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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "neuroscience", "cognitive neuroscience", "mathematics", "computational neuroscience", "electroencephalography", "circuit models", "clinical neurophysiology", "biology", "nonlinear dynamics", "visual system", "diagnostic medicine", "physiology", "sensory systems", "computatio...	Modeling Brain Resonance Phenomena Using a Neural Mass Model	journal.pcbi.1002298	null	[ [ "Electrophysiological measurements such as magneto- and electroencephalography ( M/EEG ) , local field potentials ( LFP ) or single unit recordings contain rich information on brain function , which may be related to specific cognitive processes , to general brain states , or to certain pathological condition...	[ "Stimulation with rhythmic light flicker ( photic driving ) plays an important role in the diagnosis of schizophrenia , mood disorder , migraine , and epilepsy .", "In particular , the adjustment of spontaneous brain rhythms to the stimulus frequency ( entrainment ) is used to assess the functional flexibility of...	[ "Neuroscience aims to understand the enormously complex function of the normal and diseased brain .", "This , in turn , is the key to explaining human behavior and to developing novel diagnostic and therapeutic procedures .", "We develop and use models of mean activity in a single brain area , which provide a b...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Identification of microRNA Genes in Three Opisthorchiids	journal.pntd.0003680	null	[ [ "Opisthorchis felineus , O . viverrini , and Clonorchis sinensis ( class Trematoda; order Plagiorchiida; family Opisthorchiidae ) are parasitic flatworms with complex life cycles , which include three hosts , with human and piscivorous mammals as definitive hosts [1] .", "These three flukes cause diseases...	[ "Opisthorchis felineus , O . viverrini , and Clonorchis sinensis ( family Opisthorchiidae ) are parasitic flatworms that pose a serious threat to humans in some countries and cause opisthorchiasis/clonorchiasis .", "Chronic disease may lead to a risk of carcinogenesis in the biliary ducts .", "MicroRNAs ( miRNA...	[ "Liver flukes of the family Opisthorchiidae cause diseases of the hepatobiliary system , known as opisthorchiasis/clonorchiasis .", "The chronic forms of these diseases greatly increase the risk of cancer developing in the biliary ducts .", "Much has been elucidated regarding the developmental biology of opisth...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "medicine", "oncology", "cancer genetics", "model organisms", "lung and intrathoracic tumors", "genetics", "cancer treatment", "biology", "cancers and neoplasms", "mouse", "genetics and genomics" ]	Twist1 Suppresses Senescence Programs and Thereby Accelerates and Maintains Mutant Kras-Induced Lung Tumorigenesis	journal.pgen.1002650	null	[ [ "Lung cancer is responsible for more cancer deaths in the US than colorectal , breast , and prostate cancer combined with a dismal overall survival of 15% [1] .", "The majority of human lung cancers are adenocarcinomas carrying somatic mutations in the genes that encode the EGFR/KRAS/BRAF pathway [2] .", ...	[ "KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents .", "To date , the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful , suggesting that other approaches are required .", "We demonstrate in both a novel transgenic mutant Kras lung cancer mou...	[ "Lung cancer is the most common cause of cancer death worldwide .", "The Twist1 gene encodes for an essential transcription factor required for embryogenesis and overexpressed in many cancer types .", "It has yet to be shown in vivo whether Twist1 plays a role in the initiation or maintenance of cancer .", "H...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell physiology", "medicine and health sciences", "liver", "applied mathematics", "metabolic networks", "cell metabolism", "simulation and modeling", "algorithms", "mathematics", "metabolites", "network analysis", "exchange reactions", "pharmacology", "drug metabolism", "research and an...	Reconstruction of Tissue-Specific Metabolic Networks Using CORDA	journal.pcbi.1004808	null	[ [ "Genome-wide Metabolic Reconstructions ( GEMs ) computationally model the molecules and reactions responsible for metabolism in any given organism , and have been applied across a variety of fields including metabolic engineering and evolutionary analysis [1] .", "Computational methods developed to study ...	[ "Human metabolism involves thousands of reactions and metabolites .", "To interpret this complexity , computational modeling becomes an essential experimental tool .", "One of the most popular techniques to study human metabolism as a whole is genome scale modeling .", "A key challenge to applying genome scal...	[ "Cellular metabolism is defined by a large , intricate network of thousands of components , and plays a fundamental role in many diseases .", "To study this network in its entirety , metabolic models have been built which encompass all known biochemical reactions in the human metabolism .", "However , since not...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "immunology", "biology", "microbiology", "molecular cell biology", "genetics and genomics" ]	The Polymorphic Pseudokinase ROP5 Controls Virulence in Toxoplasma gondii by Regulating the Active Kinase ROP18	journal.ppat.1002992	null	[ [ "Toxoplasma gondii is an obligate intracellular parasite that infects a wide range of vertebrate animal hosts and causes zoonotic infection in humans , leading to potentially severe congenital infections and risk of reactivation in immunocompromised patients [1] .", "In North America and Europe , T . gond...	[ "Secretory polymorphic serine/threonine kinases control pathogenesis of Toxoplasma gondii in the mouse .", "Genetic studies show that the pseudokinase ROP5 is essential for acute virulence , but do not reveal its mechanism of action .", "Here we demonstrate that ROP5 controls virulence by blocking IFN-γ mediate...	[ "The ability of microorganisms to cause disease in their hosts is often mediated by proteins that are secreted by the pathogen into the host cell as a means of disarming host signaling .", "Previous studies with the protozoan parasite Toxoplasma gondii have revealed that secretion of parasite protein kinases into...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/alternative splicing", "molecular biology/rna splicing", "genetics and genomics/comparative genomics", "computational biology/genomics" ]	Predicting Functional Alternative Splicing by Measuring RNA Selection Pressure from Multigenome Alignments	journal.pcbi.1000608	null	[ [ "Global analyses of alternative splicing ( AS ) have established its importance in protein diversity and gene regulation in higher eukaryotes [1] , [2] .", "Alternative splicing can regulate biological function by altering the sequence of protein products and modulating transcript expression levels [3] ."...	[ "High-throughput methods such as EST sequencing , microarrays and deep sequencing have identified large numbers of alternative splicing ( AS ) events , but studies have shown that only a subset of these may be functional .", "Here we report a sensitive bioinformatics approach that identifies exons with evidence o...	[ "Alternative splicing is an important mechanism for regulating gene function in complex organisms , and has been shown to play a key role in human diseases such as cancer .", "Recently , high-throughput technologies have been used in an effort to detect alternative splicing events throughout the human genome .", ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/bioinformatics", "computational biology/systems biology", "computational biology/genomics", "computational biology/transcriptional regulation" ]	Simultaneous Clustering of Multiple Gene Expression and Physical Interaction Datasets	journal.pcbi.1000742	null	[ [ "Heterogeneous genome-wide datasets provide different views of the biology of a cell , and their rapid accumulation demands integrative approaches that exploit the diversity of views .", "For instance , data on physical interactions such as interactions between two proteins ( protein-protein ) , or regula...	[ "Many genome-wide datasets are routinely generated to study different aspects of biological systems , but integrating them to obtain a coherent view of the underlying biology remains a challenge .", "We propose simultaneous clustering of multiple networks as a framework to integrate large-scale datasets on the in...	[ "The generation of high-dimensional datasets in the biological sciences has become routine ( protein interaction , gene expression , and DNA/RNA sequence data , to name a few ) , stretching our ability to derive novel biological insights from them , with even less effort focused on integrating these disparate datas...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "biochemistry/rna structure", "microbiology/parasitology", "infectious diseases/protozoal infections", "biochemistry/transcription and translation", "genetics and genomics/epigenetics", "molecular biology/chromatin structure" ]	A Complex Small RNA Repertoire Is Generated by a Plant/Fungal-Like Machinery and Effected by a Metazoan-Like Argonaute in the Single-Cell Human Parasite Toxoplasma gondii	journal.ppat.1000920	null	[ [ "Apicomplexa are unicellular eukaryotes that multiply intracellularly in their mammalian hosts .", "They include parasites of major medical importance like Plasmodium species , the causative agent of malaria , and Toxoplasma gondii , the most widespread apicomplexan parasite , present virtually everywhere...	[ "In RNA silencing , small RNAs produced by the RNase-III Dicer guide Argonaute-like proteins as part of RNA-induced silencing complexes ( RISC ) to regulate gene expression transcriptionally or post-transcriptionally .", "Here , we have characterized the RNA silencing machinery and exhaustive small RNAome of Toxo...	[ "Toxoplasma gondii is an important human parasite that causes life-threatening diseases in developing fetuses and in immunocompromised individuals , especially AIDS and transplant patients .", "Curiously , the Toxoplasma genome is deprived of most of the basic transcription factors that regulate gene expression i...	2010
[ "Introduction", "Results", "Methods", "Discussion" ]	[ "medicine and health sciences", "applied mathematics", "electrophysiology", "neuroscience", "simulation and modeling", "algorithms", "membrane proteins", "ion channels", "mathematics", "statistics (mathematics)", "membrane receptor signaling", "cellular structures and organelles", "macromole...	Numerical Approach to Spatial Deterministic-Stochastic Models Arising in Cell Biology	journal.pcbi.1005236	null	[ [ "It is not uncommon for a cell-biological model to include some components that might be stochastic in nature ( small copy numbers , rare events ) , whereas others , if uncoupled , would behave deterministically ( large copy numbers , fast reactions ) .", "Through their interaction , fluctuations in a sto...	[ "Hybrid deterministic-stochastic methods provide an efficient alternative to a fully stochastic treatment of models which include components with disparate levels of stochasticity .", "However , general-purpose hybrid solvers for spatially resolved simulations of reaction-diffusion systems are not widely availabl...	[ "Mechanisms of some cellular phenomena involve interactions of molecular systems of which one can be described deterministically , while the other is inherently stochastic .", "Calcium ‘sparks’ in cardiomyocytes is one such example , in which dynamics of calcium ions , which are usually present in large numbers ,...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology/aging", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "nephrology/chronic kidney disease", "genetics and genomics/epigenetics" ]	Altering a Histone H3K4 Methylation Pathway in Glomerular Podocytes Promotes a Chronic Disease Phenotype	journal.pgen.1001142	null	[ [ "The process of embryonic development determines the differentiated state of all cells by establishing unique gene expression patterns , or signatures , for individual cell types that define their phenotypes .", "Once a differentiated state is established , it is difficult to erase that epigenetic imprint...	[ "Methylation of specific lysine residues in core histone proteins is essential for embryonic development and can impart active and inactive epigenetic marks on chromatin domains .", "The ubiquitous nuclear protein PTIP is encoded by the Paxip1 gene and is an essential component of a histone H3 lysine 4 ( H3K4 ) m...	[ "While all cells contain essentially the same genome , adult differentiated cells have specific patterns of gene expression for unique physiological functions .", "Gene expression depends on specific proteins that activate some genes and repress others so that a stable pattern of expression is maintained .", "D...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "mus (mouse)", "viruses", "eukaryotes", "virology" ]	A Novel Inhibitory Mechanism of Mitochondrion-Dependent Apoptosis by a Herpesviral Protein	journal.ppat.0030174	null	[ [ "Apoptosis , or programmed cell death , has a key role in a variety of eukaryotic biological processes such as development and immune responses .", "Whether initiated by receptor ligation at the cell surface or through signal transduction from intracellular organelles , both caspase-dependent and -indepen...	[ "Upon viral infection , cells undergo apoptosis as a defense against viral replication .", "Viruses , in turn , have evolved elaborate mechanisms to subvert apoptotic processes .", "Here , we report that a novel viral mitochondrial anti-apoptotic protein ( vMAP ) of murine γ-herpesvirus 68 ( γHV-68 ) interacts ...	[ "Apoptosis is a conserved cell death program that contributes to restriction of viral replication and elimination of infected cells .", "Whether triggered via internal inducers such as DNA damage or via external stimuli such as engagement of the death receptor , apoptosis takes place through a cascade of regulate...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "infectious disease epidemiology", "microbiology", "parasitic diseases", "parasitology", "preventive medicine", "neglected tropical diseases", "infectious diseases", "environmental epidemiology", "epidemiology", "biology", "public health", "sch...	Five-Year Longitudinal Assessment of the Downstream Impact on Schistosomiasis Transmission following Closure of the Three Gorges Dam	journal.pntd.0001588	null	[ [ "Zoonotic schistosomiasis , caused by Schistosoma japonicum , is a chronic debilitating disease in the south of the People's Republic of China ( PRC ) , with about 800 , 000 infected and 65 million people at risk of infection .", "[1] , [2] The majority of transmission occurs in the lake and marshland are...	[ "Schistosoma japonicum is a major public health concern in the Peoples' Republic of China ( PRC ) , with about 800 , 000 people infected and another 50 million living in areas at risk of infection .", "Based on ecological , environmental , population genetic and molecular factors , schistosomiasis transmission in...	[ "Schistosomiasis , caused by Schistosoma japonicum , is a significant parasitic disease and public health problem in China .", "How the parasite is transmitted there can be categorized into four distinct modes ( modes I–IV ) and it is predicted that the Three Gorges Dam , recently completed , will affect the way ...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "action potentials", "membrane potential", "social sciences", "electrophysiology", "neuroscience", "animals", "animal models", "drosophila melanogaster", "model organisms", "ion channels", "monomers (chemistry)", "experimental organism syste...	Drosophila Gr64e mediates fatty acid sensing via the phospholipase C pathway	journal.pgen.1007229	null	[ [ "Animals use gustatory systems to evaluate the quality of food .", "Gustation is essential not only to prevent ingestion of toxic chemicals but also to ensure ingestion of essential nutrients such as sugars , amino acids , and lipids .", "The detection and consumption of energy-dense foods can confer ...	[ "Animals use taste to sample and ingest essential nutrients for survival .", "Free fatty acids ( FAs ) are energy-rich nutrients that contribute to various cellular functions .", "Recent evidence suggests FAs are detected through the gustatory system to promote feeding .", "In Drosophila , phospholipase C ( P...	[ "Fatty acids ( FAs ) are energy-rich nutrients that are detected through the gustatory system to promote feeding .", "Here , we show FA detection requires a Drosophila gustatory receptor , Gr64e .", "Although GR64e functions as a ligand-gated ion channel for glycerol detection , in FA sensing , it acts downstre...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "neurochemistry", "immune cells", "leptospira", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "neuroscience", "animal models", "bacterial diseases", "model organisms", ...	Innate immune memory through TLR2 and NOD2 contributes to the control of Leptospira interrogans infection	journal.ppat.1007811	null	[ [ "Leptospira belong to the phylum Spirochetes and are the etiological agents of leptospirosis , a reemerging worldwide zoonosis [1] .", "Pathogenic leptospires , including Leptospira interrogans , can infect and colonize multiple hosts , and leptospirosis constitutes a global burden affecting both human he...	[ "Leptospira interrogans are pathogenic spirochetes responsible for leptospirosis , a worldwide reemerging zoonosis .", "Many Leptospira serovars have been described , and prophylaxis using inactivated bacteria provides only short-term serovar-specific protection .", "Therefore , alternative approaches to limit ...	[ "Leptospirosis is a worldwide zoonotic neglected disease caused by pathogenic Leptospira .", "In addition to cattle and pets , it affects one million people per year and causes 60000 deaths .", "Antibiotics are efficient when given early after infection , but because the symptoms are not specific , leptospirosi...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biochemistry", "nucleotide excision repair", "meiosis", "cell biology", "chromosome biology", "molecular biology", "cell cycle and cell division", "mismatch repair", "biology and life sciences", "dna", "gene conversion", "dna recombination", "dna repair", "cell processes", "genetics", ...	Eliminating Both Canonical and Short-Patch Mismatch Repair in Drosophila melanogaster Suggests a New Meiotic Recombination Model	journal.pgen.1004583	null	[ [ "Meiotic recombination is initiated by a DSB on one chromatid followed by repair using the homologous chromosome as a template , resulting in crossover ( CO ) or noncrossover ( NCO ) products [1] .", "In the predominant model of repair , NCOs are produced when an early intermediate – a D-loop extended by ...	[ "In most meiotic systems , recombination is essential to form connections between homologs that ensure their accurate segregation from one another .", "Meiotic recombination is initiated by DNA double-strand breaks that are repaired using the homologous chromosome as a template .", "Studies of recombination in ...	[ "During meiosis , breaks are introduced into the DNA , then repaired to give either crossovers between homologous chromosomes ( these help to ensure correct segregation of these chromosomes from one another ) , or non-crossover products .", "Meiotic break repair mechanisms have been best studied in budding yeast ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "public health and epidemiology/preventive medicine", "infectious diseases/epidemiology and control of infectious diseases", "infectious diseases/neglected tropical diseases" ]	Spatial Clustering of Porcine Cysticercosis in Mbulu District, Northern Tanzania	journal.pntd.0000652	null	[ [ "Porcine cysticercosis is caused by the larval stage of the tapeworm Taenia solium , which also infects human and may cause serious neurological disorders such as epilepsy [1] .", "The lifecycle of T . solium involves a human as the sole natural definitive host carrying the adult parasite in the small int...	[ "Porcine cysticercosis is caused by a zoonotic tapeworm , Taenia solium , which causes serious disease syndromes in human .", "Effective control of the parasite requires knowledge on the burden and pattern of the infections in order to properly direct limited resources .", "The objective of this study was to es...	[ "Taenia solium is a tapeworm that causes two different disease conditions .", "In its adult stage , it inhabits the small intestine of human , a condition known as taeniosis , which is characterised by mild symptoms including abdominal disconfort .", "In the larval stage , T . solium can infect humans and vario...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "microbiology" ]	Phagosomal Rupture by Mycobacterium tuberculosis Results in Toxicity and Host Cell Death	journal.ppat.1002507	null	[ [ "The intracellular localization of bacterial pathogens has important consequences for the sensing by the host and the induced host immune responses .", "Hence , numerous studies have investigated the intracellular niche of the microbes .", "Particularly , phagolysosome fusion is a central cellular mec...	[ "Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis .", "Despite significant advances in identifying new immunological parameters associated with mycobacterial disease , some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-...	[ "Mycobacterium tuberculosis is one of the most life-threatening pathogens of all time .", "Despite the development of vaccines and antibiotics , this pathogen is still a major public health problem .", "Also the HIV epidemic has an important impact on the rise of M . tuberculosis infections since immunodeficien...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience" ]	Neuronal Correlates of the Set-Size Effect in Monkey Lateral Intraparietal Area	journal.pbio.0060158	Single-neuron activity in the lateral intraparietal area declines with the number of distractors and provides the first known neural correlate of the set-size effect in visual search.	[ [ "It has long been known that the visual system is limited in its ability to process multiple simultaneous inputs .", "Psychophysical evidence for visual capacity limitations comes from the observation that irrelevant distractors impair the ability to detect or discriminate a task-relevant target .", "...	[ "It has long been known that the brain is limited in the amount of sensory information that it can process at any given time .", "A well-known form of capacity limitation in vision is the set-size effect , whereby the time needed to find a target increases in the presence of distractors .", "The set-size effect...	[ "It is well known that the brain is limited in the amount of sensory information that it can process at any given time .", "During an everyday task such as finding an object in a cluttered environment ( known as visual search ) , observers take longer to find a target as the number of distractors increases .", ...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "dengue virus", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "pathology and laboratory medicine", "chemical compounds", "pathogens", "immunology", "microbiology", "organic compounds", "cell differentiation", "vir...	Human macrophages differentiated in the presence of vitamin D3 restrict dengue virus infection and innate responses by downregulating mannose receptor expression	journal.pntd.0005904	null	[ [ "During the last decades , there has been an expansion in the geographic range and incidence of dengue virus ( DENV ) due to spreading of its mosquito vectors , globalization and the lack of a protective tetravalent dengue vaccine [1–3] .", "It is estimated that nearly a third of the world population is a...	[ "Severe dengue disease is associated with high viral loads and overproduction of pro-inflammatory cytokines , suggesting impairment in the control of dengue virus ( DENV ) and the mechanisms that regulate cytokine production .", "Vitamin D3 has been described as an important modulator of immune responses to sever...	[ "Dengue represents a major worldwide concern for public health .", "Clinical complications rely on vascular leak of fluids and molecules from the bloodstream that leads to a potentially fatal hemodynamic compromise .", "Disease progression has been related to poor control of dengue virus ( DENV ) dissemination ...	2017
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "blood cells", "invertebrates", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "helminths", "antiviral therapy", "pathogens", "immunology", "hookworms", "microbiology", "parasitic diseases", "animals", "retroviruses", "viruses", "immunodeficiency v...	Hookworm infection is associated with decreased CD4+ T cell counts in HIV-infected adult Ugandans	journal.pntd.0005634	null	[ [ "Five soil transmitted helminth species Ascaris lumbricoides , Trichuris trichiura , hookworm species Necator americanus and Ancylostoma duodenale , and Strongyloides stercoralis infect over a billion people worldwide . [1 , 2]", "The burden of parasitic infection is greatest in low-income areas , particu...	[ "Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era , and evidence of the impact of helminth infections on HIV disease progression remains conflicting .", "Less is known about helminth infection and clinical outcomes in HIV-infected adults receivin...	[ "Intestinal parasites , diseases of poverty that infect low-income populations and decrease school attendance and earning potential , infect more than 1 billion people worldwide .", "Current international guidelines focus deworming campaigns on high-risk populations of preschool- and school-aged children , and wo...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "neonatology", "medicine and health sciences", "milk", "radiochemistry", "immune physiology", "enzyme-linked immunoassays", "body fluids", "maternal health", "breast milk", "animal models of disease", "immunology", "tropical diseases", "microbiology", "pediatrics", "nuclear decay", "an...	Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice	journal.pntd.0004805	null	[ [ "Dengue is a mosquito-borne viral disease responsible for an estimated 390 million annual dengue infections in the tropical and sub-tropical regions [1] .", "While most infected individuals manifest as asymptomatic or self-limiting dengue fever ( DF ) , a significant proportion progresses to more severe c...	[ "Dengue virus ( DENV ) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome .", "Antibody-dependent enhancement ( ADE ) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising...	[ "Epidemiological observations showed that 5–9 month old infants born to dengue immune mothers have increased risk of developing severe disease upon primary dengue infection .", "This disease enhancement has been associated with the presence of binding but non-neutralizing maternal dengue antibodies .", "The rec...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "kala-azar", "innate immune system", "medicine and health sciences", "body fluids", "immune physiology", "cytokines", "immune cells", "drugs", "immunology", "tropical diseases", "parasitic diseases", "developmental biology", "molecular development", "neglected tropical dis...	Successful Treatment of Human Visceral Leishmaniasis Restores Antigen-Specific IFN-γ, but not IL-10 Production	journal.pntd.0004468	null	[ [ "Visceral leishmaniasis ( VL ) is a neglected tropical disease caused by parasites of the Leishmania ( L . ) donovani complex .", "An estimated 200 , 000 to 400 , 000 new cases of VL with an incidence of 50 , 000 deaths occur each year , however these numbers are widely acknowledged to be a gross underest...	[ "One of the key immunological characteristics of active visceral leishmaniasis ( VL ) is a profound immunosuppression and impaired production of Interferon-γ ( IFN-γ ) .", "However , recent studies from Bihar in India showed using a whole blood assay , that whole blood cells have maintained the capacity to produc...	[ "The leishmaniases , a group of diseases caused by Leishmania parasites , belong to the most neglected tropical diseases: they are mainly found in low-income countries and affect the poorest populations .", "These parasites infect cells of the immune system called macrophages , which can kill the intracellular pa...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	C-di-GMP Regulates Motile to Sessile Transition by Modulating MshA Pili Biogenesis and Near-Surface Motility Behavior in Vibrio cholerae	journal.ppat.1005068	null	[ [ "Vibrio cholerae , the causative agent of the human intestinal disease cholera , is a natural inhabitant of aquatic ecosystems [1] .", "Cholera infection results from consumption of food and water contaminated with V . cholerae .", "Subsequently the bacteria turn on regulatory networks that facilitate...	[ "In many bacteria , including Vibrio cholerae , cyclic dimeric guanosine monophosphate ( c-di-GMP ) controls the motile to biofilm life style switch .", "Yet , little is known about how this occurs .", "In this study , we report that changes in c-di-GMP concentration impact the biosynthesis of the MshA pili , r...	[ "The human pathogen Vibrio cholerae causes the debilitating disease cholera through ingestion of contaminated food and water .", "V . cholerae is a natural inhabitant of aquatic environments .", "Transmission of V . cholerae to the human host is dependent on survival of the pathogen in aquatic reservoirs where ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry", "cell biology", "microbiology", "evolutionary biology", "molecular biology", "genetics and genomics" ]	Group II Intron Protein Localization and Insertion Sites Are Affected by Polyphosphate	journal.pbio.0060150	A novel cell microarray method uncovers connections between group II intron mobility, cell stress, and polyphosphate metabolism, including the finding that polyphosphate can influence intracellular protein localization.	[ [ "Mobile group II introns , found in bacterial and organelle genomes , consist of a catalytic intron RNA and a multifunctional intron-encoded protein ( IEP ) , which interact to promote RNA splicing and intron mobility [1 , 2] .", "The IEP binds to the intron in unspliced precursor RNA , promotes its splic...	[ "Mobile group II introns consist of a catalytic intron RNA and an intron-encoded protein with reverse transcriptase activity , which act together in a ribonucleoprotein particle to promote DNA integration during intron mobility .", "Previously , we found that the Lactococcus lactis Ll . LtrB intron-encoded protei...	[ "Group II introns are bacterial mobile elements thought to be ancestors of introns—genetic material that is discarded from messenger RNA transcripts—and retroelements—genetic elements and viruses that replicate via reverse transcription—in higher organisms .", "They propagate by forming a complex consisting of th...	2008
[ "Introduction", "Material and methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "drugs", "microbiology", "salmonella typhi", "health care", "bacterial diseases", "signs and symptoms", "enterobacteriaceae", "pharmacology", "bacteria", "bacterial pathogen...	A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital	journal.pntd.0006051	null	[ [ "Enteric ( typhoid ) fever is a systemic disease caused by Salmonella serovars Typhi ( S . Typhi ) and Paratyphi A ( S . Paratyphi A ) .", "Global estimates suggest that 12 to 27 million new cases of enteric fever occur annually resulting in 130 , 000 to 220 , 000 deaths , which predominantly occur in low...	[ "Salmonella serovars Typhi ( S . Typhi ) and Paratyphi A ( S . Paratyphi A ) , the causative agents of enteric fever , have been routinely isolated organisms from the blood of febrile patients in the Kathmandu Valley since the early 1990s .", "Susceptibility against commonly used antimicrobials for treating enter...	[ "Aiming to understand the epidemiology and changing patterns of the Salmonella enterica serovars Typhi and Paratyphi A within a single healthcare facility in Kathmandu , we retrospectively analysed 23 years of microbiological blood culture data .", "From 224 , 741 blood cultures performed , 30 , 353 were confirme...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "infectious disease epidemiology", "population dynamics", "immunology", "epidemiological methods and statistics", "preventive medicine", "plant science", "mathematics", "statistics (mathematics)", "population modeling", "global health", "plant pathology", "pop...	Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks	journal.ppat.1004452	null	[ [ "Many infections only occur as isolated cases , short chains of transmission , or as small infection clusters ( i . e . intertwined transmission chains ) .", "Examples include zoonotic infections with relatively weak human-to-human transmission as well as vaccine-preventable infections in settings of high...	[ "Our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals .", "Here , we identify epidemiological traits of self-limited infections ( i . e . infections with an effective reproduction number satisfying ) that...	[ "The goal of this paper is to identify epidemiological factors that correlate with either an increased or decreased risk of transmitting a particular disease .", "We are particularly interested in identifying such factors for diseases that are self-limited ( meaning that infections tend to occur in isolated clust...	2014
[ "Introduction", "Results", "Discussion", "Materials/methods" ]	[ "invertebrates", "medicine and health sciences", "toxins", "pathology and laboratory medicine", "enzymes", "enzymology", "parasitic diseases", "animals", "toxic agents", "toxicology", "nematode infections", "toxicity", "venoms", "proteins", "gene expression", "insects", "arthropoda",...	A core set of venom proteins is released by entomopathogenic nematodes in the genus Steinernema	journal.ppat.1007626	null	[ [ "Parasitic nematodes continue to be a major source of mortality and morbidity worldwide , infecting nearly 25% of the global population [1 , 2] .", "The molecules that are released by these parasites , including the excreted/secreted proteins ( ESPs ) , represent the major interface between hosts and para...	[ "Parasitic helminths release molecular effectors into their hosts and these effectors can directly damage host tissue and modulate host immunity .", "Excreted/secreted proteins ( ESPs ) are one category of parasite molecular effectors that are critical to their success within the host .", "However , most studie...	[ "In this study we found a core set of 52 venom proteins conserved between two insect-parasitic nematodes Steinernema feltiae and Steinernema carpocapsae , that are released when initially exposed to host tissue .", "Most of these proteins are conserved in mammalian-parasitic nematodes suggesting that this core se...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "stroke", "medicine and health sciences", "cerebrovascular diseases", "ischemic stroke", "genome analysis", "neurology", "gene expression", "genetics", "atherosclerosis", "biology and life sciences", "computational biology", "vascular medicine", "cardiolo...	A Novel MMP12 Locus Is Associated with Large Artery Atherosclerotic Stroke Using a Genome-Wide Age-at-Onset Informed Approach	journal.pgen.1004469	null	[ [ "Genome-wide association studies ( GWAS ) in ischaemic stroke have begun to identify the common genetic variants that confer risk of the disease .", "However , there is considerable heterogeneity present in stroke phenotypes: GWAS analyses have primarily looked at the three main subtypes; cardioembolic ( ...	[ "Genome-wide association studies ( GWAS ) have begun to identify the common genetic component to ischaemic stroke ( IS ) .", "However , IS has considerable phenotypic heterogeneity .", "Where clinical covariates explain a large fraction of disease risk , covariate informed designs can increase power to detect a...	[ "Ischaemic stroke places an enormous burden on global healthcare .", "However , the disease processes that lead to stroke are not fully understood .", "Genome-wide association studies have recently established that common genetic variants can increase risk of ischaemic stroke and its subtypes .", "In this stu...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "medicine", "infectious diseases", "clinical immunology", "genetics", "immunology", "biology", "genomics", "molecular cell biology" ]	A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication	journal.ppat.1003514	null	[ [ "Up to 90% of the global population is infected with the α-herpesvirus Herpes simplex virus type I ( HSV-1 ) .", "Whilst HSV-1 is largely responsible for outbreaks of vesicular oral skin lesions ( fever blisters , or cold sores ) , it can also cause a variety of more severe diseases including encephalitis...	[ "Herpes simplex virus type 1 ( HSV-1 ) is a neurotropic virus causing vesicular oral or genital skin lesions , meningitis and other diseases particularly harmful in immunocompromised individuals .", "To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale scr...	[ "Herpes simplex virus type 1 ( HSV-1 ) infects the vast majority of the global population .", "Whilst most people experience the relatively mild symptoms of cold sores , some individuals suffer more serious diseases like viral meningitis and encephalitis .", "HSV-1 is also becoming more common as a cause of gen...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunodeficiency viruses", "medicine", "infectious diseases", "mechanisms of resistance and susceptibility", "viral transmission and infection", "hiv", "virology", "retrovirology and hiv immunopathogenesis", "biology", "antivirals", "microbiology", "viral replication", "viral diseases" ]	Highly Active Antiretroviral Therapies Are Effective against HIV-1 Cell-to-Cell Transmission	journal.ppat.1003982	null	[ [ "Highly active antiretroviral therapy ( HAART ) has significantly reduced the mortality rate and has increased the life span of HIV-infected patients by maintaining viral loads below detection levels , thus preventing the onset of AIDS [1] , [2] , [3] , [4] .", "However , the presence of a stable latent r...	[ "HIV-1 cell-to-cell transmission allows for 2–3 orders of magnitude more efficient viral spread than cell-free dissemination .", "The high local multiplicity of infection ( MOI ) observed at cell-cell contact sites may lower the efficacy of antiretroviral therapies ( ART ) .", "Here we test the efficacy of comm...	[ "HIV-1 cell-to-cell transmission has gained interest due to its potential role in AIDS pathogenesis .", "It has recently been suggested that antiretroviral therapies fail during cell-to-cell transmission because of the high number of particles transferred at sites of cell-cell contacts .", "However , these find...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "molecular cell biology", "genetics", "population biology", "biology", "genomics", "evolutionary biology" ]	Vitellogenin Underwent Subfunctionalization to Acquire Caste and Behavioral Specific Expression in the Harvester Ant Pogonomyrmex barbatus	journal.pgen.1003730	null	[ [ "Division of labor is the cornerstone of insect societies and implies the coexistence of individuals that differ in morphology , reproduction and behavior [1] , [2] .", "There are usually two levels of division of labor among individuals in social insect colonies .", "The first relates to a reproducti...	[ "The reproductive ground plan hypothesis ( RGPH ) proposes that the physiological pathways regulating reproduction were co-opted to regulate worker division of labor .", "Support for this hypothesis in honeybees is provided by studies demonstrating that the reproductive potential of workers , assessed by the leve...	[ "One of the main features of social insects is the division of labor , whereby queens monopolize reproduction while sterile workers perform all of the tasks related to colony maintenance .", "The workers usually do so in an age-dependent sequence: young workers tend to nurse the brood inside the nest and older wo...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biology" ]	Behavioral Lateralization and Optimal Route Choice in Flying Budgerigars	journal.pcbi.1003473	null	[ [ "A bird flying through a complex and cluttered environment relies heavily on the use of visual cues to rapidly choose between alternative routes and avoid collisions with intervening obstacles .", "Goshawks , for example , display an impressive ability to fly through dense environments at high speeds [1] ...	[ "Birds flying through a cluttered environment require the ability to choose routes that will take them through the environment safely and quickly .", "We have investigated some of the strategies by which they achieve this .", "We trained budgerigars to fly through a tunnel in which they encountered a barrier th...	[ "Birds display a clear mastery of the skill of flying rapidly and safely through complex and cluttered environments .", "An example of this can be viewed at http://www . youtube . com/watch ?", "v=p-_RHRAzUHM , which shows a bird flying at high speed through a dense forest .", "Such mastery requires the abili...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "american samoa", "geomorphology", "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "education", "landforms", "sociology", "geographical locations", "age distribution", "social sciences", "topography", "tropical diseases", "parasitic diseases", "anima...	Detecting and confirming residual hotspots of lymphatic filariasis transmission in American Samoa 8 years after stopping mass drug administration	journal.pntd.0005914	null	[ [ "Lymphatic filariasis ( LF ) is a mosquito-borne parasitic infection caused by Wuchereria or Brugia species of helminths .", "Mosquito vectors vary between countries and regions , and include Aedes , Anopheles , Culex and Mansonia species .", "Globally , it is estimated that 68 million people are affe...	[ "The Global Programme to Eliminate Lymphatic Filariasis ( LF ) aims to eliminate the disease as a public health problem by 2020 by conducting mass drug administration ( MDA ) and controlling morbidity .", "Once elimination targets have been reached , surveillance is critical for ensuring that programmatic gains a...	[ "Lymphatic filariasis ( LF ) is caused by infection with filarial worms that are transmitted by mosquito bites .", "The Global Programme to Eliminate Lymphatic Filariasis aims to eliminate the disease as a public health problem by 2020 .", "Once elimination targets have been reached , cost-effective surveillanc...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "statistical noise", "ellipses", "nervous system", "random variables", "geometry", "neuroscience", "covariance", "mathematics", "statistics (mathematics)", "algebra", "computational neuroscience", "neuronal tuning", "coding mechanisms", "gaussian noise", ...	Robust information propagation through noisy neural circuits	journal.pcbi.1005497	null	[ [ "Neurons in sensory systems gather information about the environment , and transmit that information to other parts of the nervous system .", "This information is encoded in the activity of neural populations , and that activity is variable: repeated presentations of the same stimulus lead to different ne...	[ "Sensory neurons give highly variable responses to stimulation , which can limit the amount of stimulus information available to downstream circuits .", "Much work has investigated the factors that affect the amount of information encoded in these population responses , leading to insights about the role of covar...	[ "Information about the outside world , which originates in sensory neurons , propagates through multiple stages of processing before reaching the neural structures that control behavior .", "While much work in neuroscience has investigated the factors that affect the amount of information contained in peripheral ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "genetic networks", "cardiovascular anatomy", "protein interaction networks", "alleles", "developmental biology", "network analysis", "genome analysis", "morphogenesis", "cardiology", "computer and information sciences", "genomics", "birth defects", "gene ex...	De Novo and Rare Variants at Multiple Loci Support the Oligogenic Origins of Atrioventricular Septal Heart Defects	journal.pgen.1005963	null	[ [ "Congenital heart disease ( CHD ) is the most common congenital malformation and the most common cause of mortality during the first year of life in the United States [1 , 2] .", "Most cases occur sporadically without a strong family history or identifiable genetic syndrome , and the primary heritable bas...	[ "Congenital heart disease ( CHD ) has a complex genetic etiology , and recent studies suggest that high penetrance de novo mutations may account for only a small fraction of disease .", "In a multi-institutional cohort surveyed by exome sequencing , combining analysis of 987 individuals ( discovery cohort of 59 a...	[ "Congenital heart disease ( CHD ) is a leading cause of childhood morbidity in the developed world .", "There are few prevalent clinical risk factors and though it is possible that up to 90% of risk for CHD may be genetic , the number of genes clinically associated with disease is small .", "Rather than groupin...	2016
[ "Introduction", "Results and Discussion", "Methods" ]	[ "sequence analysis", "systems biology", "evolutionary biology", "genomic evolution", "natural selection", "gene regulation", "regulatory networks", "molecular genetics", "comparative genomics", "biology", "genomics", "population genetics", "signaling networks", "computational biology", "...	Functional Divergence and Evolutionary Turnover in Mammalian Phosphoproteomes	journal.pgen.1004062	null	[ [ "Most proteins undergo chemical modifications after their synthesis ( post-translational modifications , PTMs ) .", "These modifications allow a fine-tuning of protein functions and represent a mechanism to expand the coding capacity of genes [1] .", "Over the past decade , methods based on mass spect...	[ "Protein phosphorylation is a key mechanism to regulate protein functions .", "However , the contribution of this protein modification to species divergence is still largely unknown .", "Here , we studied the evolution of mammalian phosphoregulation by comparing the human and mouse phosphoproteomes .", "We fo...	[ "Understanding how differences in cellular regulation lead to phenotypic differences between species remains an open challenge in evolutionary genetics .", "The extensive phosphorylation data currently available allows to compare the human and mouse phosphoproteomes and to measure changes in their phosphoregulati...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4+ Memory T Cells	journal.ppat.1004928	null	[ [ "The Vpx accessory protein is encoded by HIV-2 , related SIVsm strains , SIVmnd , and SIVrcm [1–4] .", "Vpx has been reported to antagonize restriction imposed by SAMHD1 in cultured myeloid lineage ( dendritic cells , monocytes , and macrophages ) and quiescent CD4+ T cells [5–8] .", "Early studies al...	[ "For nearly 20 years , the principal biological function of the HIV-2/SIV Vpx gene has been thought to be required for optimal virus replication in myeloid cells .", "Mechanistically , this Vpx activity was recently reported to involve the degradation of Sterile Alpha Motif and HD domain-containing protein 1 ( SA...	[ "Primate lentiviruses , such as HIV and its SIV simian relative , encode accessory proteins that suppress cellular restriction factors interfering with efficient replication .", "One of these , designated Vpx , is produced in infected cells by HIV-2 and some SIV strains , which cause endemic infections in African...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "osteichthyes", "animal models", "zebrafish", "medicine and health sciences", "alcoholic liver disease", "model organisms", "fishes", "gastroenterology and hepatology", "genetics", "biology and life sciences", "vertebrates", "genetics of disease", "animals", "liver diseases", "organisms"...	Activating Transcription Factor 6 Is Necessary and Sufficient for Alcoholic Fatty Liver Disease in Zebrafish	journal.pgen.1004335	null	[ [ "The unfolded protein response ( UPR ) acts in most cells to maintain homeostasis within the protein secretory pathway during physiological conditions .", "During stress , the UPR becomes further induced to mitigate the accumulation of misfolded or unfolded proteins in the endoplasmic reticulum ( ER ) .",...	[ "Fatty liver disease ( FLD ) is characterized by lipid accumulation in hepatocytes and is accompanied by secretory pathway dysfunction , resulting in induction of the unfolded protein response ( UPR ) .", "Activating transcription factor 6 ( ATF6 ) , one of three main UPR sensors , functions to both promote FLD d...	[ "Fatty liver disease ( steatosis ) is the most common liver disease worldwide and is commonly caused by obesity , type 2 diabetes , or alcohol abuse .", "All of these conditions are associated with impaired hepatocyte protein secretion , resulting in hypoproteinemia that contributes to the systemic complications ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neutral theory", "population genetics", "evolutionary selection", "mutation", "effective population size", "genetic polymorphism", "comparative genomics", "biology", "evolutionary theory", "evolutionary genetics", "genetic drift", "adaptation", "natural selection", "genetics", "evolutio...	Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome	journal.pgen.1002326	null	[ [ "A substantial amount of effort in human population genetics has been aimed at understanding how natural selection operates in the human genome .", "However , we lack a basic understanding of the importance of positive natural selection versus negative selection at shaping overall patterns of genome varia...	[ "A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome .", "Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates .", "However , it is unclear whether other summaries of gen...	[ "While researchers have identified candidate genes that have evolved under positive Darwinian natural selection , less is known about how much of the human genome has been affected by natural selection or whether positive selection has had a greater role at shaping patterns of variation across the human genome than...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "markov models", "gene regulation", "regulatory proteins", "dna-binding proteins", "simulation and modeling", "mathematics", "stem cells", "network analysis", "transcription factors", "epigenetics", "research and analysis methods", "computer and information sciences", "cell potency", "anim...	Rare-event sampling of epigenetic landscapes and phenotype transitions	journal.pcbi.1006336	null	[ [ "In multicellular organisms , differentiation of pluripotent stem cells into tissue-specific cells was traditionally considered to be an irreversible process .", "The discovery of cell reprogramming revealed that the identity of a cell is not irreversibly stable , but rather plastic and amenable to contro...	[ "Stochastic simulation has been a powerful tool for studying the dynamics of gene regulatory networks , particularly in terms of understanding how cell-phenotype stability and fate-transitions are impacted by noisy gene expression .", "However , gene networks often have dynamics characterized by multiple attracto...	[ "Cell phenotypes are controlled by complex interactions between genes , proteins , and other molecules within a cell , along with signals from the cell’s environment .", "Gene regulatory networks ( GRNs ) describe these interactions mathematically .", "In principle , a GRN model can produce a map of possible ce...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biotechnology", "chemical biology/small molecule chemistry", "pathology", "infectious diseases/helminth infections", "biochemistry/drug discovery" ]	Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening	journal.pntd.0000478	null	[ [ "Treatment and control of the flatworm disease , schistosomiasis , relies on a single drug , praziquantel ( PZQ ) .", "Since the first clinical trials in the late 1970's [1] , PZQ has proven safe and effective against all three major forms of the disease , and today , declining costs make the drug more af...	[ "Praziquantel ( PZQ ) is the only widely available drug to treat schistosomiasis .", "Given the potential for drug resistance , it is prudent to search for novel therapeutics .", "Identification of anti-schistosomal chemicals has traditionally relied on phenotypic ( whole organism ) screening with adult worms i...	[ "The flatworm disease schistosomiasis infects over 200 million people with just one drug ( praziquantel ) available—a concern should drug resistance develop .", "Present drug discovery approaches for schistosomiasis are slow and not conducive to automation in a high-throughput format .", "Therefore , we designe...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "parasite groups", "ecology and environmental sciences", "plasmodium", "immunology", "tropical diseases", "vertebrates", "parasitic diseases", "parasitic protozoans", "animals", "parasitology", "mammals", "primates", "apicomplexa", "protozoans", "infecti...	Exposure and infection to Plasmodium knowlesi in case study communities in Northern Sabah, Malaysia and Palawan, The Philippines	journal.pntd.0006432	null	[ [ "After the initial recognition of a large number of human cases of the zoonotic malaria Plasmodium knowlesi in 2004 and advent of routine diagnosis of malaria cases by molecular methods , increasing numbers of human P . knowlesi cases have been reported in Southeast Asia and P . knowlesi is now the most commo...	[ "Primarily impacting poor , rural populations , the zoonotic malaria Plasmodium knowlesi is now the main cause of human malaria within Malaysian Borneo .", "While data is increasingly available on symptomatic cases , little is known about community-level patterns of exposure and infection .", "Understanding the...	[ "Plasmodium knowlesi is a species of malaria parasite found in wild macaque populations which is now the main cause of human malaria in Malaysian Borneo .", "Spread from macaques to people through infected mosquitoes , human P . knowlesi malaria cases have primarily been reported in adult men working in forests o...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "crystal structure", "pathology and laboratory medicine", "enzymes", "hepacivirus", "pathogens", "condensed matter physics", "enzymology", "microbiology", "precursor cells", "viruses", "rna viruses", "crystallography", "enzyme chemistry", "polypeptides", ...	NS2 proteases from hepatitis C virus and related hepaciviruses share composite active sites and previously unrecognized intrinsic proteolytic activities	journal.ppat.1006863	null	[ [ "Approximately 63–79 million individuals were estimated to be chronically infected by hepatitis C virus ( HCV ) worldwide in 2015 and are at risk of developing severe liver disease including fibrosis , cirrhosis and hepatocellular carcinoma .", "While the total number of HCV infections is expected to decl...	[ "Over the recent years , several homologues with varying degrees of genetic relatedness to hepatitis C virus ( HCV ) have been identified in a wide range of mammalian species .", "HCV infectious life cycle relies on a first critical proteolytic event of its single polyprotein , which is carried out by nonstructur...	[ "Despite remarkable progress in the development of therapeutic options , more than 70 million individuals are chronically infected by hepatitis C virus ( HCV ) worldwide and major challenges in basic and translational research remain .", "Phylogenetically-related HCV homologues have recently been identified in th...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Npvf: Hypothalamic Biomarker of Ambient Temperature Independent of Nutritional Status	journal.pgen.1005287	null	[ [ "Reduced ambient temperature will increase thermogenesis and reduce obesity .", "However its long-term effectiveness as a strategy to reduce obesity has been questioned because of the expectation that increased energy expenditure for the cold environment will increase food intake , thereby neutralizing th...	[ "The mechanism by which mice , exposed to the cold , mobilize endogenous or exogenous fuel sources for heat production is unknown .", "To address this issue we carried out experiments using 3 models of obesity in mice: C57BL/6J+/+ ( wild-type B6 ) mice with variable susceptibility to obesity in response to being ...	[ "Current knowledge does not provide a clear , definite view of central mechanisms controlling energy balance upon cold-activated thermogenesis .", "Here we show that upon cold exposure lean mice maintain body composition but increase food intake to fuel thermogenesis , whereas cold-exposed mice with DIO utilize e...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "viral vaccines", "emerging viral diseases", "microbiology", "viral structure", "adaptive immunity", "infectious disease control", "immunizations", "infectious diseases", "viral immune evasion", "biology", "viral envelope", "immunity", "virology" ]	Cross-Neutralizing Antibodies to Pandemic 2009 H1N1 and Recent Seasonal H1N1 Influenza A Strains Influenced by a Mutation in Hemagglutinin Subunit 2	journal.ppat.1002081	null	[ [ "In June 2009 the World Health Organization declared a new influenza pandemic due to sustained human to human transmission in several geographic regions of the novel swine-origin influenza A H1N1 virus , which was first identified in April by the Centers for Disease Control and Prevention ( CDC ) of the Unite...	[ "Pandemic 2009 H1N1 influenza A virus ( 2009 H1N1 ) differs from H1N1 strains that circulated in the past 50 years , but resembles the A/New Jersey/1976 H1N1 strain used in the 1976 swine influenza vaccine .", "We investigated whether sera from persons immunized with the 1976 swine influenza or recent seasonal in...	[ "Influenza A viruses mutate to escape neutralization by antibodies .", "These mutations predominantly occur in the globular head of the hemagglutinin protein , while the stalk is more conserved .", "Pandemic 2009 H1N1 influenza virus differs from seasonal H1N1 strains that circulated in the past 50 years and re...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "taxonomy", "vertebrates", "animals", "blastulas", "animal taxonomy", "developmental biology", "data management", "embryos", "zoology", "ectoderm", "embryology", "computer and information sciences", "gastrulas", "signal transduction", "eukaryota", "acorn worms", "cell biology", "bi...	Anteroposterior axis patterning by early canonical Wnt signaling during hemichordate development	journal.pbio.2003698	null	[ [ "The Wnt family of secreted ligand proteins is involved in a wide range of developmental functions during animal development , from embryonic induction to cell fate specification and the generation of cell polarity [1 , 2] .", "The presence of Wnt ligands , receptors , and Wnt antagonists in cnidarians , ...	[ "The Wnt family of secreted proteins has been proposed to play a conserved role in early specification of the bilaterian anteroposterior ( A/P ) axis .", "This hypothesis is based predominantly on data from vertebrate embryogenesis as well as planarian regeneration and homeostasis , indicating that canonical Wnt ...	[ "The anteroposterior ( A/P ) axis is a conserved feature of bilateral animals and is defined in the anterior by a head and in the posterior by a trunk .", "The secreted family of Wnt proteins and their antagonists play a conserved role in setting up this axis during early development in many bilaterians .", "Th...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "phosphorylation", "luciferase", "crystal structure", "molecular dynamics", "enzymes", "electricity", "condensed matter physics", "enzymology", "multivariate analysis", "electrostatics", "mathematics", "statistics (mathematics)", "crystallography", "thermodynamics", "research and analysi...	Polymodal allosteric regulation of Type 1 Serine/Threonine Kinase Receptors via a conserved electrostatic lock	journal.pcbi.1005711	null	[ [ "Serine/Threonine Kinase Receptors ( STKRs ) , also known as Transforming Growth Factor beta ( TGF-β ) receptors , are ubiquitous transmembrane proteins that play central roles in many biological processes ranging from cell differentiation , migration , proliferation and adhesion to development [1 , 2] .", ...	[ "Type 1 Serine/Threonine Kinase Receptors ( STKR1 ) transduce a wide spectrum of biological signals mediated by TGF-β superfamily members .", "The STKR1 activity is tightly controlled by their regulatory glycine-serine rich ( GS ) domain adjacent to the kinase domain .", "Despite decades of studies , it remains...	[ "Kinases play central role in essential physiological process and are attractive therapeutic drug targets .", "One of the important kinase families is Type 1 Serine/Threonine Kinase Receptors ( STKR1 ) , which control gene expression in response to extracellular growth factors .", "The activities of STKR1 are t...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "microbiology", "molecular cell biology", "genetics and genomics" ]	Long-Range Chromosome Organization in E. coli: A Site-Specific System Isolates the Ter Macrodomain	journal.pgen.1002672	null	[ [ "The large size of genomes compared to cell dimensions imposes an extensive compaction of chromosomes compatible with various processes of DNA metabolism such as gene expression , replication and segregation of the genetic information .", "The organized bacterial chromosome , named the nucleoid , is a com...	[ "The organization of the Escherichia coli chromosome into a ring composed of four macrodomains and two less-structured regions influences the segregation of sister chromatids and the mobility of chromosomal DNA .", "The structuring of the terminus region ( Ter ) into a macrodomain relies on the interaction of the...	[ "The large size of genomes compared to cell dimensions imposes an extensive compaction of chromosomes compatible with various processes of DNA metabolism , such as gene expression or segregation of the genetic information .", "Most bacterial genomes are circular molecules , and DNA replication proceeds bidirectio...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Clathrin Facilitates the Morphogenesis of Retrovirus Particles	journal.ppat.1002119	null	[ [ "To establish a productive infection in host cells , retroviruses have evolved strategies that employ numerous host factors to facilitate their replication .", "Recently , several groups have applied genome-wide RNAi screens to identify hundreds of candidate host factors that may facilitate human immunode...	[ "The morphogenesis of retroviral particles is driven by Gag and GagPol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation .", "In addition , a number of cellular proteins are found in retrovirus particles; some of these are important for vir...	[ "The assembly and maturation of infectious retroviruses is driven by two viral proteins , Gag and Pol .", "Additionally , a number of cellular proteins are found in retrovirus particles , many of which lack a known functional role .", "One such protein is clathrin , which normally mediates several physiological...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational neuroscience", "neuroscience", "biology and life sciences", "computational biology" ]	Spike-Threshold Adaptation Predicted by Membrane Potential Dynamics In Vivo	journal.pcbi.1003560	null	[ [ "Neurons encode information in sequences of stereotypical action potentials or spikes .", "Spikes are all-or-none voltage deflections triggered when the membrane potential of a neuron crosses a threshold .", "In vivo , the spiking threshold , as measured as the voltage at the upstroke of spikes , vari...	[ "Neurons encode information in sequences of spikes , which are triggered when their membrane potential crosses a threshold .", "In vivo , the spiking threshold displays large variability suggesting that threshold dynamics have a profound influence on how the combined input of a neuron is encoded in the spiking ."...	[ "Neurons spike when their membrane potential exceeds a threshold value , but this value has been shown to be variable in the same neuron recorded in vivo .", "This variability could reflect noise , or deterministic processes that make the threshold vary with the membrane potential .", "The second alternative wo...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biophysics/protein chemistry and proteomics", "biochemistry/protein chemistry", "biophysics/theory and simulation" ]	On the Zwitterionic Nature of Gas-Phase Peptides and Protein Ions	journal.pcbi.1000775	null	[ [ "Predicting the structural properties of proteins in the gas phase is crucial to interpret mass spectrometry data , yet this is far from being understood [1]–[10] .", "So far , it has been established that", "( i ) compact structures acquire smaller net charges than unfolded ones [11]–[13] ,", "( ...	[ "Determining the total number of charged residues corresponding to a given value of net charge for peptides and proteins in gas phase is crucial for the interpretation of mass-spectrometry data , yet it is far from being understood .", "Here we show that a novel computational protocol based on force field and mas...	[ "In the last two decades mass spectrometry has given an impressive contribution to biochemistry , protein science , proteomics and structural biology .", "This technique offers powerful insights into protein structure and dynamics along with useful information on the role of solvent in protein stability as it is ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "enzyme-linked immunoassays", "pathology and laboratory medicine", "microbial cultures", "pathogens", "biological cultures", "microbiology", "salmonella typhi", "bacterial diseases", "signs and symptoms", "enterobacteriaceae", "immunologic techn...	Comparison of the Performance of the TPTest, Tubex, Typhidot and Widal Immunodiagnostic Assays and Blood Cultures in Detecting Patients with Typhoid Fever in Bangladesh, Including Using a Bayesian Latent Class Modeling Approach	journal.pntd.0004558	null	[ [ "Typhoid and paratyphoid fevers ( collectively referred to as enteric fever ) are caused by Salmonella enterica serovar Typhi ( S . Typhi ) and serovar Paratyphi A , B , C [1] .", "Enteric fever causes high morbidity and mortality worldwide [2 , 3] .", "The majority of cases of enteric fever are cause...	[ "There is an urgent need for an improved diagnostic assay for typhoid fever .", "In this current study , we compared the recently developed TPTest ( Typhoid and Paratyphoid Test ) with the Widal test , blood culture , and two commonly used commercially available kits , Tubex and Typhidot .", "For analysis , we ...	[ "We compared the performance of the recently developed TPTest ( Typhoid and Paratyphoid Test ) with the Widal test , blood culture , and commercially available kits , Tubex and Typhidot in diagnosing the patients with typhoid fever .", "There is no acceptable gold standard; therefore , we estimated the sensitivit...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutagenesis", "signal transduction", "gram negative", "genetic mutation", "tyrosine kinase signaling cascade", "genetics", "microbial pathogens", "host-pathogen interaction", "biology", "microbiology", "molecular cell biology", "bacterial pathogens", "signaling cascades" ]	The Chlamydia trachomatis Type III Secretion Chaperone Slc1 Engages Multiple Early Effectors, Including TepP, a Tyrosine-phosphorylated Protein Required for the Recruitment of CrkI-II to Nascent Inclusions and Innate Immune Signaling	journal.ppat.1003954	null	[ [ "The gram-negative bacterium Chlamydia trachomatis is the causative agent of trachoma , the leading cause of infectious blindness worldwide , and the major cause of bacterial sexually transmitted infections ( STI ) in the developed world [1] .", "Approximately 2 . 9 million cases of visual impairment and ...	[ "Chlamydia trachomatis , the causative agent of trachoma and sexually transmitted infections , employs a type III secretion ( T3S ) system to deliver effector proteins into host epithelial cells to establish a replicative vacuole .", "Aside from the phosphoprotein TARP , a Chlamydia effector that promotes actin r...	[ "Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes a range of human diseases of significant public health importance .", "To create a suitable replicative niche within its host , Chlamydia delivers effector proteins across mammalian membranes via a syringe-like apparatus termed a T...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Dengue Virus in Sub-tropical Northern and Central Viet Nam: Population Immunity and Climate Shape Patterns of Viral Invasion and Maintenance	journal.pntd.0002581	null	[ [ "Dengue viruses ( DENV ) are single-stranded , positive-sense , mosquito-borne RNA viruses ( family Flaviviridae ) , within which considerable genetic diversity is present on both global and local scales [1] .", "All four serotypes ( DENV-1 to DENV-4 ) are capable of infecting humans and result in a spect...	[ "Dengue virus transmission occurs in both epidemic and endemic cycles across tropical and sub-tropical regions of the world .", "Incidence is particularly high in much of Southeast Asia , where hyperendemic transmission plagues both urban and rural populations .", "However , endemicity has not been established ...	[ "Reports from sub-tropical regions of the world suggest a growing risk of introduction and establishment of dengue viruses ( DENV ) in new locales .", "Recent dengue epidemics in northern Viet Nam present an opportunity to study how DENV invades and spreads in these environments .", "The proximity of this regio...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "stem cells", "evolutionary biology", "genetics", "population genetics", "biology", "evolutionary genetics", "genetics and genomics", "evolutionary developmental biology" ]	Age-Dependent Transition from Cell-Level to Population-Level Control in Murine Intestinal Homeostasis Revealed by Coalescence Analysis	journal.pgen.1003326	null	[ [ "Development and tissue homeostasis of multi-cellular organisms is an extraordinary cellular orchestra starting from a single zygote [1] .", "Cascades of cell divisions generate and subsequently maintain a great diversity of cells in an organism [2] .", "This life-long balance is strictly controlled a...	[ "In multi-cellular organisms , tissue homeostasis is maintained by an exquisite balance between stem cell proliferation and differentiation .", "This equilibrium can be achieved either at the single cell level ( a . k . a . cell asymmetry ) , where stem cells follow strict asymmetric divisions , or the population...	[ "In multi-cellular organisms , there is a static equilibrium maintaining cells of various forms .", "This homeostasis is achieved by an exquisite balance between stem cell proliferation and differentiation .", "Understanding how different species and organ types maintain this dynamic equilibrium has been an int...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational neuroscience", "neuroscience", "biology and life sciences", "computational biology" ]	Bilinearity in Spatiotemporal Integration of Synaptic Inputs	journal.pcbi.1004014	null	[ [ "For information processing , a neuron receives and integrates thousands of synaptic inputs from its dendrites and then induces the change of its membrane potential at the soma .", "This process is usually known as dendritic integration [1]–[3] .", "The dendritic integration of synaptic inputs is cruc...	[ "Neurons process information via integration of synaptic inputs from dendrites .", "Many experimental results demonstrate dendritic integration could be highly nonlinear , yet few theoretical analyses have been performed to obtain a precise quantitative characterization analytically .", "Based on asymptotic ana...	[ "A neuron , as a fundamental unit of brain computation , exhibits extraordinary computational power in processing input signals from neighboring neurons .", "It usually integrates thousands of synaptic inputs from its dendrites to achieve information processing .", "This process is known as dendritic integratio...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/molecular dynamics", "computational biology/macromolecular structure analysis", "biochemistry/bioinformatics" ]	Computer-Based Screening of Functional Conformers of Proteins	journal.pcbi.1000009	null	[ [ "Proteins are dynamic molecules that adopt multiple structures in vitro and in vivo [1] .", "To study the role protein dynamics has in protein function , a combination of approaches has been used [1]–[6] .", "For instance , crystallographic structures of proteins associated with different substrate's ...	[ "A long-standing goal in biology is to establish the link between function , structure , and dynamics of proteins .", "Considering that protein function at the molecular level is understood by the ability of proteins to bind to other molecules , the limited structural data of proteins in association with other bi...	[ "Proteins participate in most of the doings of the cells through a variety of interactions .", "There is an intimate relationship between the function of a protein and its three-dimensional structure , but understanding this relationship remains an unsolved problem , in part due to the limited information on prot...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics", "eubacteria" ]	Conformational Motion of the ABC Transporter MsbA Induced by ATP Hydrolysis	journal.pbio.0050271	Analysis of the conformational changes that occur in a conserved ATP-binding cassette (ABC) transporter challenges current models of this clinically important class of molecules.	[ [ "ATP-binding cassette ( ABC ) transporters harness the free energy of ATP hydrolysis to power the thermodynamically unfavorable trafficking of a wide spectrum of substrates in and out of the cell [1–3] .", "Cooperative ATP binding and hydrolysis occur in a molecular motor composed of two ATP-binding and h...	[ "We measured the amplitude of conformational motion in the ATP-binding cassette ( ABC ) transporter MsbA upon lipopolysaccharide ( LPS ) binding and following ATP turnover by pulse double electron-electron resonance and fluorescence homotransfer .", "The distance constraints from both methods reveal large-scale m...	[ "Clinical multidrug resistance in the treatment of bacterial and fungal infections and cancer chemotherapy can result from the expression of pumps that extrude toxic molecules from the cell .", "A subclass of these pumps—ATP-binding cassette ( ABC ) transporters—use energy from ATP to remove a wide range of molec...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria	journal.pgen.1005612	null	[ [ "Horizontal gene transfer ( HGT ) is a major force in bacterial evolution [1–3] .", "Comparative genomic analyses show that HGT events can be broadly classified into three types:", "a ) acquisition of a new gene not present in the taxa ,", "b ) acquisition of an orthologous gene in addition to the...	[ "Horizontal gene transfer ( HGT ) plays a central role in bacterial evolution , yet the molecular and cellular constraints on functional integration of the foreign genes are poorly understood .", "Here we performed inter-species replacement of the chromosomal folA gene , encoding an essential metabolic enzyme dih...	[ "Horizontal gene transfer ( HGT ) is central to bacterial evolution .", "The outcome of an HGT event ( fixation in a population , elimination , or separation as a subdominant clone ) depends not only on the availability of a new gene but crucially on the fitness cost or benefit of the genomic incorporation of the...	2015
[ "Introduction", "Results", "Discussion" ]	[]	Shaping Neuronal Network Activity by Presynaptic Mechanisms	journal.pcbi.1004438	null	[ [ "Oscillatory activity patterns in the brain have been linked to sleep , sensorimotor gating , short-term memory storage and selective attention [1 , 2] .", "Neuronal microcircuits in the brain spontaneously generate oscillatory activity patterns via synaptic interaction between groups of neurons [1 , 2] ....	[ "Neuronal microcircuits generate oscillatory activity , which has been linked to basic functions such as sleep , learning and sensorimotor gating .", "Although synaptic release processes are well known for their ability to shape the interaction between neurons in microcircuits , most computational models do not s...	[ "The activity of neuronal networks underlies basic neural functions such as sleep , learning and sensorimotor gating .", "Computational models of neuronal networks have been developed to capture the complexity of the network activity and predict how neuronal networks generate spontaneous activity .", "However ,...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/bioinformatics", "computational biology/metabolic networks", "computational biology/systems biology" ]	A Genome-Scale Metabolic Reconstruction of Mycoplasma genitalium, iPS189	journal.pcbi.1000285	null	[ [ "Genome-scale metabolic reconstructions are already in place or under development for a growing number of organisms including eukaryotic , prokaryotic and archaeal species [1] .", "Metabolic pathway reconstructions are increasingly being queried by systems engineering approaches to refine the quality of t...	[ "With a genome size of ∼580 kb and approximately 480 protein coding regions , Mycoplasma genitalium is one of the smallest known self-replicating organisms and , additionally , has extremely fastidious nutrient requirements .", "The reduced genomic content of M . genitalium has led researchers to suggest that the...	[ "There is growing interest in elucidating the minimal number of genes needed for life .", "This challenge is important not just for fundamental but also practical considerations arising from the need to design microorganisms exquisitely tuned for particular applications .", "The genome of the pathogen Mycoplasm...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "t helper cells", "medicine and health sciences", "immune cells", "immune physiology", "spleen", "immunology", "tropical diseases", "parasitic diseases", "preventive medicine", "pharmaceutics", "neglected tropical diseases", "vaccination and immunization", "public and occupa...	Combined Immune Therapy for the Treatment of Visceral Leishmaniasis	journal.pntd.0004415	null	[ [ "Immune check point inhibitors show great potential for the treatment of various cancers[1 , 2] .", "These drugs modulate regulatory pathways which suppress anti-tumour immune responses .", "Major targets for blockade include CTLA4 , PD1 , PDL1 , LAG3 , TIM3 and IL-10 , but a number of molecules are a...	[ "Chronic disease caused by infections , cancer or autoimmunity can result in profound immune suppression .", "Immunoregulatory networks are established to prevent tissue damage caused by inflammation .", "Although these immune checkpoints preserve tissue function , they allow pathogens and tumors to persist , a...	[ "Despite a decline in the numbers of visceral leishmaniasis ( VL ) cases and the availability of drugs to treat patients , there is still a need for more efficient treatment options .", "This is especially important as many VL endemic areas enter phases of disease elimination where parasite burdens need to be red...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Tracking Cholera through Surveillance of Oral Rehydration Solution Sales at Pharmacies: Insights from Urban Bangladesh	journal.pntd.0004230	null	[ [ "Despite well over a hundred years of research on the disease , cholera remains a threat to public health in many parts of the world , causing more than 2–3 million cases each year and over 100 , 000 deaths [1] .", "While many of the global cholera deaths come from large unexpected outbreaks , thousands d...	[ "In Bangladesh , pharmacy-purchased oral rehydration solution ( ORS ) is often used to treat diarrhea , including cholera .", "Over-the-counter sales have been used for epidemiologic surveillance in the past , but rarely , if ever , in low-income countries .", "With few early indicators for cholera outbreaks in...	[ "In Bangladesh , people often purchase oral rehydration solution ( ORS ) at their neighborhood pharmacy to treat diarrhea , including cholera .", "Over-the-counter sales have been used for epidemiologic surveillance , but rarely in low-income countries .", "With few early indicators for cholera outbreaks in end...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "circuit models", "auditory system", "computational neuroscience", "biology", "computational biology", "sensory systems", "neuroscience", "sensory perception", "coding mechanisms" ]	Neural Computation via Neural Geometry: A Place Code for Inter-whisker Timing in the Barrel Cortex?	journal.pcbi.1002188	null	[ [ "A fundamental question in computational neuroscience asks how the brain represents the relative timing of stimuli as they move between sensory receptors , e . g . as a light source moves relative to the retina , or as contact moves between touch sensors on the fingertip .", "For over 60 years Jeffress’ p...	[ "The place theory proposed by Jeffress ( 1948 ) is still the dominant model of how the brain represents the movement of sensory stimuli between sensory receptors .", "According to the place theory , delays in signalling between neurons , dependent on the distances between them , compensate for time differences in...	[ "To perceive how stimuli move over sensor surfaces like the retina or the fingertips , neurons in the brain must report the relative timing of signals arriving at different locations on the sensor surface .", "The rat whisker system is ideal for exploring how the brain performs this computation , because the layo...	2011
[ "Introduction", "Results", "Methods", "Discussion" ]	[]	Cyclooxygenase-2 and Prostaglandin E2 Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection	journal.pntd.0004025	null	[ [ "Chagas disease is a multisystemic disorder caused by Trypanosoma cruzi infection that affects more than 8 million people worldwide , being endemic in Latin America .", "Due to the scarcity of preventive and therapeutic tools and population at risk , it is considered as a neglected tropical disease [1 , 2...	[ "Inflammation plays an important role in the pathophysiology of Chagas disease , caused by Trypanosoma cruzi .", "Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells , being cyclooxygenases , COX-1 and COX-2 , the key enzymes in their biosynthesis from arachidonic a...	[ "The role of prostanoids , products of the arachidonic acid pathway , during Trypanosoma cruzi infection has been studied by inhibiting key enzymes in prostanoid synthesis as cyclooxygenases ( COX-1 and COX-2 ) , with opposed results .", "Here we analyzed the expression of cyclooxygenases , prostanoid synthases a...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Dynamic Change of Global and Local Information Processing in Propofol-Induced Loss and Recovery of Consciousness	journal.pcbi.1003271	null	[ [ "Despite the centrality of consciousness to our experience , no agreement has yet emerged on which aspects of brain function underlie its presence , and what changes are connected to its disappearance in the healthy brain ( e . g . , during sleep ) as well as in pathological conditions ( e . g . , coma ) .", ...	[ "Whether unique to humans or not , consciousness is a central aspect of our experience of the world .", "The neural fingerprint of this experience , however , remains one of the least understood aspects of the human brain .", "In this paper we employ graph-theoretic measures and support vector machine classific...	[ "One of the most elusive aspects of the human brain is the neural fingerprint of the subjective feeling of consciousness .", "While a growing body of experimental evidence is starting to address this issue , to date we are still hard pressed to answer even basic questions concerning the nature of consciousness in...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "histoplasmosis", "pathogens", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "drug delivery system preparation", "antigen encapsulation", "rna viruses", "pharmaceutics", "fungal diseases", "resear...	Histoplasma capsulatum antigen detection tests as an essential diagnostic tool for patients with advanced HIV disease in low and middle income countries: A systematic review of diagnostic accuracy studies	journal.pntd.0006802	null	[ [ "Histoplasmosis was first described in Panama in 1906 in a patient who appeared to have miliary tuberculosis , a confusion that is still very much present today . [1]", "Disseminated histoplasmosis has been an AIDS-defining infection since 1987 . [2 , 3] Recent estimates using different methods converge o...	[ "Disseminated histoplasmosis , a disease that often resembles and is mistaken for tuberculosis , is a major cause of death in patients with advanced HIV disease .", "Histoplasma antigen detection tests are an important addition to the diagnostic arsenal for patients with advanced HIV disease and should be conside...	[ "Disseminated histoplasmosis , a disease that often resembles and is mistaken for tuberculosis , is a major cause of death in patients with advanced HIV disease .", "Histoplasma antigen detection tests are an important addition to the diagnostic arsenal for patients with advanced HIV disease and should be conside...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	MiR-21 in Extracellular Vesicles Leads to Neurotoxicity via TLR7 Signaling in SIV Neurological Disease	journal.ppat.1005032	null	[ [ "HIV-associated neurocognitive disorder ( HAND ) is a central nervous system ( CNS ) associated neurological disease where neurodegeneration is a consequence of CNS inflammation .", "The pathological characteristics of the most extreme form of this disease include astrogliosis , microgliosis , presence of...	[ "Recent studies have found that extracellular vesicles ( EVs ) play an important role in normal and disease processes .", "In the present study , we isolated and characterized EVs from the brains of rhesus macaques , both with and without simian immunodeficiency virus ( SIV ) induced central nervous system ( CNS ...	[ "HIV associated neurocognitive disorder ( HAND ) are neurological disorders caused due to the entry of HIV infection in the brain .", "HIV-1 does not directly infect central or peripheral neurons , however , virus-infected cells of the monocyte/macrophage lineage maintain a low-level HIV infection in the CNS .", ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "plant and algal models", "molecular cell biology", "cell division", "immunity", "innate immunity", "microbial pathogens", "yeast and fungal models", "host-pathogen interaction", "biology", "salmonella", "microbiology", "saccharomyces cerevisiae", "bacterial pathogens", ...	The Salmonella Type III Effector SspH2 Specifically Exploits the NLR Co-chaperone Activity of SGT1 to Subvert Immunity	journal.ppat.1003518	null	[ [ "Salmonella enterica serovar Typhimurium ( S . Typhimurium ) , a causative agent of gastroenteritis and typhoid-like fever in mammals , encodes two type III secretion systems ( T3SS ) on Salmonella pathogenicity islands ( SPI ) -1 and SPI-2 .", "T3SSs are proteinaceous channels encoded by Gram negative ba...	[ "To further its pathogenesis , S . Typhimurium delivers effector proteins into host cells , including the novel E3 ubiquitin ligase ( NEL ) effector SspH2 .", "Using model systems in a cross-kingdom approach we gained further insight into the molecular function of this effector .", "Here , we show that SspH2 mo...	[ "Salmonella enterica serovar Typhimurium injects a suite of type III effectors into host cells , but their contributions to pathogenesis remain incompletely understood .", "We performed cross-kingdom analyses of the S . Typhimurium novel E3 ubiquitin ligase ( NEL ) effector SspH2 using animal , plant and yeast mo...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Molecular Typing of Pathogenic Leptospira Serogroup Icterohaemorrhagiae Strains Circulating in China during the Past 50 Years	journal.pntd.0003762	null	[ [ "Leptospirosis , caused by pathogenic Leptospira species , is emerging as one of the most widespread zoonosis with an estimated global burden of more than 500 , 000 cases of severe human leptospirosis and 100 , 000 deaths as well as great economic burden in farm and pet animals per year [1] .", "However ,...	[ "Leptospirosis is one of the most important neglected tropical infectious diseases worldwide .", "Icterohaemorrhagiae has been throughout recent history , and still is , the predominant serogroup of this pathogen in China .", "However , very little in detail is known about the serovars or genotypes of this sero...	[ "Leptospirosis , caused by pathogenic Leptospira spp , is a globally widespread zoonosis .", "In this study , our focusing on serogroup Icterohaemorrhagiae strains of Leptospira using MLST as a tool for phylogenetic analysis that has led to a better understanding of evolution of Leptospira .", "This totally con...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "virology/virus evolution and symbiosis", "virology/immunodeficiency viruses", "virology/animal models of infection", "virology", "virology/mechanisms of resistance and susceptibility, including host genetics" ]	TRIM5 Suppresses Cross-Species Transmission of a Primate Immunodeficiency Virus and Selects for Emergence of Resistant Variants in the New Species	journal.pbio.1000462	Cross-species transmission of simian immunodeficiency virus from sooty mangabeys (SIVsm) into rhesus macaques, and subsequent emergence of pathogenic SIVmac, required adaptation to overcome restriction encoded by the macaque TRIM5 gene.	[ [ "The Simian immunodeficiency viruses ( SIVs ) are widespread among African primates [1] .", "However , host and viral phylogenies are not completely congruent; such a pattern argues against co-divergence of virus and host lineages since the time of a common , infected primate ancestor and argues instead t...	[ "Simian immunodeficiency viruses of sooty mangabeys ( SIVsm ) are the source of multiple , successful cross-species transmissions , having given rise to HIV-2 in humans , SIVmac in rhesus macaques , and SIVstm in stump-tailed macaques .", "Cellular assays and phylogenetic comparisons indirectly support a role for...	[ "The human immunodeficiency viruses HIV-1 and HIV-2 originated from cross-species transmission of simian immunodeficiency viruses ( SIVs ) from chimpanzees ( SIVcpz ) and sooty mangabeys ( SIVsm ) , respectively .", "A related virus , SIVmac , causes AIDS-like pathogenesis in rhesus macaques; like HIV-2 , SIVmac ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/plant genetics and gene expression", "developmental biology/plant growth and development", "plant biology/plant genetics and gene expression", "genetics and genomics/plant genetics and gene expression" ]	Penetration of the Stigma and Style Elicits a Novel Transcriptome in Pollen Tubes, Pointing to Genes Critical for Growth in a Pistil	journal.pgen.1000621	null	[ [ "Cell-cell interactions can regulate the fate , morphology , and migration patterns of cells during development of multicellular organisms .", "Cell surface molecules mediate these interactions by initiating intracellular signal transduction cascades that cause changes in nuclear gene expression patterns ...	[ "Pollen tubes extend through pistil tissues and are guided to ovules where they release sperm for fertilization .", "Although pollen tubes can germinate and elongate in a synthetic medium , their trajectory is random and their growth rates are slower compared to growth in pistil tissues .", "Furthermore , inter...	[ "For successful reproduction in flowering plants , a single-celled pollen tube must rapidly extend through female pistil tissue , locate female gametes , and deliver sperm .", "Pollen tubes undergo a dramatic transformation while growing in the pistil; they grow faster compared to tubes grown in vitro and become ...	2009
[ "Introduction", "Materials and methods", "Results and discussion" ]	[ "medicine and health sciences", "employment", "engineering and technology", "applied mathematics", "sociology", "social sciences", "simulation and modeling", "algorithms", "mutation", "mathematics", "pharmacology", "discrete mathematics", "combinatorics", "research and analysis methods", ...	Efficient algorithms to discover alterations with complementary functional association in cancer	journal.pcbi.1006802	null	[ [ "Several recent methods have used mutual exclusivity signals to identify sets of genes important for cancer [24] .", "RME [25] identifies mutually exclusive sets using a score derived from information theory .", "Dendrix [26] defines a combinatorial gene set score and uses a Markov Chain Monte Carlo (...	[ "Recent large cancer studies have measured somatic alterations in an unprecedented number of tumours .", "These large datasets allow the identification of cancer-related sets of genetic alterations by identifying relevant combinatorial patterns .", "Among such patterns , mutual exclusivity has been employed by ...	[ "Sequencing technologies allow the measurement of somatic alterations in a large number of cancer samples .", "Several methods have been designed to analyze these alterations , but the characterization of the functional effects of such alterations is still challenging .", "A recent promising approach for such c...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunopathology", "mycology", "immunity", "microbial pathogens", "immunology", "biology", "microbiology", "immune response" ]	TNF-α and CD8+ T Cells Mediate the Beneficial Effects of Nitric Oxide Synthase-2 Deficiency in Pulmonary Paracoccidioidomycosis	journal.pntd.0002325	null	[ [ "Phagocytes are important effector cells of innate and adaptative immunity and use several mediators and mechanisms to control pathogen growth .", "The production of nitric oxide ( NO ) has been shown to be an important microbicidal mechanism of macrophages in the protective immune responses against diffe...	[ "Nitric oxide ( NO ) , a key antimicrobial molecule , was previously shown to exert a dual role in paracoccidioidomycosis , an endemic fungal infection in Latin America .", "In the intravenous and peritoneal models of infection , NO production was associated with efficient fungal clearance but also with non-organ...	[ "Paracoccidiodomycosis is a human systemic mycosis endemic in Latin America that has a wide spectrum of manifestations ranging from localized to fatal disseminated forms .", "Both in humans and experimental models , immunoprotection is mediated by T cell immunity whereas immunosuppression is associated with the s...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Multiple Origins of Mutations in the mdr1 Gene—A Putative Marker of Chloroquine Resistance in P. vivax	journal.pntd.0004196	null	[ [ "Malaria is one of the world’s leading causes of mortality and morbidity .", "Since late in the 1940s the antimalarial drug chloroquine ( CQ ) has been the primary chemotherapeutic for prophylaxis and treatment of malaria because of its good safety profile , low cost and high efficacy against the blood st...	[ "Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance ( CQR ) .", "Single nucleotide polymorphisms ( SNPs ) in the multidrug resistance gene , P...	[ "Chloroquine combined with primaquine has been the recommended antimalarial treatment for Plasmodium vivax malaria infections for sixty years but the efficacy of this treatment regimen is threatened by chloroquine resistance .", "In this study we describe the prevalence of mutations in the P . vivax gene , Pvmdr1...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "learning", "decision making", "reaction time", "social sciences", "neuroscience", "learning and memory", "cognitive neuroscience", "cognitive psychology", "mathematics", "probability distribution", "computer vision", "cognition", "memory", "vision", "computer and information sciences", ...	Inter-trial effects in visual pop-out search: Factorial comparison of Bayesian updating models	journal.pcbi.1006328	null	[ [ "In everyday life , we are continuously engaged in selecting visual information to achieve our action goals , as the amount of information we receive at any time exceeds the available processing capacity .", "The mechanisms mediating attentional selection enable us to act efficiently by prioritizing task-...	[ "Many previous studies on visual search have reported inter-trial effects , that is , observers respond faster when some target property , such as a defining feature or dimension , or the response associated with the target repeats versus changes across consecutive trial episodes .", "However , what processes dri...	[ "When a perceptual task is performed repeatedly , performance becomes faster and more accurate when there is little or no change of critical stimulus attributes across consecutive trials .", "This phenomenon has been explored in previous studies on visual ‘pop-out’ search , showing that participants can find and ...	2018
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Reproductive Mode and the Evolution of Genome Size and Structure in Caenorhabditis Nematodes	journal.pgen.1005323	null	[ [ "Self reproduction increases the probability of homozygosity at single loci , reducing the effective size of the population by a factor of two [1–3] .", "At the level of whole genomes , the reduced probability that two loci will be heterozygous within a single individual greatly decreases the efficacy of ...	[ "The self-fertile nematode worms Caenorhabditis elegans , C . briggsae , and C . tropicalis evolved independently from outcrossing male-female ancestors and have genomes 20-40% smaller than closely related outcrossing relatives .", "This pattern of smaller genomes for selfing species and larger genomes for closel...	[ "Closely related species can vary widely in genome size , yet the genetic and evolutionary forces responsible for these differences are poorly understood .", "Among Caenorhabditis nematodes , self-fertilizing species have genomes 20–40% smaller than outcrossing species .", "Constructing a high quality de novo g...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "psychology", "social and behavioral sciences", "biology", "neuroscience" ]	Learning and Generalization under Ambiguity: An fMRI Study	journal.pcbi.1002346	null	[ [ "Successful behavior in new situations often requires us to apply ‘rules-of-thumb’ .", "However , acquiring and applying abstract rules from limited experience presents a fundamental computational problem [1]: in which both over- or under-generalization must be avoided [2] , .", "Despite their importa...	[ "Adaptive behavior often exploits generalizations from past experience by applying them judiciously in new situations .", "This requires a means of quantifying the relative importance of prior experience and current information , so they can be balanced optimally .", "In this study , we ask whether the brain ge...	[ "Intelligent behavior requires flexible responses to new situations , which exploit learned principles or abstractions .", "When no such principles exist , the imperative is to learn quickly from scratch .", "Behaviorally , we show that subjects learn action-reward relationships in a manner that enables them to...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "antimicrobials", "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "drugs", "microbiology", "pseudomonas aeruginosa", "antibiotic resistance", "pharmaceutics", "antibiotics", "microbial evolution", "evolutionary adapt...	History of antibiotic adaptation influences microbial evolutionary dynamics during subsequent treatment	journal.pbio.2001586	null	[ [ "Antibiotic resistance is a growing healthcare concern whereby bacterial infections are increasingly difficult to eradicate due to their ability to survive antibiotic treatments [1] .", "There have been reported cases of resistance for nearly every antibiotic we have available [2] .", "Coupled with th...	[ "Antibiotic regimens often include the sequential changing of drugs to limit the development and evolution of resistance of bacterial pathogens .", "It remains unclear how history of adaptation to one antibiotic can influence the resistance profiles when bacteria subsequently adapt to a different antibiotic .", ...	[ "Bacteria readily adapt to their environments and can develop ways to survive and grow in the presence of antibiotics .", "While many studies have investigated how bacteria evolve to become resistant to single drugs , it is unclear how adaptation to other drugs and environments in the past affect the way bacteria...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	IL-33-Mediated Protection against Experimental Cerebral Malaria Is Linked to Induction of Type 2 Innate Lymphoid Cells, M2 Macrophages and Regulatory T Cells	journal.ppat.1004607	null	[ [ "Malaria remains a major health problem for humans infected with Plasmodium species .", "Cerebral malaria ( CM ) is a severe and potentially fatal neurological manifestation of infection and accounts for approximately one million deaths annually of children in sub-Saharan Africa alone [1] .", "CM is c...	[ "Cerebral malaria ( CM ) is a complex parasitic disease caused by Plasmodium sp .", "Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to the development of cerebral pathology .", "Using the blood-stage PbA ( Plasmodium berghei ANKA ) model...	[ "Cerebral malaria ( CM ) caused by the parasite Plasmodium sp .", "is a fatal disease , especially in children .", "Currently there is no effective treatment .", "We report here our investigation on the role of a recently discovered cytokine IL-33 , in treating experimental cerebral malaria ( ECM ) in the sus...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine" ]	Increased Birth Weight Associated with Regular Pre-Pregnancy Deworming and Weekly Iron-Folic Acid Supplementation for Vietnamese Women	journal.pntd.0001608	null	[ [ "Low birth weight is widely recognised as a risk factor for neonatal mortality and morbidity , as well as reduced cognitive function and the development of chronic diseases in later life [1]–[3] .", "Iron deficiency anaemia during pregnancy is an important cause of restricted foetal growth leading to low ...	[ "Hookworm infections are significant public health issues in South-East Asia .", "In women of reproductive age , chronic hookworm infections cause iron deficiency anaemia , which , upon pregnancy , can lead to intrauterine growth restriction and low birth weight .", "Low birth weight is an important risk factor...	[ "Low birth weight is an important risk factor for neonatal and infant morbidity and mortality and may impact on growth and development .", "Maternal iron deficiency anaemia contributes to intrauterine growth restriction and low birth weight .", "Hookworm infections and an iron-depleted diet may lead to iron def...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "infectious diseases/skin infections" ]	Development and Validation of a Severity Scale for Leprosy Type 1 Reactions	journal.pntd.0000351	null	[ [ "Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae .", "More than 254 000 new cases were reported to the World Health Organization in 2007 [1] .", "The disease predominantly affects the skin and nerves .", "The nerve involvement associated with the disease may lead to perma...	[ "To develop a valid and reliable quantitative measure of leprosy Type 1 reactions .", "A scale was developed from previous scales which had not been validated .", "The face and content validity were assessed following consultation with recognised experts in the field .", "The construct validity was determined...	[ "Leprosy is caused by a bacterium and is curable with a combination of antibiotics known as multi-drug therapy which patients take for six or 12 months .", "However , a significant proportion of leprosy patients experience inflammation in their skin and/or nerves which may occur even after successful completion o...	2008
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "medicine", "endocrinology", "genetics", "molecular genetics", "biology", "human genetics", "neuroendocrinology", "genetics of disease", "diabetes and endocrinology", "genetics and genomics" ]	SEMA3A, a Gene Involved in Axonal Pathfinding, Is Mutated in Patients with Kallmann Syndrome	journal.pgen.1002896	null	[ [ "Kallmann syndrome ( KS , MIM 147950 , 244200 , 308700 , 610628 , 612370 , 612702 ) is an inherited neurodevelopmental disorder defined as the association of hypogonadotropic hypogonadism , due to gonadotropin-releasing hormone ( GnRH ) deficiency , and the inability to smell ( anosmia or hyposmia ) , related...	[ "Kallmann syndrome ( KS ) associates congenital hypogonadism due to gonadotropin-releasing hormone ( GnRH ) deficiency and anosmia .", "The genetics of KS involves various modes of transmission , including oligogenic inheritance .", "Here , we report that Nrp1sema/sema mutant mice that lack a functional semapho...	[ "Kallmann syndrome is a hereditary developmental disease that affects both the hormonal reproductive axis and the sense of smell .", "There is a developmental link between the reproductive and olfactory disorders: neuroendocrine cells producing the gonadotropin-releasing hormone that is deficient in the patients ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "functional genomics", "x chromosome inactivation", "genomic imprinting", "gene expression", "genetics", "epigenetics", "biology", "dna modification", "genetics and genomics" ]	Analysis of DNA Methylation in a Three-Generation Family Reveals Widespread Genetic Influence on Epigenetic Regulation	journal.pgen.1002228	null	[ [ "Methylation of the 5 carbon of a large number of cytosines in the genome is necessary in mammalian development [1] .", "Aberrant patterns of DNA methylation have been reported in a wide variety of human diseases , including cancer [2] , [3] , psychiatric disorders [4] , autoimmune diseases [5] and diabet...	[ "The methylation of cytosines in CpG dinucleotides is essential for cellular differentiation and the progression of many cancers , and it plays an important role in gametic imprinting .", "To assess variation and inheritance of genome-wide patterns of DNA methylation simultaneously in humans , we applied reduced ...	[ "DNA methylation is a dynamic epigenetic mark that is essential for mammalian organismal development .", "DNA methylation levels can be influenced by environment , a chromosome's parental origin , and genome sequence .", "In this study , we evaluated the impact that DNA sequence has on DNA methylation by analyz...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetic mutation", "genetics", "biology", "human genetics", "genetics of disease" ]	The Rate of Nonallelic Homologous Recombination in Males Is Highly Variable, Correlated between Monozygotic Twins and Independent of Age	journal.pgen.1004195	null	[ [ "Homologous recombination ( HR ) , leading to crossing over and exchange between homologous DNA sequences , occurs during meiosis and ensures that each gamete contains a unique mixture of maternal and paternal DNA .", "Occasionally HR occurs ectopically between highly similar duplicated sequences or paral...	[ "Nonallelic homologous recombination ( NAHR ) between highly similar duplicated sequences generates chromosomal deletions , duplications and inversions , which can cause diverse genetic disorders .", "Little is known about interindividual variation in NAHR rates and the factors that influence this .", "We estim...	[ "Many genetic disorders are caused by deletions of specific regions of DNA in sperm or egg cells that go on to produce a child .", "This can occur through ectopic homologous recombination between highly similar segments of DNA at different positions within the genome .", "Little is known about the differences i...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biotechnology", "bioengineering", "animal behavior", "evolutionary biology", "biology", "zoology", "neuroscience", "biomimetics" ]	Do Ants Need to Estimate the Geometrical Properties of Trail Bifurcations to Find an Efficient Route? A Swarm Robotics Test Bed	journal.pcbi.1002903	null	[ [ "Various ant species build networks of trails that link together nesting sites and exploited resources [1] .", "These networks are generally formed by one or several dendritic trees originating from the nest of the colony .", "They can stretch over large distances and display very intricate patterns ....	[ "Interactions between individuals and the structure of their environment play a crucial role in shaping self-organized collective behaviors .", "Recent studies have shown that ants crossing asymmetrical bifurcations in a network of galleries tend to follow the branch that deviates the least from their incoming di...	[ "Most ant species form transportation networks , be they foraging trails linking food sources to the main colony or underground galleries connecting the different parts of the nest .", "As for human transportation networks ( roads , airlines , etc . ) , the design and the placement of the connecting points ( or n...	2013
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "medicine", "pituitary", "applied mathematics", "anatomy and physiology", "homeostatic mechanisms", "neuroscience", "hormones", "endocrine physiology", "mathematics", "endocrine glands", "endocrine cells", "theoretical biology", "endocrinology", "diabetes and endocrinology", "biology", ...	The Origin of Glucocorticoid Hormone Oscillations	journal.pbio.1001341	Characterization of a peripheral hormonal system identifies the origin and mechanisms of regulation of glucocorticoid hormone oscillations in rats.	[ [ "A fundamental requisite for survival is the ability to respond and adapt to a changing environment .", "This ability to respond to change or “stress” becomes more complex in multicellular organisms , and mammals have developed a well-integrated organization of hormonal , neural , and immunological system...	[ "Oscillating levels of adrenal glucocorticoid hormones are essential for optimal gene expression , and for maintaining physiological and behavioural responsiveness to stress .", "The biological basis for these oscillations is not known , but a neuronal “pulse generator” within the hypothalamus has remained a popu...	[ "Glucocorticoid steroid hormones , such as cortisol and corticosterone , provide a rapid response to both physical and psychological stress , and act on areas of the brain that influence learning , memory , and behaviour .", "Glucocorticoids are released from the adrenal glands in near-hourly pulses , which resul...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "protons", "medicine and health sciences", "fungal genetics", "gene regulation", "rna extraction", "fungal structure", "physiological processes", "mycelium", "mitochondria", "bioenergetics", "cellular structures and organelles", "extraction techniques", "oxygen consumption", "research and ...	Regulation of Aerobic Energy Metabolism in Podospora anserina by Two Paralogous Genes Encoding Structurally Different c-Subunits of ATP Synthase	journal.pgen.1006161	null	[ [ "Most energy-transducing membranes in bacteria , mitochondria and chloroplasts contain an F-ATP synthase .", "Historically this enzyme has been described in terms of an integral membrane domain ( FO ) and a peripheral domain ( F1 ) .", "High-definition structural data now available reveal that FO and ...	[ "Most of the ATP in living cells is produced by an F-type ATP synthase .", "This enzyme uses the energy of a transmembrane electrochemical proton gradient to synthesize ATP from ADP and inorganic phosphate .", "Proton movements across the membrane domain ( FO ) of the ATP synthase drive the rotation of a ring o...	[ "In mitochondria , the ATP synthase ( also referred to as complex V ) catalyzes the late steps of oxidative phosphorylation ( OXPHOS ) , which is a process that provides aerobic eukaryotes with most of their energy requirements by generating adenosine triphosphate ( ATP ) molecules .", "While the structure and me...	2016
[ "Introduction", "Results", "Methods", "Discussion" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "rna extraction", "microbiology", "organisms", "cytotoxic t cells", "extraction techniques", "bacteria", "bacterial pathogens", "research and a...	B. abortus RNA is the component involved in the down-modulation of MHC-I expression on human monocytes via TLR8 and the EGFR pathway	journal.ppat.1006527	null	[ [ "Host control of brucellosis requires a set of cells and components of the immune system which together promote a complex response against Brucella spp .", "[1] .", "Yet , from the many defensive resources that adaptive immunity brings into play , cytotoxic CD8+ T cells are determinant to restrain Bru...	[ "Despite eliciting a potent CD8+ T cell response , Brucella abortus is able to persist and establish a chronic infection inside its host .", "We have previously reported that the infection of human monocytes/macrophages with B . abortus inhibits the IFN-γ-induced MHC-I cell surface expression down-modulating cyto...	[ "Brucella abortus is one of the intracellular bacterial species that cause brucellosis , a zoonotic worldwide disease .", "An intricate enigma of Brucella immunity is its long-term persistence inside host despite a vigorous and specific immune response .", "Our study describes a novel immune evasion strategy ex...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	How MicroRNA and Transcription Factor Co-regulatory Networks Affect Osteosarcoma Cell Proliferation	journal.pcbi.1003210	null	[ [ "Osteosarcoma ( OS ) is a rare type of cancer frequently occurring in children and young adolescents [1] .", "It is a complex tumor typically accompanied by severe genomic instability and extensive mutations hampering the identification of a genetic root [2]–[4] .", "These genomic alterations affect s...	[ "Osteosarcomas ( OS ) are complex bone tumors with various genomic alterations .", "These alterations affect the expression and function of several genes due to drastic changes in the underlying gene regulatory network .", "However , we know little about critical gene regulators and their functional consequence...	[ "Osteosarcomas ( OS ) are bone tumors most frequently affecting children and young adolescents .", "We do not know much about its molecular pathogenesis hampering personalized therapies to more effectively cure patients .", "To this day , almost all patients receive adjuvant chemotherapies independent of its ne...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods", "Ethics statement" ]	[ "parasite groups", "medicine and health sciences", "vacuoles", "parasitic cell cycles", "cell cycle and cell division", "cell processes", "dna-binding proteins", "parasitic diseases", "parasitic protozoans", "parasitology", "developmental biology", "apicomplexa", "tachyzoites", "protozoans...	Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis	journal.ppat.1007035	null	[ [ "Toxoplasma gondii is an obligate intracellular parasite that exhibits a multi-host and multi-stage developmental life cycle .", "Sexual stages are restricted to the gut mucosa of the feline definitive host and asexual stages of the intermediate life cycle occur within any warm-blooded host , including hu...	[ "Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst .", "The factors that control this important life cycle transition a...	[ "The Toxoplasma biology that underlies the establishment of a chronic infection is developmental conversion of the acute tachyzoite stage into the latent bradyzoite-tissue cyst stage .", "Despite the important clinical consequences of this developmental pathway , the molecular basis of the switch mechanisms that ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics", "developmental biology" ]	Microtubule Actin Crosslinking Factor 1 Regulates the Balbiani Body and Animal-Vegetal Polarity of the Zebrafish Oocyte	journal.pgen.1001073	null	[ [ "The animal-vegetal axis is the first axis to form in the vertebrate embryo; however , the cellular and genetic pathways by which it is specified are the least well understood .", "In lower vertebrates , such as frogs and fish , this axis forms during early oogenesis , while in mouse , it becomes apparent...	[ "Although of fundamental importance in developmental biology , the genetic basis for the symmetry breaking events that polarize the vertebrate oocyte and egg are largely unknown .", "In vertebrates , the first morphological asymmetry in the oocyte is the Balbiani body , a highly conserved , transient structure fo...	[ "How the axes of the embryo are established is an important question in developmental biology .", "In many organisms , the axes of the embryo are established during oogenesis through the generation of a polarized egg .", "Very little is known regarding the mechanisms of polarity establishment and maintenance in...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell motility", "developmental biology", "cell biology", "parasitic cell cycles", "cell migration", "life cycles", "parasitology", "biology and life sciences", "cell processes", "microbiology", "molecular cell biology", "cell aggregation", "molecular biology", "cell differentiation", "p...	Social Motility of African Trypanosomes Is a Property of a Distinct Life-Cycle Stage That Occurs Early in Tsetse Fly Transmission	journal.ppat.1004493	null	[ [ "Various sub-species of the protozoan parasite Trypanosoma brucei cause sleeping sickness in humans and Nagana in domestic animals .", "Irrespective of their mammalian host range , all these parasites are dependent on tsetse flies for their transmission .", "Two features enable trypanosomes to establi...	[ "The protozoan pathogen Trypanosoma brucei is transmitted between mammals by tsetse flies .", "The first compartment colonised by trypanosomes after a blood meal is the fly midgut lumen .", "Trypanosomes present in the lumen—designated as early procyclic forms—express the stage-specific surface glycoproteins EP...	[ "African trypanosomes , single-celled parasites that cause human sleeping sickness and Nagana in animals , are transmitted by tsetse flies .", "Bloodstream form trypanosomes ingested by tsetse differentiate into procyclic forms in the midgut lumen of the insect .", "Successful transmission to a new mammalian ho...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "infectious disease epidemiology", "tropical diseases", "animals", "parasitology", "global health", "neglected tropical diseases", "infectious disease control", "zoology", "veterinary science", "public and occupational health", "infectious dis...	Comparative Host Feeding Patterns of the Asian Tiger Mosquito, Aedes albopictus, in Urban and Suburban Northeastern USA and Implications for Disease Transmission	journal.pntd.0003037	null	[ [ "Understanding the blood feeding patterns of mosquitoes is of paramount importance in determining their vector status in the maintenance and epidemic transmission of arboviruses .", "Blood feeding patterns of mosquito vectors provide insight into the ecological transmission cycles of pathogens and lead to...	[ "Aedes albopictus is an invasive species which continues expanding its geographic range and involvement in mosquito-borne diseases such as chikungunya and dengue .", "Host selection patterns by invasive mosquitoes are critically important because they increase endemic disease transmission and drive outbreaks of e...	[ "Aedes albopictus is one of the most invasive and aggressive disease vectors in the world .", "The range of this species is currently still expanding , particularly into highly dense human population centers in temperate areas in the USA and Europe , raising the public health threat of emerging and re-emerging di...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "inflammatory diseases", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "multiple sclerosis", "neurodegenerative diseases", "immunology", "data mining", "developmental biology", "demyelinating disorders", "clinical medicine", "inflammasomes", "mol...	Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease	journal.pgen.1008180	null	[ [ "Multiple sclerosis ( MS ) is a common autoimmune disease of the central nervous system ( CNS ) affecting over two million people worldwide [1] .", "Although described as early as the 14th century , it was Jean-Martin Charcot in 1868 who recognised MS as a distinct entity , and provided the first detailed...	[ "Multiple sclerosis ( MS ) is an inflammatory disease of the central nervous system characterized by myelin loss and neuronal dysfunction .", "Although the majority of patients do not present familial aggregation , Mendelian forms have been described .", "We performed whole-exome sequencing analysis in 132 pati...	[ "Although the majority of patients diagnosed with multiple sclerosis do not have a family history of disease , 13% report having a close relative also diagnosed with multiple sclerosis .", "In these families , the cause of multiple sclerosis can be largely attributed to a single genetic variant that is transmitte...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "rheumatology/cartilage biology and osteoarthritis", "developmental biology/aging", "pathology/histopathology", "genetics and genomics/disease models", "radiology and medical imaging/computer tomography", "nutrition/deficiencies", "cell biology/gene expression" ]	Osteo-Chondroprogenitor–Specific Deletion of the Selenocysteine tRNA Gene, Trsp, Leads to Chondronecrosis and Abnormal Skeletal Development: A Putative Model for Kashin-Beck Disease	journal.pgen.1000616	null	[ [ "Kashin-Beck disease , an environmentally-induced musculoskeletal syndrome , is prevalent in millions of individuals residing within specific regions of Tibet , China , Siberia , and North Korea [1]–[3] .", "The disease first becomes evident in childhood with affected individuals exhibiting short stature ...	[ "Kashin-Beck disease , a syndrome characterized by short stature , skeletal deformities , and arthropathy of multiple joints , is highly prevalent in specific regions of Asia .", "The disease has been postulated to result from a combination of different environmental factors , including contamination of barley by...	[ "Kashin-Beck disease ( KBD ) is a severe , chronic , and deforming musculoskeletal disease affecting millions of individuals in specific regions of Asia .", "Starting in childhood , the disorder leads to joint and limb deformities , short stature , and delayed skeletal development .", "Articular cartilage damag...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host-Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection	journal.ppat.1005341	null	[ [ "Staphylococcus aureus is a major human pathogen , capable of causing a variety of life-threatening , invasive diseases and infecting nearly every organ in the human body .", "Yet S . aureus also innocuously colonizes the skin and nares of one-third to one-half of the population [1] .", "These facts s...	[ "Staphylococcus aureus is capable of infecting nearly every organ in the human body .", "In order to infiltrate and thrive in such diverse host tissues , staphylococci must possess remarkable flexibility in both metabolic and virulence programs .", "To investigate the genetic requirements for bacterial survival...	[ "Staphylococcus aureus is a leading cause of infectious death , yet is also capable of harmlessly colonizing healthy individuals .", "These disparate observations imply that S . aureus can modulate its growth and virulence in response to different host environments .", "To characterize the staphylococcal geneti...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "electricity", "brain electrophysiology", "social sciences", "electrophysiology", "neuroscience", "learning and memory", "surgical and invasive medical procedures", "number theory", "cognitive neuroscience", "transcranial alternating current stimulation", "mathe...	The speed of parietal theta frequency drives visuospatial working memory capacity	journal.pbio.2005348	null	[ [ "The theta–gamma cross-frequency coupling theory [1] ( Fig 1A ) proposes that individual fast brain waves ( gamma cycles ) represent individual memory items that are bound together to a multi-item memory by slow brain waves ( theta oscillations ) .", "Consequently , individual differences in the length of...	[ "The speed of theta brain oscillatory activity is thought to play a key role in determining working memory ( WM ) capacity .", "Individual differences in the length of a theta cycle ( ranging between 4 and 7 Hz ) might determine how many gamma cycles ( >30 Hz ) can be nested into a theta wave .", "Gamma cycles ...	[ "Our ability to temporarily retain sensory information is limited to a handful of items and is referred to as working memory capacity .", "Such memory capacity has been shown to vary across the general population , with some people retaining a higher number of items than others .", "An influential theory sugges...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "material fatigue", "medicine and health sciences", "legs", "classical mechanics", "limbs (anatomy)", "biomechanics", "collagens", "physiological processes", "homeostasis", "materials science", "damage mechanics", "materials physics", "musculoskeletal mechanics", "muscle physiology", "mu...	Adaptive Remodeling of Achilles Tendon: A Multi-scale Computational Model	journal.pcbi.1005106	null	[ [ "Tendons are dense fibrous tissues that transfer tensile forces from muscles to bones .", "During normal daily activity , human Achilles tendon experiences high intensity cyclic loads , up to 4–8 times the body weight [1–3] .", "Achilles tendon stores potential strain energy as it is stretched , which...	[ "While it is known that musculotendon units adapt to their load environments , there is only a limited understanding of tendon adaptation in vivo .", "Here we develop a computational model of tendon remodeling based on the premise that mechanical damage and tenocyte-mediated tendon damage and repair processes mod...	[ "It is now widely acknowledged that tendon plays a vital role in locomotion , while experiments have revealed that tendon is much more metabolically active than previously believed .", "There have been increasing numbers of papers describing the responses of tenocytes to mechanical loading and speculation about t...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "nervous system", "immunology", "neuroscience", "microglial cells", "animal models", "developmental biology", "model organisms", "molecular development", "cytotoxic t ...	CD4+ T Cells Are as Protective as CD8+ T Cells against Rickettsia typhi Infection by Activating Macrophage Bactericidal Activity	journal.pntd.0005089	null	[ [ "Rickettsiae ( R . ) are small obligate intracellular bacteria that are transmitted to humans by arthropod vectors .", "R . prowazekii and R . typhi represent the two members of the typhus group ( TG ) of Rickettsiae [1 , 2] and are the causative agents of epidemic and endemic typhus , respectively .", ...	[ "Rickettsia typhi is an intracellular bacterium that causes endemic typhus , a febrile disease that can be fatal due to complications including pneumonia , hepatitis and meningoencephalitis , the latter being a regular outcome in T and B cell-deficient C57BL/6 RAG1-/- mice upon Rickettsia typhi infection .", "Her...	[ "Endemic typhus caused by Rickettsia typhi usually is a relatively mild disease .", "However , CNS inflammation and neurological symptoms are complications that can occur in severe cases .", "This outcome of disease is regularly observed in T and B cell-deficient C57BL/6 RAG1-/- mice upon infection with R . typ...	2016

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