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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 and health sciences", "vertebrates", "pigments", "animals", "alleles", "feathers", "epithelial cells", "mutation", "animal anatomy", "stem cells", "materials science", "chromatophores", "zoology", "missense mutation", "birds", "animal cells", "melanocytes", "materials by ...	The evolution of Sex-linked barring alleles in chickens involves both regulatory and coding changes in CDKN2A	journal.pgen.1006665	null	[ [ "Birds show an astonishing variety of plumage coloration and pattern , both across the body as well as on individual feathers .", "The phenotypic diversity in plumage color is due to the distribution of melanin ( both eu- and pheomelanin ) , deposition of carotenoids ( yellow and red colors ) , and struct...	[ "Sex-linked barring is a fascinating plumage pattern in chickens recently shown to be associated with two non-coding and two missense mutations affecting the ARF transcript at the CDKN2A tumor suppressor locus .", "It however remained a mystery whether all four mutations are indeed causative and how they contribu...	[ "Barring patterns on individual feathers are widespread phenomena in a number of wild bird species .", "Still , the genetic background and molecular mechanisms that give rise to barring remains poorly understood .", "Sex-linked barring is a striping pattern present on individual feathers in domestic chickens , ...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "population genetics", "parasitic diseases", "food-borne trematodes", "neglected tropical diseases", "infectious diseases", "genetic polymorphism", "epidemiology", "biology", "public health", "opisthorchiasis", "ecology", "genetics", "gene fl...	Population Genetic Structuring in Opisthorchis viverrini over Various Spatial Scales in Thailand and Lao PDR	journal.pntd.0001906	null	[ [ "The liver fluke , Opisthorchis viverrini is a food-borne trematode endemic in Southeast Asia , including Thailand , Lao PDR , Vietnam and Cambodia with more than 10 million people infected [1] , [2] , [3] .", "Infection occurs by eating raw or uncooked cyprinid fish containing metacercariae [4] , [5] .",...	[ "Khon Kaen Province in northeast Thailand is known as a hot spot for opisthorchiasis in Southeast Asia .", "Preliminary allozyme and mitochondrial DNA haplotype data from within one endemic district in this Province ( Ban Phai ) , indicated substantial genetic variability within Opisthorchis viverrini .", "Here...	[ "Infection with the liver fluke ( Opisthorchis viverrini ) is a risk factor for cholangiocarcinoma ( CCA ) , which is highly prevalent in Khon Kaen Province , Thailand .", "Within this Province , there is considerable variation in the epidemiology of opisthorchiasis among districts .", "Preliminary allozyme and...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "chemical compounds", "immunology", "blood groups", "carbohydrates", "animals", "organic compounds", "parasitic diseases", "nematode infections", "materials science", "materials physics", "sedimentation", "proteins", "chem...	Characterization of novel bangle lectin from Photorhabdus asymbiotica with dual sugar-binding specificity and its effect on host immunity	journal.ppat.1006564	null	[ [ "Photorhabdus is a genus of three species belonging to the gram-negative entomopathogenic bacteria of the family Morganellaceae .", "Unlike the other two species of the genus , P . asymbiotica is not only an insect pathogen .", "Using a still poorly understood mechanism , P . asymbiotica can infect hu...	[ "Photorhabdus asymbiotica is one of the three recognized species of the Photorhabdus genus , which consists of gram-negative bioluminescent bacteria belonging to the family Morganellaceae .", "These bacteria live in a symbiotic relationship with nematodes from the genus Heterorhabditis , together forming a comple...	[ "Photorhabdus asymbiotica , originally isolated in 1989 from a patient in the USA , was revealed to be not only effective insect pathogen but also bacteria causing serious and difficultly treatable diseases in humans .", "The genome of P . asymbiotica is being intensively studied but little is known about the det...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/functional genomics", "genetics and genomics/nuclear structure and function", "molecular biology/chromosome structure", "cell biology/nuclear structure and function" ]	Replication Timing of Human Telomeres Is Chromosome Arm–Specific, Influenced by Subtelomeric Structures and Connected to Nuclear Localization	journal.pgen.1000920	null	[ [ "Cell proliferation potential is a critical attribute that directly influences embryogenesis , development and growth .", "For instance , insufficient proliferation capacity compromises organogenesis , tissue regeneration and repair , while unrestrained cell proliferation promotes cancer progression [1] ....	[ "The mechanisms governing telomere replication in humans are still poorly understood .", "To fill this gap , we investigated the timing of replication of single telomeres in human cells .", "Using in situ hybridization techniques , we have found that specific telomeres have preferential time windows for replica...	[ "Functional telomeres are essential for genome stability .", "While replication of telomeres has been extensively studied in model organisms such as the baker's yeast , little is known about the mechanisms that govern the replication of human telomeres .", "In this study , we have determined the timing of repli...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "mathematics", "statistics", "proteomics", "biology", "cardiovascular" ]	Computational Biomarker Pipeline from Discovery to Clinical Implementation: Plasma Proteomic Biomarkers for Cardiac Transplantation	journal.pcbi.1002963	null	[ [ "After the first successful human-to-human heart transplant in 1967 , cardiac transplantation became the primary therapy for patients with end-stage heart failure due to dilated cardiomyopathy or ischemic heart disease .", "Improvements in immunosuppressive drug therapies have significantly increased the ...	[ "Recent technical advances in the field of quantitative proteomics have stimulated a large number of biomarker discovery studies of various diseases , providing avenues for new treatments and diagnostics .", "However , inherent challenges have limited the successful translation of candidate biomarkers into clinic...	[ "Novel proteomic technology has led to the generation of vast amounts of biological data and the identification of numerous potential biomarkers .", "However , computational approaches to translate this information into knowledge capable of impacting clinical care have been lagging .", "We propose a computation...	2013
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "applied microbiology", "virology", "medical microbiology", "emerging viral diseases", "microbial pathogens", "biology", "microbiology", "viral disease diagnosis" ]	Second International Diagnostic Accuracy Study for the Serological Detection of West Nile Virus Infection	journal.pntd.0002184	null	[ [ "West Nile virus ( WNV ) is a mosquito-transmitted flavivirus of the family Flaviviridae [1] .", "It is maintained in a cycle between birds and mosquitoes mostly belonging to the Culex genus [2] .", "Ochlerotatus , Culiseta , and Aedes mosquitoes are also competent vectors [2] .", "Besides horses ...	[ "In recent decades , sporadic cases and outbreaks in humans of West Nile virus ( WNV ) infection have increased .", "Serological diagnosis of WNV infection can be performed by enzyme-linked immunosorbent assay ( ELISA ) , immunofluorescence assay ( IFA ) neutralization test ( NT ) and by hemagglutination-inhibiti...	[ "West Nile virus ( WNV ) is mantained in the environment in a cycle between mosquitoes and birds .", "The virus has been isolated on almost all the continents , and several migratory bird species are primarily responsible for virus spread and dispersal .", "Humans acquire the infection through WNV-infected mosq...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "skin", "invertebrates", "medicine and health sciences", "rna interference", "classical mechanics", "integumentary system", "pathology and laboratory medicine", "heavy metals", "toxins", "caenorhabditis", "pathogens", "microbiology", "mechanical stress", "animals", "toxicology", "toxic...	Hypodermal responses to protein synthesis inhibition induce systemic developmental arrest and AMPK-dependent survival in Caenorhabditis elegans	journal.pgen.1007520	null	[ [ "The differing phenotypes stemming from the loss of essential cellular functions , such as protein synthesis , are specific to the time in life ( development or adulthood ) when the deficit occurs .", "Under such deficits , arresting development is an established strategy at the disposal of animals to ens...	[ "Across organisms , manipulation of biosynthetic capacity arrests development early in life , but can increase health- and lifespan post-developmentally .", "Here we demonstrate that this developmental arrest is not sickness but rather a regulated survival program responding to reduced cellular performance .", ...	[ "Protein synthesis is an essential cellular process , but post-developmental reduction of protein synthesis across multiple species leads to improved health- and lifespan .", "To better understand the physiological responses to impaired protein synthesis , we characterize a novel developmental arrest state that o...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biophysics/theory and simulation", "biochemistry/theory and simulation" ]	Circadian KaiC Phosphorylation: A Multi-Layer Network	journal.pcbi.1000568	null	[ [ "Cyanobacteria are the simplest organisms known that exhibit circadian rhythms .", "The endogenous timing system coordinates a wide range of cellular processes in cyanobacteria to the day-night cycle , including genome-wide expression [1] .", "For individual cyanobacterial cell , the circadian clock i...	[ "Circadian KaiC phosphorylation in cyanobacteria reconstituted in vitro recently initiates a series of studies experimentally and theoretically to explore its mechanism .", "In this paper , we report a dynamic diversity in hexameric KaiC phosphoforms using a multi-layer reaction network based on the nonequivalenc...	[ "Circadian clocks are endogenous timing mechanisms that allow living organisms to coordinate their activities with daily environmental fluctuations .", "In cyanobacteria , almost all the genes are rhythmically expressed with the same ∼24 h period yet exhibit a variety of phase relationships and waveforms .", "R...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "gene regulation", "regulatory proteins", "dna-binding proteins", "light microscopy", "dna transcription", "physiological processes", "fungi", "model organisms", "homeostasis", "microscopy", "experimental organism systems", "transcription ...	A fungal ABC transporter FgAtm1 regulates iron homeostasis via the transcription factor cascade FgAreA-HapX	journal.ppat.1007791	null	[ [ "Iron is an essential element for growth , and can be present in various forms such as iron ions , heme and iron sulfur clusters that play critical roles in respiration , DNA synthesis and repair , ribosome biogenesis , metabolism and other cellular processes in all organisms [1–3] .", "In mammals , iron ...	[ "Iron homeostasis is important for growth , reproduction and other metabolic processes in all eukaryotes .", "However , the functions of ATP-binding cassette ( ABC ) transporters in iron homeostasis are largely unknown .", "Here , we found that one ABC transporter ( named FgAtm1 ) is involved in regulating iron...	[ "Essential element iron plays important roles in many cellular processes in all organisms .", "The function of an ATP-binding cassette ( ABC ) transporter Atm1 in iron homeostasis has been characterized in Saccharomyces cerevisiae .", "Our study found that FgAtm1 regulates iron homeostasis via the transcription...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Growth factor independent-1 Maintains Notch1-Dependent Transcriptional Programming of Lymphoid Precursors	journal.pgen.1003713	null	[ [ "Growth factor independent-1 ( Gfi1 ) is a transcriptional repressor originally identified as a common proviral insertion site of the murine Moloney leukemia virus ( MMLV ) that conferred IL-2 independent growth to IL-2 dependent T-cell lymphomas [1] .", "Subsequently , Gfi1 was identified as the most com...	[ "Growth factor independent 1 ( Gfi1 ) is a transcriptional repressor originally identified as a gene activated in T-cell leukemias induced by Moloney-murine-leukemia virus infection .", "Notch1 is a transmembrane receptor that is frequently mutated in human T-cell acute lymphoblastic leukemia ( T-ALL ) .", "Gfi...	[ "Understanding the mechanisms that protect lymphoid cells from transformation is a critical first step in developing therapies against blood cancers .", "Recently , we demonstrated that the Growth factor independent-1 transcriptional repressor protein is required for cancer development driven by activation of Not...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "animal models", "meta-research article", "peer review", "medicine and health sciences", "clinical medicine", "drug research and development", "phase i clinical investigation", "clinical trials", "phase ii clinical investigation", "experimental organism systems", "safety studies", "pharmacolog...	Preclinical efficacy studies in investigator brochures: Do they enable risk–benefit assessment?	journal.pbio.2004879	null	[ [ "Early phase human studies ( phase I and II trials ) aim to establish the safety , rationale , and conditions for testing new drugs in rigorous , randomized controlled phase III trials .", "Because early phase human studies expose human research subjects to unproven—and in some cases previously untested—i...	[ "Human protection policies require favorable risk–benefit judgments prior to launch of clinical trials .", "For phase I and II trials , evidence for such judgment often stems from preclinical efficacy studies ( PCESs ) .", "We undertook a systematic investigation of application materials ( investigator brochure...	[ "To make a clinical trial ethical , regulatory agencies and institutional review boards have to judge whether the trial-related benefits ( the knowledge gain ) outweigh the trial-inherent risks .", "For early-phase human research , these risk–benefit assessments are often based on evidence from preclinical animal...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "population dynamics", "tropical diseases", "geographical locations", "argentina", "spatial epidemiology", "parasitic diseases", "peru", "neglected tropical diseases", "population biology", "infectious diseases", "zoonoses", "south america", "epidemiology", ...	Exploring Spatial and Temporal Distribution of Cutaneous Leishmaniasis in the Americas, 2001–2011	journal.pntd.0005086	null	[ [ "Leishmaniasis is an important health problem for several countries in the Americas .", "It is caused by different species of protozoans of the genus Leishmania and transmitted to humans and animals by insect vectors of the Psycodidae family infected during blood feeding on vertebrate reservoirs and hosts...	[ "Cases reported in the period of 2001–2011 from 14/18 CL endemic countries were included in this study by using two spreadsheet to collect the data .", "Two indicators were analyzed: CL cases and incidence rate .", "The local regression method was used to analyze case trends and incidence rates for all the stud...	[ "In the Americas , cutaneous leishmaniasis ( CL ) cases are notified across a wide geographic area , extending from southern United States to northern Argentina .", "Currently , 70–75% of all estimated cases of CL worldwide occur in ten countries , including four in the Americas ( Brazil , Colombia , Nicaragua , ...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cystic echinococcosis", "invertebrates", "palestinian territories", "medicine and health sciences", "pathology and laboratory medicine", "helminths", "tropical diseases", "geographical locations", "vertebrates", "parasitic diseases", "animals", "mammals", "surgical and invasive medical proc...	The clinical burden of human cystic echinococcosis in Palestine, 2010-2015	journal.pntd.0005717	null	[ [ "Cystic Echinococcosis ( CE ) is a zoonotic parasitic infection caused by the metacestode larval stage of species within the genus Echinococcus .", "CE as the most frequently encountered disease is caused by Echinococcus granulosus sensu lato ( s . l . ) with the dog as the main definitive host and ungula...	[ "Cystic echinococcosis ( CE ) is classified by the WHO as a neglected disease inflicting economic losses on the health systems of many countries worldwide .", "The aim of this case-series study was to investigate the burden of human CE in Palestine during the period between 2010 and 2015 .", "Records of surgica...	[ "Cystic echinococcosis ( CE ) is a neglected disease caused by a parasite called Echinococcus granulosus .", "The dog as a definitive host plays a major role in transmitting the infection to human .", "The study aimed to investigate the clinical burden of human CE in Palestine during the period between 2010 and...	2017
[ "Introduction", "Results and discussion", "Conclusions", "Methods" ]	[ "taxonomy", "census", "research design", "data management", "phylogenetics", "metagenomics", "genome analysis", "bacteria", "research and analysis methods", "sequence analysis", "computer and information sciences", "genomics", "sequence alignment", "bioinformatics", "biological databases...	A census-based estimate of Earth's bacterial and archaeal diversity	journal.pbio.3000106	A massive survey of Earth's Bacteria and Archaea reveals that their diversity is orders of magnitude lower than previously thought. The study also indicates that extinctions played an important role in prokaryotic evolution.	[ [ "Microorganisms are the most ancient and the most widespread form of life on Earth , inhabiting virtually every ecosystem and driving the bulk of global biogeochemical cycles .", "Culture-independent methods such as amplicon sequencing of 16S ribosomal RNA genes revealed the existence of a potentially vas...	[ "The global diversity of Bacteria and Archaea , the most ancient and most widespread forms of life on Earth , is a subject of intense controversy .", "This controversy stems largely from the fact that existing estimates are entirely based on theoretical models or extrapolations from small and biased data sets .",...	[ "The global diversity of Bacteria and Archaea ( \"prokaryotes\" ) , the most ancient and most widespread forms of life on Earth , is subject to high uncertainty .", "Here , to estimate the global diversity of prokaryotes , we analyzed a large number of 16S ribosomal RNA gene sequences , found in all prokaryotes a...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "cell physiology", "vero cells", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "biological cultures", "immunology", "microbiology", "reoviruses", "plasmid construction", "viruses", "rna viruses", "dna construction",...	Cell–cell fusion induced by reovirus FAST proteins enhances replication and pathogenicity of non-enveloped dsRNA viruses	journal.ppat.1007675	null	[ [ "Proteins of the fusion-associated small transmembrane ( FAST ) family , which are encoded by some members of the Reoviridae family , are the only viral fusogenic proteins known in non-enveloped viruses , which do not require fusion to enter the host cell [1] .", "FAST proteins are small ( 95–198 amino ac...	[ "Fusogenic reoviruses encode fusion-associated small transmembrane ( FAST ) protein , which induces cell–cell fusion .", "FAST protein is the only known fusogenic protein in non-enveloped viruses , and its role in virus replication is not yet known .", "We generated replication-competent , FAST protein-deficien...	[ "Among diverse viral proteins of non-enveloped viruses , only FAST protein encoded by fusogenic reoviruses belonging to the family Reoviridae induces cell–cell fusion during viral replication cycle .", "Unlike enveloped viruses , non-enveloped viruses do not require fusion proteins to enter cells .", "Although ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "drosophila", "biochemistry", "computational biology", "cell biology" ]	PERIOD–TIMELESS Interval Timer May Require an Additional Feedback Loop	journal.pcbi.0030154	null	[ [ "Circadian rhythmicity is the product of a robust [1] , free-running , temperature-compensated [2] , and adaptable [3 , 4] biological clock found in diverse organisms ranging from bacteria to humans .", "The model organism Drosophila is commonly used to study this phenomenon due to the relative ease of ex...	[ "In this study we present a detailed , mechanism-based mathematical framework of Drosophila circadian rhythms .", "This framework facilitates a more systematic approach to understanding circadian rhythms using a comprehensive representation of the network underlying this phenomenon .", "The possible mechanisms ...	[ "The ability of an organism to adapt to daily changes in the environment , via a circadian clock , is an inherently interesting phenomenon recently connected to several human health issues .", "Decades of experiments on one of the smallest model animals , the fruit fly Drosophila , has illustrated significant sim...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology and life sciences", "computer and information sciences" ]	Metadynamics Simulations Reveal a Na+ Independent Exiting Path of Galactose for the Inward-Facing Conformation of vSGLT	journal.pcbi.1004017	null	[ [ "Secondary active transporters are membrane proteins involved in the translocation of small organic molecules across the cellular membrane using the energy stored as transmembrane electrochemical gradient of ions ( mostly Na+ or H+ ) .", "Sodium symporters in particular use this alkali metal ion to cotran...	[ "Sodium-Galactose Transporter ( SGLT ) is a secondary active symporter which accumulates sugars into cells by using the electrochemical gradient of Na+ across the membrane .", "Previous computational studies provided insights into the release process of the two ligands ( galactose and sodium ion ) into the cytopl...	[ "Membrane proteins are crucial for the communication of the cell with the environment .", "Among these , symporters are in charge of the transport of molecules ( like sugars , amino acids , osmolytes ) inside the cells , exploiting the concentration gradient of an ion to perform the task .", "Here we investigat...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "messenger rna", "bifurcation theory", "vertebrates", "light", "animals", "electromagnetic radiation", "mammals", "circadian oscillators", "animal models", "drosophila melanogaster", "model organisms", "systems science", "mathematics", "experimental organism systems", ...	A saturated reaction in repressor synthesis creates a daytime dead zone in circadian clocks	journal.pcbi.1006787	null	[ [ "Circadian clocks in various organisms are composed of cell autonomous gene expression rhythms with a nearly 24-hour period .", "Transcriptional-translational feedback loops ( TTFL ) in single cells drive such rhythmic gene expression [1–3] .", "One of the most important roles of circadian clocks is t...	[ "Negative feedback loops ( NFLs ) for circadian clocks include light-responsive reactions that allow the clocks to shift their phase depending on the timing of light signals .", "Phase response curves ( PRCs ) for light signals in various organisms include a time interval called a dead zone where light signals ca...	[ "Light-entrainable circadian clocks form behavioral and physiological rhythms in organisms .", "The light-entrainment properties of these clocks have been studied by measuring phase shifts caused by light pulses administered at different times .", "The phase response curves of various organisms include a time w...	2019
[ "Introduction", "Methodology", "Results", "Discussion" ]	[]	Inter-epidemic Acquisition of Rift Valley Fever Virus in Humans in Tanzania	journal.pntd.0003536	null	[ [ "Rift Valley fever ( RVF ) is one of the major viral zoonoses in Africa .", "The disease is caused by the Rift Valley fever virus ( RVFV ) of the genus Phlebovirus in the family Bunyaviridae [1] , and it is transmitted to animals through infectious mosquito bites and other arthropod vectors [2] .", "P...	[ "In East Africa , epidemics of Rift Valley fever ( RVF ) occur in cycles of 5–15 years following unusually high rainfall .", "RVF transmission during inter-epidemic periods ( IEP ) generally passes undetected in absence of surveillance in mammalian hosts and vectors .", "We studied IEP transmission of RVF and e...	[ "Rift Valley fever ( RVF ) is a disease of animals and people that is caused by the RVF virus .", "During epidemics , humans get RVF through direct contact with animals or through mosquito bites .", "In East Africa , epidemics occur every 5–15 years following unusually high rainfall .", "In between epidemics ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "reverse transcriptase-polymerase chain reaction", "sequencing techniques", "molecular probe techniques", "gene regulation", "northern blot", "micrornas", "methylation", "immunoprecipitation", "molecular biology techniques", "seedlings", "rna sequencing", "plants", "gel electrophoresis", "...	ARGONAUTE10 promotes the degradation of miR165/6 through the SDN1 and SDN2 exonucleases in Arabidopsis	journal.pbio.2001272	null	[ [ "Arabidopsis ARGONAUTE10 ( AGO10 ) , also known as ZWILLE ( ZLL ) or PINHEAD ( PNH ) , maintains stem cell homeostasis in the shoot apical meristem ( SAM ) and floral meristems through repression of miR165/6 activity [1–5] .", "The conserved miR165/6 family acts through AGO1 to downregulate the type III h...	[ "The degradation of small RNAs in plants and animals is associated with small RNA 3′ truncation and 3′ uridylation and thus relies on exonucleases and nucleotidyl transferases .", "ARGONAUTE ( AGO ) proteins associate with small RNAs in vivo and are essential for not only the activities but also the stability of ...	[ "MicroRNAs ( miRNAs ) are 21–24 nucleotide regulatory RNAs that impact nearly all biological processes in plants and animals .", "The abundance of miRNAs is determined by their biogenesis and degradation .", "miRNA degradation is associated with trimming and tailing of their 3′ ends .", "The relationship betw...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/comparative sequence analysis", "evolutionary biology/bioinformatics", "evolutionary biology/evolutionary and comparative genetics" ]	The Emergence and Fate of Horizontally Acquired Genes in Escherichia coli	journal.pcbi.1000059	null	[ [ "The wide variation in bacterial genome sizes was originally detected in the 1960s by DNA reassociation analyses [1] .", "And because bacteria have gene dense chromosomes , the differences in genome sizes implied that there were likely to be vast differences in the gene contents of bacterial species .", ...	[ "Bacterial species , and even strains within species , can vary greatly in their gene contents and metabolic capabilities .", "We examine the evolution of this diversity by assessing the distribution and ancestry of each gene in 13 sequenced isolates of Escherichia coli and Shigella .", "We focus on the emergen...	[ "Changes in genetic repertoires can alter the adaptive strategy of an organism , especially in bacteria , in which genes are continually gained and lost .", "Mapping the gains and losses of genes in the densely sequenced clade of Escherichia coli and Shigella shows that these genomes harbour two types of acquired...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "immunology" ]	HSCARG Negatively Regulates the Cellular Antiviral RIG-I Like Receptor Signaling Pathway by Inhibiting TRAF3 Ubiquitination via Recruiting OTUB1	journal.ppat.1004041	null	[ [ "Innate immunity is the first line of defense for organisms to defeat disease-causing pathogens , such as viruses , bacteria , and parasites .", "The production of interferons ( IFNs ) is the core of the cellular antiviral response [1] .", "IFNs are secreted by virus-infected cells and are recognized ...	[ "RIG-I like receptors ( RLRs ) recognize cytosolic viral RNA and initiate innate immunity; they increase the production of type I interferon ( IFN ) and the transcription of a series of antiviral genes to protect the host organism .", "Accurate regulation of the RLR pathway is important for avoiding tissue injury...	[ "Innate immunity is critical for the host to defeat pathogen invasion , and the production of interferon ( IFN ) is the core of the cellular antiviral response , this is mediated by the Toll-like receptor ( TLR ) and RIG-I like receptor ( RLR ) signaling pathways in most cell types .", "As aberrant activity of th...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "dermatology", "genetic networks", "genetic mutation", "cancer genetics", "population genetics", "cancer risk factors", "cancers and neoplasms", "algorithms", "genome sequencing", "skin neoplasms", "mutation", "genome analysis tools", "oncology", "mutation types", "malignan...	VarWalker: Personalized Mutation Network Analysis of Putative Cancer Genes from Next-Generation Sequencing Data	journal.pcbi.1003460	null	[ [ "Next-generation sequencing ( NGS ) technologies have enabled genome-wide identification of somatic mutations in large scale cancer samples .", "One major challenge in interpreting the large volume of mutation data is to distinguish ‘driver’ mutations from numerous neutral ‘passenger’ mutations to facilit...	[ "A major challenge in interpreting the large volume of mutation data identified by next-generation sequencing ( NGS ) is to distinguish driver mutations from neutral passenger mutations to facilitate the identification of targetable genes and new drugs .", "Current approaches are primarily based on mutation frequ...	[ "A cancer genome typically harbors both driver mutations , which contribute to tumorigenesis , and passenger mutations , which tend to be neutral and occur randomly .", "Cancer genomes differ dramatically due to genetic and environmental factors .", "A major challenge in interpreting the large volume of mutatio...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biology", "microbiology", "evolutionary biology" ]	A Genome-Wide Analysis of Promoter-Mediated Phenotypic Noise in Escherichia coli	journal.pgen.1002443	null	[ [ "The phenotype of an individual is often considered to be a product of the individual's genotype and the environment in which it lives .", "However , significant phenotypic differences may exist between genetically identical individuals living in a homogeneous environment [1]–[7] .", "In the absence o...	[ "Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production .", "As a consequence , for any given protein , genetically identical organisms living in a constant environment will contain different amounts of that particular protein , resulting in different phenot...	[ "Many biological processes in a cell involve small numbers of molecules and therefore fluctuate over time .", "As a consequence , genetically identical cells that live in the same environment differ from each other in many phenotypic traits , including the expression level of different genes .", "Our aim was to...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome evolution", "ecology", "evolutionary biology", "genetics", "plant genetics", "population genetics", "biology", "genomics", "gene flow", "plant ecology", "computational biology", "evolutionary genetics", "crop genetics" ]	The Genomic Signature of Crop-Wild Introgression in Maize	journal.pgen.1003477	null	[ [ "Hybridization and subsequent introgression have long been appreciated as agents of evolution .", "Adaptations can be transferred through these processes upon secondary contact of uniquely adapted populations or species , in many instances producing the variation necessary for further diversification [1] ...	[ "The evolutionary significance of hybridization and subsequent introgression has long been appreciated , but evaluation of the genome-wide effects of these phenomena has only recently become possible .", "Crop-wild study systems represent ideal opportunities to examine evolution through hybridization .", "For e...	[ "Hybridization and introgression have been shown to play a critical role in the evolution of species .", "These processes can generate the diversity necessary for novel adaptations and continued diversification of taxa .", "Previous research has suggested that not all regions of a genome are equally permeable t...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	NLR-Associating Transcription Factor bHLH84 and Its Paralogs Function Redundantly in Plant Immunity	journal.ppat.1004312	null	[ [ "Plants have evolved a sophisticated immune system to fight against invading microbial pathogens that threaten their normal growth and development .", "Plant immunity is in part mediated by resistance ( R ) proteins that recognize pathogen proteins known as effectors [1]–[3] .", "The majority of R pro...	[ "In plants and animals , nucleotide-binding and leucine-rich repeat domain containing ( NLR ) immune receptors are utilized to detect the presence or activities of pathogen-derived molecules .", "However , the mechanisms by which NLR proteins induce defense responses remain unclear .", "Here , we report the cha...	[ "In plants and animals , NLR immune receptors are utilized to detect pathogen-derived molecules and activate immunity .", "However , the mechanisms of plant NLR activation remain unclear .", "Here , we report on bHLH84 , which functions as a transcriptional activator .", "Simultaneously knocking out three clo...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "mycobacterium leprae", "medicine and health sciences", "purification techniques", "tropical diseases", "condensed matter physics", "drug screening", "organisms", "bacterial diseases", "mycobacterium lepromatosis", "neglected tropical diseases", "molecular biology tech...	qPCR-High resolution melt analysis for drug susceptibility testing of Mycobacterium leprae directly from clinical specimens of leprosy patients	journal.pntd.0005506	null	[ [ "Current leprosy control depends solely on case detection and treatment with multi-drug therapy ( MDT ) including dapsone ( DDS ) , rifampin ( RMP ) and clofazimine [1] .", "This strategy is based on the principle that identifying and treating chronic infectious diseases with combinations of bactericidal ...	[ "Real-Time PCR-High Resolution Melting ( qPCR-HRM ) analysis has been recently described for rapid drug susceptibility testing ( DST ) of Mycobacterium leprae .", "The purpose of the current study was to further evaluate the validity , reliability , and accuracy of this assay for M . leprae DST in clinical specim...	[ "Despite three decades of effective treatment with multidrug therapy ( MDT ) , leprosy persists as a public health problem in many regions of the world .", "The recent increase in relapse cases , MDT treatment failures , and the emergence of drug-resistant strains of Mycobacterium leprae could undermine existing ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "cell motility", "cell biology", "biophysics theory", "biology and life sciences", "computational biology", "biophysics" ]	Behaviors and Strategies of Bacterial Navigation in Chemical and Nonchemical Gradients	journal.pcbi.1003672	null	[ [ "Living systems detect changes in the environment and try to find optimal conditions for their survival and growth .", "As one of the best-studied systems in biology , bacterial chemotaxis allows bacteria ( such as Escherichia coli ) to sense chemical gradients and navigate toward attractant or away from ...	[ "Navigation of cells to the optimal environmental condition is critical for their survival and growth .", "Escherichia coli cells , for example , can detect various chemicals and move up or down those chemical gradients ( i . e . , chemotaxis ) .", "Using the same signaling machinery , they can also sense other...	[ "Bacteria , such as E . coli , live in a complex environment with varying chemical and/or non-chemical stimuli .", "They constantly seek for and migrate to optimal environmental conditions .", "A well-known example is E . coli chemotaxis which direct cell movements up or down chemical gradients .", "Using the...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Connecting Replication and Repair: YoaA, a Helicase-Related Protein, Promotes Azidothymidine Tolerance through Association with Chi, an Accessory Clamp Loader Protein	journal.pgen.1005651	null	[ [ "All cells must balance ongoing DNA synthesis with repair reactions that are necessary to overcome problems in replication .", "Persistent , unreplicated single-strand gaps in DNA may be caused by lesions or by DNA structures that impede DNA polymerization in either the replication template or the nascent...	[ "Elongating DNA polymerases frequently encounter lesions or structures that impede progress and require repair before DNA replication can be completed .", "Therefore , directing repair factors to a blocked fork , without interfering with normal replication , is important for proper cell function , and it is a pro...	[ "During the replication of the cell’s genetic material , difficulties are often encountered .", "These problems require the recruitment of special proteins to repair DNA so that replication can be completed .", "The failure to do so causes cell death or deleterious changes to the cell’s genetic material .", "...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "cell motility", "medicine and health sciences", "actin filaments", "membrane staining", "cadherins", "cloning", "animals", "reproductive physiology", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "molecular biology techniq...	Epithelial rotation is preceded by planar symmetry breaking of actomyosin and protects epithelial tissue from cell deformations	journal.pgen.1007107	null	[ [ "Functional organ morphogenesis [1–3] has been linked to turns and rotations of epithelial sheets [4–9] relative to the organ or body anterior-posterior ( AP ) axis .", "The primary determinant of this chirality has been associated with the cytoskeleton in different species [10–14] .", "In rotating Dr...	[ "Symmetry breaking is involved in many developmental processes that form bodies and organs .", "One of them is the epithelial rotation of developing tubular and acinar organs .", "However , how epithelial cells move , how they break symmetry to define their common direction , and what function rotational epithe...	[ "Movement of epithelial tissues is essential for organ and body formation as well as function .", "To facilitate epithelial movements , cells need an internal or external source of mechanical force and a collective decision in which direction to move .", "However , little is known about the underlying mechanism...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetic screens", "genetics", "molecular genetics", "biology", "genomics", "microbiology", "genetics and genomics", "gene function" ]	Identification of Two Legionella pneumophila Effectors that Manipulate Host Phospholipids Biosynthesis	journal.ppat.1002988	null	[ [ "Legionella pneumophila , the causative agent of Legionnaires' disease , is an aerobic Gram-negative pathogen that multiplies intracellularly in human phagocytic cells and in freshwater protozoa [1] , [2] .", "The bacteria enter the cells by phagocytosis and reside within a unique phagosome , known as the...	[ "The intracellular pathogen Legionella pneumophila translocates a large number of effector proteins into host cells via the Icm/Dot type-IVB secretion system .", "Some of these effectors were shown to cause lethal effect on yeast growth .", "Here we characterized one such effector ( LecE ) and identified yeast ...	[ "Legionella pneumophila is an intracellular pathogen that causes a severe pneumonia known as Legionnaires' disease .", "Following infection , the bacteria use a Type-IVB secretion system to translocate multiple effector proteins into macrophages and generate the Legionella-containing vacuole ( LCV ) .", "The fo...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "rheumatology", "emerging infectious diseases", "neglected tropical diseases", "biology", "microbiology" ]	Chikungunya Virus-associated Long-term Arthralgia: A 36-month Prospective Longitudinal Study	journal.pntd.0002137	null	[ [ "Chikungunya virus ( CHIKV ) is an arthropod-borne virus that belongs to the Alphavirus genus .", "Chikungunya disease is characterized by polyarthralgia , sometimes associated with rash .", "The articular symptoms , often debilitating , usually resolve within weeks , but have been reported to last fo...	[ "Arthritogenic alphaviruses , including Chikungunya virus ( CHIKV ) , are responsible for acute fever and arthralgia , but can also lead to chronic symptoms .", "In 2006 , a Chikungunya outbreak occurred in La Réunion Island , during which we constituted a prospective cohort of viremic patients ( n = 180 ) and de...	[ "Chikungunya virus ( CHIKV ) is transmitted to human by mosquitoes .", "It is a re-emerging virus that has a risk to spread globally , given the expanding dissemination of its mosquito vectors .", "Chikungunya disease is characterized by acute transient febrile arthralgic illness , but can also lead to chronic ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biology", "neuroscience" ]	Representational Switching by Dynamical Reorganization of Attractor Structure in a Network Model of the Prefrontal Cortex	journal.pcbi.1002266	null	[ [ "The prefrontal cortex ( PFC ) is believed to play crucial roles in flexible decision making and action planning that are essential for adapting to an ever-changing real world .", "Prefrontal neurons hold not only multiple sets of discrete information and parametric magnitudes of stimuli in their working ...	[ "The prefrontal cortex ( PFC ) plays a crucial role in flexible cognitive behavior by representing task relevant information with its working memory .", "The working memory with sustained neural activity is described as a neural dynamical system composed of multiple attractors , each attractor of which correspond...	[ "The prefrontal cortex plays a highly flexible role in various cognitive tasks e . g . , decision making and action planning .", "Neurons in the prefrontal cortex exhibit flexible representation or selectivity for task relevant information and are involved in working memory with sustained activity , which can be ...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cancer detection and diagnosis", "machine learning algorithms", "medicine and health sciences", "neural networks", "applied mathematics", "cancers and neoplasms", "neuroscience", "simulation and modeling", "oncology", "algorithms", "mathematics", "artificial intelligence", "research and ana...	Machine learning analysis of gene expression data reveals novel diagnostic and prognostic biomarkers and identifies therapeutic targets for soft tissue sarcomas	journal.pcbi.1006826	null	[ [ "Soft tissue sarcomas are rare malignancies arising in the tissues that connect , support and surround other body structures , such as fat or muscle [1] .", "Soft tissue sarcomas annually affect approximately one per 50 million population , and represent <1% of all malignant tumors [2] .", "Soft tissu...	[ "Based on morphology it is often challenging to distinguish between the many different soft tissue sarcoma subtypes .", "Moreover , outcome of disease is highly variable even between patients with the same disease .", "Machine learning on transcriptome sequencing data could be a valuable new tool to understand ...	[ "Soft-tissue sarcomas are a group of rare cancers that can be challenging to diagnose and treat .", "The morphology of the different soft-tissue sarcoma subtypes can overlap and the prognosis differs significantly between , and also within , the different subtypes .", "Moreover , targeted therapies are often no...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "algorithms", "genome-wide association studies", "mathematics", "evolutionary biology", "evolutionary modeling", "genetics", "applied mathematics", "population genetics", "biology", "computational biology", "evolutionary genetics", "genetics and genomics" ]	An Evolutionary Perspective on Epistasis and the Missing Heritability	journal.pgen.1003295	null	[ [ "There exists a paradox in evolutionary biology .", "Despite a near-ubiquitous abundance of genetic variation [1] traits under selection often evolve more slowly than expected and , contrary to expectation , genetic variation is maintained under selection .", "This problem is known as ‘stasis’ [2] , [...	[ "The relative importance between additive and non-additive genetic variance has been widely argued in quantitative genetics .", "By approaching this question from an evolutionary perspective we show that , while additive variance can be maintained under selection at a low level for some patterns of epistasis , th...	[ "In this study we have shown that two independent problems may have a common cause .", "Why do traits under selection exhibit additive genetic variance , and why is the proportion of the heritability explained by additive effects much smaller than the total heritability estimated to exist ?", "Our results indic...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfer rna", "b vitamins", "chemical compounds", "nucleotides", "organic compounds", "plasmid construction", "fungi", "model organisms", "anticodons", "experimental organism systems", "dna construction", "molecular biology techniques", "schizosaccharomyces", "saccharomyces", "research...	Lack of 2'-O-methylation in the tRNA anticodon loop of two phylogenetically distant yeast species activates the general amino acid control pathway	journal.pgen.1007288	null	[ [ "During biogenesis , tRNAs acquire extensive post-transcriptional modifications that are important for their function as an adaptor molecule during translation .", "Modifications in the main body of the tRNA generally affect folding or stability of specific tRNAs [1–3] , whereas modifications in and aroun...	[ "Modification defects in the tRNA anticodon loop often impair yeast growth and cause human disease .", "In the budding yeast Saccharomyces cerevisiae and the phylogenetically distant fission yeast Schizosaccharomyces pombe , trm7Δ mutants grow poorly due to lack of 2'-O-methylation of C32 and G34 in the tRNAPhe a...	[ "The ubiquitous tRNA anticodon loop modifications have important but poorly understood functions in decoding mRNAs in the ribosome to ensure accurate and efficient protein synthesis , and their lack often impairs yeast growth and causes human disease .", "Here we investigate why ribose methylation of residues 32 ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Enteropathogenic Escherichia coli Uses NleA to Inhibit NLRP3 Inflammasome Activation	journal.ppat.1005121	null	[ [ "Enteropathogenic and Enterohemorrhagic Escherichia coli ( EPEC and EHEC ) are major causative agents of food poisoning worldwide [1] .", "EPEC causes infantile diarrhea , and EHEC causes bloody diarrhea and hemolytic uremic syndrome ( HUS ) in patients who ingest contaminated food [2] .", "These inva...	[ "Enteropathogenic and enterohemorrhagic Escherichia coli ( EPEC and EHEC ) are related strains capable of inducing severe gastrointestinal disease .", "For optimal infection , these pathogens actively modulate cellular functions through the deployment of effector proteins in a type three secretion system ( T3SS )...	[ "Enteropathogenic Escherichia coli ( EPEC ) and enterohemorrhagic E . coli ( EHEC ) cause severe intestinal dysfunction , including watery diarrhea or severe bloody diarrhea , and acute kidney failure ( hemolytic uremic syndrome ) .", "Transmitted through ingestion of contaminated food , these pathogens colonize ...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	The Schistosoma mansoni Cytochrome P450 (CYP3050A1) Is Essential for Worm Survival and Egg Development	journal.pntd.0004279	null	[ [ "Schistosomiasis is a helminthiasis caused by trematode worms of three main schistosome species , Schistosoma mansoni , S . haematobium , and S . japonicum .", "The disease is responsible for approximately 280 , 000 deaths annually and significant morbidity in more than 200 million people [1 , 2] .", ...	[ "Schistosomiasis affects millions of people in developing countries and is responsible for more than 200 , 000 deaths annually .", "Because of toxicity and limited spectrum of activity of alternatives , there is effectively only one drug , praziquantel , available for its treatment .", "Recent data suggest that...	[ "Over 600 million people in endemic countries are at risk of contracting schistosomiasis , which results in over 200 , 000 deaths each year and significant illness to most people that are infected .", "There are concerns that the drug widely used for the treatment of schistosomiasis , praziquantel , may be losing...	2015
[ "Introduction", "Methods and materials", "Results", "Discussion", "Conclusions" ]	[ "animal types", "medicine and health sciences", "body fluids", "domestic animals", "tropical diseases", "vertebrates", "parasitic diseases", "parasitic protozoans", "animals", "mammals", "dogs", "protozoans", "neglected tropical diseases", "insect vectors", "zoology", "infectious disea...	Implementation science: Epidemiology and feeding profiles of the Chagas vector Triatoma dimidiata prior to Ecohealth intervention for three locations in Central America	journal.pntd.0006952	null	[ [ "Chagas disease or American trypanosomiasis , is a neglected , zoonotic vector-borne disease , transmitted by insect vectors in the subfamily Triatominae ( Hemiptera: Reduviidae ) known colloquially as “kissing bugs” [1 , 2] .", "The disease , caused by the parasite Trypanosoma cruzi ( Kinetoplastea: Tryp...	[ "The Ecohealth strategy is a multidisciplinary data-driven approach used to improve the quality of people’s lives in Chagas disease endemic areas , such as regions of Central America .", "Chagas is a vector-borne disease caused by the parasite Trypanosoma cruzi .", "In Central America , the main vector is Triat...	[ "Blood feeding insects from the subfamily Triatomine are involved in the transmission of Chagas disease , caused by the protozoan parasite Trypanosoma cruzi , a neglected tropical disease endemic from southern Mexico through Central to northern South America .", "Chagas disease mostly affects rural areas and espe...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "pathology and laboratory medicine", "chemical compounds", "drugs", "immunology", "tropical diseases", "microbiology", "organic compounds", "bacterial diseases", "streptomycin", "genetic predisposition", "signs and symptoms", "antibiotics",...	Genetic Susceptibility and Predictors of Paradoxical Reactions in Buruli Ulcer	journal.pntd.0004594	null	[ [ "The neglected tropical disease Buruli ulcer ( BU ) is the third most frequent mycobacterial disease in immunocompetent persons after tuberculosis and leprosy [1–2] .", "It is caused by Mycobacterium ulcerans .", "Central to the pathogenesis is the immunosuppressant and necrosis inducing toxin mycolac...	[ "Buruli ulcer ( BU ) is the third most frequent mycobacterial disease in immunocompetent persons after tuberculosis and leprosy .", "During the last decade , eight weeks of antimicrobial treatment has become the standard of care .", "This treatment may be accompanied by transient clinical deterioration , known ...	[ "Buruli ulcer is an infectious disease of skin , subcutaneous fat and sometimes bone , mainly affecting children in West Africa .", "It is considered as one of the Neglected Tropical Diseases but the disease occurs also in moderate climates like South East Australia and Japan where it may also affect adults .", ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Detection of Rickettsia spp in Ticks by MALDI-TOF MS	journal.pntd.0003473	null	[ [ "Ticks are obligate hematophagous arthropods that parasitize vertebrates in almost all regions of the world and are currently considered to be the second-most important vectors of human infectious diseases worldwide , after mosquitoes [1] .", "Tick-borne rickettsioses are caused by obligate intracellular ...	[ "Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry ( MALDI-TOF MS ) has been shown to be an effective tool for the rapid identification of arthropods , including tick vectors of human diseases .", "The objective of the present study was to evaluate the use of MALDI-TOF MS to identify ti...	[ "Tick-borne rickettsioses include mild to life-threatening diseases in humans worldwide .", "When removing an attached tick from the human body , patients and physicians may have two questions:", "1 ) is the tick a known vector of a human infectious disease , and", "2 ) is the tick infected by a pathogenic ag...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "flow cytometry", "complement system", "medicine and health sciences", "immune physiology", "body fluids", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "vertebrates", "animals", "mammals", "developmental biology", "nymphs", "bacteria", "bacterial path...	Polymorphic factor H-binding activity of CspA protects Lyme borreliae from the host complement in feeding ticks to facilitate tick-to-host transmission	journal.ppat.1007106	null	[ [ "Lyme disease is caused by spirochetes of Bbsl and is transmitted to humans by the bites of infected Ixodes ticks .", "It is the most common vector-borne disease in North America and Europe [1 , 2] .", "Upon blood feeding , spirochetes migrate from the ticks’ midguts to salivary glands , where they ar...	[ "Borrelia burgdorferi sensu lato ( Bbsl ) , the causative agent of Lyme disease , establishes an initial infection in the host’s skin following a tick bite , and then disseminates to distant organs , leading to multisystem manifestations .", "Tick-to-vertebrate host transmission requires that Bbsl survives during...	[ "Lyme disease , the most common vector-borne disease in the United States , is caused by the bacterium , Borrelia burgdorferi .", "This bacterium is transmitted to humans via the bite of a tick , and then spreads from the bite site to multiple tissues .", "Tick-to-human transmission of this bacterium requires b...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "systems biology", "biochemistry", "genomics", "astrobiology", "biology", "computational biology", "evolutionary biology", "microbiology", "proteomics", "genetics and genomics" ]	Origin and Evolution of Protein Fold Designs Inferred from Phylogenomic Analysis of CATH Domain Structures in Proteomes	journal.pcbi.1003009	null	[ [ "The polypeptide chains of proteins generally fold into highly ordered and well-packed three-dimensional ( 3D ) atomic structures [1] .", "These protein folds represent spatial arrangements of more or less wound helices ( generally α-helices ) and extended chain segments ( β-strands ) that are separated b...	[ "The spatial arrangements of secondary structures in proteins , irrespective of their connectivity , depict the overall shape and organization of protein domains .", "These features have been used in the CATH and SCOP classifications to hierarchically partition fold space and define the architectural make up of p...	[ "Proteins are vital and central macromolecular players necessary for the functioning of the cell .", "The redundant and highly conserved structural makeup of proteins reflects their ability to act as genomic repositories of evolutionary history .", "These structures are fundamental subjects for the study of mol...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "biophysics", "biochemistry", "none", "computational biology" ]	Natively Unstructured Loops Differ from Other Loops	journal.pcbi.0030140	null	[ [ "One central paradigm of structural biology is that the intricate details of 3-D protein structures determine protein function [1 , 2] .", "In the last few years , many studies have shown that often the lack of a unique , native 3-D structure in physiological conditions can be crucial for function [3–21] ...	[ "Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination .", "Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures...	[ "The details of protein structures are important for function .", "Regions that do not adopt any regular structure in isolation ( natively unstructured or disordered regions ) initially appeared as a curious exception to this structure–function paradigm .", "It has become increasingly clear that unstructured re...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virus evolution and symbiosis" ]	Analysis of Virion Structural Components Reveals Vestiges of the Ancestral Ichnovirus Genome	journal.ppat.1000923	null	[ [ "Polydnaviruses ( PDVs ) are unique viruses symbiotically associated with endoparasitic wasps belonging to the families Braconidae and Ichneumonidae .", "Virus particles produced in the ovaries [1] are injected into lepidopteran hosts during wasp oviposition .", "The PDV genomes packaged in the partic...	[ "Many thousands of endoparasitic wasp species are known to inject polydnavirus ( PDV ) particles into their caterpillar host during oviposition , causing immune and developmental dysfunctions that benefit the wasp larva .", "PDVs associated with braconid and ichneumonid wasps , bracoviruses and ichnoviruses respe...	[ "The polydnaviruses ( PDVs ) are a unique virus type used by an organism ( a parasitic wasp ) to manipulate the physiology of another organism ( a lepidopteran host ) in order to ensure successful parasitism .", "The evolutionary origin of these unusual viruses , found in ∼17 , 500 braconid wasps ( Bracoviruses )...	2010
[ "Introduction", "Models", "Results", "Discussion" ]	[ "experimental psychology", "cognitive neuroscience", "behavioral neuroscience", "social and behavioral sciences", "psychology", "cognitive psychology", "behavior", "computational neuroscience", "biology", "sensory perception", "neuroscience", "learning and memory", "animal cognition" ]	Emotional Valence and the Free-Energy Principle	journal.pcbi.1003094	null	[ [ "Free-energy is an information theoretic quantity that upper bounds the surprise on sampling some data , given a generative model of how data were caused .", "The free-energy principle assumes that biological agents encode a probabilistic model of the causes of their sensations , and postulates that any a...	[ "The free-energy principle has recently been proposed as a unified Bayesian account of perception , learning and action .", "Despite the inextricable link between emotion and cognition , emotion has not yet been formulated under this framework .", "A core concept that permeates many perspectives on emotion is v...	[ "Emotion plays a crucial role in the adaptation of humans and other animals to changes in their world .", "Nevertheless , emotion has been neglected in Bayesian models of learning in non-stationary environments .", "The free-energy principle has recently been proposed as a unified account of learning , percepti...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "taxonomy", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "animals", "mammals", "dogs", "phylogenetics", "data management", "phylogenetic analysis", "bacteria", "bacterial pathogens", "research and analysis methods", "s...	Prevalence, diversity, and host associations of Bartonella strains in bats from Georgia (Caucasus)	journal.pntd.0005428	null	[ [ "Bats ( Order: Chiroptera ) are hosts of a wide range of zoonotic pathogens .", "Their significance as reservoirs of emerging infectious diseases , predominantly of viral origin , has been increasinglyecognized during recent decades [1 , 2] .", "In contrast , the study of bacterial infections in bats ...	[ "Bartonella infections were investigated in seven species of bats from four regions of the Republic of Georgia .", "Of the 236 bats that were captured , 212 ( 90% ) specimens were tested for Bartonella infection .", "Colonies identified as Bartonella were isolated from 105 ( 49 . 5% ) of 212 bats Phylogenetic a...	[ "Bacteria of the genus Bartonella parasitize erythrocytes and endothelial cells of a wide range of mammals and recently were reported in bats from Africa , Asia , America , and northern Europe .", "A human disease case in the USA was associated with a novel Bartonella species , which later was identified in bats ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics", "biology and life sciences", "genomics", "computational biology" ]	Apoptotic Lymphocytes of H. sapiens Lose Nucleosomes in GC-Rich Promoters	journal.pcbi.1003760	null	[ [ "A nucleosome is the basic unit responsible for packing eukaryotic DNA into chromatin .", "Nucleosome position is determined during chromatin assembly and related to regulatory elements of gene expression such as promoters , transcription factors and others .", "The precise position of a nucleosome is...	[ "We analyzed two sets of human CD4+ nucleosomal DNA directly sequenced by Illumina ( Solexa ) high throughput sequencing method .", "The first set has ∼40 M sequences and was produced from the normal CD4+ T lymphocytes by micrococcal nuclease .", "The second set has ∼44 M sequences and was obtained from periphe...	[ "We analyzed nucleosomal DNA of human CD4+ T normal and apoptotic lymphocytes .", "Dinucleotide positions ( pattern ) of AA/TT , GG/CC , WW/SS ( W is adenine or thymine , S is guanine or cytosine ) and RR/YY ( R is purine , Y - pyrimidine ) of nucleosome sequences in both cell conditions are similar and have peri...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "diagnostic medicine", "epidemiology", "public health" ]	A Comparison of the Sensitivity and Fecal Egg Counts of the McMaster Egg Counting and Kato-Katz Thick Smear Methods for Soil-Transmitted Helminths	journal.pntd.0001201	null	[ [ "Infection with soil-transmitted helminths ( STH ) , including Ascaris lumbricoides , Trichuris trichiura and hookworm ( Ancylostoma duodenale and Necator americanus ) are of major importance for public health in tropical and subtropical countries [1] , [2] .", "Current approaches proposed for controlling...	[ "The Kato-Katz thick smear ( Kato-Katz ) is the diagnostic method recommended for monitoring large-scale treatment programs implemented for the control of soil-transmitted helminths ( STH ) in public health , yet it is difficult to standardize .", "A promising alternative is the McMaster egg counting method ( McM...	[ "Currently , in public health , the reduction in the number of eggs excreted in stools after drug administration is used to monitor the efficacy of drugs against parasitic worms .", "Yet , studies comparing diagnostic methods for the enumeration of eggs in stool are few .", "We compared the Kato-Katz thick smea...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Natural Selection Promotes Antigenic Evolvability	journal.ppat.1003766	null	[ [ "The ability of a biological trait to evolve by natural selection , or evolvability , varies substantially among species , among populations within species , and even among traits within populations .", "The hypothesis that differences in evolvability result from past natural selection acting on the abili...	[ "The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence .", "The antigenic variation mechanisms of microbial pathogens provide an experi...	[ "The hypothesis that natural selection shapes the ability of a population to evolve is highly controversial due primarily to a paucity of empirical evidence .", "However , the ability to constantly and rapidly evolve may be selectively adaptive in pathogens due to the constantly changing environment created by th...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "biochemistry", "virology/viral replication and gene regulation", "gastroenterology and hepatology/hepatology", "microbiology/innate immunity", "immunology/innate immunity", "virology/antivirals, including modes of action and resistance", "infectious diseases/viral infections", "vir...	Persistent Growth of a Human Plasma-Derived Hepatitis C Virus Genotype 1b Isolate in Cell Culture	journal.ppat.1000910	null	[ [ "Hepatitis C virus ( HCV ) , a member of the Flaviviridae family , is an enveloped , positive-sense RNA virus that infects approximately 170 million people worldwide .", "Chronic HCV infection can lead to serious liver disease , including cirrhosis and hepatocellular carcinoma .", "Current therapy wit...	[ "HCV ( hepatitis C virus ) research , including therapeutics and vaccine development , has been hampered by the lack of suitable tissue culture models .", "Development of cell culture systems for the growth of the most drug-resistant HCV genotype ( 1b ) as well as natural isolates has remained a challenge .", "...	[ "Hepatitis C virus ( HCV ) causes a persistent infection that can lead to hepatocellular carcinoma and liver cirrhosis .", "Interferon ( IFN ) -based treatments are ineffective for some HCV genotypes .", "HCV research has been hampered by the lack of suitable cell culture systems .", "With the discovery of a ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/immunodeficiency viruses", "immunology/immune response", "infectious diseases/hiv infection and aids", "virology/immune evasion", "virology/host antiviral responses" ]	Limited Neutralizing Antibody Specificities Drive Neutralization Escape in Early HIV-1 Subtype C Infection	journal.ppat.1000598	null	[ [ "Neutralizing antibody ( nAb ) responses which target the Env of HIV-1 and block viral entry develop in most HIV-1 infected individuals , reaching detectable levels within a few months of infection when measured against the autologous Env [1] , [2] , [3] , [4] .", "Much of the variation that occurs in the...	[ "We previously showed that HIV-1 subtype C viruses elicit potent but highly type-specific neutralizing antibodies ( nAb ) within the first year of infection .", "In order to determine the specificity and evolution of these autologous nAbs , we examined neutralization escape in four individuals whose responses aga...	[ "Most HIV-1 infected individuals develop neutralizing antibodies against their own virus , termed an autologous neutralizing response .", "It is known that this response exerts pressure on the envelope of HIV , the target of such antibodies , resulting in neutralization escape .", "Here we have identified the t...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biochemistry", "biology", "zoology", "parasitology" ]	Towards an Understanding of the Function of the Phytochelatin Synthase of Schistosoma mansoni	journal.pntd.0002037	null	[ [ "Phytochelatin synthase ( PCS ) proteins are γ-glutamylcysteine dipetidyltranspeptidases ( EC 2 . 3 . 2 . 15 ) known for their ability to synthesize phytochelatins , which have the general structure ( γ-Glu-Cys ) n-Gly ( n≥2 , where PC2 is a polymer with n = 2; PC3 , n = 3; etc . ) , from glutathione ( γ-Glu-...	[ "Phytochelatin synthase ( PCS ) is a protease-like enzyme that catalyzes the production of metal chelating peptides , the phytochelatins , from glutathione ( GSH ) .", "In plants , algae , and fungi phytochelatin production is important for metal tolerance and detoxification .", "PCS proteins also function in x...	[ "Schistosomiasis is a chronic , debilitating disease that affects hundreds of millions of people .", "The treatment of schistosomiasis relies solely on monotherapy with praziquantel and there is concern that drug-resistant parasites will evolve .", "Therefore , it is imperative to identify new drugs for schisto...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "developmental biology/plant growth and development" ]	Imprinting of the Polycomb Group Gene MEDEA Serves as a Ploidy Sensor in Arabidopsis	journal.pgen.1000663	null	[ [ "Polyploidy , the presence of more than two complete sets of chromosomes within an organism , is known to be common in plants and in some animals such as amphibians , fish and reptiles [1] , [2] .", "The widespread occurrence of polyploids among plant species suggests that polyploidy is evolutionary benef...	[ "Balanced maternal and paternal genome contributions are a requirement for successful seed development .", "Unbalanced contributions often cause seed abortion , a phenomenon that has been termed “triploid block . ”", "Misregulation of imprinted regulatory genes has been proposed to be the underlying cause for a...	[ "Crosses between plants of different ploidy often fail because seed development does not proceed normally and non-viable seeds are produced .", "It is assumed that abnormalities in growth and structure of the endosperm ( the nutritional tissue of the seed ) are the cause of triploid seed failure , consistent with...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal genetics", "gene identification and analysis", "genetics", "molecular genetics", "biology" ]	Mutation of SLC35D3 Causes Metabolic Syndrome by Impairing Dopamine Signaling in Striatal D1 Neurons	journal.pgen.1004124	null	[ [ "The worldwide prevalence of obesity ( OMIM 601665 , http://www . ncbi . nlm . nih . gov/omim/ ) is increasing ( data from the International Obesity Taskforce ( IOTF ) website , http://www . iaso . org/iotf/obesity/ ) .", "This has resulted in a significant increase in morbidity and mortality associated w...	[ "Obesity is one of the largest health problems facing the world today .", "Although twin and family studies suggest about two-thirds of obesity is caused by genetic factors , only a small fraction of this variance has been unraveled .", "There are still large numbers of genes to be identified that cause variati...	[ "Genome-wide linkage analyses have revealed that an STS marker D6S1009 ( about 55 kb from the SLC35D3 gene ) is linked to obesity or BMI in the Framingham Heart Study , but its genetic entity is unknown .", "Here we characterized the features of obesity and metabolic syndrome with reduced physical activity levels...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "agriculture", "biology" ]	The U-Box E3 Ubiquitin Ligase TUD1 Functions with a Heterotrimeric G α Subunit to Regulate Brassinosteroid-Mediated Growth in Rice	journal.pgen.1003391	null	[ [ "Brassinosteroids ( BRs ) are a class of polyhydroxylated sterol derivatives , structurally similar to animal steroids , which appear to be ubiquitously distributed throughout the plant kingdom [1] .", "As a group of growth-promoting steroid hormones , they play pivotal roles in promoting cell expansion a...	[ "Heterotrimeric G proteins are an important group of signaling molecules found in eukaryotes .", "They function with G-protein-coupled-receptors ( GPCRs ) to transduce various signals such as steroid hormones in animals .", "Nevertheless , their functions in plants are not well-defined .", "Previous studies s...	[ "Rice is an important and staple grain food .", "Understanding the molecular basis of rice growth and development is crucial to safeguarding our food security .", "Hormone signaling pathways are key regulators of plant growth and development .", "Heterotrimeric G-protein complexes serve as signal transducers ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "global health", "public health" ]	A Field Trial of Alternative Targeted Screening Strategies for Chagas Disease in Arequipa, Peru	journal.pntd.0001468	null	[ [ "Chagas disease has historically occurred in poor rural settings of Latin America [1] , [2] , [3] .", "In the rural areas of the Department of Arequipa in southern Peru , reports of Chagas disease and its vectors date back to the early 20th century [4] , [5] , [6] , where the disease has persisted in an e...	[ "Chagas disease is endemic in the rural areas of southern Peru and a growing urban problem in the regional capital of Arequipa , population ∼860 , 000 .", "It is unclear how to implement cost-effective screening programs across a large urban and periurban environment .", "We compared four alternative screening ...	[ "In the wake of emerging T . cruzi infection in children of periurban Arequipa , Peru , we conducted a prospective field trial to evaluate alternative targeted screening strategies for Chagas disease across the city .", "Using insect vector data that is routinely collected during Ministry of Health insecticide ap...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/animal models of infection" ]	A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis	journal.ppat.1000648	null	[ [ "Inoculation of the neurotropic JHMV strain of mouse hepatitis virus ( a positive-strand RNA virus and member of the Coronaviridae family ) into the CNS of susceptible strains of mice results in an acute encephalomyelitis , characterized by wide spread infection and replication within astrocytes , microglia ,...	[ "The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined .", "Inoculation of the neurotropic JHM strain of mouse hepatitis virus ( JHMV ) into the central nervous system ( CNS ) of mice resulted in the rapid mobilization of PMNs expressing the...	[ "Consequences of viral infection of the central nervous system ( CNS ) can range from encephalitis and paralytic poliomyelitis to relatively benign infections with limited clinical outcomes .", "The localized expression of proinflammatory chemokines within the CNS in response to viral infection has been shown to ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "respiratory syncytial virus infection", "virology", "viral nucleic acid", "viral enzymes", "biology", "microbiology", "viral replication", "viral replication complex", "viral diseases" ]	The Respiratory Syncytial Virus Polymerase Has Multiple RNA Synthesis Activities at the Promoter	journal.ppat.1002980	null	[ [ "Respiratory syncytial virus ( RSV ) is the major cause of respiratory tract disease in infants and young children worldwide , causing 3 . 4 million cases of severe acute lower respiratory infection , and between 66 , 000 and 199 , 000 deaths per annum [1] .", "As yet , there is no vaccine available to pr...	[ "Respiratory syncytial virus ( RSV ) is an RNA virus in the Family Paramyxoviridae .", "Here , the activities performed by the RSV polymerase when it encounters the viral antigenomic promoter were examined .", "RSV RNA synthesis was reconstituted in vitro using recombinant , isolated polymerase and an RNA oligo...	[ "Respiratory syncytial virus ( RSV ) is a major pathogen of infants with the potential to cause severe respiratory disease .", "RSV has an RNA genome and one approach to developing a drug against this virus is to gain a greater understanding of the mechanisms used by the viral polymerase to generate new RNA .", ...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "population genetics", "cell processes", "variant genotypes", "alleles", "genetic mapping", "mutation", "developmental biology", "population biology", "morphogenesis", "genetic polymorphism", "cell proliferation", "imaginal discs", "genetic loci", "cell biology", "phenotypes", "heredit...	How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects	journal.pgen.1007075	null	[ [ "In any given genetic pathway , or even in a single gene , different mutations ( whether they are natural variants or lab-induced lesions ) can have a wide range of phenotypic effects , and these effects are often modulated by the environment and alleles at other genes throughout the genome ( the genetic back...	[ "For a given gene , different mutations influence organismal phenotypes to varying degrees .", "However , the expressivity of these variants not only depends on the DNA lesion associated with the mutation , but also on factors including the genetic background and rearing environment .", "The degree to which the...	[ "Different mutations in a gene , or in genes with related functions , can have effects of varying severity .", "Studying sets of mutations and analyzing how they interact are essential components of a geneticist's toolkit .", "However , the effects caused by a mutation depend not only on the mutation itself , b...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/morphogenesis and cell biology", "genetics and genomics/nuclear structure and function", "molecular biology/chromosome structure", "molecular biology/recombination", "genetics and genomics/chromosome biology", "genetics and genomics/cancer genetics", "molecular biology/dna repair" ]	Caenorhabditis elegans HIM-18/SLX-4 Interacts with SLX-1 and XPF-1 and Maintains Genomic Integrity in the Germline by Processing Recombination Intermediates	journal.pgen.1000735	null	[ [ "DNA double-strand breaks ( DSBs ) can arise in various ways , including as a result of the collapse of stalled replication forks , exposure to DNA damaging agents and the formation of programmed meiotic DSBs [1] .", "The importance of DSB repair is therefore highlighted by its critical roles in replicati...	[ "Homologous recombination ( HR ) is essential for the repair of blocked or collapsed replication forks and for the production of crossovers between homologs that promote accurate meiotic chromosome segregation .", "Here , we identify HIM-18 , an ortholog of MUS312/Slx4 , as a critical player required in vivo for ...	[ "Homologous recombination ( HR ) is a process that provides for the accurate and efficient repair of DNA double-strand breaks ( DSBs ) incurred by cells , thereby maintaining genomic integrity .", "Proper processing of HR intermediates is critical for biological processes ranging from replication fork restart to ...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "xenobiotic metabolism", "pathology and laboratory medicine", "honey bees", "invertebrate genomics", "animals", "toxicology", "genome analysis", "bees", "agrochemicals", "genomic libraries", "hymenoptera", "metabolic pathways", "animal gen...	Genomic insights into neonicotinoid sensitivity in the solitary bee Osmia bicornis	journal.pgen.1007903	null	[ [ "Bee pollinators encounter a wide range of natural and synthetic xenobiotics while foraging or in the hive , including phytochemicals , mycotoxins produced by fungi , and pesticides [1] .", "Understanding the toxicological outcomes of bee exposure to these chemicals , in isolation or combination , is esse...	[ "The impact of pesticides on the health of bee pollinators is determined in part by the capacity of bee detoxification systems to convert these compounds to less toxic forms .", "For example , recent work has shown that cytochrome P450s of the CYP9Q subfamily are critically important in defining the sensitivity o...	[ "Bees have evolved sophisticated metabolic systems to detoxify the natural toxins encountered in their environment .", "Recent work has shown that specific enzymes ( cytochrome P450s ) in these biotransformation pathways can be recruited to protect honey bees and bumblebees against certain synthetic insecticides ...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genome-wide association studies", "cancer genetics", "genetics", "biology", "genetics and genomics" ]	Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk	journal.pgen.1003173	null	[ [ "The lifetime risk of breast cancer associated with carrying a BRCA2 mutation varies from 40 to 84% [1] .", "To determine whether common genetic variants modify breast cancer risk for BRCA2 mutation carriers , we previously conducted a GWAS of BRCA2 mutation carriers from the Consortium of Investigators o...	[ "Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies ( GWAS ) .", "To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers ...	[ "Women who carry BRCA2 mutations have an increased risk of breast cancer that varies widely .", "To identify common genetic variants that modify the breast cancer risk associated with BRCA2 mutations , we have built upon our previous work in which we examined genetic variants across the genome in relation to brea...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physiology/neuronal signaling mechanisms", "biophysics/biomacromolecule-ligand interactions", "neuroscience/neurobiology of disease and regeneration", "pharmacology" ]	Fast- or Slow-inactivated State Preference of Na+ Channel Inhibitors: A Simulation and Experimental Study	journal.pcbi.1000818	null	[ [ "Sodium channels are the key proteins in action potential firing for most excitable cells .", "They exhibit a complex , membrane potential-dependent gating behavior [1] .", "Even minor disturbances in the gating behavior can lead to hyperexcitability , which can be one of the causes of various disorde...	[ "Sodium channels are one of the most intensively studied drug targets .", "Sodium channel inhibitors ( e . g . , local anesthetics , anticonvulsants , antiarrhythmics and analgesics ) exert their effect by stabilizing an inactivated conformation of the channels .", "Besides the fast-inactivated conformation , s...	[ "Sodium channels are the key proteins for action potential firing in most excitable cells .", "Inhibitor drugs prevent excitation ( local anesthetics ) , regulate excitability ( antiarrhythmics ) , or prevent overexcitation ( antiepileptic , antispastic and neuroprotective drugs ) by binding to the channel and ke...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "rna interference", "parasitic cell cycles", "cell cycle and cell division", "split-decomposition method", "cell processes", "drugs", "microbiology", "parasitic protozoans", "parasitology", "multiple alignment calculation", "developmental bio...	The ubiquitin-conjugating enzyme CDC34 is essential for cytokinesis in contrast to putative subunits of a SCF complex in Trypanosoma brucei	journal.pntd.0005626	null	[ [ "Transition from one cell cycle stage to the next is achieved in eukaryotes through mechanisms that provide an all-or-none cyclin-dependent kinases ( CDKs ) activation .", "The activity of these enzymes is regulated by several mechanisms , including association with regulatory subunits ( cyclins ) , phosp...	[ "The ubiquitin-proteasome system is a post-translational regulatory pathway for controlling protein stability and activity that underlies many fundamental cellular processes , including cell cycle progression .", "Target proteins are tagged with ubiquitin molecules through the action of an enzymatic cascade compo...	[ "African sleeping sickness is a neglected tropical disease caused by infection with the protozoan parasite Trypanosoma brucei , which is transmitted to humans by tsetse flies ( Glossina genus ) .", "Treatment of the disease is complex and relies on limited pharmaceutical options .", "Understanding how T . bruce...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Exploring Consumer Perceptions and Economic Burden of Onchocerciasis on Households in Enugu State, South-East Nigeria	journal.pntd.0004231	null	[ [ "Onchocerciasis , otherwise called river blindness is one of the Neglected Tropical Diseases ( NTDs ) that constitute a public health problem [1] .", "It is commonly a burden to affected households and results to significant reduction in household productivity [2] .", "The disease is predominantly chr...	[ "Onchocerciasis or river blindness constitutes a major burden to households especially in resource-poor settings , causing a significant reduction in household productivity .", "There has been renewed interest from policy makers to reduce the burden of Neglected Tropical Diseases ( NTDs ) such as onchocerciasis o...	[ "Onchocerciasis is a public health problem in Nigeria , especially among the poor living in endemic communities .", "There is a dearth of evidence on the burden of onchocerciasis and studies suggest poor knowledge of the cause of onchocerciasis .", "This information could facilitate evidence-informed decisions ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology/evolutionary ecology", "immunology/immunity to infections", "immunology/innate immunity", "microbiology/parasitology", "infectious diseases/protozoal infections", "microbiology/cellular microbiology and pathogenesis" ]	Phosphorylation of Mouse Immunity-Related GTPase (IRG) Resistance Proteins Is an Evasion Strategy for Virulent Toxoplasma gondii	journal.pbio.1000576	GTPases of the mouse IRG protein family, mediators of resistance against Toxoplasma gondii in the mouse, are inactivated by a polymorphic kinase of the parasite, resulting in enhanced parasite virulence.	[ [ "Toxoplasma gondii is an intracellular protozoan parasite with a complex life cycle and is distantly related to the malarial genus Plasmodium .", "The sexual phase occurs only in the true cats ( Felidae ) , while all warm-blooded animals including humans can be intermediate hosts .", "The infection is...	[ "Virulence of complex pathogens in mammals is generally determined by multiple components of the pathogen interacting with the functional complexity and multiple layering of the mammalian immune system .", "It is most unusual for the resistance of a mammalian host to be overcome by the defeat of a single defence ...	[ "Many pathogens manipulate the immune system of their hosts to facilitate infection and ensure transmission to subsequent hosts .", "The intracellular protozoan Toxoplasma gondii , a relative of the malaria parasite , is able to infect and persist in a remarkable variety of warm-blooded hosts .", "Indeed roughl...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "fluorescence imaging", "plant anatomy", "trichomes", "chromosome structure and function", "nucleases", "centromeres", "gene regulation", "enzymes", "dna-binding proteins", "enzymology", "developmental biology", "insulators", "plant science", "materials science", "embryos", "research a...	Functional Dissection of the Blocking and Bypass Activities of the Fab-8 Boundary in the Drosophila Bithorax Complex	journal.pgen.1006188	null	[ [ "Special elements called chromatin boundaries or insulators are thought to subdivide chromosomes in multi-cellular eukaryotes into topologically and genetically autonomous domains [1–10] .", "Boundaries/insulators have both architectural and genetic functions .", "The architectural functions depend up...	[ "Functionally autonomous regulatory domains direct the parasegment-specific expression of the Drosophila Bithorax complex ( BX-C ) homeotic genes .", "Autonomy is conferred by boundary/insulator elements that separate each regulatory domain from its neighbors .", "For six of the nine parasegment ( PS ) regulato...	[ "Boundary elements in the Bithorax complex have two seemingly contradictory activities .", "They must block crosstalk between neighboring regulatory domains , but at the same time be permissive ( insulator bypass ) for regulatory interactions between the domains and the BX-C homeotic genes .", "We have used a r...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome-Wide Association Study of Golden Retrievers Identifies Germ-Line Risk Factors Predisposing to Mast Cell Tumours	journal.pgen.1005647	null	[ [ "Mastocytosis is a term that covers a broad range of human conditions involving the uncontrolled proliferation and infiltration of mast cells in tissues .", "A common characteristic for these diseases is a high frequency of activating mutations in the C-KIT oncogene [1–3] .", "An intriguing feature of...	[ "Canine mast cell tumours ( CMCT ) are one of the most common skin tumours in dogs with a major impact on canine health .", "Certain breeds have a higher risk of developing mast cell tumours , suggesting that underlying predisposing germ-line genetic factors play a role in the development of this disease .", "T...	[ "Pet dogs develop many of the same diseases as humans .", "Hence , studying diseases in dogs can be valuable for learning about human conditions .", "The genetic structure caused by inbreeding within dog breeds has proven to be advantageous to map genetic diseases .", "Golden retrievers have a very high risk ...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/bacterial infections", "infectious diseases/helminth infections", "immunology/immune response", "infectious diseases/neglected tropical diseases" ]	Helminth Coinfection Does Not Affect Therapeutic Effect of a DNA Vaccine in Mice Harboring Tuberculosis	journal.pntd.0000700	null	[ [ "Helminth parasites cause significant morbidity worldwide , with estimates indicating that approximately one-third of the almost three billion people living on less than two US dollars per day in developing regions of sub-Saharan Africa , Asia , and the Americas are infected with one or more helminths [1] , [...	[ "Helminthiasis and tuberculosis ( TB ) coincide geographically and there is much interest in exploring how concurrent worm infections might alter immune responses against bacilli and might necessitate altered therapeutic approaches .", "A DNA vaccine that codifies heat shock protein Hsp65 from M . leprae ( DNAhsp...	[ "From 14 diseases considered by WHO as Neglected Tropical Diseases , four involve helminth infections , such as schistosomiasis and soil-transmitted helminthiasis .", "Toxocariasis is a soil-transmitted worm highly prevalent in many developing countries , while schistosomiasis causes an annual mortality of 14 , 0...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion", "Conclusion" ]	[ "biotechnology", "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "engineering and technology", "tropical diseases", "parasitic diseases", "animals", "toxicology", "blastulas", "age groups", "developmental biology", "toxicity", "gastropods", "nanotech...	Molluscicidal activities of curcumin-nisin polylactic acid nanoparticle on Biomphalaria pfeifferi	journal.pntd.0005855	null	[ [ "Trematodes , the causal agents of schistosomiasis and fascioliasis are important parasites of economic and public health implications in most of sub-Saharan Africa .", "Schistosomiasis affects over 240 million people worldwide , with up to 700 million individuals living at risk of infection [1] .", "...	[ "Snail intermediate host control is a widely canvassed strategy for schistosomiasis control in endemic countries .", "While there have been increasing studies on the search for potent molluscicides in the past years , the use of nanoparticulate agents as molluscicides is yet to gain wide attention .", "The aim ...	[ "Elimination of snail intermediate host of schistosomiasis has been widely advocated as an arm of integrated control for schistosomiasis .", "This becomes important as reports now abound on development of praziquantel resistance in schistosomes .", "Nanotechnology has been applied in control of tropical disease...	2017
[ "Introduction", "Results", "Discussion", "Experimental Procedures" ]	[ "death rates", "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "chemical compounds", "demography", "pathogens", "immunology", "microbiology", "carbohydrates", "animals", "organic compounds", "glucose", "animal models", "drosophila melanogaster", "m...	How Many Parameters Does It Take to Describe Disease Tolerance?	journal.pbio.1002435	Experiments using fruit flies infected with Listeria monocytogenes show that changes in the shape of a disease tolerance curve can reveal the source of pathology for an infectious system.	[ [ "The clinical goal of treating infectious diseases is to reduce the levels of sickness experienced by infected hosts .", "One approach to studying this problem is to quantitate illness by correlating the dose response of pathology to pathogen load; graphs like these are called “disease tolerance curves” [...	[ "The study of infectious disease has been aided by model organisms , which have helped to elucidate molecular mechanisms and contributed to the development of new treatments; however , the lack of a conceptual framework for unifying findings across models , combined with host variability , has impeded progress and ...	[ "It is an intuitive assumption that the severity of symptoms suffered during an infection must be linked to pathogen loads .", "However , the dose–response relationship explaining how health varies with respect to pathogen load is non-linear and can be described as a “disease tolerance curve;” this relationship c...	2016
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "genome sequencing", "medicine", "infectious diseases", "plasmodium malariae", "neglected tropical diseases", "biology", "genomics", "malaria", "parasitic diseases", "genetics and genomics" ]	Whole Genome Sequencing of Field Isolates Provides Robust Characterization of Genetic Diversity in Plasmodium vivax	journal.pntd.0001811	null	[ [ "Plasmodium vivax is the most widely distributed human malaria species and causes more illness than P . falciparum in many regions [1] .", "Its global public health burden is estimated to be US$1 . 4 to 4 . 0 billion [2] .", "Even in areas of low transmission , up to 20% of the population can have a s...	[ "An estimated 2 . 85 billion people live at risk of Plasmodium vivax transmission .", "In endemic countries vivax malaria causes significant morbidity and its mortality is becoming more widely appreciated , drug-resistant strains are increasing in prevalence , and an increasing number of reports indicate that P ....	[ "Plasmodium vivax is the most frequently transmitted and widely distributed cause of malaria in the world .", "Each year P . vivax is responsible for approximately 250 million clinical cases of malaria and its global economic burden , placed largely on the poor , has been estimated to exceed US$1 . 4 billion .", ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "ocular anatomy", "social sciences", "neuroscience", "learning and memory", "probability distribution", "mathematics", "cognition", "memory", "vision", "eyes", "sensory physiology", "computer and information sciences", "head", "probability theory", "visu...	Causal Inference for Spatial Constancy across Saccades	journal.pcbi.1004766	null	[ [ "During saccadic eye movements , the image of the world shifts across our retina .", "Despite these shifts , we perceive targets as having world-stable positions , and have no problem to act upon them whenever necessary .", "It has been suggested that a combination of predictive and feedback mechanism...	[ "Our ability to interact with the environment hinges on creating a stable visual world despite the continuous changes in retinal input .", "To achieve visual stability , the brain must distinguish the retinal image shifts caused by eye movements and shifts due to movements of the visual scene .", "This process ...	[ "During saccadic eye movements , the image on our retinas is , contrary to subjective experience , highly unstable .", "This study examines how the brain distinguishes the image perturbations caused by saccades and those due to changes in the visual scene .", "We first show that participants made severe errors ...	2016
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "cell physiology", "cryptococcus neoformans", "medicine and health sciences", "cryptococcus", "pathology and laboratory medicine", "pathogens", "microbiology", "cell metabolism", "fungi", "hypoxia", "mitochondria", "stat proteins", "bioenergetics", "cellular structures and organelles", "...	Cryptococcus neoformans resists to drastic conditions by switching to viable but non-culturable cell phenotype	journal.ppat.1007945	null	[ [ "All microorganisms are exposed to fluctuating environments and periodic external stresses , which inhibit their growth .", "Some microbes may overcome these stress periods by entering into a resistant non-replicative state , assessed by /associated with a decreased culturability [1] .", "This decreas...	[ "Metabolically quiescent pathogens can persist in a viable non-replicating state for months or even years .", "For certain infectious diseases , such as tuberculosis , cryptococcosis , histoplasmosis , latent infection is a corollary of this dormant state , which has the risk for reactivation and clinical disease...	[ "Quiescence/dormancy in microorganism is a common feature that enables survival at the population level .", "In fungi , quiescence has been studied in the baker yeast Saccharomyces cerevisiae .", "In Cryptococcus neoformans , dormancy is of great interest since it is known from the natural history of cryptococc...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mathematics", "statistics", "genetics", "population genetics", "biology", "genetics and genomics", "probability theory" ]	Familial Identification: Population Structure and Relationship Distinguishability	journal.pgen.1002469	null	[ [ "Forensic identification via exact genetic profile matching has become common practice in the United States [1] .", "In exact genetic identification , genetic markers found in a crime scene sample are genotyped and exactly matched to a suspect or database entry , suggesting that the sample originates from...	[ "With the expansion of offender/arrestee DNA profile databases , genetic forensic identification has become commonplace in the United States criminal justice system .", "Implementation of familial searching has been proposed to extend forensic identification to family members of individuals with profiles in offen...	[ "The forensic identification of criminal suspects through DNA profiling is now common in the United States .", "Indirect identification by familial DNA profiling is increasingly proposed to extend the utility of DNA databases .", "In familial searching , a DNA profile from a crime scene partially matches a data...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "nervous system", "fingers", "brain", "social sciences", "limbs (anatomy)", "neuroscience", "learning and memory", "magnetic resonance imaging", "face recognition", "perception", "multivariate ...	Multivariate pattern dependence	journal.pcbi.1005799	null	[ [ "Cognitive tasks recruit multiple brain regions [1–4] .", "How do these regions work together to generate behavior ?", "A variety of methods have been developed to study connectivity both in terms of the anatomical structure of the brain [5] , and of the relations between timecourses of responses duri...	[ "When we perform a cognitive task , multiple brain regions are engaged .", "Understanding how these regions interact is a fundamental step to uncover the neural bases of behavior .", "Most research on the interactions between brain regions has focused on the univariate responses in the regions .", "However , ...	[ "Human behavior is supported by systems of brain regions that exchange information to complete a task .", "This exchange of information between brain regions leads to statistical relationships between their responses over time .", "Most likely , these relationships do not link only the mean responses in two bra...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology/cell differentiation", "cell biology", "genetics and genomics/functional genomics" ]	Genome-Wide Interrogation of Mammalian Stem Cell Fate Determinants by Nested Chromosome Deletions	journal.pgen.1001241	null	[ [ "Mouse ESCs , derived from the inner cell mass of the blastocyst [1] , [2] , are a lineage of choice to perform functional genomic studies for several reasons .", "First , ESCs constitute a sustained source of starting material since they indefinitely self-renew symmetrically in defined culture conditions...	[ "Understanding the function of important DNA elements in mammalian stem cell genomes would be enhanced by the availability of deletion collections in which segmental haploidies are precisely characterized .", "Using a modified Cre-loxP–based system , we now report the creation and characterization of a collection...	[ "Stem cells have received considerable public attention in part because of their potential application in regenerative therapies .", "Stem cells can be operationally defined as cells that have the unique property to self-renew , as well as to generate more differentiated progeny ( differentiation ) .", "However...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "yolk sac", "medicine and health sciences", "gene regulation", "regulatory proteins", "dna-binding proteins", "bone marrow cells", "animal models", "physiological processes", "developmental biology", "model organisms", "red blood cells", "stem cells", "experimental organism ...	A novel prospective isolation of murine fetal liver progenitors to study in utero hematopoietic defects	journal.pgen.1007127	null	[ [ "Definitive hematopoiesis is a complex , multistep process involving increasingly restrictive cell fate decisions by self-renewing , multipotent hematopoietic stem cells ( HSCs ) .", "Commitment to lymphoid , granulocytic/monocytic ( GM ) , megakaryocytic and erythroid lineages occurs through the differen...	[ "In recent years , highly detailed characterization of adult bone marrow ( BM ) myeloid progenitors has been achieved and , as a result , the impact of somatic defects on different hematopoietic lineage fate decisions can be precisely determined .", "Fetal liver ( FL ) hematopoietic progenitor cells ( HPCs ) are ...	[ "The production of red blood cells , platelet-producing megakaryocytes , and immune response-directing granulocytes and monocytes is initiated at an early stage in the developing embryo and continues throughout life .", "The proportion of each cell type varies depending on the specific needs of the organism .", ...	2018
[ "Introduction", "Methods and models", "Results", "Discussion" ]	[ "medicine and health sciences", "cardiovascular anatomy", "notch signaling", "arteries", "cardiology", "blood vessels", "aortic valve", "blood pressure", "heart rate", "signal transduction", "anatomy", "cell biology", "aorta", "biology and life sciences", "coronary arteries", "vascular...	Pulse transit time estimation of aortic pulse wave velocity and blood pressure using machine learning and simulated training data	journal.pcbi.1007259	null	[ [ "This paper considers continuous monitoring of cardiac health using computational modelling .", "Stiffening of the arterial wall , such as aorta , causes reduction in the pulsatile properties in the vascular tree , accelerates the vascular premature ageing and predisposes to the dysfunction of the heart ,...	[ "Recent developments in cardiovascular modelling allow us to simulate blood flow in an entire human body .", "Such model can also be used to create databases of virtual subjects , with sizes limited only by computational resources .", "In this work , we study if it is possible to estimate cardiovascular health ...	[ "Recently there has been a strong trend for self-monitoring of your cardiovascular health and new wearable sport trackers and mobile applications are coming to the market everyday .", "However , such solutions are mostly taking advantage of heart rate measurement .", "Other health indices such as blood pressure...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in Caenorhabditis elegans	journal.pgen.1004985	null	[ [ "Caenorhabditis elegans is a ubiquitous model animal often employed in studies of aging and metabolic disease , processes intimately associated with mitochondrial health .", "However , comparatively little is known of mtDNA maintenance in this organism [1 , 2] .", "Early studies of mitochondrial DNA (...	[ "Mitochondrial DNA ( mtDNA ) encodes respiratory complex subunits essential to almost all eukaryotes; hence respiratory competence requires faithful duplication of this molecule .", "However , the mechanism ( s ) of its synthesis remain hotly debated .", "Here we have developed Caenorhabditis elegans as a conve...	[ "Defects in the mitochondrial DNA ( mtDNA ) that encodes protein subunits of the respiratory complexes may cause severe metabolic disease in humans .", "Such defects are often caused by errors during mtDNA synthesis , motivating ongoing studies of this process .", "The nematode Caenorhabditis elegans has been p...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/parasitology", "cell biology/cell growth and division", "chemical biology/chemical biology of the cell" ]	The Aurora Kinase in Trypanosoma brucei Plays Distinctive Roles in Metaphase-Anaphase Transition and Cytokinetic Initiation	journal.ppat.1000575	null	[ [ "The Aurora-like kinases are essential mitotic regulators among eukaryotes .", "In metazoa , there are three such enzymes; Aurora A regulating spindle assembly , Aurora B promoting chromosome segregation and cytokinesis and Aurora C controlling chromosome segregation during male meiosis .", "But only ...	[ "Aurora B kinase is an essential regulator of chromosome segregation with the action well characterized in eukaryotes .", "It is also implicated in cytokinesis , but the detailed mechanism remains less clear , partly due to the difficulty in separating the latter from the former function in a growing cell .", "...	[ "The chromosomal passenger complex ( CPC ) is essential for chromosome segregation and cytokinesis in eukaryotes , but the detailed mechanism of cytokinetic regulation remains less clear , partly due to the difficulty in separating the two functions in a growing cell .", "A chemical genetic approach by adding an ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "molecular neuroscience", "animal genetics", "neuroscience", "animals", "animal models", "mutation", "drosophila melanogaster", "model organisms", "zoology", "drosophila", "research and analysis methods", "insects", "arthropoda", "animal physiology", "phenotypes", "h...	Role for Circadian Clock Genes in Seasonal Timing: Testing the Bünning Hypothesis	journal.pgen.1004603	null	[ [ "Seasonal changes in day-length provide a reliable environmental cue used by many temperate species to adapt to their fluctuating environments .", "While the available evidence suggests that changes in day-length are monitored by an internal photoperiodic timer [1] , intensive studies of photoperiodicity ...	[ "A major question in chronobiology focuses around the “Bünning hypothesis” which implicates the circadian clock in photoperiodic ( day-length ) measurement and is supported in some systems ( e . g . plants ) but disputed in others .", "Here , we used the seasonally-regulated thermotolerance of Drosophila melanoga...	[ "The circadian clock consists of an extensive genetic network that drives daily rhythms of physiological , biochemical and behavioural processes .", "The network is evolutionary conserved and has been extensively studied in a broad range of organisms .", "Another genetic network constitutes the photoperiodic cl...	2014
[ "Introduction", "Results", "T3SS-effectors epitopes have a much lower affinity than other epitopes in bacteria", "Intracellular bacterial toxins are similar to Gram Negative T3SS effectors in terms of immune-induced evolution", "", "", "", "The interesting case of ExoU – an indirect killer", "Valida...	[ "algorithms", "computer science", "immunology", "biology", "evolutionary biology" ]	Bacteria Modulate the CD8+ T Cell Epitope Repertoire of Host Cytosol-Exposed Proteins to Manipulate the Host Immune Response	journal.pcbi.1002220	null	[ [ "CD8+ T-cells recognize mainly cytosolic epitopes presented on MHC-I molecules .", "Their response is thus assumed to be directed mainly against viruses [1] , [2] , [3] .", "Bacterial proteins , on the other hand , are typically expressed outside the cytosol , and as such , induce CD4+ T-cells and B c...	[ "The main adaptive immune response to bacteria is mediated by B cells and CD4+ T-cells .", "However , some bacterial proteins reach the cytosol of host cells and are exposed to the host CD8+ T-cells response .", "Both gram-negative and gram-positive bacteria can translocate proteins to the cytosol through type ...	[ "Bacterial proteins are mainly exposed to B-cells and CD4+ T-cells , while CD8+ T-cells ( CTL ) typically respond to viruses .", "The limitation of the CTL response to viruses results from processing pathways of epitopes presented to CTLs .", "These epitopes usually stem from proteins expressed in the cytosol ....	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "chemical compounds", "aliphatic amino acids", "gene regulation", "applied mathematics", "brassica", "organic compounds", "simulation and modeling", "algorithms", "gene function", "leucine", "model organisms", "mathematics", "clustering algorithms", "amino acids", "plants", "research a...	Utility and Limitations of Using Gene Expression Data to Identify Functional Associations	journal.pcbi.1005244	null	[ [ "With the ease of sequencing , an ever increasing number of genomes from a wide range of species are available .", "One major challenge is to ascribe functions to genomic features .", "For example , while ~70% of Arabidopsis thaliana genes have annotated functions [1] , only ~40% of these annotations ...	[ "Gene co-expression has been widely used to hypothesize gene function through guilt-by association .", "However , it is not clear to what degree co-expression is informative , whether it can be applied to genes involved in different biological processes , and how the type of dataset impacts inferences about gene ...	[ "There remain genes with no known function even in the most well studied , model species .", "One common way to hypothesize gene function is based on the assumption that genes with similar expression profiles tend to have similar functions .", "However , using datasets and biological pathway information from th...	2016
[ "Introduction", "Results/Discussion", "Methods" ]	[ "physics", "computer science", "chemistry", "biology" ]	Molecular Mechanism of Cyclodextrin Mediated Cholesterol Extraction	journal.pcbi.1002020	null	[ [ "Among all cyclodextrins ( CDs ) , the most abundant are - , - , and -CDs with six , seven and eight glucopyranose monomers , respectively .", "They have a rigid conical molecular structure with a hydrophobic interior and a hydrophilic exterior .", "The internal cavity of these molecules is able to in...	[ "The depletion of cholesterol from membranes , mediated by β-cyclodextrin ( β-CD ) is well known and documented , but the molecular details of this process are largely unknown .", "Using molecular dynamics simulations , we have been able to study the CD mediated extraction of cholesterol from model membranes , in...	[ "The ability of certain molecules to capture other molecules forming so-called inclusion complexes has a range of potential important applications in e . g . drug delivery and chemical sensing .", "Here we study the complexation of cholesterol by small oligosaccharide rings named cyclodextrins ( CDs ) .", "Chol...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "bacteriology", "cell death", "medicine and health sciences", "immune cells", "nuclear staining", "pathology and laboratory medicine", "pathogens", "immunology", "cell processes", "microbiology", "inflammasomes", "bacteria", "bacterial pathogens", "research and analysis me...	Inhibition of caspase-1 or gasdermin-D enable caspase-8 activation in the Naip5/NLRC4/ASC inflammasome	journal.ppat.1006502	null	[ [ "Legionella pneumophila is the causative agent of Legionnaires’ disease .", "It was identified for the first time in 1976 , after an atypical pneumonia affected the participants of the American Legion Convention in Philadelphia , United States [1] .", "After isolation , L . pneumophila were characteri...	[ "Legionella pneumophila is a Gram-negative , flagellated bacterium that survives in phagocytes and causes Legionnaires’ disease .", "Upon infection of mammalian macrophages , cytosolic flagellin triggers the activation of Naip/NLRC4 inflammasome , which culminates in pyroptosis and restriction of bacterial replic...	[ "Legionella pneumophila is the causative agent of Legionnaires’ disease , an atypical pneumophila that affects people worldwide .", "Besides the clinical importance , L . pneumophila is a very useful model of pathogenic bacteria for investigation of the interactions of innate immune cells with bacterial pathogens...	2017
[ "Introduction", "Results and Discussion", "Materials And Methods" ]	[ "complex systems", "physics", "population ecology", "urban ecology", "mathematics", "theoretical biology", "ecology", "population modeling", "interdisciplinary physics", "applied mathematics", "biology", "computational biology", "infectious disease modeling" ]	Decelerating Spread of West Nile Virus by Percolation in a Heterogeneous Urban Landscape	journal.pcbi.1002104	null	[ [ "Urbanization , due to both population growth in cities and immigration from rural communities , now concentrates almost half of the global human population ( 3 . 3 out of 6 . 8 billion people ) into urban centres where crowding promotes the spread of infectious diseases [1] .", "Transmission of vector-bo...	[ "Vector-borne diseases are emerging and re-emerging in urban environments throughout the world , presenting an increasing challenge to human health and a major obstacle to development .", "Currently , more than half of the global population is concentrated in urban environments , which are highly heterogeneous in...	[ "Current theory of the spatial spread of pathogens predicts travelling waves at constant or increasing speed in homogeneous environments .", "However , in urban environments , increasing and often unregulated development produces a highly heterogeneous landscape .", "Such heterogeneity affects pathogens spread ...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "learning", "ellipses", "social sciences", "mathematical models", "geometry", "learning and memory", "neuroscience", "cognitive psychology", "mathematics", "statistics (mathematics)", "cognition", "memory", "distribution curves", "vision", "research and analysis methods", "statistical ...	Suboptimal Criterion Learning in Static and Dynamic Environments	journal.pcbi.1005304	null	[ [ "Understanding how humans make decisions based on uncertain sensory information is crucial to understanding how humans interpret and act on the world .", "For over 60 years , signal detection theory has been used to analyze detection and discrimination tasks [1] .", "Typically , sensory data are assum...	[ "Humans often make decisions based on uncertain sensory information .", "Signal detection theory ( SDT ) describes detection and discrimination decisions as a comparison of stimulus “strength” to a fixed decision criterion .", "However , recent research suggests that current responses depend on the recent histo...	[ "Understanding how humans make decisions based on uncertain sensory information is crucial to understanding how humans interpret and act on the world .", "Signal detection theory models discrimination and detection decisions as a comparison of “stimulus strength” to a fixed criterion .", "In a world that is con...	2017
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[]	Fitness and Phenotypic Characterization of Miltefosine-Resistant Leishmania major	journal.pntd.0003948	null	[ [ "Leishmaniasis is caused by protozoan parasites of the genus Leishmania , and presents as a variety of clinical manifestations ranging from lesions on the skin to disseminated visceral infections [1] .", "Cutaneous leishmaniasis ( CL ) often results in self-resolving lesions , whereas visceral leishmanias...	[ "Trypanosomatid parasites of the genus Leishmania are the causative agents of leishmaniasis , a neglected tropical disease with several clinical manifestations .", "Leishmania major is the causative agent of cutaneous leishmaniasis ( CL ) , which is largely characterized by ulcerative lesions appearing on the ski...	[ "Cutaneous Leishmaniasis ( CL ) is characterized by the appearance of ulcerative lesions on the skin , and results from infection with trypanosomatid parasites such as Leishmania major .", "Current treatments for CL are expensive and have a wide range of toxic side effects of variable severity .", "Miltefosine ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "chromosome structure and function", "microbiology", "escherichia coli", "prokaryotic models", "model organisms", "dna replication", "forms of dna", "dna recombination", "dna", "bacterial pathogens", "research and analysis methods", "chromosome biology", "medical microbiolo...	Roles of Type 1A Topoisomerases in Genome Maintenance in Escherichia coli	journal.pgen.1004543	null	[ [ "Type 1A topoisomerases ( topos ) are essential and ubiquitous enzymes found in bacteria , archaea and eukarya [1] , [2] .", "They all require single-stranded DNA ( ssDNA ) regions for activity .", "Such substrates can already be present , for example , in negatively supercoiled DNA , at the replicati...	[ "In eukaryotes , type 1A topoisomerases ( topos ) act with RecQ-like helicases to maintain the stability of the genome .", "Despite having been the first type 1A enzymes to be discovered , much less is known about the involvement of the E . coli topo I ( topA ) and III ( topB ) enzymes in genome maintenance .", ...	[ "DNA topoisomerases are ubiquitous enzymes that solve the topological problems associated with replication , transcription and recombination .", "Eukaryotic enzymes of the type 1A family work with RecQ-like helicases such as BLM and Sgs1 and are involved in genome maintenance .", "Interestingly , E . coli topo ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Explaining Diversity in Metagenomic Datasets by Phylogenetic-Based Feature Weighting	journal.pcbi.1004186	null	[ [ "Thanks to the possibility to characterize microbial communities through next generation sequencing , microbial ecology has become a central topic in many environmental and therapeutic applications .", "Extensive explorative studies of the microbiota colonizing several districts of the human body have bee...	[ "Metagenomics is revolutionizing our understanding of microbial communities , showing that their structure and composition have profound effects on the ecosystem and in a variety of health and disease conditions .", "Despite the flourishing of new analysis methods , current approaches based on statistical compari...	[ "In metagenomics , the composition of complex microbial communities is characterized using Next Generation Sequencing technologies .", "Thanks to the decreasing cost of sequencing , large amounts of data have been generated for environmental samples and for a variety of health-associated conditions .", "In para...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "species colonization", "ecology and environmental sciences", "medicine and health sciences", "invasive species", "population genetics", "geographical locations", "animals", "genetic mapping", "population biology", "insect vectors", "africa", "infectious diseases", "camero...	Update on the geographical distribution and prevalence of Aedes aegypti and Aedes albopictus (Diptera: Culicidae), two major arbovirus vectors in Cameroon	journal.pntd.0007137	null	[ [ "Aedes-borne arboviral diseases such as dengue , Zika , and chikungunya are increasing global public health problems due to their rapid geographical spread and rising disease burden [1 , 2] .", "The viruses causing these infections are transmitted to vertebrates , including human , mainly by bites of infe...	[ "Arboviral diseases including dengue are increasingly spreading in the tropical/subtropical world including Africa .", "Updated knowledge on the distribution and abundance of the major vectors Aedes aegypti and Aedes albopictus constitutes crucial surveillance action to prepare African countries such as Cameroon ...	[ "Aedes albopictus and Ae .", "aegypti are the most important arbovirus vectors worldwide .", "Ae .", "albopictus , native of Asia , was recorded for the first time in early 2000s in Cameroon , central Africa .", "Previous studies performed a decade ago in Cameroon showed that Ae .", "albopictus has a geog...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "invertebrates", "medicine and health sciences", "reproductive system", "retrotransposons", "chromosome structure and function", "animals", "invertebrate genomics", "animal models", "telomeres", "drosophila melanogaster", "model organisms", "experimental organism sys...	Natural variation of piRNA expression affects immunity to transposable elements	journal.pgen.1006731	null	[ [ "The main function of the PIWI-interacting RNA ( piRNA ) system in Drosophila is suppression of transposon activity in the germline .", "piRNAs are processed from long transcripts , piRNA-precursors , encoded by distinct genomic regions enriched in TE remnants , termed piRNA clusters [1] .", "piRNAs r...	[ "In the Drosophila germline , transposable elements ( TEs ) are silenced by PIWI-interacting RNA ( piRNA ) that originate from distinct genomic regions termed piRNA clusters and are processed by PIWI-subfamily Argonaute proteins .", "Here , we explore the variation in the ability to restrain an alien TE in differ...	[ "Transposon activity in the germline is suppressed by the PIWI-interacting RNA ( piRNA ) pathway .", "The resistance of natural Drosophila strains to transposon invasion varies considerably , but the nature of this variability is unknown .", "We discovered that natural variation in the efficiency of primary piR...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "none", "neurological disorders", "neuroscience" ]	Serotonin, Inhibition, and Negative Mood	journal.pcbi.0040004	null	[ [ "Serotonin ( 5-hydroxytryptamine [5-HT] ) is a neuromodulator that", "appears to play a critical role in a wealth of psychiatric conditions , including", "depression , anxiety , panic , and obsessive compulsions .", "However , despite the", "importance of serotonergic pharmacotherapies , notab...	[ "Pavlovian predictions of future aversive outcomes lead to behavioral inhibition ,", "suppression , and withdrawal .", "There is considerable evidence for the involvement", "of serotonin in both the learning of these predictions and the inhibitory", "consequences that ensue , although less for a causal rela...	[ "Serotonin is an evolutionarily ancient neuromodulator probably best known for", "its role in psychiatric disorders .", "However , that role has long appeared", "contradictory to its role in normal function , and indeed its various roles", "in normal affective behaviors have been hard to reconcile .", "He...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "body fluids", "cardiovascular anatomy", "oxygen", "blood counts", "capillaries", "hemodynamics", "arterioles", "blood vessels", "chemistry", "hematology", "blood plasma", "blood flow", "hematocrit", "blood", "anatomy", "physiology", "biology and lif...	Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex	journal.pcbi.1006549	null	[ [ "There is agreement that the neurovascular unit locally controls the cerebral blood flow response .", "Yet , oxygen supply exceeds the metabolic demand of neuronal activation for reasons that still remain uncertain [5] .", "Because of the massive size of the mammalian brain with its immense number of ...	[ "Recent advances in modeling oxygen supply to cortical brain tissue have begun to elucidate the functional mechanisms of neurovascular coupling .", "While the principal mechanisms of blood flow regulation after neuronal firing are generally known , mechanistic hemodynamic simulations cannot yet pinpoint the exact...	[ "The brain’s astonishing cognitive capacity depends on the coordination between neurons and the cerebral circulation , a system known as the neurovascular unit .", "The spatial and temporal coupling between these two networks is the object of intense research .", "However , the concise anatomical description of...	2018
[ "Introduction", "Results/Discussion", "Methods", "Supporting Information" ]	[ "eukaryotes", "infectious diseases", "genetics and genomics", "microbiology" ]	Genome Sequence of Babesia bovis and Comparative Analysis of Apicomplexan Hemoprotozoa	journal.ppat.0030148	null	[ [ "Babesiosis is a tick-borne , hemoprotozoan disease enzootic in ruminants in most sub-temperate and tropical areas of the world ( reviewed in [1] ) .", "It is recognized as an emerging zoonotic disease of humans , particularly in immunocompromised individuals [2] , and is of historical significance as the...	[ "Babesia bovis is an apicomplexan tick-transmitted pathogen of cattle imposing a global risk and severe constraints to livestock health and economic development .", "The complete genome sequence was undertaken to facilitate vaccine antigen discovery , and to allow for comparative analysis with the related apicomp...	[ "Vector-transmitted blood parasites cause some of the most widely distributed , serious , and poorly controlled diseases globally , including the most severe form of human malaria caused by Plasmodium falciparum .", "In livestock , tick-transmitted blood parasites include the protozoa Theileria parva , the cause ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "medicine and health sciences", "face", "variant genotypes", "genetic mapping", "mathematics", "statistics (mathematics)", "genome analysis", "research and analysis methods", "genomic signal processing", "mathematical and statistical techniques", "statistical...	Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology	journal.pgen.1006149	null	[ [ "Numerous lines of converging evidence indicate that variation in facial morphology has a strong genetic basis .", "These include the results of human heritability studies using twin and parent-offspring designs [1–5] , Mendelian craniofacial syndromes [6] , transgenic animal models with distinctive crani...	[ "Numerous lines of evidence point to a genetic basis for facial morphology in humans , yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features .", "We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived f...	[ "There is a great deal of evidence that genes influence facial appearance .", "This is perhaps most apparent when we look at our own families , since we are more likely to share facial features in common with our close relatives than with unrelated individuals .", "Nevertheless , little is known about how varia...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "antimicrobials", "invertebrates", "medicine and health sciences", "parasite groups", "gut bacteria", "body fluids", "plasmodium", "drugs", "microbiology", "enterobacter infections", "parasitic diseases", "animals", "parasitology", "bacterial diseases", "apicomplexa", "antibiotics", ...	PGRP-LD mediates A. stephensi vector competency by regulating homeostasis of microbiota-induced peritrophic matrix synthesis	journal.ppat.1006899	null	[ [ "Malaria is caused by parasites from the genus Plasmodium .", "The disease kills over 500 , 000 people annually , most of which are children under the age of 5 [1] .", "In order to transmit between humans , Plasmodium must overcome several obstacles to complete its development in Anopheles mosquitoes ...	[ "Peptidoglycan recognition proteins ( PGRPs ) and commensal microbes mediate pathogen infection outcomes in insect disease vectors .", "Although PGRP-LD is retained in multiple vectors , its role in host defense remains elusive .", "Here we report that Anopheles stephensi PGRP-LD protects the vector from malari...	[ "Malaria parasites must overcome several obstacles to complete their development in mosquito .", "Understanding the interactions between parasites and mosquitoes will provide potential targets to control malaria transmission .", "PGRP-LD is a peptidoglycan recognition protein , of which limit information is ava...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "cell biology", "biology and life sciences", "microbiology", "molecular cell biology" ]	The Kinase Regulator Mob1 Acts as a Patterning Protein for Stentor Morphogenesis	journal.pbio.1001861	Here we demonstrate that RNAi can be used in molecular studies of the giant single-celled ciliate Stentor coeruleus, revealing morphogenetic functions of Mob1 and highlighting the potential of this classical model for studies of morphogenesis and regeneration.	[ [ "The ability to develop and regenerate complex morphologies from a simpler starting point is among the properties that set living organisms apart from inanimate matter .", "Although these processes are most often considered in the context of embryos and multicellular organisms , even individual cells need...	[ "Morphogenesis and pattern formation are vital processes in any organism , whether unicellular or multicellular .", "But in contrast to the developmental biology of plants and animals , the principles of morphogenesis and pattern formation in single cells remain largely unknown .", "Although all cells develop p...	[ "Cells have the ability to develop complex morphologies , but the mechanisms that determine these varied shapes are not well understood .", "Cell shape determination can be challenging to study in multicellular organisms because it can be difficult to know whether shape changes are determined internally within an...	2014

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