R, Dubois B, Ellinghaus D, Elovaara I, Esposito F, Fontenille C, Foote S, Franke A, Galimberti D, Ghezzi A, Glessner J, Gomez R, Gout O, Graham C, Grant SF, Guerini FR, Hakonarson H, Hall P, Hamsten A, Hartung HP, Heard RN, Heath S, Hobart J, Hoshi M, Infante-Duarte C, Ingram G, Ingram W, Islam T, Jagodic M, Kabesch M, Kermode AG, Kilpatrick TJ, Kim C, Klopp N, Koivisto K, Larsson M, Lathrop M, Lechner-Scott JS, Leone MA, Leppa V, Liljedahl U, Bomfim IL, Lincoln RR, Link J, Liu J, Lorentzen AR, Lupoli S, Macciardi F, Mack T, Marriott M, Martinelli V, Mason D, McCauley JL, Mentch F, Mero IL, Mihalova T, Montalban X, Mottershead J, Myhr KM, Naldi P, Ollier W, Page A, Palotie A, Pelletier J, Piccio L, Pickersgill T, Piehl F, Pobywajlo S, Quach HL, Ramsay PP, Reunanen M, Reynolds R, Rioux JD, Rodegher M, Roesner S, Rubio JP, Ruckert IM, Salvetti M, Salvi E, Santaniello A, Schaefer CA, Schreiber S, Schulze C, Scott RJ, Sellebjerg F, Selmaj KW, Sexton D, Shen L, Simms-Acuna B, Skidmore S, Sleiman PM, Smestad C, Sorensen PS, Sondergaard HB, Stankovich J, Strange RC, Sulonen AM, Sundqvist E, Syvanen AC, Taddeo F, Taylor B, Blackwell JM, Tienari P, Bramon E, Tourbah A, Brown MA, Tronczynska E, Casas JP, Tubridy N, Corvin A, Vickery J, Jankowski J, Villoslada P, Markus HS, Wang K, Mathew CG, Wason J, Palmer CN, Wichmann HE, Plomin R, Willoughby E, Rautanen A, Winkelmann J, Wittig M, Trembath RC, Yaouanq J, Viswanathan AC, Zhang H, Wood NW, Zuvich R, Deloukas P, Langford C, Duncanson A, Oksenberg JR, Pericak-Vance MA, Haines JL, Olsson T, Hillert J, Ivinson AJ, De Jager PL, Peltonen L, Stewart GJ, Hafler DA, Hauser SL, McVean G, Donnelly P, Compston A"		"Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis."	"http://www.ncbi.nlm.nih.gov/pubmed/21833088"
 2	"english"	"USA."	"USA"	"0.030487804878"	"0.030487804878"	"0.0548780487805"	"164"	"14.9090909091"	"Database(Oxford)"	"Schaeffer ML, Harper LC, Gardiner JM, Andorf CM, Campbell DA, Cannon EK, Sen TZ, Lawrence CJ"	"USDA-ARS Plant Genetics Research Unit and Division of Plant Sciences, Department of Agronomy, University of Missouri, Columbia, MO 65211, USA. mary.schaeffer@ars.usda.gov"	"First released in 1991 with the name MaizeDB, the Maize Genetics and Genomics Database, now MaizeGDB, celebrates its 20th anniversary this year. MaizeGDB has transitioned from a focus on comprehensive curation of the literature, genetic maps and stocks to a paradigm that accommodates the recent release of a reference maize genome sequence, multiple diverse maize genomes and sequence-based gene expression data sets. The MaizeGDB Team is relatively small, and relies heavily on the research community to provide data, nomenclature standards and most importantly, to recommend future directions, priorities and strategies. Key aspects of MaizeGDBs intimate interaction with the community are the co-location of curators with maize research groups in multiple locations across the USA as well as coordination with MaizeGDBs close partner, the Maize Genetics Cooperation--Stock Center. In this report, we describe how the MaizeGDB Team currently interacts with the maize research community and our plan for future interactions that will support updates to the functional and structural annotation of the B73 reference genome."	"http://www.ncbi.nlm.nih.gov/pubmed/21624896"
 1	"english"	"Chicago, Chicago, USA."	"USA"	"0.0172413793103"	"0.0172413793103"	"0.103448275862"	"116"	"12.8888888889"	"Immunity"	"Scharf L, Li NS, Hawk AJ, Garzon D, Zhang T, Fox LM, Kazen AR, Shah S, Haddadian EJ, Gumperz JE, Saghatelian A, Faraldo-Gomez JD, Meredith SC, Piccirilli JA, Adams EJ"	"Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA."	"CD1 molecules function to present lipid-based antigens to T cells. Here we present the crystal structure of CD1c at 2.5 A resolution, in complex with the pathogenic Mycobacterium tuberculosis antigen mannosyl-beta1-phosphomycoketide (MPM). CD1c accommodated MPMs methylated alkyl chain exclusively in the A pocket, aided by a unique exit portal underneath the alpha1 helix. Most striking was an open F pocket architecture lacking the closed cavity structure of other CD1 molecules, reminiscent of peptide binding grooves of classical major histocompatibility complex molecules. This feature, combined with tryptophan-fluorescence quenching during loading of a dodecameric lipopeptide antigen, provides a compelling model by which both the lipid and peptide moieties of the lipopeptide are involved in CD1c presentation of lipopeptides."	"http://www.ncbi.nlm.nih.gov/pubmed/21167756"
 2	"english"	"Boston, United States of America"	"USA"	"0.013201320132"	"0.023102310231"	"0.108910891089"	"303"	"14.4761904762"	"PLoS One"	"Scheer FA, Michelson AD, Frelinger AL 3rd, Evoniuk H, Kelly EE, McCarthy M, Doamekpor LA, Barnard MR, Shea SA"	"Medical Chronobiology Program, Division of Sleep Medicine, Brigham and Womens Hospital, Boston, Massachusetts, United States of America."	"BACKGROUND: Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning ( approximately 9AM), potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1) platelet function and (2) platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise. METHODOLOGY/PRINCIPAL FINDINGS: We studied 12 healthy adults (6 female) who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP) IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p</=0.01). These circadian peaks occurred at a circadian phase corresponding to 8-9AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8PM). The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors. CONCLUSIONS/SIGNIFICANCE: These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans-independent of the sleep/wake cycle, other behavioral influences and the environment. The  approximately 9AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous circadian influences on platelet function could contribute to the morning peak in adverse cardiovascular events as seen in many epidemiological studies."	"http://www.ncbi.nlm.nih.gov/pubmed/21931750"
 2	"english"	"UK."	"UK"	"0.00793650793651"	"0.0198412698413"	"0.0396825396825"	"252"	"14.8235294118"	"Nature"	"Seitan VC, Hao B, Tachibana-Konwalski K, Lavagnolli T, Mira-Bontenbal H, Brown KE, Teng G, Carroll T, Terry A, Horan K, Marks H, Adams DJ, Schatz DG, Aragon L, Fisher AG, Krangel MS, Nasmyth K, Merkenschlager M"	"Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK."	"Cohesin enables post-replicative DNA repair and chromosome segregation by holding sister chromatids together from the time of DNA replication in S phase until mitosis. There is growing evidence that cohesin also forms long-range chromosomal cis-interactions and may regulate gene expression in association with CTCF, mediator or tissue-specific transcription factors. Human cohesinopathies such as Cornelia de Lange syndrome are thought to result from impaired non-canonical cohesin functions, but a clear distinction between the cell-division-related and cell-division-independent functions of cohesion--as exemplified in Drosophila--has not been demonstrated in vertebrate systems. To address this, here we deleted the cohesin locus Rad21 in mouse thymocytes at a time in development when these cells stop cycling and rearrange their T-cell receptor (TCR) alpha locus (Tcra). Rad21-deficient thymocytes had a normal lifespan and retained the ability to differentiate, albeit with reduced efficiency. Loss of Rad21 led to defective chromatin architecture at the Tcra locus, where cohesion-binding sites flank the TEA promoter and the Ealpha enhancer, and demarcate Tcra from interspersed Tcrd elements and neighbouring housekeeping genes. Cohesin was required for long-range promoter-enhancer interactions, Tcra transcription, H3K4me3 histone modifications that recruit the recombination machinery and Tcra rearrangement. Provision of pre-rearranged TCR transgenes largely rescued thymocyte differentiation, demonstrating that among thousands of potential target genes across the genome, defective Tcra rearrangement was limiting for the differentiation of cohesin-deficient thymocytes. These findings firmly establish a cell-division-independent role for cohesin in Tcra locus rearrangement and provide a comprehensive account of the mechanisms by which cohesin enables cellular differentiation in a well-characterized mammalian system."	"http://www.ncbi.nlm.nih.gov/pubmed/21832993"
 3	"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."	"http://www.ncbi.nlm.nih.gov/pubmed/21865344"
 3	"english"	"Carolina, USA."	"USA"	"0.0199335548173"	"0.0166112956811"	"0.093023255814"	"301"	"11.1481481481"	"PLoS Computational Biology"	"Selz KA"	"Fetzer Franklin Laboratory of the Cielo Institute, Asheville, North Carolina, USA. selz@cieloinstitute.org"	"Human polymorphonuclear leucocytes, PMN, are highly motile cells with average 12-15 microm diameters and prominent, loboid nuclei. They are produced in the bone marrow, are essential for host defense, and are the most populous of white blood cell types. PMN also participate in acute and chronic inflammatory processes, in the regulation of the immune response, in angiogenesis, and interact with tumors. To accommodate these varied functions, their behavior is adaptive, but still definable in terms of a set of behavioral states. PMN morphodynamics have generally involved a non-equilibrium stationary, spheroid Idling state that transitions to an activated, ellipsoid translocating state in response to chemical signals. These two behavioral shape-states, spheroid and ellipsoid, are generally recognized as making up the vocabulary of a healthy PMN. A third, random state has occasionally been reported as associated with disease states. I have observed this third, Treadmilling state, in PMN from healthy subjects, the cells demonstrating metastable dynamical behaviors known to anticipate phase transitions in mathematical, physical, and biological systems. For this study, human PMN were microscopically imaged and analyzed as single living cells. I used a microscope with a novel high aperture, cardioid annular condenser with better than 100 nanometer resolution of simultaneous, mixed dark field and intrinsic fluorescent images to record shape changes in 189 living PMNs. Relative radial roundness, R(t), served as a computable order parameter. Comparison of R(t) series of 10 cells in the Idling and 10 in the Treadmilling state reveals the robustness of the random appearing Treadmilling state, and the emergence of behaviors observed in the neighborhood of global state transitions, including increased correlation length and variance (divergence), sudden jumps, mixed phases, bimodality, power spectral scaling and temporal slowing. Wavelet transformation of an R(t) series of an Idling to Treadmilling state change, demonstrated behaviors concomitant with the observed transition."	"http://www.ncbi.nlm.nih.gov/pubmed/21490721"
+"unk"	"english"	"unknown"	"unknown"	"0.0185185185185"	"0.037037037037"	"0.172839506173"	"162"	"5.96551724138"	"Bioinformatics"	"Semegni JY, Wamalwa M, Gaujoux R, Harkins GW, Gray A, Martin DP"	"Computational Biology Group, Department of Clinical Laboratory Sciences, IIDMM, University of Cape Town, 7925 Anzio Road, Observatory and South Africa National Bioinformatics Institute, University of the Western Cape, Private Bag X17, Bellville 7535, Cape Town, South Africa."	"SUMMARY: Many natural nucleic acid sequences have evolutionarily conserved secondary structures with diverse biological functions. A reliable computational tool for identifying such structures would be very useful in guiding experimental analyses of their biological functions. NASP (Nucleic Acid Structure Predictor) is a program that takes into account thermodynamic stability, Boltzmann base pair probabilities, alignment uncertainty, covarying sites and evolutionary conservation to identify biologically relevant secondary structures within multiple sequence alignments. Unique to NASP is the consideration of all this information together with a recursive permutation-based approach to progressively identify and list the most conserved probable secondary structures that are likely to have the greatest biological relevance. By focusing on identifying only evolutionarily conserved structures, NASP forgoes the prediction of complete nucleotide folds but outperforms various other secondary structure prediction methods in its ability to selectively identify actual base pairings. AVAILABILITY: Downloable and web-based versions of NASP are freely available at http://web.cbio.uct.ac.za/~yves/nasp_portal.php CONTACT: yves@cbio.uct.ac.za SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21757466"
 1	"english"	"USA."	"USA"	"0.0"	"0.0325203252033"	"0.0569105691057"	"123"	"13.6666666667"	"Immunity"	"Sette A, Rappuoli R"	"La Jolla Institute for Allergy and Immunology, San Diego, CA 92130, USA."	"The sequence of microbial genomes made all potential antigens of each pathogen available for vaccine development. This increased by orders of magnitude potential vaccine targets in bacteria, parasites, and large viruses and revealed virtually all their CD4(+) and CD8(+) T cell epitopes. The genomic information was first used for the development of a vaccine against serogroup B meningococcus, and it is now being used for several other bacterial vaccines. In this review, we will first summarize the impact that genome sequencing has had on vaccine development, and then we will analyze how the genomic information can help further our understanding of immunity to infection or vaccination and lead to the design of better vaccines by diving into the world of T cell immunity."	"http://www.ncbi.nlm.nih.gov/pubmed/21029963"
 3	"english"	"unknown"	"unknown"	"0.0115606936416"	"0.00578034682081"	"0.0635838150289"	"173"	"5.08571428571"	"ANNUAL REVIEW OF PSYCHOLOGY"	"Seyfarth RM, Cheney DL"	"Departments of Psychology and Biology, University of Pennsylvania, Philadelphia, PA 19104; email: seyfarth@psych.upenn.edu."	"Convergent evidence from many species reveals the evolutionary origins of human friendship. In horses, elephants, hyenas, dolphins, monkeys, and chimpanzees, some individuals form friendships that last for years. Bonds occur among females, among males, or between males and females. Genetic relatedness affects friendships. In species where males disperse, friendships are more likely among females. If females disperse, friendships are more likely among males. Not all friendships, however, depend on kinship; many are formed between unrelated individuals. Friendships often involve cooperative interactions that are separated in time. They depend, at least in part, on the memory and emotions associated with past interactions. Applying the term friendship to animals is not anthropomorphic: Many studies have shown that the animals themselves recognize others relationships. Friendships are adaptive. Male allies have superior competitive ability and improved reproductive success; females with the strongest, most enduring friendships experience less stress, higher infant survival, and live longer. Expected final online publication date for the Annual Review of Psychology Volume 63 is November 30, 2011. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates."	"http://www.ncbi.nlm.nih.gov/pubmed/21740224"
 1	"english"	"Chicago, USA."	"USA"	"0.0222222222222"	"0.0"	"0.111111111111"	"45"	"15.0"	"Nature Genetics"	"Shah MY, Licht JD"	"Division of Hematology and Oncology, Northwestern University, Chicago, Illinois, USA."	"New studies reveal that 20% of individuals with acute myeloid leukemia harbor somatic mutations in DNMT3A (encoding DNA methyltransferase 3A). Although these leukemias have some gene expression and DNA methylation changes, a direct link between mutant DNMT3A, epigenetic changes and pathogenesis remains to be established."	"http://www.ncbi.nlm.nih.gov/pubmed/21445072"
 "unk"	"english"	"Frederick, Frederick, USA."	"USA"	"0.0"	"0.0"	"0.0555555555556"	"36"	"5.14285714286"	"Immunity"	"Stewart CA, Trinchieri G"	"Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, NCI-Frederick, Frederick, MD 21702, USA."	"In this issue of Immunity, Chaudhry et al. (2011) and Huber et al. (2011) report that control of Th17 cell responses during colonic inflammation requires direct signaling by IL-10 in regulatory T cells and Th17 cells."	"http://www.ncbi.nlm.nih.gov/pubmed/21511180"
 "unk"	"english"	"Texas, Texas, United States of America"	"USA"	"0.00662251655629"	"0.0198675496689"	"0.105960264901"	"151"	"8.88235294118"	"PLoS One"	"Stewart R, Flechner L, Montminy M, Berdeaux R"	"Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, Texas, United States of America."	"The cAMP response element binding protein (CREB) plays key roles in differentiation of embryonic skeletal muscle progenitors and survival of adult skeletal muscle. However, little is known about the physiologic signals that activate CREB in normal muscle. Here we show that CREB phosphorylation and target genes are induced after acute muscle injury and during regeneration due to genetic mutation. Activated CREB localizes to both myogenic precursor cells and newly regenerating myofibers within regenerating areas. Moreover, we found that signals from damaged skeletal muscle tissue induce CREB phosphorylation and target gene expression in primary mouse myoblasts. An activated CREB mutant (CREBY134F) potentiates myoblast proliferation as well as expression of early myogenic transcription factors in cultured primary myocytes. Consistently, activated CREB-YF promotes myoblast proliferation after acute muscle injury in vivo and enhances muscle regeneration in dystrophic mdx mice. Our findings reveal a new physiologic function for CREB in contributing to skeletal muscle regeneration."	"http://www.ncbi.nlm.nih.gov/pubmed/21931825"
 1	"english"	"USA."	"USA"	"0.0131578947368"	"0.0328947368421"	"0.0690789473684"	"304"	"7.58536585366"	"Database(Oxford)"	"Stojmirovic A, Yu YK"	"National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA."	"Robust advances in interactome analysis demand comprehensive, non-redundant and consistently annotated data sets. By non-redundant, we mean that the accounting of evidence for every interaction should be faithful: each independent experimental support is counted exactly once, no more, no less. While many interactions are shared among public repositories, none of them contains the complete known interactome for any model organism. In addition, the annotations of the same experimental result by different repositories often disagree. This brings up the issue of which annotation to keep while consolidating evidences that are the same. The iRefIndex database, including interactions from most popular repositories with a standardized protein nomenclature, represents a significant advance in all aspects, especially in comprehensiveness. However, iRefIndex aims to maintain all information/annotation from original sources and requires users to perform additional processing to fully achieve the aforementioned goals. Another issue has to do with protein complexes. Some databases represent experimentally observed complexes as interactions with more than two participants, while others expand them into binary interactions using spoke or matrix model. To avoid untested interaction information buildup, it is preferable to replace the expanded protein complexes, either from spoke or matrix models, with a flat list of complex members. To address these issues and to achieve our goals, we have developed ppiTrim, a script that processes iRefIndex to produce non-redundant, consistently annotated data sets of physical interactions. Our script proceeds in three stages: mapping all interactants to gene identifiers and removing all undesired raw interactions, deflating potentially expanded complexes, and reconciling for each interaction the annotation labels among different source databases. As an illustration, we have processed the three largest organismal data sets: yeast, human and fruitfly. While ppiTrim can resolve most apparent conflicts between different labelings, we also discovered some unresolvable disagreements mostly resulting from different annotation policies among repositories. Database URL: http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads/ppiTrim.html."	"http://www.ncbi.nlm.nih.gov/pubmed/21873645"
+"unk"	"english"	"United Kingdom"	"UK"	"0.0"	"0.0169491525424"	"0.101694915254"	"177"	"9.31578947368"	"Molecular Biology and Evolution"	"Stoletzki N, Eyre-Walker A"	"Centre for Study of Evolution, School of Life Sciences, University of Sussex, Brighton, United Kingdom. nstoletzki@googlemail.com"	"A positive correlation between omega, the ratio of the nonsynonymous and synonymous substitution rates, and dS, the synonymous substitution rate has recently been reported. This correlation is unexpected under simple evolutionary models. Here, we investigate two explanations for this correlation: first, whether it is a consequence of a statistical bias in the estimation of omega and second, whether it is due to substitutions at adjacent sites. Using simulations, we show that estimates of omega are biased when levels of divergence are low. This is true using the methods of Yang and Nielsen, Nei and Gojobori, and Muse and Gaut. Although the bias could generate a positive correlation between omega and dS, we show that it is unlikely to be the main determinant. Instead we show that the correlation is reduced when genes that are high quality in sequence, annotation, and alignment are used. The remaining--likely genuine--positive correlation appears to be due to adjacent tandem substitutions; single substitutions, though far more numerous, do not contribute to the correlation. Genuine adjacent substitutions may be due to mutation or selection."	"http://www.ncbi.nlm.nih.gov/pubmed/21115654"
 "unk"	"english"	"United Kingdom"	"UK"	"0.00529100529101"	"0.031746031746"	"0.047619047619"	"189"	"17.1818181818"	"Molecular Biology and Evolution"	"Stoletzki N, Eyre-Walker A"	"Centre for the Study of Evolution, School of Life Sciences, University of Sussex, Brighton, United Kingdom."	"The McDonald-Kreitman (MK) test is a simple and widely used test of selection in which the numbers of nonsilent and silent substitutions (D(n) and D(s)) are compared with the numbers of nonsilent and silent polymorphisms (P(n) and P(s)). The neutrality index (NI = D(s)P(n)/D(n)P(s)), the odds ratio (OR) of the MK table, measures the direction and degree of departure from neutral evolution. The mean of NI values across genes is often taken to summarize patterns of selection in a species. Here, we show that this leads to statistical bias in both simulated and real data to the extent that species, which show a pattern of adaptive evolution, can apparently be subject to weak purifying selection and vice versa. We show that this bias can be removed by using a variant of the Cochran-Mantel-Haenszel procedure for estimating a weighted average OR. We also show that several point estimators of NI are statistically biased even when cutoff values are employed. We therefore suggest that a new statistic be used to study patterns of selection when data are sparse, the direction of selection: DoS = D(n)/(D(n) + D(s)) - P(n)/(P(n) + P(s))."	"http://www.ncbi.nlm.nih.gov/pubmed/20837603"
-"unk"	"english"	"United Kingdom"	"UK"	"0.0"	"0.0169491525424"	"0.101694915254"	"177"	"9.31578947368"	"Molecular Biology and Evolution"	"Stoletzki N, Eyre-Walker A"	"Centre for Study of Evolution, School of Life Sciences, University of Sussex, Brighton, United Kingdom. nstoletzki@googlemail.com"	"A positive correlation between omega, the ratio of the nonsynonymous and synonymous substitution rates, and dS, the synonymous substitution rate has recently been reported. This correlation is unexpected under simple evolutionary models. Here, we investigate two explanations for this correlation: first, whether it is a consequence of a statistical bias in the estimation of omega and second, whether it is due to substitutions at adjacent sites. Using simulations, we show that estimates of omega are biased when levels of divergence are low. This is true using the methods of Yang and Nielsen, Nei and Gojobori, and Muse and Gaut. Although the bias could generate a positive correlation between omega and dS, we show that it is unlikely to be the main determinant. Instead we show that the correlation is reduced when genes that are high quality in sequence, annotation, and alignment are used. The remaining--likely genuine--positive correlation appears to be due to adjacent tandem substitutions; single substitutions, though far more numerous, do not contribute to the correlation. Genuine adjacent substitutions may be due to mutation or selection."	"http://www.ncbi.nlm.nih.gov/pubmed/21115654"
 2	"english"	"UK."	"UK"	"0.0357142857143"	"0.0214285714286"	"0.0357142857143"	"140"	"12.7272727273"	"Nature Genetics"	"Strange A, Capon F, Spencer CC, Knight J, Weale ME, Allen MH, Barton A, Band G, Bellenguez C, Bergboer JG, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Cork MJ, Corvin A, Deloukas P, Dilthey A, Duncanson A, Edkins S, Estivill X, Fitzgerald O, Freeman C, Giardina E, Gray E, Hofer A, Huffmeier U, Hunt SE, Irvine AD, Jankowski J, Kirby B, Langford C, Lascorz J, Leman J, Leslie S, Mallbris L, Markus HS, Mathew CG, McLean WH, McManus R, Mossner R, Moutsianas L, Naluai AT, Nestle FO, Novelli G, Onoufriadis A, Palmer CN, Perricone C, Pirinen M, Plomin R, Potter SC, Pujol RM, Rautanen A, Riveira-Munoz E, Ryan AW, Salmhofer W, Samuelsson L, Sawcer SJ, Schalkwijk J, Smith CH, Stahle M, Su Z, Tazi-Ahnini R, Traupe H, Viswanathan AC, Warren RB, Weger W, Wolk K, Wood N, Worthington J, Young HS, Zeeuwen PL, Hayday A, Burden AD, Griffiths CE, Kere J, Reis A, McVean G, Evans DM, Brown MA, Barker JN, Peltonen L, Donnelly P, Trembath RC"	"Wellcome Trust Centre for Human Genetics, Oxford, UK."	"To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 x 10 and two loci with a combined P < 5 x 10). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 x 10). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis."	"http://www.ncbi.nlm.nih.gov/pubmed/20953190"
 3	"english"	"India, india"	"India"	"0.0236966824645"	"0.0189573459716"	"0.104265402844"	"211"	"16.2307692308"	"Molecular Biology and Evolution"	"Strasburg JL, Kane NC, Raduski AR, Bonin A, Michelmore R, Rieseberg LH"	"Department of Biology, Indiana University. jstrasbu@indiana.edu"	"The role of adaptation in the divergence of lineages has long been a central question in evolutionary biology, and as multilocus sequence data sets have become available for a wide range of taxa, empirical estimates of levels of adaptive molecular evolution are increasingly common. Estimates vary widely among taxa, with high levels of adaptive evolution in Drosophila, bacteria, and viruses but very little evidence of widespread adaptive evolution in hominids. Although estimates in plants are more limited, some recent work has suggested that rates of adaptive evolution in a range of plant taxa are surprisingly low and that there is little association between adaptive evolution and effective population size in contrast to patterns seen in other taxa. Here, we analyze data from 35 loci for six sunflower species that vary dramatically in effective population size. We find that rates of adaptive evolution are positively correlated with effective population size in these species, with a significant fraction of amino acid substitutions driven by positive selection in the species with the largest effective population sizes but little or no evidence of adaptive evolution in species with smaller effective population sizes. Although other factors likely contribute as well, in sunflowers effective population size appears to be an important determinant of rates of adaptive evolution."	"http://www.ncbi.nlm.nih.gov/pubmed/20952500"
 "unk"	"english"	"USA."	"USA"	"0.020979020979"	"0.013986013986"	"0.048951048951"	"143"	"9.53333333333"	"Immunity"	"Stritesky GL, Muthukrishnan R, Sehra S, Goswami R, Pham D, Travers J, Nguyen ET, Levy DE, Kaplan MH"	"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA."	"Signal transducer and activator of transcription (STAT) family members direct the differentiation of T helper cells, with specific STAT proteins promoting distinct effector subsets. STAT6 is required for the development of T helper 2 (Th2) cells, whereas STAT3 promotes differentiation of Th17 and follicular helper T cell subsets. We demonstrated that STAT3 was also activated during Th2 cell development and was required for the expression of Th2 cell-associated cytokines and transcription factors. STAT3 bound directly to Th2 cell-associated gene loci and was required for the ability of STAT6 to bind target genes. In vivo, STAT3 deficiency in T cells eliminated the allergic inflammation in mice sensitized and challenged with ovalbumin or transgenic for constitutively active STAT6. Thus, STAT3 cooperates with STAT6 in promoting Th2 cell development. These results demonstrate that differentiating T helper cells integrate multiple STAT protein signals during Th2 cell development."	"http://www.ncbi.nlm.nih.gov/pubmed/21215659"
 "unk"	"english"	"United Kingdom"	"UK"	"0.015"	"0.02"	"0.07"	"200"	"9.57142857143"	"Blood"	"Telfer PT, Evanson J, Butler P, Hemmaway C, Abdulla C, Gadong N, Whitmarsh S, Kaya B, Kirkham FJ"	"Department of Pediatric Hematology, Barts and The London NHS Trust, London, United Kingdom;"	"Cervical Internal carotid artery (cICA) occlusion is a recognised cause of acute ischemic stroke (AIS) in Sickle cell disease (SCD), but clinical and radiological features are not well described. We reviewed Cervical Magnetic Resonance Angiography (cMRA) performed prospectively in 67 patients (55 children), for indications including transcranial Doppler (TCD) abnormalities, AIS or previous AIS. cICA lesions were seen in 10 (15%), including 4/7 patients presenting with AIS. They appear to have been missed on first presentation in 4/10 patients with previous AIS. Radiological features in 7 cases were consistent with dissection. In two patients, there was strong clinical and radiological evidence for thromboembolic AIS, and this was also considered possible in four other cases. Three of the four AIS patients were anti-coagulated acutely, and the non-treated patient had recurrent, probably thromboembolic, AIS. Transcranial Doppler findings were variable, but in four cases there were high velocities in the cerebral vessels contralateral to the cICA stenosis. We suggest that all cases of AIS should have cMRA during acute evaluation, to identify cICA occlusions which may require anti-coagulation. Routine screening of SCD children should also include evaluation of neck vessels by carotid Doppler followed by cMRA if a cervical vascular lesion is suspected."	"http://www.ncbi.nlm.nih.gov/pubmed/21885600"
 "unk"	"english"	"USA."	"USA"	"0.0186335403727"	"0.0310559006211"	"0.0683229813665"	"161"	"9.47058823529"	"Nature Genetics"	"Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M"	"Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA."	"Because only a small fraction of asbestos-exposed individuals develop malignant mesothelioma, and because mesothelioma clustering is observed in some families, we searched for genetic predisposing factors. We discovered germline mutations in the gene encoding BRCA1 associated protein-1 (BAP1) in two families with a high incidence of mesothelioma, and we observed somatic alterations affecting BAP1 in familial mesotheliomas, indicating biallelic inactivation. In addition to mesothelioma, some BAP1 mutation carriers developed uveal melanoma. We also found germline BAP1 mutations in 2 of 26 sporadic mesotheliomas; both individuals with mutant BAP1 were previously diagnosed with uveal melanoma. We also observed somatic truncating BAP1 mutations and aberrant BAP1 expression in sporadic mesotheliomas without germline mutations. These results identify a BAP1-related cancer syndrome that is characterized by mesothelioma and uveal melanoma. We hypothesize that other cancers may also be involved and that mesothelioma predominates upon asbestos exposure. These findings will help to identify individuals at high risk of mesothelioma who could be targeted for early intervention."	"http://www.ncbi.nlm.nih.gov/pubmed/21874000"
 "unk"	"english"	"California, USA."	"USA"	"0.00595238095238"	"0.0238095238095"	"0.0535714285714"	"168"	"11.2"	"Glycobiology"	"Thon V, Lau K, Yu H, Tran BK, Chen X"	"Department of Chemistry, University of California, Davis, CA 95616, USA."	"Pasteurella multocida (Pm) is a multi-species pathogen that causes diseases in animals and humans. Sialyltransferase activity has been detected in multiple Pm strains and sialylation has been shown to be important for the pathogenesis of Pm. Three putative sialyltransferase genes have been identified in Pm genomic strain Pm70. We have reported previously that a Pm0188 gene homolog in Pm strain P-1059 (ATCC 15742) encodes a multifunctional sialyltransferase (PmST1). We demonstrate here that while PmST1 prefers to use oligosaccharides as acceptors, PmST2 encoded by the Pm0508 gene homolog in the same Pm strain is a novel glycolipid alpha2-3-sialyltransferase that prefers to use lactosyl lipids as acceptor substrates. PmST2 and PmST1 thus complement each other for an efficient synthesis of alpha2-3-linked sialosides with or without lipid portion. In addition, beta1-4-linked galactosyl lipids are better PmST2 substrates than beta1-3-linked galactosyl lipids. PmST2 has been used successfully in the preparative scale synthesis of sialyllactosyl sphingosine (lyso-GM3), which is an important glycolipid and an intermediate for synthesizing more complex glycolipids such as gangliosides."	"http://www.ncbi.nlm.nih.gov/pubmed/21515586"
+"unk"	"english"	"unknown"	"unknown"	"0.0"	"0.0243902439024"	"0.0325203252033"	"123"	"24.6"	"Nature Genetics"	"Thorleifsson G, Walters GB, Hewitt AW, Masson G, Helgason A, DeWan A, Sigurdsson A, Jonasdottir A, Gudjonsson SA, Magnusson KP, Stefansson H, Lam DS, Tam PO, Gudmundsdottir GJ, Southgate L, Burdon KP, Gottfredsdottir MS, Aldred MA, Mitchell P, St Clair D, Collier DA, Tang N, Sveinsson O, Macgregor S, Martin NG, Cree AJ, Gibson J, Macleod A, Jacob A, Ennis S, Young TL, Chan JC, Karwatowski WS, Hammond CJ, Thordarson K, Zhang M, Wadelius C, Lotery AJ, Trembath RC, Pang CP, Hoh J, Craig JE, Kong A, Mackey DA, Jonasson F, Thorsteinsdottir U, Stefansson K"	"deCODE genetics Inc, Reykjavik, Iceland. gudmar.thorleifsson@decode.is"	"We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[A], odds ratio (OR) = 1.36, P = 5.0 x 10(1)). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG."	"http://www.ncbi.nlm.nih.gov/pubmed/20835238"
 "unk"	"english"	"Boston, United States of America"	"USA"	"0.0"	"0.0272373540856"	"0.108949416342"	"257"	"11.1739130435"	"PLoS One"	"Thurber GM, Weissleder R"	"Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America."	"Recent advances in genome inspired target discovery, small molecule screens, development of biological and nanotechnology have led to the introduction of a myriad of new differently sized agents into the clinic. The differences in small and large molecule delivery are becoming increasingly important in combination therapies as well as the use of drugs that modify the physiology of tumors such as anti-angiogenic treatment. The complexity of targeting has led to the development of mathematical models to facilitate understanding, but unfortunately, these studies are often only applicable to a particular molecule, making pharmacokinetic comparisons difficult. Here we develop and describe a framework for categorizing primary pharmacokinetics of drugs in tumors. For modeling purposes, we define drugs not by their mechanism of action but rather their rate-limiting step of delivery. Our simulations account for variations in perfusion, vascularization, interstitial transport, and non-linear local binding and metabolism. Based on a comparison of the fundamental rates determining uptake, drugs were classified into four categories depending on whether uptake is limited by blood flow, extravasation, interstitial diffusion, or local binding and metabolism. Simulations comparing small molecule versus macromolecular drugs show a sharp difference in distribution, which has implications for multi-drug therapies. The tissue-level distribution differs widely in tumors for small molecules versus macromolecular biologic drugs, and this should be considered in the design of agents and treatments. An example using antibodies in mouse xenografts illustrates the different in vivo behavior. This type of transport analysis can be used to aid in model development, experimental data analysis, and imaging and therapeutic agent design."	"http://www.ncbi.nlm.nih.gov/pubmed/21935441"
 "unk"	"english"	"New York, USA."	"USA"	"0.0217391304348"	"0.00724637681159"	"0.0507246376812"	"138"	"10.6153846154"	"Nature Genetics"	"Tian F, Bradbury PJ, Brown PJ, Hung H, Sun Q, Flint-Garcia S, Rocheford TR, McMullen MD, Holland JB, Buckler ES"	"Institute for Genomic Diversity, Cornell University, Ithaca, New York, USA."	"US maize yield has increased eight-fold in the past 80 years, with half of the gain attributed to selection by breeders. During this time, changes in maize leaf angle and size have altered plant architecture, allowing more efficient light capture as planting density has increased. Through a genome-wide association study (GWAS) of the maize nested association mapping panel, we determined the genetic basis of important leaf architecture traits and identified some of the key genes. Overall, we demonstrate that the genetic architecture of the leaf traits is dominated by small effects, with little epistasis, environmental interaction or pleiotropy. In particular, GWAS results show that variations at the liguleless genes have contributed to more upright leaves. These results demonstrate that the use of GWAS with specially designed mapping populations is effective in uncovering the basis of key agronomic traits."	"http://www.ncbi.nlm.nih.gov/pubmed/21217756"
 "unk"	"english"	"California, USA."	"USA"	"0.0"	"0.0197628458498"	"0.0395256916996"	"253"	"10.12"	"Nature"	"Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, de Sauvage FJ"	"Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA."	"The small intestine epithelium renews every 2 to 5 days, making it one of the most regenerative mammalian tissues. Genetic inducible fate mapping studies have identified two principal epithelial stem cell pools in this tissue. One pool consists of columnar Lgr5-expressing cells that cycle rapidly and are present predominantly at the crypt base. The other pool consists of Bmi1-expressing cells that largely reside above the crypt base. However, the relative functions of these two pools and their interrelationship are not understood. Here we specifically ablated Lgr5-expressing cells in mice using a human diphtheria toxin receptor (DTR) gene knocked into the Lgr5 locus. We found that complete loss of the Lgr5-expressing cells did not perturb homeostasis of the epithelium, indicating that other cell types can compensate for the elimination of this population. After ablation of Lgr5-expressing cells, progeny production by Bmi1-expressing cells increased, indicating that Bmi1-expressing stem cells compensate for the loss of Lgr5-expressing cells. Indeed, lineage tracing showed that Bmi1-expressing cells gave rise to Lgr5-expressing cells, pointing to a hierarchy of stem cells in the intestinal epithelium. Our results demonstrate that Lgr5-expressing cells are dispensable for normal intestinal homeostasis, and that in the absence of these cells, Bmi1-expressing cells can serve as an alternative stem cell pool. These data provide the first experimental evidence for the interrelationship between these populations. The Bmi1-expressing stem cells may represent both a reserve stem cell pool in case of injury to the small intestine epithelium and a source for replenishment of the Lgr5-expressing cells under non-pathological conditions."	"http://www.ncbi.nlm.nih.gov/pubmed/21927002"
 "unk"	"europe_not_latin"	"Germany"	"Germany"	"0.0148148148148"	"0.0222222222222"	"0.0518518518519"	"135"	"10.3846153846"	"Nature"	"Faelber K, Posor Y, Gao S, Held M, Roske Y, Schulze D, Haucke V, Noe F, Daumke O"	"Crystallography, Max-Delbruck-Centrum for Molecular Medicine, Robert-Rossle-Strasse 10, 13125 Berlin, Germany."	"Dynamin is a mechanochemical GTPase that oligomerizes around the neck of clathrin-coated pits and catalyses vesicle scission in a GTP-hydrolysis-dependent manner. The molecular details of oligomerization and the mechanism of the mechanochemical coupling are currently unknown. Here we present the crystal structure of human dynamin 1 in the nucleotide-free state with a four-domain architecture comprising the GTPase domain, the bundle signalling element, the stalk and the pleckstrin homology domain. Dynamin 1 oligomerized in the crystals via the stalks, which assemble in a criss-cross fashion. The stalks further interact via conserved surfaces with the pleckstrin homology domain and the bundle signalling element of the neighbouring dynamin molecule. This intricate domain interaction rationalizes a number of disease-related mutations in dynamin 2 and suggests a structural model for the mechanochemical coupling that reconciles previous models of dynamin function."	"http://www.ncbi.nlm.nih.gov/pubmed/21927000"
 "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."	"http://www.ncbi.nlm.nih.gov/pubmed/21878685"
 "unk"	"europe_not_latin"	"Germany"	"Germany"	"0.00896860986547"	"0.0179372197309"	"0.0493273542601"	"223"	"6.24324324324"	"Bioinformatics"	"Fazius E, Shelest V, Shelest E"	"Research group Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoll Institute, Beutenbergstr. 11 a, 07745 Jena, Germany."	"MOTIVATION: Prediction of transcription factor binding sites (TFBSs) is crucial for promoter modeling and network inference. Quality of the predictions is spoiled by numerous false positives, which persist as the main problem for all presently available TFBS search methods. RESULTS: We suggest a novel approach, which is alternative to widely used position weight matrices (PWMs) and Hidden Markov Models. Each motif of the input set is used as a search template to scan a query sequence. Found motifs are assigned scores depending on the non-randomness of the motifs occurrence, the number of matching searching motifs, and the number of mismatches. The non-randomness is estimated by comparison of observed numbers of matching motifs with those predicted to occur by chance. The latter can be calculated given the base compositions of the motif and the query sequence. The method does not require preliminary alignment of the input motifs, hence avoiding uncertainties introduced by the alignment procedure. In comparison with PWM-based tools, our method demonstrates higher precision by the same sensitivity and specificity. It also tends to outperform methods combining pattern and PWM search. Most important, it allows reducing the number of false positive predictions significantly. AVAILABILITY: The method is implemented in a tool called SiTaR (Site Tracking and Recognition) and is available at http://sbi.hkijena.de/sitar/index.php. CONTACT: ekaterina.shelest@hki-jena.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21893518"
+"unk"	"europe_not_latin"	"unknown"	"unknown"	"0.0"	"0.031914893617"	"0.0531914893617"	"94"	"13.4285714286"	"Molecular Biology and Evolution"	"Felekkis K, Voskarides K, Dweep H, Sticht C, Gretz N, Deltas C"	"Department of Biological Sciences and Molecular Medicine Research Center, University of Cyprus, Nicosia, Cyprus."	"MicroRNAs (miRNAs) and copy number variations (CNVs) are two newly discovered genetic elements that have revolutionized the field of molecular biology and genetics. By performing in silico whole genome analysis, we demonstrate that both the number of miRNAs that target genes found in CNV regions as well as the number of miRNA-binding sites are significantly higher than those of genes found in non-CNV regions. This suggests that miRNAs may have acted as equilibrators of gene expression during evolution in an attempt to regulate aberrant gene expression and to increase the tolerance to genome plasticity."	"http://www.ncbi.nlm.nih.gov/pubmed/21441354"
 "unk"	"europe_not_latin"	"Switzerland"	"Switzerland"	"0.0110701107011"	"0.0110701107011"	"0.0811808118081"	"271"	"11.8260869565"	"PLoS One"	"Fenner L, Malla B, Ninet B, Dubuis O, Stucki D, Borrell S, Huna T, Bodmer T, Egger M, Gagneux S"	"Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland."	"BACKGROUND: Mycobacterium tuberculosis has a global population structure consisting of six main phylogenetic lineages associated with specific geographic regions and human populations. One particular M. tuberculosis genotype known as Beijing has repeatedly been associated with drug resistance and has been emerging in some parts of the world. Beijing strains are traditionally defined based on a characteristic spoligotyping pattern. We used three alternative genotyping techniques to revisit the phylogenetic classification of M. tuberculosis complex (MTBC) strains exhibiting the typical Beijing spoligotyping pattern. METHODS AND FINDINGS: MTBC strains were obtained from an ongoing molecular epidemiological study in Switzerland and Nepal. MTBC genotyping was performed based on SNPs, genomic deletions, and 24-loci MIRU-VNTR. We identified three MTBC strains from patients originating from Tibet, Portugal and Nepal which exhibited a spoligotyping patterns identical to the classical Beijing signature. However, based on three alternative molecular markers, these strains were assigned to Lineage 3 (also known as Delhi/CAS) rather than to Lineage 2 (also known as East-Asian lineage). Sequencing of the RD207 in one of these strains showed that the deletion responsible for this Pseudo-Beijing spoligotype was about 1,000 base pairs smaller than the usual deletion of RD207 in classical Beijing strains, which is consistent with an evolutionarily independent deletion event in the direct repeat (DR) region of MTBC. CONCLUSIONS: We provide an example of convergent evolution in the DR locus of MTBC, and highlight the limitation of using spoligotypes for strain classification. Our results indicate that a proportion of Beijing strains may have been misclassified in the past. Markers that are more phylogenetically robust should be used when exploring strain-specific differences in experimental or clinical phenotypes."	"http://www.ncbi.nlm.nih.gov/pubmed/21935448"
 "unk"	"europe_not_latin"	"Germany"	"Germany"	"0.00460829493088"	"0.0276497695853"	"0.0599078341014"	"217"	"10.3333333333"	"Molecular Biology and Evolution"	"Feuerbach L, Lyngso RB, Lengauer T, Hein J"	"Computational Biology and Applied Algorithmics, Max Planck Institute fur Informatik, Saarbrucken, Germany. lfbach@mpi-inf.mpg.de"	"One of the key objectives of comparative genomics is the characterization of the forces that shape genomes over the course of evolution. In the last decades, evidence has been accumulated that for vertebrate genomes also epigenetic modifications have to be considered in this context. Especially, the elevated mutation frequency of 5-methylcytosine (5mC) is assumed to facilitate the depletion of CpG dinucleotides in species that exhibit global DNA methylation. For instance, the underrepresentation of CpG dinucleotides in many mammalian genomes is attributed to this effect, which is only neutralized in so-called CpG islands (CGIs) that are preferentially unmethylated and thus partially protected from rapid CpG decay. For primate-specific CpG-rich transposable elements from the ALU family, it is unclear whether their elevated CpG frequency is caused by their small age or by the absence of DNA methylation. In consequence, these elements are often misclassified in CGI annotations. We present a method for the estimation of germ line methylation from pairwise ancestral-descendant alignments. The approach is validated in a simulation study and tested on DNA repeats from the AluSx family. We conclude that a predicted unmethylated state in the germ line is highly correlated with epigenetic activity of the respective genomic region. Thus, CpG-rich repeats can be facilitated as in silico probes for the epigenetic potential of their genomic neighborhood."	"http://www.ncbi.nlm.nih.gov/pubmed/21212152"
 "unk"	"europe_not_latin"	"Germany"	"Germany"	"0.00675675675676"	"0.00675675675676"	"0.027027027027"	"148"	"11.3846153846"	"Immunity"	"Flach H, Rosenbaum M, Duchniewicz M, Kim S, Zhang SL, Cahalan MD, Mittler G, Grosschedl R"	"Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany."	"Marginal zone (MZ) B cells of the spleen and B1 cells, termed innate-like B cells, differ from follicular B cells by their attenuated Ca(2+) mobilization, fast antibody secretion, and increased cell adhesion. We identified and characterized Mzb1 as an endoplasmic reticulum-localized and B cell-specific protein that was most abundantly expressed in MZ B and B1 cells. Knockdown of Mzb1 in MZ B cells increased Ca(2+) mobilization and nuclear NFAT transcription factor localization, but reduced lipopolysaccharide-induced antibody secretion and integrin-mediated cell adhesion. Conversely, ectopic expression of an Lck-Mzb1 transgene in peripheral T cells resulted in attenuated Ca(2+) mobilization and augmented integrin-mediated cell adhesion. In addition to its interaction with the substrate-specific chaperone Grp94, Mzb1 augmented the function of the oxidoreductase ERp57 in favoring the expression of integrins in their activated conformation. Thus, Mzb1 helps to diversify peripheral B cell functions by regulating Ca(2+) stores, antibody secretion, and integrin activation."	"http://www.ncbi.nlm.nih.gov/pubmed/21093319"
 "unk"	"europe_not_latin"	"Poland"	"Poland"	"0.00396825396825"	"0.0198412698413"	"0.0555555555556"	"252"	"12.0"	"Molecular Biology and Evolution"	"Lipinski KA, Puchta O, Surendranath V, Kudla M, Golik P"	"Faculty of Biology, Institute of Genetics and Biotechnology, University of Warsaw, Warsaw, Poland."	"Pentatricopeptide repeat (PPR) proteins are the largest known RNA-binding protein family, and are found in all eukaryotes, being particularly abundant in higher plants. PPR proteins localize mostly to mitochondria and chloroplasts, and many were shown to modulate organellar genome expression on the posttranscriptional level. Although the genomes of land plants encode hundreds of PPR proteins, only a few have been identified in Fungi and Metazoa. As the current PPR motif profiles are built mainly on the basis of the predominant plant sequences, they are unlikely to be optimal for detecting fungal and animal members of the family, and many putative PPR proteins in these genomes may remain undetected. In order to verify this hypothesis, we designed a hidden Markov model-based bioinformatic tool called Supervised Clustering-based Iterative Phylogenetic Hidden Markov Model algorithm for the Evaluation of tandem Repeat motif families (SCIPHER) using sequence data from orthologous clusters from available yeast genomes. This approach allowed us to assign 12 new proteins in Saccharomyces cerevisiae to the PPR family. Similarly, in other yeast species, we obtained a 5-fold increase in the detection of PPR motifs, compared with the previous tools. All the newly identified S. cerevisiae PPR proteins localize in the mitochondrion and are a part of the RNA processing interaction network. Furthermore, the yeast PPR proteins seem to undergo an accelerated divergent evolution. Analysis of single and double amino acid substitutions in the Dmr1 protein of S. cerevisiae suggests that cooperative interactions between motifs and pseudoreversion could be the force driving this rapid evolution."	"http://www.ncbi.nlm.nih.gov/pubmed/21546354"
 "unk"	"europe_not_latin"	"Netherlands"	"Netherlands"	"0.00694444444444"	"0.0277777777778"	"0.104166666667"	"144"	"11.1538461538"	"PLoS Computational Biology"	"Lopez CA, de Vries AH, Marrink SJ"	"Groningen Biomolecular Sciences and Biotechnology Institute & Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands."	"The depletion of cholesterol from membranes, mediated by beta-cyclodextrin (beta-CD) is well known and documented, but the molecular details of this process are largely unknown. Using molecular dynamics simulations, we have been able to study the CD mediated extraction of cholesterol from model membranes, in particular from a pure cholesterol monolayer, at atomic resolution. Our results show that efficient cholesterol extraction depends on the structural distribution of the CDs on the surface of the monolayer. With a suitably oriented dimer, cholesterol is extracted spontaneously on a nanosecond time scale. Additional free energy calculations reveal that the CDs have a strong affinity to bind to the membrane surface, and, by doing so, destabilize the local packing of cholesterol molecules making their extraction favorable. Our results have implications for the interpretation of experimental measurements, and may help in the rational design of efficient CD based nano-carriers."	"http://www.ncbi.nlm.nih.gov/pubmed/21455285"
 "unk"	"europe_not_latin"	"Germany"	"Germany"	"0.0324675324675"	"0.0194805194805"	"0.038961038961"	"154"	"8.42105263158"	"BMC Bioinformatics"	"Loyek C, Rajpoot NM, Khan M, Nattkemper TW"	"Biodata Mining Group, Faculty of Technology, Bielefeld University, Universitatsstrasse 25, 33615 Bielefeld, Germany. cloyek@techfak.uni-bielefeld.de."	"ABSTRACT: BACKGROUND: Innovations in biological and biomedical imaging produce complex high-content and multivariate image data. For decision-making and generation of hypotheses, scientists need novel information technology tools that enable them to visually explore and analyze the data and to discuss and communicate results or findings with collaborating experts from various places. RESULTS: In this paper, we present a novel Web2.0 approach, BioIMAX, for the collaborative exploration and analysis of multivariate image data by combining the webs collaboration and distribution architecture with the interface interactivity and computation power of desktop applications, recently called rich internet application. CONCLUSIONS: BioIMAX allows scientists to discuss and share data or results with collaborating experts and to visualize, annotate, and explore multivariate image data within one web-based platform from any location via a standard web browser requiring only a username and a password. BioIMAX can be accessed at http://ani.cebitec.uni-bielefeld.de/BioIMAX with the username test and the password test1 for testing purposes."	"http://www.ncbi.nlm.nih.gov/pubmed/21777450"
+"unk"	"europe_not_latin"	"unknown"	"unknown"	"0.0078125"	"0.0234375"	"0.09375"	"256"	"11.1304347826"	"BMC Bioinformatics"	"Ludwig C, Gunther UL"		"ABSTRACT: BACKGROUND: Despite wide-spread use of Nuclear Magnetic Resonance (NMR) in metabolomics for the analysis of biological samples there is a lack of graphically driven, publicly available software to process large one and two-dimensional NMR data sets for statistical analysis. RESULTS: Here we present MetaboLab, a MATLAB based software package that facilitates NMR data processing by providing automated algorithms for processing series of spectra in a reproducible fashion. A graphical user interface provides easy access to all steps of data processing via a script builder to generate MATLAB scripts, providing an option to alter code manually. The analysis of two-dimensional spectra (1H,13C-HSQC spectra) is facilitated by the use of a spectral library derived from publicly available databases which can be extended readily. The software allows to display specific metabolites in small regions of interest where signals can be picked. To facilitate the analysis of series of two-dimensional spectra, different spectra can be overlaid and assignments can be transferred between spectra. The software includes mechanisms to account for overlapping signals by highlighting neighboring and ambiguous assignments. CONCLUSIONS: The MetaboLab software is an integrated software package for NMR data processing and analysis, closely linked to the previously developed NMRLab software. It includes tools for batch processing and gives access to a wealth of algorithms available in the MATLAB framework. Algorithms within MetaboLab help to optimize the flow of metabolomics data preparation for statistical analysis. The combination of an intuitive graphical user interface along with advanced data processing algorithms facilitates the use of MetaboLab in a broader metabolomics context."	"http://www.ncbi.nlm.nih.gov/pubmed/21914187"
 "unk"	"europe_not_latin"	"Germany"	"Germany"	"0.0120481927711"	"0.0240963855422"	"0.078313253012"	"166"	"8.73684210526"	"PLoS Computational Biology"	"Luling H, Siveke I, Grothe B, Leibold C"	"Department of Biology II, Ludwig-Maximilians Universitat Munchen, Planegg-Martinsried, Germany."	"Interaural time differences (ITDs) are the major cue for localizing low-frequency sounds. The activity of neuronal populations in the brainstem encodes ITDs with an exquisite temporal acuity of about 10 mus. The response of single neurons, however, also changes with other stimulus properties like the spectral composition of sound. The influence of stimulus frequency is very different across neurons and thus it is unclear how ITDs are encoded independently of stimulus frequency by populations of neurons. Here we fitted a statistical model to single-cell rate responses of the dorsal nucleus of the lateral lemniscus. The model was used to evaluate the impact of single-cell response characteristics on the frequency-invariant mutual information between rate response and ITD. We found a rough correspondence between the measured cell characteristics and those predicted by computing mutual information. Furthermore, we studied two readout mechanisms, a linear classifier and a two-channel rate difference decoder. The latter turned out to be better suited to decode the population patterns obtained from the fitted model."	"http://www.ncbi.nlm.nih.gov/pubmed/21445227"
 "unk"	"europe_not_latin"	"Sweden"	"Sweden"	"0.0117647058824"	"0.0176470588235"	"0.0941176470588"	"170"	"8.33333333333"	"BMC Bioinformatics"	"Lysholm F, Andersson B, Persson B"	"IFM Bioinformatics and SeRC (Swedish e-Science Research Centre), Linkoping University, S-581 83 Linkoping, Sweden. frely@ifm.liu.se."	"ABSTRACT: BACKGROUND: High throughput pyrosequencing (454 sequencing) is the major sequencing platform for producing long read high throughput data. While most other sequencing techniques produce reading errors mainly comparable with substitutions, pyrosequencing produce errors mainly comparable with gaps. These errors are less efficiently detected by most conventional alignment programs and may produce inaccurate alignments. RESULTS: We suggest a novel algorithm for calculating the optimal local alignment which utilises flowpeak information in order to improve alignment accuracy. Flowpeak information can be retained from a 454 sequencing run through interpretation of the binary SFF-file format. This novel algorithm has been implemented in a program named FAAST (Flow-space Assisted Alignment Search Tool). CONCLUSIONS: We present and discuss the results of simulations that show that FAAST, through the use of the novel algorithm, can gain several percentage points of accuracy compared to Smith-Waterman-Gotoh alignments, depending on the 454 data quality. Furthermore, through an efficient multi-thread aware implementation, FAAST is able to perform these high quality alignments at high speed.The tool is available at http://www.ifm.liu.se/bioinfo/"	"http://www.ncbi.nlm.nih.gov/pubmed/21771335"
 "unk"	"europe_not_latin"	"Finland"	"Finland"	"0.0119760479042"	"0.0179640718563"	"0.0658682634731"	"167"	"6.03448275862"	"Bioinformatics"	"Makela J, Huttunen H, Kandhavelu M, Yli-Harja O, Ribeiro AS"	"Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, FI-33101 Tampere, Finland."	"MOTIVATION: Production and degradation of RNA and proteins are stochastic processes, difficulting the distinction between spurious fluctuations in their numbers and changes in the dynamics of a genetic circuit. An accurate method of change detection is key to analyze plasticity and robustness of stochastic genetic circuits. RESULTS: We use automatic change point detection methods to detect non-spurious changes in the dynamics of delayed stochastic models of gene networks at run time. We test the methods in detecting changes in mean and noise of protein numbers, and in the switching frequency of a genetic switch. We also detect changes, following genes silencing, in the dynamics of a model of the core gene regulatory network of Saccharomyces cerevisiae with 328 genes. Finally, from images, we determine when RNA molecules tagged with fluorescent proteins are first produced in Escherichia coli. Provided prior knowledge on the time scale of the changes, the methods detect them accurately and are robust to fluctuations in protein and RNA levels. AVAILABILITY: Simulator: www.cs.tut.fi/~sanchesr/SGN/SGNSim.html CONTACT: andre.ribeiro@tut.fi."	"http://www.ncbi.nlm.nih.gov/pubmed/21835771"
 "unk"	"europe_not_latin"	"Poland"	"Poland"	"0.0119760479042"	"0.0179640718563"	"0.0838323353293"	"334"	"11.5172413793"	"BMC Bioinformatics"	"Sroka J, Bieniasz-Krzywiec L, Gwozdz S, Leniowski D, Lacki J, Markowski M, Avignone-Rossa C, Bushell ME, McFadden J, Kierzek AM"	"Institute of Informatics University of Warsaw, Poland."	"BACKGROUND: Constraint-based approaches facilitate the prediction of cellular metabolic capabilities, based, in turn on predictions of the repertoire of enzymes encoded in the genome. Recently, genome annotations have been used to reconstruct genome scale metabolic reaction networks for numerous species, including Homo sapiens, which allow simulations that provide valuable insights into topics, including predictions of gene essentiality of pathogens, interpretation of genetic polymorphism in metabolic disease syndromes and suggestions for novel approaches to microbial metabolic engineering. These constraint-based simulations are being integrated with the functional genomics portals, an activity that requires efficient implementation of the constraint-based simulations in the web-based environment. RESULTS: Here, we present Acorn, an open source (GNU GPL) grid computing system for constraint-based simulations of genome scale metabolic reaction networks within an interactive web environment. The grid-based architecture allows efficient execution of computationally intensive, iterative protocols such as Flux Variability Analysis, which can be readily scaled up as the numbers of models (and users) increase. The web interface uses AJAX, which facilitates efficient model browsing and other search functions, and intuitive implementation of appropriate simulation conditions. Research groups can install Acorn locally and create user accounts. Users can also import models in the familiar SBML format and link reaction formulas to major functional genomics portals of choice. Selected models and simulation results can be shared between different users and made publically available. Users can construct pathway map layouts and import them into the server using a desktop editor integrated within the system. Pathway maps are then used to visualise numerical results within the web environment. To illustrate these features we have deployed Acorn and created a web server allowing constraint based simulations of the genome scale metabolic reaction networks of E. coli, S. cerevisiae and M. tuberculosis. CONCLUSIONS: Acorn is a free software package, which can be installed by research groups to create a web based environment for computer simulations of genome scale metabolic reaction networks. It facilitates shared access to models and creation of publicly available constraint based modelling resources."	"http://www.ncbi.nlm.nih.gov/pubmed/21609434"
 "unk"	"europe_not_latin"	"Switzerland"	"Switzerland"	"0.0"	"0.0140845070423"	"0.0985915492958"	"142"	"15.7777777778"	"Molecular Biology and Evolution"	"Stadler T, Florez-Rueda AM, Paris M"	"Plant Ecological Genetics, Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland."	"Two recent high-profile studies offered empirical evidence for a snowballing accumulation of postzygotic incompatibilities in Drosophila and Solanum (tomatoes). Here we present a reanalysis of the Solanum data that is motivated by population-genetic principles. Specifically, the high levels of intraspecific nucleotide polymorphism in wild tomato species and presumably large effective population size throughout the divergence history of this clade imply that ancestral polymorphism should be taken into account when evaluating sequence divergence between species. Based on our reanalyses of synonymous-site divergence between the four focal Solanum species and a wide range of ancestral polymorphism, we assessed under which conditions the reported accumulation of seed sterility factors supports the snowball effect. Our results highlight the pivotal impact of levels of ancestral polymorphism and alternate divergence values, and they illustrate that robust tests of the snowball effect in Solanum require genome-wide estimates of divergence."	"http://www.ncbi.nlm.nih.gov/pubmed/21890474"
 "unk"	"europe_not_latin"	"Switzerland"	"Switzerland"	"0.0"	"0.0526315789474"	"0.0526315789474"	"114"	"10.3636363636"	"Molecular Biology and Evolution"	"Stadler T, Kouyos R, von Wyl V, Yerly S, Booni J, Burgisser P, Klimkait T, Joos B, Rieder P, Xie D, Gunthard HF, Drummond AJ, Bonhoeffer S"	"Institute of Integrative Biology, ETH Zurich, Universitatstrasse 16, 8092 Zurich, Switzerland."	"Epidemiological processes leave a fingerprint in the pattern of genetic structure of virus populations. Here, we provide a new method to infer epidemiological parameters directly from viral sequence data. The method is based on phylogenetic analysis using a birth-death model rather than the commonly used coalescent as the model for the epidemiological transmission of the pathogen. Using the birth-death model has the advantage that transmission and death rates are estimated independently, and therefore enables for the first time the estimation of the basic reproductive number of the pathogen using only sequence data, without further assumptions like the average duration of infection. We apply the method to genetic data of the HIV-1 epidemic in Switzerland."	"http://www.ncbi.nlm.nih.gov/pubmed/21890480"
+"unk"	"europe_not_latin"	"unknown"	"unknown"	"0.00440528634361"	"0.00881057268722"	"0.11013215859"	"227"	"11.9473684211"	"BMC Bioinformatics"	"Stamatakis M, Zygourakis K"		"ABSTRACT: BACKGROUND: The lac operon genetic switch is considered as a paradigm of genetic regulation. This system has a positive feedback loop due to the LacY permease boosting its own production by the facilitated transport of inducer into the cell and the subsequent de-repression of the lac operon genes. Previously, we have investigated the effect of stochasticity in an artificial lac operon network at the single cell level by comparing corresponding deterministic and stochastic kinetic models. RESULTS: This work focuses on the dynamics of cell populations by incorporating the above kinetic scheme into two Monte Carlo (MC) simulation frameworks. The first MC framework assumes stochastic reaction occurrence, accounts for stochastic DNA duplication, division and partitioning and tracks all daughter cells to obtain the statistics of the entire cell population. In order to better understand how stochastic effects shape cell population distributions, we develop a second framework that assumes deterministic reaction dynamics. By comparing the predictions of the two frameworks, we conclude that stochasticity can create or destroy bimodality, and may enhance phenotypic heterogeneity. CONCLUSIONS: Our results show how various sources of stochasticity act in synergy with the positive feedback architecture, thereby shaping the behavior at the cell population level. Further, the insights obtained from the present study allow us to construct simpler and less computationally intensive models that can closely approximate the dynamics of heterogeneous cell populations."	"http://www.ncbi.nlm.nih.gov/pubmed/21791088"
 "unk"	"europe_not_latin"	"Sweden"	"Sweden"	"0.0193798449612"	"0.0271317829457"	"0.0968992248062"	"258"	"10.32"	"PLoS Computational Biology"	"Staneva I, Wallin S"	"Department of Astronomy and Theoretical Physics, Computational Biology and Biological Physics Group, Lund University, Lund, Sweden."	"Peptide recognition domains (PRDs) are ubiquitous protein domains which mediate large numbers of protein interactions in the cell. How these PRDs are able to recognize peptide sequences in a rapid and specific manner is incompletely understood. We explore the peptide binding process of PDZ domains, a large PRD family, from an equilibrium perspective using an all-atom Monte Carlo (MC) approach. Our focus is two different PDZ domains representing two major PDZ classes, I and II. For both domains, a binding free energy surface with a strong bias toward the native bound state is found. Moreover, both domains exhibit a binding process in which the peptides are mostly either bound at the PDZ binding pocket or else interact little with the domain surface. Consistent with this, various binding observables show a temperature dependence well described by a simple two-state model. We also find important differences in the details between the two domains. While both domains exhibit well-defined binding free energy barriers, the class I barrier is significantly weaker than the one for class II. To probe this issue further, we apply our method to a PDZ domain with dual specificity for class I and II peptides, and find an analogous difference in their binding free energy barriers. Lastly, we perform a large number of fixed-temperature MC kinetics trajectories under binding conditions. These trajectories reveal significantly slower binding dynamics for the class II domain relative to class I. Our combined results are consistent with a binding mechanism in which the peptide C terminal residue binds in an initial, rate-limiting step."	"http://www.ncbi.nlm.nih.gov/pubmed/21876662"
 "unk"	"europe_not_latin"	"Norway"	"Norway"	"0.0"	"0.010752688172"	"0.112903225806"	"186"	"10.9411764706"	"Nature"	"Star B, Nederbragt AJ, Jentoft S, Grimholt U, Malmstrom M, Gregers TF, Rounge TB, Paulsen J, Solbakken MH, Sharma A, Wetten OF, Lanzen A, Winer R, Knight J, Vogel JH, Aken B, Andersen O, Lagesen K, Tooming-Klunderud A, Edvardsen RB, Tina KG, Espelund M, Nepal C, Previti C, Karlsen BO, Moum T, Skage M, Berg PR, Gjoen T, Kuhl H, Thorsen J, Malde K, Reinhardt R, Du L, Johansen SD, Searle S, Lien S, Nilsen F, Jonassen I, Omholt SW, Stenseth NC, Jakobsen KS"	"Centre for Ecological and Evolutionary Synthesis, Department of Biology, University of Oslo, PO Box 1066, Blindern, N-0316 Oslo, Norway."	"Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC) II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates."	"http://www.ncbi.nlm.nih.gov/pubmed/21832995"
 3	"europe_not_latin"	"Germany"	"Germany"	"0.00934579439252"	"0.00934579439252"	"0.0934579439252"	"107"	"9.72727272727"	"ANNUAL REVIEW OF PSYCHOLOGY"	"Staudinger UM, Gluck J"	"Jacobs Center on Lifelong Learning and Institutional Development, Jacobs University, 28759 Bremen, Germany. sekstaudinger@jacobs-university.de"	"Wisdom represents a fruitful topic for psychological investigations for at least two reasons. First, the study of wisdom emphasizes the search for the continued optimization and the further cultural evolution of the human condition. Second, it exemplifies the collaboration of cognitive, emotional, and motivational processes. The growth and scope of psychological wisdom research over the past few decades demonstrate that it is possible to investigate this complex construct with empirical rigor. Since the 1970s, five main areas have been established: lay definitions of wisdom, conceptualizing and measuring wisdom, understanding the development of wisdom, investigating the plasticity of wisdom, and applying psychological knowledge about wisdom in life contexts."	"http://www.ncbi.nlm.nih.gov/pubmed/20822439"
 3	"latin"	"France"	"France"	"0.00418410041841"	"0.0334728033473"	"0.0543933054393"	"239"	"11.380952381"	"Molecular Biology and Evolution"	"Dequard-Chablat M, Sellem CH, Golik P, Bidard F, Martos A, Bietenhader M, di Rago JP, Sainsard-Chanet A, Hermann-Le Denmat S, Contamine V"	"Univ Paris-Sud, Orsay, France."	"An F(1)F(O) ATP synthase in the inner mitochondrial membrane catalyzes the late steps of ATP production via the process of oxidative phosphorylation. A small protein subunit (subunit c or ATP9) of this enzyme shows a substantial genetic diversity, and its gene can be found in both the mitochondrion and/or nucleus. In a representative set of 26 species of fungi for which the genomes have been entirely sequenced, we found five Atp9 gene repartitions. The phylogenetic distribution of nuclear and mitochondrial Atp9 genes suggests that their evolution has included two independent transfers to the nucleus followed by several independent episodes of the loss of the mitochondrial and/or nuclear gene. Interestingly, we found that in Podospora anserina, subunit c is exclusively produced from two nuclear genes (PaAtp9-5 and PaAtp9-7), which display different expression profiles through the life cycle of the fungus. The PaAtp9-5 gene is specifically and strongly expressed in germinating ascospores, whereas PaAtp9-7 is mostly transcribed during sexual reproduction. Consistent with these observations, deletion of PaAtp9-5 is lethal, whereas PaAtp9-7 deletion strongly impairs ascospore production. The P. anserina PaAtp9-5 and PaAtp9-7 genes are therefore nonredundant. By swapping the 5 and 3 flanking regions between genes we demonstrated, however, that the PaAtp9 coding sequences are functionally interchangeable. These findings show that after transfer to the nucleus, the subunit c gene in Podospora became a key target for the modulation of cellular energy metabolism according to the requirements of the life cycle."	"http://www.ncbi.nlm.nih.gov/pubmed/21273631"
 3	"latin"	"France"	"France"	"0.00597014925373"	"0.0119402985075"	"0.0865671641791"	"335"	"12.5925925926"	"BMC Bioinformatics"	"Dereeper A, Nicolas S, Le Cunff L, Bacilieri R, Doligez A, Peros JP, Ruiz M, This P"	"Diversity, Genetics and Genomics of grapevine, UMR DIAPC, INRA, Montpellier, France. alexis.dereeper@ird.fr"	"BACKGROUND: High-throughput re-sequencing, new genotyping technologies and the availability of reference genomes allow the extensive characterization of Single Nucleotide Polymorphisms (SNPs) and insertion/deletion events (indels) in many plant species. The rapidly increasing amount of re-sequencing and genotyping data generated by large-scale genetic diversity projects requires the development of integrated bioinformatics tools able to efficiently manage, analyze, and combine these genetic data with genome structure and external data. RESULTS: In this context, we developed SNiPlay, a flexible, user-friendly and integrative web-based tool dedicated to polymorphism discovery and analysis. It integrates:1) a pipeline, freely accessible through the internet, combining existing softwares with new tools to detect SNPs and to compute different types of statistical indices and graphical layouts for SNP data. From standard sequence alignments, genotyping data or Sanger sequencing traces given as input, SNiPlay detects SNPs and indels events and outputs submission files for the design of Illuminas SNP chips. Subsequently, it sends sequences and genotyping data into a series of modules in charge of various processes: physical mapping to a reference genome, annotation (genomic position, intron/exon location, synonymous/non-synonymous substitutions), SNP frequency determination in user-defined groups, haplotype reconstruction and network, linkage disequilibrium evaluation, and diversity analysis (Pi, Wattersons Theta, Tajimas D).Furthermore, the pipeline allows the use of external data (such as phenotype, geographic origin, taxa, stratification) to define groups and compare statistical indices.2) a database storing polymorphisms, genotyping data and grapevine sequences released by public and private projects. It allows the user to retrieve SNPs using various filters (such as genomic position, missing data, polymorphism type, allele frequency), to compare SNP patterns between populations, and to export genotyping data or sequences in various formats. CONCLUSIONS: Our experiments on grapevine genetic projects showed that SNiPlay allows geneticists to rapidly obtain advanced results in several key research areas of plant genetic diversity. Both the management and treatment of large amounts of SNP data are rendered considerably easier for end-users through automation and integration. Current developments are taking into account new advances in high-throughput technologies.SNiPlay is available at: http://sniplay.cirad.fr/."	"http://www.ncbi.nlm.nih.gov/pubmed/21545712"
 3	"latin"	"France"	"France"	"0.0208333333333"	"0.0347222222222"	"0.111111111111"	"144"	"6.12"	"Bioinformatics"	"Despalins A, Marsit S, Oberto J"	"Universite Paris-Sud 11, CNRS, UMR8621, Institut de Genetique et Microbiologie, 91405 Orsay Cedex, France."	"SUMMARY: Absynte (Archaeal and Bacterial Synteny Explorer) is a web-based service designed to display local syntenies in completely sequenced prokaryotic chromosomes. The genomic contexts are determined with a multiple center star clustering topology on the basis of a user-provided protein sequence and all (or a set of) chromosomes from the publicly available archaeal and bacterial genomes. The results consist in a dynamic web page where a consistent color coding permits a rapid visual evaluation of the relative positioning of genes with similar sequences within the synteny. Each gene composing the synteny can be further queried interactively using either local or remote databases. Absynte results can be exported in .CSV or high resolution .PDF formats for printing, archival, further editing or publication purposes. Performance, real-time computation, user-friendliness and daily database updates constitute the principal advantages of Absynte over similar web services. AVAILABILITY: http://archaea.u-psud.fr/absynte CONTACT: jacques.oberto@igmors.u-psud.fr."	"http://www.ncbi.nlm.nih.gov/pubmed/21840875"
+"unk"	"latin"	"unknown"	"spain"	"0.0"	"0.0205761316872"	"0.0699588477366"	"243"	"11.619047619"	"BMC Bioinformatics"	"Diaz-Diaz N, Aguilar-Ruiz JS"		"ABSTRACT: BACKGROUND: The Gene Ontology (GO) provides a controlled vocabulary for describing the functions of genes and can be used to evaluate the functional coherence of gene sets. Many functional coherence measures consider each pair of gene functions in a set and produce an output based on all pairwise distances. A single gene can encode multiple proteins that may differ in function. For each functionality, other proteins that exhibit the same activity may also participate. Therefore, an identification of the most common function for all of the genes involved in a biological process is important in evaluating the functional similarity of groups of genes and a quantification of functional coherence can helps to clarify the role of a group of genes working together. RESULTS: To implement this approach to functional assessment, we present GFD (GO-based Functional Dissimilarity), a novel dissimilarity measure for evaluating groups of genes based on the most relevant functions of the whole set. The measure assigns a numerical value to the gene set for each of the three GO sub-ontologies. CONCLUSIONS: Results show that GFD performs robustly when applied to gene set of known functionality (extracted from KEGG). It performs particularly well on randomly generated gene sets. An ROC analysis reveals that the performance of GFD in evaluating the functional dissimilarity of gene sets is very satisfactory. A comparative analysis against other functional measures, such as GS2 and those presented by Resnik and Wang, also demonstrates the robustness of GFD."	"http://www.ncbi.nlm.nih.gov/pubmed/21884611"
 3	"latin"	"Spain"	"Spain"	"0.0"	"0.0184049079755"	"0.0736196319018"	"163"	"23.2857142857"	"PLoS One"	"Echenique P, Cavasotto CN, De Marco M, Garca-Risueno P, Alonso JL"	"Instituto de Quimica Fisica Rocasolano, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain."	"In this work, we introduce an algorithm to compute the derivatives of physical observables along the constrained subspace when flexible constraints are imposed on the system (i.e., constraints in which the constrained coordinates are fixed to configuration-dependent values). The presented scheme is exact, it does not contain any tunable parameter, and it only requires the calculation and inversion of a sub-block of the Hessian matrix of second derivatives of the function through which the constraints are defined. We also present a practical application to the case in which the sought observables are the Euclidean coordinates of complex molecular systems, and the function whose minimization defines the flexible constraints is the potential energy. Finally, and in order to validate the method, which, as far as we are aware, is the first of its kind in the literature, we compare it to the natural and straightforward finite-differences approach in a toy system and in three molecules of biological relevance: methanol, N-methyl-acetamide and a tri-glycine peptide."	"http://www.ncbi.nlm.nih.gov/pubmed/21931757"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21935369"
 3	"latin"	"France"	"France"	"0.0142857142857"	"0.0142857142857"	"0.052380952381"	"210"	"11.0526315789"	"PLoS One"	"El Khechine A, Couderc C, Flaudrops C, Raoult D, Drancourt M"	"URMITE UMR CNRS 6236 IRD198, Institut Hospitalier Universitaire POLMIT, IFR48, Universite de la Mediterranee et Pole de Maladies Infectieuses, Assistance Publique-Hopitaux de Marseille, Marseille, France."	"BACKGROUND: Non-tuberculous mycobacteria recovered from respiratory tract specimens are emerging confounder organisms for the laboratory diagnosis of tuberculosis worldwide. There is an urgent need for new techniques to rapidly identify mycobacteria isolated in clinical practice. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) has previously been proven to effectively identify mycobacteria grown in high-concentration inocula from collections. However, a thorough evaluation of its use in routine laboratory practice has not been performed. METHODOLOGY: We set up an original protocol for the MALDI-TOF MS identification of heat-inactivated mycobacteria after dissociation in Tween-20, mechanical breaking of the cell wall and protein extraction with formic acid and acetonitrile. By applying this protocol to as few as 10(5) colony-forming units of reference isolates of Mycobacterium tuberculosis, Mycobacterium avium, and 20 other Mycobacterium species, we obtained species-specific mass spectra for the creation of a local database. Using this database, our protocol enabled the identification by MALDI-TOF MS of 87 M. tuberculosis, 25 M. avium and 12 non-tuberculosis clinical isolates with identification scores >/=2 within 2.5 hours. CONCLUSIONS: Our data indicate that MALDI-TOF MS can be used as a first-line method for the routine identification of heat-inactivated mycobacteria. MALDI-TOF MS is an attractive method for implementation in clinical microbiology laboratories in both developed and developing countries."	"http://www.ncbi.nlm.nih.gov/pubmed/21935444"
 3	"latin"	"France"	"France"	"0.0"	"0.0337078651685"	"0.0730337078652"	"178"	"11.9333333333"	"PLoS Computational Biology"	"Gueroult M, Picot D, Abi-Ghanem J, Hartmann B, Baaden M"	"CNRS UPR9080, Institut de Biologie Physico-Chimique, Paris, France."	"DNase I requires Ca(2)+ and Mg(2)+ for hydrolyzing double-stranded DNA. However, the number and the location of DNase I ion-binding sites remain unclear, as well as the role of these counter-ions. Using molecular dynamics simulations, we show that bovine pancreatic (bp) DNase I contains four ion-binding pockets. Two of them strongly bind Ca(2)+ while the other two sites coordinate Mg(2)+. These theoretical results are strongly supported by revisiting crystallographic structures that contain bpDNase I. One Ca(2)+ stabilizes the functional DNase I structure. The presence of Mg(2)+ in close vicinity to the catalytic pocket of bpDNase I reinforces the idea of a cation-assisted hydrolytic mechanism. Importantly, Poisson-Boltzmann-type electrostatic potential calculations demonstrate that the divalent cations collectively control the electrostatic fit between bpDNase I and DNA. These results improve our understanding of the essential role of cations in the biological function of bpDNase I. The high degree of conservation of the amino acids involved in the identified cation-binding sites across DNase I and DNase I-like proteins from various species suggests that our findings generally apply to all DNase I-DNA interactions."	"http://www.ncbi.nlm.nih.gov/pubmed/21124947"
 3	"latin"	"France"	"France"	"0.0153846153846"	"0.025641025641"	"0.0307692307692"	"195"	"9.28571428571"	"Blood"	"Guery L, Benikhlef N, Gautier T, Paul C, Jego G, Dufour E, Jacquel A, Cally R, Manoury B, Vanden Berghe T, Vandenabeele P, Droin N, Solary E"	"Inserm UMR866, Faculte de Medecine, Dijon, France;"	"M-CSF-driven differentiation of peripheral blood monocytes is one of the sources of tissue macrophages. In humans and mice, the differentiation process involves the activation of caspases that cleave a limited number of proteins. One of these proteins is nucleophosmin (NPM1), a multifunctional and ubiquitous protein. Here, we show that caspases activated in monocytes exposed to M-CSF cleave NPM1 at D213 to generate a 30 kDa N-terminal fragment. The protein is further cleaved into a 20 kDa fragment, which involves cathepsin B. NPM1 fragments contribute to the limited motility, migration and phagocytosis capabilities of resting macrophages. Their activation with lipopolysacchararides (LPS) inhibits the proteolytic processes and restores the expression of the full-length protein that negatively regulates the transcription of genes encoding inflammatory cytokines, e.g. NPM1 is recruited with NF-kappaB on MCP1 gene promoter to decrease its transcription. In mice with heterozygous npm gene deletion, cytokine production in response to LPS, including CXCL1 (KC), MCP1 and MIP2, is dramatically enhanced. These results indicate a dual function of NPM1 in M-CSF-differentiated macrophages. Proteolysis of the protein participates in the establishment of a mature macrophage phenotype. In response to inflammatory stimuli, the full-length protein negatively regulates inflammatory cytokine production."	"http://www.ncbi.nlm.nih.gov/pubmed/21876121"
 3	"latin"	"Italy"	"Italy"	"0.030303030303"	"0.020202020202"	"0.0656565656566"	"198"	"7.20689655172"	"Blood"	"Guglielmelli P, Biamonte F, Score J, Hidalgo-Curtis C, Cervantes F, Maffioli M, Fanelli T, Ernst T, Winkelmann N, Jones AV, Zoi K, Reiter A, Duncombe A, Villani L, Bosi A, Barosi G, Cross NC, Vannucchi AM"	"Dept of Medical and Surgical Critical Care, Section of Hematology, University of Florence, Florence, Italy;"	"We genotyped 370 subjects with primary myelofibrosis (PMF) and 148 with post-polycythemia vera/post-essential thrombocythemia myelofibrosis (PPV/PET-MF) for mutations of EZH2. Mutational status at diagnosis was correlated with hematological parameters, clinical manifestations and outcome. A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF and 9.4% of PET-MF patients; most were exonic heterozygous missense changes. EZH2 mutation coexisted with JAK2V617F or ASXL1 mutation in 12/29 (41.4%) and 6/27 (22.2%) evaluated patients; TET2 and CBL mutations were found in 2 and 1 subject, respectively. EZH2 mutated PMF patients had significantly higher leukocyte count, blast cell count and larger spleen at diagnosis, and most of them (52.6%) were high IPSS-risk category. After a median follow-up of 39 months, 128 patients (25.9%) died, 81 (63.3%) because of leukemia. Leukemia-free and overall survival were significantly reduced in EZH2 mutated PMF patients (P=.028 and P<.001 respectively); possibly due to low number of mutated cases, no such impact was seen for PPV/PET-MF. In multivariate analysis, survival of PMF patients was predicted by IPSS high-risk category, a <25% JAK2V617F allele burden and EZH2 mutated status. We conclude that EZH2 mutations are independently associated with shorter survival in patients with PMF."	"http://www.ncbi.nlm.nih.gov/pubmed/21921040"
+"unk"	"latin"	"unknown"	"unknown"	"0.00452488687783"	"0.0180995475113"	"0.0769230769231"	"221"	"13.0"	"Molecular Biology and Evolution"	"Guillemin Y, Cornut-Thibaut A, Gillet G, Penin F, Aouacheria A"	"From the."	"Insertions or deletions (indels) of amino acids residues have been recognized as an important source of genetic and structural divergence between paralogous Bcl-2 family members. However, these signature sequences have not so far been extensively investigated amongst orthologous Bcl-2 family proteins. Bcl2l10 is an anti-apoptotic member of the Bcl-2 family that has evolved rapidly throughout the vertebrate lineage, and which shows conserved abundant expression in eggs and oocytes. In this paper, we have unraveled two major sites of divergence between human Bcl2l10 and its vertebrate homologues. The first one provides length variation at the N-terminus (before the BH4 domain), and the second one is located between the predicted alpha5-alpha6 pore-forming helices, providing an unprecedented case in the superfamily of helix-bundled pore-forming proteins. These two particular indels were studied phylogenetically, and through biochemical and cell biological techniques, including truncation and site-directed mutagenesis. While deletion of the N-terminal extension had no significant functional impact in HeLa cells, our results suggest that the human Bcl2l10 protein evolved a calcium-binding motif in its alpha5-alpha6 interhelical region by acquiring critical negatively charged residues. Considering the reliance of female eggs on calcium-dependent proteins and calcium-regulated processes, and the exceptional longevity of oocytes in the primate lineage, we propose that this micro-structural variation may be an adaptive feature associated with high maternal expression of this Bcl-2 family member."	"http://www.ncbi.nlm.nih.gov/pubmed/21705382"
 3	"latin"	"Barcelona, Barcelona, Spain"	"Spain"	"0.00636942675159"	"0.00636942675159"	"0.0636942675159"	"157"	"14.2727272727"	"Molecular Biology and Evolution"	"Guirao-Rico S, Aguade M"	"Departament de Genetica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain."	"Drosophila melanogaster, unlike mammals, has seven insulin-like peptides (DILPS). In Drosophila, all seven genes (dilp1-7) are single copy in the 12 species studied, except for D. grimshawi with two tandem copies of dilp2. Our comparative analysis revealed that genes dilp1-dilp7 exhibit differential functional constraint, which is indicative of some functional divergence. Species of the subgenera Sophophora and Drosophila differ in some traits likely affected by the insulin-signaling pathway, such as adult body size. It is in the branch connecting the two subgenera that we found the footprint left by positive selection driving nonsynonymous changes at some dilp1 codons to fixation. Finally, the similar rate at which the two dilp2 copies of D. grimshawi have evolved since their duplication and the presence of a putative regulatory region highly conserved between the two paralogs would suggest that both copies were preserved either because of subfunctionalization or dose dependency rather than by the neofunctionalization of one of the two copies."	"http://www.ncbi.nlm.nih.gov/pubmed/21196470"
 2	"latin"	"France"	"France"	"0.0120967741935"	"0.00403225806452"	"0.0524193548387"	"248"	"10.7826086957"	"Molecular Biology and Evolution"	"Hayashi S, Rocancourt D, Buckingham M, Relaix F"	"Universite Pierre et Marie Curie, Univ Paris 06, UMR-S 787, Paris, France."	"Pax genes encode evolutionarily conserved transcription factors that play critical roles in embryonic development and organogenesis. Pax proteins are subdivided into four subfamilies: group I (Pax1and 9), II (Pax2, 5, and 8), III (Pax3 and 7), and IV (Pax4 and 6), based on the presence of a paired domain, an octapeptide motif and part or all of the homeodomain. Studies of the evolution of this gene family are incomplete. Nevertheless, it is known that each family evolved via duplication from four corresponding ancestral genes. Pax gene functions have been shown to be conserved within subgroups. It remains unclear, however, whether any (early) conserved function is shared between subgroups. To investigate conserved functions between subfamily II and III, we replaced an allele of Pax3 with a Pax8-coding sequence via gene targeting in the mouse. Homozygote Pax3(Pax8/Pax8) embryos display phenotypes indistinguishable from Pax3-deficient mutant embryos, with neural tube closure defects, a deficit in neural crest cells in the trunk, and skeletal muscle defects including absence of long-range migratory myogenic progenitors and impaired somite development. Interestingly, despite Pax8 expression in the neural tube in a domain ventral to that of Pax3, Pax8 cannot replace Pax3 function in the dorsal neural tube. Altogether, our results demonstrate that expression of Pax8 fails to compensate for Pax3 deficiency, demonstrating the absence of functional compensation between one subfamily of Pax genes and another in the mouse embryo. Our result suggests that Pax3/7 and Pax2/5/8 functions evolved independently after duplication of the ancestral progenitor Pax genes."	"http://www.ncbi.nlm.nih.gov/pubmed/21512107"
 3	"latin"	"France"	"France"	"0.0245098039216"	"0.0196078431373"	"0.0833333333333"	"204"	"10.7894736842"	"Nature"	"Hayes M, Scarlata C, Siana B"	"Universite de Toulouse, UPS-OMP, IRAP, Toulouse, France. matthew.hayes@ast.obs-mip.fr"	"High-redshift Lyman-alpha (Lyalpha) blobs are extended, luminous but rare structures that seem to be associated with the highest peaks in the matter density of the Universe. Their energy output and morphology are similar to those of powerful radio galaxies, but the source of the luminosity is unclear. Some blobs are associated with ultraviolet or infrared bright galaxies, suggesting an extreme starburst event or accretion onto a central black hole. Another possibility is gas that is shock-excited by supernovae. But not all blobs are associated with galaxies, and these ones may instead be heated by gas falling into a dark-matter halo. The polarization of the Lyalpha emission can in principle distinguish between these options, but a previous attempt to detect this signature returned a null detection. Here we report observations of polarized Lyalpha from the blob LAB1 (ref. 2). Although the central region shows no measurable polarization, the polarized fraction (P) increases to  approximately 20 per cent at a radius of 45 kiloparsecs, forming an almost complete polarized ring. The detection of polarized radiation is inconsistent with the in situ production of Lyalpha photons, and we conclude that they must have been produced in the galaxies hosted within the nebula, and re-scattered by neutral hydrogen."	"http://www.ncbi.nlm.nih.gov/pubmed/21850104"
+"unk"	"latin"	"unknown"	"spain"	"0.00444444444444"	"0.0222222222222"	"0.0622222222222"	"225"	"15.0"	"BMC Bioinformatics"	"Herman D, Ochoa D, Juan D, Lopez D, Valencia A, Pazos F"		"ABSTRACT: BACKGROUND: The prediction and study of protein interactions and functional relationships based on similarity of phylogenetic trees, exemplified by the mirrortree and related methodologies, is being widely used. Although dependence between the performance of these methods and the set of organisms used to build the trees was suspected, so far nobody assessed it in an exhaustive way, and, in general, previous works used as many organisms as possible. In this work we asses the effect of using different sets of organism (chosen according with various phylogenetic criteria) on the performance of this methodology in detecting protein interactions of different nature. RESULTS: We show that the performance of three mirrortree-related methodologies depends on the set of organisms used for building the trees, and it is not always directly related to the number of organisms in a simple way. Certain subsets of organisms seem to be more suitable for the predictions of certain types of interactions. This relationship between type of interaction and optimal set of organism for detecting them makes sense in the light of the phylogenetic distribution of the organisms and the nature of the interactions. CONCLUSIONS: In order to obtain an optimal performance when predicting protein interactions, it is recommended to use different sets of organisms depending on the available computational resources and data, as well as the type of interactions of interest."	"http://www.ncbi.nlm.nih.gov/pubmed/21910884"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21931716"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21935423"
 3	"latin"	"Italy"	"Italy"	"0.00653594771242"	"0.0392156862745"	"0.117647058824"	"306"	"11.3703703704"	"PLoS Computational Biology"	"Iozzi F, Trusiano F, Chinazzi M, Billari FC, Zagheni E, Merler S, Ajelli M, Del Fava E, Manfredi P"	"Department of Decision Sciences, Bocconi University, Milan, Italy."	"Knowledge of social contact patterns still represents the most critical step for understanding the spread of directly transmitted infections. Data on social contact patterns are, however, expensive to obtain. A major issue is then whether the simulation of synthetic societies might be helpful to reliably reconstruct such data. In this paper, we compute a variety of synthetic age-specific contact matrices through simulation of a simple individual-based model (IBM). The model is informed by Italian Time Use data and routine socio-demographic data (e.g., school and workplace attendance, household structure, etc.). The model is named Little Italy because each artificial agent is a clone of a real person. In other words, each agents daily diary is the one observed in a corresponding real individual sampled in the Italian Time Use Survey. We also generated contact matrices from the socio-demographic model underlying the Italian IBM for pandemic prediction. These synthetic matrices are then validated against recently collected Italian serological data for Varicella (VZV) and ParvoVirus (B19). Their performance in fitting sero-profiles are compared with other matrices available for Italy, such as the Polymod matrix. Synthetic matrices show the same qualitative features of the ones estimated from sample surveys: for example, strong assortativeness and the presence of super- and sub-diagonal stripes related to contacts between parents and children. Once validated against serological data, Little Italy matrices fit worse than the Polymod one for VZV, but better than concurrent matrices for B19. This is the first occasion where synthetic contact matrices are systematically compared with real ones, and validated against epidemiological data. The results suggest that simple, carefully designed, synthetic matrices can provide a fruitful complementary approach to questionnaire-based matrices. The paper also supports the idea that, depending on the transmissibility level of the infection, either the number of different contacts, or repeated exposure, may be the key factor for transmission."	"http://www.ncbi.nlm.nih.gov/pubmed/21152004"
 3	"latin"	"France"	"France"	"0.0126582278481"	"0.0189873417722"	"0.0696202531646"	"158"	"7.0"	"Blood"	"Nicolini FE, Basak GW, Soverini S, Martinelli G, Mauro MJ, Muller MC, Hochhaus A, Chuah C, Dufva IH, Rege-Cambrin G, Saglio G, Michallet M, Labussiere H, Morisset S, Hayette S, Etienne G, Olavarria E, Zhou W, Peter S, Apperley JF, Cortes J"	"Hematology department, Hopital Edouard Herriot, Lyon, France;"	"T315I(+) Ph+ leukemias are inherently resistant to all licensed TKI and therapeutic options remain limited. We report the outcome of allogeneic SCT in 64 patients with documented BCR-ABL(T315I) mutations. Median follow-ups were 52 months from mutation detection and 26 months from transplantation. At transplant, 51.5% of CML patients were in CP and 40.5% in advanced phases. Median overall survival from transplant was 10.3 (5.7-NR) months for BP and 7.4 (1.4-NR) months for Ph+ ALL but has not yet been reached for CP and AP. The occurrence of chronic GVHD had a positive impact on overall survival (p=0.047). TRM rates were low. Multivariate analysis identified only BP at transplant (HR 3.68, p=0.0011) and unrelated stem cell donor (HR 2.98, p=0.011) as unfavorable factors. Before the availability of third generation TKI, we conclude that allogeneic SCT represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation; a tool which may or may not be replaced by third generation TKI."	"http://www.ncbi.nlm.nih.gov/pubmed/21926354"
 3	"latin"	"France"	"France"	"0.00537634408602"	"0.0215053763441"	"0.0537634408602"	"186"	"14.3076923077"	"Blood"	"Nurden AT, Fiore M, Nurden P, Pillois X"	"Centre de Reference des Pathologies Plaquettaires, Plateforme Technologique dInnovation Biomedicale, Hopital Xavier Arnozan, Pessac, France."	"Characterized by mucocutaneous bleeding arising from a lack of platelet aggregation to physiologic stimuli, Glanzmann thrombasthenia (GT) is the archetype-inherited disorder of platelets. Transmitted by autosomal recessive inheritance, platelets in GT have quantitative or qualitative deficiencies of the fibrinogen receptor, alphaIIbbeta3, an integrin coded by the ITGA2B and ITGB3 genes. Despite advances in our understanding of the disease, extensive phenotypic variability with respect to severity and intensity of bleeding remains poorly understood. Importantly, genetic defects of ITGB3 also potentially affect other tissues for beta3 has a wide tissue distribution when present as alphavbeta3 (the vitronectin [Vn] receptor). We now look at the repertoire of ITGA2B and ITGB3 gene defects; re-examine the relationship between phenotype and genotype and review integrin structure in the many variant forms. Evidence for modifications in platelet production is assessed, as is the multifactorial etiology of the clinical expression of the disease. Reports of cardiovascular disease and deep vein thrombosis, cancer, brain disease, bone disorders and pregnancy defects in GT are discussed in the context of the results obtained for mouse models where non-hemostatic defects of beta3-deficiency or non-function are being increasingly described."	"http://www.ncbi.nlm.nih.gov/pubmed/21917754"
 3	"latin"	"Portugal"	"Portugal"	"0.0123456790123"	"0.0082304526749"	"0.082304526749"	"243"	"16.2"	"PLoS Computational Biology"	"Oliveira AS, Baptista AM, Soares CM"	"Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Oeiras, Portugal."	"ATP-Binding Cassette transporters are ubiquitous membrane proteins that convert the energy from ATP-binding and hydrolysis into conformational changes of the transmembrane region to allow the translocation of substrates against their concentration gradient. Despite the large amount of structural and biochemical data available for this family, it is still not clear how the energy obtained from ATP hydrolysis in the ATPase domains is transmitted to the transmembrane domains. In this work, we focus our attention on the consequences of hydrolysis and inorganic phosphate exit in the maltose uptake system (MalFGK(2)E) from Escherichia coli. The prime goal is to identify and map the structural changes occurring during an ATP-hydrolytic cycle. For that, we use extensive molecular dynamics simulations to study three potential intermediate states (with 10 replicates each): an ATP-bound, an ADP plus inorganic phosphate-bound and an ADP-bound state. Our results show that the residues presenting major rearrangements are located in the A-loop, in the helical sub-domain, and in the EAA motif (especially in the coupling helices region). Additionally, in one of the simulations with ADP we were able to observe the opening of the NBD dimer accompanied by the dissociation of ADP from the ABC signature motif, but not from its corresponding P-loop motif. This work, together with several other MD studies, suggests a common communication mechanism both for importers and exporters, in which ATP-hydrolysis induces conformational changes in the helical sub-domain region, in turn transferred to the transmembrane domains via the coupling helices."	"http://www.ncbi.nlm.nih.gov/pubmed/21829343"
+"unk"	"latin"	"unknown"	"unknown"	"0.00454545454545"	"0.0409090909091"	"0.1"	"440"	"14.1935483871"	"BMC Bioinformatics"	"Olivera-Nappa A, Andrews BA, Asenjo JA"	"Centre for Biochemical Engineering and Biotechnology, Institute for Cell Dynamics and Biotechnology: a Centre for Systems Biology, University of Chile, Santiago, Chile. aolivera@ing.uchile.cl"	"BACKGROUND: Functionally relevant artificial or natural mutations are difficult to assess or predict if no structure-function information is available for a protein. This is especially important to correctly identify functionally significant non-synonymous single nucleotide polymorphisms (nsSNPs) or to design a site-directed mutagenesis strategy for a target protein. A new and powerful methodology is proposed to guide these two decision strategies, based only on conservation rules of physicochemical properties of amino acids extracted from a multiple alignment of a protein family where the target protein belongs, with no need of explicit structure-function relationships. RESULTS: A statistical analysis is performed over each amino acid position in the multiple protein alignment, based on different amino acid physical or chemical characteristics, including hydrophobicity, side-chain volume, charge and protein conformational parameters. The variances of each of these properties at each position are combined to obtain a global statistical indicator of the conservation degree of each property. Different types of physicochemical conservation are defined to characterize relevant and irrelevant positions. The differences between statistical variances are taken together as the basis of hypothesis tests at each position to search for functionally significant mutable sites and to identify specific mutagenesis targets. The outcome is used to statistically predict physicochemical consensus sequences based on different properties and to calculate the amino acid propensities at each position in a given protein. Hence, amino acid positions are identified that are putatively responsible for function, specificity, stability or binding interactions in a family of proteins. Once these key functional positions are identified, position-specific statistical distributions are applied to divide the 20 common protein amino acids in each position of the proteins primary sequence into a group of functionally non-disruptive amino acids and a second group of functionally deleterious amino acids. CONCLUSIONS: With this approach, not only conserved amino acid positions in a protein family can be labeled as functionally relevant, but also non-conserved amino acid positions can be identified to have a physicochemically meaningful functional effect. These results become a discriminative tool in the selection and elaboration of rational mutagenesis strategies for the protein. They can also be used to predict if a given nsSNP, identified, for instance, in a genomic-scale analysis, can have a functional implication for a particular protein and which nsSNPs are most likely to be functionally silent for a protein. This analytical tool could be used to rapidly and automatically discard any irrelevant nsSNP and guide the research focus toward functionally significant mutations. Based on preliminary results and applications, this technique shows promising performance as a valuable bioinformatics tool to aid in the development of new protein variants and in the understanding of function-structure relationships in proteins."	"http://www.ncbi.nlm.nih.gov/pubmed/21524307"
 3	"latin"	"Italy"	"Italy"	"0.025"	"0.0333333333333"	"0.0833333333333"	"240"	"14.1176470588"	"PLoS Computational Biology"	"Osella M, Bosia C, Cora D, Caselle M"	"Dipartimento di Fisica Teorica and INFN University of Torino, Torino, Italy. mosella@to.infn.it"	"MicroRNAs are endogenous non-coding RNAs which negatively regulate the expression of protein-coding genes in plants and animals. They are known to play an important role in several biological processes and, together with transcription factors, form a complex and highly interconnected regulatory network. Looking at the structure of this network, it is possible to recognize a few overrepresented motifs which are expected to perform important elementary regulatory functions. Among them, a special role is played by the microRNA-mediated feedforward loop in which a master transcription factor regulates a microRNA and, together with it, a set of target genes. In this paper we show analytically and through simulations that the incoherent version of this motif can couple the fine-tuning of a target protein level with an efficient noise control, thus conferring precision and stability to the overall gene expression program, especially in the presence of fluctuations in upstream regulators. Among the other results, a nontrivial prediction of our model is that the optimal attenuation of fluctuations coincides with a modest repression of the target expression. This feature is coherent with the expected fine-tuning function and in agreement with experimental observations of the actual impact of a wide class of microRNAs on the protein output of their targets. Finally, we describe the impact on noise-buffering efficiency of the cross-talk between microRNA targets that can naturally arise if the microRNA-mediated circuit is not considered as isolated, but embedded in a larger network of regulations."	"http://www.ncbi.nlm.nih.gov/pubmed/21423718"
 3	"latin"	"France"	"France"	"0.0"	"0.0121951219512"	"0.0894308943089"	"246"	"6.97297297297"	"Bioinformatics"	"Ouangraoua A, Tannier E, Chauve C"	"INRIA Lille-Nord-Europe, Universite Lille 1, LIFL, UMR CNRS 8022, Villeneuve d7rsquo;Ascq, France."	"MOTIVATION: The ancestor of birds and mammals lived approximately 300 million years ago. Inferring its genome organization is key to understand the differentiated evolution of these two lineages. However, detecting traces of its chromosomal organization in its extant descendants is difficult due to the accumulation of molecular evolution since bird and mammals lineages diverged. RESULTS: We address several methodological issues for the detection and assembly of ancestral genomic features of ancient vertebrate genomes, which encompass adjacencies, contiguous segments, syntenies and double syntenies in the context of a whole genome duplication. Using generic, but stringent, methods for all these problems, some of them new, we analyze 15 vertebrate genomes, including 12 amniotes and 3 teleost fishes, and infer a high resolution genome organization of the amniote ancestral genome, composed of 39 ancestral linkage groups at a resolution of 100Kb. We extensively discuss the validity and robustness of the method to variations of data and parameters. We introduce a support value for each of the groups, and show that 36 out of 39 ones have maximum support, and the proportion increases while the resolution decreases. Conclusions: A single methodological principle can not currently be used to infer the organization of the amniote ancestral genome. We demonstrate that it is possible to gather several principles into a computational paleogenomics pipeline, which offers a solid methodological base for the reconstruction of ancient vertebrate genomes. AVAILABILITY: Source code, in C++ and Python, is available at http://www.cecm.sfu.ca/~cchauve/SUPP/AMNIOTE2010/ CONTACT: cedric.chauve@sfu.ca SUPPLEMENTARY INFORMATION: http://www.cecm.sfu.ca/~cchauve/SUPP/AMNIOTE2010."	"http://www.ncbi.nlm.nih.gov/pubmed/21846735"
 3	"latin"	"France"	"France"	"0.00507614213198"	"0.0355329949239"	"0.0609137055838"	"197"	"17.9090909091"	"Blood"	"Ouederni M, Vincent QB, Frange P, Touzot F, Scerra S, Bejaoui M, Bousfiha A, Levy Y, Lisowska-Grospierre B, Canioni D, Bruneau J, Debre M, Blanche S, Abel L, Casanova JL, Fischer A, Picard C"	"Pediatric Hematology-Immunology Unit, Assistance Publique Hopitaux de Paris (APHP), Necker Hospital, Paris, France;"	"Inherited deficiency of major histocompatibility complex (MHC) class II molecules impairs antigen presentation to CD4(+) T cells and results in combined immunodeficiency (CID). Autosomal recessive mutations in the RFXANK gene account for two thirds of all cases of MHC class II deficiency. We describe here the genetic, clinical and immunological features of 35 patients from 30 unrelated kindreds from North Africa sharing the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1), and date the founder event responsible for this mutation in this population to about 2,250 years ago (95%, CI: 1,750-3,025 years). Ten of the 23 patients who underwent hematopoietic stem cell transplantation (HSCT) were cured, with the recovery of almost normal immune functions. Five of the patients from this cohort that did not undergo HSCT had a poor prognosis and eventually died (at ages of 1 to 17 years). However, 7 patients that did not undergo HSCT (aged 6 to 32 years) are still alive on immunoglobulin treatment and antibiotic prophylaxis. RFXANK deficiency is, thus, a severe, often fatal CID, for which HSCT is the only curative treatment. However, some patients may survive for relatively long periods, provided that multiple prophylactic measures are implemented."	"http://www.ncbi.nlm.nih.gov/pubmed/21908431"
 2	"latin"	"USA."	"USA"	"0.0101351351351"	"0.0168918918919"	"0.0810810810811"	"296"	"10.962962963"	"Molecular Biology and Evolution"	"Pacheco MA, Battistuzzi FU, Lentino M, Aguilar RF, Kumar S, Escalante AA"	"Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, AZ, USA."	"Mitochondrial (mt) genes and genomes are among the major sources of data for evolutionary studies in birds. This places mitogenomic studies in birds at the core of intense debates in avian evolutionary biology. Indeed, complete mt genomes are actively been used to unveil the phylogenetic relationships among major orders, whereas single genes (e.g., cytochrome c oxidase I [COX1]) are considered standard for species identification and defining species boundaries (DNA barcoding). In this investigation, we study the time of origin and evolutionary relationships among Neoaves orders using complete mt genomes. First, we were able to solve polytomies previously observed at the deep nodes of the Neoaves phylogeny by analyzing 80 mt genomes, including 17 new sequences reported in this investigation. As an example, we found evidence indicating that columbiforms and charadriforms are sister groups. Overall, our analyses indicate that by improving the taxonomic sampling, complete mt genomes can solve the evolutionary relationships among major bird groups. Second, we used our phylogenetic hypotheses to estimate the time of origin of major avian orders as a way to test if their diversification took place prior to the Cretaceous/Tertiary (K/T) boundary. Such timetrees were estimated using several molecular dating approaches and conservative calibration points. Whereas we found time estimates slightly younger than those reported by others, most of the major orders originated prior to the K/T boundary. Finally, we used our timetrees to estimate the rate of evolution of each mt gene. We found great variation on the mutation rates among mt genes and within different bird groups. COX1 was the gene with less variation among Neoaves orders and the one with the least amount of rate heterogeneity across lineages. Such findings support the choice of COX 1 among mt genes as target for developing DNA barcoding approaches in birds."	"http://www.ncbi.nlm.nih.gov/pubmed/21242529"
 3	"latin"	"Italy"	"Italy"	"0.0102564102564"	"0.0410256410256"	"0.0974358974359"	"195"	"10.2631578947"	"Blood"	"Palumbo A, Bringhen S, Ludwig H, Dimopoulos MA, Blade J, Mateos MV, Rosinol L, Boccadoro M, Cavo M, Lokhorst H, Zweegman S, Terpos E, Davies F, Driessen C, Gimsing P, Gramatzki M, Hajek R, Johnsen HE, Leal Da Costa F, Sezer O, Spencer A, Beksac M, Morgan G, Einsele H, San Miguel JF, Sonneveld P"	"Myeloma Unit, Division of Hematology, University of Torino, AOU S. Giovanni Battista, Torino, Italy;"	"The majority of patients with newly diagnosed multiple myeloma (MM) are aged >65 years with 30% aged >75 years. Many elderly patients are also vulnerable due to comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time due to an aging population. Most elderly MM patients are ineligible for autologous transplantation and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib and lenalidomide, has improved outcomes; however, elderly MM patients are more susceptible to side effects and are often unable to tolerate full drug doses. For these patients, lower-dose-intensity regimens improve the safety profile and thus optimize treatment outcome. Further research into the best treatment strategies for vulnerable elderly patients is urgently needed. Appropriate screening for vulnerability and an assessment of cardiac, pulmonary, renal, hepatic and neurological function, as well as age >75 years, at the start of therapy allows treatment strategies to be individualized and drug doses to be tailored to improve tolerability and optimize efficacy. Similarly, occurrence of serious non-hematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes."	"http://www.ncbi.nlm.nih.gov/pubmed/21841166"
 3	"latin"	"Italy"	"Italy"	"0.00420168067227"	"0.0252100840336"	"0.0882352941176"	"238"	"15.8666666667"	"PLoS Computational Biology"	"Papaleo E, Ranzani V, Tripodi F, Vitriolo A, Cirulli C, Fantucci P, Alberghina L, Vanoni M, De Gioia L, Coccetti P"	"Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy. elena.papaleo@unimib.it"	"E2 ubiquitin-conjugating enzymes are crucial mediators of protein ubiquitination, which strongly influence the ultimate fate of the target substrates. Recently, it has been shown that the activity of several enzymes of the ubiquitination pathway is finely tuned by phosphorylation, an ubiquitous mechanism for cellular regulation, which modulates protein conformation. In this contribution, we provide the first rationale, at the molecular level, of the regulatory mechanism mediated by casein kinase 2 (CK2) phosphorylation of E2 Cdc34-like enzymes. In particular, we identify two co-evolving signature elements in one of the larger families of E2 enzymes: an acidic insertion in beta4alpha2 loop in the proximity of the catalytic cysteine and two conserved key serine residues within the catalytic domain, which are phosphorylated by CK2. Our investigations, using yeast Cdc34 as a model, through 2.5 micros molecular dynamics simulations and biochemical assays, define these two elements as an important phosphorylation-controlled switch that modulates opening and closing of the catalytic cleft. The mechanism relies on electrostatic repulsions between a conserved serine phosphorylated by CK2 and the acidic residues of the beta4alpha2 loop, promoting E2 ubiquitin charging activity. Our investigation identifies a new and unexpected pivotal role for the acidic loop, providing the first evidence that this loop is crucial not only for downstream events related to ubiquitin chain assembly, but is also mandatory for the modulation of an upstream crucial step of the ubiquitin pathway: the ubiquitin charging in the E2 catalytic cleft."	"http://www.ncbi.nlm.nih.gov/pubmed/21637798"
+"unk"	"latin"	"unknown"	"italy"	"0.0134529147982"	"0.0269058295964"	"0.0896860986547"	"223"	"10.619047619"	"Glycobiology"	"Parra A, Veraldi N, Locatelli M, Fini M, Martini L, Torri G, Sangiorgi L, Bisio A"	"S.S.D. Genetica Medica e Malattie Rare Ortopediche, Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136, Bologna, Italia."	"Glycosaminoglycans were extracted from both young rabbit growth plate and articular cartilage tissues and enzymatically treated to selectively eliminate chondroitin sulfates and hyaluronic acid. The procedure avoided any fractionation step that could enrich the extract with over- or under-sulfated species. Isolated HS was characterized by mono- and bidimensional NMR spectroscopy to quantify their specific structural features and/or by mass spectrometry to establish the disaccharide composition. Both growth plate and articular HSs, despite differing in their yield (growth plate at least one hundred times greater than articular), exhibited a surprisingly high degree of sulfation. Quantitative 2D-HSQC NMR analysis of growth plate HS revealed unusually high N-sulfated glucosamine and 2-O-sulfated iduronic acid contents, similar to heparin. The unique pentasaccharide sequence of the binding site for antithrombin was also detected in a significant amount. HPLC-MS analysis of the enzymatic digests with a cocktail of heparin lyases of both cartilaginous HSs confirmed the NMR results. As well as the discovery of an unusual HS structure in the two different types of rabbit cartilage, the feasibility of the analytical method adopted here has been demonstrated within this study. Such a method can be used to isolate and analyze HS from both normal and pathologic tissues. Characterization of healthy and pathological HS structures will contribute to improve the understanding of diseases related to malfunctions of HS biosynthesis and/or metabolism."	"http://www.ncbi.nlm.nih.gov/pubmed/21933839"
 3	"latin"	"France"	"France"	"0.004329004329"	"0.021645021645"	"0.0952380952381"	"231"	"13.5882352941"	"BMC Bioinformatics"	"Paulet D, Claustres M, Beroud C"	"Universite Montpellier, France. damien.paulet@inserm.fr"	"BACKGROUND: Few high-resolution structures of integral membranes proteins are available, as crystallization of such proteins needs yet to overcome too many technical limitations. Nevertheless, prediction of their transmembrane (TM) structure by bioinformatics tools provides interesting insights on the topology of these proteins. METHODS: We describe here how to extract new information from the analysis of hydrophobicity variations or hydrophobic pulses (HPulses) in the sequence of integral membrane proteins using the Hydrophobic Pulse Predictor, a new tool we developed for this purpose. To analyze the primary sequence of 70 integral membrane proteins we defined two levels of analysis: G1-HPulses for sliding windows of n = 2 to 6 and G2-HPulses for sliding windows of n = 12 to 16. RESULTS: The G2-HPulse analysis of 541 transmembrane helices allowed the definition of the new concept of transmembrane unit (TMU) that groups together transmembrane helices and segments with potential adjacent structures. In addition, the G1-HPulse analysis identified helix irregularities that corresponded to kinks, partial helices or unannotated structural events. These irregularities could represent key dynamic elements that are alternatively activated depending on the channel status as illustrated by the crystal structures of the lactose permease in different conformations. CONCLUSIONS: Our results open a new way in the understanding of transmembrane secondary structures: hydrophobicity through hydrophobic pulses strongly impacts on such embedded structures and is not confined to define the transmembrane status of amino acids."	"http://www.ncbi.nlm.nih.gov/pubmed/21545751"
 3	"latin"	"Portugal"	"Portugal"	"0.0120481927711"	"0.00803212851406"	"0.116465863454"	"249"	"13.1052631579"	"PLoS One"	"Paulo AC, Sampaio A, Santos NC, Costa PS, Cunha P, Zihl J, Cerqueira J, Palha JA, Sousa N"	"Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal."	"BACKGROUND: The Minho Integrative Neuroscience Database (MIND)-Ageing project aims to identify predictors of healthy cognitive ageing, including socio-demographic factors. In this exploratory analysis we sought to establish baseline cohorts for longitudinal assessment of age-related changes in cognition. METHODS: The population sample (472 individuals) was strictly a convenient one, but similar to the Portuguese population in the age profile. Participants older than 55 years of age were included if they did not present defined disabling pathologies or dementia. A standardized clinical interview was conducted to assess medical history and a battery of neuropsychological tests was administered to characterize global cognition (Mini Mental State Examination), memory and executive functions (Selective Reminding Test; Stroop Color and Word Test; and Block Design subtest of the Wechsler Adult Intelligence Scale). Cross-sectional analysis of the neuropsychological performance with individual characteristics such as age, gender, educational level and setting (retirement home, senior university, day care center or community), allowed the establishment of baseline clusters for subsequent longitudinal studies. RESULTS: Based on different socio-demographic characteristics, four main clusters that group distinctive patterns of cognitive performance were identified. The type of institution where the elders were sampled from, together with the level of formal education, were the major hierarchal factors for individual distribution in the four clusters. Of notice, education seems to delay the cognitive decline that is associated with age in all clusters. CONCLUSIONS: Social-inclusion/engagement and education seem to have a protective effect on mental ageing, although this effect may not be effective in the eldest elders."	"http://www.ncbi.nlm.nih.gov/pubmed/21931752"
 1	"latin"	"France"	"France"	"0.00840336134454"	"0.00840336134454"	"0.126050420168"	"238"	"12.6315789474"	"BMC Bioinformatics"	"Pauwels E, Stoven V, Yamanishi Y"	"Mines ParisTech, Centre for Computational Biology, 35 Rue Saint-Honore, F-77305 Fontainebleau Cedex, France."	"BACKGROUND: Drug side-effects, or adverse drug reactions, have become a major public health concern. It is one of the main causes of failure in the process of drug development, and of drug withdrawal once they have reached the market. Therefore, in silico prediction of potential side-effects early in the drug discovery process, before reaching the clinical stages, is of great interest to improve this long and expensive process and to provide new efficient and safe therapies for patients. RESULTS: In the present work, we propose a new method to predict potential side-effects of drug candidate molecules based on their chemical structures, applicable on large molecular databanks. A unique feature of the proposed method is its ability to extract correlated sets of chemical substructures (or chemical fragments) and side-effects. This is made possible using sparse canonical correlation analysis (SCCA). In the results, we show the usefulness of the proposed method by predicting 1385 side-effects in the SIDER database from the chemical structures of 888 approved drugs. These predictions are performed with simultaneous extraction of correlated ensembles formed by a set of chemical substructures shared by drugs that are likely to have a set of side-effects. We also conduct a comprehensive side-effect prediction for many uncharacterized drug molecules stored in DrugBank, and were able to confirm interesting predictions using independent source of information. CONCLUSIONS: The proposed method is expected to be useful in various stages of the drug development process."	"http://www.ncbi.nlm.nih.gov/pubmed/21586169"
 3	"latin"	"Spain"	"Spain"	"0.0122950819672"	"0.0"	"0.0860655737705"	"244"	"8.12903225806"	"BMC Bioinformatics"	"Segura-Bedmar I, Martinez P, de Pablo-Sanchez C"	"Computer Science Department, University Carlos III of Madrid, Leganes, 28911, Spain. isegura@inf.uc3m.es"	"BACKGROUND: A drug-drug interaction (DDI) occurs when one drug influences the level or activity of another drug. The increasing volume of the scientific literature overwhelms health care professionals trying to be kept up-to-date with all published studies on DDI. METHODS: This paper describes a hybrid linguistic approach to DDI extraction that combines shallow parsing and syntactic simplification with pattern matching. Appositions and coordinate structures are interpreted based on shallow syntactic parsing provided by the UMLS MetaMap tool (MMTx). Subsequently, complex and compound sentences are broken down into clauses from which simple sentences are generated by a set of simplification rules. A pharmacist defined a set of domain-specific lexical patterns to capture the most common expressions of DDI in texts. These lexical patterns are matched with the generated sentences in order to extract DDIs. RESULTS: We have performed different experiments to analyze the performance of the different processes. The lexical patterns achieve a reasonable precision (67.30%), but very low recall (14.07%). The inclusion of appositions and coordinate structures helps to improve the recall (25.70%), however, precision is lower (48.69%). The detection of clauses does not improve the performance. CONCLUSIONS: Information Extraction (IE) techniques can provide an interesting way of reducing the time spent by health care professionals on reviewing the literature. Nevertheless, no approach has been carried out to extract DDI from texts. To the best of our knowledge, this work proposes the first integral solution for the automatic extraction of DDI from biomedical texts."	"http://www.ncbi.nlm.nih.gov/pubmed/21489220"
 3	"latin"	"Barcelona, Barcelona, Spain"	"Spain"	"0.00778210116732"	"0.011673151751"	"0.101167315175"	"257"	"15.1176470588"	"PLoS Computational Biology"	"Selivanov VA, Votyakova TV, Pivtoraiko VN, Zeak J, Sukhomlin T, Trucco M, Roca J, Cascante M"	"Departament de Bioquimica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, and IBUB, Barcelona, Spain."	"Reactive oxygen species (ROS) produced in the mitochondrial respiratory chain (RC) are primary signals that modulate cellular adaptation to environment, and are also destructive factors that damage cells under the conditions of hypoxia/reoxygenation relevant for various systemic diseases or transplantation. The important role of ROS in cell survival requires detailed investigation of mechanism and determinants of ROS production. To perform such an investigation we extended our rule-based model of complex III in order to account for electron transport in the whole RC coupled to proton translocation, transmembrane electrochemical potential generation, TCA cycle reactions, and substrate transport to mitochondria. It fits respiratory electron fluxes measured in rat brain mitochondria fueled by succinate or pyruvate and malate, and the dynamics of NAD(+) reduction by reverse electron transport from succinate through complex I. The fitting of measured characteristics gave an insight into the mechanism of underlying processes governing the formation of free radicals that can transfer an unpaired electron to oxygen-producing superoxide and thus can initiate the generation of ROS. Our analysis revealed an association of ROS production with levels of specific radicals of individual electron transporters and their combinations in species of complexes I and III. It was found that the phenomenon of bistability, revealed previously as a property of complex III, remains valid for the whole RC. The conditions for switching to a state with a high content of free radicals in complex III were predicted based on theoretical analysis and were confirmed experimentally. These findings provide a new insight into the mechanisms of ROS production in RC."	"http://www.ncbi.nlm.nih.gov/pubmed/21483483"
 3	"latin"	"Spain"	"Spain"	"0.0175438596491"	"0.0263157894737"	"0.149122807018"	"228"	"9.91304347826"	"PLoS Computational Biology"	"Serra F, Arbiza L, Dopazo J, Dopazo H"	"Evolutionary Genomics Lab, Bioinformatics & Genomics Department, Centro de Investigacion Principe Felipe, Valencia, Spain."	"Classically, the functional consequences of natural selection over genomes have been analyzed as the compound effects of individual genes. The current paradigm for large-scale analysis of adaptation is based on the observed significant deviations of rates of individual genes from neutral evolutionary expectation. This approach, which assumed independence among genes, has not been able to identify biological functions significantly enriched in positively selected genes in individual species. Alternatively, pooling related species has enhanced the search for signatures of selection. However, grouping signatures does not allow testing for adaptive differences between species. Here we introduce the Gene-Set Selection Analysis (GSSA), a new genome-wide approach to test for evidences of natural selection on functional modules. GSSA is able to detect lineage specific evolutionary rate changes in a notable number of functional modules. For example, in nine mammal and Drosophilae genomes GSSA identifies hundreds of functional modules with significant associations to high and low rates of evolution. Many of the detected functional modules with high evolutionary rates have been previously identified as biological functions under positive selection. Notably, GSSA identifies conserved functional modules with many positively selected genes, which questions whether they are exclusively selected for fitting genomes to environmental changes. Our results agree with previous studies suggesting that adaptation requires positive selection, but not every mutation under positive selection contributes to the adaptive dynamical process of the evolution of species."	"http://www.ncbi.nlm.nih.gov/pubmed/21390268"
+"unk"	"latin"	"unknown"	"italy"	"0.00985221674877"	"0.0197044334975"	"0.0591133004926"	"203"	"11.9411764706"	"Molecular Biology and Evolution"	"Severi F, Chicca A, Conticello SG"		"The Activation Induced Deaminase (AID)/APOBEC family of deaminases targeting nucleic acids arose at the beginning of the vertebrate radiation and further expanded in mammals. Following an analysis of the available genomic data, we report the identification of the APOBEC5, a novel group of paralogues in tetrapods. Moreover, we find bona fide homologues of Apolipoprotein B Editing Complex 1 (APOBEC1) in the genomes of anole lizard and zebra finch, thus implying its appearance prior to the divergence of the amniotes. apolipoprotein B editing complex 1 (APOBEC1), in contrast with other AID/APOBECs acting on DNA, is an RNA-editing enzyme that targets the transcript of Apolipoprotein B (ApoB), thereby causing the translation of a truncated form of the protein. 3RACE experiments reveal a lizard APOBEC1-like molecule lacking a C-terminal region important for mammalian ApoB RNA editing. This observation pairs with the finding that lizard ApoB is not deaminated at the region corresponding to the mammalian site of editing. Similar to mammalian APOBEC1, the lizard protein is able to deaminate DNA in bacteria and shows a conserved mutational context. Although not precluding the possibility that lizard APOBEC1 acts on unknown mRNA targets, these findings suggest that its ability to target DNA predates its role in RNA editing."	"http://www.ncbi.nlm.nih.gov/pubmed/21172829"
 3	"latin"	"Italy"	"Italy"	"0.0036496350365"	"0.0255474452555"	"0.0839416058394"	"274"	"11.9130434783"	"PLoS Computational Biology"	"Siciliano V, Menolascina F, Marucci L, Fracassi C, Garzilli I, Moretti MN, di Bernardo D"	"Telethon Institute of Genetics and Medicine, Naples, Italy."	"Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL) by generating a clonal population of mammalian cells (CHO) carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA), whose expression is regulated by a tTA responsive promoter (CMV-TET), thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP), thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL), by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off), and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the switch off times, as comparared to the non[Formula: see text]autoregulatated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour."	"http://www.ncbi.nlm.nih.gov/pubmed/21765813"
 3	"latin"	"France"	"France"	"0.00952380952381"	"0.0047619047619"	"0.0714285714286"	"210"	"10.0476190476"	"PLoS Computational Biology"	"Silhol R, Boelle PY"	"Universite Pierre et Marie Curie-Paris 6, Paris, France. silhol@u707.jussieu.fr"	"Realistic, individual-based models based on detailed census data are increasingly used to study disease transmission. Whether the rich structure of such models improves predictions is debated. This is studied here for the spread of varicella, a childhood disease, in a realistic population of children where infection occurs in the household, at school, or in the community at large. A methodology is first presented for simulating households with births and aging. Transmission probabilities were fitted for schools and community, which reproduced the overall cumulative incidence of varicella over the age range of 0-11 years old.Moreover, the individual-based model structure allowed us to reproduce several observed features of VZV epidemiology which were not included as hypotheses in the model: the age at varicella in first-born children was older than in other children, in accordance with observation; the same was true for children residing in rural areas. Model predicted incidence was comparable to observed incidence over time. These results show that models based on detailed census data on a small scale provide valid small scale prediction. By simulating several scenarios, we evaluate how varicella epidemiology is shaped by policies, such as age at first school enrolment, and school eviction. This supports the use of such models for investigating outcomes of public health measures."	"http://www.ncbi.nlm.nih.gov/pubmed/21814504"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21935446"
 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."	"http://www.ncbi.nlm.nih.gov/pubmed/21892159"
 "unk"	"other"	"Nairobi"	"Nairobi"	"0.0121951219512"	"0.0182926829268"	"0.0579268292683"	"328"	"21.8666666667"	"PLoS One"	"Nyandigisi A, Memusi D, Mbithi A, Angwa N, Shieshia M, Muturi A, Sudoi R, Githinji S, Juma E, Zurovac D"	"Division of Malaria Control, Ministry of Public Health & Sanitation, Nairobi, Kenya."	"BACKGROUND: The change of malaria case-management policy in Kenya to recommend universal parasitological diagnosis and targeted treatment with artemether-lumefantrine (AL) is supported with activities aiming by 2013 at universal coverage and adherence to the recommendations. We evaluated changes in health systems and case-management indicators between the baseline survey undertaken before implementation of the policy and the follow-up survey following the first year of the implementation activities. METHODS/FINDINGS: National, cross-sectional surveys using quality-of-care methods were undertaken at public facilities. Baseline and follow-up surveys respectively included 174 and 176 facilities, 224 and 237 health workers, and 2,405 and 1,456 febrile patients. Health systems indicators showed variable changes between surveys: AL stock-out (27% to 21%; p = 0.152); availability of diagnostics (55% to 58%; p = 0.600); training on the new policy (0 to 22%; p = 0.001); exposure to supervision (18% to 13%; p = 0.156) and access to guidelines (0 to 6%; p = 0.001). At all facilities, there was an increase among patients tested for malaria (24% vs 31%; p = 0.090) and those who were both tested and treated according to test result (16% to 22%; p = 0.048). At facilities with AL and malaria diagnostics, testing increased from 43% to 50% (p = 0.196) while patients who were both, tested and treated according to test result, increased from 28% to 36% (p = 0.114). Treatment adherence improved for test positive patients from 83% to 90% (p = 0.150) and for test negative patients from 47% to 56% (p = 0.227). No association was found between testing and exposure to training, supervision and guidelines, however, testing was significantly associated with facility ownership, type of testing, and patients caseload, age and clinical presentation. CONCLUSIONS: Most of the case-management indicators have shown some improvement trends; however differences were smaller than expected, rarely statistically significant and still leaving a substantial gap towards optimistic targets. The quantitative and qualitative improvement of interventions will ultimately determine the success of the new policy."	"http://www.ncbi.nlm.nih.gov/pubmed/21935464"
 "unk"	"other"	"Nairobi, Nairobi"	"Nairobi"	"0.0"	"0.00952380952381"	"0.0571428571429"	"105"	"5.73684210526"	"Database(Oxford)"	"Visendi P, Nganga W, Bulimo W, Bishop R, Ochanda J, de Villiers EP"	"Center for Biotechnology and Bioinformatics, University of Nairobi, Nairobi."	"We describe the development of TparvaDB, a comprehensive resource to facilitate research towards development of an East Coast fever vaccine, by providing an integrated user-friendly database of all genome and related data currently available for Theileria parva. TparvaDB is based on the Generic Model Organism Database (GMOD) platform. It contains a complete reference genome sequence, Expressed Sequence Tags (ESTs), Massively Parallel Signature Sequencing (MPSS) expression tag data and related information from both public and private repositories. The Artemis annotation workbench provides online annotation functionality. TparvaDB represents a resource that will underpin and promote ongoing East Coast fever vaccine development and biological research. Database URL: http://tparvadb.ilri.cgiar.org."	"http://www.ncbi.nlm.nih.gov/pubmed/21546359"
+"unk"	"spain"	"unknown"	"unknown"	"0.00606060606061"	"0.00606060606061"	"0.0424242424242"	"165"	"12.6923076923"	"Glycobiology"	"Garcia VP, Bermejo J, Rubio S, Quintana J, Estevez F"	"Departamento de Quimica de Productos Naturales y Biotecnologia, Instituto de Productos Naturales y Agrobiologia de Canarias, La Laguna, Tenerife, Canary Islands. vpergarw@gobiernodecanarias.org"	"Four new steroidal glycosides such as 3-O-6-deoxy-3-O-methyl-beta-D-allopyranosyl-(1 --> 4)-beta-D-oleandropyranosyl-(1 --> 4)-beta-D-cymaropyranosyl-(1 --> 4)-beta-D-cymaropyranoside-12-beta-tigloyl-14-beta-hydroxy-17-beta-pregnan e (1), 3-O-6-deoxy-3-O-methyl-beta-D-allopyranosyl-(1 --> 4)-beta-D-oleandropyranosyl-(1 --> 4)-beta-D-cymaropyranosyl-(1 --> 4)-beta-D-cymaropyranoside-12-beta-(2-amino)-benzoyl-14-beta-hydroxy-17-b eta-pregnane (2), 3-O-6-deoxy-3-O-methyl-beta-D-allopyranosyl-(1 --> 4)-beta-D-oleandropyranosyl-(1 --> 4)-beta-D-cymaropyranosyl-(1 --> 4)-beta-D-cymaropyranoside-12-beta-14-beta-dihydroxy-17-alpha-pregnane (3) and 3-O-6-deoxy-3-O-methyl-beta-D-allopyranosyl-(1 --> 4)-beta-D-oleandropyranosyl-(1 --> 4)-beta-D-cymaropyranosyl-(1 --> 4)-beta-D-cymaropyranoside-12-beta-14-beta-dihydroxy-17-beta-pregnane (4) were isolated from the aerial parts of Ceropegia fusca Bolle (Asclepiadaceae), a crassulacean acid metabolism plant, an endemic species to the Canary Islands that has been used in traditional medicine as a cicatrizant, vulnerary and disinfectant. The dichloromethane extract exhibited significant cytostatic activity against HL-60, A-431 and SK-MEL-1 cells, human leukemic, epidermoid carcinoma and melanoma cells, respectively. As shown in Table I, compounds 1 and 2 showed very similar IC(50) values. The acetylation of 1 to give the diacetate 5 increases 5-fold the cytotoxicity against HL-60 cells. Compounds 3 and 4 did not show cytotoxicity at the assayed concentrations. With respect to the compounds containing only the steroid ring (6-8), the presence of a charged O-amino-benzoyl but not a tigloyl group improved the cytotoxicity."	"http://www.ncbi.nlm.nih.gov/pubmed/21147757"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0106382978723"	"0.00354609929078"	"0.0425531914894"	"282"	"9.22580645161"	"PLoS One"	"Ait-Mohamed O, Battisti V, Joliot V, Fritsch L, Pontis J, Medjkane S, Redeuilh C, Lamouri A, Fahy C, Rholam M, Atmani D, Ait-Si-Ali S"	"Laboratoire de Biochimie Appliquee, Faculte des Sciences de la Nature et de la vie, Universite de Bejaia, Bejaia, Algeria."	"Plants are an invaluable source of potential new anti-cancer drugs. Here, we investigated the cytotoxic activity of the acetonic extract of Buxus sempervirens on five breast cancer cell lines, MCF7, MCF10CA1a and T47D, three aggressive triple positive breast cancer cell lines, and BT-20 and MDA-MB-435, which are triple negative breast cancer cell lines. As a control, MCF10A, a spontaneously immortalized but non-tumoral cell line has been used. The acetonic extract of Buxus sempervirens showed cytotoxic activity towards all the five studied breast cancer cell lines with an IC(50) ranging from 7.74 microg/ml to 12.5 microg/ml. Most importantly, the plant extract was less toxic towards MCF10A with an IC(50) of 19.24 microg/ml. Fluorescence-activated cell sorting (FACS) analysis showed that the plant extract induced cell death and cell cycle arrest in G0/G1 phase in MCF7, T47D, MCF10CA1a and BT-20 cell lines, concomitant to cyclin D1 downregulation. Application of MCF7 and MCF10CA1a respective IC(50) did not show such effects on the control cell line MCF10A. Propidium iodide/Annexin V double staining revealed a pre-apoptotic cell population with extract-treated MCF10CA1a, T47D and BT-20 cells. Transmission electron microscopy analyses indicated the occurrence of autophagy in MCF7 and MCF10CA1a cell lines. Immunofluorescence and Western blot assays confirmed the processing of microtubule-associated protein LC3 in the treated cancer cells. Moreover, we have demonstrated the upregulation of Beclin-1 in these cell lines and downregulation of Survivin and p21. Also, Caspase-3 detection in treated BT-20 and T47D confirmed the occurrence of apoptosis in these cells. Our findings indicate that Buxus sempervirens extract exhibit promising anti-cancer activity by triggering both autophagic cell death and apoptosis, suggesting that this plant may contain potential anti-cancer agents for single or combinatory cancer therapy against breast cancer."	"http://www.ncbi.nlm.nih.gov/pubmed/21935420"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00990099009901"	"0.0049504950495"	"0.0891089108911"	"202"	"11.8823529412"	"BMC Bioinformatics"	"Angiuoli SV, Matalka M, Gussman A, Galens K, Vangala M, Riley DR, Arze C, White JR, White O, Fricke WF"		"ABSTRACT: BACKGROUND: Next-generation sequencing technologies have decentralized sequence acquisition, increasing the demand for new bioinformatics tools that are easy to use, portable across multiple platforms, and scalable for high-throughput applications. Cloud computing platforms provide on-demand access to computing infrastructure over the Internet and can be used in combination with custom built virtual machines to distribute pre-packaged with pre-configured software. RESULTS: We describe the Cloud Virtual Resource, CloVR, a new desktop application for push-button automated sequence analysis that can utilize cloud computing resources. CloVR is implemented as a single portable virtual machine (VM) that provides several automated analysis pipelines for microbial genomics, including 16S, whole genome and metagenome sequence analysis. The CloVR VM runs on a personal computer, utilizes local computer resources and requires minimal installation, addressing key challenges in deploying bioinformatics workflows. In addition CloVR supports use of remote cloud computing resources to improve performance for large-scale sequence processing. In a case study, we demonstrate the use of CloVR to automatically process next-generation sequencing data on multiple cloud computing platforms. CONCLUSION: The CloVR VM and associated architecture lowers the barrier of entry for utilizing complex analysis protocols on both local single- and multi-core computers and cloud systems for high throughput data processing."	"http://www.ncbi.nlm.nih.gov/pubmed/21878105"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0234899328859"	"0.00335570469799"	"0.0536912751678"	"298"	"14.2380952381"	"PLoS One"	"Barakat A, Ihazmad H, Benkaroum S, Cherkaoui I, Benmamoun A, Youbi M, El Aouad R"	"Centre National de Reference de la Grippe, Institut National dHygiene, Ministere de la Sante, Rabat, Morocco."	"BACKGROUND: There is limited information about the epidemiology of influenza in Africa. We describe the epidemiology and seasonality of influenza in Morocco from 1996 to 2009 with particular emphasis on the 2007-2008 and 2008-2009 influenza seasons. Successes and challenges of the enhanced surveillance system introduced in 2007 are also discussed. METHODS: Virologic sentinel surveillance for influenza virus was initiated in Morocco in 1996 using a network of private practitioners that collected oro-pharyngeal and naso-pharyngeal swabs from outpatients presenting with influenza-like-illness (ILI). The surveillance network expanded over the years to include inpatients presenting with severe acute respiratory illness (SARI) at hospitals and syndromic surveillance for ILI and acute respiratory infection (ARI). Respiratory samples and structured questionnaires were collected from eligible patients, and samples were tested by immunofluorescence assays and by viral isolation for influenza viruses. RESULTS: We obtained a total of 6465 respiratory specimens during 1996 to 2009, of which, 3102 were collected during 2007-2009. Of those, 2249 (72%) were from patients with ILI, and 853 (27%) were from patients with SARI. Among the 3,102 patients, 98 (3%) had laboratory-confirmed influenza, of whom, 85 (87%) had ILI and 13 (13%) had SARI. Among ILI patients, the highest proportion of laboratory-confirmed influenza occurred in children less than 5 years of age (3/169; 2% during 2007-2008 and 23/271; 9% during 2008-2009) and patients 25-59 years of age (8/440; 2% during 2007-2009 and 21/483; 4% during 2008-2009). All SARI patients with influenza were less than 14 years of age. During all surveillance years, influenza virus circulation was seasonal with peak circulation during the winter months of October through April. CONCLUSION: Influenza results in both mild and severe respiratory infections in Morocco, and accounted for a large proportion of all hospitalizations for severe respiratory illness among children 5 years of age and younger."	"http://www.ncbi.nlm.nih.gov/pubmed/21931764"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00813008130081"	"0.0243902439024"	"0.0731707317073"	"123"	"11.1818181818"	"Molecular Biology and Evolution"	"Battistuzzi FU, Billing-Ross P, Paliwal A, Kumar S"	"Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University."	"Phylogenetic analyses are using increasingly larger data sets for estimating divergence times. With this increase in data sizes, the computation time required is becoming a bottleneck in evolutionary investigations. Our recent study of two relaxed-clock programs (BEAST and MultiDivTime [MDT]) showed their usefulness in time estimation; however, they place a significant computational time burden on biologists even for moderately small data sets. Here, we report speed and accuracy of another relaxed-clock program (MCMCTree, MC2T). We find it to be much faster than both MDT and BEAST while producing comparable time estimates. These results will encourage the analysis of larger data sets as well as the evaluation of the robustness of estimated times to changes in the model of evolutionary rates and clock calibrations."	"http://www.ncbi.nlm.nih.gov/pubmed/21498604"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0267558528428"	"0.0133779264214"	"0.0602006688963"	"299"	"9.21212121212"	"PLoS One"	"Bernabe-Ortiz A, Carcamo CP, Scott JD, Hughes JP, Garcia PJ, Holmes KK"	"School of Public Health and Administration, Universidad Peruana Cayetano Heredia, Lima, Peru."	"BACKGROUND: Data on hepatitis B virus (HBV) prevalence are limited in developing countries. There is also limited information of consistent condom use efficacy for reducing HBV transmission at the population level. The study goal was to evaluate the prevalence and factors associated with HBV infection in Peru, and the relationship between anti-HBc positivity and consistent condom use. METHODS AND FINDINGS: Data from two different surveys performed in 28 mid-sized Peruvian cities were analyzed. Participants aged 18-29 years were selected using a multistage cluster sampling. Information was collected through a validated two-part questionnaire. The first part (face-to-face) concerned demographic data, while the second part (self-administered using handheld computers) concerned sexual behavior. Hepatitis B core antibody (anti-HBc) was tested in 7,000 blood samples. Prevalences and associations were adjusted for sample strata, primary sampling units and population weights. Anti-HBc prevalence was 5.0% (95%CI 4.1%-5.9%), with the highest prevalence among jungle cities: 16.3% (95%CI 13.8%-19.1%). In the multivariable analysis, Anti-HBc positivity was directly associated with geographic region (highlands OR = 2.05; 95%CI 1.28-3.27, and jungle OR = 4.86; 95%CI 3.05-7.74; compared to coastal region); and inversely associated with age at sexual debut (OR = 0.90; 95%CI 0.85-0.97). Consistent condom use, evaluated in about 40% of participants, was associated with reduced prevalence (OR = 0.34; 95%CI 0.15-0.79) after adjusting for gender, geographic region, education level, lifetime number of sex partners, age at sexual debut and year of survey. CONCLUSION: Residence in highlands or jungle cities is associated with higher anti-HBc prevalences, whereas increasing age at sexual debut were associated with lower prevalences. Consistent condom use was associated with decreased risk of anti-HBc. Findings from this study emphasize the need of primary prevention programs (vaccination) especially in the jungle population, and imply that condom use promotion might be a potential strategy to prevent HBV infection."	"http://www.ncbi.nlm.nih.gov/pubmed/21931828"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00471698113208"	"0.0188679245283"	"0.103773584906"	"212"	"10.0952380952"	"PLoS One"	"Brantley-Sieders DM, Jiang A, Sarma K, Badu-Nkansah A, Walter DL, Shyr Y, Chen J"	"Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United State of America."	"Pre-clinical studies provide compelling evidence that Eph family receptor tyrosine kinases (RTKs) and ligands promote cancer growth, neovascularization, invasion, and metastasis. Tumor suppressive roles have also been reported for the receptors, however, creating a potential barrier for clinical application. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. We investigated eph and ephrin expression in human breast cancer relative to endpoints of overall and/or recurrence-free survival in large microarray datasets. We also investigated protein expression in commercial human breast tissue microarrays (TMA) and Stage I prognostic TMAs linked to recurrence outcome data. We found significant correlations between ephA2, ephA4, ephA7, ephB4, and ephB6 and overall and/or recurrence-free survival in large microarray datasets. Protein expression in TMAs supported these trends. While observed no correlation between ephrin ligand expression and clinical outcome in microarray datasets, ephrin-A1 and EphA2 protein co-expression was significantly associated with recurrence in Stage I prognostic breast cancer TMAs. Our data suggest that several Eph family members are clinically relevant and tractable targets for intervention in human breast cancer. Moreover, profiling Eph receptor expression patterns in the context of relevant ligands and in the context of stage may be valuable in terms of diagnostics and treatment."	"http://www.ncbi.nlm.nih.gov/pubmed/21935409"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0152284263959"	"0.0152284263959"	"0.0609137055838"	"197"	"10.5263157895"	"BMC Bioinformatics"	"Bult CJ, Drabkin HJ, Evsikov A, Natale D, Arighi C, Roberts N, Ruttenberg A, DEustachio P, Smith B, Blake JA, Wu C"		"ABSTRACT: BACKGROUND: Representing species-specific proteins and protein complexes in ontologies that are both human- and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protein-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. Description: We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. Conclusion: PRO is a unique database resource for species-specific protein complexes. PRO facilitates robust annotation of variations in composition and function contexts for protein complexes within and between species."	"http://www.ncbi.nlm.nih.gov/pubmed/21929785"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00378787878788"	"0.0227272727273"	"0.0606060606061"	"264"	"15.5294117647"	"Molecular Biology and Evolution"	"Campsteijn C, Inge Ovrebo J, Karlsen BO, Thompson EM"	"Sars International Centre for Marine Molecular Biology."	"Proliferative and endoreduplicative cell cycles are used to variable extents during the ontogeny of individual organisms and in different evolutionary lineages. Chordate growth and development is typically dominated by proliferative cycles, but the urochordate, Oikopleura dioica, has systemically elaborated a number of endocycling modes to support rapid development and growth in an extraordinarily short chordate life cycle. Here we identify the O. dioica cyclin and cyclin-dependent kinase (CDK) complements and assess their deployment with respect to mitotic, meiotic and endoreduplicative life cycle phases. O. dioicas transcriptional cyclin and CDK complements are similar to other complex invertebrates, whereas both the cell cycle cyclin and CDK complements display astonishing amplifications centered on the cyclin D, cyclin B and CDK1 families. Somatic endocycles in O. dioica involve down regulation of cyclins B and A, as in other endocycle model systems, but are also characterized by overlapping expression of an array of cyclin D isoforms. Amplification of the mitotic CDK1 family to 5 paralogs, which continue to be expressed in endocycling phases, is unexpected, as suppression of CDK1 activity is central to endocycle transitions in Drosophila and mammals. This amplification is unique among metazoans and substitutions in odCDK1 paralogs in the nearly invariant cyclin interaction PSTAIRE helix show striking parallels to those in the only other known eukaryotic CDK1 paralogs, plant CDKA and CDKB. As plant CDK1 paralogs exhibit an expanded repertoire of cyclin partners, including cyclin D, the evolutionary co-expansion of odCDK1 and odCyclin D families suggests that multiple CDK1-cyclin D complexes may modulate spatio-temporal control of kinase activity and substrate specificity in diverse cell cycle variants."	"http://www.ncbi.nlm.nih.gov/pubmed/21734012"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0100334448161"	"0.0167224080268"	"0.0535117056856"	"299"	"9.87096774194"	"PLoS One"	"Chelimo K, Embury PB, Odada Sumba P, Vulule J, Ofulla AV, Long C, Kazura JW, Moormann AM"	"Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya."	"Naturally acquired immunity to Plasmodium falciparum malaria in malaria holoendemic areas is characterized by the gradual, age-related development of protection against high-density parasitemia and clinical malaria. Animal studies, and less commonly, observations of humans with malaria, suggest that T-cell responses are important in the development and maintenance of this immunity, which is mediated primarily by antibodies that slow repeated cycles of merozoites through erythrocytes. To advance our rather limited knowledge on human T-cell immunity to blood stage malaria infection, we evaluated CD4 and CD8 T-cell effector memory subset responses to the 42 kDa C-terminal fragment of Merozoite Surface Protein 1 (MSP1(42)), a malaria vaccine candidate, by 49 healthy 0.5 to >/=18 year old residents of a holoendemic area in western Kenya. The proportion of individuals with peripheral blood mononuclear cell MSP1(42) driven IFN-gamma ELISPOT responses increased from 20% (2/20) among 0.5-1 year old children to 90% (9/10) of adults >/=18 years (P = 0.01); parallel increases in the magnitude of IFN-gamma responses were observed across all age groups (0.5, 1, 2, 5 and >/=18 years, P = 0.001). Less than 1% of total CD4 and CD8 T-cells from both children and adults produced IFN-gamma in response to MSP1(42). However, adults had higher proportions of MSP1(42) driven IFN-gamma secreting CD4 and CD8 effector memory (CD45RA(-) CD62L(-)) T-cells than children (CD4: 50.9% vs. 28.8%, P = 0.036; CD8: 52.1% vs. 18.3%, respectively P = 0.009). In contrast, MSP1(42) driven IFN-gamma secreting naive-like, transitional (CD45RA(+) CD62L(+)) CD4 and CD8 cells were the predominant T-cell subset among children with significantly fewer of these cells in adults (CD4: 34.9% vs. 5.1%, P = 0.002; CD8: 47.0% vs. 20.5%, respectively, P = 0.030). These data support the concept that meaningful age-related differences exist in the quality of T-cell immunity to malaria antigens such as MSP1."	"http://www.ncbi.nlm.nih.gov/pubmed/21935482"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0137614678899"	"0.045871559633"	"0.0596330275229"	"218"	"6.78787878788"	"BMC Bioinformatics"	"Cheng F, Zhang X, Zhang Y, Li C, Zeng C"		"ABSTRACT: BACKGROUND: Generally, SNPs are abundant in the genome; however, they display low power in linkage analysis because of their limited heterozygosity. Haplotype markers, on the other hand, which are composed of many SNPs, greatly increase heterozygosity and have superiority in linkage statistics. RESULTS: Here we developed Haplo2Ped to automatically transform SNP data into haplotype markers and then to compute the logarithm (base 10) of odds (LOD) scores of regional haplotypes that are homozygous within the disease co-segregation haploid group. The results are reported as a hypertext file and a 3D figure to help users to obtain the candidate linkage regions. The hypertext file contains parameters of the disease linked regions, candidate genes, and their links to public databases. The 3D figure clearly displays the linkage signals in each chromosome. We tested Haplo2Ped in a simulated SNP dataset and also applied it to data from a real study. It successfully and accurately located the causative genomic regions. Comparison of Haplo2Ped with other existing software for linkage analysis further indicated the high effectiveness of this software. CONCLUSIONS: Haplo2Ped uses haplotype fragments as mapping markers in whole genome linkage analysis. The advantages of Haplo2Ped over other existing software include straightforward output files, increased accuracy and superior ability to deal with pedigrees showing incomplete penetrance. Haplo2Ped is freely available at: http://bighapmap.big.ac.cn/software.html."	"http://www.ncbi.nlm.nih.gov/pubmed/21854652"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0116279069767"	"0.0232558139535"	"0.0503875968992"	"258"	"9.55555555556"	"BMC Bioinformatics"	"Chiang GT, Clapham P, Qi G, Sale K, Coates G"		"ABSTRACT: BACKGROUND: Increasingly large amounts of DNA sequencing data are being generated within the Wellcome Trust Sanger Institute (WTSI). The traditional file system thus struggles to handle these increasing amounts of sequence data. A good data management system therefore needs to be implemented and integrated into the current WTSI infrastructure. With such a system, the IT infrastructure of sequencing pipeline can be well managed and biologists are able track their data. RESULTS: A data grid system iRODS (Rule-Oriented Data management systems) is chosen by as the data management system for WTSI. iRODS provides a rule-based system management approach which makes data replication much easier and provides extra data protection. Unlike the metadata provided by traditional file system, the metadata system of iRODS is more comprehensive and allows users to customize their own application level metadata. Users and IT experts in WTSI can then query the metadata to find and to track the data. The aim of this paper is to describe how we designed and used (from both system and user viewpoints) iRODS as a data management system. Details are given about the problems faced and the solutions found when iRODS was implemented. A simple use case describing how users within WTSI use iRODS is also introduced. CONCLUSIONS: iRODS has been implemented and working as the production system of the sequencing pipeline of WTSI. Both biologists and IT experts can now track and manage data, which cannot be achieved before. This novel approach allows biologists to define their own metadata and query the genomic data using those metadata."	"http://www.ncbi.nlm.nih.gov/pubmed/21906284"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00977198697068"	"0.0358306188925"	"0.0912052117264"	"307"	"10.5862068966"	"BMC Bioinformatics"	"Chitale M, Palakodety S, Kihara D"		"ABSTRACT: BACKGROUND: Genomics and proteomics experiments produce a large amount of data that are awaiting functional elucidation. An important step in analyzing such data is to identify functional units, which consist of proteins that play coherent roles to carry out the function. Importantly, functional coherence is not identical with functional similarity. For example, proteins in the same pathway may not share the same Gene Ontology (GO) terms, but they work in a coordinated fashion so that the aimed function can be performed. Thus, simply applying existing functional similarity measures might not be the best solution to identify functional units in omics data. RESULTS: We have designed two scores for quantifying the functional coherence by considering association of GO terms observed in two biological contexts, co-occurrences in protein annotations and co-mentions in literature in the PubMed database. The counted co-occurrences of GO terms were normalized in a similar fashion as the statistical amino acid contact potential is computed in the protein structure prediction field. We demonstrate that the developed scores can identify functionally coherent protein sets, i.e. proteins in the same pathways, co-localized proteins, and protein complexes, with statistically significant score values showing a better accuracy than existing functional similarity scores. The scores are also capable of detecting protein pairs that interact with each other. It is further shown that the functional coherence scores can accurately assign proteins to their respective pathways. CONCLUSION: We have developed two scores which quantify the functional coherence of sets of proteins. The scores reflect the actual associations of GO terms observed either in protein annotations or in literature. It has been shown that they have the ability to accurately distinguish biologically relevant groups of proteins from random ones as well as a good discriminative power for detecting interacting pairs of proteins. The scores were further successfully applied for assigning proteins to pathways."	"http://www.ncbi.nlm.nih.gov/pubmed/21929787"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00859598853868"	"0.00859598853868"	"0.106017191977"	"349"	"16.619047619"	"BMC Bioinformatics"	"Clark ST, Verwoerd WS"		"ABSTRACT: BACKGROUND: The numerous diverse metabolic pathways by which plant compounds can be produced make it difficult to predict how colour pigmentation is lost for different tissues and plants. This study employs mathematical and in silico methods to identify correlated gene targets for the loss of colour pigmentation in plants from a whole cell perspective based on the full metabolic network of Arabidopsis. This involves extracting a self-contained flavonoid subnetwork from the AraCyc database and calculating feasible metabolic routes or elementary modes (EMs) for it. Those EMs leading to anthocyanin compounds are taken to constitute the anthocyanin biosynthetic pathway (ABP) and their interplay with the rest of the EMs are used to study the minimal cut sets (MCSs), which are different combinations of reactions to block for eliminating colour pigmentation. By relating the reactions to their corresponding genes, the MCSs are used to explore the phenotypic roles of the ABP genes, their relevance to the ABP and the impact their eliminations would have on other processes in the cell. RESULTS: Simulation and prediction results of the effect of different MCSs for eliminating colour pigmentation correspond with existing experimental observations. Two examples are: i) two MCSs which require the simultaneous suppression of genes DFR and ANS to eliminate colour pigmentation, correspond to observational results of the same genes being co-regulated for eliminating floral pigmentation in Aquilegia and; ii) the impact of another MCS requiring CHS suppression, corresponds to findings where the suppression of the early gene CHS eliminated nearly all flavonoids but did not affect the production of volatile benzenoids responsible for floral scent. CONCLUSIONS: From the various MCSs identified for eliminating colour pigmentation, several correlate to existing experimental observations, indicating that different MCSs are suitable for different plants, different cells, and different conditions and could also be related to regulatory genes. Being able to correlate the predictions with experimental results gives credence to the use of these mathematical and in silico analyses methods in the design of experiments. The methods could be used to prioritize target enzymes for different objectives to achieve desired outcomes, especially for less understood pathways."	"http://www.ncbi.nlm.nih.gov/pubmed/21849042"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0168067226891"	"0.0672268907563"	"119"	"9.15384615385"	"Molecular Biology and Evolution"	"Clay OK, Bernardi G"		"In an article published in these pages, Elhaik et al. (Elhaik E, Landan G, Graur D. 2009. Can GC content at third-codon positions be used as a proxy for isochore composition? Mol Biol Evol. 26:1829-1833) asked if GC3, the GC level of the third-codon positions in protein-coding genes, can be used as a proxy to estimate the GC level of the surrounding isochore. We use available data to directly answer this simple question in the affirmative and show how the use of indirect methods can lead to apparently conflicting conclusions. The answer reasserts that in human and other vertebrates, genes have a strong tendency to reside in compositionally corresponding isochores, which has far-reaching implications for genome structure and evolution."	"http://www.ncbi.nlm.nih.gov/pubmed/20817719"
 "unk"	"unknown"	"unknown"	"unknown"	"0.008"	"0.032"	"0.084"	"250"	"16.6666666667"	"Molecular Biology and Evolution"	"Crandall ED, Sbrocco EJ, Deboer TS, Barber PH, Carpenter KE"	"Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, U.S.A."	"The rate of change in DNA is an important parameter for understanding molecular evolution, and hence for inferences drawn from studies of phylogeography and phylogenetics. Most rate calibrations for mitochondrial coding regions in marine species have been made from divergence dating for fossils and vicariant events older than 1-2 million years, and are typically 0.5% - 2% per lineage per million years. Recently, calibrations made with ancient DNA from younger dates have yielded faster rates, suggesting that estimates of the molecular rate of change depend on the time of calibration, decaying from the instantaneous mutation rate to the phylogenetic substitution rate. Ancient DNA methods for recent calibrations are not available for most marine taxa so instead we use radiometric dates for sea-level rise onto the Sunda Shelf following the Last Glacial Maximum (starting  approximately 18,000 years ago), which led to massive population expansions for marine species. Instead of divergence dating, we use a two-epoch coalescent model of logistic population growth preceded by a constant population size to infer a time in mutational units for the beginning of these expansion events. This model compares favorably to simpler coalescent models of constant population size, and exponential or logistic growth, and is far more precise than estimates from the mismatch distribution. Mean rates estimated with this method for mitochondrial coding genes in three invertebrate species are elevated in comparison to older calibration points (2.3% - 6.6% per lineage per million years), lending additional support to the hypothesis of calibration time-dependency for molecular rates."	"http://www.ncbi.nlm.nih.gov/pubmed/21926069"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0143369175627"	"0.00716845878136"	"0.0752688172043"	"279"	"11.16"	"BMC Bioinformatics"	"Cule E, Vineis P, De Iorio M"		"ABSTRACT: BACKGROUND: Technological developments have increased the feasibility of large scale genetic association studies. Densely typed genetic markers are obtained using SNP arrays, next-generation sequencing technologies and imputation. However, SNPs typed using these methods can be highly correlated due to linkage disequilibrium among them, and standard multiple regression techniques fail with these data sets due to their high dimensionality and correlation structure. There has been increasing interest in using penalised regression in the analysis of high dimensional data. Ridge regression is one such penalised regression technique which does not perform variable selection, instead estimating a regression coefficient for each predictor variable. It is therefore desirable to obtain an estimate of the significance of each ridge regression coefficient. RESULTS: We develop and evaluate a test of significance for ridge regression coefficients. Using simulation studies, we demonstrate that the performance of the test is comparable to that of a permutation test, with the advantage of a much-reduced computational cost. We introduce the p-value trace, a plot of the negative logarithm of the p-values of ridge regression coefficients with increasing shrinkage parameter, which enables the visualisation of the change in p-value of the regression coefficients with increasing penalisation. We apply the proposed method to a lung cancer case-control data set from EPIC, the European Prospective Investigation into Cancer and Nutrition. CONCLUSIONS: The proposed test is a useful alternative to a permutation test for the estimation of the significance of ridge regression coefficients, at a much-reduced computational cost. The p-value trace is an informative graphical tool for evaluating the results of a test of significance of ridge regression coefficients as the shrinkage parameter increases, and the proposed test makes its production computationally feasible."	"http://www.ncbi.nlm.nih.gov/pubmed/21929786"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0046511627907"	"0.0279069767442"	"0.102325581395"	"215"	"11.4736842105"	"BMC Bioinformatics"	"Daniluk P, Lesyng B"		"ABSTRACT: BACKGROUND: Protein structure comparison is one of the most widely performed tasks in bioinformatics. However, currently used methods have problems with the so-called difficult similarities, including considerable shifts and distortions of structure, sequential swaps and circular permutations. There is a demand for efficient and automated systems capable of overcoming these difficulties, which may lead to the discovery of previously unknown structural relationships. RESULTS: We present a novel method for protein structure comparison based on the formalism of local descriptors of protein structure - DEscriptor Defined Alignment (DEDAL). Local similarities identified by pairs of similar descriptors are extended into global structural alignments. We demonstrate the methods capability by aligning structures in difficult benchmark sets: curated alignments in the SISYPHUS database, as well as SISY and RIPC sets, including non-sequential and non-rigid-body alignments. On the most difficult RIPC set of sequence alignment pairs the method achieves an accuracy of 77% (the second best method tested achieves 60% accuracy). CONCLUSIONS: DEDAL is fast enough to be used in whole proteome applications, and by lowering the threshold of detectable structure similarity it may shed additional light on molecular evolution processes. It is well suited to improving automatic classification of structure domains, helping analyze protein fold space, or to improving protein classification schemes. DEDAL is available online at http://bioexploratorium.pl/EP/DEDAL."	"http://www.ncbi.nlm.nih.gov/pubmed/21849047"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0253807106599"	"0.0304568527919"	"0.0558375634518"	"197"	"6.0"	"Bioinformatics"	"Dao P, Wang K, Collins C, Ester M, Lapuk A, Sahinalp SC"	"School of Computing Science, Simon Fraser University."	"MOTIVATION: Molecular profiles of tumour samples have been widely and successfully used for classification problems. A number of algorithms have been proposed to predict classes of tumor samples based on expression profiles with relatively high performance. However, prediction of response to cancer treatment has proved to be more challenging and novel approaches with improved generalizability are still highly needed. Recent studies have clearly demonstrated the advantages of integrating protein-protein interaction (PPI) data with gene expression profiles for the development of subnetwork markers in classification problems. RESULTS: We describe a novel network-based classification algorithm (OptDis) using color coding technique to identify optimally discriminative subnetwork markers. Focusing on PPI networks, we apply our algorithm to drug response studies: we evaluate our algorithm using published cohorts of breast cancer patients treated with combination chemotherapy. We show that our OptDis method improves over previously published subnetwork methods and provides better and more stable performance compared with other subnetwork and single gene methods. We also show that our subnetwork method produces predictive markers that are more reproducible across independent cohorts and offer valuable insight into biological processes underlying response to therapy. AVAILABILITY: The implementation is available at: http://www.cs.sfu.ca/~pdao/personal/OptDis.html CONTACT: cenk@cs.sfu.ca; alapuk@prostatecentre.com; ccollins@prostatecentre.com."	"http://www.ncbi.nlm.nih.gov/pubmed/21685072"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0219298245614"	"0.00877192982456"	"0.0614035087719"	"228"	"12.0"	"Molecular Biology and Evolution"	"Debarry JD, Kissinger JC"	"Center for Tropical and Emerging Global Diseases, University of Georgia."	"Whole-genome comparisons provide insight into genome evolution by informing on gene repertoires, gene gains/losses, and genome organization. Most of our knowledge about eukaryotic genome evolution is derived from studies of multicellular model organisms. The eukaryotic phylum Apicomplexa contains obligate intracellular protist parasites responsible for a wide range of human and veterinary diseases (e.g., malaria, toxoplasmosis, and theileriosis). We have developed an in silico protein-encoding gene based pipeline to investigate synteny across 12 apicomplexan species from six genera. Genome rearrangement between lineages is extensive. Syntenic regions (conserved gene content and order) are rare between lineages and appear to be totally absent across the phylum, with no group of three genes found on the same chromosome and in the same order within 25 kb up- and downstream of any orthologous genes. Conserved synteny between major lineages is limited to small regions in Plasmodium and Theileria/Babesia species, and within these conserved regions, there are a number of proteins putatively targeted to organelles. The observed overall lack of synteny is surprising considering the divergence times and the apparent absence of transposable elements (TEs) within any of the species examined. TEs are ubiquitous in all other groups of eukaryotes studied to date and have been shown to be involved in genomic rearrangements. It appears that there are different criteria governing genome evolution within the Apicomplexa relative to other well-studied unicellular and multicellular eukaryotes."	"http://www.ncbi.nlm.nih.gov/pubmed/21504890"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00826446280992"	"0.0206611570248"	"0.0619834710744"	"242"	"18.6153846154"	"Molecular Biology and Evolution"	"Deschamps P, Lara E, Marande W, Lopez-Garcia P, Ekelund F, Moreira D"		"Kinetoplastids are a large group of free-living and parasitic eukaryotic flagellates, including the medically important trypanosomatids (e.g., Trypanosoma and Leishmania) and the widespread free-living and parasitic bodonids. Small subunit rRNA- and conserved protein-based phylogenies support the division of kinetoplastids into five orders (Prokinetoplastida, Neobodonida, Parabodonida, Eubodonida, and Trypanosomatida), but they produce incongruent results regarding their relative branching order, in particular for the position of the Trypanosomatida. In general, small subunit rRNA tends to support their early emergence, whereas protein phylogenies most often support a more recent origin from within bodonids. In order to resolve this question through a phylogenomic approach, we carried out massive parallel sequencing of cDNA from representatives of three bodonid orders (Bodo saltans -Eubodonida-, Procryptobia sorokini -Parabodonida-, and Rhynchomonas nasuta -Neobodonida-). We identified 64 well-conserved proteins shared by these species, four trypanosomatids, and two closely related outgroup species (Euglena gracilis and Diplonema papillatum). Phylogenetic analysis of a concatenated data set yielded a strongly supported tree showing the late emergence of trypanosomatids as a sister group of the Eubodonida. In addition, we identified homologues of proteins involved in trypanosomatid mitochondrial mRNA editing in the three bodonid species, suggesting that editing may be widespread in kinetoplastids. Comparison of expressed sequences from mitochondrial genes showed variability at U positions, in agreement with the existence of editing activity in the three bodonid orders most closely related to trypanosomatids (Neobodonida, Parabodonida, and Eubodonida). Mitochondrial mRNA editing appears to be an ancient phenomenon in kinetoplastids."	"http://www.ncbi.nlm.nih.gov/pubmed/21030427"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0205761316872"	"0.0699588477366"	"243"	"11.619047619"	"BMC Bioinformatics"	"Diaz-Diaz N, Aguilar-Ruiz JS"		"ABSTRACT: BACKGROUND: The Gene Ontology (GO) provides a controlled vocabulary for describing the functions of genes and can be used to evaluate the functional coherence of gene sets. Many functional coherence measures consider each pair of gene functions in a set and produce an output based on all pairwise distances. A single gene can encode multiple proteins that may differ in function. For each functionality, other proteins that exhibit the same activity may also participate. Therefore, an identification of the most common function for all of the genes involved in a biological process is important in evaluating the functional similarity of groups of genes and a quantification of functional coherence can helps to clarify the role of a group of genes working together. RESULTS: To implement this approach to functional assessment, we present GFD (GO-based Functional Dissimilarity), a novel dissimilarity measure for evaluating groups of genes based on the most relevant functions of the whole set. The measure assigns a numerical value to the gene set for each of the three GO sub-ontologies. CONCLUSIONS: Results show that GFD performs robustly when applied to gene set of known functionality (extracted from KEGG). It performs particularly well on randomly generated gene sets. An ROC analysis reveals that the performance of GFD in evaluating the functional dissimilarity of gene sets is very satisfactory. A comparative analysis against other functional measures, such as GS2 and those presented by Resnik and Wang, also demonstrates the robustness of GFD."	"http://www.ncbi.nlm.nih.gov/pubmed/21884611"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00436681222707"	"0.0174672489083"	"0.0742358078603"	"229"	"8.51851851852"	"BMC Bioinformatics"	"Domanova O, Borbe S, Muhlfeld S, Becker M, Kubitz R, Haussinger D, Berlage T"		"ABSTRACT: BACKGROUND: Intra-cellular and inter-cellular protein translocation can be observed by microscopic imaging of tissue sections prepared immunohistochemically. A manual densitometric analysis is time-consuming, subjective and error-prone. An automated quantification is faster, more reproducible, and should yield results comparable to manual evaluation. The automated method presented here was developed on rat liver tissue sections to study the translocation of bile salt transport proteins in hepatocytes. For validation, the cholestatic liver state was compared to the normal biological state. RESULTS: An automated quantification method was developed to analyze the translocation of membrane proteins and evaluated in comparison to an established manual method. Firstly, regions of interest (membrane fragments) are identified in confocal microscopy images. Further, densitometric intensity profiles are extracted orthogonally to membrane fragments, following the direction from the plasma membrane to cytoplasm. Finally, several different quantitative descriptors were derived from the densitometric profiles and were compared regarding their statistical significance with respect to the transport protein distribution. Stable performance, robustness and reproducibility were tested using several independent experimental datasets. A fully automated workflow for the information extraction and statistical evaluation has been developed and produces robust results. CONCLUSIONS: New descriptors for the intensity distribution profiles were found to be more discriminative, i.e. more significant, than those used in previous research publications for the translocation quantification. The slow manual calculation can be substituted by the fast and unbiased automated method."	"http://www.ncbi.nlm.nih.gov/pubmed/21929784"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.031914893617"	"0.0531914893617"	"94"	"13.4285714286"	"Molecular Biology and Evolution"	"Felekkis K, Voskarides K, Dweep H, Sticht C, Gretz N, Deltas C"	"Department of Biological Sciences and Molecular Medicine Research Center, University of Cyprus, Nicosia, Cyprus."	"MicroRNAs (miRNAs) and copy number variations (CNVs) are two newly discovered genetic elements that have revolutionized the field of molecular biology and genetics. By performing in silico whole genome analysis, we demonstrate that both the number of miRNAs that target genes found in CNV regions as well as the number of miRNA-binding sites are significantly higher than those of genes found in non-CNV regions. This suggests that miRNAs may have acted as equilibrators of gene expression during evolution in an attempt to regulate aberrant gene expression and to increase the tolerance to genome plasticity."	"http://www.ncbi.nlm.nih.gov/pubmed/21441354"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0114942528736"	"0.0804597701149"	"174"	"11.6"	"PLoS Computational Biology"	"Finn NA, Findley HW, Kemp ML"	"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia."	"Although doxorubicin toxicity in cancer cells is multifactorial, the enzymatic bioactivation of the drug can significantly contribute to its cytotoxicity. Previous research has identified most of the components that comprise the doxorubicin bioactivation network; however, adaptation of the network to changes in doxorubicin treatment or to patient-specific changes in network components is much less understood. To investigate the properties of the coupled reduction/oxidation reactions of the doxorubicin bioactivation network, we analyzed metabolic differences between two patient-derived acute lymphoblastic leukemia (ALL) cell lines exhibiting varied doxorubicin sensitivities. We developed computational models that accurately predicted doxorubicin bioactivation in both ALL cell lines at high and low doxorubicin concentrations. Oxygen-dependent redox cycling promoted superoxide accumulation while NADPH-dependent reductive conversion promoted semiquinone doxorubicin. This fundamental switch in control is observed between doxorubicin sensitive and insensitive ALL cells and between high and low doxorubicin concentrations. We demonstrate that pharmacological intervention strategies can be employed to either enhance or impede doxorubicin cytotoxicity in ALL cells due to the switching that occurs between oxygen-dependent superoxide generation and NADPH-dependent doxorubicin semiquinone formation."	"http://www.ncbi.nlm.nih.gov/pubmed/21935349"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00584795321637"	"0.0116959064327"	"0.093567251462"	"171"	"9.05263157895"	"Glycobiology"	"Fischer K, Stein K, Ulmer AJ, Lindner B, Heine H, Holst O"	"Division of Structural Biochemistry."	"It was established in a mouse model that the cowshed Gram-positive bacterium Lactococcus lactis G121 modulates the immune system resulting in allergy protection. However, the molecules and mechanisms involved in this process have not been elucidated yet. Lipoteichoic acids (LTA) represent one major cell envelope component of Gram-positive bacteria that is considered a pathogen-associated molecular pattern. In the investigations presented here, the isolation as well as structural and functional analyses of the LTA of L. lactis G 121 were performed. Extraction with butan-1-ol and purification by hydrophobic interaction chromatography yielded pure LTA. Structural investigations included chemical analytical methods, nuclear magnetic resonance spectroscopy and high resolution electrospray ionization Fourier-transformed ion cyclotron mass spectrometry. LTA comprised a heterogeneous mixture of molecules composed of a 1,3-linked poly(glycerol phosphate) backbone which was randomly substituted at C-2 by d-alanine and alpha-d-galactopyranose. The lipid anchor constituents were kojibiose linked to a heterogeneous diglyceride comprising in total six different fatty acid compositions. This LTA preparation possesses Toll-like receptor (TLR) 2- and TLR4-independent cytokine-inducing activity in human mononuclear cells."	"http://www.ncbi.nlm.nih.gov/pubmed/21666273"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00877192982456"	"0.0219298245614"	"0.0745614035088"	"228"	"11.0476190476"	"BMC Bioinformatics"	"Fruehwirth R, Mani DR, Pyne S"		"ABSTRACT: BACKGROUND: Clustering is a widely applicable pattern recognition method for discovering groups of similar observations in data. While there are a large variety of clustering algorithms, very few of these can enforce constraints on the variation of attributes for data points included in a given cluster. In particular, a clustering algorithm that can limit variation within a cluster according to that clusters position (centroid location) can produce effective and optimal results in many important applications ranging from clustering of silicon pixels or calorimeter cells in high-energy physics to label-free liquid chromatography based mass spectrometry (LC-MS) data analysis in proteomics and metabolomics. RESULTS: We present MEDEA (M-Estimator with DEterministic Annealing), an M-estimator based, new unsupervised algorithm that is designed to enforce position-specific constraints on variance during the clustering process. The utility of MEDEA is demonstrated by applying it to the problem of peak matching--identifying the common LC-MS peaks across multiple samples--in proteomic biomarker discovery. Using real-life datasets, we show that MEDEA not only outperforms current state-of-the-art model-based clustering methods, but also results in an implementation that is significantly more efficient, and hence applicable to much larger LC-MS data sets. CONCLUSIONS: MEDEA is an effective and efficient solution to the problem of peak matching in label-free LC-MS data. The program implementing the MEDEA algorithm, including datasets, clustering results, and supplementary information is available from the author website at http://wwwhephy.oeaw.ac.at/u3w/f/fru/www/medea/."	"http://www.ncbi.nlm.nih.gov/pubmed/21884583"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0034965034965"	"0.0384615384615"	"0.101398601399"	"286"	"10.5925925926"	"BMC Bioinformatics"	"Gao S, Wang X"		"ABSTRACT: BACKGROUND: Bayesian Network (BN) is a powerful approach to reconstructing genetic regulatory networks from gene expression data. However, expression data by itself suffers from high noise and lack of power. Incorporating prior biological knowledge can improve the performance. As each type of prior knowledge on its own may be incomplete or limited by quality issues, integrating multiple sources of prior knowledge to utilize their consensus is desirable. RESULTS: We introduce a new method to incorporate the quantitative information from multiple sources of prior knowledge. It first uses the Naive Bayesian classifier to assess the likelihood of functional linkage between gene pairs based on prior knowledge. In this study we included co-citation in PubMed and schematic similarity in Gene Ontology annotation. A candidate network edge reservoir is then created in which the copy number of each edge is proportional to the estimated likelihood of linkage between the two corresponding genes. In network simulation the Markov Chain Monte Carlo sampling algorithm is adopted, and samples from this reservoir at each iteration to generate new candidate networks. We evaluated the new algorithm using both simulated and real gene expression data including that from a yeast cell cycle and a mouse pancreas development/growth study. Incorporating prior knowledge led to a ~2 fold increase in the number of known transcription regulations recovered, without significant change in false positive rate. In contrast, without the prior knowledge BN modeling is not always better than a random selection, demonstrating the necessity in network modeling to supplement the gene expression data with additional information. CONCLUSION: our new development provides a statistical means to utilize the quantitative information in prior biological knowledge in the BN modeling of gene expression data, which significantly improves the performance."	"http://www.ncbi.nlm.nih.gov/pubmed/21884587"
-"unk"	"unknown"	"unknown"	"unknown"	"0.00606060606061"	"0.00606060606061"	"0.0424242424242"	"165"	"12.6923076923"	"Glycobiology"	"Garcia VP, Bermejo J, Rubio S, Quintana J, Estevez F"	"Departamento de Quimica de Productos Naturales y Biotecnologia, Instituto de Productos Naturales y Agrobiologia de Canarias, La Laguna, Tenerife, Canary Islands. vpergarw@gobiernodecanarias.org"	"Four new steroidal glycosides such as 3-O-6-deoxy-3-O-methyl-beta-D-allopyranosyl-(1 --> 4)-beta-D-oleandropyranosyl-(1 --> 4)-beta-D-cymaropyranosyl-(1 --> 4)-beta-D-cymaropyranoside-12-beta-tigloyl-14-beta-hydroxy-17-beta-pregnan e (1), 3-O-6-deoxy-3-O-methyl-beta-D-allopyranosyl-(1 --> 4)-beta-D-oleandropyranosyl-(1 --> 4)-beta-D-cymaropyranosyl-(1 --> 4)-beta-D-cymaropyranoside-12-beta-(2-amino)-benzoyl-14-beta-hydroxy-17-b eta-pregnane (2), 3-O-6-deoxy-3-O-methyl-beta-D-allopyranosyl-(1 --> 4)-beta-D-oleandropyranosyl-(1 --> 4)-beta-D-cymaropyranosyl-(1 --> 4)-beta-D-cymaropyranoside-12-beta-14-beta-dihydroxy-17-alpha-pregnane (3) and 3-O-6-deoxy-3-O-methyl-beta-D-allopyranosyl-(1 --> 4)-beta-D-oleandropyranosyl-(1 --> 4)-beta-D-cymaropyranosyl-(1 --> 4)-beta-D-cymaropyranoside-12-beta-14-beta-dihydroxy-17-beta-pregnane (4) were isolated from the aerial parts of Ceropegia fusca Bolle (Asclepiadaceae), a crassulacean acid metabolism plant, an endemic species to the Canary Islands that has been used in traditional medicine as a cicatrizant, vulnerary and disinfectant. The dichloromethane extract exhibited significant cytostatic activity against HL-60, A-431 and SK-MEL-1 cells, human leukemic, epidermoid carcinoma and melanoma cells, respectively. As shown in Table I, compounds 1 and 2 showed very similar IC(50) values. The acetylation of 1 to give the diacetate 5 increases 5-fold the cytotoxicity against HL-60 cells. Compounds 3 and 4 did not show cytotoxicity at the assayed concentrations. With respect to the compounds containing only the steroid ring (6-8), the presence of a charged O-amino-benzoyl but not a tigloyl group improved the cytotoxicity."	"http://www.ncbi.nlm.nih.gov/pubmed/21147757"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0049504950495"	"0.019801980198"	"0.0940594059406"	"202"	"7.1724137931"	"Bioinformatics"	"Gavranovic H, Chauve C, Salse J, Tannier E"	"Faculty of Natural Sciences, University of Sarajevo, Bosnia and Herzegovina. haris.gavranovic@gmail.com"	"MOTIVATION: Ancestral genomes provide a better way to understand the structural evolution of genomes than the simple comparison of extant genomes. Most ancestral genome reconstruction methods rely on universal markers, that is, homologous families of DNA segments present in exactly one exemplar in every considered species. Complex histories of genes or other markers, undergoing duplications and losses, are rarely taken into account. It follows that some ancestors are inaccessible by these methods, such as the proto-monocotyledon whose evolution involved massive gene loss following a whole genome duplication. RESULTS: We propose a mapping approach based on the combinatorial notion of sandwich consecutive ones matrix, which explicitly takes gene losses into account. We introduce combinatorial optimization problems related to this concept, and propose a heuristic solver and a lower bound on the optimal solution. We use these results to propose a configuration for the proto-chromosomes of the monocot ancestor, and study the accuracy of this configuration. We also use our method to reconstruct the ancestral boreoeutherian genomes, which illustrates that the framework we propose is not specific to plant paleogenomics but is adapted to reconstruct any ancestral genome from extant genomes with heterogeneous marker content. AVAILABILITY: Upon request to the authors. CONTACT: haris.gavranovic@gmail.com; eric.tannier@inria.fr."	"http://www.ncbi.nlm.nih.gov/pubmed/21685079"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0"	"0.0"	"10"	"3.33333333333"	"PLoS Computational Biology"	"Gemp IM, Carthew RW, Hilgenfeldt S"		"[This corrects the article on p. e1002115 in vol. 7.]."	"http://www.ncbi.nlm.nih.gov/pubmed/21857815"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0133928571429"	"0.00892857142857"	"0.0758928571429"	"224"	"11.7894736842"	"Glycobiology"	"Goetze AM, Liu YD, Arroll T, Chu L, Flynn GC"	"From the department of Process and Product Development, Amgen, Inc, Thousand Oaks, CA 91320."	"Glycation of IgG can result from incubation with a reducing sugar in vitro or during circulation in vivo. Upon injection of a recombinantly produced human therapeutic IgG into humans, changes in the glycation levels could be observed as a function of circulation time. Mass changes on the individual IgG polypeptide chains as the results of glycation were determined using reversed phase liquid chromatography/mass spectrometry. Changes to the light and heavy chains were low but easily detectable at 0.00092 and 0.0021 glucose additions per chain per day, respectively. Levels of glycation found on the Fc portion of IgG isolated from healthy subjects, using a similar analytical approach, were on average 0.045 glucose molecules per fragment. In vivo glycation rates could be approximated in vitro by modeling the physiological glycation reaction with a simplified incubation containing physiological glucose concentrations, pH and temperature but with a high concentration of a single purified IgG. To test the impact of glycation on IgG function, highly glycated IgG1 and IgG2 were prepared containing on average 42-49 glucose molecules per IgG. Binding to FcgammaIIIa receptors, FcRn, or protein A were similar or identical to the non-glycated IgG controls. Although the modifications were well distributed throughout the protein sequence, and at high enough levels to affect the elution position by size exclusion chromatography, no changes in the tested Fc functions were observed."	"http://www.ncbi.nlm.nih.gov/pubmed/21930650"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00704225352113"	"0.00704225352113"	"0.112676056338"	"142"	"10.9230769231"	"Molecular Biology and Evolution"	"Gray VE, Kumar S"	"Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University."	"Posttranslational modifications (PTMs) are chemical alterations that are critical to protein conformation and activation states. Despite their functional importance and reported involvement in many diseases, evolutionary analyses have produced enigmatic results because only weak or no selective pressures have been attributed to many types of PTMs. In a large-scale analysis of 16,836 PTM positions from 4,484 human proteins, we find that positions harboring PTMs show evidence of higher purifying selection in 70% of the phosphorylated and N-linked glycosylated proteins. The purifying selection is up to 42% more severe at PTM residues as compared with the corresponding unmodified amino acids. These results establish extensive selective pressures in the long-term history of positions that experience PTMs in the human proteins. Our findings will enhance our understanding of the historical function of PTMs over time and help in predicting PTM positions by using evolutionary comparisons."	"http://www.ncbi.nlm.nih.gov/pubmed/21273632"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0144230769231"	"0.100961538462"	"208"	"9.04347826087"	"BMC Bioinformatics"	"Gruel J, Leborgne M, Lemeur N, Theret N"		"ABSTRACT: BACKGROUND: Regulation of gene expression plays a pivotal role in cellular functions. However, understanding the dynamics of transcription remains a challenging task. A host of computational approaches have been developed to identify regulatory motifs, mainly based on the recognition of DNA sequences for transcription factor binding sites. Recent integration of additional data from genomic analyses or phylogenetic footprinting has significantly improved these methods. RESULTS: Here, we propose a different approach based on the compilation of Simple Shared Motifs (SSM), groups of sequences defined by their length and similarity and present in conserved sequences of gene promoters. We developed an original algorithm to search and count SSM in pairs of genes. An exceptional number of SSM is considered as a common regulatory pattern. The SSM approach is applied to a sample set of genes and validated using functional gene-set enrichment analyses. We demonstrate that the SSM approach selects genes that are over-represented in specific biological categories (Ontology and Pathways) and are enriched in co-expressed genes. Finally we show that genes co-expressed in the same tissue or involved in the same biological pathway have increased SSM values. CONCLUSIONS: Using unbiased clustering of genes, Simple Shared Motifs analysis constitutes an original contribution to provide a clearer definition of expression networks."	"http://www.ncbi.nlm.nih.gov/pubmed/21910886"
-"unk"	"unknown"	"unknown"	"unknown"	"0.00452488687783"	"0.0180995475113"	"0.0769230769231"	"221"	"13.0"	"Molecular Biology and Evolution"	"Guillemin Y, Cornut-Thibaut A, Gillet G, Penin F, Aouacheria A"	"From the."	"Insertions or deletions (indels) of amino acids residues have been recognized as an important source of genetic and structural divergence between paralogous Bcl-2 family members. However, these signature sequences have not so far been extensively investigated amongst orthologous Bcl-2 family proteins. Bcl2l10 is an anti-apoptotic member of the Bcl-2 family that has evolved rapidly throughout the vertebrate lineage, and which shows conserved abundant expression in eggs and oocytes. In this paper, we have unraveled two major sites of divergence between human Bcl2l10 and its vertebrate homologues. The first one provides length variation at the N-terminus (before the BH4 domain), and the second one is located between the predicted alpha5-alpha6 pore-forming helices, providing an unprecedented case in the superfamily of helix-bundled pore-forming proteins. These two particular indels were studied phylogenetically, and through biochemical and cell biological techniques, including truncation and site-directed mutagenesis. While deletion of the N-terminal extension had no significant functional impact in HeLa cells, our results suggest that the human Bcl2l10 protein evolved a calcium-binding motif in its alpha5-alpha6 interhelical region by acquiring critical negatively charged residues. Considering the reliance of female eggs on calcium-dependent proteins and calcium-regulated processes, and the exceptional longevity of oocytes in the primate lineage, we propose that this micro-structural variation may be an adaptive feature associated with high maternal expression of this Bcl-2 family member."	"http://www.ncbi.nlm.nih.gov/pubmed/21705382"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0652173913043"	"0.0434782608696"	"46"	"15.3333333333"	"Nature Genetics"	"Haigis KM, Sweet-Cordero A"		"Expression of oncogenes in otherwise normal cells often leads to the activation of anti-oncogenic pathways through a poorly understood process described as oncogenic stress. A new study implicates the Jnk pathway signaling in the activation of p53 in response to both K-Ras and Neu oncogene expression."	"http://www.ncbi.nlm.nih.gov/pubmed/21350495"
-"unk"	"unknown"	"unknown"	"unknown"	"0.00444444444444"	"0.0222222222222"	"0.0622222222222"	"225"	"15.0"	"BMC Bioinformatics"	"Herman D, Ochoa D, Juan D, Lopez D, Valencia A, Pazos F"		"ABSTRACT: BACKGROUND: The prediction and study of protein interactions and functional relationships based on similarity of phylogenetic trees, exemplified by the mirrortree and related methodologies, is being widely used. Although dependence between the performance of these methods and the set of organisms used to build the trees was suspected, so far nobody assessed it in an exhaustive way, and, in general, previous works used as many organisms as possible. In this work we asses the effect of using different sets of organism (chosen according with various phylogenetic criteria) on the performance of this methodology in detecting protein interactions of different nature. RESULTS: We show that the performance of three mirrortree-related methodologies depends on the set of organisms used for building the trees, and it is not always directly related to the number of organisms in a simple way. Certain subsets of organisms seem to be more suitable for the predictions of certain types of interactions. This relationship between type of interaction and optimal set of organism for detecting them makes sense in the light of the phylogenetic distribution of the organisms and the nature of the interactions. CONCLUSIONS: In order to obtain an optimal performance when predicting protein interactions, it is recommended to use different sets of organisms depending on the available computational resources and data, as well as the type of interactions of interest."	"http://www.ncbi.nlm.nih.gov/pubmed/21910884"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0285714285714"	"0.0190476190476"	"0.0761904761905"	"105"	"15.1428571429"	"Nature Genetics"	"Holm H, Gudbjartsson DF, Sulem P, Masson G, Helgadottir HT, Zanon C, Magnusson OT, Helgason A, Saemundsdottir J, Gylfason A, Stefansdottir H, Gretarsdottir S, Matthiasson SE, Thorgeirsson GM, Jonasdottir A, Sigurdsson A, Stefansson H, Werge T, Rafnar T, Kiemeney LA, Parvez B, Muhammad R, Roden DM, Darbar D, Thorleifsson G, Walters GB, Kong A, Thorsteinsdottir U, Arnar DO, Stefansson K"	"deCODE Genetics, Sturlugata 8, Reykjavik, Iceland. hilma.holm@decode.is"	"Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5 x 10(2). We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C>T but is approximately 50% for carriers of the c.2161C>T variant."	"http://www.ncbi.nlm.nih.gov/pubmed/21378987"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00558659217877"	"0.00558659217877"	"0.0391061452514"	"179"	"13.8461538462"	"Glycobiology"	"Hreggvidsson GO, Dobruchowska JM, Fridjonsson OH, Jonsson JO, Gerwig GJ, Aevarsson A, Kristjansson JK, Curti D, Redgwell RR, Hansen CE, Kamerling JP, Debeche-Boukhit T"	"Matis Ltd, 113 Reykjavik, Iceland. gudmundur.o.hreggvidsson@matis.is"	"Over the years several beta-glucan transferases from yeast and fungi have been reported, but enzymes with such an activity from bacteria have not been characterized so far. In this work, we describe the cloning and expression of genes encoding beta-glucosyltransferase domains of glycosyl hydrolase family GH17 from three species of proteobacteria: Pseudomonas aeruginosa PAO1, P. putida KT2440 and Azotobacter vinelandii ATCC BAA-1303. The encoded enzymes of these GH17 domains turned out to have a non-Leloir trans-beta-glucosylation activity, as they do not use activated nucleotide sugar as donor, but transfer a glycosyl group from a beta-glucan donor to a beta-glucan acceptor. More particularly, the activity of the three recombinant enzymes on linear (beta1 --> 3)-linked gluco-oligosaccharides (Lam-Glc(4-9)) and their corresponding alditols (Lam-Glc(4-9)-ol) was studied. Detailed structural analysis, based on thin-layer chromatography, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, electrospray ionization mass spectrometry, and 1D/2D (1)H and (13)C nuclear magnetic resonance data, revealed diverse product spectra. Depending on the enzyme used, besides (beta1 --> 3)-elongation activity, (beta1 --> 4)- or (beta1 --> 6)-elongation, or (beta1 --> 6)-branching activities were also detected."	"http://www.ncbi.nlm.nih.gov/pubmed/21030539"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00303951367781"	"0.0212765957447"	"0.118541033435"	"329"	"11.3793103448"	"BMC Bioinformatics"	"Hu T, Sinnott-Armstrong NA, Kiralis JW, Andrew AS, Karagas MR, Moore JH"		"ABSTRACT: BACKGROUND: Epistasis is recognized ubiquitous in the genetic architecture of complex traits such as disease susceptibility. Experimental studies in model organisms have revealed extensive evidence of biological interactions among genes. Meanwhile, statistical and computational studies in human populations have suggested non-additive effects of genetic variation on complex traits. Although these studies form a baseline for understanding the genetic architecture of complex traits, to date they have only considered interactions among a small number of genetic variants. Our goal here is to use network science to determine the extent to which non-additive interactions exist beyond small subsets of genetic variants. We infer statistical epistasis networks to characterize the global space of pairwise interactions among approximately 1500 Single Nucleotide Polymorphisms (SNPs) spanning nearly 500 cancer susceptibility genes in a large population-based study of bladder cancer. Results: The statistical epistasis network was built by linking pairs of SNPs if their pairwise interactions were stronger than a systematically derived threshold. Its topology clearly differentiated this real-data network from networks obtained from permutations of the same data under the null hypothesis that no association exists between genotype and phenotype. The network had a signiffcantly higher number of hub SNPs and, interestingly, these hub SNPs were not necessarily with high main effects. The network had a largest connected component of 39 SNPs that was absent in any other permuted-data networks. In addition, the vertex degrees of this network were distinctively found following an approximate power-law distribution and its topology appeared scale-free. Conclusions: In contrast to many existing techniques focusing on high main-effect SNPs or models of several interating SNPs, our network approach characterized a global picture of gene-gene interactions in a population-based genetic data. The network was built using pairwise interactions, and its distinctive network topology and large connected components indicated joint effects in a large set of SNPs. Our observations suggested that this particular statistical epistasis network captured important features of the genetic architecture of bladder cancer that have not been described previously."	"http://www.ncbi.nlm.nih.gov/pubmed/21910885"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0113636363636"	"0.0189393939394"	"0.0795454545455"	"264"	"8.70967741935"	"BMC Bioinformatics"	"Hu Y, Flockhart I, Vinayagam A, Bergwitz C, Berger B, Perrimon N, Mohr SE"		"ABSTRACT: BACKGROUND: Mapping of orthologous genes among species serves an important role in functional genomics by allowing researchers to develop hypotheses about gene function in one species based on what is known about the functions of orthologs in other species. Several tools for predicting orthologous gene relationships are available. However, these tools can give different results and identification of predicted orthologs is not always straightforward. RESULTS: We report a simple but effective tool, the Drosophila RNAi Screening Center Integrative Ortholog Prediction Tool (DIOPT; http://www.flyrnai.org/diopt), for rapid identification of orthologs. DIOPT integrates existing approaches, facilitating rapid identification of orthologs among human, mouse, zebrafish, C. elegans, Drosophila, and S. cerevisiae. As compared to individual tools, DIOPT shows increased sensitivity with only a modest decrease in specificity. Moreover, flexibility built into the DIOPT graphical user interface allows researchers with different goals to appropriately cast a wide net or limit results to highest confidence predictions. DIOPT also displays protein and domain alignments, including percent amino acid identity, for predicted ortholog pairs. This helps users identify the most appropriate matches among multiple possible orthologs. To facilitate using model organisms for functional analysis of human disease-associated genes, we used DIOPT to predict high-confidence orthologs of disease genes in Online Mendelian Inheritance in Man (OMIM) and genes in genome-wide association study (GWAS) data sets. The results are accessible through the DIOPT diseases and traits query tool (DIOPT-DIST; http://www.flyrnai.org/diopt-dist). CONCLUSION: DIOPT and DIOPT-DIST are useful resources for researchers working with model organisms, especially those who are interested in exploiting model organisms such as Drosophila to study the functions of human disease genes."	"http://www.ncbi.nlm.nih.gov/pubmed/21880147"
-"unk"	"unknown"	"unknown"	"unknown"	"0.00970873786408"	"0.0242718446602"	"0.0436893203883"	"206"	"22.8888888889"	"PLoS One"	"Hussain AR, Uddin S, Bu R, Khan OS, Ahmed SO, Ahmed M, Al-Kuraya KS"	"Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia."	"BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4, 5-trihydroxystilbene), a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL) cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS). Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway."	"http://www.ncbi.nlm.nih.gov/pubmed/21931821"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0059880239521"	"0.0119760479042"	"0.107784431138"	"167"	"7.47826086957"	"Bioinformatics"	"Isci S, Ozturk C, Jones J, Otu HH"	"Bogazici University, Institute of Biomedical Engineering, 34342, Istanbul, Turkey."	"MOTIVATION: Most current approaches to high-throughput biological data (HTBD) analysis either perform individual gene/protein analysis or, gene/protein set enrichment analysis for a list of biologically relevant molecules. Bayesian Networks (BNs) capture linear and non-linear interactions, handle stochastic events accounting for noise, and focus on local interactions, which can be related to causal inference. Here, we describe for the first time an algorithm that models biological pathways as BNs and identifies pathways that best explain given HTBD by scoring fitness of each network. RESULTS: Proposed method takes into account the connectivity and relatedness between nodes of the pathway through factoring pathway topology in its model. Our simulations using synthetic data demonstrated robustness of our approach. We tested proposed method, Bayesian Pathway Analysis (BPA), on human microarray data regarding renal cell carcinoma (RCC) and compared our results with gene set enrichment analysis. BPA was able to find broader and more specific pathways related to RCC. AVAILABILITY: Accompanying BPA software (BPAS) package is freely available for academic use at http://bumil.boun.edu.tr/bpa."	"http://www.ncbi.nlm.nih.gov/pubmed/21551144"
-"unk"	"unknown"	"unknown"	"unknown"	"0.01953125"	"0.0078125"	"0.0703125"	"256"	"7.87878787879"	"PLoS One"	"Jewkes R, Sikweyiya Y, Morrell R, Dunkle K"	"School of Public Health, University of the Witwatersrand, Johannesburg, South Africa."	"OBJECTIVE: To investigate the associations between intimate partner violence, rape and HIV among South African men. DESIGN: Cross-sectional study involving a randomly-selected sample of men. METHODS: We tested hypotheses that perpetration of physical intimate partner violence and rape were associated with prevalent HIV infections in a cross-sectional household study of 1229 South African men aged 18-49. Violence perpetration was elicited in response to a questionnaire administered using an Audio-enhanced Personal Digital Assistant and blood samples were tested for HIV. A multivariable logistic regression model was built to identify factors associated with HIV. RESULTS: 18.3% of men had HIV. 29.6% (358/1211) of men disclosed rape perpetration, 5.2% (63/1208) rape in the past year and 30.7% (362/1180) of had been physically violent towards an intimate partner more than once. Overall rape perpetration was not associated with HIV. The model of factors associated with having HIV showed men under 25 years who had been physically violent towards partners were more likely to have HIV than men under 25 who had not (aOR 2.08 95% CI 1.07-4.06, p = 0.03). We failed to detect any association in older men. CONCLUSIONS: Perpetration of physical IPV is associated with HIV sero-prevalence in young men, after adjusting for other risk factors. This contributes to our understanding of why women who experience violence have a higher HIV prevalence. Rape perpetration was not associated, but the HIV prevalence among men who had raped was very high. HIV prevention in young men must seek to change ideals of masculinity in which male partner violence is rooted."	"http://www.ncbi.nlm.nih.gov/pubmed/21935392"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0"	"0.0"	"32"	"4.57142857143"	"Immunity"	"Jonjic S, Trsan T"	"Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. jstipan@medri.hr"	"NK cells play a key role in the control of ectromelia virus. In this issue of Immunity, Fang et al. (2011) demonstrate that the deletion of CD94 abolishes resistance to mousepox infection."	"http://www.ncbi.nlm.nih.gov/pubmed/21511179"
-"unk"	"unknown"	"unknown"	"unknown"	"0.00961538461538"	"0.0144230769231"	"0.100961538462"	"208"	"8.44"	"BMC Bioinformatics"	"Jung SK, McDonald K"		"ABSTRACT: BACKGROUND: Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. RESULTS: The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. CONCLUSION: Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net."	"http://www.ncbi.nlm.nih.gov/pubmed/21846353"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0140845070423"	"0.0281690140845"	"71"	"10.1428571429"	"Nature Genetics"	"Kalay E, Yigit G, Aslan Y, Brown KE, Pohl E, Bicknell LS, Kayserili H, Li Y, Tuysuz B, Nurnberg G, Kiess W, Koegl M, Baessmann I, Buruk K, Toraman B, Kayipmaz S, Kul S, Ikbal M, Turner DJ, Taylor MS, Aerts J, Scott C, Milstein K, Dollfus H, Wieczorek D, Brunner HG, Hurles M, Jackson AP, Rauch A, Nurnberg P, Karaguzel A, Wollnik B"	"Department of Medical Biology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. ersankalay@hotmail.com"	"Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation."	"http://www.ncbi.nlm.nih.gov/pubmed/21131973"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00769230769231"	"0.00769230769231"	"0.0615384615385"	"130"	"4.86206896552"	"Bioinformatics"	"Kalyanaraman A, Cannon WR, Latt B, Baxter DJ"	"School of Electrical Engineering and Computer Science, Washington State University, Pullman, WA 99164-2752."	"SUMMARY: A MapReduce based implementation called MR-MSPolygraph for parallelizing peptide identification from mass spectrometry data is presented. The underlying serial method, MSPoly-graph, uses a novel hybrid approach to match an experimental spectrum against a combination of a protein sequence database and a spectral library. Our MapReduce implementation can run on any Hadoop cluster environment. Experimental results demonstrate that, relative to the serial version, MR-MSPolygraph reduces the time to solution from weeks to hours, for processing tens of thousands of experimental spectra. Speedup and other related performance studies are also reported on a 400-core Hadoop cluster using spectral data sets from environmental microbial communities as inputs. AVAILABILITY: The source code along with user documentation are available on http://compbio.eecs.wsu.edu/MR-MSPolygraph. CONTACT: ananth@eecs.wsu.edu regarding the MapReduce implementation; and william.cannon@pnnl.gov regarding the serial hybrid implementation."	"http://www.ncbi.nlm.nih.gov/pubmed/21926122"
-1	"unknown"	"unknown"	"unknown"	"0.0159362549801"	"0.0159362549801"	"0.0557768924303"	"251"	"8.22580645161"	"Database(Oxford)"	"Katz LS, Humphrey JC, Conley AB, Nelakuditi V, Kislyuk AO, Agrawal S, Jayaraman P, Harcourt BH, Olsen-Rasmussen MA, Frace M, Sharma NV, Mayer LW, Jordan IK"	"School of Biology, Georgia Institute of Technology."	"Neisseria meningitidis is an important pathogen, causing life-threatening diseases including meningitis, septicemia and in some cases pneumonia. Genomic studies hold great promise for N. meningitidis research, but substantial database resources are needed to deal with the wealth of information that comes with completely sequenced and annotated genomes. To address this need, we developed Neisseria Base (NBase), a comparative genomics database and genome browser that houses and displays publicly available N. meningitidis genomes. In addition to existing N. meningitidis genome sequences, we sequenced and annotated 19 new genomes using 454 pyrosequencing and the CG-Pipeline genome analysis tool. In total, NBase hosts 27 complete N. meningitidis genome sequences along with their associated annotations. The NBase platform is designed to be scalable, via the underlying database schema and modular code architecture, such that it can readily incorporate new genomes and their associated annotations. The front page of NBase provides user access to these genomes through searching, browsing and downloading. NBase search utility includes BLAST-based sequence similarity searches along with a variety of semantic search options. All genomes can be browsed using a modified version of the GBrowse platform, and a plethora of information on each gene can be viewed using a customized details page. NBase also has a whole-genome comparison tool that yields single-nucleotide polymorphism differences between two user-defined groups of genomes. Using the virulent ST-11 lineage as an example, we demonstrate how this comparative genomics utility can be used to identify novel genomic markers for molecular profiling of N. meningitidis. Database URL: http://nbase.biology.gatech.edu."	"http://www.ncbi.nlm.nih.gov/pubmed/21930505"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0354330708661"	"0.11811023622"	"254"	"12.1428571429"	"Molecular Biology and Evolution"	"Keebaugh ES, Schlenke TA"	"institution: Emory University."	"Drosophila melanogaster has long been used as a model for the molecular genetics of innate immunity. Such work has uncovered several immune receptors that recognize bacterial and fungal pathogens by binding unique components of their cell walls and membranes. Drosophila also act as hosts to metazoan pathogens such as parasitic wasps, which can infect a majority of individuals in natural populations, but many aspects of their immune responses against these more closely related pathogens are poorly understood. Here, we present data describing the transcriptional induction and molecular evolution of a candidate Drosophila anti-wasp immunity gene, lectin-24A. Lectin-24A has a secretion signal sequence and its lectin domain suggests a function in sugar group binding. Transcript levels of lectin-24A were induced significantly stronger and faster following wasp attack than following wounding or bacterial infection, demonstrating lectin-24A is not a general stress response or defense response gene, but is instead part of a specific response against wasps. The major site of lectin-24A transcript production is the fat body, the main humoral immune tissue of flies. Interestingly, lectin-24A is a new gene of the D. melanogaster/D. simulans clade, displaying very little homology to any other Drosophila lectins. Population genetic analyses of lectin-24A DNA sequence data from African and North American populations of D. melanogaster and D. simulans revealed gene length polymorphisms segregating at high frequencies, as well as strong evidence of repeated and recent selective sweeps. Thus, lectin-24A is a rapidly evolving new gene that has seemingly developed functional importance for fly resistance against infection by parasitic wasps."	"http://www.ncbi.nlm.nih.gov/pubmed/21873297"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0297619047619"	"0.0238095238095"	"0.0654761904762"	"168"	"8.2380952381"	"BMC Bioinformatics"	"Kim H, Bi Y, Pal S, Gupta R, Davuluri RV"		"ABSTRACT: BACKGROUND: mRNA-Seq technology has revolutionized the field of transcriptomics for identification and quantification of gene transcripts not only at gene level but also at isoform level. Estimating the expression levels of transcript isoforms from mRNA-Seq data is a challenging problem due to the presence of constitutive exons. RESULTS: We propose a novel algorithm (IsoformEx) that employs weighted non-negative least squares estimation method to estimate the expression levels of transcript isoforms. Validations based on in silico simulation of mRNA-Seq and qRT-PCR experiments with real mRNA-Seq data showed that IsoformEx could accurately estimate transcript expression levels. In comparisons with published methods, the transcript expression levels estimated by IsoformEx showed higher correlation with known transcript expression levels from simulated mRNA-Seq data, and higher agreement with qRT-PCR measurements of specific transcripts for real mRNA-Seq data. CONCLUSIONS: IsoformEx is a fast and accurate algorithm to estimate transcript expression levels and gene expression levels, which takes into account short exons and alternative exons with a weighting scheme. The software is available at http://bioinformatics.wistar.upenn.edu/isoformex."	"http://www.ncbi.nlm.nih.gov/pubmed/21794104"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0106382978723"	"0.031914893617"	"0.0691489361702"	"188"	"11.0588235294"	"PLoS One"	"Kleynhans L, Du Plessis N, Black GF, Loxton AG, Kidd M, van Helden PD, Walzl G, Ronacher K"	"Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa."	"Most individuals latently infected with Mycobacterium tuberculosis (M.tb) contain the infection by a balance of effector and regulatory immune responses. This balance can be influenced by steroid hormones such as glucocorticoids. The widely used contraceptive medroxyprogesterone acetate (MPA) possesses glucocorticoid activity. We investigated the effect of this hormone on immune responses to BCG in household contacts of active TB patients. Multiplex bead array analysis revealed that MPA demonstrated both glucocorticoid and progestogenic properties at saturating and pharmacological concentrations in peripheral blood mononuclear cells (PBMCs) and suppressed antigen specific cytokine production. Furthermore we showed that PBMCs from women using MPA produced significantly lower levels of IL-1alpha, IL-12p40, IL-10, IL-13 and G-CSF in response to BCG which corresponded with lower numbers of circulating monocytes observed in these women. Our research study is the first to show that MPA impacts on infections outside the genital tract due to a systemic effect on immune function. Therefore MPA use could alter susceptibility to TB, TB disease severity as well as change the efficacy of new BCG-based vaccines, especially prime-boost vaccine strategies which may be administered to adult or adolescent women in the future."	"http://www.ncbi.nlm.nih.gov/pubmed/21931790"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0191082802548"	"0.0700636942675"	"157"	"5.25806451613"	"Bioinformatics"	"Koren S, Treangen TJ, Pop M"	"Department of Computer Science, University of Maryland, College Park, MD 20742."	"MOTIVATION: Sequencing projects increasingly target samples from non-clonal sources. In particular, metagenomics has enabled scientists to begin to characterize the structure of microbial communities. The software tools developed for assembling and analyzing sequencing data for clonal organisms are, however, unable to adequately process data derived from non-clonal sources. RESULTS: We present a new scaffolder, Bambus 2 to address some of the challenges encountered when analyzing metagenomes. Our approach relies on a combination of a novel method for detecting genomic repeats and algorithms that analyze assembly graphs to identify biologically meaningful genomic variants. We compare our software to current assemblers using simulated and real data. We demonstrate that the repeat detection algorithms have higher sensitivity than current approaches without sacrificing specificity. In metagenomic datasets, the scaffolder avoids false joins between distantly related organisms while obtaining long-range contiguity. Bambus 2 represents a first step towards automated metagenomic assembly. AVAILABILITY: Bambus 2 is open-source and available from http://amos.sf.net. CONTACT: mpop@umiacs.umd.edu."	"http://www.ncbi.nlm.nih.gov/pubmed/21926123"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0123966942149"	"0.0247933884298"	"0.123966942149"	"242"	"14.2352941176"	"Molecular Biology and Evolution"	"Kumar S, Filipski AJ, Battistuzzi FU, Kosakovsky Pond SL, Tamura K"	"Center for Evolutionary Medicine and Informatics, Biodesign Institute."	"Phylogenomics refers to the inference of historical relationships among species using genome-scale sequence data and to the use of phylogenetic analysis to infer protein function in multigene families. With rapidly decreasing sequencing costs, phylogenomics is becoming synonymous with evolutionary analysis of genome-scale and taxonomically densely sampled datasets. In phylogenetic inference applications, this translates into very large datasets that yield evolutionary and functional inferences with extremely small variances and high statistical confidence (P-value). However, reports of highly significant P-values are increasing even for contrasting phylogenetic hypotheses depending on the evolutionary model and inference method used, making it difficult to establish true relationships. We argue that the assessment of the robustness of results to biological factors, that may systematically mislead (bias) the outcomes of statistical estimation, will be a key to avoiding incorrect phylogenomic inferences. In fact, there is a need for increased emphasis on the magnitude of differences (effect sizes), in addition to the P-values of the statistical test of the null hypothesis. On the other hand, the amount of sequence data available will likely always remain inadequate for some phylogenomic applications, e.g., those involving episodic positive selection at individual codon positions and in specific lineages. Again, a focus on effect size and biological relevance, rather than the P-value, may be warranted. Here we present a theoretical overview and discuss practical aspects of the interplay between effect sizes, bias, and P-values as it relates to the statistical inference of evolutionary truth in phylogenomics."	"http://www.ncbi.nlm.nih.gov/pubmed/21873298"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00581395348837"	"0.0116279069767"	"0.116279069767"	"172"	"13.2307692308"	"PLoS Computational Biology"	"Lages M, Heron S"	"School of Psychology, University of Glasgow, Glasgow, Scotland."	"It is shown that existing processing schemes of 3D motion perception such as interocular velocity difference, changing disparity over time, as well as joint encoding of motion and disparity, do not offer a general solution to the inverse optics problem of local binocular 3D motion. Instead we suggest that local velocity constraints in combination with binocular disparity and other depth cues provide a more flexible framework for the solution of the inverse problem. In the context of the aperture problem we derive predictions from two plausible default strategies: (1) the vector normal prefers slow motion in 3D whereas (2) the cyclopean average is based on slow motion in 2D. Predicting perceived motion directions for ambiguous line motion provides an opportunity to distinguish between these strategies of 3D motion processing. Our theoretical results suggest that velocity constraints and disparity from feature tracking are needed to solve the inverse problem of 3D motion perception. It seems plausible that motion and disparity input is processed in parallel and integrated late in the visual processing hierarchy."	"http://www.ncbi.nlm.nih.gov/pubmed/21124957"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0078125"	"0.0234375"	"0.09375"	"256"	"11.1304347826"	"BMC Bioinformatics"	"Ludwig C, Gunther UL"		"ABSTRACT: BACKGROUND: Despite wide-spread use of Nuclear Magnetic Resonance (NMR) in metabolomics for the analysis of biological samples there is a lack of graphically driven, publicly available software to process large one and two-dimensional NMR data sets for statistical analysis. RESULTS: Here we present MetaboLab, a MATLAB based software package that facilitates NMR data processing by providing automated algorithms for processing series of spectra in a reproducible fashion. A graphical user interface provides easy access to all steps of data processing via a script builder to generate MATLAB scripts, providing an option to alter code manually. The analysis of two-dimensional spectra (1H,13C-HSQC spectra) is facilitated by the use of a spectral library derived from publicly available databases which can be extended readily. The software allows to display specific metabolites in small regions of interest where signals can be picked. To facilitate the analysis of series of two-dimensional spectra, different spectra can be overlaid and assignments can be transferred between spectra. The software includes mechanisms to account for overlapping signals by highlighting neighboring and ambiguous assignments. CONCLUSIONS: The MetaboLab software is an integrated software package for NMR data processing and analysis, closely linked to the previously developed NMRLab software. It includes tools for batch processing and gives access to a wealth of algorithms available in the MATLAB framework. Algorithms within MetaboLab help to optimize the flow of metabolomics data preparation for statistical analysis. The combination of an intuitive graphical user interface along with advanced data processing algorithms facilitates the use of MetaboLab in a broader metabolomics context."	"http://www.ncbi.nlm.nih.gov/pubmed/21914187"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0204081632653"	"0.069387755102"	"245"	"12.8947368421"	"Glycobiology"	"Madala NE, Leone MR, Molinaro A, Dubery IA"	"Department of Biochemistry, University of Johannesburg, Kingsway Campus, Johannesburg, South Africa."	"Lipopolysaccharides (LPSs) are major, indispensable cell surface components of Gram-negative bacteria that have diverse roles in bacterial pathogenesis of plants. Environmental strains of Burkholderia cepacia have been described as phytopathogens, growth promotors, biocontrol agents and bioremediation agents. We have previously shown that LPSs from B. cepacia can be recognized as microbe-associated molecular pattern molecules, to elicit defense responses in plants. Recent findings suggest that the lipid A moiety might be partially responsible for LPSs perception. These studies were extended by analysis of the structure and biological activity of the lipid A moiety of LPSs of B. cepacia(.) The full structure was determined by a combination of negative/positive-ion matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) on intact and partially degraded substrates. B. cepacia lipid A was found to contain a tetra- or penta-acylated, 1,4-diphosphorylated, beta-(1-6)-linked D-GlcN disaccharide and further substituted by L-Ara4N in position 4. As primary fatty acids, R-configurated 16:0(3-OH) (amide-linked in 2 and 2) and 14:0(3-OH) (ester-linked in 3 and 3, nonstoichiometric) were identified. A secondary 14:0 was located at position 2. Its biological activity to elicit defense-related responses was subsequently investigated by monitoring the changes in the transcriptome of Arabidopsis thaliana seedlings. Genes found to be upregulated code for proteins involved in signal perception and transduction, transcriptional regulation, defense and stress responses. Furthermore, genes encoding proteins involved in chaperoning, protein interactions and protein degradation were differentially expressed as part of the metabolic reprogramming of cellular activities in support of immunity and defense."	"http://www.ncbi.nlm.nih.gov/pubmed/20943675"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0127118644068"	"0.021186440678"	"0.0550847457627"	"236"	"8.74074074074"	"Molecular Biology and Evolution"	"Martin SH, Wingfield BD, Wingfield MJ, Steenkamp ET"	"Department of Genetics, Forestry and Agricultural Biotechnology Institute, University of Pretoria, South Africa."	"The reproductive genes of fungi, like those of many other organisms, are thought to diversify rapidly. This phenomenon could be associated with the formation of reproductive barriers and speciation. Ascomycetes produce two classes of mating type-specific peptide pheromones. These are required for recognition between the mating types of heterothallic species. Little is known regarding the diversity or the extent of species specificity in pheromone peptides among these fungi. We compared the putative protein-coding DNA sequences of the 2 pheromone classes from 70 species of Ascomycetes. The data set included previously described pheromones and putative pheromones identified from genomic sequences. In addition, pheromone genes from 12 Fusarium species in the Gibberella fujikuroi complex were amplified and sequenced. Pheromones were largely conserved among species in this complex and, therefore, cannot alone account for the reproductive barriers observed between these species. In contrast, pheromone peptides were highly diverse among many other Ascomycetes, with evidence for both positive diversifying selection and relaxed selective constraint. Repeats of the alpha-factor-like pheromone, which occur in tandem arrays of variable copy number, were found to be conserved through purifying selection and not concerted evolution. This implies that sequence specificity may be important for pheromone reception and that interspecific differences may indeed be associated with functional divergence. Our findings also suggest that frequent duplication and loss causes the tandem repeats to experience birth-and-death evolution, which could in fact facilitate interspecific divergence of pheromone peptide sequences."	"http://www.ncbi.nlm.nih.gov/pubmed/21252281"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00574712643678"	"0.00287356321839"	"0.0459770114943"	"348"	"10.5757575758"	"Molecular Biology and Evolution"	"Massa AN, Wanjugi H, Deal KR, OBrien K, You FM, Maiti R, Chan AP, Gu YQ, Luo MC, Anderson OD, Rabinowicz PD, Dvorak J, Devos KM"	"Institute of Plant Breeding, Genetics and Genomics (Department of Crop and Soil Sciences), and Department of Plant Biology, University of Georgia."	"Nine different regions totaling 9.7 Mb of the 4.02 Gb Aegilops tauschii genome were sequenced using the Sanger sequencing technology and compared with orthologous Brachypodium distachyon, Oryza sativa (rice), and Sorghum bicolor (sorghum) genomic sequences. The ancestral gene content in these regions was inferred and used to estimate gene deletion and gene duplication rates along each branch of the phylogenetic tree relating the four species. The total gene number in the extant Ae. tauschii genome was estimated to be 36,371. The gene deletion and gene duplication rates and total gene numbers in the four genomes were used to estimate the total gene number in each node of the phylogenetic tree. The common ancestor of the Brachypodieae and Triticeae lineages was estimated to have had 28,558 genes, and the common ancestor of the Panicoideae, Ehrhartoideae, and Pooideae subfamilies was estimated to have had 27,152 or 28,350 genes, depending on the ancestral gene scenario. Relative to the Brachypodieae and Triticeae common ancestor, the gene number was reduced in B. distachyon by 3,026 genes and increased in Ae. tauschii by 7,813 genes. The sum of gene deletion and gene duplication rates, which reflects the rate of gene synteny loss, was correlated with the rate of structural chromosome rearrangements and was highest in the Ae. tauschii lineage and lowest in the rice lineage. The high rate of gene space evolution in the Ae. tauschii lineage accounts for the fact that, contrary to the expectations, the level of synteny between the phylogenetically more related Ae. tauschii and B. distachyon genomes is similar to the level of synteny between the Ae. tauschii genome and the genomes of the less related rice and sorghum. The ratio of gene duplication to gene deletion rates in these four grass species closely parallels both the total number of genes in a species and the overall genome size. Because the overall genome size is to a large extent a function of the repeated sequence content in a genome, we suggest that the amount and activity of repeated sequences are important factors determining the number of genes in a genome."	"http://www.ncbi.nlm.nih.gov/pubmed/21470968"
 "unk"	"unknown"	"unknown"	"unknown"	"0.004"	"0.004"	"0.112"	"250"	"11.9523809524"	"Bioinformatics"	"Maver A, Peterlin B"	"Department of Obstetrics and Gynecology, Institute of Medical Genetics, University Medical Centre Ljubljana, 3, Slajmerjeva Street, Ljubljana 1000, Slovenia. ales.maver@gmail.com"	"MOTIVATION: Recent abundance of data from studies employing high-throughput technologies to reveal alterations in human disease on genomic, transcriptomic, proteomic and other levels, offer the possibility to integrate this information into a comprehensive picture of molecular events occurring in human disease. Diversity of data originating from these studies presents a methodological obstacle in the integration process, also due to difficulties in choosing the optimal unified denominator that would allow inclusion of variables from various types of studies. We present a novel approach for integration of such multi-origin data based on positions of genetic alterations occurring in human diseases. Parkinsons disease (PD) was chosen as a model for evaluation of our methodology. METHODS: Datasets from various types of studies in PD (linkage, genome-wide association, transcriptomic and proteomic studies) were obtained from online repositories or were extracted from available research papers. Subsequently, human genome assembly was subdivided into 10 kb regions, and significant signals from aforementioned studies were arranged into their corresponding regions according to their genomic position. For each region, rank product values were calculated and significance values were estimated by permuting the original dataset. RESULTS: Altogether, 179 regions (representing 33 contiguous genomic regions) had significant accumulation of signals when P-value cut-off was set at 0.0001. Identified regions with significant accumulation of signals contained 29 plausible candidate genes for PD. In conclusion, we present a novel approach for identification of candidate regions and genes for various human disorders, based on the positional integration of data across various types of omic studies."	"http://www.ncbi.nlm.nih.gov/pubmed/21596793"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0536585365854"	"0.0585365853659"	"205"	"9.7619047619"	"BMC Bioinformatics"	"McCall MN, Irizarry RA"		"ABSTRACT: BACKGROUND: A novel method of microarray preprocessing - Frozen Robust Multi-array Analysis (fRMA) - has recently been developed. This algorithm allows the user to preprocess arrays individually while retaining the advantages of multi-array preprocessing methods. The frozen parameter estimates required by this algorithm are generated using a large database of publicly available arrays. Curation of such a database and creation of the frozen parameter estimates is time-consuming; therefore, fRMA has only been implemented on the most widely used Affymetrix platforms. RESULTS: We present an R package, frmaTools, that allows the user to quickly create his or her own frozen parameter vectors. We describe how this package fits into a preprocessing workflow and explore the size of the training data set needed to generate reliable frozen parameter estimates. This is followed by a discussion of specific situations in which one might wish to create ones own fRMA implementation. For a few specific scenarios, we demonstrate that fRMA performs well even when a large database of arrays in unavailable. CONCLUSIONS: By allowing the user to easily create his or her own fRMA implementation, the frmaTools package greatly increases the applicability of the fRMA algorithm. The frmaTools package is freely available as part of the Bioconductor project."	"http://www.ncbi.nlm.nih.gov/pubmed/21923903"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0232558139535"	"0.0232558139535"	"0.0891472868217"	"258"	"17.2"	"Molecular Biology and Evolution"	"Miller JS, Kamath A, Damashek J, Levin RA"	"Department of Biology, Amherst College. jsmiller@amherst.edu"	"The plant genus Lycium (Solanaceae) originated in the Americas and includes approximately 85 species that are distributed worldwide. The vast majority of Old World species occur in southern Africa and eastern Asia. In this study, we examine biogeographic relationships among Old World species using a phylogenetic approach coupled with molecular evolutionary analyses of the S-RNase self-incompatibility gene. The phylogeny inferred from nuclear granule-bound starch synthase I (GBSSI), nuclear conserved ortholog set II (COSII) marker C2_At1g24360, and plastid spacer data (trnH-pbsA, trnD(GUC)-trnT(GGU), rpl32-trnL(UAG), and ndhF-rpl32) includes a clade of eastern Asian Lycium nested within the African species, suggesting initial dispersal from the Americas to Africa, with subsequent dispersal to eastern Asia. Molecular dating estimates suggest that these dispersal events occurred relatively recently, with dispersal from the Americas to Africa approximately 3.64 Ma (95% highest posterior density [HPD]: 1.58-6.27), followed by subsequent dispersal to eastern Asia approximately 1.21 Ma (95% HPD: 0.32-2.42). In accordance, the S-RNase genealogy shows that S-RNases isolated from Old World species are restricted to four lineages, a subset of the 14 lineages including S-RNases isolated from New World Lycium species, supporting a bottleneck of S-RNase alleles concomitant with a single dispersal event from the Americas to the Old World. Furthermore, the S-RNase genealogy is also consistent with dispersal of Lycium from Africa to Asia, as eastern Asian alleles are restricted to a subset of the lineages that also include African alleles. Such a multilocus approach, including complementary data from GBSSI, COSII, plastid spacer regions, and S-RNase, is powerful for understanding dispersal histories of closely related species."	"http://www.ncbi.nlm.nih.gov/pubmed/20855430"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00833333333333"	"0.0208333333333"	"0.075"	"240"	"11.4285714286"	"BMC Bioinformatics"	"Moughon SE, Samudrala R"		"ABSTRACT: BACKGROUND: Successful protein structure prediction requires accurate low-resolution scoring functions so that protein main chain conformations that are close to the native can be identified. Once that is accomplished, a more detailed and time-consuming treatment to produce all-atom models can be undertaken. The earliest low-resolution scoring used simple distance-based contact potentials, but more recently, the relative orientations of interacting amino acids have been taken into account to improve performance. RESULTS: We developed a new knowledge-based scoring function, LoCo, that locates the interaction partners of each individual residue within a local coordinate system based only on the position of its main chain N, Calpha and C atoms. LoCo was trained on a large set of experimentally determined structures and optimized using standard sets of modeled structures, or decoys. No structure used to train or optimize the function was included among those used to test it. When tested against 29 other published main chain functions on a group of 77 commonly used decoy sets, our function outperformed all others in Calpha RMSD rank of the best-scoring decoy, with statistically significant p-values < 0.05 for 26 out of the 29 other functions considered. LoCo is fast, requiring on average less than 6 microseconds per residue for interaction and scoring on commonly-used computer hardware. CONCLUSIONS: Our function demonstrates an unmatched combination of accuracy, speed, and simplicity and shows excellent promise for protein structure prediction. Broader applications may include protein-protein interactions and protein design."	"http://www.ncbi.nlm.nih.gov/pubmed/21920038"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0113636363636"	"0.0265151515152"	"0.0757575757576"	"264"	"12.619047619"	"Molecular Biology and Evolution"	"Nayar M, Fox GE"	"Department of Biology and Biochemistry, University of Houston."	"A portion of the 5S ribosomal RNA (rRNA) structure space in the vicinity of the Vibrio proteolyticus 5S rRNA sequence is explored in detail with the intention of establishing principles that will allow a priori prediction of which sequences would be valid members of a particular RNA structure space. Four hundred and one sequence variants differing from the V. proteolyticus 5S rRNA wild-type sequence in 1-7 positions were characterized using an in vivo assay system. Most significantly, it was found that in general, the phenotypic effects of single changes were independent of the phenotypic effect of a second change. As a result, it was possible to use the new data in conjunction with results from prior studies of the same RNA to develop truth tables to predict which multiple change variants would be functional and which would be nonfunctional. The actual phenotype of 93.8% of the multichange variants studied was consistent with the predictions made using truth tables thereby providing for perhaps the first time an upper limit estimate of how frequent unexpected interactions are. It was also observed that single changes at positions involved in secondary structure were no more likely to be invalid than changes in other regions. In particular, internal changes in long standard stems were in fact almost always tolerated. Changes at positions that were hypervariable in the context of an alignment of related sequences were, as expected, usually found to be valid. However, the potential validity of changes that were idiosyncratic to a single lineage of related sequences when placed in the V. proteolyticus 5S rRNA context was unpredictable."	"http://www.ncbi.nlm.nih.gov/pubmed/21470967"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0321285140562"	"0.0281124497992"	"0.0722891566265"	"249"	"13.1052631579"	"BMC Bioinformatics"	"Naznin F, Sarker R, Essam D"		"ABSTRACT: BACKGROUND: Many Bioinformatics studies begin with a multiple sequence alignment as the foundation for their research. This is because multiple sequence alignment can be a useful technique for studying molecular evolution and analyzing sequence structure relationships. RESULTS: In this paper, we have proposed a Vertical Decomposition with Genetic Algorithm (VDGA) for Multiple Sequence Alignment (MSA). In VDGA, we divide the sequences vertically into two or more subsequences, and then solve them individually using a guide tree approach. Finally, we combine all the subsequences to generate a new multiple sequence alignment. This technique is applied on the solutions of the initial generation and of each child generation within VDGA. We have used two mechanisms to generate an initial population in this research: the first mechanism is to generate guide trees with randomly selected sequences and the second is shuffling the sequences inside such trees. Two different genetic operators have been implemented with VDGA. To test the performance of our algorithm, we have compared it with existing well-known methods, namely PRRP, CLUSTALX, DIALIGN, HMMT, SB_PIMA, ML_PIMA, MULTALIGN, and PILEUP8, and also other methods, based on Genetic Algorithms (GA), such as SAGA, MSA-GA and RBT-GA, by solving a number of benchmark datasets from BAliBase 2.0. CONCLUSIONS: The experimental results showed that the VDGA with three vertical divisions was the most successful variant for most of the test cases in comparison to other divisions considered with VDGA. The experimental results also confirmed that VDGA outperformed the other methods considered in this research."	"http://www.ncbi.nlm.nih.gov/pubmed/21867510"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0115606936416"	"0.0578034682081"	"173"	"13.3076923077"	"Molecular Biology and Evolution"	"OFallon BD"	"Department of Genome Sciences, University of Washington."	"The serial coalescent extends traditional coalescent theory to include genealogies in which not all individuals were sampled at the same time. Inference in this framework is powerful because population size and evolutionary rate may be estimated independently. However, when the sequences in question are affected by selection acting at many sites, the genealogies may differ significantly from their neutral expectation, and inference of demographic parameters may become inaccurate. I demonstrate that this inaccuracy is severe when the mutation rate and strength of selection are jointly large, and I develop a new likelihood calculation that, while approximate, improves the accuracy of population size estimates. When used in a Bayesian parameter estimation context, the new calculation allows for estimation of the shape of the pairwise coalescent rate function and can be used to detect the presence of selection acting at many sites in a sequence. Using the new method, I investigate two sets of dengue virus sequences from Puerto Rico and Thailand, and show that both genealogies are likely to have been distorted by selection."	"http://www.ncbi.nlm.nih.gov/pubmed/21680870"
-"unk"	"unknown"	"unknown"	"unknown"	"0.00454545454545"	"0.0409090909091"	"0.1"	"440"	"14.1935483871"	"BMC Bioinformatics"	"Olivera-Nappa A, Andrews BA, Asenjo JA"	"Centre for Biochemical Engineering and Biotechnology, Institute for Cell Dynamics and Biotechnology: a Centre for Systems Biology, University of Chile, Santiago, Chile. aolivera@ing.uchile.cl"	"BACKGROUND: Functionally relevant artificial or natural mutations are difficult to assess or predict if no structure-function information is available for a protein. This is especially important to correctly identify functionally significant non-synonymous single nucleotide polymorphisms (nsSNPs) or to design a site-directed mutagenesis strategy for a target protein. A new and powerful methodology is proposed to guide these two decision strategies, based only on conservation rules of physicochemical properties of amino acids extracted from a multiple alignment of a protein family where the target protein belongs, with no need of explicit structure-function relationships. RESULTS: A statistical analysis is performed over each amino acid position in the multiple protein alignment, based on different amino acid physical or chemical characteristics, including hydrophobicity, side-chain volume, charge and protein conformational parameters. The variances of each of these properties at each position are combined to obtain a global statistical indicator of the conservation degree of each property. Different types of physicochemical conservation are defined to characterize relevant and irrelevant positions. The differences between statistical variances are taken together as the basis of hypothesis tests at each position to search for functionally significant mutable sites and to identify specific mutagenesis targets. The outcome is used to statistically predict physicochemical consensus sequences based on different properties and to calculate the amino acid propensities at each position in a given protein. Hence, amino acid positions are identified that are putatively responsible for function, specificity, stability or binding interactions in a family of proteins. Once these key functional positions are identified, position-specific statistical distributions are applied to divide the 20 common protein amino acids in each position of the proteins primary sequence into a group of functionally non-disruptive amino acids and a second group of functionally deleterious amino acids. CONCLUSIONS: With this approach, not only conserved amino acid positions in a protein family can be labeled as functionally relevant, but also non-conserved amino acid positions can be identified to have a physicochemically meaningful functional effect. These results become a discriminative tool in the selection and elaboration of rational mutagenesis strategies for the protein. They can also be used to predict if a given nsSNP, identified, for instance, in a genomic-scale analysis, can have a functional implication for a particular protein and which nsSNPs are most likely to be functionally silent for a protein. This analytical tool could be used to rapidly and automatically discard any irrelevant nsSNP and guide the research focus toward functionally significant mutations. Based on preliminary results and applications, this technique shows promising performance as a valuable bioinformatics tool to aid in the development of new protein variants and in the understanding of function-structure relationships in proteins."	"http://www.ncbi.nlm.nih.gov/pubmed/21524307"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00701754385965"	"0.0175438596491"	"0.112280701754"	"285"	"15.0"	"Molecular Biology and Evolution"	"Paar V, Gluncic M, Rosandic M, Basar I, Vlahovic I"	"Faculty of Science, University of Zagreb, Zagreb, Croatia. paar@hazu.hr"	"Much attention has been devoted to identifying genomic patterns underlying the evolution of the human brain and its emergent advanced cognitive capabilities, which lie at the heart of differences distinguishing humans from chimpanzees, our closest living relatives. Here, we identify two particular intragene repeat structures of noncoding human DNA, spanning as much as a hundred kilobases, that are present in human genome but are absent from the chimpanzee genome and other nonhuman primates. Using our novel computational method Global Repeat Map, we examine tandem repeat structure in human and chimpanzee chromosome 1. In human chromosome 1, we find three higher order repeats (HORs), two of them novel, not reported previously, whereas in chimpanzee chromosome 1, we find only one HOR, a 2mer alphoid HOR instead of human alphoid 11mer HOR. In human chromosome 1, we identify an HOR based on 39-bp primary repeat unit, with secondary, tertiary, and quartic repeat units, fully embedded in human hornerin gene, related to regenerating and psoriatric skin. Such an HOR is not found in chimpanzee chromosome 1. We find a remarkable human 3mer HOR organization based on the ~1.6-kb primary repeat unit, fully embedded within the neuroblastoma breakpoint family genes, which is related to the function of the human brain. Such HORs are not present in chimpanzees. In general, we find that human-chimpanzee differences are much larger for tandem repeats, in particularly for HORs, than for gene sequences. This may be of great significance in light of recent studies that are beginning to reveal the large-scale regulatory architecture of the human genome, in particular the role of noncoding sequences. We hypothesize about the possible importance of human accelerated HOR patterns as components in the gene expression multilayered regulatory network."	"http://www.ncbi.nlm.nih.gov/pubmed/21273634"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00487804878049"	"0.019512195122"	"0.0390243902439"	"205"	"8.44"	"Glycobiology"	"Park BH, Karpinets TV, Syed MH, Leuze MR, Uberbacher EC"	"Computer Science and Mathematics Division."	"The Carbohydrate-Active Enzyme (CAZy) database provides a rich set of manually annotated enzymes that degrade, modify, or create glycosidic bonds. Despite rich and invaluable information stored in the database, software tools utilizing this information for annotation of newly sequenced genomes by CAZy families are limited. We have employed two annotation approaches to fill the gap between manually curated high-quality protein sequences collected in the CAZy database and the growing number of other protein sequences produced by genome or metagenome sequencing projects. The first approach is based on a similarity search against the entire nonredundant sequences of the CAZy database. The second approach performs annotation using links or correspondences between the CAZy families and protein family domains. The links were discovered using the association rule learning algorithm applied to sequences from the CAZy database. The approaches complement each other and in combination achieved high specificity and sensitivity when cross-evaluated with the manually curated genomes of Clostridium thermocellum ATCC 27405 and Saccharophagus degradans 2-40. The capability of the proposed framework to predict the function of unknown protein domains and of hypothetical proteins in the genome of Neurospora crassa is demonstrated. The framework is implemented as a Web service, the CAZymes Analysis Toolkit, and is available at http://cricket.ornl.gov/cgi-bin/cat.cgi."	"http://www.ncbi.nlm.nih.gov/pubmed/20696711"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0150753768844"	"0.0201005025126"	"0.0301507537688"	"199"	"8.65217391304"	"Blood"	"Park YP, Choi SC, Kiesler P, Gil-Krzewska A, Borrego F, Weck J, Krzewski K, Coligan JE"	"Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD; and."	"Natural killer (NK) cells help protect the host against viral infections and tumors. NKG2D is a vital activating receptor, also expressed on subsets of T cells, whose ligands are up-regulated by cells in stress. Ligation of NKG2D leads to phosphorylation of the associated DAP10 adaptor protein, thereby activating immune cells. Understanding how the expression of NKG2D-DAP10 is regulated has implications for immunotherapy. We show that IL-2 and TGF-beta1 oppositely regulate NKG2D-DAP10 expression by NK cells. IL-2 stimulation increases NKG2D surface expression despite a decrease in NKG2D mRNA levels. Stimulation with IL-2 results in a small increase of DAP10 mRNA and a large up-regulation of DAP10 protein synthesis, indicating that IL-2-mediated effects are mostly posttranscriptional. Newly synthesized DAP10 undergoes glycosylation that is required for DAP10 association with NKG2D and stabilization of NKG2D expression. TGF-beta1 has an opposite and dominant effect to IL-2. TGF-beta1 treatment decreases DAP10, as its presence inhibits the association of RNA polymerase II with the DAP10 promoter, but not NKG2D mRNA levels. This leads to the down-regulation of DAP10 expression and, as a consequence, NKG2D protein as well. Finally, we show that other gamma(c) cytokines act similarly to IL-2 in up-regulating DAP10 expression and NKG2D-DAP10 surface expression."	"http://www.ncbi.nlm.nih.gov/pubmed/21816829"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0134529147982"	"0.0269058295964"	"0.0896860986547"	"223"	"10.619047619"	"Glycobiology"	"Parra A, Veraldi N, Locatelli M, Fini M, Martini L, Torri G, Sangiorgi L, Bisio A"	"S.S.D. Genetica Medica e Malattie Rare Ortopediche, Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136, Bologna, Italia."	"Glycosaminoglycans were extracted from both young rabbit growth plate and articular cartilage tissues and enzymatically treated to selectively eliminate chondroitin sulfates and hyaluronic acid. The procedure avoided any fractionation step that could enrich the extract with over- or under-sulfated species. Isolated HS was characterized by mono- and bidimensional NMR spectroscopy to quantify their specific structural features and/or by mass spectrometry to establish the disaccharide composition. Both growth plate and articular HSs, despite differing in their yield (growth plate at least one hundred times greater than articular), exhibited a surprisingly high degree of sulfation. Quantitative 2D-HSQC NMR analysis of growth plate HS revealed unusually high N-sulfated glucosamine and 2-O-sulfated iduronic acid contents, similar to heparin. The unique pentasaccharide sequence of the binding site for antithrombin was also detected in a significant amount. HPLC-MS analysis of the enzymatic digests with a cocktail of heparin lyases of both cartilaginous HSs confirmed the NMR results. As well as the discovery of an unusual HS structure in the two different types of rabbit cartilage, the feasibility of the analytical method adopted here has been demonstrated within this study. Such a method can be used to isolate and analyze HS from both normal and pathologic tissues. Characterization of healthy and pathological HS structures will contribute to improve the understanding of diseases related to malfunctions of HS biosynthesis and/or metabolism."	"http://www.ncbi.nlm.nih.gov/pubmed/21933839"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0119760479042"	"0.0239520958084"	"0.0538922155689"	"167"	"18.5555555556"	"Glycobiology"	"Patel KB, Ciepichal E, Swiezewska E, Valvano MA"	"Center for Human Immunology, Departments of Microbiology and Immunology, and."	"Two families of membrane enzymes catalyze the initiation of the synthesis of O antigen lipopolysaccharide (LPS). The Salmonella enterica Typhimurium WbaP is a prototypic member of one of these families. We report here the purification and biochemical characterization of the WbaP C-terminal domain (WbaP(CT)) harboring one putative transmembrane (TM) helix and a large cytoplasmic tail. An N-terminal thioredoxin fusion greatly improved solubility and stability of WbaP(CT) allowing us to obtain highly purified protein. We demonstrate that WbaP(CT) is sufficient to catalyze the in vitro transfer of galactose-1-phosphate (Gal-P) from UDP-Gal to the lipid carrier undecaprenyl monophosphate (Und-P). We optimized the in vitro assay to determine steady state kinetic parameters with the substrates UDP-Gal and Und-P. Using various purified polyisoprenyl phosphates of increasing length and variable saturation of the isoprene units, we also demonstrate that the purified enzyme only functions with Und-P, suggesting that the WbaP(CT) domain contains all the essential motifs to catalyze the synthesis of the Und-P-P-Gal molecule that primes the biosynthesis of bacterial surface glycans."	"http://www.ncbi.nlm.nih.gov/pubmed/21856724"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00729927007299"	"0.014598540146"	"0.0693430656934"	"274"	"16.1176470588"	"Molecular Biology and Evolution"	"Petrov DA, Fiston-Lavier AS, Lipatov M, Lenkov K, Gonzalez J"	"Department of Biology, Stanford University."	"Transposable elements (TEs) are the primary contributors to the genome bulk in many organisms and are major players in genome evolution. A clear and thorough understanding of the population dynamics of TEs is therefore essential for full comprehension of the eukaryotic genome evolution and function. Although TEs in Drosophila melanogaster have received much attention, population dynamics of most TE families in this species remains entirely unexplored. It is not clear whether the same population processes can account for the population behaviors of all TEs in Drosophila or whether, as has been suggested previously, different orders behave according to very different rules. In this work, we analyzed population frequencies for a large number of individual TEs (755 TEs) in five North American and one sub-Saharan African D. melanogaster populations (75 strains in total). These TEs have been annotated in the reference D. melanogaster euchromatic genome and have been sampled from all three major orders (non-LTR, LTR, and TIR) and from all families with more than 20 TE copies (55 families in total). We find strong evidence that TEs in Drosophila across all orders and families are subject to purifying selection at the level of ectopic recombination. We showed that strength of this selection varies predictably with recombination rate, length of individual TEs, and copy number and length of other TEs in the same family. Importantly, these rules do not appear to vary across orders. Finally, we built a statistical model that considered only individual TE-level (such as the TE length) and family-level properties (such as the copy number) and were able to explain more than 40% of the variation in TE frequencies in D. melanogaster."	"http://www.ncbi.nlm.nih.gov/pubmed/21172826"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00808625336927"	"0.0134770889488"	"0.0485175202156"	"371"	"10.6857142857"	"BMC Bioinformatics"	"Presson AP, Kim N, Xiaofei Y, Chen IS, Kim S"		"ABSTRACT: BACKGROUND: Modern gene therapy methods have limited control over where a therapeutic viral vector inserts into the host genome. Vector integration can activate local gene expression, which can cause cancer if the vector inserts near an oncogene. Viral integration hot-spots or `common insertion sites (CIS) are scrutinized to evaluate and predict patient safety. CIS are typically defined by a minimum density of insertions (such as 2-4 within a 30-100kb region), which unfortunately depends on the total number of observed VIS. This is problematic for comparing hot-spot distributions across data sets and patients, where the VIS numbers may vary. RESULTS: We develop two new methods for defining hot-spots that are relatively independent of data set size. Both methods operate on distributions of VIS across consecutive 1Mb `bins of the genome. The first method `z-threshold tallies the number of VIS per bin, converts these counts to z-scores, and applies a threshold to define high density bins. The second method `BCP applies a Bayesian change-point model to the z-scores to define hot-spots. The novel hot-spot methods are compared with a conventional CIS method using simulated data sets and data sets from five published human studies, including the X-linked ALD (adrenoleukodystrophy), CGD (chronic granulomatous disease) and SCID-X1 (X-linked severe combined immunodeficiency) trials. The BCP analysis of the human X-linked ALD data for two patients separately (774 and 1627 VIS) and combined (2401 VIS) resulted in 5-6 hot-spots covering 0.17-0.251% of the genome and containing 5.56-7.74% of the total VIS. In comparison, the CIS analysis resulted in 12-110 hot-spots covering 0.018-0.246% of the genome and containing 5.81-22.7% of the VIS, corresponding to a greater number of hot-spots as the data set size increased. Our hot-spot methods enable one to evaluate the extent of VIS clustering, and formally compare data sets in terms of hot-spot overlap. Finally, we show that the BCP hot-spots from the repopulating samples coincide with greater gene and CpG island density than the median genome density. CONCLUSIONS: The z-threshold and BCP methods are useful for comparing hot-spot patterns across data sets of disparate sizes. The methodology and software provided here should enable one to study hot-spot conservation across a variety of VIS data sets and evaluate vector safety for gene therapy trials."	"http://www.ncbi.nlm.nih.gov/pubmed/21914224"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0148367952522"	"0.0148367952522"	"0.0563798219585"	"337"	"17.7368421053"	"Molecular Biology and Evolution"	"Price DR, Duncan RP, Shigenobu S, Wilson AC"	"Department of Biology, University of Miami, Coral Gables, Florida."	"In insects, some of the most ecologically important symbioses are nutritional symbioses that provide hosts with novel traits and thereby facilitate exploitation of otherwise inaccessible niches. One such symbiosis is the ancient obligate intracellular symbiosis of aphids with the gamma-proteobacteria, Buchnera aphidicola. Although the nutritional basis of the aphid/Buchnera symbiosis is well understood, the processes and structures that mediate the intimate interactions of symbiotic partners remain uncharacterized. Here, using a de novo approach, we characterize the complement of 40 amino acid polyamine organocation (APC) superfamily member amino acid transporters (AATs) encoded in the genome of the pea aphid, Acyrthosiphon pisum. We find that the A. pisum APC superfamily is characterized by extensive gene duplications such that A. pisum has more APC superfamily transporters than other fully sequenced insects, including a ten paralog aphid-specific expansion of the APC transporter slimfast. Detailed expression analysis of 17 transporters selected on the basis of their phylogenetic relationship to five AATs identified in an earlier bacteriocyte expressed sequence tag study distinguished a subset of eight transporters that have been recruited for amino acid transport in bacteriocyte cells at the symbiotic interface. These eight transporters include transporters that are highly expressed and/or highly enriched in bacteriocytes and intriguingly, the four AATs that show bacteriocyte-enriched expression are all members of gene family expansions, whereas three of the four that are highly expressed but not enriched in bacteriocytes retain one-to-one orthology with transporters in other genomes. Finally, analysis of evolutionary rates within the large A. pisum slimfast expansion demonstrated increased rates of molecular evolution coinciding with two major shifts in expression: 1) a loss of gut expression and possibly a gain of bacteriocyte expression and 2) loss of expression in all surveyed tissues in asexual females. Taken together, our characterization of nutrient AATs at the aphid/Buchnera symbiotic interface provides the first examination of the processes and structures operating at the interface of an obligate intracellular insect nutritional symbiosis, offering unique insight into the types of genomic change that likely facilitated evolutionary maintenance of the symbiosis."	"http://www.ncbi.nlm.nih.gov/pubmed/21613235"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0142857142857"	"0.0238095238095"	"0.109523809524"	"210"	"10.0"	"Molecular Biology and Evolution"	"Roy SW, Hudson AJ, Joseph J, Yee J, Russell AG"	"Department of Biology, Stanford University, 371 Serra Mall, Stanford, CA 94305."	"Spliceosomal introns are hallmarks of eukaryotic genomes, dividing coding regions into separate exons which are joined during mRNA intron removal catalyzed by the spliceosome. With few known exceptions, spliceosomal introns are cis-spliced, that is, removed from one contiguous pre-mRNA transcript. The protistan intestinal parasite Giardia lamblia exhibits one of the most reduced eukaryotic genomes known, with short intergenic regions and only four known spliceosomal introns. Our genome-wide search for additional introns revealed four unusual cases of spliceosomal intron fragmentation, with consecutive exons of conserved protein-coding genes being dispersed to distant genomic sites. Independent transcripts are trans-spliced to yield contiguous mature mRNAs. Most strikingly, a dynein heavy chain subunit is both interrupted by two fragmented introns, and also predicted to be assembled as two separately translated polypeptides, a remarkably complex expression pathway for a nuclear-encoded sequence. For each case, we observe extensive base-pairing potential between intron halves. This basepairing provides both a rationale for the in vivo association of independently transcribed mRNAs transcripts and the apparent specificity of splicing. Similar base-pairing potential in two cis-spliced G. lamblia introns suggests an evolutionary pathway whereby intron fragmentation of cis-spliced introns is permissible and a preliminary evolutionary step to complete gene fission. These results reveal remarkably complex genome dynamics in a severely genomically-reduced parasite."	"http://www.ncbi.nlm.nih.gov/pubmed/21482665"
 "unk"	"unknown"	"unknown"	"unknown"	"0.010101010101"	"0.0"	"0.0909090909091"	"198"	"10.4210526316"	"BMC Bioinformatics"	"Salazar GA, Jimenez RC, Garcia A, Hermjakob H, Mulder N, Blake E"	"Computer Sciences Department, University of Cape Town, South Africa. gsalazar@cs.uct.ac.za"	"BACKGROUND: Centralised resources such as GenBank and UniProt are perfect examples of the major international efforts that have been made to integrate and share biological information. However, additional data that adds value to these resources needs a simple and rapid route to public access. The Distributed Annotation System (DAS) provides an adequate environment to integrate genomic and proteomic information from multiple sources, making this information accessible to the community. DAS offers a way to distribute and access information but it does not provide domain experts with the mechanisms to participate in the curation process of the available biological entities and their annotations. RESULTS: We designed and developed a Collaborative Annotation System for proteins called DAS Writeback. DAS writeback is a protocol extension of DAS to provide the functionalities of adding, editing and deleting annotations. We implemented this new specification as extensions of both a DAS server and a DAS client. The architecture was designed with the involvement of the DAS community and it was improved after performing usability experiments emulating a real annotation task. CONCLUSIONS: We demonstrate that DAS Writeback is effective, usable and will provide the appropriate environment for the creation and evolution of community protein annotation."	"http://www.ncbi.nlm.nih.gov/pubmed/21569281"
-"unk"	"unknown"	"unknown"	"unknown"	"0.00803212851406"	"0.0401606425703"	"0.10843373494"	"249"	"16.6"	"Nature"	"Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, Dilthey A, Su Z, Freeman C, Hunt SE, Edkins S, Gray E, Booth DR, Potter SC, Goris A, Band G, Oturai AB, Strange A, Saarela J, Bellenguez C, Fontaine B, Gillman M, Hemmer B, Gwilliam R, Zipp F, Jayakumar A, Martin R, Leslie S, Hawkins S, Giannoulatou E, Dalfonso S, Blackburn H, Boneschi FM, Liddle J, Harbo HF, Perez ML, Spurkland A, Waller MJ, Mycko MP, Ricketts M, Comabella M, Hammond N, Kockum I, McCann OT, Ban M, Whittaker P, Kemppinen A, Weston P, Hawkins C, Widaa S, Zajicek J, Dronov S, Robertson N, Bumpstead SJ, Barcellos LF, Ravindrarajah R, Abraham R, Alfredsson L, Ardlie K, Aubin C, Baker A, Baker K, Baranzini SE, Bergamaschi L, Bergamaschi R, Bernstein A, Berthele A, Boggild M, Bradfield JP, Brassat D, Broadley SA, Buck D, Butzkueven H, Capra R, Carroll WM, Cavalla P, Celius EG, Cepok S, Chiavacci R, Clerget-Darpoux F, Clysters K, Comi G, Cossburn M, Cournu-Rebeix I, Cox MB, Cozen W, Cree BA, Cross AH, Cusi D, Daly MJ, Davis E, de Bakker PI, Debouverie M, Dhooghe MB, Dixon K, Dobosi R, Dubois B, Ellinghaus D, Elovaara I, Esposito F, Fontenille C, Foote S, Franke A, Galimberti D, Ghezzi A, Glessner J, Gomez R, Gout O, Graham C, Grant SF, Guerini FR, Hakonarson H, Hall P, Hamsten A, Hartung HP, Heard RN, Heath S, Hobart J, Hoshi M, Infante-Duarte C, Ingram G, Ingram W, Islam T, Jagodic M, Kabesch M, Kermode AG, Kilpatrick TJ, Kim C, Klopp N, Koivisto K, Larsson M, Lathrop M, Lechner-Scott JS, Leone MA, Leppa V, Liljedahl U, Bomfim IL, Lincoln RR, Link J, Liu J, Lorentzen AR, Lupoli S, Macciardi F, Mack T, Marriott M, Martinelli V, Mason D, McCauley JL, Mentch F, Mero IL, Mihalova T, Montalban X, Mottershead J, Myhr KM, Naldi P, Ollier W, Page A, Palotie A, Pelletier J, Piccio L, Pickersgill T, Piehl F, Pobywajlo S, Quach HL, Ramsay PP, Reunanen M, Reynolds R, Rioux JD, Rodegher M, Roesner S, Rubio JP, Ruckert IM, Salvetti M, Salvi E, Santaniello A, Schaefer CA, Schreiber S, Schulze C, Scott RJ, Sellebjerg F, Selmaj KW, Sexton D, Shen L, Simms-Acuna B, Skidmore S, Sleiman PM, Smestad C, Sorensen PS, Sondergaard HB, Stankovich J, Strange RC, Sulonen AM, Sundqvist E, Syvanen AC, Taddeo F, Taylor B, Blackwell JM, Tienari P, Bramon E, Tourbah A, Brown MA, Tronczynska E, Casas JP, Tubridy N, Corvin A, Vickery J, Jankowski J, Villoslada P, Markus HS, Wang K, Mathew CG, Wason J, Palmer CN, Wichmann HE, Plomin R, Willoughby E, Rautanen A, Winkelmann J, Wittig M, Trembath RC, Yaouanq J, Viswanathan AC, Zhang H, Wood NW, Zuvich R, Deloukas P, Langford C, Duncanson A, Oksenberg JR, Pericak-Vance MA, Haines JL, Olsson T, Hillert J, Ivinson AJ, De Jager PL, Peltonen L, Stewart GJ, Hafler DA, Hauser SL, McVean G, Donnelly P, Compston A"		"Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis."	"http://www.ncbi.nlm.nih.gov/pubmed/21833088"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0185185185185"	"0.037037037037"	"0.172839506173"	"162"	"5.96551724138"	"Bioinformatics"	"Semegni JY, Wamalwa M, Gaujoux R, Harkins GW, Gray A, Martin DP"	"Computational Biology Group, Department of Clinical Laboratory Sciences, IIDMM, University of Cape Town, 7925 Anzio Road, Observatory and South Africa National Bioinformatics Institute, University of the Western Cape, Private Bag X17, Bellville 7535, Cape Town, South Africa."	"SUMMARY: Many natural nucleic acid sequences have evolutionarily conserved secondary structures with diverse biological functions. A reliable computational tool for identifying such structures would be very useful in guiding experimental analyses of their biological functions. NASP (Nucleic Acid Structure Predictor) is a program that takes into account thermodynamic stability, Boltzmann base pair probabilities, alignment uncertainty, covarying sites and evolutionary conservation to identify biologically relevant secondary structures within multiple sequence alignments. Unique to NASP is the consideration of all this information together with a recursive permutation-based approach to progressively identify and list the most conserved probable secondary structures that are likely to have the greatest biological relevance. By focusing on identifying only evolutionarily conserved structures, NASP forgoes the prediction of complete nucleotide folds but outperforms various other secondary structure prediction methods in its ability to selectively identify actual base pairings. AVAILABILITY: Downloable and web-based versions of NASP are freely available at http://web.cbio.uct.ac.za/~yves/nasp_portal.php CONTACT: yves@cbio.uct.ac.za SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online."	"http://www.ncbi.nlm.nih.gov/pubmed/21757466"
-"unk"	"unknown"	"unknown"	"unknown"	"0.00985221674877"	"0.0197044334975"	"0.0591133004926"	"203"	"11.9411764706"	"Molecular Biology and Evolution"	"Severi F, Chicca A, Conticello SG"		"The Activation Induced Deaminase (AID)/APOBEC family of deaminases targeting nucleic acids arose at the beginning of the vertebrate radiation and further expanded in mammals. Following an analysis of the available genomic data, we report the identification of the APOBEC5, a novel group of paralogues in tetrapods. Moreover, we find bona fide homologues of Apolipoprotein B Editing Complex 1 (APOBEC1) in the genomes of anole lizard and zebra finch, thus implying its appearance prior to the divergence of the amniotes. apolipoprotein B editing complex 1 (APOBEC1), in contrast with other AID/APOBECs acting on DNA, is an RNA-editing enzyme that targets the transcript of Apolipoprotein B (ApoB), thereby causing the translation of a truncated form of the protein. 3RACE experiments reveal a lizard APOBEC1-like molecule lacking a C-terminal region important for mammalian ApoB RNA editing. This observation pairs with the finding that lizard ApoB is not deaminated at the region corresponding to the mammalian site of editing. Similar to mammalian APOBEC1, the lizard protein is able to deaminate DNA in bacteria and shows a conserved mutational context. Although not precluding the possibility that lizard APOBEC1 acts on unknown mRNA targets, these findings suggest that its ability to target DNA predates its role in RNA editing."	"http://www.ncbi.nlm.nih.gov/pubmed/21172829"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00645161290323"	"0.0193548387097"	"0.0903225806452"	"155"	"5.0"	"Bioinformatics"	"Shivashankar S, Srivathsan S, Ravindran B, Tendulkar AV"	"Department of Computer Science and Engineering, IIT Madras, Chennai-600 036."	"MOTIVATION: With rapidly expanding protein structure databases, efficiently retrieving structures similar to a given protein is an important problem. It involves two major issues: (i) effective protein structure representation that captures inherent relationship between fragments and facilitates efficient comparison between the structures and (ii) effective framework to address different retrieval requirements. Recently, researchers proposed vector space model of proteins using bag of fragments representation (FragBag), which corresponds to the basic information retrieval model. RESULTS: In this article, we propose an improved representation of protein structures using latent dirichlet allocation topic model. Another important requirement is to retrieve proteins, whether they are either close or remote homologs. In order to meet diverse objectives, we propose multi-viewpoint based framework that combines multiple representations and retrieval techniques. We compare the proposed representation and retrieval framework on the benchmark dataset developed by Kolodny and co-workers. The results indicate that the proposed techniques outperform state-of-the-art methods. AVAILABILITY: http://www.cse.iitm.ac.in/~ashishvt/research/protein-lda/. CONTACT: ashishvt@cse.iitm.ac.in."	"http://www.ncbi.nlm.nih.gov/pubmed/21685102"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0625"	"0.0972222222222"	"144"	"16.0"	"Molecular Biology and Evolution"	"Siltberg-Liberles J"		"Protein structure is generally more conserved than sequence, but for regions that can adopt different structures in different environments, does this hold true? Understanding how structurally disordered regions evolve altered secondary structure element propensities as well as conformational flexibility among paralogs are fundamental questions for our understanding of protein structural evolution. We have investigated the evolutionary dynamics of structural disorder in protein families containing both orthologs and paralogs using phylogenetic tree reconstruction, protein structure disorder prediction, and secondary structure prediction in order to shed light upon these questions. Our results indicate that the extent and location of structurally disordered regions are not universally conserved. As structurally disordered regions often have high conformational flexibility, this is likely to have an effect on how protein structure evolves as spatially altered conformational flexibility can also change the secondary structure propensities for homologous regions in a protein family."	"http://www.ncbi.nlm.nih.gov/pubmed/21037204"
-"unk"	"unknown"	"unknown"	"unknown"	"0.00440528634361"	"0.00881057268722"	"0.11013215859"	"227"	"11.9473684211"	"BMC Bioinformatics"	"Stamatakis M, Zygourakis K"		"ABSTRACT: BACKGROUND: The lac operon genetic switch is considered as a paradigm of genetic regulation. This system has a positive feedback loop due to the LacY permease boosting its own production by the facilitated transport of inducer into the cell and the subsequent de-repression of the lac operon genes. Previously, we have investigated the effect of stochasticity in an artificial lac operon network at the single cell level by comparing corresponding deterministic and stochastic kinetic models. RESULTS: This work focuses on the dynamics of cell populations by incorporating the above kinetic scheme into two Monte Carlo (MC) simulation frameworks. The first MC framework assumes stochastic reaction occurrence, accounts for stochastic DNA duplication, division and partitioning and tracks all daughter cells to obtain the statistics of the entire cell population. In order to better understand how stochastic effects shape cell population distributions, we develop a second framework that assumes deterministic reaction dynamics. By comparing the predictions of the two frameworks, we conclude that stochasticity can create or destroy bimodality, and may enhance phenotypic heterogeneity. CONCLUSIONS: Our results show how various sources of stochasticity act in synergy with the positive feedback architecture, thereby shaping the behavior at the cell population level. Further, the insights obtained from the present study allow us to construct simpler and less computationally intensive models that can closely approximate the dynamics of heterogeneous cell populations."	"http://www.ncbi.nlm.nih.gov/pubmed/21791088"
-"unk"	"unknown"	"unknown"	"unknown"	"0.00657894736842"	"0.0197368421053"	"0.0855263157895"	"152"	"13.8181818182"	"Molecular Biology and Evolution"	"Subramanian S"		"Previous studies on human mitochondrial genomes showed that the ratio of intra-specific diversities at nonsynonymous-to-synonymous positions was two to ten times higher than the ratio of interspecific divergences at these positions, suggesting an excess of slightly deleterious nonsynonymous polymorphisms. However, such an overabundance of nonsynonymous single nucleotide polymorphisms (SNPs) was not found in human nuclear genomes. Here, genome-wide estimates using >14,000 human-chimp nuclear genes and 1 million SNPs from four human genomes showed a significant proportion of deleterious nonsynonymous SNPs ( approximately  15%). Importantly, this study reveals a negative correlation between the magnitude of selection pressure and the proportion of deleterious SNPs on human genes. The proportion of deleterious amino acid replacement polymorphisms is 3.5 times higher in genes under high purifying selection compared with that in less constrained genes (28% vs. 8%). These results are explained by differences in the extent of contribution of mildly deleterious mutations to diversity and substitution."	"http://www.ncbi.nlm.nih.gov/pubmed/20974690"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0493827160494"	"0.0987654320988"	"162"	"10.8"	"Molecular Biology and Evolution"	"Sun YB, Shen YY, Irwin DM, Zhang YP"		"Mitochondria are the power plant of cells, which play critical roles not only in energy metabolism but also in thermoregulation. These two roles have been individually suggested to influence mitochondrial DNA (mtDNA) evolution, however their relative importance is still rarely considered. Here, we conduct a comparative genomic analysis of 401 teleost complete mitochondrial genomes and test the roles of these dual functional constraints on mitochondria to provide a more complete view of mtDNA evolution. We found that mitochondrial protein-coding genes of migratory fishes have significantly smaller Ka/Ks than nonmigratory fishes. The same data set showed that the genes of fishes living in cold climates have significantly smaller Ka/Ks than tropical fishes. In contrast, these trends were not observed for two nuclear genes that are not involved in energy metabolism. The differences in selection patterns observed between mitochondrial and nuclear genes suggest that the functional constraints acting on mitochondria, due to energy metabolism and/or thermoregulation, influence the evolution of mitochondrial-encoded proteins in teleosts."	"http://www.ncbi.nlm.nih.gov/pubmed/20924083"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0134228187919"	"0.0134228187919"	"0.0671140939597"	"149"	"11.4615384615"	"Molecular Biology and Evolution"	"Szczesniak MW, Ciomborowska J, Nowak W, Rogozin IB, Makalowska I"		"Retroposition, a leading mechanism for gene duplication, is an important process shaping the evolution of genomes. Retrogenes are also involved in the gene structure evolution as a major player in the process of intron deletion. Here, we demonstrate the role of retrogenes in intron gain in mammals. We identified one case of intronization, the transformation of exonic sequences into an intron, in the primate specific retrogene RNF113B and two independent intronization events in the retrogene DCAF12L2, one in the common ancestor of primates and rodents and another one in the rodent lineage. Intron gain resulted from the origin of new splice variants, and both genes have two transcript forms, one with retained intron and one with the intron spliced out. Evolution of these genes, especially RNF113B, has been very dynamic and has been accompanied by several additional events including parental gene loss, secondary retroposition, and exaptation of transposable elements."	"http://www.ncbi.nlm.nih.gov/pubmed/20889727"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0243902439024"	"0.0325203252033"	"123"	"24.6"	"Nature Genetics"	"Thorleifsson G, Walters GB, Hewitt AW, Masson G, Helgason A, DeWan A, Sigurdsson A, Jonasdottir A, Gudjonsson SA, Magnusson KP, Stefansson H, Lam DS, Tam PO, Gudmundsdottir GJ, Southgate L, Burdon KP, Gottfredsdottir MS, Aldred MA, Mitchell P, St Clair D, Collier DA, Tang N, Sveinsson O, Macgregor S, Martin NG, Cree AJ, Gibson J, Macleod A, Jacob A, Ennis S, Young TL, Chan JC, Karwatowski WS, Hammond CJ, Thordarson K, Zhang M, Wadelius C, Lotery AJ, Trembath RC, Pang CP, Hoh J, Craig JE, Kong A, Mackey DA, Jonasson F, Thorsteinsdottir U, Stefansson K"	"deCODE genetics Inc, Reykjavik, Iceland. gudmar.thorleifsson@decode.is"	"We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[A], odds ratio (OR) = 1.36, P = 5.0 x 10(1)). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG."	"http://www.ncbi.nlm.nih.gov/pubmed/20835238"
 "unk"	"unknown"	"unknown"	"unknown"	"0.0"	"0.0428571428571"	"0.1"	"70"	"4.86666666667"	"Bioinformatics"	"Thorleifsson SG, Thiele I"	"Center for Systems Biology, Mechanical Engineering and Computer Science, University of Iceland, Reykjavik, Iceland."	"MOTIVATION: Genome-scale metabolic networks are widely used in systems biology. However, to date no freely available tool exists that ensures quality control during the reconstruction process. RESULTS: Here, we present a COBRA toolbox extension, rBioNet, enabling the construction of publication-level biochemical networks while enforcing necessary quality control measures. rBioNet has an intuitive user interface facilitating the reconstruction process for novices and experts. AVAILABILITY: The rBioNet is freely available from http://opencobra.sourceforge.net."	"http://www.ncbi.nlm.nih.gov/pubmed/21596791"
 "unk"	"unknown"	"unknown"	"unknown"	"0.00709219858156"	"0.0283687943262"	"0.120567375887"	"141"	"12.8181818182"	"Molecular Biology and Evolution"	"Toups MA, Kitchen A, Light JE, Reed DL"		"Clothing use is an important modern behavior that contributed to the successful expansion of humans into higher latitudes and cold climates. Previous research suggests that clothing use originated anywhere between 40,000 and 3 Ma, though there is little direct archaeological, fossil, or genetic evidence to support more specific estimates. Since clothing lice evolved from head louse ancestors once humans adopted clothing, dating the emergence of clothing lice may provide more specific estimates of the origin of clothing use. Here, we use a Bayesian coalescent modeling approach to estimate that clothing lice diverged from head louse ancestors at least by 83,000 and possibly as early as 170,000 years ago. Our analysis suggests that the use of clothing likely originated with anatomically modern humans in Africa and reinforces a broad trend of modern human developments in Africa during the Middle to Late Pleistocene."	"http://www.ncbi.nlm.nih.gov/pubmed/20823373"
-"unk"	"unknown"	"unknown"	"unknown"	"0.0157068062827"	"0.0104712041885"	"0.0890052356021"	"191"	"9.2380952381"	"BMC Bioinformatics"	"Tuszynska I, Bujnicki JM"		"ABSTRACT: BACKGROUND: Protein-RNA interactions play fundamental roles in many biological processes. Understanding the molecular mechanism of protein-RNA recognition and formation of protein-RNA complexes is a major challenge in structural biology. Unfortunately, the experimental determination of protein-RNA complexes is tedious and difficult, both by X-ray crystallography and NMR. For many interacting proteins and RNAs the individual structures are available, enabling computational prediction of complex structures by computational docking. However, methods for protein-RNA docking remain scarce, in particular in comparison to the numerous methods for protein-protein docking. RESULTS: We developed two medium-resolution, knowledge-based potentials for scoring protein-RNA models obtained by docking: the quasichemical potential (QUASI-RNP) and the Decoys As the Reference State potential (DARS-RNP). Both potentials use a coarse-grained representation for both RNA and protein molecules and are capable of dealing with RNA structures with posttranscriptionally modified residues. We compared the discriminative power of DARS-RNP and QUASI-RNP for selecting rigid-body docking poses with the potentials previously developed by the Varani and Fernandez groups. CONCLUSIONS: In both bound and unbound docking tests, DARS-RNP showed the highest ability to identify native-like structures. Python implementations of DARS-RNP and QUASI-RNP are freely available for download at http://iimcb.genesilico.pl/RNP/"	"http://www.ncbi.nlm.nih.gov/pubmed/21851628"
 1	"unknown"	"unknown"	"unknown"	"0.0"	"0.0"	"0.10101010101"	"99"	"14.1428571429"	"Molecular Biology and Evolution"	"Yokoyama S, Altun A, DeNardo DF"		"It has been discovered that the transient receptor potential ankyrin 1 (TRPA1) proteins of Boidae (boas), Pythonidae (pythons), and Crotalinae (pit vipers) are used to detect infrared radiation, but the molecular mechanism for detecting the infrared radiation is unknown. Here, relating the amino acid substitutions in their TRPA1 proteins and the functional differentiations, we propose that three parallel amino acid changes (L330M, Q391H, and S434T) are responsible for the development of infrared vision in the three groups of snakes. Protein modeling shows that the three amino acid changes alter the structures of the central region of their ankyrin repeats."	"http://www.ncbi.nlm.nih.gov/pubmed/20937734"
-1	"unknown"	"unknown"	"unknown"	"0.0121951219512"	"0.0243902439024"	"0.0569105691057"	"246"	"9.14814814815"	"Glycobiology"	"Yoshida E, Sakurama H, Kiyohara M, Nakajima M, Kitaoka M, Ashida H, Hirose J, Katayama T, Yamamoto K, Kumagai H"	"Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi, Ishikawa 921-8836."	"The breast-fed infant intestine is often colonized by particular bifidobacteria, and human milk oligosaccharides (HMOs) are considered to be bifidogenic. Recent studies showed that Bifidobacterium longum subsp. infantis can grow on HMOs as the sole carbon source. This ability has been ascribed to the presence of a gene cluster (HMO cluster-1) contained in its genome. However, the metabolism of HMOs by the organism remains unresolved because no enzymatic studies have been completed. In the present study, we characterized beta-galactosidases of this subspecies to understand how the organism degrades type-1 (Galbeta1-3GlcNAc) and type-2 (Galbeta1-4GlcNAc) isomers of HMOs. The results revealed that the locus tag Blon_2016 gene, which is distantly located from the HMO culster-1, encodes a novel beta-galactosidase (Bga42A) with a significantly higher specificity for LNT (Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc) than for lacto-N-biose I (Galbeta1-3GlcNAc), lactose and type-2 HMOs. The proposed name of Bga42A is lacto-N-tetraose beta-1,3-galactosidase. The Blon_2334 gene (Bga2A) located within the HMO cluster-1 encodes a beta-galactosidase specific for lactose and type-2 HMOs. Real-time quantitative reverse transcription PCR analysis revealed the physiological significance of Bga42A and Bga2A in HMO metabolism. The organism therefore uses two different beta-galactosidases to selectively degrade type-1 and type-2 HMOs. Despite the quite rare occurrence in nature of beta-galactosidases acting on type-1 chains, the close homologues of Bga42A were present in the genomes of infant-gut associated bifidobacteria that are known to consume LNT. The predominance of type-1 chains in HMOs and the conservation of Bga42A homologues suggest the coevolution of these bifidobacteria with humans."	"http://www.ncbi.nlm.nih.gov/pubmed/21926104"

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