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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", "public health and epidemiology", "statistics", "population genetics", "algorithms", "genome analysis tools", "genome databases", "mathematics", "epidemiology", "biology", "metabolic disorders", "computer science", "genetics", "genomics", "computational biology", "genetics ...	Type 2 Diabetes Risk Alleles Demonstrate Extreme Directional Differentiation among Human Populations, Compared to Other Diseases	journal.pgen.1002621	null	[ [ "The global rise in incidence of type 2 diabetes ( T2D ) has been called a pandemic , and is now commonly identified as a major international health concern [1] .", "Although environmental factors play a substantial role in the etiology of T2D , genetic susceptibility has been established as a key compone...	[ "Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations .", "While previous studies have examined population differentiation of alleles at specific SNPs , global ethnic patterns of ensembles of disease risk alleles across human diseases...	[ "We identified 12 risk alleles that had been validated to increase the risk of type 2 diabetes ( T2D ) in five or more different subpopulations .", "These risk alleles share a consistent pattern of decreasing frequencies in the human genomes from Sub-Saharan Africa and through Europe to East Asia regions .", "T...	2012
[ "Introduction", "Material and methods", "Results", "Discussion" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "immunology", "parasitic diseases", "nematode infections", "developmental biology", "molecular development", "cytotoxic t cells", "cell enumeration techniques", "researc...	Altered levels of memory T cell subsets and common γc cytokines in Strongyloides stercoralis infection and partial reversal following anthelmintic treatment	journal.pntd.0006481	null	[ [ "Strongyloides stercoralis ( Ss ) , a soil transmitted nematode that resides in the small intestine of humans , infects approximately 30–100 million people worldwide [1] .", "The clinical manifestations of Ss infection can range from the clinically asymptomatic to , at its most severe , the potentially fa...	[ "CD4+ and CD8+ T cells are central players in immunity to helminth infections .", "However , the role of T cell subsets in human helminth infections is not well understood .", "In addition , the common γc cytokines , IL-2 , IL-4 , IL-7 , IL-9 and IL-15 play an important role in the maintenance of these CD4+ and...	[ "Strongyloides stercoralis ( Ss ) , an intestinal nematode , the causative agent of strongyloidiasis , infects 30–100 million people worldwide .", "Ss infection is often clinically asymptomatic and long lasting due , in large part , to the parasites auto-infective life cycle and their ability to modulate the host...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "cell biology/cell signaling", "physiology", "diabetes and endocrinology/obesity", "physiology/endocrinology", "pharmacology", "diabetes and endocrinology", "biochemistry/transcription and translation", "molecular biology", "cell biology/gene expression", "diabetes and endocrinol...	Metabolic Actions of Estrogen Receptor Beta (ERβ) are Mediated by a Negative Cross-Talk with PPARγ	journal.pgen.1000108	null	[ [ "The estrogen receptors ( ERs ) are members of the nuclear hormone receptor family ( NHR ) which act as eukaryotic ligand-dependent transcription factors .", "ERs are involved in the regulation of embryonic development , homeostasis and reproduction .", "Two major estrogen receptors , alpha and beta (...	[ "Estrogen receptors ( ER ) are important regulators of metabolic diseases such as obesity and insulin resistance ( IR ) .", "While ERα seems to have a protective role in such diseases , the function of ERβ is not clear .", "To characterize the metabolic function of ERβ , we investigated its molecular interactio...	[ "In the present study , we demonstrate for the first time a pro-diabetogenic function of the ERβ .", "Our experiments indicate that ERβ impairs insulin sensitivity and glucose tolerance in mice challenged with a high fat diet ( HFD ) .", "Loss of ERβ , studied in ERβ -/- mice ( βERKO mice ) , results in increas...	2008
[ "Introduction", "Results", "Materials and Methods" ]	[ "molecular biology/bioinformatics", "mathematics/statistics", "computational biology/systems biology", "computational biology/signaling networks" ]	Identification of Crosstalk between Phosphoprotein Signaling Pathways in RAW 264.7 Macrophage Cells	journal.pcbi.1000654	null	[ [ "Cells regulate their function through a complex circuitry that involves myriad interacting networks from intracellular signaling and metabolic pathways to genetic regulatory pathways .", "Intracellular signaling is the first step in translating the environmental cue in regulating various processes e . g ...	[ "Signaling pathways mediate the effect of external stimuli on gene expression in cells .", "The signaling proteins in these pathways interact with each other and their phosphorylation levels often serve as indicators for the activity of signaling pathways .", "Several signaling pathways have been identified in ...	[ "Cellular systems are dynamic in nature , perform various biological functions and can adapt to their environment through compositional and structural remodeling .", "This remodeling is initiated by the binding of external ligands to receptor proteins on the cell surface or other stimuli resulting in the activati...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cardiovascular disorders/coronary artery disease", "genetics and genomics/complex traits", "genetics and genomics/cancer genetics", "genetics and genomics/gene expression" ]	Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression	journal.pgen.1000899	null	[ [ "The chromosome 9p21 . 3 region adjacent to the loci encoding the cyclin-dependent kinase inhibitors CDKN2A ( ENSG00000147889 ) and CDKN2B ( ENSG00000147883 ) is an important susceptibility locus for several diseases with a complex genetic background .", "Recent genome-wide association ( GWA ) studies hav...	[ "Single nucleotide polymorphisms ( SNPs ) on chromosome 9p21 are associated with coronary artery disease , diabetes , and multiple cancers .", "Risk SNPs are mainly non-coding , suggesting that they influence expression and may act in cis .", "We examined the association between 56 SNPs in this region and perip...	[ "Genetic variants on chromosome 9p21 have been associated with several important diseases including coronary artery disease , diabetes , and multiple cancers .", "Most of the risk variants in this region do not alter any protein sequence and are therefore likely to act by influencing the expression of nearby gene...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "public health and epidemiology/global health", "public health and epidemiology/infectious diseases", "infectious diseases/epidemiology and control of infectious diseases" ]	A Bayesian Approach to Quantifying the Effects of Mass Poultry Vaccination upon the Spatial and Temporal Dynamics of H5N1 in Northern Vietnam	journal.pcbi.1000683	null	[ [ "Highly pathogenic avian influenza subtype H5N1 was first identified in Vietnam in December 2003 [1] and was followed by a major wave of outbreaks dispersed widely throughout the country around the 2004 festival of Tê′t , a New Year celebration representing a peak in annual poultry production and consumption ...	[ "Outbreaks of H5N1 in poultry in Vietnam continue to threaten the livelihoods of those reliant on poultry production whilst simultaneously posing a severe public health risk given the high mortality associated with human infection .", "Authorities have invested significant resources in order to control these outb...	[ "Highly pathogenic avian influenza H5N1 continues to spread rapidly between flocks of poultry in many parts of the world including areas in Southeast Asia and Africa where infection has become endemic .", "Meanwhile the number of human cases and fatalities are steadily accumulating .", "As a result , the contro...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "body fluids", "immune cells", "pathology and laboratory medicine", "melioidosis", "immunology", "cell processes", "animal models", "bacterial diseases", "sepsis", "model organisms", "signs and symptoms", "neutrophils", "research and analysi...	Triggering Receptor Expressed on Myeloid Cells (TREM)-2 Impairs Host Defense in Experimental Melioidosis	journal.pntd.0004747	null	[ [ "In sepsis , defined as a deregulated host response to a life-threatening infection , a careful balance between inflammatory and anti-inflammatory responses is vital [1–3] .", "Pathogen- or danger-associated molecular patterns are recognized by intracellular sensory complexes and cell surface receptors ex...	[ "Triggering receptor expressed on myeloid cells ( TREM ) -1 and TREM-2 are key regulators of the inflammatory response that are involved in the clearance of invading pathogens .", "Melioidosis , caused by the \"Tier 1\" biothreat agent Burkholderia pseudomallei , is a common form of community-acquired sepsis in S...	[ "Triggering receptor expressed on myeloid cells ( TREM ) -1 and -2 are receptors on immune cells that act as mediators of the innate immune response .", "It is thought that TREM-1 amplifies the immune response , while TREM-2 acts as a negative regulator .", "Previously , we found that TREM-1 is upregulated in m...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "action potentials", "nervous system", "membrane potential", "brain", "electrophysiology", "neuroscience", "synaptic plasticity", "nerve fibers", "interneurons", "excitatory postsynaptic potentials", "developmental neuroscience", "animal cells", "axons", "...	Plasticity in Single Axon Glutamatergic Connection to GABAergic Interneurons Regulates Complex Events in the Human Neocortex	journal.pbio.2000237	null	[ [ "Evolution has shaped the human neocortex producing microcircuit features that are specific to our species [1] .", "Neuronal density , ultrastructural features , and functional properties of neurons [2–4] reflect specific adaptations in the human neocortex to perform complex and fast signal processing [5–...	[ "In the human neocortex , single excitatory pyramidal cells can elicit very large glutamatergic EPSPs ( VLEs ) in inhibitory GABAergic interneurons capable of triggering their firing with short ( 3–5 ms ) delay .", "Similar strong excitatory connections between two individual neurons have not been found in nonhum...	[ "Many microscale features in the human neocortex—a part of the brain involved in higher functions such as sensory perception , generation of motor commands , spatial reasoning , and language—are closely similar to those reported in experimental animals commonly used in neuroscience , like mice .", "However , the ...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "oxidative stress", "brassica", "light", "plant physiology", "electromagnetic radiation", "plant science", "model organisms", "experimental organism systems", "seedlings", "plants", "research and analysis methods", "arabidopsis thaliana", "plant reproduction", "animal st...	polyamine uptake transporter 2 (put2) and decaying seeds enhance phyA-mediated germination by overcoming PIF1 repression of germination	journal.pgen.1008292	null	[ [ "Seeds are capsules maintaining the plant embryo in a resistant state and promoting plant dispersal .", "To successfully produce a seedling , seeds are able to remain viable over time and block their germination under potentially fatal conditions for the seedling .", "However , over time seeds irremed...	[ "Red light promotes germination after activating phytochrome phyB , which destabilizes the germination repressor PIF1 .", "Early upon seed imbibition , canopy light , unfavorable for photosynthesis , represses germination by stabilizing PIF1 after inactivating phyB .", "Paradoxically , later upon imbibition , c...	[ "Canopy light , unfavorable for photosynthesis , elicits paradoxical responses in seeds .", "Depending on the timing of irradiation upon seed imbibition , canopy light can either block or promote germination .", "The promotion effect is mediated by the light sensor phyA and , intriguingly , it is poorly efficie...	2019
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "molecular probe techniques", "dna-binding proteins", "organisms", "fungi", "model organisms", "experimental organism systems", "molecular biology techniques", "epigenetics", "gel electrophoresis", "chromatin", "schizosaccharomyces", "heterochromatin", "research and analysis methods", "ele...	New insights into donor directionality of mating-type switching in Schizosaccharomyces pombe	journal.pgen.1007424	null	[ [ "The fission yeast S . pombe exists as two haploid cell types , plus ( P ) and minus ( M ) , that differ at the mat1 locus .", "When starved for nitrogen , haploid cells undergo sexual differentiation , mate with the opposite cell type and sporulate .", "These events are driven by master regulators ex...	[ "Mating-type switching in Schizosaccharomyces pombe entails programmed gene conversion events regulated by DNA replication , heterochromatin , and the HP1-like chromodomain protein Swi6 .", "The whole mechanism remains to be fully understood .", "Using a gene deletion library , we screened ~ 3400 mutants for de...	[ "Effects of chromatin structure on recombination can be studied in the fission yeast S . pombe where two heterochromatic loci , mat2 and mat3 , are chosen in a cell-type specific manner to convert the expressed mat1 locus and switch the yeast mating-type .", "The system has previously revealed the determining rol...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "china", "economic analysis", "pathogens", "tropical diseases", "geographical locations", "microbiology", "social sciences", "viruses", "rna viruses", "network analysis", "global health", "neglected tropical diseases", ...	Revisiting the concept of Innovative Developing Countries (IDCs) for its relevance to health innovation and neglected tropical diseases and for the prevention and control of epidemics	journal.pntd.0006469	null	[ [ "Countries have traditionally been divided into two broad categories according to their capacity to innovate: leaders , which have infrastructure along with the human and financial resources for the production and management of innovation; and followers , those that do not have the capacity for innovation and...	[ "Countries have traditionally been split into two major groups: developed or industrialized ( “the North” ) and developing or underdeveloped ( “the South” ) .", "Several authors and organizations have challenged this classification to recognize countries that have reached an intermediate stage of social and econo...	[ "Splitting countries into two groups—rich and poor; developed ( the “North” ) and developing ( the “South” ) ; leaders and followers—appears to us to be progressively more simplistic , unrealistic and a heritage from colonial times .", "Triggered by the first wave of globalization , the share of world income goin...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "animal models of disease", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "animal models", "physiological processes", ...	HIV-1 infection depletes human CD34+CD38- hematopoietic progenitor cells via pDC-dependent mechanisms	journal.ppat.1006505	null	[ [ "Human immunodeficiency virus-1 ( HIV-1 ) infection in patients leads to multi-lineage hematopoietic abnormalities , including anemia , granulocytopenia and thrombocytopenia [1 , 2] .", "Abnormalities in fetal hematopoiesis have also been reported in aborted fetuses from HIV-1 seropositive women [3] .", ...	[ "Chronic human immunodeficiency virus-1 ( HIV-1 ) infection in patients leads to multi-lineage hematopoietic abnormalities or pancytopenia .", "The deficiency in hematopoietic progenitor cells ( HPCs ) induced by HIV-1 infection has been proposed , but the relevant mechanisms are poorly understood .", "We repor...	[ "Multi-lineage hematopoietic abnormalities generally occur during chronic infection which results in a disorder of human leukocyte development and differentiation , contributing to human immunodeficiency virus-1 ( HIV-1 ) -infection induced immune-pathogenesis in AIDS patients .", "Although successful antiretrovi...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome sequencing", "genomics", "genome evolution", "chromosome biology", "genetics", "population genetics", "biology", "evolutionary biology", "genomic evolution", "evolutionary genetics", "genetics and genomics" ]	A High-Resolution View of Genome-Wide Pneumococcal Transformation	journal.ppat.1002745	null	[ [ "Genetic transformation is the process by which cells take up DNA from the environment and integrate the sequence into their genome .", "Over sixty bacterial species , found in both Gram positive and negative phyla , have been shown to be naturally transformable in the laboratory [1] .", "These includ...	[ "Transformation is an important mechanism of microbial evolution through which bacteria have been observed to rapidly adapt in response to clinical interventions; examples include facilitating vaccine evasion and the development of penicillin resistance in the major respiratory pathogen Streptococcus pneumoniae .",...	[ "Transformation is the process by which cells take up DNA from the environment and integrate it into their genome .", "It was first observed in the bacterium Streptococcus pneumoniae , a common cause of pneumonia and meningitis .", "This ability has allowed S . pneumoniae to evolve resistance to penicillin and ...	2012
[ "Introduction", "Methods", "Discussion" ]	[]	Multi-timescale Modeling of Activity-Dependent Metabolic Coupling in the Neuron-Glia-Vasculature Ensemble	journal.pcbi.1004036	null	[ [ "The mammalian brain exhibits remarkable processing power .", "It is at the same time energy efficient .", "The design features that allow such efficient computation are mapped in cellular and molecular components and their roles in information processing .", "Concurrently , these features are anc...	[ "Glucose is the main energy substrate in the adult brain under normal conditions .", "Accumulating evidence , however , indicates that lactate produced in astrocytes ( a type of glial cell ) can also fuel neuronal activity .", "The quantitative aspects of this so-called astrocyte-neuron lactate shuttle ( ANLS )...	[ "The brain has remarkable information processing capacity , yet is also very energy efficient .", "How this metabolic efficiency is achieved given the spatial and metabolic constraints inherent to the designs and energy requirements of brain cells is a fundamental question in neurobiology .", "The major cell cl...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viruses", "mus", "virology", "in vitro", "microbiology", "homo" ]	TRIM E3 Ligases Interfere with Early and Late Stages of the Retroviral Life Cycle	journal.ppat.0040016	null	[ [ "Host cells express specific proteins to interfere with the replication of retroviruses .", "These proteins are referred to as restriction factors and are considered to be a part of an innate or intrinsic immune system [1–5] .", "The interferon inducible cytidine deaminase APOBEC3G is packaged into re...	[ "Members of the TRIpartite interaction Motif ( TRIM ) family of E3 ligases have been shown to exhibit antiviral activities .", "Here we report a near comprehensive screen for antiretroviral activities of 55 TRIM proteins ( 36 human , 19 mouse ) .", "We identified ∼20 TRIM proteins that , when transiently expres...	[ "A lot of excitement in the field of innate immunity to retroviruses such as HIV has come from the discovery of TRIM5 as a key player in cross species restriction .", "TRIM5 belongs to a family of E3 ligases with over 70 members , a number of which have exhibited antiviral activity .", "These findings have led ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mathematics", "saccharomyces", "genetics and genomics", "computational biology" ]	Binding Site Graphs: A New Graph Theoretical Framework for Prediction of Transcription Factor Binding Sites	journal.pcbi.0030090	null	[ [ "Transcription factors ( TFs ) bind short stretches ( usually 6–18 bp ) of DNA near the gene's transcription start site .", "This event is thought to facilitate regulation of expression of the downstream gene through TF interaction with the RNA polymerase and other factors in the pre-initiation complex [1...	[ "Computational prediction of nucleotide binding specificity for transcription factors remains a fundamental and largely unsolved problem .", "Determination of binding positions is a prerequisite for research in gene regulation , a major mechanism controlling phenotypic diversity .", "Furthermore , an accurate d...	[ "A historically difficult problem in computational biology is the identification of transcription factor binding sites ( TFBS ) in the promoters of co-regulated genes .", "With increasing emphasis on research in transcriptional regulation , this problem is also uniquely relevant to emerging results from recent ex...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Hepatitis B Virus Disrupts Mitochondrial Dynamics: Induces Fission and Mitophagy to Attenuate Apoptosis	journal.ppat.1003722	null	[ [ "Hepatitis B virus ( HBV ) infection affects nearly 350 million people worldwide and leads to chronic liver disease , liver failure , and hepatocellular carcinoma ( HCC ) [1] , [2] .", "HBV is an enveloped DNA virus that belongs to the Hepadnavirus family .", "HBV DNA genome encodes four overlapping o...	[ "Human hepatitis B virus ( HBV ) causes chronic hepatitis and is associated with the development of hepatocellular carcinoma .", "HBV infection alters mitochondrial metabolism .", "The selective removal of damaged mitochondria is essential for the maintenance of mitochondrial and cellular homeostasis .", "Her...	[ "Hepatitis B virus ( HBV ) chronic infections represent the common cause for the development of hepatocellular carcinoma .", "Mitochondrial liver injury has been long recognized as one of the consequences of HBV infection during chronic hepatitis .", "Mitochondria are dynamic organelles that undergo fission , f...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "leptospira", "pathology and laboratory medicine", "medical microbiology", "microbial pathogens", "pathogens", "biology and life sciences", "leptospira interrogans", "microbiology", "bacteria", "bacterial pathogens", "organisms" ]	Kinetics of Leptospira interrogans Infection in Hamsters after Intradermal and Subcutaneous Challenge	journal.pntd.0003307	null	[ [ "Leptospirosis is a zoonosis with worldwide distribution caused by spirochetes that are spread by reservoir animals to humans and other accidental hosts .", "Up to 500 , 000 severe human infections are documented annually in tropical areas with an incidence of >10 cases per 100 , 000 population [1]–[3] ."...	[ "Leptospirosis is a zoonosis caused by highly motile , helically shaped bacteria that penetrate the skin and mucous membranes through lesions or abrasions , and rapidly disseminate throughout the body .", "Although the intraperitoneal route of infection is widely used to experimentally inoculate hamsters , this c...	[ "Leptospirosis is the most widespread bacterial infection transmitted from animals to man .", "Humans are exposed to infection when host animals that harbor the bacteria in their kidneys shed them in their urine .", "Human infections , caused by the bacterium Leptospira interrogans , frequently result in a life...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Wolbachia Utilize Host Actin for Efficient Maternal Transmission in Drosophila melanogaster	journal.ppat.1004798	null	[ [ "Wolbachia pipientis is an intracellular α-proteobacterium that forms symbioses with an extremely broad array of hosts , including isopods , nematodes , and insects [1] .", "Wolbachia were first noted in the tissues of the mosquito , Culex pipiens , by Hertig and Wolbach in 1924 , but subsequently , many ...	[ "Wolbachia pipientis is a ubiquitous , maternally transmitted bacterium that infects the germline of insect hosts .", "Estimates are that Wolbachia infect nearly 40% of insect species on the planet , making it the most prevalent infection on Earth .", "The bacterium , infamous for the reproductive phenotypes it...	[ "The world’s most common intracellular infection , Wolbachia pipientis , infects 40% of insect species and is currently used to prevent transmission of Dengue by mosquitoes .", "The bacterium targets the germline of insects , where it is faithfully transmitted to the developing oocyte and the next generation .", ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "cell death", "medicine and health sciences", "muscle tissue", "gene regulation", "cell processes", "population genetics", "immunology", "gene pool", "non-coding rna", "stem cells", "population biology", "small interfering rnas", "animal cells", "proteins", "gene exp...	DUX4-induced dsRNA and MYC mRNA stabilization activate apoptotic pathways in human cell models of facioscapulohumeral dystrophy	journal.pgen.1006658	null	[ [ "Facioscapulohumeral dystrophy ( FSHD ) is a progressive muscular dystrophy caused by mis-expression of the double-homeobox transcription factor DUX4 in skeletal muscle [1] .", "Normally , DUX4 is not expressed in skeletal muscle nor in most somatic tissues examined [2 , 3] .", "Ectopic expression of ...	[ "Facioscapulohumeral dystrophy ( FSHD ) is caused by the mis-expression of DUX4 in skeletal muscle cells .", "DUX4 is a transcription factor that activates genes normally associated with stem cell biology and its mis-expression in FSHD cells results in apoptosis .", "To identify genes and pathways necessary for...	[ "Facioscapulohumeral dystrophy ( FSHD ) is a common form of muscular dystrophy which is currently untreatable .", "It is caused by the inappropriate expression in skeletal muscle of the gene DUX4 that encodes a transcription factor normally expressed in some stem cells .", "When DUX4 is expressed in cultured hu...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "genetic networks", "protein interactions", "protein interaction networks", "brain", "mutation", "mathematics", "network analysis", "genome analysis", "discrete mathematics", "combinatorics", "computer and information sciences", "protein-protein interactions",...	Network Analysis of Genome-Wide Selective Constraint Reveals a Gene Network Active in Early Fetal Brain Intolerant of Mutation	journal.pgen.1006121	null	[ [ "Genetic variation is introduced into the human genome by spontaneously arising de novo mutations in the germline .", "The majority of these mutations have , at most , modest effects on phenotype; they are thus subject to nearly neutral drift and can be transmitted through the population , with some incre...	[ "Using robust , integrated analysis of multiple genomic datasets , we show that genes depleted for non-synonymous de novo mutations form a subnetwork of 72 members under strong selective constraint .", "We further show this subnetwork is preferentially expressed in the early development of the human hippocampus a...	[ "Some genes are extremely intolerant of mutations that alter their amino acid sequence .", "Such mutations are highly likely to drive disease , and previous reports have implicated these genes in multiple diseases .", "To better understand the function of these constrained genes and their place in cellular orga...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biology", "genomics", "neuroscience", "genetics and genomics" ]	Brain-Specific Rescue of Clock Reveals System-Driven Transcriptional Rhythms in Peripheral Tissue	journal.pgen.1002835	null	[ [ "Circadian rhythms are daily oscillations of behavior and physiology that allow organisms to anticipate and respond to predictable daily changes in their environment [1]–[4] .", "In animals , these environmental variables include light , temperature , food availability , and predation .", "As a conseq...	[ "The circadian regulatory network is organized in a hierarchical fashion , with a central oscillator in the suprachiasmatic nuclei ( SCN ) orchestrating circadian oscillations in peripheral tissues .", "The nature of the relationship between central and peripheral oscillators , however , is poorly understood .", ...	[ "Circadian rhythms confer adaptive advantage by allowing organisms to anticipate daily rhythms in their environment , such as light and temperature cycles .", "In mammals , the central circadian time-keeping mechanism resides within the hypothalamus , integrating information from the retina and synchronizing circ...	2012
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "biotechnology", "medicine", "infectious diseases", "model organisms", "genetics", "biology", "microbiology", "molecular cell biology", "genetics and genomics" ]	Cytomegalovirus Replicon-Based Regulation of Gene Expression In Vitro and In Vivo	journal.ppat.1002728	null	[ [ "Herpesviruses are among the most complex DNA viruses , encoding up to 200 genes .", "The characteristic temporal control of viral gene expression ensures the appropriate regulation of the morphogenic process .", "Transcription factors , activated immediately upon virion entry into cells or after reac...	[ "There is increasing evidence for a connection between DNA replication and the expression of adjacent genes .", "Therefore , this study addressed the question of whether a herpesvirus origin of replication can be used to activate or increase the expression of adjacent genes .", "Cell lines carrying an episomal ...	[ "All herpesviruses show a precisely regulated gene expression profile , including true-late genes , which are turned on only after the onset of DNA replication .", "We used this intrinsic viral mechanism to generate a versatile conditional gene expression system that exploits the activity of the murine cytomegalo...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "rna interference", "gene regulation", "membrane proteins", "plant science", "plant pathology", "epigenetics", "cellular structures and organelles", "small interfering rnas", "genetic interference", "proteins", "gene expression", "subcellular localization", "leaves", "ce...	S‐acylation mediates Mungbean yellow mosaic virus AC4 localization to the plasma membrane and in turns gene silencing suppression	journal.ppat.1007207	null	[ [ "Viruses are obligate intracellular parasites that exploit host machineries to propagate and spread in the host .", "Their presence and activity deploy diverse plant mechanisms to combat viral infections at both the cellular and the whole-organism levels .", "Double-stranded ( ds ) RNA forming during ...	[ "RNA silencing plays a critical role in plant resistance against viruses .", "To counteract host defense , plant viruses encode viral suppressors of RNA silencing ( VSRs ) that interfere with the cellular silencing machinery through various mechanisms not always well understood .", "We examined the role of Mung...	[ "Plants have developed small RNA ( siRNA ) -mediated post-transcriptional gene silencing as a defense mechanism against viruses .", "In response , plant viruses encode viral suppressors of RNA silencing ( VSRs ) that can interfere with various steps of the silencing pathway .", "Mungbean yellow mosaic virus ( M...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "chromosome biology", "gene expression", "genetics", "biology and life sciences", "epigenetics", "chromatin", "dna transcription" ]	Uncoupling Transcription from Covalent Histone Modification	journal.pgen.1004202	null	[ [ "Transcription in eukaryotes occurs in the context of chromatin .", "At most genes , transcriptional activation is accompanied by alterations to the chromatin template , exemplified by the enhanced DNase I sensitivity of coding regions and the presence of associated DNase I hypersensitive sites at linked ...	[ "It is widely accepted that transcriptional regulation of eukaryotic genes is intimately coupled to covalent modifications of the underlying chromatin template , and in certain cases the functional consequences of these modifications have been characterized .", "Here we present evidence that gene activation in th...	[ "The proper regulation of gene expression is of fundamental importance in the maintenance of normal growth and development .", "Misregulation of genes can lead to such outcomes as cancer , diabetes and neurodegenerative disease .", "A key step in gene regulation occurs during the transcription of the chromosoma...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "293t cells", "enzymes", "pathogens", "biological cultures", "enzymology", "dna-binding proteins", "microbiology", "viral structure", "plasmid construction", "viruses", "sumoylation", "dna viruses", "dna construction", ...	A genome-wide screen of Epstein-Barr virus proteins that modulate host SUMOylation identifies a SUMO E3 ligase conserved in herpesviruses	journal.ppat.1007176	null	[ [ "The functions of many cellular and viral proteins are controlled by the addition of small ubiquitin-like modifiers ( SUMO ) , in the form of SUMO1 or SUMO2 or SUMO3 chains ( referred to as SUMOylation ) .", "These modifications can affect protein stability or localization and can promote protein-protein ...	[ "Many cellular processes pertinent for viral infection are regulated by the addition of small ubiquitin-like modifiers ( SUMO ) to key regulatory proteins , making SUMOylation an important mechanism by which viruses can commandeer cellular pathways .", "Epstein-Barr virus ( EBV ) is a master at manipulating of ce...	[ "The functions of many cellular proteins important for anti-viral responses and oncogenesis are controlled by modifications by small ubiquitin-like modifiers ( SUMOs ) .", "Here we present the first screen of Epstein-Barr virus ( EBV ) proteins for those that can globally alter SUMO modifications of cellular prot...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	DDX24 Negatively Regulates Cytosolic RNA-Mediated Innate Immune Signaling	journal.ppat.1003721	null	[ [ "The principal purpose of the immediate innate immune response is the rapid synthesis and secretion of type I interferons ( IFNβ and IFNα ) as well as inducing other key host defense genes [1] , [2] .", "Innate immune signaling is initiated by pattern recognition receptors ( PRRs ) that specifically recog...	[ "RIG-I-Like Receptors ( RLRs ) sense cytosolic viral RNA to transiently activate type I IFN production .", "Here , we report that a type I IFN inducible DExD/H helicase , DDX24 , exerts a negative-regulatory effect on RLR function .", "Expression of DDX24 specifically suppressed RLR activity , while DDX24 loss ...	[ "Innate immunity is the first and most rapid host defense against virus infection .", "Viral RNAs , which are generated during RNA virus replication in host cells , can be recognized through RIG-I-Like Receptors ( RLRs ) to transiently produce type I interferon , which further induce abundant interferon stimulate...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "research funding", "medicine and health sciences", "tropical diseases", "parasitic diseases", "health care", "bacterial diseases", "pharmaceutics", "eye diseases", "neglected tropical diseases", "onchocerciasis", "public and occupational health", "infectious diseases", "health systems stren...	Integrated Healthcare Delivery: A Qualitative Research Approach to Identifying and Harmonizing Perspectives of Integrated Neglected Tropical Disease Programs	journal.pntd.0005085	null	[ [ "A major challenge facing health systems in low-resource settings is the often ad-hoc and vertically silo-ed approach to organizational structure .", "Many global health leaders are promoting the integration of vertical programs into a shared delivery infrastructure to strengthen the efficiency , effectiv...	[ "While some evidence supports the beneficial effects of integrating neglected tropical disease ( NTD ) programs to optimize coverage and reduce costs , there is minimal information regarding when or how to effectively operationalize program integration .", "The lack of systematic analyses of integration experienc...	[ "Neglected tropical diseases are a group of parasitic , viral , and bacterial diseases that are often co-endemic in low resource settings .", "Five of these diseases ( lymphatic filariasis , onchocerciasis , schistosomiasis , soil transmitted helminths , and trachoma ) are addressed specifically through a method ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/epidemiology", "infectious diseases/helminth infections", "public health and epidemiology/infectious diseases" ]	Evaluation of a 25-Year-Program for the Control of Schistosomiasis Mansoni in an Endemic Area in Brazil	journal.pntd.0000990	null	[ [ "Schistosomiasis is a social disease , found at poor rural regions and periphery of cities , with a precarious socioeconomic development , where the inhabitants have frequent contact with contaminated waters , as well no available of adequate sewerage system .", "WHO considers schistosomiasis as the secon...	[ "Various studies showed that chemotherapy can control schistosomiasis morbidity , but association of measures ( water supply , sewage disposal and increase of socioeconomic conditions ) is necessary for transmission control .", "A survey dealing with socioeconomic conditions , snail survey , contact with natural ...	[ "A clinical-epidemiological reevaluation on schistosomiasis mansoni was performed in 2005 , in the urban area of a little town , Comercinho , MG , specifically focusing on the inhabitants of the same area in 1981 , when a first survey and treatment with oxamniquine were carried out .", "The surveys included: iden...	2011
[ "Introduction", "Results/Discussion", "Materials & methods" ]	[ "cancer genomics", "medicine and health sciences", "computational biology", "cancers and neoplasms", "basic cancer research", "oncology", "mutation", "genome analysis", "sequence motif analysis", "mutation databases", "frameshift mutation", "research and analysis methods", "sequence analysis...	Recurrent promoter mutations in melanoma are defined by an extended context-specific mutational signature	journal.pgen.1006773	null	[ [ "A major challenge in cancer genomics is the separation of functional somatic driver mutations from non-functional passengers .", "This problem is relevant not only in coding regions , but also in the context of non-coding regulatory regions such as promoters , where putative driver mutations are now mapp...	[ "Sequencing of whole tumor genomes holds the promise of revealing functional somatic regulatory mutations , such as those described in the TERT promoter .", "Recurrent promoter mutations have been identified in many additional genes and appear to be particularly common in melanoma , but convincing functional data...	[ "Cancer is caused by somatic mutations that alter cell behavior .", "While such mutations typically occur in protein-coding genes , recent studies describe individual positions in gene regulatory regions ( promoters ) that are recurrently mutated in many independent tumors .", "This suggests that positive selec...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "forms of evolution", "directed evolution", "evolutionary biology", "chemical biology", "biology" ]	Directed Evolution of a Model Primordial Enzyme Provides Insights into the Development of the Genetic Code	journal.pgen.1003187	null	[ [ "Nature uses monodisperse , sequence-specific polymers to perform a plethora of functions essential to survival .", "While ancient life forms are believed to have harnessed RNA molecules to accelerate vital metabolic reactions [1]–[3] , proteins assumed most catalytic functions in the course of natural ev...	[ "The contemporary proteinogenic repertoire contains 20 amino acids with diverse functional groups and side chain geometries .", "Primordial proteins , in contrast , were presumably constructed from a subset of these building blocks .", "Subsequent expansion of the proteinogenic alphabet would have enhanced thei...	[ "Proteins are linear polymers of a set of typically 20 different amino acid building blocks .", "The amino acid sequence—encoded by a genetic template—directs the folding of newly synthesized proteins into compact 3D structures and dictates the function of the protein product .", "Monomers containing distinct p...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biology", "evolutionary biology" ]	Under-Dominance Constrains the Evolution of Negative Autoregulation in Diploids	journal.pcbi.1002992	null	[ [ "Negative autoregulation is a network motif in which a transcription factor inhibits its own expression .", "Theoretical work has shown that this type of regulation reduces intrinsic noise and quickens the response time to environmental perturbations [1]–[3] and experiments using artificial gene regulator...	[ "Regulatory networks have evolved to allow gene expression to rapidly track changes in the environment as well as to buffer perturbations and maintain cellular homeostasis in the absence of change .", "Theoretical work and empirical investigation in Escherichia coli have shown that negative autoregulation confers...	[ "All genes have to deal with intrinsic noise , and a variety of mechanisms have evolved to reduce it .", "One important mechanism of noise reduction for transcription factors is negative autoregulation , in which a gene product represses its own rate of transcription .", "Negative auotregulation occurs frequent...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "virology/persistence and latency", "virology/viral replication and gene regulation", "genetics and genomics/gene expression", "virology/viruses and cancer", "genetics and genomics/epigenetics" ]	The Epigenetic Landscape of Latent Kaposi Sarcoma-Associated Herpesvirus Genomes	journal.ppat.1000935	null	[ [ "Herpesviruses are able to establish latent infections , enabling them to persist for the lifetime of their host [1] .", "During latency , no viral progeny is produced; instead , the largely quiescent genome persists as an extrachromosomal episome in the nucleus of the infected cell .", "Unfavorable c...	[ "Herpesvirus latency is generally thought to be governed by epigenetic modifications , but the dynamics of viral chromatin at early timepoints of latent infection are poorly understood .", "Here , we report a comprehensive spatial and temporal analysis of DNA methylation and histone modifications during latent in...	[ "A characteristic feature of herpesviruses is their ability to establish a latent infection during which most of the viral genes are silenced .", "As a consequence , no viral progeny is produced and the host cell remains viable .", "While the viral genome may persist in the nucleus of such cells indefinitely , ...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "b vitamins", "children", "medicine and health sciences", "body fluids", "chemical compounds", "geographical locations", "beriberi", "organic compounds", "age groups", "nutrition", "infants", "families", "chemistry", "vitamins", "nutritional deficiencies", "people and places", "blood...	High prevalence of thiamine (vitamin B1) deficiency in early childhood among a nationally representative sample of Cambodian women of childbearing age and their children	journal.pntd.0005814	null	[ [ "Beriberi is a ‘forgotten disease’ [1–4] that remains a public health issue in Southeast Asia despite near eradication elsewhere [5–7] .", "Beriberi is caused by thiamine ( vitamin B1 ) deficiency , and is most serious in infants due to the rapid growth and development that occurs during this time , and t...	[ "Thiamine deficiency is thought to be an issue in Cambodia and throughout Southeast Asia due to frequent clinical reports of infantile beriberi .", "However the extent of this public health issue is currently unknown due to a lack of population-representative data .", "Therefore we assessed the thiamine status ...	[ "Thiamine is an often-overlooked micronutrient of concern in Cambodia and throughout Southeast Asia , where reports of beriberi are not uncommon due to a diet of thiamine-poor , white , polished rice .", "Thiamine plays a critical role in cellular energy generation , and also modulates neuronal and neuromuscular ...	2017
[ "Introduction", "Results", "Discussion", "Methods and materials" ]	[ "velocity", "classical mechanics", "engineering and technology", "statistics", "signal processing", "marmosets", "vertebrates", "social sciences", "neuroscience", "animals", "mammals", "signal filtering", "animal models", "primates", "multivariate analysis", "singular value decompositi...	Detection and analysis of spatiotemporal patterns in brain activity	journal.pcbi.1006643	null	[ [ "Recent advances in brain recording techniques have led to a rapid influx of high spatial- and temporal-resolution datasets of large neural populations [1–4] .", "One of the major challenges in modern neuroscience is to identify and extract important population-level structures and dynamics from these dat...	[ "There is growing evidence that population-level brain activity is often organized into propagating waves that are structured in both space and time .", "Such spatiotemporal patterns have been linked to brain function and observed across multiple recording methodologies and scales .", "The ability to detect and...	[ "Structured activity such as propagating wave patterns at the level of neural circuits can arise from highly variable firing activity of individual neurons .", "This property makes the brain , a quintessential example of a complex system , analogous to other complex physical systems such as turbulent fluids , in ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "microbial metabolism", "neurochemistry", "small molecules", "enzymes", "metabolic networks", "microbiology", "host-pathogen interaction", "bacterial biochemistry", "escherichia coli", "biological systems engineering", "prokaryotic models", "model organisms", "enzyme kineti...	A Kinetic Platform to Determine the Fate of Nitric Oxide in Escherichia coli	journal.pcbi.1003049	null	[ [ "NO• is an uncharged , highly diffusible , membrane-permeable metabolite , generated by mammalian NO• synthases ( NOS ) for use in signaling and defense [1] , [2] .", "The diversity of functions performed by NO• , from pathogen detoxification to vasodilation , reflect its broad reactivity .", "NO• dir...	[ "Nitric oxide ( NO• ) is generated by the innate immune response to neutralize pathogens .", "NO• and its autoxidation products have an extensive biochemical reaction network that includes reactions with iron-sulfur clusters , DNA , and thiols .", "The fate of NO• inside a pathogen depends on a kinetic competit...	[ "Nitric oxide ( NO• ) is a highly reactive metabolite used by immune cells to combat pathogens .", "Since the biological effects of NO• are governed by its broad reactivity , it is desirable to determine how NO• distributes among its many targets inside a cell .", "A quantitative understanding of this distribut...	2013
[ "Introduction", "Methods", "Results", "Discussion", "Conclusion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "animal models of disease", "geographical locations", "microbiology", "saliva", "animals", "animal models", "physiological processes", "model organisms", "salivation", "experimental organism systems", "insect vectors", "dige...	European Aedes albopictus and Culex pipiens Are Competent Vectors for Japanese Encephalitis Virus	journal.pntd.0005294	null	[ [ "Japanese encephalitis is one of the major viral encephalitides in Asia , with an estimated 68 , 000 human cases per year [1] .", "Up to 30% of the symptomatic cases are fatal , and long-term neurologic sequelae can occur in 30 to 50% of survivors [2] .", "Japanese encephalitis virus ( JEV ) is the ca...	[ "Japanese encephalitis virus ( JEV ) is the causative agent of Japanese encephalitis , the leading cause of viral encephalitis in Asia .", "JEV transmission cycle involves mosquitoes and vertebrate hosts .", "The detection of JEV RNA in a pool of Culex pipiens caught in 2010 in Italy raised the concern of a put...	[ "Japanese encephalitis virus ( JEV ) is the leading cause of viral encephalitis in Asia .", "JEV is maintained in a cycle involving mosquitoes and vertebrate hosts , mainly pigs and wading birds .", "Humans can be infected when bitten by an infected mosquito .", "Culex tritaeniorhynchus is the main vector of ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Crosstalk between the Circadian Clock and Innate Immunity in Arabidopsis	journal.ppat.1003370	null	[ [ "Plants are challenged by various pathogens on a daily basis .", "Accumulating evidence implicates a role of the circadian clock in regulating plant innate immunity .", "The circadian clock is the internal time measuring machinery important for plant growth and development .", "However , our under...	[ "The circadian clock integrates temporal information with environmental cues in regulating plant development and physiology .", "Recently , the circadian clock has been shown to affect plant responses to biotic cues .", "To further examine this role of the circadian clock , we tested disease resistance in mutan...	[ "Plants are frequently challenged by various pathogens .", "The circadian clock , which is the internal time measuring machinery , has been implicated in regulating plant responses to biotic cues .", "To better understand the role of the circadian clock in defense control , we tested disease resistance with Ara...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "antimicrobials", "cell walls", "medicine and health sciences", "cell cycle and cell division", "drugs", "cell processes", "immunology", "microbiology", "dna transcription", "antibiotic resistance", "clinical medicine", "antibiotics", "materials science", "pharmacology", "hypersensitivit...	A global regulatory system links virulence and antibiotic resistance to envelope homeostasis in Acinetobacter baumannii	journal.ppat.1007030	null	[ [ "Infections with multidrug-resistant ( MDR ) bacteria pose a serious threat to public health .", "The ability to withstand multiple antibiotic treatments derives from a diverse array of genetic resistance determinants , many of which are deeply intertwined with aspects of microbial physiology including vi...	[ "The nosocomial pathogen Acinetobacter baumannii is a significant threat due to its ability to cause infections refractory to a broad range of antibiotic treatments .", "We show here that a highly conserved sensory-transduction system , BfmRS , mediates the coordinate development of both enhanced virulence and re...	[ "Infections with the hospital-acquired bacterium Acinetobacter baumannii are highly difficult to treat .", "The pathogen has evolved multiple lines of defense against antimicrobial stress , including a barrier-forming cell envelope as well as control systems that respond to antimicrobial stresses by enhancing ant...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biology and life sciences", "medicine and health sciences" ]	De Novo Mutations in Moderate or Severe Intellectual Disability	journal.pgen.1004772	null	[ [ "Intellectual disability ( ID ) is defined by significant impairment of cognitive and adaptive functions with onset before 18 years of age .", "It has an estimated worldwide prevalence of 1–3% , with moderate or severe forms of ID ( IQ<50 ) affecting up to 0 . 5 % of the population in Western countries [1...	[ "Genetics is believed to have an important role in intellectual disability ( ID ) .", "Recent studies have emphasized the involvement of de novo mutations ( DNMs ) in ID but the extent to which they contribute to its pathogenesis and the identity of the corresponding genes remain largely unknown .", "Here , we ...	[ "Intellectual disability ( ID ) is the most frequent severe handicap of childhood .", "Several observations indicate that genetic factors explain a large fraction of cases with ID .", "We and others have recently found that de novo mutations ( DNMs; genetic changes not transmitted from the parents ) represent a...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biofilms", "sequencing techniques", "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "pathogens", "vibrio", "regulatory proteins", "microbiology", "dna-binding proteins", "regulator genes", "vibrio cholerae", "transcription factors", "gene types", ...	ToxR Antagonizes H-NS Regulation of Horizontally Acquired Genes to Drive Host Colonization	journal.ppat.1005570	null	[ [ "Bacteria emerge as pathogens by horizontally acquiring new genetic functions from their environment and neighboring organisms [1 , 2] .", "Vibrio cholerae , the etiological agent of cholera , is a paradigm of this process .", "Benign environmental V . cholerae isolates emerge as pandemic pathogens th...	[ "The virulence regulator ToxR initiates and coordinates gene expression needed by Vibrio cholerae to colonize the small intestine and cause disease .", "Despite its prominence in V . cholerae virulence , our understanding of the direct ToxR regulon is limited to four genes: toxT , ompT , ompU and ctxA .", "Here...	[ "The transcription factor ToxR initiates a virulence regulatory cascade required for V . cholerae to express essential host colonization factors and cause disease .", "Genome-wide expression studies suggest that ToxR regulates many genes important for V . cholerae pathogenesis , yet our knowledge of the direct re...	2016
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biotechnology", "biofuels", "biology", "genomics", "microbiology", "agricultural biotechnology", "genetics and genomics", "agriculture" ]	Comparative Genomic Analysis of the Endosymbionts of Herbivorous Insects Reveals Eco-Environmental Adaptations: Biotechnology Applications	journal.pgen.1003131	null	[ [ "Insects represent one of the most diverse groups of organisms on the planet that can adapt to the extremely diverse eco-environments .", "In particular , herbivorous insects can exploit a wide range of the plant species as food sources [1] .", "Insect gut symbionts play an essential role in the insec...	[ "Metagenome analysis of the gut symbionts of three different insects was conducted as a means of comparing taxonomic and metabolic diversity of gut microbiomes to diet and life history of the insect hosts .", "A second goal was the discovery of novel biocatalysts for biorefinery applications .", "Grasshopper an...	[ "The symbiotic gut microbiome of herbivorous insects is vital for their ability to utilize and specialize on plants with very different nutrient qualities .", "Moreover , the gut microbiome is a significant resource for the discovery of biocatalysts and microbes with applications to various biotechnologies .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Membrane Binding of MinE Allows for a Comprehensive Description of Min-Protein Pattern Formation	journal.pcbi.1003347	null	[ [ "Nature presents an overwhelming variety of forms and patterns .", "While system specific conditions can play an important role for their formation , also a few general principles underlying biological pattern formation have been proposed in the past .", "A particularly attractive concept is the spont...	[ "The rod-shaped bacterium Escherichia coli selects the cell center as site of division with the help of the proteins MinC , MinD , and MinE .", "This protein system collectively oscillates between the two cell poles by alternately binding to the membrane in one of the two cell halves .", "This dynamic behavior ...	[ "Cellular protein structures have long been suggested to form by protein self-organization .", "A particularly clear example is provided by the proteins MinC , MinD , and MinE selecting the center as site of cell division in the rod-shaped bacterium Escherichia coli .", "Based on binding of MinD to the cytoplas...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "genetics and genomics/gene expression", "genetics and genomics/chromosome biology", "evolutionary biology/genomics", "evolutionary biology/bioinformatics" ]	Stochasticity in Protein Levels Drives Colinearity of Gene Order in Metabolic Operons of Escherichia coli	journal.pbio.1000115	Gene order in some bacterial metabolic operons reflects ordering in the metabolic pathway. That this is true uniquely for operons expressed at low levels highlights the selective importance of fluctuations in protein levels.	[ [ "It is well established that the chromosomal distribution of genes is not random , and in many genomes , genes that need to be coexpressed tend to cluster [1]–[4] .", "The coexpression of adjacent genes can be enforced by the action of bidirectional promoters [5] , simultaneous opening and closing of chro...	[ "In bacterial genomes , gene order is not random .", "This is most evident when looking at operons , these often encoding enzymes involved in the same metabolic pathway or proteins from the same complex .", "Is gene order within operons nonrandom , however , and if so why ?", "We examine this issue using meta...	[ "In bacteria , different enzymes from the same metabolic pathway are often encoded within one transcriptional unit , an operon .", "There is also , we show , a tendency for the enzymes that are needed earlier in the pathway to feature earlier in the operon , so-called colinearity .", "Why might this be ?", "W...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "agriculture", "biology" ]	Role of the DSC1 Channel in Regulating Neuronal Excitability in Drosophila melanogaster: Extending Nervous System Stability under Stress	journal.pgen.1003327	null	[ [ "Voltage-gated sodium channels are primarily responsible for the initiation and propagation of action potentials , playing a critical role in regulating neuronal excitability .", "They are members of a superfamily that also includes voltage-gated potassium channels and voltage gated calcium channel [1] ."...	[ "Voltage-gated ion channels are essential for electrical signaling in neurons and other excitable cells .", "Among them , voltage-gated sodium and calcium channels are four-domain proteins , and ion selectivity is strongly influenced by a ring of amino acids in the pore regions of these channels .", "Sodium cha...	[ "Voltage-gated sodium and calcium channels are four-domain proteins that are essential for electrical signaling in neurons and other excitable cells .", "Recent genomic and functional analyses reveal a novel family of four-domain , Ca2+-selective cation channels in a variety of invertebrates , from sea anemones t...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break	journal.pgen.1005653	null	[ [ "Meiotic recombination is a highly regulated process that faithfully repairs programed DSBs , ensuring accurate reductional chromosome segregation at meiosis I[1] .", "Following pre-meiotic DNA replication , Spo11 introduces DSBs across the genome .", "These DSBs are nucleolytically resected , reveali...	[ "The Eukaryotic RecA-like proteins Rad51 and Dmc1 cooperate during meiosis to promote recombination between homologous chromosomes by repairing programmed DNA double strand breaks ( DSBs ) .", "Previous studies showed that Rad51 and Dmc1 form partially overlapping co-foci .", "Here we show these Rad51-Dmc1 co-f...	[ "During meiosis , a specialized form of chromosome segregation ensures that gametes contain only one copy of the parental chromosome complement .", "Accurate segregation of maternal and paternal chromosomes requires them to first become connected in pairs .", "Homologous recombination forms these needed connect...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna replication", "molecular biology/histone modification", "molecular biology/recombination", "molecular biology/centromeres", "molecular biology/chromosome structure", "molecular biology/dna repair" ]	Rad3ATR Decorates Critical Chromosomal Domains with γH2A to Protect Genome Integrity during S-Phase in Fission Yeast	journal.pgen.1001032	null	[ [ "During DNA replication cells are particularly vulnerable to loss of genetic information and mutation [1] .", "The DNA replication checkpoint pathway monitors the genome to detect and stabilize stalled forks , initiate repair , and delay mitotic entry until DNA damage is repaired [2] .", "Checkpoint a...	[ "Schizosaccharomyces pombe Rad3 checkpoint kinase and its human ortholog ATR are essential for maintaining genome integrity in cells treated with genotoxins that damage DNA or arrest replication forks .", "Rad3 and ATR also function during unperturbed growth , although the events triggering their activation and t...	[ "Eukaryotic genomes , which range in size from ∼107 to ∼1011 base pairs , are replicated with nearly absolute fidelity every cell cycle .", "This amazing feat happens despite the frequent stalling or collapse of replication forks .", "The checkpoint kinase ATR is activated by replication fork stalling and phosp...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell’s Viper Bites with Coagulopathy	journal.pntd.0003968	null	[ [ "Snake envenoming is a major health issue in the Asia-Pacific region with between 250 , 000 and 1 million cases occurring annually . [1]", "Russell’s viper ( Daboia russelii ) is one of the most medically important snakes in the region , [1 , 2] with bites causing death in 2 to 5% of cases , accounting fo...	[ "Russell’s viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy .", "This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell’s viper envenoming .", "In a prospective cohort of 146 patients with Russell’s viper envenoming ...	[ "Snake envenoming is an important health issue in many parts of the world and coagulopathy is one of the commonest manifestations .", "Russell’s viper envenoming occurs throughout south-east and south Asia and most commonly causes a venom induced consumption coagulopathy which may be complicated by bleeding .", ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "viruses", "immunoprecipitation", "dna viruses", "viral genome", "inflammasomes", "mammalian genomics", "antibodies", "cellular structures and organelles", ...	Histone H2B-IFI16 Recognition of Nuclear Herpesviral Genome Induces Cytoplasmic Interferon-β Responses	journal.ppat.1005967	null	[ [ "RNA and DNA genomes of viruses are recognized by several host innate immune response sensors in different subcellular locations , resulting in antiviral responses of type 1 interferon ( IFN ) and inflammasome activation [1] .", "We have shown that IFI16 ( interferon inducible protein 16 ) , a resident nu...	[ "IFI16 ( gamma-interferon-inducible protein 16 ) , a predominantly nuclear protein involved in transcriptional regulation , also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β ( IFN-β ) cytokines .", "We have shown that IFI16 , in association with BRCA1 ,...	[ "Eukaryotic cells elicit innate immune responses against invading microbes including viruses .", "IFI16 , a predominantly nuclear protein , has emerged as an innate response nuclear DNA sensor .", "Recognition of nuclear KSHV , HSV-1 and EBV dsDNA genomes by IFI16-BRCA1 leads to IFI16 acetylation , cytoplasmic ...	2016
[ "Introduction", "Results/Discussion", "Conclusion and Prospects", "Methods" ]	[ "population genetics", "biology", "population biology", "genetics and genomics" ]	Population Genomics of Inversion Polymorphisms in Drosophila melanogaster	journal.pgen.1003056	null	[ [ "Since their initial discovery in Drosophila melanogaster [1] , chromosomal inversions have been the topic of many analyses and much speculation .", "A growing body of literature suggests that inversions may play a role in speciation [2] , [3] , local adaptation [4] , and the maintenance of segregation di...	[ "Chromosomal inversions have been an enduring interest of population geneticists since their discovery in Drosophila melanogaster .", "Numerous lines of evidence suggest powerful selective pressures govern the distributions of polymorphic inversions , and these observations have spurred the development of many ex...	[ "Chromosomal inversions are known to respond to powerful natural selection in many species .", "Despite this evidence , little progress has been made towards understanding the nature of selection that affects inversions .", "Here , we utilize two recently released population-resequencing projects from D . melan...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "signal transduction", "cell biology", "nucleic acids", "biology and life sciences", "dna", "nuclear receptor signaling", "molecular cell biology", "cell signaling" ]	Live Cell Imaging Unveils Multiple Domain Requirements for In Vivo Dimerization of the Glucocorticoid Receptor	journal.pbio.1001813	The glucocorticoid receptor's oligomerization state is revealed to not correlate with its activity; this challenges the current prevailing view that this state defines its transcriptional activity.	[ [ "Glucocorticoids influence the activity of almost every cell in mammalian organisms , mainly through binding to the glucocorticoid receptor ( GR ) .", "In the absence of ligand GR primarily localizes in the cytoplasm while the activated GR-ligand complex is mainly nuclear .", "Once in the nucleus , th...	[ "Glucocorticoids are essential for life , but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses .", "Glucocorticoid receptor ( GR ) transcriptional activity and clinical outcome have been linked to its oligomerization state .", "Although a point mutation withi...	[ "The powerful anti-inflammatory and immunosuppressive action of glucocorticoids have made them one of the most prescribed drugs worldwide .", "Unfortunately , acute or chronic treatment may have severe side-effects .", "Glucocorticoids bind to the glucocorticoid receptor ( GR ) , a ligand-dependent transcriptio...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "infectious disease epidemiology", "pathogens", "immunology", "microbiology", "viruses", "preventive medicine", "physiological processes", "vaccines", "rna viruses", "infectious disease control", "vac...	Assessing the stability of polio eradication after the withdrawal of oral polio vaccine	journal.pbio.2002468	null	[ [ "Wild polioviruses ( WPVs ) have been eliminated from all but three countries [1 , 2] by mass vaccination with the oral polio vaccine ( OPV ) .", "The annual burden of paralytic polio infections has been reduced 10 , 000-fold since the start of vaccination efforts [1] .", "OPV has been the preferred v...	[ "The oral polio vaccine ( OPV ) contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts .", "Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10 , 000 or more and ha...	[ "Oral polio vaccine ( OPV ) has played an essential role in the elimination of wild poliovirus ( WPV ) .", "OPV contains attenuated ( weakened ) yet transmissible viruses that can spread from person to person .", "In its attenuated form , this spread is beneficial as it generates population immunity .", "Howe...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "non-clinical medicine/sociology", "infectious diseases/helminth infections", "non-clinical medicine/bioethics", "infectious diseases/neglected tropical diseases" ]	Health Education through Analogies: Preparation of a Community for Clinical Trials of a Vaccine against Hookworm in an Endemic Area of Brazil	journal.pntd.0000749	null	[ [ "In research involving human subjects , the ethical relationship that must be established and maintained between investigators and research subjects is essential to successfully conduct investigational clinical trials of experimental drugs or vaccines , especially ones in which the participants are drawn from...	[ "Obtaining informed consent for clinical trials is especially challenging when working in rural , resource-limited areas , where there are often high levels of illiteracy and lack of experience with clinical research .", "Such an area , a remote field site in the northeastern part of the state of Minas Gerais , B...	[ "Conducting clinical trials of new vaccines in rural , resource-limited areas can be challenging since the people living in these areas often have high levels of illiteracy , little experience with clinical research , and limited access to routine health care .", "Especially difficult is obtaining informed consen...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "biochemistry", "gram negative", "microbial pathogens", "biology", "microbiology", "host-pathogen interaction", "toxic agents", "bacterial biochemistry", "bacterial pathogens", "toxicology", "pathogenesis" ]	Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans	journal.ppat.1003101	null	[ [ "The Gram-negative bacterium Pseudomonas aeruginosa , a pathogen of both plants and metazoans , is a prevalent and pernicious pathogen in persons who are immunocompromised or suffer from cystic fibrosis ( CF ) [1] , [2] .", "P . aeruginosa employs many mechanisms to antagonize its hosts , including the pr...	[ "Pathogenic microbes employ a variety of methods to overcome host defenses , including the production and dispersal of molecules that are toxic to their hosts .", "Pseudomonas aeruginosa , a Gram-negative bacterium , is a pathogen of a diverse variety of hosts including mammals and the nematode Caenorhabditis ele...	[ "The bacterium Pseudomonas aeruginosa is a pathogen of a wide variety of organisms .", "It has been shown that P . aeruginosa factors that are critical for its toxicity to the nematode worm Caenorhabditis elegans are also important for its pathogenicity in mammals .", "In this report we show that phenazines , a...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "geometry", "simulation and modeling", "probability distribution", "mathematics", "protein structure prediction", "protein structure", "research and analysis methods", "proteins", "peptide mapping", "salt bridges", "chemistry", "proteomics", "molecular biology", "probability theory", "di...	Is the Conformational Ensemble of Alzheimer’s Aβ10-40 Peptide Force Field Dependent?	journal.pcbi.1005314	null	[ [ "Aβ peptides linked to the development of Alzheimer’s disease ( AD ) are produced , through a normal cellular proteolysis , in a variety of alloforms , which differ with respect to sequence length and the extent of amino- or C-terminal truncation [1–3] .", "The most abundant form is a 40-residue version A...	[ "By applying REMD simulations we have performed comparative analysis of the conformational ensembles of amino-truncated Aβ10-40 peptide produced with five force fields , which combine four protein parameterizations ( CHARMM36 , CHARMM22* , CHARMM22/cmap , and OPLS-AA ) and two water models ( standard and modified T...	[ "Dependence of protein conformational ensembles on force field parameterizations limits the predictive power of molecular dynamics simulations .", "To address this problem , we evaluated five all-atom force fields for their consistency in reproducing the conformational ensemble of Alzheimer’s Aβ10-40 peptide .", ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "body weight", "medicine and health sciences", "breast tumors", "body fluids", "cancers and neoplasms", "oncology", "mathematics", "forecasting", "statistics (mathematics)", "physiological parameters", "genome analysis", "obesity", "research and analysis ...	Trans-ethnic predicted expression genome-wide association analysis identifies a gene for estrogen receptor-negative breast cancer	journal.pgen.1006727	null	[ [ "Breast cancer is the most common cancer in women in the United States and in the world [1] .", "It is a heterogeneous disease and the two main subgroups of breast cancer are estrogen receptor ( ER ) -positive and ER-negative cancer .", "Genome-wide association studies ( GWAS ) have identified more th...	[ "Genome-wide association studies ( GWAS ) have identified more than 90 susceptibility loci for breast cancer , but the underlying biology of those associations needs to be further elucidated .", "More genetic factors for breast cancer are yet to be identified but sample size constraints preclude the identificatio...	[ "Although individual genetic variant-based genome-wide association studies have greatly increased our understanding of the genetic susceptibility to breast cancer , the genetic variants identified to date account for a relatively small proportion of the heritability .", "Shifting the focus of analysis from indivi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "antimicrobials", "gram negative bacteria", "medicine and health sciences", "genome evolution", "evolutionary biology", "food chains", "infectious disease epidemiology", "plasmids", "population genetics", "microbiology", "gene transfer", "antibiotic resistance", "plant scie...	Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages	journal.pgen.1004776	null	[ [ "Antibiotic resistance among opportunistic pathogens is rapidly rising globally , hampering treatment of infections and increasing morbidity , mortality and health care costs [1] , [2] .", "Of particular concern is the increased incidence of infections caused by Escherichia coli isolates producing extende...	[ "Third-generation cephalosporins are a class of β-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria , especially Escherichia coli .", "Worryingly , the incidence of human infections caused by third-generation cephalosporin-resistant E . coli is increasin...	[ "The rapid global rise of infections caused by Escherichia coli that are resistant to clinically relevant antimicrobials , including third-generation cephalosporins , is cause for concern .", "The intestinal tract of livestock , in particular poultry , is an important reservoir for drug resistant E . coli , but i...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunizations", "immunity", "host-pathogen interaction", "biology", "microbiology", "parasitology" ]	Repeated Exposure to Lutzomyia intermedia Sand Fly Saliva Induces Local Expression of Interferon-Inducible Genes Both at the Site of Injection in Mice and in Human Blood	journal.pntd.0002627	null	[ [ "Leishmania protozoan parasites induce a broad spectrum of disease including cutaneous lesions and visceral leishmaniasis the latter being fatal if not treated .", "L . braziliensis parasites can be transmitted by Lu .", "intermedia sand flies in Central and South America where they are the leading ca...	[ "During a blood meal , Lutzomyia intermedia sand flies transmit Leishmania braziliensis , a parasite causing tegumentary leishmaniasis .", "In experimental leishmaniasis , pre-exposure to saliva of most blood-feeding sand flies results in parasite establishment in absence of any skin damages in mice challenged wi...	[ "Leishmaniasis is a vector-borne parasitic disease of serious public health importance .", "No efficient vaccine is currently available .", "Parasites are transmitted to mammalian hosts during sand fly bites .", "During this process , both parasites and sand fly salivary products are delivered into the skin ....	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/embryology", "genetics and genomics/animal genetics", "neuroscience/sensory systems", "developmental biology/morphogenesis and cell biology", "cell biology/cell signaling", "cell biology/morphogenesis and cell biology", "cell biology/developmental molecular mechanisms", "develop...	Dynamic Coupling of Pattern Formation and Morphogenesis in the Developing Vertebrate Retina	journal.pbio.1000214	In this Research Article, Picker et al. show how cells in the retina get their spatial coordinates.	[ [ "Map-like representation of sensory information is an evolutionary conserved principle of brain organization and function [1] .", "The point-to-point mapping of retinal ganglion cell ( RGC ) axons onto the midbrain tectum/superior colliculus of the vertebrate , is a hallmark example for the requirement of...	[ "During embryonic development , pattern formation must be tightly synchronized with tissue morphogenesis to coordinate the establishment of the spatial identities of cells with their movements .", "In the vertebrate retina , patterning along the dorsal-ventral and nasal-temporal ( anterior-posterior ) axes is req...	[ "The vertebrate brain contains a point-to-point representation of sensory input from the eye .", "This visual map forms during embryonic development , by neuronal cells of the retina sending targeted axon projections to the brain .", "Since the projection needs to wire up neighboring cell positions in the retin...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "arthropods", "eukaryotes", "evolutionary biology", "drosophila", "animals", "insects" ]	Evolution of hydra, a Recently Evolved Testis-Expressed Gene with Nine Alternative First Exons in Drosophila melanogaster	journal.pgen.0030107	null	[ [ "Much of the genetic novelty that accompanies speciation and organismal evolution is driven by reutilization of pre-existing genetic information .", "In an influential essay , Francois Jacob likened evolution to a process of tinkering [1] .", "After the primordial evolution of truly new macromolecules...	[ "We describe here the Drosophila gene hydra that appears to have originated de novo in the melanogaster subgroup and subsequently evolved in both structure and expression level in Drosophila melanogaster and its sibling species .", "D . melanogaster hydra encodes a predicted protein of ~300 amino acids with no ap...	[ "Similar groups of animals have similar numbers of genes , but not all of these genes are the same .", "While some genes are highly conserved and can be easily and uniquely identified in species ranging from yeast to plants to humans , other genes are sometimes found in only a small number or even in a single spe...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Acknowledgments" ]	[ "computational biology/systems biology" ]	Shape, Size, and Robustness: Feasible Regions in the Parameter Space of Biochemical Networks	journal.pcbi.1000256	null	[ [ "Robustness , in the context of biological networks , broadly indicates that the system remains viable under different perturbations .", "Defining robustness in a precise form is a challenging task , given that robustness to different kinds of perturbations , e . g . , environmental variation , intrinsic ...	[ "The concept of robustness of regulatory networks has received much attention in the last decade .", "One measure of robustness has been associated with the volume of the feasible region , namely , the region in the parameter space in which the system is functional .", "In this paper , we show that , in additio...	[ "Developing models with a large number of parameters for describing the dynamics of a biochemical network is a common exercise today .", "The dependence of predictions of such a network model on the choice of parameters is important to understand for two reasons .", "For the purpose of fitting biological data a...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres	journal.pgen.1003859	null	[ [ "During mitosis , different surveillance mechanisms ensure that the replicated genomic material is protected from damage and correctly distributed between the daughter and the mother cells .", "In this way , chromosomal DNA damage triggers a stress response pathway known as the DNA damage checkpoint ( DDC...	[ "When chromosomal DNA is damaged , progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells .", "In Saccharomyces cerevisiae , this cell cycle arrest occurs at the G2/M transition .", "However , it i...	[ "A key aspect of the division of cells is that the genomic material must be carefully duplicated , protected from damage , and correctly distributed during this process .", "When the cells detect problems that affect the integrity or the proper distribution of the genome , they trigger different surveillance mech...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral classification", "immunology", "microbiology", "host-pathogen interaction", "adaptive immunity", "rna viruses", "emerging infectious diseases", "animal models of infection", "biology", "pathogenesis", "viral replication", "immune response", "immunity", "virology", "innate immunity...	Interferon Regulatory Factor-1 (IRF-1) Shapes Both Innate and CD8+ T Cell Immune Responses against West Nile Virus Infection	journal.ppat.1002230	null	[ [ "The rapid triggering of an IFN-αβ response results in the early control of virus infection in mammalian cells .", "Detection of RNA viruses occurs through the recognition of specific sequence motifs , secondary structure , or modification of viral nucleic acids by pattern recognition receptors ( PRR ) in...	[ "Interferon regulatory factor ( IRF ) -1 is an immunomodulatory transcription factor that functions downstream of pathogen recognition receptor signaling and has been implicated as a regulator of type I interferon ( IFN ) -αβ expression and the immune response to virus infections .", "However , this role for IRF-...	[ "Interferon regulatory factor ( IRF ) -1 is a transcription factor that has been implicated in immune regulation and induction of type I IFN gene expression .", "To better understand the contribution of IRF-1 to antiviral immunity , we infected cells and mice lacking IRF-1 with West Nile virus ( WNV ) , an enceph...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequence analysis", "genomics", "functional genomics", "regulatory networks", "biology", "computational biology", "genetics and genomics" ]	High Resolution Genome Wide Binding Event Finding and Motif Discovery Reveals Transcription Factor Spatial Binding Constraints	journal.pcbi.1002638	null	[ [ "Genomic sequences facilitate both cooperative and competitive regulatory factor-factor interactions that implement cellular transcriptional regulatory logic .", "The functional syntax of DNA motifs in regulatory elements is thus an essential component of cellular regulatory control .", "Appropriately...	[ "An essential component of genome function is the syntax of genomic regulatory elements that determine how diverse transcription factors interact to orchestrate a program of regulatory control .", "A precise characterization of in vivo spacing constraints between key transcription factors would reveal key aspects...	[ "The letters in our genome spell words and phrases that control when each gene is activated .", "To understand how these words and phrases function in health and disease , we have developed a new computational method to determine what word positions in our genomic text are used by each genome regulatory protein ,...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Modulation of Network Excitability by Persistent Activity: How Working Memory Affects the Response to Incoming Stimuli	journal.pcbi.1004059	null	[ [ "Memory allows an organism to store information about past events and then use it to modify its behavior in response to future ones .", "As a simple example , consider the classic delayed match-to-sample ( DMS ) task , where the appropriate behavior upon presentation of the test stimulus is conditional on...	[ "Persistent activity and match effects are widely regarded as neuronal correlates of short-term storage and manipulation of information , with the first serving active maintenance and the latter supporting the comparison between memory contents and incoming sensory information .", "The mechanistic and functional ...	[ "Over short time periods , memories are stored by sustained patterns of spiking activity which , once initiated by the stimulus , persist over the entire retention interval .", "How the information stored by such persistent activity is later retrieved is presently unclear .", "Here we propose that , besides tem...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "reverse transcriptase-polymerase chain reaction", "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "immunology", "tropical diseases", "microbiology", "rna extraction", "alphaviruses", "viruses", "chik...	A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus	journal.pntd.0004953	null	[ [ "Chikungunya virus ( CHIKV ) is a mosquito-borne virus belonging to the genus alphavirus , family Togaviridae and spread by Aedes mosquitoes .", "CHIKV is the aetiological agent of chikungunya fever ( CF ) and was first isolated in 1952 from the serum of a febrile patient during an outbreak in Tanzania , ...	[ "Chikungunya virus ( CHIKV ) is a mosquito-borne virus currently transmitted in about 60 countries .", "CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain .", "Detection of the infection is mostly done using RT-RCR or ELISA , which are not suitable for point-of-care ...	[ "CHIKV is transmitted to humans via mosquitos .", "CHIKV induces clinical signs similar to Influenza , Dengue , and Zika viruses .", "We have developed a molecular assay for the detection of CHIKV genome based on isothermal„recombinase polymerase amplification ( RPA ) assay”performed at 42°C .", "The result w...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "ecology and environmental sciences", "ixodes", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "vertebrates", "dogs", "animals", "mammals", "rickettsia", "developmental biology", "nymphs", "si...	Ticks and serosurvey of anti-Rickettsia spp. antibodies in wild boars (Sus scrofa), hunting dogs and hunters of Brazil	journal.pntd.0007405	null	[ [ "The genus Rickettsia ( family Rickettsiaceae; order Rickettsiales ) comprises gram-negative and obligate intracellular bacteria , which are phylogenetically classified into the spotted fever group ( SFG ) rickettsiae , the typhus group rickettsiae , the Rickettsia bellii group rickettsiae and the Rickettsia ...	[ "Rickettsia bacteria are responsible for diseases in humans and animals around the world , however few details are available regarding its ecology and circulation among wild animals and human populations at high transmission risk in Brazil .", "The aim of this study was to investigate the occurrence of ticks and ...	[ "The present study reported serological findings and molecular assays of Rickettsia spp and ticks of wild boars , simultaneous to their correspondent hunting dogs and hunters .", "Seropositivity for Rickettsia spp .", "was higher in wild boars when compared to dogs and humans but was similar between dogs and hu...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "evolutionary biology", "host-pathogen interactions", "coevolution", "microbial evolution", "virology", "viral transmission and infection", "biology and life sciences", "evolutionary adaptation", "micr...	Vertical Transmission Selects for Reduced Virulence in a Plant Virus and for Increased Resistance in the Host	journal.ppat.1004293	null	[ [ "Understanding which factors determine the evolution of virulence–the negative effect of parasites on host fitness [1] , [2] –and how they act , is a long-standing goal in evolutionary biology , and central for the control of infectious diseases [3] , [4] .", "Indeed , changes in virulence have been assoc...	[ "For the last three decades , evolutionary biologists have sought to understand which factors modulate the evolution of parasite virulence .", "Although theory has identified several of these modulators , their effect has seldom been analysed experimentally .", "We investigated the role of two such major factor...	[ "Virulence is a key property of parasites , and is linked to the emergence of new diseases and to the reduction of ecosystem biodiversity .", "Consequently , scientists have devoted a great effort to build theoretical models that predict which factors may modulate virulence evolution .", "However , whether ( an...	2014
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "molecular biology/dna repair" ]	Hypermutability of Damaged Single-Strand DNA Formed at Double-Strand Breaks and Uncapped Telomeres in Yeast Saccharomyces cerevisiae	journal.pgen.1000264	null	[ [ "Accurate DNA synthesis and repair of DNA lesions assure low rates of mutation .", "Genetic defects in either lead to increased , genome-wide mutator phenotypes which can manifest in cancer predisposition [1] .", "Strong mutators can cause reduced fitness due to the accumulation of dysfunctional allel...	[ "The major DNA repair pathways operate on damage in double-strand DNA because they use the intact strand as a template after damage removal .", "Therefore , lesions in transient single-strand stretches of chromosomal DNA are expected to be especially threatening to genome stability .", "To test this hypothesis ...	[ "A variety of error avoidance mechanisms assure low mutation rates across the genome .", "Genetic defects in DNA replication or repair can lead to genome-wide increase in mutation frequency that may result in cancer predisposition and genetic disease .", "Transient localized hypermutability drastically differs ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	JAK/STAT and Hox Dynamic Interactions in an Organogenetic Gene Cascade	journal.pgen.1005412	null	[ [ "Organogenesis is controlled by the activation of complex gene regulatory networks in precise positions of the organism [1] .", "Selector genes , or master regulator genes , encode transcription factors required for the expression of entire organogenetic gene regulatory networks and , when expressed ectop...	[ "Organogenesis is controlled by gene networks activated by upstream selector genes .", "During development the gene network is activated stepwise , with a sequential deployment of successive transcription factors and signalling molecules that modify the interaction of the elements of the network as the organ form...	[ "Organogenesis is controlled by gene networks activated by upstream selector genes .", "To address how the network organization changes during development and how the target genes integrate the genetic information it provides , we analyze in Drosophila the induction of posterior spiracle organogenesis by the Hox ...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "dengue virus", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "cloning", "viruses", "bacterial diseases", "rna viruses", "molecular biology techniques", "cytotoxic t cells", "cell enumeration...	MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection	journal.pntd.0006154	null	[ [ "Dengue virus ( DENV ) and Zika virus ( ZIKV ) are members of Flaviviridae and both are transmitted mostly via mosquito bites .", "It is estimated that around 400 million people are infected with DENV annually[1] .", "DENV infection symptoms range from mild disease , to dengue fever , dengue hemorrhag...	[ "Dengue virus ( DENV ) and Zika virus ( ZIKV ) are members of the Flaviviridae and are predominantly transmitted via mosquito bites .", "Both viruses are responsible for a growing number of infections in tropical and subtropical regions .", "DENV infection can cause lethargy with severe morbidity and dengue sho...	[ "Dengue virus ( DENV ) and Zika virus ( ZIKV ) are responsible for a growing number of infections in tropical and subtropical regions .", "DENV infection can cause dengue shock syndrome leading to death in some cases , while ZIKV is now linked with Guillain-Barré syndrome and congenital anomalies including microc...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "microbiology", "genetics and genomics" ]	Candida albicans Commensalism and Pathogenicity Are Intertwined Traits Directed by a Tightly Knit Transcriptional Regulatory Circuit	journal.pbio.1001510	The identification of regulators, circuits, and target genes employed by the fungus Candida albicans to thrive in disparate niches in a mammalian host reveals interconnection between commensal and pathogenic lifestyles.	[ [ "Mammalian mucosal surfaces harbor trillions of microorganisms from all three domains of life [1]–[4] .", "While most of these microorganisms are harmless ( or beneficial ) to their host , a few of them are able to cross the host's protective barriers and colonize internal organs that offer little apparen...	[ "Systemic , life-threatening infections in humans are often caused by bacterial or fungal species that normally inhabit a different locale in our body , particularly mucosal surfaces .", "A hallmark of these opportunistic pathogens , therefore , is their ability to thrive in disparate niches within the host .", ...	[ "Our skin and mouth , as well as our genital and gastrointestinal tracts , are laden with microorganisms belonging to all three domains of life ( bacteria , archaea , and eukaryotes ) .", "Much of the time these commensal microorganisms are not only harmless but provide advantages to us .", "However , when the ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "genetics and genomics", "genetics and genomics/population genetics" ]	Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene	journal.pgen.1000360	null	[ [ "A large proportion of healthy African Americans have been observed to have a white blood cell count ( WBC ) that is persistently lower than the normal range defined for individuals of European ancestry [1]–[5] .", "This condition , called “benign ethnic neutropenia” , can have important effects on medica...	[ "Persistently low white blood cell count ( WBC ) and neutrophil count is a well-described phenomenon in persons of African ancestry , whose etiology remains unknown .", "We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1 , where ancestry status ( African or European ...	[ "Many African Americans have white blood cell counts ( WBC ) that are persistently below the normal range for people of European descent , a condition called “benign ethnic neutropenia . ”", "Because most African Americans have both African and European ancestors , selected genetic variants can be analyzed to ass...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "nervous system", "neuroscience", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism systems", "nerve fibers", "embryos", "drosophila", "research and analysis methods", ...	A conserved role for Syntaxin-1 in pre- and post-commissural midline axonal guidance in fly, chick, and mouse	journal.pgen.1007432	null	[ [ "Axonal growth and guidance are responsible for the correct formation of neural circuits .", "These processes rely on the tightly regulated response of the growth cone to both diffusible and membrane-bound guidance cues .", "In response to such cues , several intracellular signaling cascades are activ...	[ "Axonal growth and guidance rely on correct growth cone responses to guidance cues .", "Unlike the signaling cascades that link axonal growth to cytoskeletal dynamics , little is known about the crosstalk mechanisms between guidance and membrane dynamics and turnover .", "Recent studies indicate that whereas ax...	[ "Syntaxin-1 is a core factor in tethering synaptic vesicles and mediating their fusion to the cell membrane at the synapse .", "Thus , Syntaxin-1 mediates neurotransmission in the adult nervous system .", "Here we show that this protein is also involved in axonal guidance in the CNS of vertebrates and invertebr...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "cell cycle and cell division", "cell processes", "membrane potential", "electrophysiology", "parasitic protozoans", "mitosis", "trypanosoma brucei", "trypanosoma brucei gambiense", "protozoans", "dna replication", "pharmaceutics", "mitochondria", "dna", "...	Insights into antitrypanosomal drug mode-of-action from cytology-based profiling	journal.pntd.0006980	null	[ [ "Chemotherapy is central to the control of the neglected tropical diseases caused by African trypanosomes ( Trypanosoma brucei spp ) , South American trypanosomes ( Trypanosoma cruzi ) and Leishmania spp; the related kinetoplastid parasites [1] .", "The current drugs suffer problems with complex administr...	[ "Chemotherapy continues to have a major impact on reducing the burden of disease caused by trypanosomatids .", "Unfortunately though , the mode-of-action ( MoA ) of antitrypanosomal drugs typically remains unclear or only partially characterised .", "This is the case for four of five current drugs used to treat...	[ "African trypanosomes cause devastating and lethal diseases in humans and livestock .", "These parasites are transmitted among mammals by tsetse flies and circulate and grow in blood and tissue fluids .", "There are several drugs available to treat patients but , despite their use for many decades , we know rel...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology/epidemiology", "infectious diseases/helminth infections", "public health and epidemiology/infectious diseases", "infectious diseases/respiratory infections", "public health and epidemiology/environmental health", "infecti...	Rapid Identification of Paragonimiasis Foci by Lay Informants in Lao People's Democratic Republic	journal.pntd.0000521	null	[ [ "Paragonimiasis is a food-borne trematodiasis and belongs to the so-called neglected tropical diseases although today an estimated 21 million people are infected [1] and 293 millions are at risk for infection [2] .", "Six of the 40 known species of Paragonimus genus [3] may lead to human infection , and m...	[ "Paragonimiasis is a food-borne trematodiasis leading to lung disease .", "Worldwide , an estimated 21 million people are infected .", "Foci of ongoing transmission remain often unnoticed .", "We evaluated a simple questionnaire approach using lay-informants at the village level to identify paragonimiasis foc...	[ "Paragonimiasis is a neglected pulmonary disease provoked by a food-borne trematode parasite .", "The infection may develop into severe pulmonary disease , often diagnosed with delay and confused with tuberculosis .", "Globally an estimated 21 millions people are infected .", "Human infection is acquired thro...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "enzyme-linked immunoassays", "pathology and laboratory medicine", "body fluids", "immune physiology", "pathogens", "immunology", "microbiology", "viruses", "urine", "lymph nodes", "rna viruses", "lymphatic system", "antibo...	Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues	journal.ppat.1006219	null	[ [ "Zika virus ( ZIKV ) , once a little-studied member of the family Flaviviridae , forcefully emerged across the Western Hemisphere in 2015–16 .", "As of October , 2016 , the Centers for Disease Control and Prevention ( CDC ) lists 60 countries worldwide , including the continental U . S . , that have repor...	[ "Zika virus ( ZIKV ) , an emerging flavivirus , has recently spread explosively through the Western hemisphere .", "In addition to symptoms including fever , rash , arthralgia , and conjunctivitis , ZIKV infection of pregnant women can cause microcephaly and other developmental abnormalities in the fetus .", "W...	[ "Although it was first identified almost 70 years ago , Zika virus had rarely been associated with pathology in humans until the 21st century .", "Recent outbreaks in the South Pacific and the Americas have been characterized by numerous confirmed cases , some involving neurologic sequelae and , of most concern ,...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/pattern formation", "cell biology/morphogenesis and cell biology", "developmental biology/organogenesis", "developmental biology/morphogenesis and cell biology" ]	Arginylation-Dependent Neural Crest Cell Migration Is Essential for Mouse Development	journal.pgen.1000878	null	[ [ "Coordinated cell migration during development is crucial for tissue and organ morphogenesis from early gastrulation to adulthood .", "The largest cell populations that are capable of long-range migration at different developmental stages originate from the neural crest lineage .", "Neural crest cells...	[ "Coordinated cell migration during development is crucial for morphogenesis and largely relies on cells of the neural crest lineage that migrate over long distances to give rise to organs and tissues throughout the body .", "Recent studies of protein arginylation implicated this poorly understood posttranslationa...	[ "Formation of many organs during development depends on the coordinated migration of individual cells and cell layers throughout the embryo .", "The majority of migrating cells originate from the neural crest lineage that gives rise to peripheral neurons , ganglia , pigment cells , and craniofacial structures , a...	2010
[ "Introduction", "Results", "Discussion" ]	[ "genetics", "biology", "computational biology" ]	Leveraging Prior Information to Detect Causal Variants via Multi-Variant Regression	journal.pcbi.1003093	null	[ [ "Next-generation DNA sequencing technologies allow discovery of genetic variants across the full spectrum of allele frequencies , thereby enabling exhaustive screens for association between diseases and variants .", "Numerous statistical methods [1] have been developed for analyzing sequence variants .", ...	[ "Although many methods are available to test sequence variants for association with complex diseases and traits , methods that specifically seek to identify causal variants are less developed .", "Here we develop and evaluate a Bayesian hierarchical regression method that incorporates prior information on the lik...	[ "The decline in DNA sequencing cost permits the interrogation of potentially all variants across the entire allele frequency spectrum for their associations with complex human diseases and traits .", "However , the identification of causal variants remains challenging .", "Existing single variant tests do not d...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "immunology", "biology" ]	Ebola GP-Specific Monoclonal Antibodies Protect Mice and Guinea Pigs from Lethal Ebola Virus Infection	journal.pntd.0001575	null	[ [ "Ebola virus ( EBOV ) is a filovirus causing severe viral haemorrhagic fever in humans and non-human primates ( NHPs ) [1] .", "There are five species of EBOV: Zaire ebolavirus ( ZEBOV ) , Sudan ebolavirus ( SEBOV ) , Cote d'Ivoire ebolavirus ( CIEBOV ) , Reston ebolavirus ( REBOV ) , and Bundibugyo ebola...	[ "Ebola virus ( EBOV ) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90% .", "So far there are no effective treatments available .", "This study evaluates the protective efficacy of 8 monoclonal antibodies ( MAbs ) against Ebola glycoprotein in mice and guinea pigs ."...	[ "Ebola virus ( EBOV ) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90% .", "So far there are no effective treatments available .", "This study evaluates the protective efficacy of 8 monoclonal antibodies ( MAbs ) against the Ebola virus surface glycoprotein , in mic...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Association of the Long Non-coding RNA Steroid Receptor RNA Activator (SRA) with TrxG and PRC2 Complexes	journal.pgen.1005615	null	[ [ "Histone H3 modifications involving lysine 4 trimethylation ( H3K4me3 ) and lysine 27 trimethylation ( H3K27me3 ) represent activating and repressive histone marks , respectively .", "However , when present together , as they are in bivalent sites , they mark genes that are poised for induction .", "G...	[ "Long non-coding RNAs ( lncRNAs ) have been recognized as key players in transcriptional regulation .", "We show that the lncRNA steroid receptor RNA activator ( SRA ) participates in regulation through complex formation with trithorax group ( TrxG ) and polycomb repressive complex 2 ( PRC2 ) complexes .", "Bin...	[ "Long non-coding RNAs ( lncRNAs ) can play an important role in regulation of gene expression .", "In a number of cases , individual lncRNAs have been shown to interact with either the trithorax group ( TrxG ) or polycomb repressive complex 2 ( PRC2 ) protein complexes , which deliver histone modifications associ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "action potentials", "medicine and health sciences", "neurochemistry", "chemical compounds", "depolarization", "membrane potential", "electrophysiology", "neuroscience", "ion channels", "nerve fibers", "neurotransmitters", "sodium channels", "animal cells", "axons", "proteins", "chemis...	Combined Changes in Chloride Regulation and Neuronal Excitability Enable Primary Afferent Depolarization to Elicit Spiking without Compromising its Inhibitory Effects	journal.pcbi.1005215	null	[ [ "Synaptic inhibition regulates transmission of sensory signals through the spinal cord .", "Importantly , numerous chronic pain conditions are associated with diminished inhibition [1–5] and pharmacological blockade of inhibition at the spinal level has been shown to reproduce many features of those chron...	[ "The central terminals of primary afferent fibers experience depolarization upon activation of GABAA receptors ( GABAAR ) because their intracellular chloride concentration is maintained above electrochemical equilibrium .", "Primary afferent depolarization ( PAD ) normally mediates inhibition via sodium channel ...	[ "Postsynaptic GABAAR mediate inhibition by causing hyperpolarization or by preventing ( shunting ) the depolarization caused by concurrent excitatory input .", "Presynaptic GABAAR work differently , in the spinal cord at least .", "Because of their higher-than-equilibrium intracellular chloride concentration , ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "molecular cell biology", "cell biology", "cell adhesion", "microbial pathogens", "biology", "microbiology", "quantitative parasitology", "parasitology" ]	Giardia Flagellar Motility Is Not Directly Required to Maintain Attachment to Surfaces	journal.ppat.1002167	null	[ [ "Giardiasis is caused by acute or chronic infection with the single-celled , zoonotic parasite Giardia intestinalis [1] .", "Giardiasis is one of the most prevalent intestinal protozoal parasitic infections worldwide [2] , resulting in several hundred million acute cases of malabsorptive diarrhea each yea...	[ "Giardia trophozoites attach to the intestinal microvilli ( or inert surfaces ) using an undefined “suction-based” mechanism , and remain attached during cell division to avoid peristalsis .", "Flagellar motility is a key factor in Giardia's pathogenesis and colonization of the host small intestine .", "Specifi...	[ "Giardia is a widespread , single-celled , intestinal parasite that infects millions of people and animals each year .", "Colonization of the small intestine is a critical part of Giardia's life cycle in any host .", "This colonization is initiated when cells attach to the intestinal wall via a specialized suct...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "organismal evolution", "medicine and health sciences", "microbial mutation", "poxviruses", "myxoma virus", "pathology and laboratory medicine", "genome evolution", "insertion mutation", "pathogens", "microbiology", "vertebrates", "rabbits", "animals", "mammals", "animal models", "viru...	Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia	journal.ppat.1006252	null	[ [ "The establishment and spread of Myxoma virus ( MYXV; genus Leporipoxvirus; family Poxviridae ) in the wild European rabbit ( Oryctolagus cuniculus ) population of Australia in 1950 initiated the textbook case study of host-pathogen co-evolution on a continental scale [1 , 2] .", "The virus was novel to t...	[ "The co-evolution of myxoma virus ( MYXV ) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses .", "Although this is the canonical study of the evolution of virulence , whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observe...	[ "Species jumps and subsequent pathogen evolution are of increasing importance in a globally connected world .", "The co-evolution of myxoma virus and the European rabbit following the introduction of the virus into Australia in 1950 is the canonical case of host jumping and host-pathogen co-evolution on a contine...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Large-Scale Phenomics Identifies Primary and Fine-Tuning Roles for CRKs in Responses Related to Oxidative Stress	journal.pgen.1005373	null	[ [ "Receptor protein kinases play key roles in mediating perception of extracellular signals .", "These signals trigger intracellular signalling cascades allowing cells to respond and adapt to internal and external stimuli .", "Receptor kinases contain an extracellular signal-sensing domain connected by ...	[ "Cysteine-rich receptor-like kinases ( CRKs ) are transmembrane proteins characterized by the presence of two domains of unknown function 26 ( DUF26 ) in their ectodomain .", "The CRKs form one of the largest groups of receptor-like protein kinases in plants , but their biological functions have so far remained l...	[ "Receptor-like kinases ( RLKs ) are important regulators in signal transduction in plants .", "However , the large number of RLKs and their high sequence similarity has hampered the analysis of RLKs .", "One of the largest subgroups of RLKs , the cysteine-rich receptor-like kinases ( CRKs ) , has been suggested...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "neurological disorders", "neurology", "genetics", "biology", "genetics and genomics", "cardiovascular" ]	Intracranial Aneurysm Risk Locus 5q23.2 Is Associated with Elevated Systolic Blood Pressure	journal.pgen.1002563	null	[ [ "Intracranial aneurysms ( IA ) are berry-shaped pouches at the branching sites of cerebral arteries .", "2–5% of the world population is estimated to harbor IA [1] .", "Most IA go unnoticed during one's lifetime .", "However , when they become symptomatic , it is usually due to rupture , causing s...	[ "Although genome-wide association studies ( GWAS ) have identified hundreds of complex trait loci , the pathomechanisms of most remain elusive .", "Studying the genetics of risk factors predisposing to disease is an attractive approach to identify targets for functional studies .", "Intracranial aneurysms ( IA ...	[ "When multiple genes or genetic regions contribute to the inherited risk of a disease , it is referred to as a complex disease .", "Genome-wide association studies ( GWAS ) aim to detect common genetic variations that associate with complex traits or diseases .", "Although GWAS have been successful in identifyi...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis	journal.ppat.1005269	null	[ [ "All gram-negative bacteria express fibrous adhesive organelles that mediate targeting to sites of infection .", "The major class of these adhesive pili ( or fimbriae ) is assembled via the classical , alternative and archaic chaperone-usher ( CU ) pathways [1] .", "CU pili are linear polymers made of...	[ "Gram-negative pathogens express fibrous adhesive organelles that mediate targeting to sites of infection .", "The major class of these organelles is assembled via the classical , alternative and archaic chaperone-usher pathways .", "Although non-classical systems share a wider phylogenetic distribution and are...	[ "Gram-negative pathogens depend on fibrous adhesive organelles to attach to target tissues and establish infection .", "The major class of these organelles is assembled via the classical , alternative and archaic chaperone-usher ( CU ) pathways .", "CU pathways are recognized as promising new targets for the ne...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "virology", "microbiology", "molecular biology" ]	Viral Bcl-2-Mediated Evasion of Autophagy Aids Chronic Infection of γHerpesvirus 68	journal.ppat.1000609	null	[ [ "Apoptosis and autophagy , characterized by distinctive morphological and biochemical changes , are tightly regulated processes essential for homeostasis , development , and human diseases [1] , [2] .", "Once triggered by internal inducers , such as DNA damage and viral replication , or by external stimul...	[ "γ-herpesviruses ( γHVs ) have developed an interaction with their hosts wherein they establish a life-long persistent infection and are associated with the onset of various malignancies .", "One critical virulence factor involved in the persistency of murine γ-herpesvirus 68 ( γHV68 ) is the viral homolog of the...	[ "Autophagy ( ‘self-eating’ , lysosome-dependent degradation and recycling of the intracellular components in response to stress ) and apoptosis ( ‘self-killing’ , cells commit suicide in response to stress ) are important host defense mechanisms against viral infections .", "γ-herpesvirus 68 ( γHV68 ) encodes a B...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immune cells", "immune activation", "antigen-presenting cells", "immunity to infections", "immunology", "adaptive immunity", "hepatitis", "immune defense", "hepatitis c", "infectious diseases", "hiv", "t cells", "biology", "immune response", "antigen processing and recogni...	Polyfunctional Type-1, -2, and -17 CD8+ T Cell Responses to Apoptotic Self-Antigens Correlate with the Chronic Evolution of Hepatitis C Virus Infection	journal.ppat.1002759	null	[ [ "The fate of the enormous number of apoptotic cells that derive from effector Tcells undergoing apoptosis after performing their functions during acute or chronic infections remain to be determined [1] , [2] .", "Phagocytosis of apoptotic cells by dendritic cells ( DCs ) leads to the processing of apoptot...	[ "Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8+ T cell responses in various infectious diseases .", "We found that the emergence of a large population of autoreactive CD8+ T effector cells specific for apoptotic T cell-associated self-epitop...	[ "The emergence of a large population of mixed polyfunctional ( type-1 , -2 , -17 ) CD8+ T cell effector responses specific for apoptotic T cell-associated self-epitopes rather than the dysfunction or altered quality of virus-specific CD8+ T cells is associated with the progression toward chronic disease in the huma...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "neural networks", "mathematical models", "neuroscience", "fungal structure", "fungi", "mycelium", "network analysis", "biological transport", "research and analysis methods", "computer and information sciences", "mycology", "mathematical and statistical techniques", "centrality", "biochem...	Comparing two classes of biological distribution systems using network analysis	journal.pcbi.1006428	null	[ [ "Transport networks—which are a subset of complex networks commonly studied using methods from network science [1]—represent structures throughout which entities are transferred between different regions of the system .", "Such networks are prevalent in both the engineered and natural world .", "One c...	[ "Distribution networks—from vasculature to urban transportation pathways—are spatially embedded networks that must route resources efficiently in the face of pressures induced by the costs of building and maintaining network infrastructure .", "Such requirements are thought to constrain the topological and spatia...	[ "Distribution networks such as vasculature systems or urban transportation pathways are prevalent in our world .", "Understanding how different kinds of transport systems are organized to allow for efficient function in their environments and in the presence of constraints on material costs is currently an open a...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "ecology", "genetics", "neglected tropical diseases", "arboviral infections", "biology", "genetics and genomics" ]	Evidence of Habitat Structuring Aedes albopictus Populations in Réunion Island	journal.pntd.0002111	null	[ [ "In recent years , the emergence of arboviruses and some of their vectors has caused major health and economic problems worldwide .", "Chikungunya ( CHIK ) , an arbovirus infection that was not considered to be a major health problem before 2005 , recently caused a major pandemic affecting Africa , Asia a...	[ "Arbovirus vector dynamics and spread are influenced by climatic , environmental and geographic factors .", "Major Chikungunya and Dengue fever outbreaks occurring the last 10 years have coincided with the expansion of the mosquito vector Aedes albopictus to nearly all the continents .", "We characterized the e...	[ "The objective of our research was to study the movements the mosquito Aedes albopictus .", "This mosquito transmits more than 20 viruses to humans throughout the world and is the vector of the recent major epidemics of Dengue and Chikungunya on Reunion Island and the Indian Ocean Region and is , therefore , of g...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "trophozoites", "parasite groups", "lysosomes", "medicine and health sciences", "vesicles", "parasitic protozoans", "parasitology", "physiological processes", "apicomplexa", "protozoans", "cellular structures and organelles", "endosomes", "entamoeba histolytica", "amoebas", "cell membran...	Plasma membrane damage repair is mediated by an acid sphingomyelinase in Entamoeba histolytica	journal.ppat.1008016	null	[ [ "It is well established that the plasma membrane ( PM ) is the most important component of the cell that maintains its integrity and homeostasis during physiological changes .", "However , its integrity is regularly infringed by many mechanical or biochemical factors that endanger cell viability .", "...	[ "Entamoeba histolytica is a pathogen that during its infective process confronts the host defenses , which damages the amoebic plasma membrane ( PM ) , resulting in the loss of viability .", "However , it is unknown whether amoebic trophozoites are able to repair their PM when it is damaged .", "Acid sphingomye...	[ "The host-amoeba relationship is based on a series of interplays between host defense mechanisms and parasite survival strategies .", "While host cells elaborate diverse mechanisms for pathogen elimination , Entamoeba histolytica trophozoites have also developed complex strategies to counteract host immune respon...	2019
[ "Introduction", "Results and Discussion", "Material and Methods" ]	[ "biology", "genomics", "evolutionary biology", "microbiology", "population biology", "genetics and genomics" ]	Patterns of Gene Flow Define Species of Thermophilic Archaea	journal.pbio.1001265	A genomic view of speciation in Archaea shows higher rates of gene flow within coexisting microbial species than between them.	[ [ "Molecular sequence analyses of microbial populations commonly reveal discrete clusters of sequence diversity indicative of closely related , but distinct , coexisting , lineages [1]–[9] .", "Such clusters are sometimes given the status of species , especially when they are shown to be ecologically distin...	[ "Despite a growing appreciation of their vast diversity in nature , mechanisms of speciation are poorly understood in Bacteria and Archaea .", "Here we use high-throughput genome sequencing to identify ongoing speciation in the thermoacidophilic Archaeon Sulfolobus islandicus .", "Patterns of homologous gene fl...	[ "Microorganisms from the bacterial and archaeal domains of the tree of life comprise the greatest breadth of biodiversity on earth .", "Yet the essential evolutionary process of speciation ( through which biodiversity is generated ) is poorly understood in microbes .", "At issue is the fundamental question of w...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "immune cells", "immunology", "microbiology", "parasitology", "disease susceptibility", "neutrophils", "bacterial pathogens", "antibody response", "white blood cells", "inflammation", "animal cells", "medical microbiology", "microbial pathogens", "immune response", "cell...	Evaluation of the Murine Immune Response to Xenopsylla cheopis Flea Saliva and Its Effect on Transmission of Yersinia pestis	journal.pntd.0003196	null	[ [ "Yersinia pestis , the etiologic agent of plague , is adapted to flea-borne transmission and is a highly invasive , virulent pathogen .", "Infected fleas typically transmit small numbers of Y . pestis into the dermis while attempting to feed on a mammalian host .", "The bacteria are able to rapidly di...	[ "Arthropod-borne pathogens are transmitted into a unique intradermal microenvironment that includes the saliva of their vectors .", "Immunomodulatory factors in the saliva can enhance infectivity; however , in some cases the immune response that develops to saliva from prior uninfected bites can inhibit infectivi...	[ "The saliva of blood-feeding arthropods contains a variety of components that prevent blood clotting and interfere with the immune system of the vertebrate host .", "These properties have been shown to enhance or inhibit the transmission of different pathogens transmitted by arthropods .", "Yersinia pestis , th...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion", "Conclusion" ]	[ "biliary system", "medicine and health sciences", "liver", "diagnostic radiology", "fibrosis", "vertebrates", "animals", "mammals", "liver diseases", "magnetic resonance imaging", "developmental biology", "gastroenterology and hepatology", "research and analysis methods", "hamsters", "li...	Magnetic resonance imaging and spectroscopy for differential assessment of liver abnormalities induced by Opisthorchis felineus in an animal model	journal.pntd.0005778	null	[ [ "Two liver fluke species of the genus Opisthorchis—O .", "felineus and O . viverrini—are known as human pathogenic agents .", "This fluke parasite inhabits the bile duct of the host liver , causing local mechanical damage and chronic inflammation , and having general toxic effects on the whole body [1...	[ "European liver fluke Opisthorchis felineus , causing opisthorchiasis disease , is widespread in Russia , Ukraine , Kazakhstan and sporadically detected in the EU countries .", "O . felineus infection leads to hepatobiliary pathological changes , cholangitis , fibrosis and , in severe cases , malignant transforma...	[ "Opisthorchiasis caused by Opisthorchis felineus is a fish-borne parasitic worm infection spread in Russia and some European countries .", "The morbidities provoked by O . felineus infection are cholangitis and bile duct fibrosis .", "Long-term infection is associated with high risk of developing cholangiocarci...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "caffeine", "glycosylamines", "medicine and health sciences", "alkaloids", "pathology and laboratory medicine", "chemical compounds", "physiological parameters", "signs and symptoms", "body temperature", "inosine", "adenosine", "cardiology", "chemistry", "blood pressure", "uridine", "h...	Physiology and effects of nucleosides in mice lacking all four adenosine receptors	journal.pbio.3000161	A study of mice lacking all four adenosine receptors shows that while they mediate effects of uridine, inosine and adenosine, these receptors are dispensable for growth, metabolism, breeding, and body temperature regulation. This suggests that extracellular adenosine is a damage or danger signal, rather than a major re...	[ [ "The nucleoside adenosine is incorporated covalently into many molecules of life , including those involved in information archiving and translation , energy storage and use , regulation of gene expression and function , and intermediary metabolism .", "Free , extracellular adenosine levels are normally l...	[ "Adenosine is a constituent of many molecules of life; increased free extracellular adenosine indicates cell damage or metabolic stress .", "The importance of adenosine signaling in basal physiology , as opposed to adaptive responses to danger/damage situations , is unclear .", "We generated mice lacking all fo...	[ "Elevated extracellular adenosine generally indicates metabolic stress or cell damage and regulates many aspects of physiology .", "We studied “QKO” mice lacking all four adenosine receptors .", "Young QKO mice do not appear obviously ill , but do show decreased survival later in life .", "QKO mice demonstrat...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "messenger rna", "microbiology", "parasitic diseases", "parasitic protozoans", "protozoan life cycles", "developmental biology", "trypomastigotes", "protozoans", "epimastigotes", "cellular structures and organelles", "kinetoplasts", "gene expression", "life ...	Translational repression by an RNA-binding protein promotes differentiation to infective forms in Trypanosoma cruzi	journal.ppat.1007059	null	[ [ "Gene expression regulation is required to balance the synthesis of the necessary protein components that a cell needs to survive , divide or differentiate .", "In eukaryotes , the first layer of regulation is at the level of transcription .", "Beyond this layer of regulation reside several mechanisms...	[ "Trypanosomes , protozoan parasites of medical importance , essentially rely on post-transcriptional mechanisms to regulate gene expression in insect vectors and vertebrate hosts .", "RNA binding proteins ( RBPs ) that associate to the 3’-UTR of mature mRNAs are thought to orchestrate master developmental program...	[ "Trypanosoma cruzi epimastigotes proliferate in the midgut of the hematophagous insect vector .", "Insect vectors can spend long periods of time without feeding , during which epimastigotes differentiate to infective metacyclic trypomastigotes in a process termed metacyclogenesis .", "This metamorphosis involve...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genome-wide association studies", "animal genetics", "statistics", "quantitative traits", "mathematics", "biostatistics", "biology", "heredity", "genetic association studies", "genetics", "human genetics", "genetics of disease", "statistical methods", "genetics and genomics", "complex t...	Polygenic Modeling with Bayesian Sparse Linear Mixed Models	journal.pgen.1003264	null	[ [ "Both linear mixed models ( LMMs ) and sparse regression models are widely used in genetics applications .", "For example , LMMs are often used to control for population stratification , individual relatedness , or unmeasured confounding factors when performing association tests in genetic association stu...	[ "Both linear mixed models ( LMMs ) and sparse regression models are widely used in genetics applications , including , recently , polygenic modeling in genome-wide association studies .", "These two approaches make very different assumptions , so are expected to perform well in different situations .", "However...	[ "The goal of polygenic modeling is to better understand the relationship between genetic variation and variation in observed characteristics , including variation in quantitative traits ( e . g . cholesterol level in humans , milk production in cattle ) and disease susceptibility .", "Improvements in polygenic mo...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "genetics", "biology", "genetics and genomics" ]	A Pre-mRNA–Associating Factor Links Endogenous siRNAs to Chromatin Regulation	journal.pgen.1002249	null	[ [ "Small regulatory RNAs can silence gene expression in the nucleus by establishing repressive chromatin states .", "This process , termed Transcriptional Gene Silencing ( TGS ) , was first observed in plants , where small RNAs direct DNA methylation and histone modifications ( reviewed in [1] ) .", "In...	[ "In plants and fungi , small RNAs silence gene expression in the nucleus by establishing repressive chromatin states .", "The role of endogenous small RNAs in metazoan nuclei is largely unknown .", "Here we show that endogenous small interfering RNAs ( endo-siRNAs ) direct Histone H3 Lysine 9 methylation ( H3K9...	[ "Chromatin consists of DNA and proteins .", "Chromatin can exist in many different states .", "The state of chromatin in highly regulated in order to ensure that genes are expressed correctly .", "RNAs play an important role in the regulation of chromatin .", "For example , in plants and fungi small RNAs dr...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "genetics and genomics/bioinformatics", "genetics and genomics/gene expression" ]	Abundant Quantitative Trait Loci Exist for DNA Methylation and Gene Expression in Human Brain	journal.pgen.1000952	null	[ [ "With the widespread application of highly parallel SNP genotyping arrays much of the recent effort in human genetics has focused on defining the role of genetic variation in disease and physical traits .", "A small subset of this work , however , has attempted to examine the more proximal effects of gene...	[ "A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation , particularly within the context of human tissues .", "We present a set of integrated experiments that investigate the effects of common genetic variability on DNA methylation and mRNA expression i...	[ "In this paper , we describe a comprehensive assessment of the correlation between common genetic variability across the human genome , gene expression , and DNA methylation , within human brain .", "We studied the cerebellum , frontal cortex , temporal cortex , and pons regions of 150 individuals ( 600 tissue sa...	2010

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