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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" ]	[ "neurochemistry", "protein interactions", "neuroscience", "gene function", "animal models", "model organisms", "membrane receptor signaling", "membranes and sorting", "biology", "proteomics", "neuroendocrinology", "mouse", "biochemistry", "signal transduction", "cellular neuroscience", ...	Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis	journal.pbio.1001506	Body weight and energy homeostasis are regulated by leptin receptor interactions with gangliosides, a class of plasma membrane lipids, in forebrain neurons of mice.	[ [ "The investigation of pathogenetic mechanisms underlying obesity has attained significant interest , as obesity has become an endemic metabolic disturbance worldwide .", "Elevated peripheral energy storage can develop as a consequence of alterations in the neuronal feedback circuits regulating energy home...	[ "Hypothalamic neurons are main regulators of energy homeostasis .", "Neuronal function essentially depends on plasma membrane-located gangliosides .", "The present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase ( GCS; UDP-glucose:ce...	[ "Obesity is a growing health threat that affects nearly half a billion people worldwide , and its incidence rates in lower income countries are rising dramatically .", "As obesity is a major risk factor for type II diabetes and cardiovascular disease , significant effort has been put into the exploration of cause...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Stability of Neuronal Networks with Homeostatic Regulation	journal.pcbi.1004357	null	[ [ "Neurons in the brain are subject to varying conditions .", "Developmental processes , synaptic plasticity , changes in the sensory signals , and tissue damage can lead to under- or overstimulation of neurons .", "Both under- and overstimulation are undesirable: prolonged periods of excessive activity...	[ "Neurons are equipped with homeostatic mechanisms that counteract long-term perturbations of their average activity and thereby keep neurons in a healthy and information-rich operating regime .", "While homeostasis is believed to be crucial for neural function , a systematic analysis of homeostatic control has la...	[ "Despite their apparent robustness many biological system work best in controlled environments , the tightly regulated mammalian body temperature being a good example .", "Biological homeostatic control systems , not unlike those used in engineering , ensure that the right operating conditions are met .", "Simi...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "social epidemiology", "infectious diseases", "schistosomiasis", "public health and epidemiology", "tropical diseases (non-neglected)", "epidemiology", "environmental epidemiology", "infectious disease epidemiology", "neglected tropical diseases", "spatial epidemiology", "economic ...	Partnering Parasites: Evidence of Synergism between Heavy Schistosoma haematobium and Plasmodium Species Infections in Kenyan Children	journal.pntd.0001723	null	[ [ "Parasitic infections account for a large proportion of the burden of disease in Kenya , with far-reaching effects on the nation's health and economy .", "Malaria , for example , represents 30–50% of all outpatient visits to health facilities , causing more than 20% of deaths in children less than 5 years...	[ "Residents of resource-poor tropical countries carry heavy burdens of concurrent parasitic infections , leading to high rates of morbidity and mortality .", "This study was undertaken to help identify the social and environmental determinants of multiple parasite infection in one such community .", "Residents o...	[ "Parasitic diseases such as malaria and schistosomiasis account for a large proportion of global morbidity and mortality by contributing to malnutrition , developmental delays , loss of productivity , negative birth outcomes , disfigurement , physical handicap and social stigma .", "We studied these two infection...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "diagnostic radiology", "granulomas", "immunology", "vertebrates", "neuroscience", "animals", "mammals", "positron emission tomography", "primates", "developmental b...	PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis	journal.ppat.1005739	null	[ [ "The vast majority of people infected with Mycobacterium tuberculosis ( Mtb ) develop asymptomatic , latent infection ( LTBI ) .", "It is increasingly recognized that there is a spectrum of LTBI in humans , and this spectrum may correlate with the risk of reactivation [1] .", "Although reactivation ri...	[ "Mycobacterium tuberculosis infection presents across a spectrum in humans , from latent infection to active tuberculosis .", "Among those with latent tuberculosis , it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis .", ...	[ "Asymptomatic infection with Mycobacterium tuberculosis , often called latent tuberculosis , affects more than 2 billion people .", "Reactivation of latent infection to active TB occurs in only a minority of those infected , yet can lead to deadly disease and transmission .", "Here we show , using a non-human p...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/immune evasion", "immunology/antigen processing and recognition", "immunology/immunity to infections", "virology/host antiviral responses" ]	Viral Sequestration of Antigen Subverts Cross Presentation to CD8+ T Cells	journal.ppat.1000457	null	[ [ "CD8+ T cells ( TCD8+ ) play important roles in host elimination of pathogens , tumors and transplanted tissues .", "Virus-specific TCD8+ recognize major histocompatibility complex ( MHC ) class I molecules bound to peptides derived from viral proteins [1] .", "These peptide-MHC complexes can be gener...	[ "Virus-specific CD8+ T cells ( TCD8+ ) are initially triggered by peptide-MHC Class I complexes on the surface of professional antigen presenting cells ( pAPC ) .", "Peptide-MHC complexes are produced by two spatially distinct pathways during virus infection .", "Endogenous antigens synthesized within virus-inf...	[ "Understanding the pathways by which protective immunity is mediated against viral pathogens is essential to allow the design of effective vaccines .", "No effective vaccine has been designed to activate killer cells of the immune system expressing CD8 , although CD8+ T cells are the most effective cells at modul...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "animal models", "physiological processes", "developmental biology", "model organisms", "organism development", "dna", "research and analysis methods", "mouse models", "aging", "biochemistry", "cell biology", "nucleic acids", "physiology", "genetics", "biology and life ...	Cell-Autonomous Progeroid Changes in Conditional Mouse Models for Repair Endonuclease XPG Deficiency	journal.pgen.1004686	null	[ [ "If DNA damage , either inflicted from exogenous or endogenous sources , cannot be repaired , this has detrimental consequences for an organism ranging from transcription blocks , permanent cell cycle arrest and mutations , to cell death .", "In the end , this unrepaired DNA damage contributes to the onse...	[ "As part of the Nucleotide Excision Repair ( NER ) process , the endonuclease XPG is involved in repair of helix-distorting DNA lesions , but the protein has also been implicated in several other DNA repair systems , complicating genotype-phenotype relationship in XPG patients .", "Defects in XPG can cause either...	[ "Accumulation of DNA damage has been implicated in aging .", "Many premature aging syndromes are due to defective DNA repair systems .", "The endonuclease XPG is involved in repair of helix-distorting DNA lesions , and XPG defects cause the cancer-prone condition xeroderma pigmentosum ( XP ) alone or combined w...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biology", "neuroscience" ]	Learning from Sensory and Reward Prediction Errors during Motor Adaptation	journal.pcbi.1002012	null	[ [ "Our motor commands generally produce two kinds of consequences: a sensory consequence in terms of activity in our primary sensory organs ( e . g . , vision , proprioception ) , and a rewarding consequence in terms of forming a subjective measure of utility or usefulness of these sensations ( e . g . , releas...	[ "Voluntary motor commands produce two kinds of consequences .", "Initially , a sensory consequence is observed in terms of activity in our primary sensory organs ( e . g . , vision , proprioception ) .", "Subsequently , the brain evaluates the sensory feedback and produces a subjective measure of utility or use...	[ "It is thought that motor adaptation relies on sensory prediction errors to form an estimate of the perturbation .", "Here , we present evidence that motor adaptation can be driven by both sensory and reward prediction errors .", "We found that learning from sensory prediction error altered the predicted conseq...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "medicine and health sciences", "microbial mutation", "pathology and laboratory medicine", "hepacivirus", "pathogens", "rna extraction", "microbiology", "cloning", "viruses", "mutation", "substitution mutation", "rna viruses", "molecular biology techniques", "rna...	Characterization of miR-122-independent propagation of HCV	journal.ppat.1006374	null	[ [ "Hepatitis C virus ( HCV ) infects over 170 million people worldwide and is a major cause of chronic hepatitis , liver cirrhosis , and a high rate of hepatocellular carcinoma [1] .", "Chronic infection with HCV is often associated with extrahepatic manifestations ( EHMs ) such as mixed cryoglobulinemia , ...	[ "miR-122 , a liver-specific microRNA , is one of the determinants for liver tropism of hepatitis C virus ( HCV ) infection .", "Although miR-122 is required for efficient propagation of HCV , we have previously shown that HCV replicates at a low rate in miR-122-deficient cells , suggesting that HCV-RNA is capable...	[ "A liver-specific microRNA , miR-122 , is one of the key determinants of hepatitis C virus ( HCV ) hepatotropism and is required for efficient propagation of HCV .", "On the other hand , chronic infection with HCV is often associated with extrahepatic manifestations ( EHMs ) , and a low level of HCV-RNA replicati...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "luciferase", "toxins", "pathology and laboratory medicine", "gene regulation", "enzymes", "biological cultures", "cell processes", "enzymology", "light microscopy", "toxicology", "toxic agents", "microscopy", "caco-2 cells", "confocal microscopy", "cell...	Clostridium difficile Toxin A Undergoes Clathrin-Independent, PACSIN2-Dependent Endocytosis	journal.ppat.1006070	null	[ [ "Clostridium difficile , a gram-positive , spore-forming anaerobe , is the most common cause of healthcare-associated infections and gastroenteritis-associated death in the United States [1–3] .", "The pathogenesis of C . difficile is mediated by two large homologous exotoxins , TcdA and TcdB ( 308 kDa an...	[ "Clostridium difficile infection affects a significant number of hospitalized patients in the United States .", "Two homologous exotoxins , TcdA and TcdB , are the major virulence factors in C . difficile pathogenesis .", "The toxins are glucosyltransferases that inactivate Rho family-GTPases to disrupt host ce...	[ "Clostridium difficile is a bacterial pathogen that causes nearly half a million infections each year in the United States .", "It infects the human colon and causes diarrhea , colitis and , in some cases , death .", "C . difficile infection is mediated by the action of two large homologous toxins , TcdA and Tc...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA	journal.pcbi.1004303	null	[ [ "Magnesium homeostasis is essential for life .", "In humans , the misregulation of magnesium is implicated in stroke [1] , heart disease [2] , and diabetes [3] .", "Magnesium transport is also crucial for bacteria [4] .", "The movement of magnesium through cell membranes , like that of other ions ...	[ "Ion channels catalyze ionic permeation across membranes via water-filled pores .", "To understand how changes in intracellular magnesium concentration regulate the influx of Mg2+ into cells , we examine early events in the relaxation of Mg2+ channel CorA toward its open state using massively-repeated molecular d...	[ "This study shows how rapid wetting/dewetting transitions in the pores of ion channels participate in the control of biological ion permeation .", "Ion channels catalyze ionic permeation across non-polar membranes via water-filled pores .", "However , non-polar stretches or hydrophobic bottlenecks are present i...	2015
[ "Introduction", "Methods", "Discussion" ]	[ "death rates", "invertebrates", "ecology and environmental sciences", "medicine and health sciences", "plant cell biology", "chloroplasts", "pigments", "animals", "developmental biology", "plant science", "pupae", "materials science", "population biology", "insect vectors", "cellular str...	Eutrophication and predator presence overrule the effects of temperature on mosquito survival and development	journal.pntd.0006354	null	[ [ "Associations between anthropogenic pressures , disease risk and vector ecology are particularly strong for mosquito-borne infections [1–4] .", "To date , existing predictive maps of disease risk almost exclusively focus on large-scale drivers of mosquito populations , such as temperature , precipitation ...	[ "Adequate predictions of mosquito-borne disease risk require an understanding of the relevant drivers governing mosquito populations .", "Since previous studies have focused mainly on the role of temperature , here we assessed the effects of other important ecological variables ( predation , nutrient availability...	[ "Human actions have strongly altered ecosystems worldwide , through climate change , eutrophication , and biodiversity loss .", "The consequences of these global changes for mosquito populations could have important implications for mosquito-borne infections .", "Previous studies have focused on the effects of ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral transmission and infection", "plant biology", "population dynamics", "population genetics", "microbiology", "host-pathogen interaction", "plant science", "effective population size", "plant pathology", "population biology", "viral load", "viral entry", "biology", "viral evolution", ...	Circulating Virus Load Determines the Size of Bottlenecks in Viral Populations Progressing within a Host	journal.ppat.1003009	null	[ [ "Virus progression within multi-cellular hosts operates via two distinct mechanisms: cell-to-cell proximal contamination and long-distance migration ( either as free infectious units or in circulating cells ) to colonize new organs and/or tissues .", "Both animals and plants can be considered as heterogen...	[ "For any organism , population size , and fluctuations thereof , are of primary importance in determining the forces driving its evolution .", "This is particularly true for viruses—rapidly evolving entities that form populations with transient and explosive expansions alternating with phases of migration , resul...	[ "Infecting viruses progress within multi-cellular hosts via two distinct mechanisms: cell-to-cell proximal contamination and long-distance migration to remote organs through the vasculature .", "In distant susceptible organs , it seems logical that the number of initially infected cells , the number of viral geno...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "respiratory failure", "membrane staining", "vertebrates", "dogs", "animals", "mammals", "lungs", "pulmonology", "respiratory system", "genome analysis", "mammalian genomics", "research and analysis methods", "specimen preparation and treatment", "staining...	ANLN truncation causes a familial fatal acute respiratory distress syndrome in Dalmatian dogs	journal.pgen.1006625	null	[ [ "Acute respiratory distress syndrome ( ARDS ) is a multifactorial syndrome characterized by rapid-onset respiratory failure resulting from pulmonary inflammation [1] .", "ARDS is common and leads to substantial mortality in man [1] .", "Two forms of idiopathic interstitial pneumonia are found in human...	[ "Acute respiratory distress syndrome ( ARDS ) is the leading cause of death in critical care medicine .", "The syndrome is typified by an exaggerated inflammatory response within the lungs .", "ARDS has been reported in many species , including dogs .", "We have previously reported a fatal familial juvenile r...	[ "Acute respiratory distress syndrome ( ARDS ) is characterized by life-threatening impairment of pulmonary gas exchange and leads to substantial mortality in man .", "Spontaneous ARDS has also been described in dogs including a familial fatal ARDS-like syndrome in young Dalmatian dogs .", "The main clinical sig...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Toxoplasma gondii-Induced Activation of EGFR Prevents Autophagy Protein-Mediated Killing of the Parasite	journal.ppat.1003809	null	[ [ "Toxoplasma gondii is an obligate intracellular protozoan parasite that infects around a third of the human population worldwide .", "T . gondii is of clinical importance because it causes encephalitis in immunocompromised individuals and retino-choroiditis in immunocompetent and immunosuppressed patients...	[ "Toxoplasma gondii resides in an intracellular compartment ( parasitophorous vacuole ) that excludes transmembrane molecules required for endosome - lysosome recruitment .", "Thus , the parasite survives by avoiding lysosomal degradation .", "However , autophagy can re-route the parasitophorous vacuole to the l...	[ "Toxoplasma gondii resides in a parasitophorous vacuole that excludes transmembrane proteins required for recruitment of endosomes and lysosomes and thus , does not follow the path of classical lysosomal degradation .", "However , the non-fusogenic nature of the vacuole can be reverted when autophagy , a pathway ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/neurodevelopment", "neuroscience/cognitive neuroscience", "radiology and medical imaging/magnetic resonance imaging", "computational biology/computational neuroscience" ]	Development of Large-Scale Functional Brain Networks in Children	journal.pbio.1000157	Large-scale rewiring of brain circuits in children leads to emergence of hierarchical organization in the mature adult brain.	[ [ "Understanding the development of human brain organization is critical for gaining insight into brain organization and functions in adulthood as well as for investigating disorders such as autism spectrum disorders ( ASD ) and attention-deficit/hyperactivity disorder ( ADHD ) , where normal developmental proc...	[ "The ontogeny of large-scale functional organization of the human brain is not well understood .", "Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children ( ages 7–9 y ) and 22 young-adults ( ages 19–22 y ) .", "Comparison of network p...	[ "The disruption of normal brain organization in humans is believed to underlie a number of behavioral conditions , such as autism spectrum disorders ( ASD ) and attention-deficit/hyperactivity disorder ( ADHD ) .", "To gain insight into how normal brain organization develops , we mapped functional brain connectiv...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/disease models", "genetics and genomics/cancer genetics", "genetics and genomics/gene expression" ]	A Role for E2F Activities in Determining the Fate of Myc-Induced Lymphomagenesis	journal.pgen.1000640	null	[ [ "A hallmark of human cancer is genetic complexity , reflecting the acquisition of multiple mutations and gene rearrangements that give rise to the tumor phenotype .", "Indeed , recent large-scale DNA sequencing efforts have provided direct evidence for this complexity , revealing large numbers of alterati...	[ "The phenotypic heterogeneity that characterizes human cancers reflects the enormous genetic complexity of the oncogenic process .", "This complexity can also be seen in mouse models where it is frequently observed that in addition to the initiating genetic alteration , the resulting tumor harbors additional , so...	[ "The diversity of human cancers reflects the variety of genetic changes that cause tumors to emerge and progress .", "Even for mice engineered with a specific cancer-causing mutation , the resulting tumors are often divergent , reflecting different additional mutations .", "We wanted to investigate how activiti...	2009
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "immunology", "microbiology", "histology", "adaptive immunity", "animal models of infection", "inflammation", "major histocompatibility complex", "proteins", "biology", "immune response", "biochemistry", "protein chemistry", "antigen processing and recognition", "immunity", "virology", ...	Impairment of Immunoproteasome Function by β5i/LMP7 Subunit Deficiency Results in Severe Enterovirus Myocarditis	journal.ppat.1002233	null	[ [ "Unfolded or misfolded proteins are potentially harmful to cells and have to be efficiently eliminated before they intoxicate the intracellular environment .", "This is of particular importance during proteotoxic stress as a consequence of intrinsic or extrinsic factors when the levels of misfolded protei...	[ "Proteasomes recognize and degrade poly-ubiquitinylated proteins .", "In infectious disease , cells activated by interferons ( IFNs ) express three unique catalytic subunits β1i/LMP2 , β2i/MECL-1 and β5i/LMP7 forming an alternative proteasome isoform , the immunoproteasome ( IP ) .", "The in vivo function of IP...	[ "The proteasome recognizes and degrades protein substrates tagged with poly-ubiquitin chains .", "Immune cells and cells activated by inflammatory cytokines/interferons express immunoproteasomes ( IPs ) that are characterized by unique catalytic subunits with increased substrate turnover .", "In infectious dise...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "luciferase", "enzymes", "gene regulation", "regulatory proteins", "enzymology", "dna-binding proteins", "light", "electromagnetic radiation", "phosphatases", "circadian oscillators", "transcription factors", "chronobiology", "proteins", "oxidoreductases", "gene expr...	A HAD family phosphatase CSP-6 regulates the circadian output pathway in Neurospora crassa	journal.pgen.1007192	null	[ [ "Circadian clocks are endogenous timekeepers that control a wide variety of daily biochemical , physiological , molecular and behavioral rhythms in mammals , plants , insects , fungi and cyanobacteria .", "The circadian system consists of three essential parts , input , a central oscillator and output [1–...	[ "Circadian clocks are ubiquitous in eukaryotic organisms where they are used to anticipate regularly occurring diurnal and seasonal environmental changes .", "Nevertheless , little is known regarding pathways connecting the core clock to its output pathways .", "Here , we report that the HAD family phosphatase ...	[ "Though molecules and components in the core circadian oscillator are well studied in Neurospora , the mechanisms through which output pathways are coupled with core components are less well understood .", "In this study we investigated a HAD phosphatase , CSP-6; loss-of-function Δcsp-6 strains are overtly arrhyt...	2018
[ "Introduction", "Materials and methods", "Results/Discussion" ]	[ "action potentials", "medicine and health sciences", "statistics", "nervous system", "membrane potential", "electrophysiology", "neuroscience", "simulation and modeling", "systems science", "mathematics", "population biology", "research and analysis methods", "computer and information scienc...	Computational geometry for modeling neural populations: From visualization to simulation	journal.pcbi.1006729	null	[ [ "The population or mesoscopic level is now recognised as a very important description level for brain dynamics .", "Traditionally rate based models [1] have been used: models that characterize the state of a population by a single variable .", "There are inherent limitations to this approach , for exa...	[ "The importance of a mesoscopic description level of the brain has now been well established .", "Rate based models are widely used , but have limitations .", "Recently , several extremely efficient population-level methods have been proposed that go beyond the characterization of a population in terms of a sin...	[ "A group of slow , noisy and unreliable cells collectively implement our mental faculties , and how they do this is still one of the big scientific questions of our time .", "Mechanistic explanations of our cognitive skills , be it locomotion , object handling , language comprehension or thinking in general—whate...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cdna libraries", "sequencing techniques", "statistics", "rna extraction", "fungi", "mathematics", "forms of dna", "dna libraries", "molecular biology techniques", "dna", "rna sequencing", "cell enumeration techniques", "cellular structures and organelles", "extraction techniques", "rese...	A complete statistical model for calibration of RNA-seq counts using external spike-ins and maximum likelihood theory	journal.pcbi.1006794	null	[ [ "Accurate transcriptome measurements are central to understanding the fundamental mechanisms of gene expression .", "A main challenge presented by the RNA-seq method for digitizing information about cellular RNA content—both its composition and abundance—is correcting noise , errors , and biases introduce...	[ "A fundamental assumption , common to the vast majority of high-throughput transcriptome analyses , is that the expression of most genes is unchanged among samples and that total cellular RNA remains constant .", "As the number of analyzed experimental systems increases however , different independent studies dem...	[ "We present a complete statistical model for the analysis of RNA-seq data from a population of cells using external RNA spike-ins and a maximum-likelihood method for genome-wide estimation of transcripts per cell .", "The model includes biological variability of cellular transcript number and sampling noise .", ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "helminth infections", "medicine and health sciences", "schistosomiasis", "infectious disease epidemiology", "epidemiology", "neglected tropical diseases", "tropical diseases", "parasitic diseases" ]	Risk Factors and Spatial Distribution of Schistosoma mansoni Infection among Primary School Children in Mbita District, Western Kenya	journal.pntd.0002991	null	[ [ "Schistosomiasis is a parasitic disease affecting 249 million people worldwide .", "It is endemic in 78 countries with over 90% of cases occurring in sub-Saharan Africa [1] .", "About 779 million people , more than 10% of the world's population , were estimated to have been at risk of schistosome infe...	[ "An increasing risk of Schistosoma mansoni infection has been observed around Lake Victoria , western Kenya since the 1970s .", "Understanding local transmission dynamics of schistosomiasis is crucial in curtailing increased risk of infection .", "We carried out a cross sectional study on a population of 310 ch...	[ "It is estimated that more than ten percent of the world's population is at risk of schistosome transmission , with over 90% of infections occurring in sub-Saharan Africa .", "In Kenya , schistosomiasis remains a major public health concern particularly around Lake Victoria .", "The objective of this study was ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/aging" ]	Regulation of Lifespan, Metabolism, and Stress Responses by the Drosophila SH2B Protein, Lnk	journal.pgen.1000881	null	[ [ "SH2B proteins are a recently identified family of intracellular adaptor proteins that transduce signals downstream of a number of receptor tyrosine kinases ( RTKs ) .", "These include the receptors for insulin , insulin-like growth factor-1 , Janus kinase 2 ( Jak2 ) , platelet derived growth factor , fib...	[ "Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins , the SH2B proteins .", "As adaptors , they lack catalytic activity but contain several protein–protein interaction domains , thus playing a critical role in signal transduction f...	[ "Many human populations are experiencing increased life expectancy , and as populations age the incidence of age-related diseases becomes more prevalent .", "The identification of single gene mutations that extend lifespan in invertebrate model organisms has revealed that several cellular signaling pathways , inc...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome expression analysis", "mycology", "fungi", "functional genomics", "molecular cell biology", "genome evolution", "fungal evolution", "comparative genomics", "biology", "genomics", "evolutionary biology", "microbiology" ]	Zinc Finger Transcription Factors Displaced SREBP Proteins as the Major Sterol Regulators during Saccharomycotina Evolution	journal.pgen.1004076	null	[ [ "Changes in gene regulatory networks are an important mechanism of evolutionary adaptation .", "Transcriptional re-wiring can result from gene loss , gene duplication , alterations in transcription factor binding sites , or changes in protein modularity that affect the interaction of transcription factors...	[ "In most eukaryotes , including the majority of fungi , expression of sterol biosynthesis genes is regulated by Sterol-Regulatory Element Binding Proteins ( SREBPs ) , which are basic helix-loop-helix transcription activators .", "However , in yeasts such as Saccharomyces cerevisiae and Candida albicans sterol sy...	[ "All but a few eukaryotes die without oxygen and respond dynamically to changes in the level of oxygen available to them .", "One ancient oxygen-requiring biochemical pathway in eukaryotes is the pathway for the biosynthesis of sterols , leading to cholesterol in animals and ergosterol in fungi .", "Mutations i...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/host antiviral responses" ]	Evidence for Restriction of Ancient Primate Gammaretroviruses by APOBEC3 but Not TRIM5α Proteins	journal.ppat.1000181	null	[ [ "Retroviruses integrate their genomes into host-cell DNA as an essential part of their replication cycle .", "If a provirus is integrated into the germ line or its progenitors , then it may be inherited in a Mendelian manner as an ‘endogenous’ retrovirus .", "In fact , endogenous retroviruses have acc...	[ "Because of evolutionary pressures imposed through episodic colonization by retroviruses , many mammals express factors , such as TRIM5α and APOBEC3 proteins , that directly restrict retroviral replication .", "TRIM5 and APOBEC restriction factors are most often studied in the context of modern primate lentivirus...	[ "Retroviruses integrate their genomes into host-cell DNA as an essential part of their replication cycle .", "If a retrovirus is integrated into a cell that becomes a germ line cell such as a sperm or an egg , then it may be inherited as an ‘endogenous’ retrovirus .", "In fact , endogenous retroviruses are extr...	2008
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cognitive neurology", "medicine and health sciences", "respiratory infections", "vertebrates", "mice", "neuroscience", "learning and memory", "animals", "mammals", "pulmonology", "developmental biology", "cognitive neuroscience", "animal behavior", "cognition", "memory", "zoology", ...	Abnormal neurobehaviour and impaired memory function as a consequence of Toxocara canis- as well as Toxocara cati-induced neurotoxocarosis	journal.pntd.0005594	null	[ [ "Toxocarosis , caused by infective third stage larvae ( L3 ) of the worldwide occurring roundworms of dogs and cats , Toxocara canis and Toxocara cati , respectively , is one of the most common parasitic infections in humans .", "Nevertheless , the global importance of the zoonotic helminth is considered ...	[ "Neuroinvasive larvae of the worldwide occurring zoonotic roundworms Toxocara canis and T . cati may induce neurotoxocarosis ( NT ) in humans , provoking a variety of symptoms including cognitive deficits as well as neurological dysfunctions .", "An association with neuropsychological disorders has been discussed...	[ "The worldwide occurring zoonotic roundworms Toxocara canis and T . cati may cause the so-called neurotoxocarosis ( NT ) in humans , possibly resulting in a variety of behavioural alterations .", "Comparable alterations to those in humans have been described in T . canis-infected mice , however , reports on T . c...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Loss of the TGFβ-Activating Integrin αvβ8 on Dendritic Cells Protects Mice from Chronic Intestinal Parasitic Infection via Control of Type 2 Immunity	journal.ppat.1003675	null	[ [ "Gastrointestinal parasitic helminth infections are extremely prevalent , affecting nearly one quarter of the world population .", "Development of chronic infection , defined as the presence of adult worms in the host , results in severe morbidity and health problems and has been heavily linked with promo...	[ "Chronic intestinal parasite infection is a major global health problem , but mechanisms that promote chronicity are poorly understood .", "Here we describe a novel cellular and molecular pathway involved in the development of chronic intestinal parasite infection .", "We show that , early during development of...	[ "Infection with intestinal parasitic worms is a major global health problem , with billions of people infected world-wide .", "Often these worms ( known as helminths ) develop a long-lasting chronic infection , due to failure of the host to mount the correct type of immune response that would normally expel the p...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Molecular Characterization of a Novel Family of Trypanosoma cruzi Surface Membrane Proteins (TcSMP) Involved in Mammalian Host Cell Invasion	journal.pntd.0004216	null	[ [ "The kinetoplastid protozoan Trypanosoma cruzi is the etiologic agent of Chagas’ disease or American Trypanosomiasis which infects 6–7 million people worldwide , mostly in Latin America [1] .", "In the last few decades , the disease has spread to non-endemic regions , such as the United States and Europe ...	[ "The surface coat of Trypanosoma cruzi is predominantly composed of glycosylphosphatidylinositol-anchored proteins , which have been extensively characterized .", "However , very little is known about less abundant surface proteins and their role in host-parasite interactions .", "Here , we described a novel fa...	[ "Trypanosoma cruzi is the etiologic agent of Chagas’ disease , which infects 6–7 million people worldwide , mostly in Latin America .", "Currently , there are no vaccines available , and the drugs used for treatment are toxic and are not fully effective .", "To infect mammalian hosts , T . cruzi relies on the a...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "united states", "invertebrates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "california", "geographical locations", "microbiology", "vertebrates", "animals", "viruses", "north america", "rna viruses", "rna isolation", "molecular bi...	Comparative fitness of West Nile virus isolated during California epidemics	journal.pntd.0007135	null	[ [ "West Nile virus ( WNV; Flavivirus , Flaviviridae ) naturally cycles among competent avian hosts and Culex mosquitoes that serve as both amplification and bridge vectors [1] .", "Outbreaks of WNV in North America generally have occurred during the warm summer and fall months , when transmission spills ove...	[ "West Nile virus ( WNV ) has been circulating in California since its first detection in 2003 , causing repeated outbreaks affecting public , wildlife and veterinary health .", "Epidemics of WNV are difficult to predict due to the multitude of factors influencing transmission dynamics among avian and mosquito hos...	[ "West Nile virus ( WNV ) is the cause of the largest mosquito-borne epidemic in the United States in recent history , with over 46 , 000 reported human cases to date , including >2000 deaths .", "Since the detection of WNV in California in 2003 , repeated outbreaks have been associated with explosive WNV amplific...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "bioengineering", "tissue mechanics", "biomedical engineering", "biology", "biophysics", "biomechanics", "engineering" ]	A Mechanical Design Principle for Tissue Structure and Function in the Airway Tree	journal.pcbi.1003083	null	[ [ "The act of breathing creates a mechanical environment that pervades all structures in the lungs down to the molecular level [1] .", "As a pressure difference across the lungs draws air through the airway tree for gas exchange , all airways dilate and transmit mechanical stresses and strains to their cell...	[ "With every breath , the dynamically changing mechanical pressures must work in unison with the cells and soft tissue structures of the lung to permit air to efficiently traverse the airway tree and undergo gas exchange in the alveoli .", "The influence of mechanics on cell and tissue function is becoming apparen...	[ "With every breath , mechanical pressures change in the lung and permit air to efficiently traverse the airway tree and undergo gas exchange .", "These pressure variations also influence cell and tissue function , raising the question: how does the airway tree co-exist within its mechanical environment to maintai...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "dengue virus", "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "geographical locations", "indonesia", "java", "viruses", "age groups", "adults", "rna...	The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java	journal.pntd.0004390	null	[ [ "Dengue is caused by infection with one of the four dengue viruses: dengue virus 1 ( DENV-1 ) , DENV-2 , DENV-3 and DENV-4 [1] .", "Infection with any of these viruses may result in asymptomatic infection , dengue fever ( DF ) , or the more severe forms , dengue hemorrhagic fever ( DHF ) and dengue shock ...	[ "Dengue has emerged as one of the most important infectious diseases in the last five decades .", "Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics .", "The clinical manifestations of dengue virus infection ...	[ "Dengue is the fastest spreading mosquito borne diseases in the world and is endemic in most tropical and sub-tropical countries with an estimated 96 million infections resulting in clinical disease annually .", "Population-based longitudinal prospective studies are essential for understanding dengue virus in the...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "flow cytometry", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "spleen", "immunology", "microbiology", "throat", "developmental biology", "molecular development", "cytotoxic t cells", "research and analysis metho...	Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs	journal.ppat.1005799	null	[ [ "It has recently become evident that protective T cell immunity relies not only on circulating memory T cells but also on non-circulating resident memory populations [1–5] .", "These resident memory T ( Trm ) cells have been identified in a variety of different non-lymphoid and lymphoid tissues in mice [6...	[ "Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections , such as Epstein Barr virus ( EBV ) and Cytomegalovirus ( CMV ) .", "How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined .", "...	[ "Some viruses have the capacity to establish chronic infections in humans .", "How different T cell populations effectively control these infections has not been clear .", "Continuous circulation of memory T cells was thought to be crucial for effective immune surveillance against such infections .", "Recent ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Evolution of Intra-specific Regulatory Networks in a Multipartite Bacterial Genome	journal.pcbi.1004478	null	[ [ "Regulation of gene expression is recognized as a key component in the cellular response to the environment .", "This is especially true in the microbial world , for two reasons: bacterial cells are often under severe energy constraints , the most important being protein translation [1] and they usually f...	[ "Reconstruction of the regulatory network is an important step in understanding how organisms control the expression of gene products and therefore phenotypes .", "Recent studies have pointed out the importance of regulatory network plasticity in bacterial adaptation and evolution .", "The evolution of such net...	[ "The influence of transcriptional regulatory networks on the evolution of bacterial pangenomes has not yet been elucidated , even though the role of transcriptional regulation is widely recognized .", "Using the model symbiont Sinorhizobium meliloti we have predicted the regulatory targets of 41 transcription fac...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans	journal.pntd.0004029	null	[ [ "Typhoid fever is a common infection that follows oral ingestion and invasion of the Gram-negative bacterium Salmonella enterica serovar Typhi ( S . Typhi ) .", "An estimated 26 . 9 million cases occurred globally in 2010 , disproportionately affecting children in resource-limited areas of sub-Saharan Afr...	[ "Iron is a key pathogenic determinant of many infectious diseases .", "Hepcidin , the hormone responsible for governing systemic iron homeostasis , is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection ....	[ "An adequate supply of iron is essential for both human hosts and their infecting pathogens .", "Hepcidin is the human hormone that controls the quantity and distribution of iron throughout the body .", "During infections , hepcidin activity may redistribute iron away from serum and into macrophages , potential...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna", "nucleic acids", "gene expression", "biology", "genomics", "molecular cell biology", "molecular biology", "genetics and genomics" ]	A Pathogenic Mechanism in Huntington's Disease Involves Small CAG-Repeated RNAs with Neurotoxic Activity	journal.pgen.1002481	null	[ [ "Huntington disease ( HD ) , a dominantly inherited neurodegenerative disorder , is caused by an abnormal CAG expansion within the first exon of the Huntingtin gene ( HTT ) , leading to an expanded polyglutamine ( polyQ ) track in the HTT protein .", "HTT is ubiquitously expressed in the cytoplasm of most...	[ "Huntington's disease ( HD ) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin ( HTT ) gene .", "The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects .", "Here , we provide evidence to support that the mutant H...	[ "Huntington's disease ( HD ) is a neurodegenerative disorder caused by an abnormal CAG expansion in the Huntingtin gene ( HTT ) , resulting in an expanded polyglutamine track in the HTT protein .", "Longer CAG expansions correlate with an earlier more severe manifestation of the disease that produces choreic move...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "animal models of infection", "immune cells", "emerging infectious diseases", "immunity", "virology", "innate immunity", "emerging viral diseases", "antigen-presenting cells", "immunity to infections", "immunology", "host-pathogen interaction", "biology", "microbiology", "immune response" ...	Production of CXC and CC Chemokines by Human Antigen-Presenting Cells in Response to Lassa Virus or Closely Related Immunogenic Viruses, and in Cynomolgus Monkeys with Lassa Fever	journal.pntd.0002637	null	[ [ "Lassa virus ( LASV ) is the causal agent of Lassa fever ( LF ) , a hemorrhagic fever endemic to West Africa [1] .", "The virus is transmitted to humans through contact with infected Mastomys sp .", ", rodents living close to housing and constituting a natural reservoir of LASV .", "Human-to-human...	[ "The pathogenesis of Lassa fever ( LF ) , a hemorrhagic fever endemic to West Africa , remains unclear .", "We previously compared Lassa virus ( LASV ) with its genetically close , but nonpathogenic homolog Mopeia virus ( MOPV ) and demonstrated that the strong activation of antigen-presenting cells ( APC ) , inc...	[ "Lassa virus ( LASV ) causes a viral hemorrhagic fever that affects about 300 , 000 people and leads to 5 , 000 deaths annually .", "Lassa fever ( LF ) is a public health problem in West Africa , where it is endemic , because of the number of cases , deaths and disabling effects .", "There is no vaccine against...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome sequencing", "mycology", "plant science", "genome evolution", "chromosome biology", "fungal evolution", "plant pathogens", "microbial pathogens", "plant pathology", "population genetics", "comparative genomics", "biology", "genomics", "evolutionary biology", "genomic evolution", ...	Breakage-fusion-bridge Cycles and Large Insertions Contribute to the Rapid Evolution of Accessory Chromosomes in a Fungal Pathogen	journal.pgen.1003567	null	[ [ "Chromosomal rearrangements are major drivers of genome evolution .", "Dobzhansky [1] realized that chromosomal polymorphism would “supply the raw materials for evolution” , providing some of the earliest support for Darwin's theory of evolution .", "Since Dobzhansky's work on Drosophila , cytogenetic...	[ "Chromosomal rearrangements are a major driver of eukaryotic genome evolution , affecting speciation , pathogenicity and cancer progression .", "Changes in chromosome structure are often initiated by mis-repair of double-strand breaks in the DNA .", "Mis-repair is particularly likely when telomeres are lost or ...	[ "Chromosomal rearrangements are a hallmark of genetic differences between species .", "But changes in chromosome structure can also occur spontaneously within species , within populations , or even within individuals .", "The causes and consequences of chromosomal rearrangements affecting natural populations ar...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genomics", "genetic association studies", "personalized medicine", "genetics", "immunology", "biology", "human genetics", "genetics of disease", "genomic medicine", "pharmacogenomics", "autoimmunity" ]	Functional IL6R 358Ala Allele Impairs Classical IL-6 Receptor Signaling and Influences Risk of Diverse Inflammatory Diseases	journal.pgen.1003444	null	[ [ "Originally identified as a B-cell differentiation factor , interleukin-6 ( IL-6 ) is now recognized as one of the most pleiotropic cytokines in humans .", "IL-6 can activate a wide-range of cell types and is recognized as a critical regulator of acute inflammatory reactions [1] .", "In addition , IL-...	[ "Inflammation , which is directly regulated by interleukin-6 ( IL-6 ) signaling , is implicated in the etiology of several chronic diseases .", "Although a common , non-synonymous variant in the IL-6 receptor gene ( IL6R Asp358Ala; rs2228145 A>C ) is associated with the risk of several common diseases , with the ...	[ "Interleukin-6 ( IL-6 ) is a complex cytokine , which plays a critical role in the regulation of inflammatory responses .", "Genetic variation in the IL-6 receptor gene is associated with the risk of several human diseases with an inflammatory component , including coronary heart disease , rheumatoid arthritis , ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "hematology/acute lymphoblastic leukemia", "genetics and genomics/disease models", "virology/viruses and cancer", "oncology/hematological malignancies", "genetics and genomics/cancer genetics" ]	Murine Leukemias with Retroviral Insertions at Lmo2 Are Predictive of the Leukemias Induced in SCID-X1 Patients Following Retroviral Gene Therapy	journal.pgen.1000491	null	[ [ "SCID-X1 patients are deficient in the common γ chain of the interleukin-2 receptor ( IL2RG ) [1] .", "In three SCID-X1 trials , CD34+ hematopoietic stem cells were cultured ex vivo and transduced with a defective Moloney murine leukemia virus ( MuLV ) expressing IL2RG and then transplanted back to the pa...	[ "Five X-linked severe combined immunodeficiency patients ( SCID-X1 ) successfully treated with autologous bone marrow stem cells infected ex vivo with an IL2RG-containing retrovirus subsequently developed T-cell leukemia and four contained insertional mutations at LMO2 .", "Genetic evidence also suggests a role f...	[ "Twenty patients with X-linked severe combined immunodeficiency ( SCID-X1 ) have been successfully treated by gene therapy .", "Unfortunately , five of these patients have developed T-cell leukemia two or more years after receiving the therapeutic gene IL2RG on a retroviral vector .", "The leukemias developed b...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "dengue", "hepatitis", "gastroenterology and hepatology", "lipid signaling", "infectious disease control", "mapk signaling cascades", "erk signaling cascade", "hepatitis c", "infectious diseases", "signaling in cellular processes", "membranes and sorting", "biology", "infectiou...	MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles	journal.ppat.1002829	null	[ [ "Approximately 160 million people are chronically infected with hepatitis C virus ( HCV ) [1] .", "Without treatment , at least 20% of patients will develop liver cirrhosis and of these , approximately 15% will progress to liver cancer within ten years [2] .", "HCV is the sole member of the genus Hepa...	[ "Hepatitis C virus ( HCV ) has infected around 160 million individuals .", "Current therapies have limited efficacy and are fraught with side effects .", "To identify cellular HCV dependency factors , possible therapeutic targets , we manipulated signaling cascades with pathway-specific inhibitors .", "Using ...	[ "The human genome encodes more than 30 phospholipase A2s .", "These enzymes cleave fatty acids at the C2 atom of phosphoglycerides and thus modulate membrane properties .", "Among all PLA2s only PLA2G4A , which is recruited to perinuclear membranes by Ca2+ and activated by extracellular stimuli via the mitogen ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "genetics and genomics" ]	Ectopic Expression of Ptf1a Induces Spinal Defects, Urogenital Defects, and Anorectal Malformations in Danforth's Short Tail Mice	journal.pgen.1003204	null	[ [ "Danforth's short tail ( Sd ) is a semidominant spontaneous mutant mouse characterized by severe spinal defects , urogenital defects , and anorectal malformations [1] , [2] , [3] .", "Heterozygous and homozygous Sd animals display a broad range of abnormalities in the vertebral column , including reductio...	[ "Danforth's short tail ( Sd ) is a semidominant mutation on mouse chromosome 2 , characterized by spinal defects , urogenital defects , and anorectal malformations .", "However , the gene responsible for the Sd phenotype was unknown .", "In this study , we identified the molecular basis of the Sd mutation .", ...	[ "Caudal regression syndrome ( CRS ) is a congenital heterogeneous constellation of caudal anomalies that includes varying degrees of agenesis of the spinal column , anorectal malformations , and genitourinary anomalies .", "Its pathogenesis is unclear .", "However , it could be the result of excessive physiolog...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "variant genotypes", "random variables", "covariance", "factor analysis", "twins", "genetic mapping", "simulation and modeling", "multivariate analysis", "developmental biology", "mathematics", "statistics (mathematics)", "research and analysis methods", "mathematical and statistical techniq...	An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci	journal.pcbi.1005537	null	[ [ "The CONFETI framework is constructed to systematically avoid the tendency of other confounding factor analysis methods to model broad impact eQTL as confounding variation .", "This is accomplished by leveraging Independent Component Analysis ( ICA ) to identify generative sources of multivariate gene exp...	[ "Genome-wide expression Quantitative Trait Loci ( eQTL ) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases .", "While the majority of eQTL identified in genome-wide analyses impact a single gene , eQTL that impact many genes are particularly valuable ...	[ "The discovery of expression Quantitative Trait Loci ( eQTL ) from the analysis of genome-wide genotype and gene expression data has played an important role in the study of cellular processes and complex disease .", "Here , we introduce CONFETI: Confounding Factor Estimation Through Independent component analysi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics", "biology", "genetics and genomics", "toxicology" ]	Cdon Mutation and Fetal Ethanol Exposure Synergize to Produce Midline Signaling Defects and Holoprosencephaly Spectrum Disorders in Mice	journal.pgen.1002999	null	[ [ "Holoprosencephaly ( HPE ) is a congenital anomaly characterized by failure to define the midline of the forebrain and midface [1] .", "HPE occurs with the remarkable frequency of ∼1∶250 conceptions but , due to intrauterine lethality , live-born prevalence is ∼1∶10 , 000 [2] , [3] .", "A phenotypic c...	[ "Holoprosencephaly ( HPE ) is a remarkably common congenital anomaly characterized by failure to define the midline of the forebrain and midface .", "HPE is associated with heterozygous mutations in Sonic hedgehog ( SHH ) pathway components , but clinical presentation is extremely variable and many mutation carri...	[ "Holoprosencephaly ( HPE ) , a congenital anomaly characterized by failure to form the midline of the forebrain and midface , occurs as frequently as 1 in 250 conceptions .", "Mutations in genes that direct formation of the forebrain and facial midline are associated with HPE , but the clinical outcome is extreme...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "hiv", "immunology", "biology", "viral diseases", "immunomodulation", "immune response" ]	TIM-3 Does Not Act as a Receptor for Galectin-9	journal.ppat.1003253	null	[ [ "Inhibitory costimulatory signals play a decisive role in the outcome of T cell responses and there is an ever-growing number of pathways that have been implicated in such processes .", "The successful clinical use of CTLA-4 antibodies to enhance anti-melanoma T cell responses underlines the therapeutic p...	[ "T cell immunoglobulin and mucin protein 3 ( TIM-3 ) is a type I cell surface protein that was originally identified as a marker for murine T helper type 1 cells .", "TIM-3 was found to negatively regulate murine T cell responses and galectin-9 was described as a binding partner that mediates T cell inhibitory ef...	[ "Inhibitory costimulatory receptors are a hallmark of exhausted T cells , which accumulate during chronic infection with viruses like HIV-1 .", "Recently , TIM-3 was described as functional receptor on exhausted human T cells .", "Galectin-9 was reported as an inhibitory ligand for TIM-3 on murine T cells , but...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "parastic protozoans", "trypanosoma", "genetics", "molecular genetics", "biology", "microbiology", "protozoology", "genetics and genomics" ]	Genetic Engineering of Trypanosoma (Dutonella) vivax and In Vitro Differentiation under Axenic Conditions	journal.pntd.0001461	null	[ [ "Trypanosoma vivax and Trypanosoma congolense are the main parasite species responsible for Animal African Trypanosomosis ( AAT ) or Nagana .", "This disease causes about 3 million deaths annually and has a marked impact on agriculture in sub-Saharan and South American endemic countries , leading to annua...	[ "Trypanosoma vivax is one of the most common parasites responsible for animal trypanosomosis , and although this disease is widespread in Africa and Latin America , very few studies have been conducted on the parasite's biology .", "This is in part due to the fact that no reproducible experimental methods had bee...	[ "Trypanosoma vivax is a major parasite of domestic animals in Africa and Americas .", "Most studies on this parasite have focused on gathering epidemiological data in the field .", "Studies on its biology , metabolism and interaction with the host immune system have been hindered by a lack of suitable tools for...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "ecology and environmental sciences", "medicine and health sciences", "malacology", "china", "population dynamics", "tropical diseases", "geographical locations", "parasitic diseases", "animals", "oncomelania", "gastropods", "aquatic environments", "habitats", "bodies of...	Identification of high-risk habitats of Oncomelania hupensis, the intermediate host of schistosoma japonium in the Poyang Lake region, China: A spatial and ecological analysis	journal.pntd.0007386	null	[ [ "Schistosomiasis japonica , a water-borne parasitic disease , has long been prevalent in 12 provinces located along the Yangtze River in China .", "It is caused by infection with the parasite Schistosoma japonicum , which has a unique intermediate host , Oncomelania hupensis .", "During the past 60 ye...	[ "Identifying and eliminating snail habitats is the key measure for schistosomiasis control , critical for the nationwide strategy of eliminating schistosomiasis in China .", "Here , our aim was to construct a new analytical framework to predict high-risk snail habitats based on a large sample field survey for Onc...	[ "Oncomelania hupensis is the sole intermediate host of Schistosoma japonicum and it is critical for the long-term sustainable control and elimination of schistosomiasis .", "We suggest a new analytical framework to predict high-risk snail habitats based on ecological models .", "Their predictive performance wer...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "viral transmission and infection", "microbiology", "host-pathogen interaction", "viral structure", "viruslike particles", "membranes and sorting", "biology", "host cells", "cell biology", "virology", "molecular cell biology", "nucleocapsid" ]	The ESCRT Machinery Is Recruited by the Viral BFRF1 Protein to the Nucleus-Associated Membrane for the Maturation of Epstein-Barr Virus	journal.ppat.1002904	null	[ [ "The endosomal sorting complex required for transport ( ESCRT ) machinery is conserved evolutionarily and involved in catalyzing the scission of membrane necks in endosome sorting , biogenesis of multivesicular bodies ( MVBs ) , cytokinesis and release of enveloped virions .", "In contrast to the cellular...	[ "The cellular endosomal sorting complex required for transport ( ESCRT ) machinery participates in membrane scission and cytoplasmic budding of many RNA viruses .", "Here , we found that expression of dominant negative ESCRT proteins caused a blockade of Epstein-Barr virus ( EBV ) release and retention of viral B...	[ "Herpesviruses are large DNA viruses associated with human and animal diseases .", "After viral DNA replication , the herpesviral nucleocapsids egress through the nuclear membrane for subsequent cytoplasmic virion maturation .", "However , the mechanism by which the virus regulates the nuclear membrane and cell...	2012
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "molecular dynamics", "nmr spectroscopy", "simulation and modeling", "protein structure", "thermodynamics", "research and analysis methods", "proteins", "chemistry", "biophysics", "molecular biology", "free energy", "physics", "biochemistry", "biochemical simulations", "scattering", "b...	Rapid interpretation of small-angle X-ray scattering data	journal.pcbi.1006900	null	[ [ "We investigated structural transitions in three two-state protein systems , where the target structure was initially known ." ], [ "For the VHP-based polypeptide system ( Fig 1A inset ) , proof-of-concept simulations aimed at both transitions from bent to elongated and elongated to bent conformation ...	[ "The fundamental aim of structural analyses in biophysics is to reveal a mutual relation between a molecule’s dynamic structure and its physiological function .", "Small-angle X-ray scattering ( SAXS ) is an experimental technique for structural characterization of macromolecules in solution and enables time-reso...	[ "Proteins are the molecular nanomachines in biological cells and thus vital to any known form of life .", "From the evolutionary perspective , viable protein structure emerges on the basis of a ‘form-follows-function’ principle .", "A protein’s designated function is inextricably linked to dynamic conformationa...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dengue virus", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "viruses", "rna viruses", "antibodies", "immunologic techniques", "research and analysis methods", "immune syst...	A high-throughput and multiplex microsphere immunoassay based on non-structural protein 1 can discriminate three flavivirus infections	journal.pntd.0007649	null	[ [ "Despite a marked decrease of Zika virus ( ZIKV ) infection since late 2017 , the specter of congenital Zika syndrome ( CZS ) and its re-emergence in flavivirus-endemic regions highlight the need for sensitive and specific diagnostic tests [1–4] .", "Similar to the laboratory diagnosis for other flaviviru...	[ "The explosive spread of Zika virus ( ZIKV ) and associated complications in flavivirus-endemic regions underscore the need for sensitive and specific serodiagnostic tests to distinguish ZIKV , dengue virus ( DENV ) and other flavivirus infections .", "Compared with traditional envelope protein-based assays , sev...	[ "Although there was a decrease of Zika virus ( ZIKV ) infection since late 2017 , the specter of congenital Zika syndrome and its re-emergence in flavivirus-endemic regions emphasize the need for sensitive and specific serological tests to distinguish ZIKV , dengue virus ( DENV ) and other flaviviruses .", "Compa...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuropsychiatric disorders", "medicine and health sciences", "adhd", "anxiety disorders", "pervasive developmental disorders", "obsessive-compulsive disorder", "bipolar disorder", "social sciences", "autism", "developmental psychology", "neuroscience", "cognitive psychology", "behavioral di...	Comprehensive cross-disorder analyses of CNTNAP2 suggest it is unlikely to be a primary risk gene for psychiatric disorders	journal.pgen.1007535	null	[ [ "The contactin-associated protein-like 2 ( CNTNAP2 ) is located on chromosome 7q35-36 . 1 , and consists of 24 exons spanning 2 . 3Mb , making it one of the largest protein coding genes in the human genome .", "This gene encodes the CASPR2 protein , related to the neurexin superfamily , which localises wi...	[ "The contactin-associated protein-like 2 ( CNTNAP2 ) gene is a member of the neurexin superfamily .", "CNTNAP2 was first implicated in the cortical dysplasia-focal epilepsy ( CDFE ) syndrome , a recessive disease characterized by intellectual disability , epilepsy , language impairments and autistic features .", ...	[ "Genetic mutations that disrupt both copies of the CNTNAP2 gene lead to severe disease , characterized by profound intellectual disability , epilepsy , language difficulties and autistic traits , leading to the hypothesis that this gene may also be involved in autism given some overlapping clinical features with th...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Critical Slowing Down Governs the Transition to Neuron Spiking	journal.pcbi.1004097	null	[ [ "Rapid transitions to a qualitatively different state can be observed in many complex systems .", "Their sometimes catastrophic outcomes in systems from diverse fields such as climate , ecology , medicine and economics have led to an increased interest in the underlying structure and dynamics of these tra...	[ "Many complex systems have been found to exhibit critical transitions , or so-called tipping points , which are sudden changes to a qualitatively different system state .", "These changes can profoundly impact the functioning of a system ranging from controlled state switching to a catastrophic break-down; signal...	[ "Neurons efficiently convey information by being able to switch rapidly between two different states: quiescence and spiking .", "Such sudden shifts to a qualitatively different state are observed in many complex systems; the often dramatic consequences of these tipping points for diverse fields such as economics...	2015
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "biotechnology", "cryptococcus neoformans", "medicine and health sciences", "rna interference", "cryptococcus", "pathology and laboratory medicine", "fungal genetics", "gene regulation", "pathogens", "regulatory proteins", "microbiology", "dna-binding proteins", "developmental biology", "f...	Gene Network Polymorphism Illuminates Loss and Retention of Novel RNAi Silencing Components in the Cryptococcus Pathogenic Species Complex	journal.pgen.1005868	null	[ [ "Genome reduction is a common adaptation among bacterial pathogens and commensals , and has been hypothesized to occur for a number of reasons , including increased specificity to a host or environmental range , or to increase virulence more directly through loss of an antivirulence gene or gene cluster .", ...	[ "RNAi is a ubiquitous pathway that serves central functions throughout eukaryotes , including maintenance of genome stability and repression of transposon expression and movement .", "However , a number of organisms have lost their RNAi pathways , including the model yeast Saccharomyces cerevisiae , the maize pat...	[ "Genome instability and mutations provoked by transposon movement are counteracted by novel defense mechanisms in organisms as diverse as fungi , plants , and mammals .", "In the human fungal pathogen Cryptococcus neoformans , an RNAi silencing pathway operates to defend the genome against mobile elements and tra...	2016
[ "Introduction", "Models", "Results", "Discussion" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/animal cognition", "neuroscience/theoretical neuroscience" ]	Context-Dependent Encoding of Fear and Extinction Memories in a Large-Scale Network Model of the Basal Amygdala	journal.pcbi.1001104	null	[ [ "In classical fear conditioning an animal learns to associate an initially neutral stimulus ( the conditioned stimulus , CS ) with an aversive stimulus ( the unconditioned stimulus , US ) after paired exposure to the CS and the US .", "Subsequent repeated non-reinforced presentations of the CS alone resul...	[ "The basal nucleus of the amygdala ( BA ) is involved in the formation of context-dependent conditioned fear and extinction memories .", "To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA , composed of excitatory and inhibitory leaky-integrate-and-fire neuron...	[ "The amygdaloid complex is one of the key brain structures involved in fear-related processes .", "A typical way to study neural correlates of fear expression ( e . g . freezing response ) in the amygdala is to perform a fear conditioning paradigm , which yields a conditioned fear response .", "This response ca...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Short-term Forecasting of the Prevalence of Trachoma: Expert Opinion, Statistical Regression, versus Transmission Models	journal.pntd.0004000	null	[ [ "The World Health Organization ( WHO ) , the International Trachoma Initiative , Ministries of Health , and their partners aim to control blinding trachoma by 2020 , implementing surgical campaigns , antibiotic distributions , hygiene initiatives , and environmental improvements [1] .", "Trachoma control ...	[ "Trachoma programs rely on guidelines made in large part using expert opinion of what will happen with and without intervention .", "Large community-randomized trials offer an opportunity to actually compare forecasting methods in a masked fashion .", "The Program for the Rapid Elimination of Trachoma trials es...	[ "Clinicaltrials . gov NCT00792922" ]	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "antimicrobials", "deletion mutation", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "drugs", "messenger rna", "microbiology", "pigments", "antibiotic resistance", "mutation", "antibiotics", "materials science", "pharmacology", "oligomers", "dyes", ...	Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy	journal.pbio.1002552	Reducing expression of the AcrAB-TolC efflux system of Escherichia coli by antisense-mediated translation inhibition increases the susceptibility of bacteria to a wide range of antibiotics.	[ [ "Antibiotic resistance is an important public health problem that emerged shortly after the discovery of antibiotics [1 , 2] .", "Pathogenic bacteria are either intrinsically resistant to some antibiotics or they acquire resistance via spontaneous mutations or horizontal gene transfer .", "These resis...	[ "The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality .", "To improve the efficacy of existing antibiotic compounds , we introduce a new method for strategically inducing antibiotic hyperse...	[ "Antibiotic resistance is a global health threat .", "While genome sequencing and genetic manipulation tools have elucidated many resistance mechanisms , these tools have not yet been developed into successful therapeutics .", "One tool with such potential are peptide-conjugated phosphorodiamidate morpholino ol...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "next-generation sequencing", "genome expression analysis", "bacterial genomics", "genomics", "genome evolution", "genome analysis", "transcriptome analysis", "genome annotation", "biology and life sciences", "comparative genomics", "molecular evolution", "computational biology", "evolutiona...	Robust Identification of Noncoding RNA from Transcriptomes Requires Phylogenetically-Informed Sampling	journal.pcbi.1003907	null	[ [ "Genome sequencing has transformed microbiology , offering unprecedented insight into the physiology , biochemistry , and genetics of Bacteria and Archaea [1]–[4] .", "Equally , careful examination of transcriptional outputs has revealed that bacterial and archaeal transcriptomes are remarkably complex [5...	[ "Noncoding RNAs are integral to a wide range of biological processes , including translation , gene regulation , host-pathogen interactions and environmental sensing .", "While genomics is now a mature field , our capacity to identify noncoding RNA elements in bacterial and archaeal genomes is hampered by the dif...	[ "We have analysed more than 400 public transcriptomes , generated using RNA-seq , from almost 40 strains of Bacteria and Archaea .", "We discovered that the capacity to identify noncoding RNA outputs from this data is strongly dependent on phylogenetic sampling .", "Our results show that , for the full potentia...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "humoral immunity", "medicine", "viral vaccines", "immunology", "microbiology", "dengue", "adaptive immunity", "immune defense", "infectious disease control", "immunizations", "infectious diseases", "biology", "immune response", "immunity", "virology", "viral diseases" ]	Dengue-1 Envelope Protein Domain III along with PELC and CpG Oligodeoxynucleotides Synergistically Enhances Immune Responses	journal.pntd.0001645	null	[ [ "Dengue is the most important mosquito-borne flavivirus disease .", "People living in the tropical and subtropical areas are at risk of dengue virus infection , and more than 50 million dengue infected cases occur worldwide each year [1] , [2] .", "Vaccine inoculation is a cost-effective way of combat...	[ "The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy .", "Adjuvants can help to overcome some of these inherent defects with subunit vaccines .", "Here , we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system , termed PELC , in poten...	[ "Dengue is a mosquito-borne disease .", "Infection of dengue virus can cause clinical manifestations ranging from self-limiting dengue fever to potentially life-threatening dengue hemorrhagic fever or dengue shock syndrome .", "In recent years , dengue has spread to most tropical and subtropical areas , making ...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "viral transmission and infection", "plant cell biology", "microbiology", "chloroplasts", "plant science", "membrane fusion", "viral genome", "cellular structures and organelles", "microbial genomics", "viral genomics", "viral packaging", "viral replication", "cell membranes", "cytoplasm",...	Structural studies demonstrating a bacteriophage-like replication cycle of the eukaryote-infecting Paramecium bursaria chlorella virus-1	journal.ppat.1006562	null	[ [ "A fundamental and general stage in viral infection is the transfer of the viral genome into the host cell .", "After attachment to the cell membrane , viruses that infect animal cells depend on various entry pathways , mainly consisting of endocytosis , pinocytosis , phagocytosis and variants of these st...	[ "A fundamental stage in viral infection is the internalization of viral genomes in host cells .", "Although extensively studied , the mechanisms and factors responsible for the genome internalization process remain poorly understood .", "Here we report our observations , derived from diverse imaging methods on ...	[ "Although extensively studied , the mechanisms responsible for internalization of viral genomes into their host cells remain unclear .", "A particularly interesting case of genome release and internalization is provided by the large Paramecium bursaria chlorella virus-1 ( PBCV-1 ) , which infects unicellular euka...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/gene expression", "infectious diseases/neglected tropical diseases", "cell biology", "infectious diseases/helminth infections", "public health and epidemiology/preventive medicine", "microbiology/parasitology" ]	Altered Patterns of Gene Expression Underlying the Enhanced Immunogenicity of Radiation-Attenuated Schistosomes	journal.pntd.0000240	null	[ [ "The radiation-attenuated schistosome ( RA ) vaccine remains the most effective way of inducing high levels of protective immunity against Schistosoma mansoni in rodent and primate hosts ( reviewed by Coulson ) [1] .", "However , an effective recombinant vaccine based upon it , for use in humans , has thu...	[ "Schistosome cercariae only elicit high levels of protective immunity against a challenge infection if they are optimally attenuated by exposure to ionising radiation that truncates their migration in the lungs .", "However , the underlying molecular mechanisms responsible for the altered phenotype of the irradia...	[ "Schistosoma mansoni is a blood-dwelling parasitic worm that causes schistosomiasis in humans throughout Africa and parts of South America .", "A vaccine would enhance attempts to control and eradicate the disease that currently relies on treatment with a single drug .", "Although a manufactured vaccine has yet...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "action potentials", "medicine and health sciences", "neural networks", "membrane potential", "microbiology", "signaling networks", "electrophysiology", "neuroscience", "network analysis", "computational neuroscience", "excitatory postsynaptic potentials", "computer and information sciences", ...	Emergent decision-making behaviour and rhythm generation in a computational model of the ventromedial nucleus of the hypothalamus	journal.pcbi.1007092	null	[ [ "The ventromedial nucleus of the hypothalamus ( VMN ) is a large hypothalamic nucleus with an important role in diverse behaviours stretching beyond its classic role in appetite regulation and energy homeostasis [1] .", "The nucleus regulates glucose and lipid homeostasis [2–4] , appetite and energy expen...	[ "The ventromedial nucleus of the hypothalamus ( VMN ) has an important role in diverse behaviours .", "The common involvement in these of sex steroids , nutritionally-related signals , and emotional inputs from other brain areas , suggests that , at any given time , its output is in one of a discrete number of po...	[ "When the needs of an animal require the execution of particular behaviours , the brain must decide which of these needs to prioritise–whether to flee from or fight an aggressor for example , or whether to hunt for food or pursue sex .", "The ventromedial nucleus of the hypothalamus is involved in such decisions ...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	The Prevalence of Human T-Lymphotropic Virus Infection among Blood Donors in Southeast China, 2004-2013	journal.pntd.0003685	null	[ [ "Human T-lymphotropic virus ( HTLV ) is a retrovirus which has been known for about 35 years since it was first isolated from a patient with a T-cell malignancy [1] .", "Previous studies had revealed the etiologic role of HTLV infection in the diseases of adult T-cell leukemia/lymphoma ( ATL ) , HTLV-1 as...	[ "The human T-lymphotropic virus type 1 ( HTLV-1 ) which is associated with the diseases of adult T-cell leukemia/lymphoma , HTLV-1 associated myelopathy / tropical spastic paraparesis ( HAM/TSP ) and HTLV-associated uveitis , can cause transfusion-transmitted infections .", "Although HTLV screening of blood donor...	[ "The human T-lymphotropic virus type 1 ( HTLV-1 ) which is associated with the diseases of adult T-cell leukemia/lymphoma , tropical spastic paraparesis etc . , can cause transfusion-transmitted infections , it also can be transmitted by sex or breastfeeding .", "Globally , approximately 20 million people are est...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "carbohydrate metabolism", "metabolic networks", "mathematical models", "biomarkers", "glucose metabolism", "metabolomics", "mathematics", "metabolites", "forecasting", "statistics (mathematics)", "network analysis", "research and analysis methods", "random walk", "computer and information...	Biomarkers are used to predict quantitative metabolite concentration profiles in human red blood cells	journal.pcbi.1005424	null	[ [ "The data generated from deep coverage omics tools are becoming broadly available and thus their use is becoming more common [1 , 2] .", "With this data , researchers have begun to identify metabolomics biomarkers that can be used to describe systemic behavior with only a few inexpensive and reliable meas...	[ "Deep-coverage metabolomic profiling has revealed a well-defined development of metabolic decay in human red blood cells ( RBCs ) under cold storage conditions .", "A set of extracellular biomarkers has been recently identified that reliably defines the qualitative state of the metabolic network throughout this m...	[ "While deep-coverage omics data sets are allowing for more complete characterization of biological systems , there has been a concerted effort to identify a subset of measurements that are representative of qualitative network-level behavior .", "For some systems—like the human red blood cell ( RBC ) —such biomar...	2017
[ "Introduction", "Methods", "Results and Discussion" ]	[ "spectrometric identification of proteins", "organismal evolution", "invertebrates", "medicine and health sciences", "genome evolution", "animals", "developmental biology", "animal behavior", "genome analysis", "molecular genetics", "zoology", "fertilization", "epidemiology", "proteomics",...	Identification and Characterization of Seminal Fluid Proteins in the Asian Tiger Mosquito, Aedes albopictus	journal.pntd.0002946	null	[ [ "Aedes albopictus , the Asian tiger mosquito , is an important species from both an epidemiological and an ecological perspective .", "Epidemiologically , it has the potential ability to transmit over 20 viruses [1] , [2] , and it plays a significant and growing role across the world as an important vecto...	[ "The Asian tiger mosquito ( Aedes albopictus ) is an important vector for pathogens that affect human health , including the viruses that cause dengue and Chikungunya fevers .", "It is also one of the world's fastest-spreading invasive species .", "For these reasons , it is crucial to identify strategies for co...	[ "The highly invasive Asian tiger mosquito ( Aedes albopictus ) transmits several pathogens that cause disease in humans and other animals .", "Therefore , Ae .", "albopictus poses a large and growing threat to public health across the world .", "One step toward managing the reproduction and threat of this spe...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "neurological disorders", "neurology", "biology", "neuroscience" ]	Age-Related Neuronal Degeneration: Complementary Roles of Nucleotide Excision Repair and Transcription-Coupled Repair in Preventing Neuropathology	journal.pgen.1002405	null	[ [ "DNA is continuously damaged by spontaneous hydrolytic decay , endogenous metabolites ( e . g . reactive oxygen species , malondialdehyde ) , and environmental genotoxins .", "DNA lesions can give rise to irreversible mutations and chromosomal aberrations that may trigger carcinogenesis .", "Alternati...	[ "Neuronal degeneration is a hallmark of many DNA repair syndromes .", "Yet , how DNA damage causes neuronal degeneration and whether defects in different repair systems affect the brain differently is largely unknown .", "Here , we performed a systematic detailed analysis of neurodegenerative changes in mouse m...	[ "Metabolism produces reactive oxygen species that damage our DNA and other cellular components , and as such it contributes to the aging process , including neuronal degeneration .", "Accordingly , genetic disorders associated with impaired DNA damage repair are frequently associated with premature onset of aging...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "biotechnology", "synthetic biotechnology", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "engineering and technology", "synthetic biology", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "protozoans", "neglected tropical...	Next-generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes	journal.pntd.0005972	null	[ [ "Chagas disease is a major health and economic problem in Latin America , for which no vaccine or appropriate drugs for large-scale public health interventions are yet available [1] .", "It is caused by the protozoan parasite Trypanosoma cruzi , found throughout the Americas in a variety of wild and domes...	[ "Chagas Disease , caused by the protozoan Trypanosoma cruzi , is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available .", "Accurate diagnosis is essential for the early identification and follow up of vector-bo...	[ "Chagas disease , caused by the parasite Trypanosoma cruzi , is a life-long and debilitating illness of major significance throughout Latin America , and an emergent threat to global public health .", "Diagnostic tests are key tools to support disease surveillance , and to ultimately help stop transmission of the...	2017
[ "Introduction", "Results/Discussion", "Methods" ]	[ "medicine", "pathology", "drugs and devices", "sports and exercise medicine", "pediatrics", "pharmacology", "pediatrics and child health", "biology", "systems biology", "diagnostic medicine", "drug research and development", "neurological disorders", "neurology", "general pathology", "co...	Novel Approach to Meta-Analysis of Microarray Datasets Reveals Muscle Remodeling-related Drug Targets and Biomarkers in Duchenne Muscular Dystrophy	journal.pcbi.1002365	null	[ [ "Microarray-based expression profiling is a widely used , quick and inexpensive method to obtain information about the specific diseases .", "A traditional approach when searching for drug targets or candidate biomarkers for a specific disease is to look for genes differentially expressed between the dise...	[ "Elucidation of new biomarkers and potential drug targets from high-throughput profiling data is a challenging task due to a limited number of available biological samples and questionable reproducibility of differential changes in cross-dataset comparisons .", "In this paper we propose a novel computational appr...	[ "Comparison of gene expression in diseased and normal tissue is a powerful tool of studying processes involved in pathogenesis and searching for potential drug targets and biomarkers of the disease's progression and treatment outcome .", "We have developed a novel approach for systematic knowledge-driven analysis...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "liver", "body fluids", "pathology and laboratory medicine", "cancer treatment", "immunology", "bile", "cancers and neoplasms", "carcinomas", "gastrointestinal tumors", "liver diseases", "toxicology", "oncology", "signs and symptoms", "gastroenterology and...	Sustained activation of detoxification pathways promotes liver carcinogenesis in response to chronic bile acid-mediated damage	journal.pgen.1007380	null	[ [ "The microenvironment of chronically inflamed tissues is a source of multiple mediators that trigger and sustain cellular transformation and tumorigenesis [1–4] .", "Within the broad and heterogeneous group of inflammation-associated cancers , a distinct class is represented by those tumors that develop w...	[ "Chronic inflammation promotes oncogenic transformation and tumor progression .", "Many inflammatory agents also generate a toxic microenvironment , implying that adaptive mechanisms must be deployed for cells to survive and undergo transformation in such unfavorable contexts .", "A paradigmatic case is represe...	[ "Chronic inflammation associated to the sustained exposure to toxic chemicals can lead to cancer , but how transforming cells acquire the ability to oppose chemo-toxicity and eventually thrive is unclear .", "In this study , we set out to profile the molecular changes occurring in a mouse model of liver disease c...	2018
[ "Introduction", "Materials and methods", "Results" ]	[ "chemical compounds", "dna-binding proteins", "organic compounds", "materials science", "protein structure", "amino acids", "macromolecules", "materials by structure", "research and analysis methods", "polymers", "polymer chemistry", "aromatic amino acids", "protein structure determination",...	The exclusive effects of chaperonin on the behavior of proteins with 52 knot	journal.pcbi.1005970	null	[ [ "The role of knots in protein structures is still not fully understood .", "The topological complexity induces stability to the structure [1 , 2] and enforces local motifs favorable for active sites of enzymes [3] .", "The latter fact may explain , why over 80% of known knotted proteins are enzymes wi...	[ "The folding of proteins with a complex knot is still an unresolved question .", "Based on representative members of Ubiquitin C-terminal Hydrolases ( UCHs ) that contain the 52 knot in the native state , we explain how UCHs are able to unfold and refold in vitro reversibly within the structure-based model .", ...	[ "Self-tying of knotted proteins remains a challenge both for theoreticians and experimentalist .", "In this work , we study the proteins with complex , the 52 knot , in a bulk and confined within a chaperonin box .", "We show that in our model we recreate the experimental results , identify two topologically di...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/transcription and translation", "genetics and genomics/gene function", "virology/viruses and cancer" ]	CTCF Prevents the Epigenetic Drift of EBV Latency Promoter Qp	journal.ppat.1001048	null	[ [ "Epstein-Barr Virus ( EBV ) is a human gamma herpesvirus that establishes latent infection in more than 90% of the adult population world-wide [1] , [2] .", "The ∼170 kb genome encodes ∼90 viral genes but only a few of these are expressed during latent infection .", "The latent infection is a cofactor...	[ "The establishment and maintenance of Epstein-Barr Virus ( EBV ) latent infection requires distinct viral gene expression programs .", "These gene expression programs , termed latency types , are determined largely by promoter selection , and controlled through the interplay between cell-type specific transcripti...	[ "Epstein-Barr Virus ( EBV ) establishes a latent infection that is associated with several lymphoid and epithelial cell malignancies .", "The latent virus persists as a circular minichromosome in the nucleus of infected cells .", "Epigenetic modifications of the viral DNA and chromatin are known to control vira...	2010
[ "Introduction", "Materials and methods", "Results and discussion" ]	[ "blood cells", "antimicrobials", "invertebrates", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "drugs", "immunology", "microbiology", "antifungals", "parasitic protozoans", "animals", "protozoan life cycles", "developmental biology", ...	Antifungal compounds from Streptomyces associated with attine ants also inhibit Leishmania donovani	journal.pntd.0007643	null	[ [ "Leishmaniasis is designated as Neglected Tropical Diseases ( NTDs ) by the World Health Organization ( WHO ) .", "The visceral leishmaniasis is the most serious clinical form , produced by two Leishmania species , L . infantum and L . donovani [1] .", "There are between 50–90 thousands new cases and ...	[ "Bacterial strains isolated from attine ants showed activity against the insect specialized fungal pathogen Escovopsis and also against the human protozoan parasite Leishmania donovani .", "The bioassay guided fractionation of extracts from cultures of Streptomyces sp .", "ICBG292 , isolated from the exoskeleto...	[ "Visceral leishmaniasis , caused by Leishmania infantum and L . donovani , is characterized by high rate mortality worldwide .", "Current treatments for this disease suffer from toxicity , variable efficacy , requirements for parenteral administration and length of treatment regimens .", "New chemical entities ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology" ]	Diagnostic Accuracy of Kato-Katz and FLOTAC for Assessing Anthelmintic Drug Efficacy	journal.pntd.0001036	null	[ [ "Current estimates suggest that soil-transmitted helminths might still affect over a quarter of the world's population and inflict a huge public health burden , particularly on rural and deprived urban communities in the developing world [1]–[3] .", "Efforts are underway to reduce morbidity due to soil-tr...	[ "Sensitive diagnostic tools are required for an accurate assessment of prevalence and intensity of helminth infections in areas undergoing regular deworming , and for monitoring anthelmintic drug efficacy .", "We compared the diagnostic accuracy of the Kato-Katz and FLOTAC techniques in the frame of a drug effica...	[ "In areas where parasitic worm infections have been successfully reduced as a result of deworming campaigns , the level of infections and drug efficacy must be carefully monitored .", "For this purpose , diagnostic methods with a high sensitivity are needed .", "We compared the accuracy of the widely used Kato-...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "animal genetics", "model organisms", "gene regulatory networks", "genetics", "biology and life sciences", "computational biology", "research and analysis methods", "gene function" ]	Retinoic Acid Activates Two Pathways Required for Meiosis in Mice	journal.pgen.1004541	null	[ [ "Most eukaryotes reproduce sexually , with life cycles that display an alternation of diploid and haploid phases .", "The generation of haploid cells from diploid cells is achieved through meiosis , featuring a single round of DNA replication ( meiotic S ) followed by two rounds of division ( meiosis I an...	[ "In all sexually reproducing organisms , cells of the germ line must transition from mitosis to meiosis .", "In mice , retinoic acid ( RA ) , the extrinsic signal for meiotic initiation , activates transcription of Stra8 , which is required for meiotic DNA replication and the subsequent processes of meiotic proph...	[ "The transition from mitosis to meiosis is a defining feature of germ cells , the precursors of eggs and sperm .", "In mice , retinoic acid ( RA ) , a vitamin A derivative , induces expression of the gene Stra8 , which in turn is required for the first critical steps of meiosis .", "The timing of Stra8 expressi...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "genome-wide association studies", "variant genotypes", "sociology", "social sciences", "alleles", "genetic mapping", "mathematics", "statistics (mathematics)", "genome analysis", "molecular biology techniques", "genotyping", "research and analysis methods", "mathematical and statistical tec...	Evaluation and application of summary statistic imputation to discover new height-associated loci	journal.pgen.1007371	null	[ [ "Genome-wide association studies ( GWASs ) have been successfully applied to reveal genetic markers associated with hundreds of traits and diseases .", "The genotyping arrays used in these studies only interrogate a small proportion of the genome and are therefore typically unable to pinpoint the causal v...	[ "As most of the heritability of complex traits is attributed to common and low frequency genetic variants , imputing them by combining genotyping chips and large sequenced reference panels is the most cost-effective approach to discover the genetic basis of these traits .", "Association summary statistics from ge...	[ "Genome-wide association studies ( GWASs ) quantify the effect of genetic variants and traits , such as height .", "Such estimates are called association summary statistics and are typically publicly shared through publication .", "Typically , GWASs are carried out by genotyping ∼ 500′000 SNVs for each individu...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "radiochemistry", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "viral structure", "nuclear decay", "viruses", "physiological processes", "rna viruses", "sexually transmitted diseases", "antibodies", "...	A single mutation in the envelope protein modulates flavivirus antigenicity, stability, and pathogenesis	journal.ppat.1006178	null	[ [ "Flaviviruses are enveloped , positive-stranded RNA viruses typically transmitted to humans via infected ticks or mosquitoes .", "As many members of the flavivirus genus are emerging , they constitute a significant threat to global health .", "For example , approximately 390 million humans worldwide a...	[ "The structural flexibility or ‘breathing’ of the envelope ( E ) protein of flaviviruses allows virions to sample an ensemble of conformations at equilibrium .", "The molecular basis and functional consequences of virus conformational dynamics are poorly understood .", "Here , we identified a single mutation at...	[ "Flaviviruses include emerging pathogens such as WNV , DENV , and ZIKV that threaten global health .", "Despite causing significant morbidity , effective vaccines or therapeutic agents to protect humans against many flaviviruses are lacking .", "Because of the importance of antibodies in flavivirus immunity and...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "cancers and neoplasms", "basic cancer research", "gastrointestinal tumors", "hematologic cancers and related disorders", "animal models", "oncology", "model organisms", "molecular genetics", "lymphomas", "signaling in cellular processes", "gene expression", "biology", "molecul...	Mouse Genetics Suggests Cell-Context Dependency for Myc-Regulated Metabolic Enzymes during Tumorigenesis	journal.pgen.1002573	null	[ [ "Activation of one of the three MYC oncogenes is frequently selected for during tumorigenesis .", "These genes encode the transcription factors c-Myc , N-Myc and L-Myc that regulate a large number of downstream target genes .", "Although most of the work on MYC oncogenes has involved their role in cel...	[ "c-Myc ( hereafter called Myc ) belongs to a family of transcription factors that regulates cell growth , cell proliferation , and differentiation .", "Myc initiates the transcription of a large cast of genes involved in cell growth by stimulating metabolism and protein synthesis .", "Some of these , like those...	[ "Cancer occurs when cells change their behavior and start to divide in an uncontrolled manner .", "To achieve this altered behavior , cells need to change their metabolism to be able to grow even when nutrient and oxygen supplies are limiting .", "Therefore , targeting metabolic pathways could be used to treat ...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "bacteriology", "bacterial biochemistry", "escherichia coli", "genome complexity", "prokaryotic models", "model organisms", "gene regulation", "bacillus subtilis", "molecular genetics", "biology", "genomics", "microbiology", "computational biology" ]	Transcriptome-Wide Mapping of 5-methylcytidine RNA Modifications in Bacteria, Archaea, and Yeast Reveals m5C within Archaeal mRNAs	journal.pgen.1003602	null	[ [ "5-methylcytidine ( m5C ) is a modification that occurs both on DNA and RNA .", "In eukaryotes , this DNA modification has been extensively studied over the past years , and was found to play a crucial role in genomic imprinting , X-chromosome inactivation , and suppression of repetitive elements [1] , [2...	[ "The presence of 5-methylcytidine ( m5C ) in tRNA and rRNA molecules of a wide variety of organisms was first observed more than 40 years ago .", "However , detection of this modification was limited to specific , abundant , RNA species , due to the usage of low-throughput methods .", "To obtain a high resoluti...	[ "Ribonucleic acids are universally used to express genetic information in the form of gene transcripts .", "Although we envision RNA as a mere copy of the DNA four-base code , modification of specific RNA bases can expand the information code .", "Such modifications are abundant in transfer RNA ( tRNA ) and rib...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "plant biology/plant-biotic interactions", "genetics and genomics/bioinformatics", "genetics and genomics/functional genomics" ]	A Functional Genomics Approach Identifies Candidate Effectors from the Aphid Species Myzus persicae (Green Peach Aphid)	journal.pgen.1001216	null	[ [ "Like most plant parasites , aphids require intimate associations with their host plants to gain access to nutrients .", "Aphids predominantly feed from the plant phloem sieve elements , and use their stylets to navigate between the cells of different layers of leaf tissue during which plant defenses may ...	[ "Aphids are amongst the most devastating sap-feeding insects of plants .", "Like most plant parasites , aphids require intimate associations with their host plants to gain access to nutrients .", "Aphid feeding induces responses such as clogging of phloem sieve elements and callose formation , which are suppres...	[ "Aphids are insects that can induce feeding damage , achieve high population densities , and most importantly , transmit economically important plant diseases worldwide .", "To develop durable approaches to control aphids , it is critical to understand how aphids interact with plants at the molecular level .", ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Leishmania donovani Infection	journal.ppat.1004681	null	[ [ "Disruption in lymphoid tissue organisation is evident in a wide array of chronic inflammatory disorders , including cancer , infectious disease , psoriasis , liver disorders , autoimmune and metabolic diseases , and the persistence of vascular remodelling has been shown to impair immune responses and promote...	[ "The neurotrophic tyrosine kinase receptor type 2 ( Ntrk2 , also known as TrkB ) and its ligands brain derived neurotrophic factor ( Bdnf ) , neurotrophin-4 ( NT-4/5 ) , and neurotrophin-3 ( NT-3 ) are known primarily for their multiple effects on neuronal differentiation and survival .", "Here , we provide evide...	[ "Visceral leishmaniasis ( VL ) , a globally important parasitic disease responsible for over 40 , 000 deaths p . a . , results in pronounced changes in splenic organisation associated with impaired immune function and persistent parasite infection .", "We have previously shown that receptor tyrosine kinase ( RTKi...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Deciphering the Genetic Programme Triggering Timely and Spatially-Regulated Chitin Deposition	journal.pgen.1004939	null	[ [ "Organ formation requires a finely tuned temporal and spatial control of events .", "Once cells have acquired the organ cell fate , they undergo a series of consecutive morphogenetic steps until they reach the mature and physiological state , which is then maintained by homeostasis .", "Many examples ...	[ "Organ and tissue formation requires a finely tuned temporal and spatial regulation of differentiation programmes .", "This is necessary to balance sufficient plasticity to undergo morphogenesis with the acquisition of the mature traits needed for physiological activity .", "Here we addressed this issue by anal...	[ "In this work we studied the maturation of the extracellular matrix during Drosophila embryogenesis .", "Drosophila deposit a chitin-rich extracellular matrix with key physiological functions , such as the control of organ size and shape , and cuticle formation .", "Chitin synthesis depends on chitin synthases ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics and genomics/gene expression", "genetics and genomics/gene function", "developmental biology/organogenesis", "developmental biology/developmental molecular mechanisms" ]	A Mechanistic Basis for the Coordinated Regulation of Pharyngeal Morphogenesis in Caenorhabditis elegans by LIN-35/Rb and UBC-18–ARI-1	journal.pgen.1000510	null	[ [ "Genetic redundancy describes the phenomenon in which the combined inactivation of two distinct genes produces a phenotype that is not observed in either single mutant .", "One of the current challenges facing geneticists and developmental biologists alike is to understand the underlying bases of genetic ...	[ "Genetic redundancy , whereby two genes carry out seemingly overlapping functions , may in large part be attributable to the intricacy and robustness of genetic networks that control many developmental processes .", "We have previously described a complex set of genetic interactions underlying foregut development...	[ "One of the more puzzling aspects of genetics is that the inactivation of many genes fails to produce strong deleterious effects on the organisms that carry those genes .", "In some cases , however , the combined inactivation of two or more such genes can lead to the expression of robust abnormal phenotypes .", ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "protein abundance", "membrane proteins", "fungi", "molecular biology techniques", "cellular structures and organelles", "research and analysis methods", "proteins", "proteomics", "molecular biology", "cell membranes", "yeast", "biochemistry", "eukaryota", "cell ...	Proteome-scale relationships between local amino acid composition and protein fates and functions	journal.pcbi.1006256	null	[ [ "Low-complexity domains ( LCDs ) in proteins are regions enriched in only a subset of possible amino acids .", "LCDs can be composed of homopolymeric repeats of a single amino acid , short tandem repeats consisting of only a few different amino acids , or aperiodic stretches with little amino acid diversi...	[ "Proteins with low-complexity domains continue to emerge as key players in both normal and pathological cellular processes .", "Although low-complexity domains are often grouped into a single class , individual low-complexity domains can differ substantially with respect to amino acid composition .", "These dif...	[ "Low-complexity domains in protein sequences are regions that are composed of only a few amino acids in the protein “alphabet” .", "These domains often have unique chemical properties and play important biological roles in both normal and disease-related processes .", "While a number of approaches have been dev...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "hepacivirus", "pathogens", "microbiology", "human genomics", "viruses", "rna viruses", "dna viruses", "genome analysis", "microbial genomics", "research and analysis methods", "viral genomics", "genomic ...	The blood DNA virome in 8,000 humans	journal.ppat.1006292	null	[ [ "Research on the human microbiome has been primarily directed to the prokaryotic composition of the human microflora .", "Because most of the analyses use 16S rRNA gene-based amplification , the viral content has been rarely captured in large-scale microbiome studies .", "In contrast , analysis of the...	[ "The characterization of the blood virome is important for the safety of blood-derived transfusion products , and for the identification of emerging pathogens .", "We explored non-human sequence data from whole-genome sequencing of blood from 8 , 240 individuals , none of whom were ascertained for any infectious ...	[ "Novel sequencing technologies offer insight into the virome in human samples .", "Here , we identify the viral DNA sequences in blood of over 8 , 000 individuals undergoing whole genome sequencing .", "This approach serves to identify 94 viruses; however , many are shown to reflect widespread DNA contamination...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "cryptococcus neoformans", "medicine and health sciences", "cryptococcus", "immune cells", "pathology and laboratory medicine", "enzymes", "pathogens", "animal models of disease", "immunology", "enzymology", "microbiology", "fungi", "peptide libraries", "fungal pathogens",...	Integrated Activity and Genetic Profiling of Secreted Peptidases in Cryptococcus neoformans Reveals an Aspartyl Peptidase Required for Low pH Survival and Virulence	journal.ppat.1006051	null	[ [ "Cryptococcus neoformans is an opportunistic fungal pathogen responsible for 40% of all AIDS-related deaths [1 , 2] .", "Of the one million new infections occurring worldwide annually , greater than 60% result in death due to the limited efficacy and availability of therapeutics [3] .", "Only three cl...	[ "The opportunistic fungal pathogen Cryptococcus neoformans is a major cause of mortality in immunocompromised individuals , resulting in more than 600 , 000 deaths per year .", "Many human fungal pathogens secrete peptidases that influence virulence , but in most cases the substrate specificity and regulation of ...	[ "Many pathogenic organisms secrete peptidases .", "The activity of these enzymes often contributes to virulence , making their study crucial for understanding host-pathogen biology and developing therapeutics .", "In this report , we employed an unbiased , activity-based profiling assay to examine the secreted ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "action potentials", "neural networks", "nervous system", "membrane potential", "electrophysiology", "neuroscience", "simulation and modeling", "synaptic plasticity", "calcium signaling", "neuronal plasticity", "research and analysis methods", "developmental n...	Interplay of multiple pathways and activity-dependent rules in STDP	journal.pcbi.1006184	null	[ [ "Synaptic plasticity , one of the paramount biological mechanism supporting learning and memory in the brain , has been the object of a wide literature spanning from experimental works [1–3] to computational investigations [4–6] .", "In 1949 , Donald Hebb’s pioneering work postulated that long-term modifi...	[ "Hebbian plasticity describes a basic mechanism for synaptic plasticity whereby synaptic weights evolve depending on the relative timing of paired activity of the pre- and postsynaptic neurons .", "Spike-timing-dependent plasticity ( STDP ) constitutes a central experimental and theoretical synaptic Hebbian learn...	[ "The brain’s capacity to treat information , learn and store memory relies on synaptic connectivity patterns , which are altered through synaptic plasticity mechanisms .", "Experimentally , such plasticities were evidenced through protocols involving numerous repetitive stimulations of a given synapse , and were ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	NEDDylation Is Essential for Kaposi’s Sarcoma-Associated Herpesvirus Latency and Lytic Reactivation and Represents a Novel Anti-KSHV Target	journal.ppat.1004771	null	[ [ "The ubiquitin-proteasome system ( UPS ) and associated pathways are rapidly becoming accepted as major therapeutic targets for the treatment of malignancy [1] , which potentially include those associated with oncogenic viruses .", "Additionally , small molecule inhibitors have been successfully used for ...	[ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is the causative agent of Kaposi's sarcoma ( KS ) and primary effusion lymphoma ( PEL ) , which are aggressive malignancies associated with immunocompromised patients .", "For many non-viral malignancies , therapeutically targeting the ubiquitin proteasome system ...	[ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) causes Kaposi’s sarcoma ( KS ) and primary effusion lymphoma ( PEL ) , often fatal malignancies afflicting HIV-infected patients .", "Previous research has shown that blockade of the ubiquitin proteasome system ( UPS , a normal quality control pathway that degrade...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "diabetic endocrinology", "caenorhabditis", "gene regulation", "protein aggregation", "regulatory proteins", "dna-binding proteins", "light microscopy", "animals", "pulmonology", "hormones", "animal models", "caenorhabditis elegans", "lumi...	Fasting prevents hypoxia-induced defects of proteostasis in C. elegans	journal.pgen.1008242	null	[ [ "In order to survive in changing conditions , organisms need to successfully integrate a number of environmental signals and respond appropriately in order to maintain homeostasis .", "Aerobic heterotrophs must meet their requirements for food and oxygen by taking in these resources from the environment ....	[ "Low oxygen conditions ( hypoxia ) can impair essential physiological processes and cause cellular damage and death .", "We have shown that specific hypoxic conditions disrupt protein homeostasis in C . elegans , leading to protein aggregation and proteotoxicity .", "Here , we show that nutritional cues regulat...	[ "When blood flow to various parts of the body becomes restricted , those tissues suffer from a lack of oxygen , a condition called hypoxia .", "Hypoxia can cause cellular damage and death , as in stroke and cardiovascular disease .", "We have found that in the model organism C . elegans ( a roundworm ) specific...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Multi-Megabase Copy Number Gain Causes Maternal Transmission Ratio Distortion on Mouse Chromosome 2	journal.pgen.1004850	null	[ [ "Mendel’s Laws provide the theoretical foundation of transmission genetics and explain many of the inheritance patterns of biological traits in sexually reproducing organisms .", "The Laws state that each gamete receives a random collection of alleles—exactly one per pair of homologous loci—and that gamet...	[ "Significant departures from expected Mendelian inheritance ratios ( transmission ratio distortion , TRD ) are frequently observed in both experimental crosses and natural populations .", "TRD on mouse Chromosome ( Chr ) 2 has been reported in multiple experimental crosses , including the Collaborative Cross ( CC...	[ "One of the strongest expectations in genetics is that chromosomes segregate randomly during meiosis .", "However , genetic loci that exhibit transmission ratio distortion ( TRD ) are sometimes observed in offspring of F1 hybrids .", "Meiotic drive is a type of non-Mendelian inheritance in which a “selfish” gen...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immune response", "immunology/innate immunity", "cell biology/cell adhesion", "microbiology/cellular microbiology and pathogenesis", "virology/host invasion and cell entry" ]	Structure of the Extracellular Portion of CD46 Provides Insights into Its Interactions with Complement Proteins and Pathogens	journal.ppat.1001122	null	[ [ "The human CD46 receptor , also known as membrane cofactor protein ( MCP ) , is present on all nucleated cells [1] .", "It belongs to a family of proteins known as the regulators of complement activation ( RCA ) , which cluster on chromosome 1q32 [2] , [3] .", "In addition to CD46 , the RCA family inc...	[ "The human membrane cofactor protein ( MCP , CD46 ) is a central component of the innate immune system .", "CD46 protects autologous cells from complement attack by binding to complement proteins C3b and C4b and serving as a cofactor for their cleavage .", "Recent data show that CD46 also plays a role in mediat...	[ "The human membrane cofactor protein ( MCP , CD46 ) is expressed on all nucleated cells and serves as a marker that prevents host cells from destruction by the immune system .", "It functions as a cofactor that helps to inactivate the C3b and C4b molecules , which are central components of the complement system ....	2010
[ "Introduction", "Results", "Discussion and conclusions", "Materials and methods" ]	[ "cell death", "medicine and health sciences", "pathology and laboratory medicine", "cell processes", "brassica", "immune receptor signaling", "model organisms", "signs and symptoms", "membrane receptor signaling", "experimental organism systems", "sequence motif analysis", "plants", "floweri...	Genome-wide functional analyses of plant coiled–coil NLR-type pathogen receptors reveal essential roles of their N-terminal domain in oligomerization, networking, and immunity	journal.pbio.2005821	null	[ [ "Signal Transduction ATPases ( STAND proteins ) comprise an ancient group of modular proteins sharing a conserved nucleotide-binding ( NB ) domain [1] .", "STAND proteins are present in Archaea , Bacteria , and Eukaryota , implying a common , ancient evolutionary origin [1 , 2] .", "Duplications and a...	[ "The ability to induce a defense response after pathogen attack is a critical feature of the immune system of any organism .", "Nucleotide-binding leucine-rich repeat receptors ( NLRs ) are key players in this process and perceive the occurrence of nonself-activities or foreign molecules .", "In plants , coevol...	[ "The ability to induce defenses in response to pathogen attack is a critical feature of immunity in any organism .", "Nucleotide-binding leucine-rich repeat receptors ( NLRs ) are key players in this process and have evolved to perceive the occurrence of nonself-activities or foreign molecules .", "In plants , ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral vaccines", "rna viruses", "emerging infectious diseases", "immunity", "viral classification", "virology", "host-pathogen interaction", "biology", "microbiology" ]	Antibody Quality and Protection from Lethal Ebola Virus Challenge in Nonhuman Primates Immunized with Rabies Virus Based Bivalent Vaccine	journal.ppat.1003389	null	[ [ "Several members of the Ebolavirus genus and Marburgvirus genus , Family Filoviridae , cause severe and often fatal viral hemorrhagic fever in humans and nonhuman primates [1] .", "While the public health burden of filovirus infections remains low relative to other public health threats in Africa , outbre...	[ "We have previously described the generation of a novel Ebola virus ( EBOV ) vaccine platform based on", "( a ) replication-competent rabies virus ( RABV ) ,", "( b ) replication-deficient RABV , or", "( c ) chemically inactivated RABV expressing EBOV glycoprotein ( GP ) .", "Mouse studies demonstrated safe...	[ "Ebola virus ( EBOV ) has been associated with outbreaks in human and nonhuman primate populations since 1976 .", "With a fatality rate approaching 90% , EBOV is one of the most lethal infectious diseases in humans .", "The increased frequency of EBOV outbreaks along with its potential to be used as a bioterror...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "genome expression analysis", "infectious diseases", "dengue fever", "neglected tropical diseases", "biology", "genomics", "genetics and genomics" ]	Host Cell Transcriptome Profile during Wild-Type and Attenuated Dengue Virus Infection	journal.pntd.0002107	null	[ [ "Dengue viruses 1–4 ( DENV1-4 ) are the world's most prevalent arthropod-borne viruses [1] .", "DENVs are responsible for an estimated 50–100 million cases of debilitating or life-threatening infection every year and an estimated 2 . 5 billion people in over 100 endemic countries are at risk of infection ...	[ "Dengue viruses 1–4 ( DENV1-4 ) rely heavily on the host cell machinery to complete their life cycle , while at the same time evade the host response that could restrict their replication efficiency .", "These requirements may account for much of the broad gene-level changes to the host transcriptome upon DENV in...	[ "Dengue is the most common insect-borne viral disease globally .", "The continued absence of an effective therapy stems from an incomplete understanding of disease pathogenesis , of which the host response to infection is thought to play a central role .", "While previous studies have described the changes in t...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "t helper cells", "hiv infections", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "animal models", "model organisms", "rna viruses", "...	Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor	journal.ppat.1006613	null	[ [ "It is well established that T cells play an important role in controlling HIV-1 ( HIV ) replication , and that HIV-infected individuals develop robust HIV-specific T cell responses [1 , 2] .", "However , HIV evades the endogenous T cell-mediated immune response by altering key residues required for T cel...	[ "HIV is adept at avoiding naturally generated T cell responses; therefore , there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies .", "Starting with a CD4-based chimeric antigen receptor ( CAR ) that was previously used without toxicity in clinical trials , we optimiz...	[ "Conventional T cells rarely provide durable control over HIV replication .", "Chimeric antigen receptors ( CARs ) alter how T cells recognize infected T cells , bypassing many of HIV’s immune escape mechanisms .", "Therefore , we hypothesized that T cells engineered to express these receptors would be more pot...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virulence factors and mechanisms", "infectious diseases", "virology/viral replication and gene regulation", "gastroenterology and hepatology/hepatology", "biochemistry/protein folding", "cell biology", "infectious diseases/gastrointestinal infections", "virology/new therapies, including anti...	Essential Role of Cyclophilin A for Hepatitis C Virus Replication and Virus Production and Possible Link to Polyprotein Cleavage Kinetics	journal.ppat.1000546	null	[ [ "The hepatitis C virus ( HCV ) is a hepatotropic virus that has a high propensity to establish persistence .", "At present , more than 170 million people suffer from chronic hepatitis C [1] .", "Current therapy of this disease is based on the combination of pegylated interferon-alpha and ribavirin .",...	[ "Viruses are obligate intracellular parasites and therefore their replication completely depends on host cell factors .", "In case of the hepatitis C virus ( HCV ) , a positive-strand RNA virus that in the majority of infections establishes persistence , cyclophilins are considered to play an important role in RN...	[ "Owing to limited genetic information , viruses have to exploit host cells to achieve efficient production of virus progeny .", "Host cell factors and pathways therefore play an important role for virus replication and thus represent a possible target for antiviral therapy .", "In case of the hepatitis C virus ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "carbohydrate metabolism", "organismal evolution", "genome evolution", "population genetics", "microbiology", "mutation", "model organisms", "microbial evolution", "metabolic pathways", "biology", "evolutionary theory", "evolutionary genetics", "biochemistry", "adaptation", "natural sele...	Hunger Artists: Yeast Adapted to Carbon Limitation Show Trade-Offs under Carbon Sufficiency	journal.pgen.1002202	null	[ [ "R . A . Fisher's fundamental theorem of natural selection relates the rate of adaptation by populations of organisms to their genetic variance in fitness at a given time [1] .", "Understanding the mechanistic basis for this variance , and the distribution of a population's fitness variance under alternat...	[ "As organisms adaptively evolve to a new environment , selection results in the improvement of certain traits , bringing about an increase in fitness .", "Trade-offs may result from this process if function in other traits is reduced in alternative environments either by the adaptive mutations themselves or by th...	[ "Microorganisms such as yeast have been used for decades to study adaptive evolution by natural selection .", "Thirty years ago in now seminal experiments , a strain of yeast was evolved multiple times under carbon limitation .", "The adaptive changes that gave rise to increases in fitness have previously been ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "biochemistry/macromolecular assemblies and machines", "microbiology", "infectious diseases/respiratory infections", "infectious diseases/bacterial infections", "microbiology/cellular microbiology and pathogenesis" ]	Pneumococcal Pili Are Composed of Protofilaments Exposing Adhesive Clusters of Rrg A	journal.ppat.1000026	null	[ [ "The Gram-positive bacterium Streptococcus pneumoniae , also known as pneumococcus , is one of the most important human pathogens causing respiratory tract infections such as sinusitis , otitis media , and community acquired pneumonia , but also invasive diseases such as septicemia and meningitis .", "Tog...	[ "Pili have been identified on the cell surface of Streptococcus pneumoniae , a major cause of morbidity and mortality worldwide .", "In contrast to Gram-negative bacteria , little is known about the structure of native pili in Gram-positive species and their role in pathogenicity .", "Triple immunoelectron micr...	[ "Streptococcus pneumoniae ( pneumococcus ) is one of the most important human pathogens and a major cause of morbidity and mortality worldwide , causing respiratory tract infections , community acquired pneumonia , and invasive diseases .", "Although the pneumococcus is a well-studied bacterial pathogen , first d...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "parasitic diseases", "parasitic protozoans", "pediatrics", "protozoans", "signs and symptoms", "pharmaceutics", "leishmania", "antimony", "neglected tropical diseases", "inf...	Risk factors for therapeutic failure to meglumine antimoniate and miltefosine in adults and children with cutaneous leishmaniasis in Colombia: A cohort study	journal.pntd.0005515	null	[ [ "Cutaneous leishmaniasis is a public health problem with the number of cases annually ranging from 0 . 7–1 . 2 million worldwide [1] .", "Seventy-five percent of the global burden of disease is concentrated in ten countries , including Colombia , where cutaneous leishmaniasis is an important cause of morb...	[ "Reports of therapeutic failure to meglumine antimoniate ( MA ) and miltefosine in cutaneous leishmaniasis ( CL ) varies between species , populations and geographic regions .", "This study aimed to determine the clinical , drug-related factors , and Leishmania species associated with treatment failure in childre...	[ "Cutaneous leishmaniasis ( CL ) is a parasitic disease that causes chronic , often ulcerated , skin lesions .", "Treatment require administration of systemic and poorly tolerated drugs , of which , the most commonly used is meglumine antimoniate ( MA ) injections during 20 days .", "Although children and adults...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/metabolic networks" ]	Biosynthetic Potentials of Metabolites and Their Hierarchical Organization	journal.pcbi.1000049	null	[ [ "Cellular metabolism is mediated by highly efficient and specialized enzymes catalyzing chemical transformations of substrates into products .", "Since the products of a particular reaction may serve as substrates for other reactions , the entirety of the biochemical reactions forms a complex and highly c...	[ "A major challenge in systems biology is to understand how complex and highly connected metabolic networks are organized .", "The structure of these networks is investigated here by identifying sets of metabolites that have a similar biosynthetic potential .", "We measure the biosynthetic potential of a particu...	[ "Life is based on the ability of cells to convert raw materials into complex chemicals like proteins or DNA .", "This ability is obtained through the interplay of a large number of enzymes , which are specialized proteins , each facilitating one specific chemical transformation .", "Since the products of one re...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "gram negative", "protein interactions", "proteins", "microbial evolution", "chaperone proteins", "protein structure", "microbial pathogens", "biology", "microbiology", "bacterial pathogens", "microbial ecology" ]	Structural Basis for Type VI Secretion Effector Recognition by a Cognate Immunity Protein	journal.ppat.1002613	null	[ [ "The type VI secretion system ( T6SS ) is a multifaceted protein export pathway that is widely distributed in Gram-negative Proteobacteria [1] , [2] .", "With a minimal functional requirement for the products of at least 13 genes , this secretion machine rivals the complexity of the more extensively chara...	[ "The type VI secretion system ( T6SS ) has emerged as an important mediator of interbacterial interactions .", "A T6SS from Pseudomonas aeruginosa targets at least three effector proteins , type VI secretion exported 1–3 ( Tse1–3 ) , to recipient Gram-negative cells .", "The Tse2 protein is a cytoplasmic effect...	[ "Bacterial species have been at war with each other for over a billion years .", "During this period they have evolved many pathways for besting the competition; one of the most recent of these to be described is the type VI secretion system ( T6SS ) .", "The T6SS of Pseudomonas aeruginosa is a complex machine ...	2012
[ "Introduction", "Methods", "Results and discussion" ]	[ "parasite groups", "medicine and health sciences", "plasmodium", "population genetics", "geographical locations", "microbiology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "parasitology", "peru", "apicomplexa", "protozoans", "pharmacology", "population biology", ...	Genome-wide diversity and differentiation in New World populations of the human malaria parasite Plasmodium vivax	journal.pntd.0005824	null	[ [ "Plasmodium vivax is the human malaria parasite with the widest global distribution and accounts for nearly half of the combined malaria burden in South and Southeast Asia , Oceania , and Central and South America .", "Over one-third of the world's population is currently at risk of infection with this sp...	[ "The Americas were the last continent colonized by humans carrying malaria parasites .", "Plasmodium falciparum from the New World shows very little genetic diversity and greater linkage disequilibrium , compared with its African counterparts , and is clearly subdivided into local , highly divergent populations ....	[ "Plasmodium vivax is the most common human malaria parasite in the Americas , but how and when this species arrived in the New World remains unclear .", "Here we describe high-quality whole-genome sequence data for nine P . vivax isolates from Brazil , a country that accounts for 37% of the malaria burden in this...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Asymmetry of the Budding Yeast Tem1 GTPase at Spindle Poles Is Required for Spindle Positioning But Not for Mitotic Exit	journal.pgen.1004938	null	[ [ "Asymmetric cell division generates two daughter cells genetically identical but that differ in fate and/or in size and cytoplasmic material .", "During asymmetric cell division , polarity factors are first concentrated to specific locations to define the poles of cell division .", "Afterwards the spi...	[ "The asymmetrically dividing yeast S . cerevisiae assembles a bipolar spindle well after establishing the future site of cell division ( i . e . , the bud neck ) and the division axis ( i . e . , the mother-bud axis ) .", "A surveillance mechanism called spindle position checkpoint ( SPOC ) delays mitotic exit an...	[ "In asymmetrically dividing cells , proper positioning of the mitotic spindle relative to polarity determinants is crucial to ensure the unequal fate of daughter cells .", "In stem cells , derangement of the mechanisms controlling asymmetric cell division , including spindle positioning , affects the developmenta...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics" ]	Genome-Wide Screen in Saccharomyces cerevisiae Identifies Vacuolar Protein Sorting, Autophagy, Biosynthetic, and tRNA Methylation Genes Involved in Life Span Regulation	journal.pgen.1001024	null	[ [ "Yeast , worms , and flies have been studied extensively to identify the genetic determinants of aging .", "Studies conducted in these model organisms have demonstrated a partially conserved life span regulatory role for the nutrient-sensing/insulin/IGF-I-like pathways , which are found in species ranging...	[ "The study of the chronological life span of Saccharomyces cerevisiae , which measures the survival of populations of non-dividing yeast , has resulted in the identification of homologous genes and pathways that promote aging in organisms ranging from yeast to mammals .", "Using a competitive genome-wide approach...	[ "Model organisms have been instrumental in uncovering genes that function to control life span and to identify the molecular pathways whose role in aging is conserved between the evolutionarily distant unicellular yeast and mice .", "Because yeast are particularly amenable to genetics and genomics studies , they ...	2010

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