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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genome analysis tools", "diabetes mellitus type 2", "diabetic endocrinology", "gastroenterology and hepatology", "endocrinology", "gene expression", "genetics", "human genetics", "molecular genetics", "epigenetics", "biology", "genomics", "pancreas", "computational biology",...	Genome-Wide DNA Methylation Analysis of Human Pancreatic Islets from Type 2 Diabetic and Non-Diabetic Donors Identifies Candidate Genes That Influence Insulin Secretion	journal.pgen.1004160	null	[ [ "Type 2 diabetes ( T2D ) is a complex multifactorial disorder characterized by chronic hyperglycemia due to impaired insulin secretion from pancreatic β-cells , elevated glucagon secretion from pancreatic α-cells and insulin resistance in target tissues .", "As a result of aging populations and an increas...	[ "Impaired insulin secretion is a hallmark of type 2 diabetes ( T2D ) .", "Epigenetics may affect disease susceptibility .", "To describe the human methylome in pancreatic islets and determine the epigenetic basis of T2D , we analyzed DNA methylation of 479 , 927 CpG sites and the transcriptome in pancreatic isl...	[ "Epigenetic modifications such as DNA methylation are implicated in the development of human disease .", "However , genome-wide epigenetic analyses in patients with type 2 diabetes ( T2D ) remain scarce .", "In this study we aimed to unravel the epigenetic basis of T2D by analyzing DNA methylation of 479 , 927 ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "public health and epidemiology", "epidemiology", "global health", "public health", "toxicology" ]	Genome-Wide Association Study Identifies Chromosome 10q24.32 Variants Associated with Arsenic Metabolism and Toxicity Phenotypes in Bangladesh	journal.pgen.1002522	null	[ [ "Over 100 million individuals worldwide are exposed to arsenic through drinking water , including approximately 56 million people in Bangladesh [1] and 13 million in the United States [2] .", "Arsenic is a class I human carcinogen , and chronic exposure to high levels of arsenic ( >300 µg/L ) is associate...	[ "Arsenic contamination of drinking water is a major public health issue in many countries , increasing risk for a wide array of diseases , including cancer .", "There is inter-individual variation in arsenic metabolism efficiency and susceptibility to arsenic toxicity; however , the basis of this variation is not...	[ "Exposure to arsenic through drinking water is a serious public health issue in many countries , including Bangladesh and the United States .", "Although there is substantial inter-individual variation in arsenic metabolism and toxicity , the biological basis of this variation is not well understood .", "Here ,...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "methods and resources", "transposon mutagenesis", "brassica", "operons", "mutation", "model organisms", "materials science", "experimental organism systems", "dna", "molecular biology techniques", "mutagenesis and gene deletion techniques", "seedlings", "plants", "macromolecules", "mate...	Genome-wide identification of bacterial plant colonization genes	journal.pbio.2002860	null	[ [ "Plant health is intimately influenced by a diverse community of microorganisms inhabiting the root surface ( rhizoplane ) and endophytic compartment [1] .", "This root microbiome is recruited from surrounding soil communities [2–4] and is thought to be modulated by host plant immune function , root exuda...	[ "Diverse soil-resident bacteria can contribute to plant growth and health , but the molecular mechanisms enabling them to effectively colonize their plant hosts remain poorly understood .", "We used randomly barcoded transposon mutagenesis sequencing ( RB-TnSeq ) in Pseudomonas simiae , a model root-colonizing ba...	[ "Plants fix carbon to create an abundance of sugars and amino acids , thus providing an enticing environment for microorganisms that reside in soil .", "Once these microorganisms have colonized the root environment , they can dramatically influence plant growth and development .", "We set out to identify a comp...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal behavior", "theoretical biology", "ecology", "biology", "zoology", "neuroscience", "behavioral ecology" ]	Collective Animal Behavior from Bayesian Estimation and Probability Matching	journal.pcbi.1002282	null	[ [ "Animals need to make decisions without certainty in which option is best .", "This uncertainty is due to the ambiguity of sensory data but also to limited processing capabilities , and is an intrinsic and general property of the representation that animals can build about the world .", "A general way...	[ "Animals living in groups make movement decisions that depend , among other factors , on social interactions with other group members .", "Our present understanding of social rules in animal collectives is mainly based on empirical fits to observations , with less emphasis in obtaining first-principles approaches...	[ "Animals need to act on uncertain data and with limited cognitive abilities to survive .", "It is well known that our sensory and sensorimotor processing uses probabilistic estimation as a means to counteract these limitations .", "Indeed , the way animals learn , forage or select mates is well explained by pro...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/functional genomics", "evolutionary biology/evolutionary and comparative genetics", "developmental biology/developmental evolution", "computational biology/genomics", "evolutionary biology/developmental evolution" ]	Early Evolution of Conserved Regulatory Sequences Associated with Development in Vertebrates	journal.pgen.1000762	null	[ [ "Comparisons between diverse vertebrate genomes have uncovered thousands of very highly conserved sequences that show little or no evidence of coding for proteins [1]–[3] .", "Many of these sequences are found in the proximity of genes that co-ordinate early development , and an increasing number have bee...	[ "Comparisons between diverse vertebrate genomes have uncovered thousands of highly conserved non-coding sequences , an increasing number of which have been shown to function as enhancers during early development .", "Despite their extreme conservation over 500 million years from humans to cartilaginous fish , the...	[ "Recent comparative analyses of vertebrate genomes has resulted in the identification of highly conserved non-coding sequences near genes that coordinate early development .", "Many of these sequences can activate gene expression and are thought to be important regulatory elements .", "Surprisingly , a large se...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology", "microbiology", "microbial evolution", "theoretical biology", "evolutionary modeling", "biology", "evolutionary theory", "microbial ecology", "systems biology", "ecosystem modeling", "immunity", "innate immunity", "computational biology", "evolutionary biology", "genetics a...	The Evolution of Mutualism in Gut Microbiota Via Host Epithelial Selection	journal.pbio.1001424	A computer model of the gut shows how a host can readily select friendly bacteria over harmful bacteria through a process called “selectivity amplification.”	[ [ "Many microbial species live on or are associated with epithelia of multicellular organisms .", "Examples range from plants and soil bacteria interactions in the rhizosphere where plant secretions affect the composition of bacterial communities [1] , [2] , through the light organs of marine animals in whi...	[ "The human gut harbours a large and genetically diverse population of symbiotic microbes that both feed and protect the host .", "Evolutionary theory , however , predicts that such genetic diversity can destabilise mutualistic partnerships .", "How then can the mutualism of the human microbiota be explained ?",...	[ "The cells of our bodies are greatly outnumbered by the bacteria that live on us and , in particular , in our gut .", "It is now clear that many gut bacteria are highly beneficial , protecting us from pathogens and helping us with digestion .", "But what prevents beneficial bacteria from going bad ?", "Why do...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "virology", "biology", "microbiology", "viral structure", "viral diseases" ]	Structural Basis of Differential Neutralization of DENV-1 Genotypes by an Antibody that Recognizes a Cryptic Epitope	journal.ppat.1002930	null	[ [ "Dengue viruses ( DENV ) are mosquito-borne viruses of the Flavivirus genus , which include other significant human pathogens such as West Nile ( WNV ) , Japanese encephalitis , and yellow fever viruses .", "Infection with DENV can cause symptoms in humans ranging from a mild febrile illness ( Dengue Feve...	[ "We previously developed a panel of neutralizing monoclonal antibodies against Dengue virus ( DENV ) -1 , of which few exhibited inhibitory activity against all DENV-1 genotypes .", "This finding is consistent with reports observing variable neutralization of different DENV strains and genotypes using serum from ...	[ "Within each Dengue virus ( DENV ) serotype , viruses are subdivided into genotypes based upon the protein sequence variation .", "Infection with a given serotype is believed to induce neutralizing antibodies that provide long-term immunity against secondary infection by a strain of the same serotype .", "Howev...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "molecular biology", "genetics and genomics", "hematology" ]	Polycomb Repressive Complex 2 (PRC2) Restricts Hematopoietic Stem Cell Activity	journal.pbio.0060093	Epigenetic modifications are central to the maintenance of cellular identity and are dynamically regulated during differentiation. We addressed the role of Polycomb group proteins during hematopoiesis and define a series of genes that are highly responsive to Polycomb dysfunction.	[ [ "Suppressor of Zeste 12 ( Suz12 ) was identified in a genetic screen performed in Drosophila to define transcriptional repressors [1] .", "Biochemical studies subsequently identified Suz12 as a component of a multimeric protein complex , termed Polycomb Repressive Complex 2 ( PRC2 ) , which is responsible...	[ "Polycomb group proteins are transcriptional repressors that play a central role in the establishment and maintenance of gene expression patterns during development .", "Using mice with an N-ethyl-N-nitrosourea ( ENU ) -induced mutation in Suppressor of Zeste 12 ( Suz12 ) , a core component of Polycomb Repressive...	[ "The chromatin environment that surrounds a gene heavily influences the gene's transcriptional activity .", "Specific modifications on histone tails serve as signposts for the basal transcriptional machinery , reflecting a cell's developmental history and identifying genes that should be actively transcribed and ...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "rna-binding proteins", "medicine and health sciences", "reproductive system", "vertebrates", "animals", "xenopus", "germ cells", "animal models", "zygotes", "developmental biology", "oocytes", "model organisms", "amphibians", "experimental organism systems", "embryos", "research and a...	Requirement of the 3′-UTR-dependent suppression of DAZL in oocytes for pre-implantation mouse development	journal.pgen.1007436	null	[ [ "The production of functional oocytes is an essential process in the female ovary , by which genetic information is continuously passed to the next generations .", "For successful oocyte development , gene expression needs to be precisely regulated according to the developmental stages and environmental c...	[ "Functional oocytes are produced through complex molecular and cellular processes .", "In particular , the contribution of post-transcriptional gene regulation mediated by RNA-binding proteins ( RBPs ) is crucial for controlling proper gene expression during this process .", "DAZL ( deleted in azoospermia-like ...	[ "Evolutionarily conserved DAZ family genes are indispensably involved in germline development .", "Dazl ( deleted in azoospermia-like ) is a member of the mammalian DAZ family of genes , and plays crucial roles in the sexual differentiation of primordial germ cells and spermatogenesis , and is implicated in the p...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/neurodevelopment", "neuroscience/cognitive neuroscience" ]	Functional Brain Networks Develop from a “Local to Distributed” Organization	journal.pcbi.1000381	null	[ [ "In previous work regarding task-level control in adults , we applied rs-fcMRI to a set of regions derived from an fMRI meta-analysis that included studies of control-demanding tasks .", "This analysis revealed that brain regions exhibiting different combinations of control signals across many tasks are g...	[ "The mature human brain is organized into a collection of specialized functional networks that flexibly interact to support various cognitive functions .", "Studies of development often attempt to identify the organizing principles that guide the maturation of these functional networks .", "In this report , we ...	[ "The first two decades of life represent a period of extraordinary developmental change in sensory , motor , and cognitive abilities .", "One of the ultimate goals of developmental cognitive neuroscience is to link the complex behavioral milestones that occur throughout this time period with the equally intricate...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "viral vaccines", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "immune cells", "immunology", "microbiology", "vaccines", "preventive medicine", "animal models", "model organisms", "experimental organism systems", "infectious disease cont...	Chronic schistosomiasis suppresses HIV-specific responses to DNA-MVA and MVA-gp140 Env vaccine regimens despite antihelminthic treatment and increases helminth-associated pathology in a mouse model	journal.ppat.1007182	null	[ [ "Human immunodeficiency virus ( HIV ) and parasitic helminthic worm infections are highly prevalent and geographically overlap each other in sub Saharan Africa ( SSA ) [1 , 2] .", "A majority of inhabitants harbor at least one or more species of parasitic helminth infection [3–6] and an estimated 50% of t...	[ "Future HIV vaccines are expected to induce effective Th1 cell-mediated and Env-specific antibody responses that are necessary to offer protective immunity to HIV infection .", "However , HIV infections are highly prevalent in helminth endemic areas .", "Helminth infections induce polarised Th2 responses that m...	[ "Chronic parasitic worm infections are thought to reduce the efficacy of vaccines .", "Given that HIV and worm infections are common in sub-Saharan Africa ( SSA ) and their geographical distribution vastly overlaps , it is likely that future HIV vaccines in SSA will be administered to a large proportion of people...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/medical genetics", "genetics and genomics/population genetics" ]	Rapid Assessment of Genetic Ancestry in Populations of Unknown Origin by Genome-Wide Genotyping of Pooled Samples	journal.pgen.1000866	null	[ [ "Genetic ancestry , as studied through DNA sequence variation , has shed light on the history , migration patterns , and relationships among human populations [1] , [2] .", "In the context of medical population genetics , genetic ancestry forms the basis of admixture mapping [3] .", "Additionally , ge...	[ "As we move forward from the current generation of genome-wide association ( GWA ) studies , additional cohorts of different ancestries will be studied to increase power , fine map association signals , and generalize association results to additional populations .", "Knowledge of genetic ancestry as well as popu...	[ "Many association studies have been published looking for genetic variants contributing to a variety of human traits such as obesity , diabetes , and height .", "Because the frequency of genetic variants can differ across populations , it is important to have estimates of genetic ancestry in the individuals being...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "meiosis", "cell death", "nuclear staining", "nucleases", "caenorhabditis", "enzymes", "cell cycle and cell division", "cell processes", "dna-binding proteins", "enzymology", "animals", "animal models", "germ cells", "caenorhabditis elegans", "oocytes", "model organi...	The conserved LEM-3/Ankle1 nuclease is involved in the combinatorial regulation of meiotic recombination repair and chromosome segregation in Caenorhabditis elegans	journal.pgen.1007453	null	[ [ "Meiosis is comprised of two specialized cell divisions that elicit the reduction of the diploid genome to haploid gametes .", "Homologous recombination occurs in the first meiotic division and is required for meiotic crossover ( CO ) formation [1] .", "COs are needed to shuffle genetic information be...	[ "Homologous recombination is essential for crossover ( CO ) formation and accurate chromosome segregation during meiosis .", "It is of considerable importance to work out how recombination intermediates are processed , leading to CO and non-crossover ( NCO ) outcome .", "Genetic analysis in budding yeast and Ca...	[ "Meiotic recombination is required for genetic diversity and for proper chromosome segregation .", "Recombination intermediates , such as Holliday junctions ( HJs ) , are generated and eventually resolved to produce crossover ( CO ) and non-crossover ( NCO ) .", "While an excess of meiotic double-strand breaks ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell physiology", "action potentials", "medicine and health sciences", "muscle tissue", "cardiovascular anatomy", "membrane potential", "electrophysiology", "neuroscience", "ion channels", "bioassays and physiological analysis", "research and analysis methods", "curve fitting", "mathematica...	Modeling Electrophysiological Coupling and Fusion between Human Mesenchymal Stem Cells and Cardiomyocytes	journal.pcbi.1005014	null	[ [ "Ischemic heart disease , which results from reduced coronary flow of oxygenated blood , is a leading cause of myocardial infarction and heart failure .", "This insufficient oxygenation results in the death of cardiomyocytes , which are normally incapable of substantial regeneration .", "Therefore , d...	[ "Human mesenchymal stem cell ( hMSC ) delivery has demonstrated promise in preclinical and clinical trials for myocardial infarction therapy; however , broad acceptance is hindered by limited understanding of hMSC-human cardiomyocyte ( hCM ) interactions .", "To better understand the electrophysiological conseque...	[ "Myocardial infarction—better known as a heart attack—strikes on average every 43 seconds in America .", "An emerging approach to treat myocardial infarction patients involves the delivery of human mesenchymal stem cells ( hMSCs ) to the damaged heart .", "While clinical trials of this therapeutic approach have...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cardiovascular disorders/coronary artery disease", "immunology/genetics of the immune system", "genetics and genomics/complex traits" ]	Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci	journal.pgen.1001374	null	[ [ "A member of the immunoglobulin superfamily of adhesion receptors , ICAM-1 is expressed on endothelial cells where it serves as a receptor for the leukocyte integrins LFA-1 and Mac-1 [1] .", "A soluble form of ICAM-1 ( sICAM-1 ) is present in plasma and is thought to arise from proteolytic cleavage of the...	[ "Soluble ICAM-1 ( sICAM-1 ) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction , diabetes , stroke , and malaria .", "Despite evidence for a heritable component to sICAM-1 levels , few genetic loci have been identified so far .", "To comp...	[ "Soluble Intercellular Adhesion Molecule 1 ( sICAM-1 ) is an inflammatory marker that has been associated with several common diseases such as diabetes , heart disease , stroke , and malaria .", "While it is known that blood concentrations of sICAM-1 are at least partially genetically determined , our current kno...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusion" ]	[]	Is PCR the Next Reference Standard for the Diagnosis of Schistosoma in Stool? A Comparison with Microscopy in Senegal and Kenya	journal.pntd.0003959	null	[ [ "Schistosomiasis control strategies are currently based on mass drug administration ( MDA ) with praziquantel to populations at risk [1] .", "Disease mapping , MDA allocation , and post-MDA monitoring of infection are based on standard microscopy techniques: urine filtration for Schistosoma haematobium , ...	[ "The current reference test for the detection of S . mansoni in endemic areas is stool microscopy based on one or more Kato-Katz stool smears .", "However , stool microscopy has several shortcomings that greatly affect the efficacy of current schistosomiasis control programs .", "A highly specific multiplex rea...	[ "In the developing world , over 207 million people are infected with parasitic Schistosoma worms .", "Schistosoma mansoni is one of the most widespread species , and its routine diagnosis is based on microscopic detection of parasite eggs in stool samples .", "This technique is , however , highly observer-depen...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "developmental biology", "mus (mouse)" ]	An Integrated Gene Regulatory Network Controls Stem Cell Proliferation in Teeth	journal.pbio.0050159	A network comprising Activin, BMP, FGF, and Follistatin regulate incisor stem cell proliferation in the niche and account for asymmetric organogenesis.	[ [ "Stem cells reside in specific niches that regulate their self-renewal and differentiation .", "In general , these niches consist of various types of neighboring differentiated cells , which provide a milieu of extracellular matrix and signaling molecules that regulate the unique behavior of stem cells ."...	[ "Epithelial stem cells reside in specific niches that regulate their self-renewal and differentiation , and are responsible for the continuous regeneration of tissues such as hair , skin , and gut .", "Although the regenerative potential of mammalian teeth is limited , mouse incisors grow continuously throughout ...	[ "Stem cells reside in specific niches that regulate their self-renewal and differentiation , and are responsible for the continuous regeneration of tissues .", "Although the regenerative potential of mammalian teeth is limited , mouse incisors grow continuously throughout life and contain stem cells at their prox...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Improving the Modeling of Disease Data from the Government Surveillance System: A Case Study on Malaria in the Brazilian Amazon	journal.pcbi.1003312	null	[ [ "Current best practices regarding the collection of disease data consist in the unbiased sampling of individuals ( e . g . , through aggressive active case detection; [1] , [2] ) using the most sensitive pathogen detection method available ( e . g . , polymerase chain reaction ( PCR ) for malaria ) .", "T...	[ "The study of the effect of large-scale drivers ( e . g . , climate ) of human diseases typically relies on aggregate disease data collected by the government surveillance network .", "The usual approach to analyze these data , however , often ignores", "a ) changes in the total number of individuals examined ,...	[ "Disease data collected by the government surveillance system are frequently used to understand the influence of large-scale phenomena ( e . g . , climate ) on human health because these data often have a large temporal and/or geographical span .", "The down side is that", "a ) these data are often biased towar...	2013
[ "Introduction", "Results", "Discussion" ]	[ "invertebrates", "cell death", "medicine and health sciences", "rna interference", "pathology and laboratory medicine", "enzymes", "neurodegenerative diseases", "cell processes", "enzymology", "animals", "animal models", "guanine nucleotide exchange factors", "drosophila melanogaster", "mo...	Vimar Is a Novel Regulator of Mitochondrial Fission through Miro	journal.pgen.1006359	null	[ [ "Mitochondrial fission , fusion and transport play important roles for the function of this organelle [1 , 2] .", "The balance between fusion and fission controls mitochondrial morphology , which is mediated by series of large dynamin-related GTPases [3] .", "Among these GTPases , mitofusin1/mitofusin...	[ "As fundamental processes in mitochondrial dynamics , mitochondrial fusion , fission and transport are regulated by several core components , including Miro .", "As an atypical Rho-like small GTPase with high molecular mass , the exchange of GDP/GTP in Miro may require assistance from a guanine nucleotide exchang...	[ "Mitochondrial dynamics including fusion , fission and transport are essential for energy supply in eukaryotic cells; and defects in mitochondrial dynamics often result in premature aging and diseases such as Parkinson's disease ( PD ) .", "In mitochondrial transport machinery , the Miro/Milton complex loads mito...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "microbiology", "molecular cell biology" ]	HCMV-Infected Cells Maintain Efficient Nucleotide Excision Repair of the Viral Genome while Abrogating Repair of the Host Genome	journal.ppat.1003038	null	[ [ "Human Cytomegalovirus ( HCMV ) is among the leading causes of birth defects in the United States , affecting an estimated 8000 children per year [1] .", "Each year ∼1% of all newborns are congenitally infected with HCMV .", "Of these infants , 5–10% manifest signs of serious neurological defects at b...	[ "Many viruses subvert the host cell's ability to mount and complete various DNA damage responses ( DDRs ) after infection .", "HCMV infection of permissive fibroblasts activates host DDRs at the time of viral deposition and during replication , but the DDRs remain uncompleted without arrest or apoptosis .", "We...	[ "Human cytomegalovirus ( HCMV ) is a leading cause of birth defects .", "This may be due in part to this virus' ability to inflict specific damage to its host's DNA , combined with the disruption of an infected cell's ability to repair damage .", "Earlier studies found that components of the cell's repair machi...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "knees", "rheumatology", "medicine and health sciences", "legs", "diagnostic radiology", "functional magnetic resonance imaging", "limbs (anatomy)", "neuroscience", "magnetic resonance imaging", "clinical medicine", "pharmaceutics", "brain mapping", "pharmacology", "neuroimaging", "resea...	Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials	journal.pbio.1002570	The biological basis of the placebo effect is poorly understood. This study shows that connectivity of the prefrontal cortex predicts the propensity for placebo response in chronic pain patients.	[ [ "Positive medical responses to placebo treatments are a well-recognized phenomenon observed in many pathologies , with a higher prevalence for neurological and painful conditions [1 , 2] .", "Placebo analgesia is observed ubiquitously in pain treatment trials , especially in chronic pain populations , in ...	[ "Placebo response in the clinical trial setting is poorly understood and alleged to be driven by statistical confounds , and its biological underpinnings are questioned .", "Here we identified and validated that clinical placebo response is predictable from resting-state functional magnetic-resonance-imaging ( fM...	[ "Placebo response is extensively studied in healthy subjects and for experimental manipulations .", "However , in the clinical setting it has been primarily relegated to statistical confounds .", "Here , for the first time we examine the predictability of future placebo response in the clinical setting in patie...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dermatology", "medicine and health sciences", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "treponematoses", "bacterial diseases", "skin infections", "signs and symptoms", "benin", "neglected tropical diseases", "africa", "skin diseases", "infectious...	Integrated approach in the control and management of skin neglected tropical diseases in Lalo, Benin	journal.pntd.0006584	null	[ [ "Neglected Tropical Diseases ( NTD ) are a diverse group of communicable diseases prevalent in tropical and subtropical areas .", "They are endemic in 149 countries .", "At least 100 of these countries have two or more endemic NTD .", "At least 30 of these countries have 6 or more endemic NTD [1 ,...	[ "Neglected Tropical Diseases ( NTDs ) are a group of several communicable diseases prevalent in the tropical and subtropical areas .", "The co-endemicity of these diseases , the similarity of the clinical signs , and need to maximize limited financial and human resources have necessitated implementation of integr...	[ "Neglected Tropical Diseases are a group of several communicable diseases prevalent in the tropical and subtropical areas .", "The co-endemicity of these diseases , the similarity of the clinical signs , need to maximize limited financial and human resources have necessitated the integrated approach .", "Our st...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Deletion of IL-4 Receptor Alpha on Dendritic Cells Renders BALB/c Mice Hypersusceptible to Leishmania major Infection	journal.ppat.1003699	null	[ [ "Leishmania spp .", "are protozoan parasites that are transmitted by Phlebotomus spp .", "sandflies and can cause several forms of disease in humans , ranging from localized cutaneous lesions to visceral Leishmaniasis , where parasites invade internal organs such as the spleen and liver .", "The i...	[ "In BALB/c mice , susceptibility to infection with the intracellular parasite Leishmania major is driven largely by the development of T helper 2 ( Th2 ) responses and the production of interleukin ( IL ) -4 and IL-13 , which share a common receptor subunit , the IL-4 receptor alpha chain ( IL-4Rα ) .", "While IL...	[ "Leishmaniasis is a parasitic infection caused by protozoan parasites of Leishmania species and is transmitted by the sandfly .", "Disease in humans ranges from localized cutaneous lesions to disseminated visceral Leishmaniasis .", "Mouse models of Leishmania major infection have demonstrated that a “healing” r...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology and life sciences", "genomics", "computational biology" ]	MODMatcher: Multi-Omics Data Matcher for Integrative Genomic Analysis	journal.pcbi.1003790	null	[ [ "Cells employ multiple levels of regulation that enable them to respond to genetic , epigenetic , genomic , and environmental perturbations .", "With advances in high-throughput technologies , comprehensive data sets have been generated to measure multiple aspects of biological regulation , such as geneti...	[ "Errors in sample annotation or labeling often occur in large-scale genetic or genomic studies and are difficult to avoid completely during data generation and management .", "For integrative genomic studies , it is critical to identify and correct these errors .", "Different types of genetic and genomic data a...	[ "Many human diseases are complex with multiple genetic and environmental causal factors interacting together to give rise to disease phenotypes .", "Such factors affect biological systems through many layers of regulations , including transcriptional and epigenetic regulation , and protein changes .", "To fully...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1	journal.pbio.1002347	The oxygen-dependent asparagine hydroxylase FIH regulates the transcription factor HIF during the cellular response to hypoxia. This study suggests that FIH may also contribute to the hypoxia response by affecting cellular metabolism via altered deubiquitinase targeting.	[ [ "Hypoxia is a common feature of the microenvironment in a number of pathophysiologic conditions and represents a significant threat to cellular metabolic homeostasis [1] .", "Eukaryotic cells have evolved the capacity to rapidly sense changes in intracellular oxygen levels through a family of hydroxylases...	[ "The asparagine hydroxylase , factor inhibiting HIF ( FIH ) , confers oxygen-dependence upon the hypoxia-inducible factor ( HIF ) , a master regulator of the cellular adaptive response to hypoxia .", "Studies investigating whether asparagine hydroxylation is a general regulatory oxygen-dependent modification have...	[ "Hypoxia is a commonly encountered physiologic and pathophysiologic stress to which mammalian cells have evolved an effective adaptive response .", "This response is governed by a transcription factor termed the hypoxia-inducible factor ( HIF ) .", "The mechanisms linking the cellular sensing of oxygen levels t...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/plant genomes and evolution", "genetics and genomics", "genetics and genomics/comparative genomics" ]	Following Tetraploidy in Maize, a Short Deletion Mechanism Removed Genes Preferentially from One of the Two Homeologs	journal.pbio.1000409	Following genome duplication and selfish DNA expansion, maize used a heretofore unknown mechanism to shed redundant genes and functionless DNA with bias toward one of the parental genomes.	[ [ "Decades ago it was proposed that whole-genome duplication provides raw material for evolutionary innovation , as reviewed [1] .", "The angiosperm phylogenetic tree of organisms with complete genome sequence has provided evidence for repeated ancient tetraploidies in all lineages ( Figure 1 ) .", "How...	[ "Previous work in Arabidopsis showed that after an ancient tetraploidy event , genes were preferentially removed from one of the two homeologs , a process known as fractionation .", "The mechanism of fractionation is unknown .", "We sought to determine whether such preferential , or biased , fractionation exist...	[ "All genomes can accumulate dispensable DNA in the form of duplications of individual genes or even partial or whole genome duplications .", "Genomes also can accumulate selfish DNA elements .", "Duplication events specifically are often followed by extensive gene loss .", "The maize genome is particularly ex...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "sexual selection", "sexual conflict", "population genetics", "biology", "evolutionary biology", "evolutionary processes", "evolutionary genetics", "evolutionary theory" ]	Experimental Evolution of a Novel Sexually Antagonistic Allele	journal.pgen.1002917	null	[ [ "Understanding the mechanisms that promote variation in fitness-related traits within populations presents an enduring challenge in evolutionary biology [1] , [2]: intralocus sexual conflict is predicted to be one such mechanism [3]–[6] .", "Intralocus conflict occurs when the same allele at a single locu...	[ "Evolutionary conflict permeates biological systems .", "In sexually reproducing organisms , sex-specific optima mean that the same allele can have sexually antagonistic expression , i . e . beneficial in one sex and detrimental in the other , a phenomenon known as intralocus sexual conflict .", "Intralocus sex...	[ "Males and females are markedly different in many features , meaning that a trait that is beneficial for one sex may be detrimental for the other .", "Recent studies show that this type of sexual antagonism is abundant in natural populations; however , no study has tested the evolutionary fate of a sexually antag...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "cell fate determination", "neural stem cells", "stem cells", "signaling", "molecular development", "gene expression", "biology", "molecular cell biology", "cell differentiation", "dna transcription", "adult stem cells" ]	Fbw7 Repression by Hes5 Creates a Feedback Loop That Modulates Notch-Mediated Intestinal and Neural Stem Cell Fate Decisions	journal.pbio.1001586	A novel intracellular positive feedback loop connects Fbw7 and Notch: while Fbw7 down-regulates the stability of NICD protein, it is also itself transcriptionally down-regulated by NICD target Hes5.	[ [ "FBW7 belongs to the family of SCF ( Skp1 , Cul1 , F-box ) -E3 ligases , which degrades several oncoproteins that function in cellular growth and division pathways , including c-MYC , CYCLIN-E , c-JUN , and Notch proteins .", "Three FBW7 isoforms have been identified ( FBW7α , FBW7β , FBW7γ ) , each with ...	[ "FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase , which mediates degradation of an array of different target proteins .", "The Fbw7 locus comprises three different isoforms , each with its own promoter and each suspected to have a distinct set of substrates .", "Most FBW7 targets have important ...	[ "The Notch signalling pathway is a highly conserved system that controls cell differentiation decisions in a wide range of animal species and cell types , and at different steps during cell lineage progression .", "An important function of the Notch pathway is in lateral inhibition—an interaction between equal ad...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology/cell differentiation", "genetics and genomics/gene function", "cell biology" ]	Drosophila Lipophorin Receptors Mediate the Uptake of Neutral Lipids in Oocytes and Imaginal Disc Cells by an Endocytosis-Independent Mechanism	journal.pgen.1001297	null	[ [ "Organisms need to tightly regulate the balance between energy intake , usage and storage .", "Imbalances in these processes are at the heart of several major human health problems such as obesity , cardiovascular disease and diabetes [1] .", "In recent years , the use of Drosophila and other genetica...	[ "Lipids are constantly shuttled through the body to redistribute energy and metabolites between sites of absorption , storage , and catabolism in a complex homeostatic equilibrium .", "In Drosophila , lipids are transported through the hemolymph in the form of lipoprotein particles , known as lipophorins .", "T...	[ "Understanding the complex mechanisms that regulate the storage of caloric surpluses in the form of fat is critical in view of the public health problems caused by the continuous rise of obesity and diabetes .", "Important advances in the field have been obtained from studies using simple animal models like worms...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "neurochemistry", "body fluids", "parasite replication", "cardiovascular anatomy", "neuroscience", "parasitic diseases", "parasitic protozoans", "parasitology", "organisms", "parasitemia", "electrocardiography", "protozoans", "bioassays and physiological ana...	L-arginine supplementation reduces mortality and improves disease outcome in mice infected with Trypanosoma cruzi	journal.pntd.0006179	null	[ [ "Chagas disease ( or American Trypanosomiasis ) is caused by Trypanosoma cruzi , a protozoan parasite of the Kinetoplastidae family [1] .", "About 7 million people are affected , with 100 million at risk of infection in 21 Latin American countries .", "Currently , Chagas disease is considered by the W...	[ "Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America , recently emerging on other continents due to migration .", "As infection in mice is characterized by depletion of plasma L-arginine , the effect on infection outcome was tested in mice with or...	[ "Trypanosoma cruzi is the causative agent of the neglected Chagas disease in humans .", "During infection in mice , depletion of plasma L-arginine is correlated with mortality .", "L-arginine is a semi-essential amino acid needed for cell proliferation , and is the substrate of arginase 1 ( Arg-1 ) and inducibl...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "crystal structure", "caulobacter", "condensed matter physics", "microbiology", "bacterial biochemistry", "signaling complexes", "prokaryotic models", "model organisms", "crystallography", "cellular structures and organelles", "bacteria", "research and analysis methods", "p...	Cell Fate Regulation Governed by a Repurposed Bacterial Histidine Kinase	journal.pbio.1001979	The pathway that regulates asymmetric cell division in Caulobacter involves a signaling kinase whose catalytic output domain has been repurposed as an input sensor of the phosphorylation state of the response regulator – a reversal of the conventional direction of information flow; this allows wiring of simple linear s...	[ [ "Cell fate decisions driven by the spatial organization of signaling proteins are a hallmark of asymmetric divisions in systems as diverse as stem cells and bacteria .", "Caulobacter , a model system for localization-dependent signaling network studies , divides asymmetrically yielding two distinct daught...	[ "One of the simplest organisms to divide asymmetrically is the bacterium Caulobacter crescentus .", "The DivL pseudo-histidine kinase , positioned at one cell pole , regulates cell-fate by controlling the activation of the global transcription factor CtrA via an interaction with the response regulator ( RR ) DivK...	[ "Across all kingdoms of life the generation of cell-type diversity is the consequence of asymmetry at the point of cell division .", "The bacterium Caulobacter crescentus divides asymmetrically to produce daughter cells that have distinct morphology and behavior .", "As in eukaryotes , an unequal distribution o...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Mathematical Modelling of Molecular Pathways Enabling Tumour Cell Invasion and Migration	journal.pcbi.1004571	null	[ [ "Understanding the etiology of metastasis is very important in clinical perspective .", "Despite the progress with treatment of the primary tumours , the chances of survival for a patient decrease tremendously once metastases have developed [1] .", "It is estimated that metastasis accounts for 90% of ...	[ "Understanding the etiology of metastasis is very important in clinical perspective , since it is estimated that metastasis accounts for 90% of cancer patient mortality .", "Metastasis results from a sequence of multiple steps including invasion and migration .", "The early stages of metastasis are tightly cont...	[ "We provide here a logical model that proposes gene/pathway candidates that could abrogate metastasis .", "The model explores the mechanisms and interplays between pathways that are involved in the process , identifies the main players in these mechanisms and gives some insight on how the pathways could be altere...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "microbiology", "computational biology", "biophysics", "molecular biology", "eubacteria" ]	Quantitative Characteristics of Gene Regulation by Small RNA	journal.pbio.0050229	In bacteria, small RNAs can regulate the expression of genes at the translational level. The many advantages of this type of control include a tuneable threshold response and resistance to biochemical noise.	[ [ "Small noncoding RNAs ( sRNAs ) have been demonstrated in recent years to play central regulatory roles in prokaryotes and eukaryotes [1–4] .", "Organisms that use sRNAs in post-transcriptional regulation range from bacteria to mammals .", "Interestingly , sRNAs are predominantly implicated in regulat...	[ "An increasing number of small RNAs ( sRNAs ) have been shown to regulate critical pathways in prokaryotes and eukaryotes .", "In bacteria , regulation by trans-encoded sRNAs is predominantly found in the coordination of intricate stress responses .", "The mechanisms by which sRNAs modulate expression of its ta...	[ "The activation of stress response programs , while crucial for the survival of a bacterial cell under stressful conditions , is costly in terms of energy and substrates and risky to the normal functions of the cell .", "Stress response is therefore tightly regulated .", "A recently discovered layer of regulati...	2007
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biotechnology/chemical biology of the cell", "computational biology/systems biology", "biotechnology/bioengineering", "computational biology/signaling networks" ]	Phase-Locked Signals Elucidate Circuit Architecture of an Oscillatory Pathway	journal.pcbi.1001040	null	[ [ "Determining the circuit architecture of cellular signaling pathways is challenging .", "Analysis using perturbative tools including siRNA [1] , [2] , protein over-expression [3] , chemical inhibitors [4] , or caged compounds [5] usually reveal multiple plausible models that require further refinements an...	[ "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 num...	[ "Key to robust discernment of cell circuit architecture is to have as many distinct response features as possible for comparison and evaluation .", "One under-appreciated characteristic of oscillatory circuits is that under periodic stimulation , these systems will exhibit responses synchronized to this stimulato...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "engineering and technology", "signal processing", "tropical diseases", "microbiology", "parasitic diseases", "parasitology", "neglected tropical diseases", "veterinary science", "software design", "infectious diseases", "c...	INsPECT, an Open-Source and Versatile Software for Automated Quantification of (Leishmania) Intracellular Parasites	journal.pntd.0002850	null	[ [ "Intracellular protozoan parasites are responsible for worldwide infectious diseases with a high impact in public health for developing countries .", "Among them , Leishmania parasites are causative agents of leishmaniasis , a worldwide endemic disease with diverse clinical manifestations ranging from sel...	[ "Intracellular protozoan parasites are causative agents of infectious diseases that constitute major health problems for developing countries .", "Leishmania sp .", ", Trypanosoma cruzi or Toxoplasma gondii are all obligate intracellular protozoan parasites that reside and multiply within the host cells of mamm...	[ "Research on intracellular parasites require using non-invasive technologies to follow up parasite proliferation inside their natural host cells by staying in the more physiological conditions as possible .", "High Content Screening ( HCS ) technology has recently emerged as a powerful image-based approach to scr...	2014
[ "Introduction", "Results and discussion", "Conclusions", "Methods" ]	[ "fungal spores", "plant anatomy", "medicine and health sciences", "fungal genetics", "fungi", "plant science", "plant pathology", "fungal diseases", "plants", "fungal reproduction", "infectious diseases", "mycology", "grasses", "leaves", "wheat", "fungal genomics", "eukaryota", "pl...	A conserved fungal glycosyltransferase facilitates pathogenesis of plants by enabling hyphal growth on solid surfaces	journal.ppat.1006672	null	[ [ "Micro-organisms have evolved many different mechanisms to enable them to cause diseases of plants .", "Some of these mechanisms are pathogen species-host plant specific .", "For example , the evolution and deployment of suites of secreted “effector” proteins , allow pathogens to manipulate components...	[ "Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants .", "However , the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form .", "During a random T-DNA mutagenesis screen pe...	[ "All plant-pathogenic fungi must grow hyphae across host tissues and cells to establish diseases .", "We have identified a single glycosyltransferase enzyme from the pleomorphic wheat pathogen Zymoseptoria tritici which functions specifically to enable hyphal growth on solid surfaces , and is therefore essential ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "helminth infections", "medicine and health sciences", "nutrition", "epidemiology", "biology and life sciences", "soil-transmitted helminthiases", "parasitic diseases", "malnutrition" ]	Risk Factors Associated with Malnutrition in One-Year-Old Children Living in the Peruvian Amazon	journal.pntd.0003369	null	[ [ "Malnutrition is the leading cause of mortality in preschool-age children ( i . e . children under five years of age ) in low- and middle-income countries ( LMICs ) .", "Over 150 million children suffer from one or more forms of malnutrition , including stunting , underweight and wasting [1] , [2] .", ...	[ "Children under two years of age are in the most critical window for growth and development .", "As mobility increases , this time period also coincides with first exposure to soil-transmitted helminth ( STH ) infections in tropical and sub-tropical environments .", "The association between malnutrition and STH...	[ "Malnutrition , including stunting and underweight , is one of the leading causes of morbidity and mortality in preschool-age children .", "Children under two years of age are at a particularly critical period for growth and development , and for first exposure to worm infections in tropical and subtropical envir...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology" ]	Dual Role of Topoisomerase II in Centromere Resolution and Aurora B Activity	journal.pbio.0060207	Analysis of cells lacking topoisomerase II reveals that the enzyme has an essential role in the segregation of chromosomes, and specifically centromeres, at anaphase-telophase of mitosis: it prevents non-disjunction and allows activation of the Aurora B kinase, so as to correct improper attachments between microtubules...	[ [ "Ordered segregation of the genome during cell division requires bipolar attachment to spindle microtubules [1] and maintenance of sister chromatid cohesion until anaphase onset [2] .", "Cohesin provides a physical link between sister chromatids , and cleavage of cohesin subunits results from separase act...	[ "Chromosome segregation requires sister chromatid resolution .", "Condensins are essential for this process since they organize an axial structure where topoisomerase II can work .", "How sister chromatid separation is coordinated with chromosome condensation and decatenation activity remains unknown .", "We ...	[ "Successful cell division requires that chromosomes are properly condensed and that each sister chromatid is self-contained by the time the sister pairs are segregated into separate daughter cells .", "It is also essential that the kinetochores at the centromeres of each pair of sister chromatids bind microtubule...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "epidemiology", "virology", "vector biology", "biology and life sciences", "microbiology", "disease vectors" ]	Characterization of Aedes aegypti Innate-Immune Pathways that Limit Chikungunya Virus Replication	journal.pntd.0002994	null	[ [ "Arthropod-borne viruses ( arboviruses ) replicate in both their vertebrate host and arthropod vector .", "This poses a unique problem for arboviruses as they are exposed to both the vertebrate and invertebrate immune systems .", "Arthropod vectors of arboviruses , such as mosquitoes , do not have the...	[ "Replication of arboviruses in their arthropod vectors is controlled by innate immune responses .", "The RNA sequence-specific break down mechanism , RNA interference ( RNAi ) , has been shown to be an important innate antiviral response in mosquitoes .", "In addition , immune signaling pathways have been repor...	[ "Chikungunya virus ( CHIKV ) is a mosquito-borne human-pathogenic arbovirus of the Togaviridae family , genus Alphavirus .", "Arbovirus replication in vectors , such as mosquitoes , is not passively tolerated but leads to immune responses , that control virus infection .", "These responses therefore represent i...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "sequencing techniques", "suppressor genes", "cereal crops", "fungi", "model organisms", "crops", "gene types", "molecular biology techniques", "plants", "schizosaccharomyces", "research and analysis methods", "saccharomyces", "sequence analysis", "genome complexity", ...	FgPrp4 Kinase Is Important for Spliceosome B-Complex Activation and Splicing Efficiency in Fusarium graminearum	journal.pgen.1005973	null	[ [ "Pre-mRNA splicing is mediated by the spliceosome that is formed by ordered interaction of the U1 , U2 , U4/U6 , U5 snRNPs , and non-snRNP proteins [1] .", "U1 and U2 first interact with the 5’-splice site ( 5’-ss ) and the branch point ( BP ) of the introns in pre-mRNA to generate the A complex .", "...	[ "PRP4 encodes the only kinase among the spliceosome components .", "Although it is an essential gene in the fission yeast and other eukaryotic organisms , the Fgprp4 mutant was viable in the wheat scab fungus Fusarium graminearum .", "Deletion of FgPRP4 did not block intron splicing but affected intron splicing...	[ "In eukaryotic organisms , many genes containing introns that need to be spliced by the spliceosome after transcription .", "Among all the spliceosome components , Prp4 is the only protein kinase .", "Unlike other organisms , deletion of the FgPRP4 kinase gene was not lethal in the wheat scab fungus Fusarium gr...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/host antiviral responses", "molecular biology/rna-protein interactions", "immunology/innate immunity", "cell biology/cell signaling" ]	An Antiviral Response Directed by PKR Phosphorylation of the RNA Helicase A	journal.ppat.1000311	null	[ [ "The primary detection of viral infection is by the host innate immune system , with the recognition of viral double-stranded RNA ( dsRNA ) a crucial early function .", "Responses to dsRNA are mediated by several protein receptors that recognize this pathogen-associated molecular pattern ( PAMP ) .", ...	[ "The double-stranded RNA-activated protein kinase R ( PKR ) is a key regulator of the innate immune response .", "Activation of PKR during viral infection culminates in phosphorylation of the α subunit of the eukaryotic translation initiation factor 2 ( eIF2α ) to inhibit protein translation .", "A broad range ...	[ "Our manuscript explores the immune response to viral infection by investigating events triggered by the protein kinase PKR .", "This sentinel kinase is constitutively expressed in all cells as an inactive protein that is subsequently activated by viral RNA produced during an infection .", "The active kinase pe...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genetics of the immune system", "clinical immunology", "genetics", "genetics and genomics", "biology", "human genetics", "immunology", "respiratory medicine", "pulmonology", "asthma" ]	Genome-Wide Association Study Identifies HLA-DP as a Susceptibility Gene for Pediatric Asthma in Asian Populations	journal.pgen.1002170	null	[ [ "Asthma is the most common chronic disorder in children , and asthma exacerbation is an important cause of childhood morbidity and hospitalization .", "The prevalence of childhood asthma in Japan is 5 . 0% among school children in 2006 [1] , and an estimated 300 million people worldwide have asthma [2] ."...	[ "Asthma is a complex phenotype influenced by genetic and environmental factors .", "We conducted a genome-wide association study ( GWAS ) with 938 Japanese pediatric asthma patients and 2 , 376 controls .", "Single-nucleotide polymorphisms ( SNPs ) showing strong associations ( P<1×10−8 ) in GWAS were further g...	[ "Asthma is the most common chronic disorder in children , and asthma exacerbation is an important cause of childhood morbidity and hospitalization .", "Here , taking advantage of recent technological advances in human genetics , we performed a genome-wide association study and follow-up validation studies to iden...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Topological Phenotypes Constitute a New Dimension in the Phenotypic Space of Leaf Venation Networks	journal.pcbi.1004680	null	[ [ "Our topological metric quantifies the hierarchical nesting of loops within the network as well as the topological lengths of tapered veins .", "The analysis follows an existing hierarchical decomposition algorithm [25 , 26 , 28] , constructing from a weighted network a binary tree graph termed the nestin...	[ "The leaves of angiosperms contain highly complex venation networks consisting of recursively nested , hierarchically organized loops .", "We describe a new phenotypic trait of reticulate vascular networks based on the topology of the nested loops .", "This phenotypic trait encodes information orthogonal to wid...	[ "Planar reticular networks are ubiquitous in nature and engineering , formed for instance by the arterial vasculature in the mammalian neocortex , urban street grids or the vascular network of plant leaves .", "We use a topological metric to characterize the way loops are nested in such networks and analyze a lar...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Functional Constraint Profiling of a Viral Protein Reveals Discordance of Evolutionary Conservation and Functionality	journal.pgen.1005310	null	[ [ "To comprehensively describe the functional roles of a given protein , which are often diverse for many viral proteins and include catalytic activity , intermolecular interactions , and/or cofactor binding , it is necessary to identify the individual functional residues that carry out the biochemical mechanis...	[ "Viruses often encode proteins with multiple functions due to their compact genomes .", "Existing approaches to identify functional residues largely rely on sequence conservation analysis .", "Inferring functional residues from sequence conservation can produce false positives , in which the conserved residues ...	[ "The analysis of sequence conservation is a common approach to identify functional residues within a protein .", "However , not all functional residues are conserved as natural evolution and species diversification permit continuous innovation of protein functionality through the retention of advantageous mutatio...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders/neuromuscular diseases", "genetics and genomics/genetics of disease", "molecular biology/dna repair" ]	MSH2 ATPase Domain Mutation Affects CTG•CAG Repeat Instability in Transgenic Mice	journal.pgen.1000482	null	[ [ "Myotonic dystrophy type 1 ( DM1 ) is a neuromuscular disease characterized by highly variable clinical manifestations including skeletal muscle , cardiorespiratory and brain defects and endocrine abnormalities [1] .", "DM1 results from the expansion of an unstable CTG trinucleotide repeat in the 3′-untra...	[ "Myotonic dystrophy type 1 ( DM1 ) is associated with one of the most highly unstable CTG•CAG repeat expansions .", "The formation of further repeat expansions in transgenic mice carrying expanded CTG•CAG tracts requires the mismatch repair ( MMR ) proteins MSH2 and MSH3 , forming the MutSβ complex .", "It has ...	[ "Myotonic dystrophy type 1 is a neuromuscular disease characterized by highly variable clinical manifestations , including muscular and neuropsychological symptoms .", "DM1 results from the dramatic expansion of an unstable CTG repeat in the DMPK gene .", "Longer CTG repeats cause a more severe form of the dise...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Improved Estimation and Interpretation of Correlations in Neural Circuits	journal.pcbi.1004083	null	[ [ "Functional connectivity is a statistical description of observed multineuronal activity patterns not reducible to the response properties of the individual cells .", "Functional connectivity reflects local synaptic connections , shared inputs from other regions , and endogenous network activity .", "...	[ "Ambitious projects aim to record the activity of ever larger and denser neuronal populations in vivo .", "Correlations in neural activity measured in such recordings can reveal important aspects of neural circuit organization .", "However , estimating and interpreting large correlation matrices is statisticall...	[ "It is now possible to record the spiking activity of hundreds of neurons at the same time .", "A meaningful statistical description of the collective activity of these neural populations—their ‘functional connectivity’—is a forefront challenge in neuroscience .", "We addressed this problem by identifying stati...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "ecology/environmental microbiology", "infectious diseases/viral infections", "infectious diseases/epidemiology and control of infectious diseases" ]	A Virulent Wolbachia Infection Decreases the Viability of the Dengue Vector Aedes aegypti during Periods of Embryonic Quiescence	journal.pntd.0000748	null	[ [ "Aedes aegypti , the primary vector of dengue viruses throughout the tropics , is a mosquito species that has strong associations with human habitation [1] .", "In the past , control of dengue has been complicated by an inability to eradicate Ae .", "aegypti from urban environments and implement susta...	[ "A new approach for dengue control has been proposed that relies on life-shortening strains of the obligate intracellular bacterium Wolbachia pipientis to modify mosquito population age structure and reduce pathogen transmission .", "Previously we reported the stable transinfection of the major dengue vector Aede...	[ "A virulent strain of the vertically-inherited bacterium Wolbachia pipientis ( wMelPop-CLA ) from the vinegar fly Drosophila melanogaster has been established in the dengue vector Aedes aegypti as part of a biological strategy for dengue control .", "In this medically important disease vector , wMelPop-CLA infect...	2010
[ "Introduction", "Results/Discussion", "Material and methods" ]	[ "medicine and health sciences", "breast tumors", "genetic networks", "gene regulation", "protein interaction networks", "carcinomas", "cancers and neoplasms", "gastrointestinal tumors", "liver diseases", "dna transcription", "oncology", "network analysis", "gastroenterology and hepatology", ...	Network perturbation by recurrent regulatory variants in cancer	journal.pcbi.1005449	null	[ [ "Recent efforts to understand noncoding variation through epigenomic annotation have shown that disease-associated variation is frequently located in regulatory DNA marked by DNase I hypersensitive sites ( DHSs ) or particular histone modifications [1–4] .", "Noncoding somatic variants in cancer have been...	[ "Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences .", "However , a majority of cancer variants arise in noncoding regions , and some of them are thought to play a critical role through transcriptional perturbation .", "Here we identified putative ...	[ "Identifying driver variants is a current challenge facing cancer genomics .", "A well-established and robust method for this is to find recurrence in large cohorts of samples .", "Recurrence patterns of amino acid-changing variants can reveal oncogenes and tumor suppressor genes .", "However , such single-ge...	2017
[ "Introduction", "Results/Discussion", "Methods" ]	[ "computational biology/synthetic biology", "computational biology/transcriptional regulation" ]	Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family	journal.pcbi.1000989	null	[ [ "The search for principles describing how specific nucleotide sequences are recognized by proteins remains one of the most fundamental problems to be solved in Biology [1]–[5] .", "The relevance of this question is linked to the wide breadth of basic cellular processes to be better understood with its res...	[ "The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids ( AAs ) and nucleotides ( NTs ) .", "This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be identified .", "...	[ "Transcriptional factors ( TF ) are proteins that bind specific short DNA sequences adjacent to the genes whose transcription they regulate .", "Although the nucleotide sequence recognized by a given regulator depends on the amino acids contacting the DNA , the mode in which amino acids and nucleotides interact i...	2010
[ "Introduction", "Results", "Materials and methods", "Discussion" ]	[ "recreation", "learning", "medicine and health sciences", "decision making", "applied mathematics", "social sciences", "neuroscience", "theory of mind", "learning and memory", "health care", "cognitive psychology", "mathematics", "cognition", "public and occupational health", "games", ...	A model of risk and mental state shifts during social interaction	journal.pcbi.1005935	null	[ [ "We use the data set shown in King-Casas et al . ( see [6] ) , consisting of 93 healthy investors , paired with 93 trustees , of which 55 were BPD diagnosed trustees ( BPD Group , “BPD” ) and 38 were healthy trustees , matched in age , gender , IQ and socio-economic status ( SES ) with the BPD trustee group (...	[ "Cooperation and competition between human players in repeated microeconomic games offer a window onto social phenomena such as the establishment , breakdown and repair of trust .", "However , although a suitable starting point for the quantitative analysis of such games exists , namely the Interactive Partially ...	[ "In multi-round games in which players can benefit by trusting each other , swift and catastrophic breakdowns can arise amidst otherwise efficient cooperation .", "We present a model that quantifies this as a form of anger , and we exploit novel algorithmic improvements in inference based on the model to examine ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna repair", "genetics and genomics/gene function", "genetics and genomics/chromosome biology" ]	Collaborative Action of Brca1 and CtIP in Elimination of Covalent Modifications from Double-Strand Breaks to Facilitate Subsequent Break Repair	journal.pgen.1000828	null	[ [ "CtIP was isolated as a binding partner of CtBP ( C-terminal binding protein ) , and has subsequently been shown to interact with a number of molecules , including BRCA1 ( Breast Cancer Susceptibility Gene", "1 ) [1] .", "CtIP is a functional homolog of yeast Sae2 ( Sporulation in the Absence of Spo E...	[ "Topoisomerase inhibitors such as camptothecin and etoposide are used as anti-cancer drugs and induce double-strand breaks ( DSBs ) in genomic DNA in cycling cells .", "These DSBs are often covalently bound with polypeptides at the 3′ and 5′ ends .", "Such modifications must be eliminated before DSB repair can ...	[ "Induction of double-strand breaks ( DSBs ) in chromosomal DNA effectively activates a program of cellular suicide and is widely used for chemotherapy on malignant cancer cells .", "Cells resist such therapies by quickly repairing the DSBs .", "Repair is carried out by two major DSB repair pathways , homologous...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "biochemistry", "biochemical simulations", "computer and information sciences", "network analysis", "biology and life sciences", "metabolic networks", "computational biology" ]	Systematic Evaluation of Methods for Integration of Transcriptomic Data into Constraint-Based Models of Metabolism	journal.pcbi.1003580	null	[ [ "The methods presented in this survey tend to fall into one of two categories .", "One encompasses all the methods that use transcript levels in order to improve the prediction of metabolic flux distributions .", "On the other hand are the methods for creating tissue ( or context ) specific models fro...	[ "Constraint-based models of metabolism are a widely used framework for predicting flux distributions in genome-scale biochemical networks .", "The number of published methods for integration of transcriptomic data into constraint-based models has been rapidly increasing .", "So far the predictive capability of ...	[ "Constraint-based modeling has become one of the most successful approaches for modeling large-scale biochemical networks .", "There are nowadays hundreds of genome-scale reconstructions of metabolic networks available for a wide variety of organisms ranging from bacteria to human cells .", "One of the limitati...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "metabolic networks", "anatomy and physiology", "hormones", "endocrine physiology", "physiological processes", "homeostasis", "insulin", "endocrinology", "diabetes and endocrinology", "biology", "systems biology", "biochemical simulations", "physiology", "computational biolog...	Quantifying the Contribution of the Liver to Glucose Homeostasis: A Detailed Kinetic Model of Human Hepatic Glucose Metabolism	journal.pcbi.1002577	null	[ [ "The human plasma glucose is kept in a narrow range between minimum values of ∼3 mM after prolonged fasting or extensive muscle activity and maximum values of ∼9 mM reached postprandially [1] , [2] .", "Homoeostasis of plasma glucose is crucial for the organism: Hyperglycemia results in non-enzymatic glyc...	[ "Despite the crucial role of the liver in glucose homeostasis , a detailed mathematical model of human hepatic glucose metabolism is lacking so far .", "Here we present a detailed kinetic model of glycolysis , gluconeogenesis and glycogen metabolism in human hepatocytes integrated with the hormonal control of the...	[ "Glucose is an indispensable fuel for all cells and organs , but at the same time leads to problems at high concentrations .", "As a consequence , blood glucose is controlled in a narrow range to guarantee constant supply and on the other hand avoid damages associated with elevated glucose levels .", "The liver...	2012
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "genetics and genomics/functional genomics", "plant biology/plant growth and development", "genetics and genomics/plant genetics and gene expression" ]	A Collection of Target Mimics for Comprehensive Analysis of MicroRNA Function in Arabidopsis thaliana	journal.pgen.1001031	null	[ [ "MicroRNAs ( miRNAs ) are a class of small RNA ( sRNA ) molecules that has recently emerged as a key regulator of gene activity .", "In plants , miRNAs are released from larger precursors ( pri-miRNAs ) in the nucleus mainly , by DICER-LIKE1 ( DCL1 ) [1] .", "The resulting sRNA duplex is methylated an...	[ "Many targets of plant microRNAs ( miRNAs ) are thought to play important roles in plant physiology and development .", "However , because plant miRNAs are typically encoded by medium-size gene families , it has often been difficult to assess their precise function .", "We report the generation of a large-scale...	[ "MiRNAs are small RNA molecules that play an important role in regulating gene function , both in animals and in plants .", "In plants , miRNA target mimicry is an endogenous mechanism used to negatively regulate the activity of a specific miRNA family , through the production of a false target transcript that ca...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Maximizing Sensory Dynamic Range by Tuning the Cortical State to Criticality	journal.pcbi.1004576	null	[ [ "Cortical neuronal network dynamics shift among myriad states to cope with the changing needs of the organism [1–3] .", "Strikingly different cortical states are observed during different behaviors such as sleep [4] , wakeful resting [5] , active movement [6] , or vigilant attention [7] .", "Externall...	[ "Modulation of interactions among neurons can manifest as dramatic changes in the state of population dynamics in cerebral cortex .", "How such transitions in cortical state impact the information processing performed by cortical circuits is not clear .", "Here we performed experiments and computational modelin...	[ "When many simple parts interact , the collective behavior of the whole can be astonishingly complex .", "A particularly striking example is our capacity for sensory perception , which results from the collective interactions of billions of relatively simple neurons .", "Another example is found in physical sys...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Risk Factors Associated with Ebola and Marburg Viruses Seroprevalence in Blood Donors in the Republic of Congo	journal.pntd.0003833	null	[ [ "Marburg and Ebola viruses ( family Filoviridae , genera Marburgvirus and Ebolavirus ) cause severe Viral Haemorrhagic Fever ( VHF ) in humans , with a high fatality rate in symptomatic cases [1 , 2 , 3] .", "They appear to infect and persist in some species of fruit bats , that may serve as natural reser...	[ "Ebola and Marburg viruses ( family Filoviridae , genera Ebolavirus and Marburgvirus ) cause haemorrhagic fevers in humans , often associated with high mortality rates .", "The presence of antibodies to Ebola virus ( EBOV ) and Marburg virus ( MARV ) has been reported in some African countries in individuals with...	[ "Ebola and Marburg viruses cause haemorrhagic fevers often fatal to humans .", "Here , we looked for antibodies to Ebola and Marburg viruses ( i . e . , markers of previous contact with these viruses ) in Congolese blood donors with no previous history of haemorrhagic fever .", "We found serologic evidence for ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "gene regulation", "dna-binding proteins", "animal models", "dna damage", "model organisms", "polymerases", "experimental organism systems", "sequence motif analysis", "dna", "molecular biology techniques", "mammalian genomics", "homologous recombination", "research and analysis methods", ...	Analysis of DNA polymerase ν function in meiotic recombination, immunoglobulin class-switching, and DNA damage tolerance	journal.pgen.1006818	null	[ [ "In mammalian cells , a diverse group of DNA polymerases carry out genomic DNA replication and genome maintenance .", "These include the core enzymes for semi-conservative DNA replication ( pols α , δ , ε and telomerase ) , base excision repair ( pol β ) , mitochondrial DNA replication and repair ( pol γ ...	[ "DNA polymerase ν ( pol ν ) , encoded by the POLN gene , is an A-family DNA polymerase in vertebrates and some other animal lineages .", "Here we report an in-depth analysis of pol ν–defective mice and human cells .", "POLN is very weakly expressed in most tissues , with the highest relative expression in testi...	[ "The work described here fills a current gap in the study of the 16 known DNA polymerases in vertebrate genomes .", "Until now , experiments with genetically disrupted mice have been reported for all but pol ν , encoded by the POLN gene .", "To intensively analyze the role of mammalian pol ν we generated multip...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "annealing (genetics)", "pathogens", "tropical diseases", "microbiology", "rna extraction", "alphaviruses", "viruses", "chikungunya virus", "rna viruses", "neglected tropical diseas...	Development of a single-tube one-step RT-LAMP assay to detect the Chikungunya virus genome	journal.pntd.0006448	null	[ [ "Chikungunya virus ( CHIKV ) , a single-stranded positive-sense enveloped RNA virus belonging to the genus Alphavirus , family Togaviridae , was originally isolated in Tanzania in 1953 [1] .", "The RNA genome ( approximately 12 kb ) , capped at the 5’ and with a poly ( A ) tail at 3’ end , comprises two o...	[ "A single-tube one-step real-time reverse transcription loop-mediated isothermal amplification ( RT-LAMP ) assay for rapid detection of chikungunya virus ( CHIKV ) targeting the conserved 6K-E1 target region was developed .", "The assay was validated with sera collected from a CHIKV outbreak in Senegal in 2015 ."...	[ "Current chikungunya virus ( CHIKV ) outbreaks highlight the necessity of sensitive techniques to allow the virus detection even at an early stage ( before the onset of clinical symptoms ) .", "In addition , CHIKV sometimes is misdiagnosed with other pathogens ( i . e . , dengue virus or malaria ) , which implies...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physics", "neuroscience/sensory systems", "computational biology/computational neuroscience", "computational biology", "neuroscience/theoretical neuroscience" ]	Minimal Models of Multidimensional Computations	journal.pcbi.1001111	null	[ [ "There is an emerging view that the primary function of many biological systems , from the molecular level to ecosystems , is to process information [1]–[4] .", "The nature of the computations these systems perform can be quite complex [5] , often due to large numbers of components interacting over wide s...	[ "The multidimensional computations performed by many biological systems are often characterized with limited information about the correlations between inputs and outputs .", "Given this limitation , our approach is to construct the maximum noise entropy response function of the system , leading to a closed-form ...	[ "Biological systems across many scales , from molecules to ecosystems , can all be considered information processors , detecting important events in their environment and transforming them into actions .", "Detecting events of interest in the presence of noise and other overlapping events often necessitates the u...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "somatosensory system", "medicine and health sciences", "immune physiology", "immune cells", "pathology and laboratory medicine", "respiratory infections", "nervous system", "spleen", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "neuroscience", "pulmonolo...	Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase	journal.ppat.1005615	null	[ [ "Enhanced pain sensitivity is a hallmark of inflammation and is a debilitating feature of many clinical diseases , including chronic Human Immunodeficiency Virus-1 ( HIV-1 ) infections [1 , 2] .", "However the underlying causes of chronic pain remain poorly defined [3] .", "Pain hypersensitivity in ra...	[ "Increased pain sensitivity is a comorbidity associated with many clinical diseases , though the underlying causes are poorly understood .", "Recently , chronic pain hypersensitivity in rodents treated to induce chronic inflammation in peripheral tissues was linked to enhanced tryptophan catabolism in brain media...	[ "Chronic pain is a factor in diseases that afflict many people , yet the underlying causes of pain are poorly understood .", "Here we assess the effects of virus infections on pain sensitivity in mice .", "Infecting mice with two different viruses , influenza and mouse leukemia virus ( MuLV ) increased pain sen...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome sequencing", "genome evolution", "microbial evolution", "comparative genomics", "biology", "genomics", "evolutionary biology", "genomic evolution", "microbiology", "evolutionary processes", "host-pathogen interaction" ]	Comparative Genomics of Wolbachia and the Bacterial Species Concept	journal.pgen.1003381	null	[ [ "The increasing availability of genomic data for closely related strains and species enables bacterial population sizes and structures to be explored in far greater detail than was possible until now .", "A major question is whether asexually reproducing bacterial cells are organized into “clusters” that ...	[ "The importance of host-specialization to speciation processes in obligate host-associated bacteria is well known , as is also the ability of recombination to generate cohesion in bacterial populations .", "However , whether divergent strains of highly recombining intracellular bacteria , such as Wolbachia , can ...	[ "Speciation in sexual organisms is defined as the inability of two populations to get viable offspring .", "Speciation in asexual , obligate endosymbionts is thought to be an indirect consequence of host-specialization .", "An important question is if divergent endosymbionts would start blending if the host bar...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "transfer rna", "enzymes", "cell cycle and cell division", "cell processes", "dna-binding proteins", "enzymology", "dna damage", "fungi", "model organisms", "polymerases", "dna replication", "dna", "synthesis phase", "schizosaccharomyces", "research and analysis methods", "proteins", ...	Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity	journal.pgen.1006238	null	[ [ "Faithful and efficient replication of the genome is essential in every cell cycle , yet there are many naturally occurring obstacles that impede fork progression .", "These sites include stable protein complexes , DNA secondary structures , and ongoing transcription , each of which can challenge replicat...	[ "Replicative DNA helicases expose the two strands of the double helix to the replication apparatus , but accessory helicases are often needed to help forks move past naturally occurring hard-to-replicate sites , such as tightly bound proteins , RNA/DNA hybrids , and DNA secondary structures .", "Although the Schi...	[ "Progression of the DNA replication machinery is challenged in every S phase by active transcription , tightly bound protein complexes , and formation of stable DNA secondary structures .", "Using genome-wide analyses , we show that the evolutionarily conserved fission yeast Pfh1 DNA helicase promotes fork progre...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[]	The Role of Interleukin-1 cytokine family (IL-1β, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis	journal.pntd.0007098	null	[ [ "Mycetoma is a chronic granulomatous subcutaneous inflammatory disease , caused by certain bacteria ( actinomycetoma ) or fungi ( eumycetoma ) .", "This infection progresses to affect the deep structures and bones leading to massive destruction , deformities and disabilities [1] .", "It constitutes a ...	[ "Mycetoma is a neglected tropical disease , endemic in many tropical and subtropical regions , characterised by massive deformity and disability and can be fatal if untreated early and appropriately .", "Interleukins ( IL ) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing th...	[ "Mycetoma is a progressive chronic granulomatous fungal or bacterial infection that may result in massive destruction of subcutaneous tissues , muscles and bones .", "Mycetoma is a neglected disease which is endemic in many tropical and subtropical areas .", "If the disease is not treated properly , eventually ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "microbial metabolism", "microbial mutation", "population genetics", "metabolic networks", "microbiology", "bacterial biochemistry", "microbial evolution", "molecular genetics", "forms of evolution", "microbial physiology", "metabolic pathways", "gene expression", "biology"...	Mapping the Fitness Landscape of Gene Expression Uncovers the Cause of Antagonism and Sign Epistasis between Adaptive Mutations	journal.pgen.1004149	null	[ [ "The concept of a fitness landscape unites the three levels of evolutionary change – genotype , phenotype , and fitness – into a mathematical picture of the potential for , and constraints upon , adaptive evolution .", "By mapping genotypes to a measure of fitness , fitness landscapes guide our understand...	[ "How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once ?", "Here we combined independently-arising beneficial mutations that altered enzyme levels in the central metabolism of Methylobacterium extorquen...	[ "The pace and outcome of a series of adaptive steps in an evolving lineage depends upon how well different beneficial mutations stack on top of each other .", "We found that independent beneficial mutations that affected gene expression for a metabolic pathway did not work well together , and were often jointly d...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immune response", "immunology/innate immunity", "dermatology/skin infections", "infectious diseases/skin infections", "immunology/immunity to infections" ]	Keratinocytes Determine Th1 Immunity during Early Experimental Leishmaniasis	journal.ppat.1000871	null	[ [ "Experimental leishmaniasis has been the first model to directly demonstrate the relevance of the T helper 1/T helper 2 ( Th1/Th2 ) dichotomy for the outcome of an infection or disease in vivo .", "Upon cutaneous infection with L . major , C57BL/6 mice generate a Th1 response and subsequently control infe...	[ "Experimental leishmaniasis is an excellent model system for analyzing Th1/Th2 differentiation .", "Resistance to Leishmania ( L . ) major depends on the development of a L . major specific Th1 response , while Th2 differentiation results in susceptibility .", "There is growing evidence that the microenvironmen...	[ "To clear skin infections with the parasite Leishmania major , a specific T-helper ( Th ) -cell immune response has to be generated .", "The type of Th-cell response is determined early after infection by yet unknown mechanisms .", "In resistant mice a Th1-pattern is generated .", "A Th2-pattern in BALB/c mic...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Reconciling high-throughput gene essentiality data with metabolic network reconstructions	journal.pcbi.1006507	null	[ [ "With the rise of antibiotic resistance , there is a growing need to discover new therapeutic targets to treat bacterial infections .", "One attractive strategy is to target genes that are essential for growth and survival [1–4] .", "Discovery of such genes has been a long-standing interest , and adva...	[ "The identification of genes essential for bacterial growth and survival represents a promising strategy for the discovery of antimicrobial targets .", "Essential genes can be identified on a genome-scale using transposon mutagenesis approaches; however , variability between screens and challenges with interpreta...	[ "With the rise of antibiotic resistance , there is a growing need to discover new therapeutic targets to treat bacterial infections .", "One attractive strategy is to target genes that are essential for growth and survival .", "Essential genes can be identified with transposon mutagenesis approaches; however , ...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures	journal.ppat.1005318	null	[ [ "Respiratory syncytial virus ( RSV ) infects nearly every child by the age of 2 [1] .", "It causes severe lower respiratory disease in ~2% of these infants , making RSV infection the most frequent cause of hospitalization of infants and children in the developed world [2–4] .", "While supportive care ...	[ "Respiratory syncytial virus ( RSV ) is the most frequent cause of lower respiratory disease in infants , but no vaccine or effective therapy is available .", "The initiation of RSV infection of immortalized cells is largely dependent on cell surface heparan sulfate ( HS ) , a receptor for the RSV attachment ( G ...	[ "Respiratory syncytial virus ( RSV ) is the second most common infectious cause of infant death worldwide .", "Despite this great clinical impact , no effective antivirals or vaccines against RSV are available .", "Here we find that the RSV attachment ( G ) glycoprotein uses CX3CR1 as a receptor on primary huma...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "action potentials", "medicine and health sciences", "optogenetics", "neural networks", "membrane potential", "electrophysiology", "neuroscience", "simulation and modeling", "network analysis", "brain mapping", "convolution", "bioassays and physiological analysis", "neuronal tuning", "rese...	Imbalanced amplification: A mechanism of amplification and suppression from local imbalance of excitation and inhibition in cortical circuits	journal.pcbi.1006048	null	[ [ "Information about a sensory stimulus is passed along a hierarchy of neural populations , from subcortical areas to the cerebral cortex where it propagates through multiple cortical areas and layers .", "Within each layer , lateral synaptic connectivity shapes the response to synaptic input from upstream ...	[ "Understanding the relationship between external stimuli and the spiking activity of cortical populations is a central problem in neuroscience .", "Dense recurrent connectivity in local cortical circuits can lead to counterintuitive response properties , raising the question of whether there are simple arithmetic...	[ "Understanding how the brain represents and processes stimuli requires a quantitative understanding of how signals propagate through networks of neurons .", "Developing such an understanding is made difficult by the dense interconnectivity of neurons , especially in the cerebral cortex .", "One approach to quan...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neuropsychiatric disorders", "medicine and health sciences", "enzyme-linked immunoassays", "anxiety disorders", "toxoplasma gondii", "statistics", "obsessive-compulsive disorder", "metaanalysis", "database searching", "parasitic diseases", "parasitic protozoans", "protozoans", "mathematics"...	Relationship between toxoplasmosis and obsessive compulsive disorder: A systematic review and meta-analysis	journal.pntd.0007306	null	[ [ "The T . gondii is a neurotropic apicomplexan protozoan that infects one-third of the world’s human population by affecting some tissues , including brain , eyes , and testes in warm-blooded mammals [1] .", "Infection with this parasite is due to the consumption of raw or undercooked meat containing tissu...	[ "A few studies investigated the relationship between toxoplasmosis and mental disorders , such as obsessive compulsive disorder ( OCD ) .", "However , the specific nature of the association between Toxoplasma gondii ( T . gondii ) infection and OCD is not yet clear .", "The aim of this study was to collect info...	[ "Toxoplasma gondii ( T . gondii ) is an obligate neurotropic parasite that infected about 25–30% of the total human population in the developed and developing countries .", "The obsessive compulsive disorder ( OCD ) is a psychiatric disease that affects the income and quality of life .", "Some studies confirmed...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "organismal evolution", "ecology and environmental sciences", "quantitative trait loci", "microbiology", "fungi", "model organisms", "experimental organism systems", "microbial evolution", "molecular genetics", "population biology", "saccharomyces", "research and analysis methods", "ecologic...	Environment-dependent pleiotropic effects of mutations on the maximum growth rate r and carrying capacity K of population growth	journal.pbio.3000121	Mutations simultaneously influence the maximum growth rate r and carrying capacity K of a population, but the impacts can be concordant or antagonistic depending on the environment; this study uses data from thousands of yeast recombinants to reveal complex r-K relationships and the underlying causes.	[ [ "Density-dependent population growth is commonly described by a logistic curve with two parameters: r and K . The carrying capacity K is the maximum population size that can be supported by the available resource in a local environment , whereas the maximum growth rate r is the number of individuals produced ...	[ "Maximum growth rate per individual ( r ) and carrying capacity ( K ) are key life-history traits that together characterize the density-dependent population growth and therefore are crucial parameters of many ecological and evolutionary theories such as r/K selection .", "Although r and K are generally thought t...	[ "Two parameters are widely used to describe density-dependent population growth: the maximum growth rate per individual ( r ) and the maximum population size or carrying capacity ( K ) .", "The relationship between these parameters is the subject of many fundamental theories and debates in ecology and evolutionar...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "centrosomes", "gene regulation", "cell cycle and cell division", "cell processes", "green fluorescent protein", "light microscopy", "mitosis", "luminescent proteins", "microscopy", "centrioles", "cellular structures and organelles", "research and analysis methods", "specimen preparation and...	Stable centrosomal roots disentangle to allow interphase centriole independence	journal.pbio.2003998	null	[ [ "The centrosome is a major microtubule organising centre , with critical roles in cell migration , division , shape maintenance , and cilia function .", "Animal interphase cells are generally thought to have 1 centrosome , consisting of 2 mature microtubule-based structures , called centrioles .", "Ce...	[ "The centrosome is a non–membrane-bound cellular compartment consisting of 2 centrioles surrounded by a protein coat termed the pericentriolar material ( PCM ) .", "Centrioles generally remain physically associated together ( a phenomenon called centrosome cohesion ) , yet how this occurs in the absence of a boun...	[ "Many subcellular organelles are not enclosed by a lipid membrane but instead exist freely in the cellular interior .", "How the number and position of such non–membrane-bound organelles are maintained is a general unanswered question .", "Here , I study this problem by focusing on the centrosome—an organelle t...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "hiv", "viral diseases" ]	Structural Mechanism of Trimeric HIV-1 Envelope Glycoprotein Activation	journal.ppat.1002797	null	[ [ "HIV/AIDS is a global health epidemic .", "Over 2 million people die annually from the disease , which is caused by human immunodeficiency virus ( HIV ) infection .", "HIV-1 entry into target cells is initiated by the interaction of the surface envelope glycoproteins ( Env ) with CD4 and a co-receptor...	[ "HIV-1 infection begins with the binding of trimeric viral envelope glycoproteins ( Env ) to CD4 and a co-receptor on target T-cells .", "Understanding how these ligands influence the structure of Env is of fundamental interest for HIV vaccine development .", "Using cryo-electron microscopy , we describe the co...	[ "HIV infection occurs following the binding of viral envelope glycoproteins ( Env ) to receptors on target cell surfaces .", "Binding to these molecules induces conformational changes in Env , ultimately leading to the exposure of a viral fusion peptide and fusion of viral and cellular membranes .", "Understand...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "clinical research design", "pathogens", "immunology", "tropical diseases", "microbiology", "data mining", "vaccines", "preventive medicine", "research design", "viruses", "rabies", "clinical medicine", "rna viruses", ...	Post-Marketing Surveillance of Human Rabies Diploid Cell Vaccine (Imovax) in the Vaccine Adverse Event Reporting System (VAERS) in the United States, 1990‒2015	journal.pntd.0004846	null	[ [ "Three cell culture rabies vaccines are licensed in the United States: human diploid cell vaccine ( HDCV , Imovax Rabies , Sanofi Pasteur ) , purified chick embryo cell vaccine ( PCECV , RabAvert , Novartis Vaccines and Diagnostics ) , and rabies vaccine adsorbed ( RVA , Bioport Corporation ) .", "Only HD...	[ "In 1980 , human diploid cell vaccine ( HDCV , Imovax Rabies , Sanofi Pasteur ) , was licensed for use in the United States .", "To assess adverse events ( AEs ) after HDCV reported to the US Vaccine Adverse Event Reporting System ( VAERS ) , a spontaneous reporting surveillance system .", "We searched VAERS fo...	[ "In 1980 , human diploid cell rabies vaccine ( HDCV , Imovax Rabies , Sanofi Pasteur ) , was licensed for use in the United States .", "To assess adverse events ( AEs ) after HDCV reported to the US Vaccine Adverse Event Reporting System ( VAERS ) , a spontaneous reporting surveillance system .", "We searched V...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "fish", "computational biology", "drosophila", "mammals" ]	Modeling an Evolutionary Conserved Circadian Cis-Element	journal.pcbi.0040038	null	[ [ "In flies and mammals , circadian timing is controlled via interlocked transcriptional feedback loops that rely on basic helix-loop-helix ( bHLH ) , PAS domain transcription factors [1 , 2] .", "In both fly and mammalian systems an evolutionary conserved bHLH heterodimer acts as the central transcriptiona...	[ "Circadian oscillator networks rely on a transcriptional activator called CLOCK/CYCLE ( CLK/CYC ) in insects and CLOCK/BMAL1 or NPAS2/BMAL1 in mammals .", "Identifying the targets of this heterodimeric basic-helix-loop-helix ( bHLH ) transcription factor poses challenges and it has been difficult to decipher its ...	[ "Life on earth is subject to daily light/dark and temperature cycles that reflect the earth rotation about its own axis .", "Under such conditions , organisms ranging from bacteria to human have evolved molecularly geared circadian clocks that resonate with the environmental cycles .", "These clocks serve as in...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Characteristics of Heterozygous Protein Truncating Variants in the Human Genome	journal.pcbi.1004647	null	[ [ "Recent population expansion and limited purifying selection have led to an abundance of rare human genetic variation [1–3] including stop-gain and frameshift mutations .", "Thus , there is increasing interest in the identification of natural human knockouts [3–8] through the cataloguing of homozygous tru...	[ "Sequencing projects have identified large numbers of rare stop-gain and frameshift variants in the human genome .", "As most of these are observed in the heterozygous state , they test a gene’s tolerance to haploinsufficiency and dominant loss of function .", "We analyzed the distribution of truncating variant...	[ "Genome sequencing provides evidence for large numbers of putative protein truncating variants in humans .", "Most truncating variants are only observed in few individuals but are collectively prevalent and widely distributed across the coding genome .", "Most of the truncating variants are so rare that they ar...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Lymph-Node Resident CD8α+ Dendritic Cells Capture Antigens from Migratory Malaria Sporozoites and Induce CD8+ T Cell Responses	journal.ppat.1004637	null	[ [ "Sterile immunity against live sporozoite challenge is elicited by immunization with radiation-attenuated sporozoites [1] and is , in part , mediated by CD8+ T cells specific for the Plasmodium circumsporozoite ( CS ) antigen [2 , 3] .", "Using a model mimicking natural exposure to sporozoite-infected mos...	[ "Malaria infection begins when a female Anopheles mosquito injects Plasmodium sporozoites into the skin of its host during blood feeding .", "Skin-deposited sporozoites may enter the bloodstream and infect the liver , reside and develop in the skin , or migrate to the draining lymph nodes ( DLNs ) .", "Importan...	[ "Malaria is responsible for the deaths of 0 . 5–2 million people each year .", "A safe and effective vaccine is likely needed for the control or eradication of malaria .", "Immunization with irradiated sporozoites , the infectious stage of the parasite transmitted by mosquitoes , protects people against malaria...	2015
[ "Introduction", "Results", "Methods" ]	[ "blood cells", "sequencing techniques", "medicine and health sciences", "immune cells", "markov models", "insertion mutation", "applied mathematics", "immunology", "simulation and modeling", "algorithms", "mutation", "mathematics", "phylogenetic analysis", "b cell receptors", "molecular ...	Likelihood-Based Inference of B Cell Clonal Families	journal.pcbi.1005086	null	[ [ "B cells effect the antibody-mediated component of the adaptive immune system .", "The antigen-binding properties of B cells are defined by their B cell receptor , or BCR .", "BCRs bind a wide variety of antigens , and this flexibility arises from their developmental pathway .", "B cells begin lif...	[ "The human immune system depends on a highly diverse collection of antibody-making B cells .", "B cell receptor sequence diversity is generated by a random recombination process called “rearrangement” forming progenitor B cells , then a Darwinian process of lineage diversification and selection called “affinity m...	[ "Antibodies must recognize a great diversity of antigens to protect us from infectious disease .", "The binding properties of antibodies are determined by the DNA sequences of their corresponding B cell receptors ( BCRs ) .", "These BCR sequences are created in naive form by VDJ recombination , which randomly s...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "microbiology", "molecular cell biology", "genetics and genomics" ]	DNA Break Site at Fragile Subtelomeres Determines Probability and Mechanism of Antigenic Variation in African Trypanosomes	journal.ppat.1003260	null	[ [ "Several important parasites , including those that cause malaria and Human African Trypanosomiasis ( HAT ) , achieve antigenic variation and evasion of the host adaptive immune response through monoallelic expression and clonal phenotypic variation of surface proteins [1] , [2] .", "The African trypanoso...	[ "Antigenic variation in African trypanosomes requires monoallelic transcription and switching of variant surface glycoprotein ( VSG ) genes .", "The transcribed VSG , always flanked by ‘70 bp’-repeats and telomeric-repeats , is either replaced through DNA double-strand break ( DSB ) repair or transcriptionally in...	[ "Previous studies on antigenic variation in African trypanosomes relied upon positive or negative selection , yielding only cells that underwent variation .", "This made it difficult to define individual switched clones as independent , potentially introduced bias in the relative contribution of each switching me...	2013
[ "Introduction", "Results", "Discussion", "Models" ]	[ "evolutionary modeling", "sequence analysis", "biology", "computational biology" ]	Phylogenetic Gaussian Process Model for the Inference of Functionally Important Regions in Protein Tertiary Structures	journal.pcbi.1003429	null	[ [ "An important question in biology is the identification of functional residues in proteins .", "This information can help us understand the relationship between protein structures and functions as well as guide us to design new proteins by genetic engineering .", "However , experimental techniques for...	[ "A critical question in biology is the identification of functionally important amino acid sites in proteins .", "Because functionally important sites are under stronger purifying selection , site-specific substitution rates tend to be lower than usual at these sites .", "A large number of phylogenetic models h...	[ "To understand how a protein functions , a critical step is to know which regions in its protein tertiary structure may be functionally important .", "Functionally important protein regions are typically more conserved than other regions because mutations in these regions are more likely to be deleterious .", "...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "flow cytometry", "medicine and health sciences", "respiratory infections", "rna extraction", "dna-binding proteins", "microbiology", "pulmonology", "pediatrics", "polymerases", "viral genome", "pediatric infections", "extraction techniques", "microbial genomics", "research and analysis me...	A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes	journal.ppat.1007707	null	[ [ "Defective viral genomes ( DVGs ) , which are generated during the replication of most RNA viruses , potentiate the host innate immune response [1–5] and attenuate the infection in vitro and in vivo [4 , 6–9] .", "Importantly , in naturally infected humans , the presence of DVGs correlates with enhanced a...	[ "Defective viral genomes of the copy-back type ( cbDVGs ) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus ( RSV ) both in vitro and in vivo .", "However , the mechanism governing cbDVG generation remains unknown , thereby limiting our ability to manipu...	[ "Copy-back defective viral genomes ( cbDVGs ) regulate infection and pathogenesis of Mononegavirales .", "cbDVGs are believed to arise from random errors that occur during virus replication and the predominant hypothesis is that the viral polymerase is the main driver of cbDVG generation .", "Here we describe a...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "cell motility", "medicine and health sciences", "ballistics", "immune cells", "classical mechanics", "immunology", "vertebrates", "mathematical models", "mice", "animals", "fibroblasts", "mammals", "probability distribution", "mathematics", "connective tissue cells", ...	Identifying the mechanism for superdiffusivity in mouse fibroblast motility	journal.pcbi.1006732	null	[ [ "Cell motility is an integral part of biological processes such as morphogenesis [1] , wound healing [2] , and cancer invasion [3] .", "But what are the rules that govern how cells move ?", "Cell migration involves a multitude of organelles and signaling pathways [4] and therefore a fruitful , bottom-...	[ "We seek to characterize the motility of mouse fibroblasts on 2D substrates .", "Utilizing automated tracking techniques , we find that cell trajectories are super-diffusive , where displacements scale faster than t1/2 in all directions .", "Two mechanisms have been proposed to explain such statistics in other ...	[ "Cells must move through their environment in many different biological processes , from wound healing to cancer invasion to the development of an embryo .", "There are different ways for cells to explore the physical space around them—ranging from moving along a straight path at constant speed to executing a ran...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "channel capacity", "cellular stress responses", "engineering and technology", "gene regulation", "signal processing", "cell processes", "green fluorescent protein", "signal filtering", "regulator genes", "luminescent proteins", "gene types", "computer and information sciences", "proteins", ...	Customized Regulation of Diverse Stress Response Genes by the Multiple Antibiotic Resistance Activator MarA	journal.pcbi.1005310	null	[ [ "Genetic networks often feature master regulators that control suites of downstream genes .", "This type of architecture is particularly common in stress response; examples include Msn2 and Crz1 in Saccharomyces cerevisiae , σB in Bacillus subtillis , and the multiple antibiotic resistance activator MarA ...	[ "Stress response networks frequently have a single upstream regulator that controls many downstream genes .", "However , the downstream targets are often diverse , therefore it remains unclear how their expression is specialized when under the command of a common regulator .", "To address this , we focused on a...	[ "Bacteria can sense and respond to stress in their environment .", "This process is often coordinated by a master regulator that turns on or off many downstream genes , allowing the cell to survive the stress .", "However , individual genes encode products that are diverse and optimal expression for each gene m...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "taxonomy", "horizontal gene transfer", "invertebrates", "ecology and environmental sciences", "computational biology", "extremophiles", "invertebrate genomics", "animals", "gene transfer", "genomic databases", "phylogenetics", "data management", "phylogenetic analysis", "genome analysis",...	Comparative genomics of the tardigrades Hypsibius dujardini and Ramazzottius varieornatus	journal.pbio.2002266	null	[ [ "The superphylum Ecdysozoa emerged in the Precambrian , and ecdysozoans not only dominated the early Cambrian explosion but also are dominant ( in terms of species , individuals , and biomass ) today .", "The relationships of the 8 phyla within Ecdysozoa remain contentious , with morphological assessments...	[ "Tardigrada , a phylum of meiofaunal organisms , have been at the center of discussions of the evolution of Metazoa , the biology of survival in extreme environments , and the role of horizontal gene transfer in animal evolution .", "Tardigrada are placed as sisters to Arthropoda and Onychophora ( velvet worms ) ...	[ "Tardigrades are justly famous for their abilities to withstand environmental extremes .", "Many freshwater and terrestrial species can undergo anhydrobiosis—life without water—and thereby withstand desiccation , freezing , and other insults .", "We explored the comparative biology of anhydrobiosis in 2 species...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	The Distribution of Ocular Chlamydia Prevalence across Tanzanian Communities Where Trachoma Is Declining	journal.pntd.0003682	null	[ [ "Epidemic models hypothesize that the prevalence of infection across communities where an infectious disease is disappearing should approach an exponential distribution .", "Simulations of mass treatments and decreasing transmission support this .", "[1–3] However , these epidemic models typically ass...	[ "Mathematical models predict an exponential distribution of infection prevalence across communities where a disease is disappearing .", "Trachoma control programs offer an opportunity to test this hypothesis , as the World Health Organization has targeted trachoma for elimination as a public health concern by the...	[ "Trachoma is the leading infectious cause of blindness and the World Health Organization plans to eliminate it as a public health concern worldwide by the year 2020 .", "It can be difficult for local trachoma programs to assess whether disease is headed towards elimination in their area .", "Mathematical infect...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "veterinary parasitology", "parasitology", "biology and life sciences", "intestinal parasites", "veterinary science" ]	Simple Fecal Flotation Is a Superior Alternative to Guadruple Kato Katz Smear Examination for the Detection of Hookworm Eggs in Human Stool	journal.pntd.0003313	null	[ [ "Human hookworms are estimated to infect between 576–740 million people globally and are responsible for a global burden of 3 . 2 million disability-adjusted life years [1] , [2] .", "Hookworms are a leading cause of iron deficiency anemia and protein malnutrition , especially among pre- and school-aged c...	[ "Microscopy-based identification of eggs in stool offers simple , reliable and economical options for assessing the prevalence and intensity of hookworm infections , and for monitoring the success of helminth control programs .", "This study was conducted to evaluate and compare the diagnostic parameters of the K...	[ "Hookworm infection is widespread in resource-poor countries worldwide .", "Detection of hookworm eggs in human feces can be done by the Kato Katz technique ( KK ) , sodium nitrate flotation technique ( SNF ) or PCR .", "This study was conducted to evaluate and compare the diagnostic parameters of the KK and si...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immune cells", "immune activation", "antigen-presenting cells", "immunology", "microbiology", "host-pathogen interaction", "adaptive immunity", "bacterial pathogens", "t cells", "biology", "pathogenesis", "gram positive", "immunity", "innate immunity" ]	A Role for TLR4 in Clostridium difficile Infection and the Recognition of Surface Layer Proteins	journal.ppat.1002076	null	[ [ "Clostridium difficile is a Gram-positive spore-forming intestinal pathogen .", "It is the leading cause of nosocomial antibiotic-associated diarrhoea among hospital patients and in severe cases can cause pseudomembranous colitis and even death [1] , [2] .", "The pathogenesis of C . difficile has been...	[ "Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea ( AAD ) and pseudomembranous colitis in humans .", "The role of the surface layer proteins ( SLPs ) in this disease has not yet been fully explored .", "The aim of this study was to investigate a role for SLPs in the recognition ...	[ "Clostridium difficile is the leading cause of antibiotic-associated diarrhoea among hospital patients and in severe cases can cause pseudomembranous colitis and even death .", "There is currently limited information regarding how this pathogen is recognised by the immune system and the key mechanisms necessary f...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "veterinary diseases", "pest control", "african trypanosomiasis", "zoonotic diseases", "neglected tropical diseases", "veterinary science", "integrated control", "agriculture", "trypanosomiasis" ]	Contrasting Population Structures of Two Vectors of African Trypanosomoses in Burkina Faso: Consequences for Control	journal.pntd.0001217	null	[ [ "Tsetse flies ( Diptera: Glossinidae ) are the sole cyclical vectors of human and animal trypanosomoses , two major plagues that are seriously impeding African development .", "African animal trypanosomosis ( AAT ) is a major obstacle to the development of more efficient and sustainable livestock producti...	[ "African animal trypanosomosis is a major obstacle to the development of more efficient and sustainable livestock production systems in West Africa .", "Riverine tsetse species such as Glossina palpalis gambiensis Vanderplank and Glossina tachinoides Westwood are the major vectors .", "A wide variety of control...	[ "Tsetse flies are insects that transmit trypanosomes to humans ( sleeping sickness ) and animals ( nagana ) .", "Controlling these vectors is a very efficient way to control these diseases .", "In Burkina Faso , a tsetse eradication campaign is presently targeting the northern part of the Mouhoun River Basin ."...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "protein abundance", "dna transcription", "genome sequencing", "chromatin", "chromosome biology", "gene expression", "biology", "proteomics", "molecular biology", "biochemistry", "cell biology", "genomics", "molecular cell biology", "computational biology" ]	Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output	journal.pbio.1001086	null	[ [ "In eukaryotic cells , genetic information is organized in chromatin , a highly conserved structural polymer of DNA and histones whose basic unit is the nucleosome [1] .", "Dynamic changes in the local or global organization of chromatin are required in order to perform most nuclear activities , including...	[ "The basic unit of genome packaging is the nucleosome , and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription .", "Nucleosome number in cells was considered fixed , but recently aging yeast and mammalian cells were shown to contain fewer nucleosomes .", "We sh...	[ "The accurate preservation and correct retrieval of genetic information is crucial for all living organisms .", "In eukaryotes , whether single-celled yeast or complex mammals , the DNA containing the genetic information is wrapped around beads of histone proteins to form structures called nucleosomes along the l...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome-Wide High-Resolution Mapping of UV-Induced Mitotic Recombination Events in Saccharomyces cerevisiae	journal.pgen.1003894	null	[ [ "Recombination occurs in both meiotic and mitotic cells .", "In budding yeast , there are about 100 meiotic crossovers per cell [1] .", "Although mitotic recombination events in S . cerevisiae are about 105-fold less frequent than meiotic exchanges [2] , homologous recombination ( HR ) is important fo...	[ "In the yeast Saccharomyces cerevisiae and most other eukaryotes , mitotic recombination is important for the repair of double-stranded DNA breaks ( DSBs ) .", "Mitotic recombination between homologous chromosomes can result in loss of heterozygosity ( LOH ) .", "In this study , LOH events induced by ultraviole...	[ "Nearly every living organism has to cope with DNA damage caused by ultraviolet ( UV ) exposure from the sun .", "UV causes various types of DNA damage .", "Defects in the repair of these DNA lesions are associated with the human disease xeroderma pigmentosum , one symptom of which is predisposition to skin can...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "social and behavioral sciences", "microbiology", "political science", "rabies", "neglected tropical diseases", "infectious disease control", "veterinary science", "war and civil unrest", "infectious diseases", "veterinary diseases", "zoonoses", ...	Rabies in Iraq: Trends in Human Cases 2001–2010 and Characterisation of Animal Rabies Strains from Baghdad	journal.pntd.0002075	null	[ [ "The first written record of disease consistent with rabies is in the Laws of Eshunna , a Sumerian city in ancient Mesopotamia .", "Largely corresponding to the region of what is now the Republic of Iraq , Mesopotamia encompassed the Euphrates and Tigris river systems and is considered by many to be the b...	[ "Control of rabies requires a consistent supply of dependable resources , constructive cooperation between veterinary and public health authorities , and systematic surveillance .", "These are challenging in any circumstances , but particularly during conflict .", "Here we describe available human rabies survei...	[ "Control of rabies requires cooperation between government departments , consistent funding , and an understanding of the epidemiology of the disease obtained through surveillance .", "Here we describe human rabies surveillance data from Iraq and the results of renewed sampling for rabies in animals .", "In Ira...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal diseases", "medicine and health sciences", "immune physiology", "spleen", "animal prion diseases", "lymphatic system", "zoology", "digestive system", "research and analysis methods", "specimen preparation and treatment", "infectious diseases", "staining", "zoonoses", "oral diseases...	Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility	journal.ppat.1006075	null	[ [ "Prion diseases ( transmissible spongiform encephalopathies ) are a unique group of subacute neurodegenerative diseases that affect humans and animals .", "During prion disease , aggregations of PrPSc , an abnormally folded isoform of cellular PrP ( PrPC ) , accumulate in affected tissues .", "Prion i...	[ "Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture .", "Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which interventi...	[ "Prion diseases are infectious neurodegenerative disorders that affect humans and animals .", "Many natural prion diseases are orally acquired through consumption of contaminated food or pasture .", "An understanding of how prions infect the intestine will help identify factors that influence disease susceptibi...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Cascade of Iron-Containing Proteins Governs the Genetic Iron Starvation Response to Promote Iron Uptake and Inhibit Iron Storage in Fission Yeast	journal.pgen.1005106	null	[ [ "Since iron ( Fe ) is essential but also toxic , its uptake from the extracellular environment and its intracellular availability from a “disposable Fe pool” are tightly regulated .", "All cell types display wide transcriptome changes upon Fe starvation .", "These responses are triggered in very disti...	[ "Iron is an essential cofactor , but it is also toxic at high levels .", "In Schizosaccharomyces pombe , the sensor glutaredoxin Grx4 guides the activity of the repressors Php4 and Fep1 to mediate a complex transcriptional response to iron deprivation: activation of Php4 and inactivation of Fep1 leads to inhibiti...	[ "Iron is an essential biometal but it is also toxic , and therefore its intracellular availability from disposable iron pools is tightly regulated .", "From bacteria to higher eukaryotes , iron starvation triggers complex genetic responses to exacerbate the otherwise limited iron uptake and decrease intracellular...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "plant biology/plant-biotic interactions" ]	Suppression of Plant Resistance Gene-Based Immunity by a Fungal Effector	journal.ppat.1000061	null	[ [ "Long periods of co-evolution of plants and microorganisms have led to complex mechanisms of attack and defence , involving the innate immune system of plants and virulence factors of pathogens [1] .", "The first layer of plant defence , called basal immunity , is based on recognition of conserved microbi...	[ "The innate immune system of plants consists of two layers .", "The first layer , called basal resistance , governs recognition of conserved microbial molecules and fends off most attempted invasions .", "The second layer is based on Resistance ( R ) genes that mediate recognition of effectors , proteins secret...	[ "In agriculture , the most environmentally friendly way to combat plant diseases is to make use of the innate immune system of plants , for instance by crossing into crop varieties polymorphic resistance genes that occur in natural populations of the crop plant or its close relatives .", "Plant pathogens , howeve...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/genomics", "genetics and genomics", "genetics and genomics/bioinformatics", "genetics and genomics/medical genetics", "genetics and genomics/population genetics" ]	Resolving Individuals Contributing Trace Amounts of DNA to Highly Complex Mixtures Using High-Density SNP Genotyping Microarrays	journal.pgen.1000167	null	[ [ "Resolving whether an individual's genomic DNA is present at trace amounts within a complex mixture containing DNA from numerous individuals is of interest to multiple fields .", "Within forensics , determining whether a person contributed their DNA to a mixture is typically a manual process that requires...	[ "We use high-density single nucleotide polymorphism ( SNP ) genotyping microarrays to demonstrate the ability to accurately and robustly determine whether individuals are in a complex genomic DNA mixture .", "We first develop a theoretical framework for detecting an individual's presence within a mixture , then s...	[ "In this report we describe a framework for accurately and robustly resolving whether individuals are in a complex genomic DNA mixture using high-density single nucleotide polymorphism ( SNP ) genotyping microarrays .", "We develop a theoretical framework for detecting an individual's presence within a mixture , ...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "biota", "microbiology", "metagenomics", "neglected tropical diseases", "infectious disease control", "environmental protection", "infectious diseases", "biology", "vectors and hosts", "ecology", "vector biology", "leishmaniasis", "genomics", "genetics and genomics" ]	Metagenomic Analysis of Taxa Associated with Lutzomyia longipalpis, Vector of Visceral Leishmaniasis, Using an Unbiased High-Throughput Approach	journal.pntd.0001304	null	[ [ "Leishmaniasis is a vector-borne neglected infectious disease of worldwide incidence and its most severe clinical form is visceral leishmaniasis ( VL ) .", "Each year VL causes an estimated 500 , 000 new cases and more than 59 , 000 deaths [1] , a death toll that is only surpassed by malaria among the par...	[ "Leishmaniasis is one of the most diverse and complex of all vector-borne diseases worldwide .", "It is caused by parasites of the genus Leishmania , obligate intramacrophage protists characterised by diversity and complexity .", "Its most severe form is visceral leishmaniasis ( VL ) , a systemic disease that i...	[ "Leishmaniasis is a vector-borne disease with a complex ecology and epidemiology .", "It has three main clinical forms of which visceral leishmaniasis ( VL ) is the most severe , as it is fatal if untreated .", "It is caused by a protist parasite , Leishmania spp .", ", and is transmitted to humans by phlebot...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/disease models", "molecular biology/transcription elongation", "neurological disorders/neuromuscular diseases", "genetics and genomics/gene expression" ]	Progressive GAA·TTC Repeat Expansion in Human Cell Lines	journal.pgen.1000704	null	[ [ "Trinucleotide repeat disorders are caused by the expansion of unstable tandem repeats to a pathogenic size above disease-specific length thresholds [1]–[5] .", "Disease-associated trinucleotide repeat arrays include CAG·CTG , CGG·CCG , and GAA·TTC sequences .", "Disease pathology in these disorders i...	[ "Trinucleotide repeat expansion is the genetic basis for a sizeable group of inherited neurological and neuromuscular disorders .", "Friedreich ataxia ( FRDA ) is a relentlessly progressive neurodegenerative disorder caused by GAA·TTC repeat expansion in the first intron of the FXN gene .", "The expanded repeat...	[ "The human genome is comprised of the DNA base sequences used by the cell as a blueprint to direct proper cellular function .", "Changes in this sequence , known as genomic instability , often interfere with vital cellular functions , resulting in genetic disorders .", "Repetitive DNA sequences are particularly...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "progressive multifocal leukoencephalopathy", "infectious diseases", "medicine and health sciences", "major histocompatibility complex", "clinical immunology", "multiple sclerosis", "autoimmune diseases", "biology and life sciences", "immunology", "viral diseases", "immune response" ]	JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants	journal.ppat.1004084	null	[ [ "Progressive multifocal leukoencephalopathy ( PML ) was first described neuropathologically during the fifties by Karl Erik Åström [1] .", "It took until 1971 when JC virus ( JCV ) was isolated from brain tissue of a patient with PML , since then JCV was accepted as the causative agent of PML [2] .", ...	[ "JC polyomavirus ( JCV ) carriers with a compromised immune system , such as in HIV , or subjects on immune-modulating therapies , such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy ( PML ) which is a lytic infection of oligodendrocytes in the brain .", "Serum antibodies to JCV mark...	[ "JC virus infection can lead to progressive multifocal leukoencephalopathy in individuals with a compromised immune system , such as during HIV infections or when treated with immunosuppressive or immunomodulating therapies .", "Progressive multifocal leukoencephalopathy is a rare but potentially fatal disease ch...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "homo (human)", "genetics and genomics", "diabetes and endocrinology", "public health and epidemiology" ]	The Association of a SNP Upstream of INSIG2 with Body Mass Index is Reproduced in Several but Not All Cohorts	journal.pgen.0030061	null	[ [ "Body mass index ( BMI ) is a heritable measure of obesity that is routinely obtained in large cohorts , is correlated with other measures of obesity , and predicts morbidity and mortality from obesity-related diseases [1–4] .", "Thus , BMI is a readily accessible trait that can be used to screen for gene...	[ "A SNP upstream of the INSIG2 gene , rs7566605 , was recently found to be associated with obesity as measured by body mass index ( BMI ) by Herbert and colleagues .", "The association between increased BMI and homozygosity for the minor allele was first observed in data from a genome-wide association scan of 86 ,...	[ "Obesity is an epidemic in the United States of America and developing world , portending an epidemic of related diseases such as diabetes and heart disease .", "While diet and lifestyle contribute to obesity , half of the population variation in body mass index , a common measure of obesity , is determined by in...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "kala-azar", "children", "medicine and health sciences", "tropical diseases", "geographical locations", "vertebrates", "sand flies", "parasitic diseases", "dogs", "animals", "mammals", "age groups", "neglected tropical diseases", "insect vectors", "families", "public and occupational h...	Insecticide–impregnated dog collars reduce infantile clinical visceral leishmaniasis under operational conditions in NW Iran: A community–wide cluster randomised trial	journal.pntd.0007193	null	[ [ "Visceral leishmaniasis ( VL ) is a protozoan vector–borne parasitic disease of humans following infection with Leishmania donovani or L . infantum , characterized by prolonged fever , wasting , splenomegaly , and hepatomegaly , and >95% case–fatality in the absence of treatment[1] .", "Leishmania are tra...	[ "To assess the effectiveness of community-wide deployment of insecticide–impregnated collars for dogs- the reservoir of Leishmania infantum–to reduce infantile clinical visceral leishmaniasis ( VL ) .", "A pair matched–cluster randomised controlled trial involving 40 collared and 40 uncollared control villages ( ...	[ "Zoonotic visceral leishmaniasis is a sand fly-borne disease of humans and dogs caused by the intracellular parasite Leishmania infantum .", "Dogs are the proven reservoir .", "The disease is of global health significance , and usually fatal unless treated .", "There are limited options to reduce transmission...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "genetics and genomics/gene expression", "developmental biology/pattern formation", "genetics and genomics/chromosome biology", "developmental biology/molecular development", "evolutionary biology/developmental molecular mechanisms", "developmental biology/develo...	Uncoupling Time and Space in the Collinear Regulation of Hox Genes	journal.pgen.1000398	null	[ [ "Hox genes play essential roles in patterning during the development of metazoans .", "In many species , they are found clustered in the genome , such as in vertebrates , which contain four Hox gene clusters ( HoxA to HoxD ) , due to the additional two rounds of genome amplification that accompanied their...	[ "During development of the vertebrate body axis , Hox genes are transcribed sequentially , in both time and space , following their relative positions within their genomic clusters .", "Analyses of animal genomes support the idea that Hox gene clustering is essential for coordinating the various times of gene act...	[ "Hox genes encode proteins that control embryonic development along the head-to-tail axis .", "These genes are clustered in one site on the chromosome and their respective positions within the cluster determine their time and place of activation .", "Here , by using a large set of targeted mutations disturbing ...	2009

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