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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" ]	[ "biotechnology", "plant anatomy", "gene regulation", "plant physiology", "plant science", "stem cells", "genetically modified plants", "plants", "flowering plants", "flower anatomy", "genetic engineering", "genetically modified organisms", "animal cells", "stem cell niche", "proteins", ...	CLAVATA1 controls distinct signaling outputs that buffer shoot stem cell proliferation through a two-step transcriptional compensation loop	journal.pgen.1006681	null	[ [ "Co-operative receptor kinase function is a common feature in both animal and plant signaling systems .", "Receptor kinase mutants are frequently genetically additive in plants but the molecular mechanisms underlying this effect are often different .", "For instance , double mutants between the EF-TU ...	[ "The regulation of stem cell proliferation in plants is controlled by intercellular signaling pathways driven by the diffusible CLAVATA3 ( CLV3p ) peptide .", "CLV3p perception is thought to be mediated by an overlapping array of receptors in the stem cell niche including the transmembrane receptor kinase CLV1 , ...	[ "The proliferation of plant stem cells in above ground tissues is controlled by a suite of receptors in response to the CLAVATA3 peptide ligand .", "Receptor signaling in response to CLAVATA3 prevents over-proliferation of stem cells .", "It is unclear what the functional relationship is between the proposed CL...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/theoretical neuroscience", "neuroscience/sensory systems", "computational biology/computational neuroscience" ]	Combining Structural Connectivity and Response Latencies to Model the Structure of the Visual System	journal.pcbi.1000159	null	[ [ "What are the elements of the visual system in the brain and how are they connected ?", "A large amount of research in vision science has been devoted to these questions .", "The most apparent way to answer the question of connectivity is to look at the structural connections between functionally defi...	[ "Several approaches exist to ascertain the connectivity of the brain , and these approaches lead to markedly different topologies , often incompatible with each other .", "Specifically , recent single-cell recording results seem incompatible with current structural connectivity models .", "We present a novel me...	[ "Visual perception is very important to us , something we can easily come to realize if we imagine ourselves blind .", "The visual system consists of numerous interconnected brain areas .", "If we are to understand the functioning of the visual system , then we will need to understand the connectivity between t...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "velocity", "biosensors", "cell physiology", "cell motility", "classical mechanics", "engineering and technology", "light", "electromagnetic radiation", "cell polarity", "developmental biology", "mathematics", "statistical distributions", "light pulses", "probability theory", "physics", ...	Profiling cellular morphodynamics by spatiotemporal spectrum decomposition	journal.pcbi.1006321	null	[ [ "Cell morphology and morphodynamics are used to phenotype the state of a cell throughout various processes , including differentiation , proliferation , migration and apoptosis[1–5] .", "Moreover , numerous signaling pathways converge onto cytoskeleton architecture that determines morphological variation ...	[ "Cellular morphology and associated morphodynamics are widely used for qualitative and quantitative assessments of cell state .", "Here we implement a framework to profile cellular morphodynamics based on an adaptive decomposition of local cell boundary motion into instantaneous frequency spectra defined by the H...	[ "Many studies in cell biology employ global shape descriptors to probe mechanisms of cell morphogenesis .", "Here , we implement a framework in this paper to profile cellular morphodynamics very locally .", "We employ the Hilbert-Huang transform ( HHT ) to extract along the entire cell edge spectra of instantan...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "medicine and health sciences", "immune physiology", "anaphase", "hela cells", "cell cycle and cell division", "cell processes", "immunology", "biological cultures", "mitosis", "immunoprecipitation", "cytokinesis", "cell cultures", "antibodies", "cellular structures an...	Anillin Phosphorylation Controls Timely Membrane Association and Successful Cytokinesis	journal.pgen.1006511	null	[ [ "In cytokinesis , cells assemble and stabilize an actomyosin ring between segregated chromosomes to generate daughter cells .", "The positioning of the cleavage furrow is controlled by negative signals from astral microtubules and positive signals established from the central spindle [1 , 2] .", "At a...	[ "During cytokinesis , a contractile ring generates the constricting force to divide a cell into two daughters .", "This ring is composed of filamentous actin and the motor protein myosin , along with additional structural and regulatory proteins , including anillin .", "Anillin is a required scaffold protein th...	[ "Human diseases such as cancer and congenital trisomies arise from loss of genetic material during cell division .", "Yet in most divisions , cells preserve their genetic integrity by strict coordination of cell membrane cleavage ( cytokinesis ) , with accurate separation of genetic material ( mitosis ) .", "Th...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genetic Recombination Is Targeted towards Gene Promoter Regions in Dogs	journal.pgen.1003984	null	[ [ "Until recently the mechanisms controlling the localization of recombination hotspots in mammalian genomes were largely unknown .", "However , recent research has revealed that zinc-finger protein , PRDM9 , binds to specific DNA motifs in the early stages of recombination initiation in order to direct suc...	[ "The identification of the H3K4 trimethylase , PRDM9 , as the gene responsible for recombination hotspot localization has provided considerable insight into the mechanisms by which recombination is initiated in mammals .", "However , uniquely amongst mammals , canids appear to lack a functional version of PRDM9 a...	[ "Recombination in mammalian genomes tends to occur within highly localized regions known as recombination hotspots .", "These hotspots appear to be a ubiquitous feature of mammalian genomes , but tend to not be shared between closely related species despite high levels of DNA sequence similarity .", "This dispa...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "immunology/immunity to infections" ]	Immunity to Distinct Sand Fly Salivary Proteins Primes the Anti-Leishmania Immune Response towards Protection or Exacerbation of Disease	journal.pntd.0000226	null	[ [ "In leishmaniasis , phlebotomine sand flies transmit Leishmania parasites to a mammalian host by depositing the parasite in the skin during probing and feeding .", "Together with the parasite , sand flies deposit a repertoire of salivary components that assist the sand fly in getting a blood meal [1] .", ...	[ "Leishmania parasites are transmitted in the presence of sand fly saliva .", "Together with the parasite , the sand fly injects biologically active salivary components that favorably change the environment at the feeding site .", "Exposure to bites or to salivary proteins results in immunity specific to these c...	[ "In vector-borne diseases , the role of vectors has been overlooked in the search for vaccines .", "Nonetheless , there is a body of evidence showing the importance of salivary proteins of vectors in pathogen transmission .", "Leishmaniasis is a neglected vector-borne disease transmitted by sand flies .", "Pr...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "psychology", "cognitive psychology", "social sciences", "behavior", "personality", "biology and life sciences", "neuropsychology", "cognitive science", "neuroscience" ]	Optimism as a Prior Belief about the Probability of Future Reward	journal.pcbi.1003605	null	[ [ "Optimism is known to play an important role in human experience leading to more happiness , greater achievements and better health [1] , although inappropriate optimism can also lead to poor choices [2] .", "Low optimism is also closely associated with depression and anxiety [3] .", "Because of this ...	[ "Optimists hold positive a priori beliefs about the future .", "In Bayesian statistical theory , a priori beliefs can be overcome by experience .", "However , optimistic beliefs can at times appear surprisingly resistant to evidence , suggesting that optimism might also influence how new information is selected...	[ "The optimism bias is regarded as one of the most prevalent and robust cognitive biases documented in psychology and behavioral economics .", "In individuals , trait optimism is usually measured using self-report questionnaires .", "However , choices in simple behavioral tasks can also be used to infer how opti...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "legs", "diagnostic radiology", "charcot-marie-tooth disease", "genetic diseases", "limbs (anatomy)", "magnetic resonance imaging", "animal models", "mutation", "model organisms", "bioassays and physiological analysis", "muscle electrophysiology", "nerve condu...	A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy	journal.pgen.1005829	null	[ [ "Charcot-Marie-Tooth disease ( CMT ) represents a group of inherited peripheral neuropathies with a heterogeneous genetic and clinical spectrum .", "The typical CMT phenotype is characterized by distal weakness , sensory loss , foot deformities , and absence of reflexes [1] .", "CMT is broadly classif...	[ "Charcot-Marie-Tooth disease ( CMT ) is a heterogeneous group of peripheral neuropathies with diverse genetic causes .", "In this study , we identified p . I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical featur...	[ "Isolation of causative mutation is still challenging in genetic diseases with a variety of genetic causes .", "We discovered a mutation in a novel gene from a family exhibiting a peripheral neuropathy by virtue of next-generation sequencing .", "Although the family shows characteristic clinical features of her...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "streptococci", "medical microbiology", "biology", "microbiology", "bacterial pathogens" ]	Compensatory Evolution of pbp Mutations Restores the Fitness Cost Imposed by β-Lactam Resistance in Streptococcus pneumoniae	journal.ppat.1002000	null	[ [ "Streptococcus pneumoniae is the causal agent of human infections such as otitis , pneumonia and meningitis , which particularly affect pediatric patients .", "Penicillin and other β-lactams ( βLs ) are the treatments of choice for any pneumococcal infection .", "However , β-lactam resistance has been...	[ "The prevalence of antibiotic resistance genes in pathogenic bacteria is a major challenge to treating many infectious diseases .", "The spread of these genes is driven by the strong selection imposed by the use of antibacterial drugs .", "However , in the absence of drug selection , antibiotic resistance genes...	[ "For many years , pneumococcal infections have been usually treated with β-lactams .", "However , the rapid emergence of β-lactam resistance has complicated the antimicrobial treatment of these infections in the last two decades .", "The emergence and stability of antibiotic resistance is a complex biological p...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Novel Locus Harbouring a Functional CD164 Nonsense Mutation Identified in a Large Danish Family with Nonsyndromic Hearing Impairment	journal.pgen.1005386	null	[ [ "Nonsyndromic hearing impairment ( NSHI ) is the most frequent hereditary sensory defect in humans worldwide .", "The condition is clinically and genetically extremely heterogeneous , with more than 160 loci identified today .", "Autosomal dominant NSHI ( ADNSHI ) shows great variation in age of onset...	[ "Nonsyndromic hearing impairment ( NSHI ) is a highly heterogeneous condition with more than eighty known causative genes .", "However , in the clinical setting , a large number of NSHI families have unexplained etiology , suggesting that there are many more genes to be identified .", "In this study we used SNP...	[ "It is known that hearing impairment running in families can be caused by mutations in more than eighty different genes .", "However , there are still families where the responsible gene is unknown .", "By studying a large Danish family with dominant inherited hearing impairment , we found that the disorder cos...	2015
[ "Introduction", "Materials and methods", "Results/Discussion" ]	[ "medicine and health sciences", "microcephaly", "pathology and laboratory medicine", "maternal health", "obstetrics and gynecology", "pathogens", "geographical locations", "microbiology", "vector-borne diseases", "viruses", "developmental biology", "women's health", "rna viruses", "morphog...	Potential inconsistencies in Zika surveillance data and our understanding of risk during pregnancy	journal.pntd.0006991	null	[ [ "A substantial body of experimental and clinical evidence implicates Zika virus ( ZIKV ) infection in the sharp rise in the incidence of microcephaly cases in Brazil at the end of 2015 .", "[1–5] Previous population-level studies investigating the relationship between ZIKV and microcephaly incidence found...	[ "A significant increase in microcephaly incidence was reported in Northeast Brazil at the end of 2015 , which has since been attributed to an epidemic of Zika virus ( ZIKV ) infections earlier that year .", "Further incidence of congenital Zika syndrome ( CZS ) was expected following waves of ZIKV infection throu...	[ "Zika virus ( ZIKV ) infection is associated with the rise of microcephaly cases observed in Northeast Brazil at the end of 2015 .", "For women in endemic or at-risk areas , understanding how the relationship between time of infection and microcephaly risk varies through pregnancy is important in informing family...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Inferring Evolutionary Histories of Pathway Regulation from Transcriptional Profiling Data	journal.pcbi.1003255	null	[ [ "Comparative studies of gene expression across species routinely detect regulatory variation at thousands of loci [1] .", "Whether and how these expression changes are of evolutionary relevance has become a central question in the field .", "In landmark cases , experimental dissection of model phenoty...	[ "One of the outstanding challenges in comparative genomics is to interpret the evolutionary importance of regulatory variation between species .", "Rigorous molecular evolution-based methods to infer evidence for natural selection from expression data are at a premium in the field , and to date , phylogenetic app...	[ "Comparative transcriptomic studies routinely identify thousands of genes differentially expressed between species .", "The central question in the field is whether and how such regulatory changes have been the product of natural selection .", "Can the signal of evolutionarily relevant expression divergence be ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine" ]	Is Zinc Concentration in Toxic Phase Plasma Related to Dengue Severity and Level of Transaminases?	journal.pntd.0002287	null	[ [ "The immunopathogenesis of dengue viral infection ( DVI ) is not well understood , and the level of disease severity is multifactorial , depending on various factors such as viral virulence , secondary DVI , immune response to DVI , and host factors including genetic and nutritional status [1]–[3] .", "Pl...	[ "To determine the relationship between plasma zinc values and the severity of dengue viral infection ( DVI ) and DVI-caused hepatitis .", "A prospective cohort study was conducted during 2008–2010 in hospitalized children aged <15 years confirmed with DVI .", "Complete blood count , aspartate aminotransferase (...	[ "Dengue viral infection ( DVI ) is endemic in tropical counties and severe DVI is a significant cause of death , especially in children .", "Increased vascular endothelial permeability during the defervescence stage of DVI leading to plasma leakage plays an important role in dengue disease severity .", "Zinc is...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Effects on Murine Behavior and Lifespan of Selectively Decreasing Expression of Mutant Huntingtin Allele by Supt4h Knockdown	journal.pgen.1005043	null	[ [ "Huntington’s disease ( HD ) is one of a collection of untreatable and devastating neurodegenerative and neuromuscular diseases that result from expansion of segments of trinucleotide repeats ( TNRs ) present within certain genes [1–3] .", "Whereas the huntingtin ( HTT ) gene normally includes fewer than ...	[ "Production of protein containing lengthy stretches of polyglutamine encoded by multiple repeats of the trinucleotide CAG is a hallmark of Huntington’s disease ( HD ) and of a variety of other inherited degenerative neurological and neuromuscular disorders .", "Earlier work has shown that interference with produc...	[ "Huntington’s disease ( HD ) is an inherited genetic disorder that leads to degeneration of brain cells and consequently to abnormal body movements , decreased mental capacity , and death .", "It is one of a group of untreatable degenerative neurological and neuromuscular diseases caused by expansion of gene segm...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "homologous chromosomes", "spermatocytes", "cell cycle and cell division", "cell processes", "germ cells", "oocytes", "dna", "sperm", "homologous recombination", "animal cells", "chromosome biology", "proteins", "recombinant proteins", "biochemistry", "cell biology", "nucl...	Alignment of Homologous Chromosomes and Effective Repair of Programmed DNA Double-Strand Breaks during Mouse Meiosis Require the Minichromosome Maintenance Domain Containing 2 (MCMDC2) Protein	journal.pgen.1006393	null	[ [ "Chromosome segregation during the first meiotic division uniquely differs from chromosome segregation during mitosis and the second meiotic division [1 , 2] .", "Centromeres belonging to sister chromatids are pulled toward opposite spindle poles during mitosis and the second meiotic division .", "In ...	[ "Orderly chromosome segregation during the first meiotic division requires meiotic recombination to form crossovers between homologous chromosomes ( homologues ) .", "Members of the minichromosome maintenance ( MCM ) helicase family have been implicated in meiotic recombination .", "In addition , they have role...	[ "Each chromosome is present in two distinct but homologous copies in diploid organisms .", "To generate haploid gametes suitable for fertilization , these homologous chromosomes must segregate during meiosis .", "To ensure correct chromosome segregation , homologous chromosomes must align and become connected b...	2016
[ "Introduction", "Materials and Methods", "Discussion" ]	[ "infectious diseases/infectious diseases of the nervous system", "infectious diseases", "infectious diseases/neglected tropical diseases", "pathology/hematology", "infectious diseases/protozoal infections" ]	Trypanosoma brucei rhodesiense Transmitted by a Single Tsetse Fly Bite in Vervet Monkeys as a Model of Human African Trypanosomiasis	journal.pntd.0000238	null	[ [ "In human African trypanosomiasis ( HAT ) , the use of animal models has contributed enormously to what is currently known about the relationships between disease duration , parasite invasion of different body systems and the potential of resultant host clinical and biological changes as diagnostic and diseas...	[ "We have investigated the pathogenicity of tsetse ( Glossina pallidipes ) -transmitted cloned strains of Trypanosoma brucei rhodesiense in vervet monkeys .", "Tsetse flies were confirmed to have mature trypanosome infections by xenodiagnosis , after which nine monkeys were infected via the bite of a single infect...	[ "Sleeping sickness is caused by a species of trypanosome blood parasite that is transmitted by tsetse flies .", "To understand better how infection with this parasite leads to disease , we provide here the most detailed description yet of the course of infection and disease onset in vervet monkeys .", "One infe...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/nosocomial and healthcare-associated infections", "infectious diseases", "microbiology/microbial physiology and metabolism", "biotechnology/applied microbiology", "microbiology", "infectious diseases/bacterial infections", "microbiology/applied microbiology", "microbiology/microbi...	Homeostatic Interplay between Bacterial Cell-Cell Signaling and Iron in Virulence	journal.ppat.1000810	null	[ [ "Microbes translate environmental cues to coordinate and modulate gene expression such that they can adapt to different niches and overcome hostile environments .", "Adaptation and coordination of gene expression is particularly important for pathogenic microorganisms that need to colonize dynamic host en...	[ "Pathogenic bacteria use interconnected multi-layered regulatory networks , such as quorum sensing ( QS ) networks to sense and respond to environmental cues and external and internal bacterial cell signals , and thereby adapt to and exploit target hosts .", "Despite the many advances that have been made in under...	[ "Bacterial cells can communicate with one another about their surrounding environment .", "This information can be in the form of small self-secreted molecules acting as signals to activate or inhibit the expression of genes .", "Pseudomonas aeruginosa is an environmental bacterium that infects diverse organism...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "flow cytometry", "cell physiology", "phosphorylation", "vero cells", "biological cultures", "microbiology", "viral structure", "membrane proteins", "cellular structures and organelles", "research and analysis methods", "proteins", "cell lines", "viral replication", "cell membranes", "vi...	The HSV-1 mechanisms of cell-to-cell spread and fusion are critically dependent on host PTP1B	journal.ppat.1007054	null	[ [ "There are two ways that viruses can spread to uninfected cells .", "Cell-free spread occurs when virions are released from an infected cell into their surrounding environment prior to entering a new cell .", "This , of course , is how viruses spread to new hosts and often between cells within a host ...	[ "All herpesviruses have mechanisms for passing through cell junctions , which exclude neutralizing antibodies and offer a clear path to neighboring , uninfected cells .", "In the case of herpes simplex virus type 1 ( HSV-1 ) , direct cell-to-cell transmission takes place between epithelial cells and sensory neuro...	[ "It is estimated that 67% of the global population is infected with herpes simplex virus type 1 ( HSV-1 ) .", "This virus resides in sensory neurons in a quiescent state but periodically reactivates , producing virus particles that travel down the axon to infect epithelial cells of the skin , where it can be tran...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Adaptation to High Ethanol Reveals Complex Evolutionary Pathways	journal.pgen.1005635	null	[ [ "The ability to survive and proliferate in high levels of ethanol is an ecologically important and industrially relevant trait of yeast cells .", "The ethanol produced by yeast cells slows down growth of competing microbes , but at higher concentrations , it causes stress for the yeast cells themselves ."...	[ "Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes , but the molecular mechanisms underlying this complex trait remain largely unknown .", "Here , we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptat...	[ "Organisms can evolve resistance to specific stress factors , which allows them to thrive in environments where non-adapted organisms fail to grow .", "However , the molecular mechanisms that underlie adaptation to complex stress factors that interfere with basic cellular processes are poorly understood .", "In...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "cell physiology", "medicine and health sciences", "chemical characterization", "body fluids", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "staphylococcus aureus", "animal models", "clinical medicine", "model organisms", "experimental org...	Staphylococcal enterotoxin-like X (SElX) is a unique superantigen with functional features of two major families of staphylococcal virulence factors	journal.ppat.1006549	null	[ [ "Staphylococcus aureus is a serious human pathogen responsible for a large proportion of hospital acquired infections and of additional major concern , an increasing cause of community-associated antibiotic resistant infections [1 , 2] .", "Predominantly found in the anterior nares , throat , and skin it ...	[ "Staphylococcus aureus is an opportunistic pathogen that produces many virulence factors .", "Two major families of which are the staphylococcal superantigens ( SAgs ) and the Staphylococcal Superantigen-Like ( SSL ) exoproteins .", "The former are immunomodulatory toxins that induce a Vβ-specific activation of...	[ "The ability of Staphylococcus aureus to cause disease can be attributed to the wide range of toxins and immune evasion molecules it produces .", "The 25-member superantigen ( SAg ) family of toxins disrupts adaptive immunity by activating large proportions of T cells .", "In contrast , the structurally-related...	2017
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "sequencing techniques", "invertebrates", "moths and butterflies", "microbiology", "animals", "invertebrate genomics", "genomic databases", "viral genome", "genome analysis", "sequence motif analysis", "molecular biology techniques", "microbial genomics", "research and analysis methods", "...	Continuous Influx of Genetic Material from Host to Virus Populations	journal.pgen.1005838	null	[ [ "The genomes of large eukaryotic double-stranded DNA viruses contain high proportions of cellular genes resulting from host-to-virus horizontal transfers ( HT ) [1–4] .", "For example , at least 10% of giant virus genes and up to 30% of herpesvirus genes likely originated from eukaryote or prokaryote geno...	[ "Many genes of large double-stranded DNA viruses have a cellular origin , suggesting that host-to-virus horizontal transfer ( HT ) of DNA is recurrent .", "Yet , the frequency of these transfers has never been assessed in viral populations .", "Here we used ultra-deep DNA sequencing of 21 baculovirus population...	[ "While gene exchange is known to occur between viruses and their hosts , this phenomenon has never been studied at the level of the viral population .", "Here we report that each time a virus from the Baculoviridae family infects a moth , a large number ( dozens to hundreds ) and high diversity of moth DNA sequen...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "microbiome", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "salmonellosis", "bacterial diseases", "signs and symptoms", "enterobacteriaceae", "bacteria", "neutrophils", "bacterial pathogens"...	STAT2 dependent Type I Interferon response promotes dysbiosis and luminal expansion of the enteric pathogen Salmonella Typhimurium	journal.ppat.1007745	null	[ [ "A healthy gastrointestinal microbiota is characterized by the dominance of obligate anaerobic members of the phyla Bacteroidetes and Firmicutes .", "The expansion of facultative anaerobic Enterobacteriaceae ( phylum Proteobacteria ) is considered a microbial signature for gut inflammation and dysbiosis [...	[ "The mechanisms by which the gut luminal environment is disturbed by the immune system to foster pathogenic bacterial growth and survival remain incompletely understood .", "Here , we show that STAT2 dependent type I IFN signaling contributes to the inflammatory environment by disrupting hypoxia enabling the path...	[ "The spread of invading microbes is frequently contained by an inflammatory response .", "Yet , some pathogenic microbes have evolved to utilize inflammation for niche generation and to support their metabolism .", "Here , we demonstrate that S . Typhimurium exploits type I IFN signaling , a prototypical anti-v...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "gram positive bacteria", "viruses", "biochemistry", "bacterial physiology", "bacteriophages", "bacterial genes", "genetics", "biology and life sciences", "dna", "microbiology", "dna recombination", "bacterial spores", "organisms" ]	Developmentally-Regulated Excision of the SPβ Prophage Reconstitutes a Gene Required for Spore Envelope Maturation in Bacillus subtilis	journal.pgen.1004636	null	[ [ "Genetic information is normally preserved across generations in living organisms .", "However , genomic integrity is sometimes dramatically challenged by DNA rearrangement events , such as homologous recombination , viral genome integration , and transposon spreading .", "These DNA rearrangements con...	[ "Temperate phages infect bacteria by injecting their DNA into bacterial cells , where it becomes incorporated into the host genome as a prophage .", "In the genome of Bacillus subtilis 168 , an active prophage , SPβ , is inserted into a polysaccharide synthesis gene , spsM .", "Here , we show that a rearrangeme...	[ "Integration of prophages into protein-coding sequences of the host chromosome generally results in loss of function of the interrupted gene .", "In the endospore-forming organism Bacillus subtilis strain 168 , the SPβ prophage is inserted into a previously-uncharacterized spore polysaccharide synthesis gene , sp...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "transfection", "fluorescence imaging", "medicine and health sciences", "coronaviruses", "cellular stress responses", "pathology and laboratory medicine", "respiratory infections", "pathogens", "cell processes", "microbiology", "pulmonology", "plasmid construction", "viruses", "rna viruses...	Middle East Respiratory Coronavirus Accessory Protein 4a Inhibits PKR-Mediated Antiviral Stress Responses	journal.ppat.1005982	null	[ [ "Innate antiviral responses represent the first line of defense against invading viral pathogens .", "Host cells are equipped with multiple mechanisms to detect and respond to non-self , pathogen-associated molecular patterns ( PAMPs ) .", "One of these PAMPs , viral cytosolic RNA , can be detected by...	[ "Middle East respiratory syndrome coronavirus ( MERS-CoV ) causes severe respiratory infections that can be life-threatening .", "To establish an infection and spread , MERS-CoV , like most other viruses , must navigate through an intricate network of antiviral host responses .", "Besides the well-known type I ...	[ "Human coronaviruses generally cause relatively mild respiratory disease .", "In the past 15 years , the world has witnessed the emergence of two coronaviruses with high mortality rates in humans; severe acute respiratory syndrome coronavirus ( SARS-CoV ) in 2002 and Middle East respiratory syndrome coronavirus (...	2016
[ "Introduction", "Methods", "Results/Discussion" ]	[ "algorithms", "public and occupational health", "infectious diseases", "computer and information sciences", "medicine and health sciences", "environmental health", "mathematics", "epidemiology", "health care", "applied mathematics", "biology and life sciences", "infectious disease control", ...	A Likelihood-Based Approach to Identifying Contaminated Food Products Using Sales Data: Performance and Challenges	journal.pcbi.1003692	null	[ [ "In recent years global trade has significantly altered the topology of food supply chains [1] .", "As a result , the potential impact of contamination events has increased [2] .", "Worldwide , foodborne illness causes billions of dollars in healthcare related costs each year [3] , and more in economi...	[ "Foodborne disease outbreaks of recent years demonstrate that due to increasingly interconnected supply chains these type of crisis situations have the potential to affect thousands of people , leading to significant healthcare costs , loss of revenue for food companies , and—in the worst cases—death .", "When a ...	[ "Response to foodborne disease outbreaks is complicated by globalization of our food supply chains .", "Rapid identification of contaminated products is essential to limit the damage caused by foodborne disease .", "Worldwide , foodborne disease outbreaks are responsible for $9B a year in medical costs and over...	2014
[ "Introduction", "Results and discussion", "Methods" ]	[ "geomorphology", "biogeography", "irish people", "ecology and environmental sciences", "european union", "landforms", "population genetics", "geographical locations", "topography", "ireland", "ethnicities", "multivariate analysis", "mathematics", "statistics (mathematics)", "population b...	Insular Celtic population structure and genomic footprints of migration	journal.pgen.1007152	null	[ [ "Situated at the northwestern edge of Europe , Ireland is the continent’s third largest island , with a modern-day population of approximately 6 . 4 million .", "The island is politically partitioned into the Republic of Ireland and Northern Ireland , with the latter forming part of the United Kingdom ( U...	[ "Previous studies of the genetic landscape of Ireland have suggested homogeneity , with population substructure undetectable using single-marker methods .", "Here we have harnessed the haplotype-based method fineSTRUCTURE in an Irish genome-wide SNP dataset , identifying 23 discrete genetic clusters which segrega...	[ "A recent genetic study of the UK ( People of the British Isles; PoBI ) expanded our understanding of population history of the islands , using newly-developed , powerful techniques that harness the rich information embedded in chunks of genetic code called haplotypes .", "These methods revealed subtle regional d...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "evolutionary biology", "anopheles", "genetics and genomics" ]	Localization of Candidate Regions Maintaining a Common Polymorphic Inversion (2La) in Anopheles gambiae	journal.pgen.0030217	null	[ [ "Dobzhansky's studies of chromosomal inversion polymorphisms in natural populations of Drosophila provided the first evidence that selection played an indispensable role in their maintenance , helping to spark the neo-Darwinian synthesis [1 , 2] .", "More recent studies implicate selection in maintaining ...	[ "Chromosomal inversion polymorphisms are thought to play a role in adaptive divergence , but the genes conferring adaptive benefits remain elusive .", "Here we study 2La , a common polymorphic inversion in the African malaria vector Anopheles gambiae .", "The frequency of 2La varies clinally and seasonally in a...	[ "A chromosomal inversion occurs when part of the chromosome breaks , rotates 180 degrees , and rejoins the broken chromosome .", "The result is a chromosome carrying a segment whose gene order is reversed .", "Whereas the physical rearrangement itself may have no direct consequences on gene function , recombina...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "plant anatomy", "cognitive neurology", "medicine and health sciences", "fluorescence imaging", "nervous system", "electrophysiology", "neuroscience", "learning and memory", "animals", "animal models", "plant science", "model organisms", "drosophila melanogaster", "cogni...	Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release	journal.pbio.1002563	Feeding spermidine to Drosophila protects them from age-dependent memory impairment by suppressing structural and functional alterations in presynaptic performance.	[ [ "Age-dependent memory impairment ( AMI ) , which is associated with both psychiatric and neurodegenerative disorders , starts in midlife and worsens with advancing age , suggesting that the greatest driving factor is age itself .", "The lack of effective treatments that prevent , halt , or reverse the con...	[ "Memories are assumed to be formed by sets of synapses changing their structural or functional performance .", "The efficacy of forming new memories declines with advancing age , but the synaptic changes underlying age-induced memory impairment remain poorly understood .", "Recently , we found spermidine feedin...	[ "Neurons communicate by sending impulses , in the form of secretion of neurotransmitters , across small spaces called synapses .", "It is these synapses that undergo structural and functional changes during formation and retrieval of memories .", "Though alterations in synaptic performance are believed to accom...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/evolutionary modeling", "infectious diseases/viral infections", "evolutionary biology/microbial evolution and genomics", "virology/virus evolution and symbiosis" ]	Changing Selective Pressure during Antigenic Changes in Human Influenza H3	journal.ppat.1000058	null	[ [ "The rapid evolution of influenza viruses presents difficulties in recognising and predicting current and future epidemiological threats .", "One of the major sources of information about possible future threats from influenza is a study of its history as an evolving pathogen .", "Analysing how the vi...	[ "The rapid evolution of influenza viruses presents difficulties in maintaining the optimal efficiency of vaccines .", "Amino acid substitutions result in antigenic drift , a process whereby antisera raised in response to one virus have reduced effectiveness against future viruses .", "Interestingly , while amin...	[ "H3N2-type influenza is responsible for widespread disease and significant mortality .", "The virus evolves rapidly , changing its antigenic properties , allowing it to escape clearance by the immune response as well as complicating the maintenance of vaccine effectiveness .", "Part of this evolution has been t...	2008
[ "Introduction", "Methods", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "mathematics", "applied mathematics", "biology and life sciences", "immunology", "physical sciences", "immune response" ]	Antibody Responses during Hepatitis B Viral Infection	journal.pcbi.1003730	null	[ [ "Infection with hepatitis B virus ( HBV ) results in acute hepatitis followed by recovery in 85%–95% of human adults [1] .", "Recovery occurs when the organism mounts adequate immune responses against the virus .", "Such responses include production of protective , neutralizing antibodies against HBV ...	[ "Hepatitis B is a DNA virus that infects liver cells and can cause both acute and chronic disease .", "It is believed that both viral and host factors are responsible for determining whether the infection is cleared or becomes chronic .", "Here we investigate the mechanism of protection by developing a mathemat...	[ "Hepatitis B vaccine induces life-long protection in vaccinated individuals .", "In the absence of vaccination , however , hepatitis B virus can cause both self-limiting and chronic disease .", "We investigate whether antibodies against hepatitis B play a role in virus clearance .", "We developed a mathematic...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Intravenous Therapy Duration and Outcomes in Melioidosis: A New Treatment Paradigm	journal.pntd.0003586	null	[ [ "Burkholderia pseudomallei , the cause of melioidosis , is a soil- and water-borne bacterium endemic to northern Australia and parts of south-east Asia [1] .", "It most commonly causes pneumonia , bacteremia without evident focus , deep-seated abscesses and skin infection but can affect almost any part of...	[ "International melioidosis treatment guidelines recommend a minimum 10 to 14 days’ intravenous antibiotic therapy ( intensive phase ) , followed by 3 to 6 months’ oral therapy ( eradication phase ) .", "This approach is associated with rates of relapse , defined as recurrence following the eradication phase , tha...	[ "Melioidosis is an infection caused by the soil bacterium Burkholderia pseudomallei; patients usually present with pneumonia , blood-stream infection and/or skin or internal organ abscesses .", "Melioidosis occurs most commonly in northern Australia and parts of Southeast Asia .", "It has a high mortality rate ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "medicine and health sciences", "microbial mutation", "pathology and laboratory medicine", "genome evolution", "pathogens", "variant genotypes", "microbiology", "genetic mapping", "viruses", "rna viruses", "phylogenetic analysis", "microbial evolution", "molecular b...	Static and Evolving Norovirus Genotypes: Implications for Epidemiology and Immunity	journal.ppat.1006136	null	[ [ "RNA viruses evolve quickly , with mutation rates that vary between 10−3–10−4 nucleotide ( nt ) substitutions/year; up to 1000 times higher when compared with most DNA viruses [1] .", "This high mutation rate is attributed largely to the inability of their RNA polymerases to correct errors introduced duri...	[ "Noroviruses are major pathogens associated with acute gastroenteritis worldwide .", "Their RNA genomes are diverse , with two major genogroups ( GI and GII ) comprised of at least 28 genotypes associated with human disease .", "To elucidate mechanisms underlying norovirus diversity and evolution , we used a la...	[ "Efforts are underway to develop vaccines against norovirus , a leading cause of acute gastroenteritis .", "The purpose of our study was to understand how norovirus strains within different genotypes evolve and adapt as they are transmitted in the human population .", "Using large-scale genomics and computation...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genetics and genomics/gene expression" ]	Transcriptional Changes in Schistosoma mansoni during Early Schistosomula Development and in the Presence of Erythrocytes	journal.pntd.0000600	null	[ [ "The schistosome tegument , an unique double lipid bilayered syncitium that covers the external surface of the intra-mammalian developmental stages , represents the point of interaction between the parasite and mammalian host tissues .", "This structure is pivotal for parasite survival within the host and...	[ "Schistosomes cause more mortality and morbidity than any other human helminth , but control primarily relies on a single drug that kills adult worms .", "The newly transformed schistosomulum stage is susceptible to the immune response and is a target for vaccine development and rational drug design .", "To ide...	[ "Schistosome blood flukes cause more mortality and morbidity than any other human worm infection , but current control methods primarily rely on a single drug .", "There is a desperate need for new approaches to control this parasite , including vaccines .", "People become infected when the free-swimming larva ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Medically Relevant Acinetobacter Species Require a Type II Secretion System and Specific Membrane-Associated Chaperones for the Export of Multiple Substrates and Full Virulence	journal.ppat.1005391	null	[ [ "Members of the genus Acinetobacter are regarded as opportunistic human pathogens of increasing relevance worldwide due in part to the rapid emergence of multiply-drug resistant strains [1] .", "In fact , the Center for Disease Control and Prevention has recently categorized multi-drug resistant Acinetoba...	[ "Acinetobacter baumannii , A . nosocomialis , and A . pittii have recently emerged as opportunistic human pathogens capable of causing severe human disease; however , the molecular mechanisms employed by Acinetobacter to cause disease remain poorly understood .", "Many pathogenic members of the genus Acinetobacte...	[ "Members of the genus Acinetobacter , specifically , A . baumannii , A . pittii , and A . nosocomialis , have rapidly emerged as opportunistic human pathogens particularly targeting the immunocompromised patient population .", "Of significant concern is the fact that many Acinetobacter-induced infections are caus...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "plant growth and development", "enzymes", "plant embryo anatomy", "brassica", "enzymology", "phosphatases", "hormones", "membrane proteins", "developmental biology", "plant science", "model organisms", "plant hormones", "experimental organism systems", "seedlings", "p...	A subset of plasma membrane-localized PP2C.D phosphatases negatively regulate SAUR-mediated cell expansion in Arabidopsis	journal.pgen.1007455	null	[ [ "The plant hormone auxin regulates nearly all aspects of growth and development , including embryogenesis [1] , root development [2] , gravitropism [3] , leaf development [4] , vascular development [5] , phototropism [6] , shade avoidance [6] , shoot apical meristem development [7] , flower primordium formati...	[ "The plant hormone auxin regulates numerous growth and developmental processes throughout the plant life cycle .", "One major function of auxin in plant growth and development is the regulation of cell expansion .", "Our previous studies have shown that SMALL AUXIN UP RNA ( SAUR ) proteins promote auxin-induced...	[ "The plant hormone auxin is a major regulator of cell expansion , which is a fundamental cellular process essential for plant growth and development .", "The acid growth theory was proposed in the 1970s to explain auxin-induced cell expansion .", "However , the mechanistic basis of auxin-induced cell expansion ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "protein interactions", "molecular complexes", "proteins", "protein structure", "biology and life sciences", "molecular biology" ]	Crystal Structure of Calcium Binding Protein-5 from Entamoeba histolytica and Its Involvement in Initiation of Phagocytosis of Human Erythrocytes	journal.ppat.1004532	null	[ [ "Entamoeba histolytica is the etiological agent of amoebiasis ( intestinal as well as extra-intestinal ) , which results in a high level of morbidity and mortality worldwide , particularly in developing countries [1] , [2] .", "A number of studies have shown that Ca2+ and its binding proteins are centrall...	[ "Entamoeba histolytica is the etiological agent of human amoebic colitis and liver abscess , and causes a high level of morbidity and mortality worldwide , particularly in developing countries .", "There are a number of studies that have shown a crucial role for Ca2+ and its binding protein in amoebic biology .",...	[ "Entamoeba histolytica is the etiologic agent of amoebiasis , a major cause of morbidity and mortality in developing countries .", "The genome of this organism encodes 27 EF-hand containing calcium binding proteins suggesting an intricate Ca2+ signalling system that plays crucial role in phagocytosis and pathogen...	2014
[ "Introduction", "Results/Discussion", "Methods" ]	[ "protein interactions", "enzymes", "macromolecular assemblies", "globular proteins", "protein structure", "biophysics simulations", "biochemistry simulations", "proteins", "enzyme regulation", "biology", "proteomics", "biophysics", "macromolecular complex analysis", "biochemistry", "enzy...	Changes in Dynamics upon Oligomerization Regulate Substrate Binding and Allostery in Amino Acid Kinase Family Members	journal.pcbi.1002201	null	[ [ "The biological function of proteins is usually enabled by their dynamics under native state conditions , which , in turn , is encoded by their 3-dimensional ( 3D ) structure .", "Unraveling this functional code has been the aim of many experimental and theoretical studies [1]–[9] .", "In particular t...	[ "Oligomerization is a functional requirement for many proteins .", "The interfacial interactions and the overall packing geometry of the individual monomers are viewed as important determinants of the thermodynamic stability and allosteric regulation of oligomers .", "The present study focuses on the role of th...	[ "Protein function requires a three-dimensional structure with specific dynamic features for catalytic and binding events , and , in many cases , the structure results from the assembly of more than one polypeptide chain ( also called monomer or subunit ) to form an oligomer or multimer .", "Proteins such as hemog...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in Japanese Black Cattle	journal.pgen.1005433	null	[ [ "Carcass weight , as a measure of meat yield , is an economically important trait in livestock .", "Due to its economic significance , several quantitative trait locus ( QTL ) mapping and genome-wide association studies ( GWAS ) have been conducted with the objective of identifying genes for improving mea...	[ "Recessive skeletal dysplasia , characterized by joint- and/or hip bone-enlargement , was mapped within the critical region for a major quantitative trait locus ( QTL ) influencing carcass weight; previously named CW-3 in Japanese Black cattle .", "The risk allele was on the same chromosome as the Q allele that i...	[ "Livestock are typically subjected to intensive artificial selection for traits of economic value to producers .", "In spite of this strong selection , some major quantitative trait loci ( QTLs ) for an economically important trait never reach fixation in the population .", "Several studies have revealed that s...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Predominant Leptospiral Serogroups Circulating among Humans, Livestock and Wildlife in Katavi-Rukwa Ecosystem, Tanzania	journal.pntd.0003607	null	[ [ "Leptospirosis is an emerging/re-emerging , worldwide , contagious , bacterial zoonotic disease that affects all mammals , including humans , livestock and wildlife [1 , 2] .", "The disease is caused by different serovars of pathogenic species of the genus Leptospira [1 , 2] , which is common in tropical ...	[ "Leptospirosis is a worldwide zoonotic disease and a serious , under-reported public health problem , particularly in rural areas of Tanzania .", "In the Katavi-Rukwa ecosystem , humans , livestock and wildlife live in close proximity , which exposes them to the risk of a number of zoonotic infectious diseases , ...	[ "Leptospirosis is a disease of worldwide significance , and it is also an important zoonotic disease , particularly in developing countries .", "Subclinically infected rodents maintain leptospires in nature , and some that recover from the primary leptospiral infection may release the bacterium in their urine for...	2015
[ "Introduction", "Methods", "Results and Discussion" ]	[ "medicine", "infectious diseases", "schistosomiasis", "functional genomics", "gene expression", "genetics", "biology", "genomics", "parasitic diseases", "genetics and genomics", "dna transcription" ]	Gene Expression Patterns in Larval Schistosoma mansoni Associated with Infection of the Mammalian Host	journal.pntd.0001274	null	[ [ "Schistosomiasis mansoni remains an important water-borne disease of humans in Sub-Saharan Africa and parts of South America .", "Transmission between humans and the aquatic intermediate molluscan host is effected by a miracidium .", "This free-swimming larva hatches from eggs excreted in the faeces a...	[ "The infective schistosome cercaria develops within the intramolluscan daughter sporocyst from an undifferentiated germ ball , during which synthesis of proteins essential for infection occurs .", "When the aquatic cercaria locates the mammalian host it rapidly penetrates into the epidermis using glandular secret...	[ "The schistosome cercaria develops from undifferentiated germ balls within the daughter sporocyst located in the hepatopancreas of its snail intermediate host .", "This is where the proteins it uses to infect humans are synthesised .", "After a brief free life in fresh water , if the cercaria locates a host , i...	2011
[ "Introduction", "Results/Discussion", "Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "virology/viral replication and gene regulation", "computational biology/systems biology" ]	Computational Fitness Landscape for All Gene-Order Permutations of an RNA Virus	journal.pcbi.1000283	null	[ [ "The gene orders in the genomes of individual negative-sense single-stranded RNA viruses have been conserved [1]–[3] .", "More specifically , most viruses in the order Mononegavirales , abbreviated here as ( – ) ssRNA viruses , share a similar genome organization: 3′-cap-phos-mat-env-pol-5′ , where cap en...	[ "How does the growth of a virus depend on the linear arrangement of genes in its genome ?", "Answering this question may enhance our basic understanding of virus evolution and advance applications of viruses as live attenuated vaccines , gene-therapy vectors , or anti-tumor therapeutics .", "We used a mathemati...	[ "Although many viruses are linked to diseases that adversely impact the health of their human , animal , and plant hosts , viruses could help promote wellness and treat disease if their “good traits” could be harnessed .", "Potentially useful virus traits include their abilities to stimulate a robust immune respo...	2009
[ "Results", "Discussion" ]	[ "medicine and health sciences", "methods and resources", "neural networks", "nervous system", "vertebrates", "neuroscience", "animals", "mammals", "data mining", "primates", "animal models", "model organisms", "mathematics", "brain mapping", "network analysis", "experimental organism s...	A multiscale cerebral neurochemical connectome of the rat brain	journal.pbio.2002612	null	[ [ "Automatic keyword-based search ( 1 , 750 keywords ) and manual grey search on electronic databases revealed 124 , 694 abstracts , titles , or both identified as original publications .", "Out of these , 4 , 517 studies were relevant for data mining and data from 1 , 560 original research articles with 36...	[ "Understanding the rat neurochemical connectome is fundamental for exploring neuronal information processing .", "By using advanced data mining , supervised machine learning , and network analysis , this study integrates over 5 decades of neuroanatomical investigations into a multiscale , multilayer neurochemical...	[ "The mammalian brain consists of a network of chemically diverse , multiscale , and multilayer neuronal wiring patterns that form the physical infrastructure underlying the processing of motoric , sensory , emotional , and cognitive information .", "Decades of histological track-tracing studies have generated a s...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/computational neuroscience", "neuroscience/neural homeostasis", "neuroscience/neuronal signaling mechanisms", "computational biology/signaling networks", "computational biology/systems biology" ]	Signaling Logic of Activity-Triggered Dendritic Protein Synthesis: An mTOR Gate But Not a Feedback Switch	journal.pcbi.1000287	null	[ [ "Protein synthesis is a necessary stage in long-term synaptic plasticity , both for strengthening synapses ( long-term potentiation , LTP ) and weakening them ( long-term depression , LTD ) [1] , [2] .", "A substantial part of this synthesis occurs in the dendrites , and possibly close to the modified syn...	[ "Changes in synaptic efficacy are believed to form the cellular basis for memory .", "Protein synthesis in dendrites is needed to consolidate long-term synaptic changes .", "Many signals converge to regulate dendritic protein synthesis , including synaptic and cellular activity , and growth factors .", "The c...	[ "Memory formation involves the controlled production of new proteins close to the site of input stimuli on nerve cells .", "Strong inputs , in combination with growth factors , stimulate the synthesis of several kinds of synaptic proteins .", "These new proteins are believed to participate in remodeling the con...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology/evolutionary ecology", "ecology/behavioral ecology", "evolutionary biology/animal behavior", "computational biology/evolutionary modeling", "computational biology/systems biology" ]	Differences in Nutrient Requirements Imply a Non-Linear Emergence of Leaders in Animal Groups	journal.pcbi.1000917	null	[ [ "Social animals have to coordinate their activities in order to maintain the advantages of group living [1]–[3] .", "This coordination constitutes one of the major challenges of any animal society , including human beings , and arouses the interest of scientists , sociologists , and politicians [4]–[9] ."...	[ "Collective decision making and especially leadership in groups are among the most studied topics in natural , social , and political sciences .", "Previous studies have shown that some individuals are more likely to be leaders because of their social power or the pertinent information they possess .", "One cha...	[ "Making decisions together to reach a consensus is one of the most important challenges of any society .", "In some communities , however , some leaders have more weight in the decisions than the other individuals .", "Similar rules exist in animal societies .", "Studies on animal groups have shown that some ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry/biocatalysis", "biochemistry/protein chemistry", "infectious diseases/helminth infections", "biophysics/protein chemistry and proteomics", "microbiology/parasitology" ]	The Importance of pH in Regulating the Function of the Fasciola hepatica Cathepsin L1 Cysteine Protease	journal.pntd.0000369	null	[ [ "Fasciolosis is a disease caused by helminths of the genus Fasciola .", "F . hepatica is found in temperate climates whereas F . gigantica is predominant in tropical regions .", "However , the distribution of the two species overlap in the Asia-Pacific region where hybrid forms have been isolated [1] ...	[ "The helminth parasite Fasciola hepatica secretes cathepsin L cysteine proteases to invade its host , migrate through tissues and digest haemoglobin , its main source of amino acids .", "Here we investigated the importance of pH in regulating the activity and functions of the major cathepsin L protease FheCL1 .",...	[ "Fasciola hepatica is a helminth parasite that causes liver fluke disease ( fasciolosis ) in domestic animals ( sheep and cattle ) and humans worldwide .", "Cathepsin L cysteine proteases ( FheCL ) are secreted by the parasite to invade its host , migrate through tissues and to degrade host haemoglobin ( Hb ) , a...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "invertebrates", "medicine and health sciences", "immune physiology", "onchocerca volvulus", "immune cells", "helminths", "immunology", "animals", "onchocerca", "physiological processes", "developmental biology", "antibodies", "neutrophils", "antibody response", "immune ...	Antibody responses against the vaccine antigens Ov-103 and Ov-RAL-2 are associated with protective immunity to Onchocerca volvulus infection in both mice and humans	journal.pntd.0007730	null	[ [ "Onchocerca volvulus , a filarial nematode , is the etiologic agent of river blindness that infects approximately 17 million people in Africa with more than 10 million people living with skin disease and 1 million with visual impairment [1] .", "The current strategy for elimination of O . volvulus focuses...	[ "The current strategy for the elimination of onchocerciasis is based on annual or bi-annual mass drug administration with ivermectin .", "However , due to several limiting factors there is a growing concern that elimination of onchocerciasis cannot be achieved solely through the current strategy .", "Additional...	[ "Onchocerca volvulus is the causative agent of river blindness that infects approximately 17 million people , mostly in Africa .", "The current strategy for elimination of O . volvulus focuses on controlling transmission through ivermectin-based mass drug administration programs .", "Due to potential ivermectin...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis	journal.pntd.0002412	null	[ [ "Dengue infection is a major health problem in tropical and subtropical countries .", "Each year , more than 250 , 000 cases of DHF/DSS are reported from an estimated 50 million dengue infections [1] .", "Dengue disease ranges from asymptomatic or self-limiting dengue fever ( DF ) to severe dengue cha...	[ "The pathogenesis of dengue shock syndrome ( DSS , grade 3 and 4 ) is not yet completely understood .", "Several factors are reportedly associated with DSS , a more severe form of dengue infection that reportedly causes 50 times higher mortality compared to that of dengue patients without DSS .", "However , the...	[ "Dengue is one of the most common viral diseases transmitted by infected mosquitoes .", "It may range from asymptomatic or self-limiting dengue fever ( DF ) to severe dengue characterized by plasma leakage ( dengue hemorrhagic fever , DHF ) and dengue shock syndrome ( DSS ) .", "Death from dengue infection occu...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "biophysics", "neuroscience/motor systems" ]	Dimensionality and Dynamics in the Behavior of C. elegans	journal.pcbi.1000028	null	[ [ "The study of animal behavior is rooted in two divergent traditions .", "One approach creates well-controlled situations , in which animals are forced to choose among a small discrete set of behaviors , as in psychophysical experiments [1] .", "The other , taken by ethologists [2] , describes the rich...	[ "A major challenge in analyzing animal behavior is to discover some underlying simplicity in complex motor actions .", "Here , we show that the space of shapes adopted by the nematode Caenorhabditis elegans is low dimensional , with just four dimensions accounting for 95% of the shape variance .", "These dimens...	[ "A great deal of work has been done in characterizing the genes , proteins , neurons , and circuits that are involved in the biology of behavior , but the techniques used to quantify behavior have lagged behind the advancements made in these areas .", "Here , we address this imbalance in a domain rich enough to a...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "innate immune system", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "emerging infectious diseases", "infectious diseases", "inflammation", "pathogenesis", "immune response", "immune system", "immunopathology", "clinical im...	The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis	journal.ppat.1004320	null	[ [ "Severe acute respiratory syndrome coronavirus ( SARS-CoV ) was identified as the etiological agent of a respiratory disease that emerged in Southeast China at the end of 2002 .", "SARS-CoV spread to more than 30 countries within six months , infecting 8000 people with an average mortality of 10% [1] .", ...	[ "A recombinant severe acute respiratory syndrome coronavirus ( SARS-CoV ) lacking the envelope ( E ) protein is attenuated in vivo .", "Here we report that E protein PDZ-binding motif ( PBM ) , a domain involved in protein-protein interactions , is a major determinant of virulence .", "Elimination of SARS-CoV E...	[ "SARS-CoV caused a worldwide epidemic infecting 8000 people with a mortality of about 10% .", "A recombinant SARS-CoV lacking the E protein was attenuated in vivo .", "The E protein contains a PDZ-binding motif ( PBM ) , a domain potentially involved in the interaction with more than 400 cellular proteins , whi...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "medicine", "developmental biology", "drosophila melanogaster", "model organisms", "neural stem cells", "stem cells", "neurological disorders", "neurology", "biology", "cell differentiation", "motor neuron diseases", "adult stem cells" ]	Survival Motor Neuron Protein Regulates Stem Cell Division, Proliferation, and Differentiation in Drosophila	journal.pgen.1002030	null	[ [ "Proximal spinal muscular atrophy ( SMA ) is characterised by the loss of the α-motor neurons in the anterior horns of the spinal cord , leading to progressive paralysis , muscle wasting , and in the most severe cases , death .", "SMA , an autosomal recessive disease , is the most common genetic form of i...	[ "Spinal muscular atrophy is a severe neurogenic disease that is caused by mutations in the human survival motor neuron 1 ( SMN1 ) gene .", "SMN protein is required for the assembly of small nuclear ribonucleoproteins and a dramatic reduction of the protein leads to cell death .", "It is currently unknown how th...	[ "Spinal muscular atrophy is a debilitating disease that affects the motor nervous system .", "The disease is caused by the reduction of the protein survival motor neuron ( SMN ) , which is involved in the assembly of ubiquitous small nuclear ribonucleoproteins .", "As SMN is required in every cell , it is impor...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/animal models of infection", "virology", "immunology/innate immunity", "infectious diseases/viral infections", "infectious diseases/respiratory infections", "immunology/immunity to infections", "virology/host antiviral responses" ]	Melanoma Differentiation-Associated Gene 5 (MDA5) Is Involved in the Innate Immune Response to Paramyxoviridae Infection In Vivo	journal.ppat.1000734	null	[ [ "Innate pathogen sensors detect viral products and respond by initiating a signaling cascade that leads to rapid anti-viral response involving secretion of type I IFNs ( i . e . IFN-α and IFN-β ) and inflammatory cytokines ( i . e . IL-6 and TNF-α ) [1] .", "In particular , type I IFNs restrict infection ...	[ "The early host response to pathogens is mediated by several distinct pattern recognition receptors .", "Cytoplasmic RNA helicases including RIG-I and MDA5 have been shown to respond to viral RNA by inducing interferon ( IFN ) production .", "Previous in vitro studies have demonstrated a direct role for MDA5 in...	[ "The innate immune system possesses an array of sensory molecules which are purposed in detecting viral nucleic acids .", "Our understanding of how these molecular sensors detect viral nucleic acids continues to evolve .", "Herein , we demonstrate that MDA5 , a member of the RIG-I-like receptor family , is invo...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gram negative", "emerging infectious diseases", "biology", "microbiology", "bacterial pathogens" ]	Surface Proteome Analysis and Characterization of Surface Cell Antigen (Sca) or Autotransporter Family of Rickettsia typhi	journal.ppat.1002856	null	[ [ "Rickettsia ( Rickettsiales: Rickettsiaceae ) are Gram-negative , obligate intracellular bacteria that are maintained in enzootic cycles involving both hematophagous arthropod vectors and vertebrate hosts [1] .", "Rickettsiae are the causative agents of significant human diseases such as Rocky Mountain sp...	[ "Surface proteins of the obligate intracellular bacterium Rickettsia typhi , the agent of murine or endemic typhus fever , comprise an important interface for host-pathogen interactions including adherence , invasion and survival in the host cytoplasm .", "In this report , we present analyses of the surface expos...	[ "Rickettsia typhi , a member of the typhus group ( TG ) rickettsia , is the agent of murine or endemic typhus fever – a disease exhibiting mild to severe flu-like symptoms resulting in significant morbidity .", "It is maintained in a flearodent transmission cycle in urban and suburban environments .", "The obli...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2'-Fluoro-4'-Chloromethyl-Cytidine Triphosphate	journal.ppat.1004995	null	[ [ "Respiratory syncytial virus ( RSV ) is a non-segmented , single-stranded , negative sense RNA virus and a member of the family Paramyxoviridae , which also includes human metapneumovirus and parainfluenza virus type-3 ( PIV-3 ) .", "RSV infection and resulting clinical sequelae usually last 1–2 weeks and...	[ "Respiratory syncytial virus ( RSV ) causes severe lower respiratory tract infections , yet no vaccines or effective therapeutics are available .", "ALS-8176 is a first-in-class nucleoside analog prodrug effective in RSV-infected adult volunteers , and currently under evaluation in hospitalized infants .", "Her...	[ "Viral RNA polymerase complexes mediate all of the enzymatic functions required for genomic replication and transcription in RNA viruses .", "Because of their essential role in the virus life cycle , RNA polymerases are major molecular targets for antiviral therapies .", "Sofosbuvir and mericitabine are related...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "model organisms", "immunity", "innate immunity", "immunology", "biology", "microbiology", "yeast and fungal models", "candida albicans" ]	A Novel Role for the NLRC4 Inflammasome in Mucosal Defenses against the Fungal Pathogen Candida albicans	journal.ppat.1002379	null	[ [ "Candida sp .", "are dimorphic fungi that commonly colonize the oral cavity of adult humans , with overgrowth prevented by competing commensal bacteria as well as local host immune responses .", "Perturbations of the normal oral flora through antibiotic treatment , for example , or immunocompromised s...	[ "Candida sp .", "are opportunistic fungal pathogens that colonize the skin and oral cavity and , when overgrown under permissive conditions , cause inflammation and disease .", "Previously , we identified a central role for the NLRP3 inflammasome in regulating IL-1β production and resistance to dissemination fr...	[ "In this manuscript we describe a new role for a group of molecules termed the “inflammasome” that process key immune response proteins including interleukin-1-β .", "In previous work , we and others have shown that the NLRP3 inflammasome is important in protecting from severe fungal infections .", "We now show...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "fish", "bmp signaling", "gene regulation", "vertebrates", "marine biology", "marine fish", "animals", "osteichthyes", "freshwater fish", "digestive system", "genome complexity", "dentition", "genomics", "marine and aquatic sciences", "gene expression", ...	An intronic enhancer of Bmp6 underlies evolved tooth gain in sticklebacks	journal.pgen.1007449	null	[ [ "Finding the genes and ultimately the mutations that drive the evolution of animal form remains an important goal in biology [1] .", "The cis-regulatory hypothesis proposes that cis-regulatory changes are the most frequent substrate for morphological evolution because these mutations are more likely to by...	[ "Threespine stickleback fish offer a powerful system to dissect the genetic basis of morphological evolution in nature .", "Marine sticklebacks have repeatedly invaded and adapted to numerous freshwater environments throughout the Northern hemisphere .", "In response to new diets in freshwater habitats , change...	[ "Understanding how traits evolve in nature remains a fundamental goal in biology .", "Threespine stickleback fish offer a powerful system to address this question .", "Ancestral marine sticklebacks have colonized new freshwater environments , where new traits evolve , including increases in tooth number .", "...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "gene regulation", "messenger rna", "animals", "dna transcription", "animal models", "drosophila melanogaster", "model organisms", "protein synthesis", "experimental organism systems", "cellular structures and organelles", "drosophila", "chemical synthesis", "research and ...	Development of a tissue-specific ribosome profiling approach in Drosophila enables genome-wide evaluation of translational adaptations	journal.pgen.1007117	null	[ [ "Recent advances in next-generation sequencing such as RNA-seq have revolutionized the measurement and quantification of genome-wide changes in transcriptional expression , without pre-existing knowledge of gene identity , at unprecedented resolution [1 , 2] .", "In addition , biochemical tagging of ribos...	[ "Recent advances in next-generation sequencing approaches have revolutionized our understanding of transcriptional expression in diverse systems .", "However , measurements of transcription do not necessarily reflect gene translation , the process of ultimate importance in understanding cellular function .", "T...	[ "Recent advances in next-generation sequencing approaches have revolutionized our understanding of transcriptional expression in diverse systems .", "However , transcriptional expression alone does not necessarily report gene translation , the process of ultimate importance in understanding cellular function .", ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "geographical locations", "microbiology", "rickettsia", "north america", "bacterial diseases", "signs and symptoms", "antibodies", "immunologic...	First Identification and Description of Rickettsioses and Q Fever as Causes of Acute Febrile Illness in Nicaragua	journal.pntd.0005185	null	[ [ "Rickettsioses , including spotted fever group ( SFGR ) and typhus group ( TGR ) , and Q fever ( caused by Coxiella burnetii ) are increasingly recognized worldwide [1] .", "Both rickettsioses and Q fever often manifest as undifferentiated fever and cannot easily be distinguished clinically from other cau...	[ "Rickettsial infections and Q fever present similarly to other acute febrile illnesses , but are infrequently diagnosed because of limited diagnostic tools .", "Despite sporadic reports , rickettsial infections and Q fever have not been prospectively studied in Central America .", "We enrolled consecutive patie...	[ "Rickettsial infections and Q fever cause illness characterized by fever and non-specific symptoms and signs .", "Not only are these infections difficult to recognize , they are also difficult to diagnose because of limitations in existing tests for them .", "Despite sporadic reports , rickettsial infections an...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/alternative splicing", "genetics and genomics/gene expression" ]	Entropy Measures Quantify Global Splicing Disorders in Cancer	journal.pcbi.1000011	null	[ [ "The majority of mammalian genes produce alternative transcripts as part of their normal expression program [1]–[4] .", "Alternative transcripts include splicing , polyadenylation and transcription initiation variants which can be expressed differentially in different tissues [4]–[7] providing the fine tu...	[ "Most mammalian genes are able to express several splice variants in a phenomenon known as alternative splicing .", "Serious alterations of alternative splicing occur in cancer tissues , leading to expression of multiple aberrant splice forms .", "Most studies of alternative splicing defects have focused on the...	[ "RNA splicing is the process by which gene products are pieced together to form a mature messenger RNA ( mRNA ) .", "In normal cells , RNA splicing is a tightly controlled process that leads to production of a well-defined set of mRNAs .", "Cancer cells , however , often produce aberrant , mis-spliced mRNAs .",...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Histone H3 Variant Regulates RNA Polymerase II Transcription Termination and Dual Strand Transcription of siRNA Loci in Trypanosoma brucei	journal.pgen.1005758	null	[ [ "Kinetoplastids are early-diverged protozoa that include the human parasites Trypanosoma brucei , Trypanosoma cruzi , and Leishmania major , which cause African sleeping sickness , Chagas disease , and leishmaniasis , respectively .", "The genomes of kinetoplastids are arranged into long gene clusters , o...	[ "Base J , β-D-glucosyl-hydroxymethyluracil , is a chromatin modification of thymine in the nuclear DNA of flagellated protozoa of the order Kinetoplastida .", "In Trypanosoma brucei , J is enriched , along with histone H3 variant ( H3 . V ) , at sites involved in RNA Polymerase ( RNAP ) II termination and telomer...	[ "Trypanosoma brucei is an early-diverged parasitic protozoan that causes African sleeping sickness in humans .", "The genome of T . brucei is organized into polycistronic gene clusters that contain multiple genes that are co-transcribed from a single promoter .", "Because of this genome arrangement , it is thou...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "organism development", "stem cells", "molecular development", "genetics", "biology", "morphogenesis", "genetics and genomics", "cell differentiation", "gene function" ]	Coordinated Regulation of Niche and Stem Cell Precursors by Hormonal Signaling	journal.pbio.1001202	In the developing Drosophila ovary, the ecdysone signaling pathway controls the differentiation of both niche and germ line stem cell precursors.	[ [ "Stem cells and their niches constitute functional units that underlie adult organ homeostasis and regeneration following injury or disease .", "Despite their great medical importance , little is known about how stem cell units , which originate from precursor cells , form during development .", "Unde...	[ "Stem cells and their niches constitute units that act cooperatively to achieve adult body homeostasis .", "How such units form and whether stem cell and niche precursors might be coordinated already during organogenesis are unknown .", "In fruit flies , primordial germ cells ( PGCs ) , the precursors of germ l...	[ "Tissue-specific stem cells reside in specialized microenvironments ( niches ) .", "How the generation of niche cells and resident stem cells is coordinated , and how their correct numerical ratios are regulated , remains poorly understood .", "Here , we examine the potential mechanisms of this process by analy...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene function", "neuroscience/neuronal and glial cell biology", "cell biology/cytoskeleton" ]	The Caenorhabditis elegans Kinesin-3 Motor UNC-104/KIF1A Is Degraded upon Loss of Specific Binding to Cargo	journal.pgen.1001200	null	[ [ "Transport of pre-synaptic vesicles from the neuronal cell body to the synapse is an essential process to ensure that the nerve terminals can effectively participate in synaptic transmission [1] , [2] .", "This transport is a regulated process that occurs primarily using the Kinesin-3 family motor UNC-104...	[ "UNC-104/KIF1A is a Kinesin-3 motor that transports synaptic vesicles from the cell body towards the synapse by binding to PI ( 4 , 5 ) P2 through its PH domain .", "The fate of the motor upon reaching the synapse is not known .", "We found that wild-type UNC-104 is degraded at synaptic regions through the ubiq...	[ "The cell body and the synapse in a neuron are often separated by significant distance , which is spanned by the axon connecting the two .", "Transport of various cargoes along the axonal highway is very important for neuronal function .", "The regulation of this complex process is not well understood .", "Us...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "immune cells", "pathology and laboratory medicine", "enzyme-linked immunoassays", "gene regulation", "immunology", "immune receptor signaling", "developmental biology", "signs and sympto...	HRS plays an important role for TLR7 signaling to orchestrate inflammation and innate immunity upon EV71 infection	journal.ppat.1006585	null	[ [ "Upon infection , viral RNAs are recognized as pathogen-associated molecular patterns ( PAMPs ) by Toll-like receptors ( TLRs ) to trigger signaling events leading to the induction of interferons ( IFNs ) and proinflammatory cytokines [1 , 2] .", "Most TLRs are intracellularly localized and must traffic f...	[ "Enterovirus 71 ( EV71 ) is an RNA virus that causes hand-foot-mouth disease ( HFMD ) , and even fatal encephalitis in children .", "Although EV71 pathogenesis remains largely obscure , host immune responses may play important roles in the development of diseases .", "Recognition of pathogens mediated by Toll-l...	[ "Enterovirus 71 ( EV71 ) is a highly infectious positive-stranded RNA virus that causes hand-foot-mouth disease ( HFMD ) .", "As a major pathogen , EV71 infection leads to host immune responses in the disease severity .", "Toll-like receptors ( TLRs ) can recognize pathogens to induce host immunity and inflamma...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Endothelial Cell Self-fusion during Vascular Pruning	journal.pbio.1002126	In vivo live imaging of zebrafish embryos reveals the diverse cellular activities involved in the pruning of unwanted blood vessels, including the self-fusion of endothelial cells.	[ [ "The vascular system of vertebrates distributes oxygen , nutrients , metabolites , and blood cells to and from all organs of the body .", "A complex network of interconnected vascular tubes develops and already functions at early stages of embryonic development and continues to expand and to remodel as th...	[ "During embryonic development , vascular networks remodel to meet the increasing demand of growing tissues for oxygen and nutrients .", "This is achieved by the pruning of redundant blood vessel segments , which then allows more efficient blood flow patterns .", "Because of the lack of an in vivo system suitabl...	[ "The blood vasculature circulates gas , nutrients , hormones , and metabolites to all organs of the body .", "It is indispensable for survival and already functions at very early stages of embryonic development .", "At this point , new blood vessels form mainly through angiogenesis—the outgrowth of new vessels ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/nucleolus and nuclear bodies", "genetics and genomics/population genetics", "genetics and genomics/chromosome biology", "evolutionary biology/genomics" ]	The Pattern of R2 Retrotransposon Activity in Natural Populations of Drosophila simulans Reflects the Dynamic Nature of the rDNA Locus	journal.pgen.1000386	null	[ [ "The abundant transposable elements present in eukaryotes have over the course of evolution helped shape the size , structure and expression of their genomes .", "Control over the spread of transposable elements has been suggested to be a consequence of the harmful effects of their insertions [1] , [2] an...	[ "The pattern and frequency of insertions that enable transposable elements to remain active in a population are poorly understood .", "The retrotransposable element R2 exclusively inserts into the 28S rRNA genes where it establishes long-term , stable relationships with its animal hosts .", "Previous studies wi...	[ "Transposable elements are abundant selfish components of all eukaryotic genomes .", "Despite the elaborate mechanisms eukaryotes have evolved to control these elements , they continue to proliferate .", "Here , we study R2 retrotransposons , highly successful elements that only insert into a site within the 28...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "infectious disease epidemiology", "parasitic diseases", "helminth infection", "hookworm infection", "neglected tropical diseases", "ascariasis", "infectious diseases", "soil-transmitted helminths", "parasitic intestinal diseases", "epidemiology", ...	Treatment for Schistosoma japonicum, Reduction of Intestinal Parasite Load, and Cognitive Test Score Improvements in School-Aged Children	journal.pntd.0001634	null	[ [ "Many children in developing countries perform below academically desired levels [1] .", "Helminth infections are a pervasive part of children's environments in these settings that may contribute to poor educational outcomes through reduced iron status , inflammation , decreased macro-nutrient nutritional...	[ "To determine whether treatment of intestinal parasitic infections improves cognitive function in school-aged children , we examined changes in cognitive testscores over 18 months in relation to:", "( i ) treatment-related Schistosoma japonicum intensity decline ,", "( ii ) spontaneous reduction of single soil-...	[ "Parasitic worm infections are associated with cognitive impairment and lower academic achievement for infected relative to uninfected children .", "However , it is unclear whether curing or reducing worm infection intensity improves child cognitive function .", "We examined the independent associations between...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organisms", "immunodeficiency viruses", "viruses", "infectious disease immunology", "clinical immunology", "medical microbiology", "viral pathogens", "microbial pathogens", "biology and life sciences", "immunology", "microbiology", "vaccination and immunization", "hiv-1", "immune response...	Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1	journal.ppat.1004552	null	[ [ "HIV transmission remains a huge global public health problem ( www . UNAIDS . org ) .", "To reduce spread of the virus new prevention methods are being developed based on recent advances in the molecular virology of HIV .", "In addition to the expanded use of ARVs in new modalities such as pre-exposu...	[ "To date , no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however , elicitation of broad and potent heavy chain only antibodies ( HCAb ) has previously been reported in llamas .", "In this study , the anti-HIV immune responses in immunized llamas we...	[ "Developing a vaccine against HIV-1 is a priority , but it remains unclear whether immunizations in humans can elicit potent broadly neutralizing antibodies able to prevent HIV-1 transmission .", "Llamas possess heavy chain only antibodies and conventional heavy and light chain antibodies .", "We previously rep...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell growth and division", "computational biology/systems biology", "biochemistry/theory and simulation", "computational biology/molecular genetics" ]	Fragilities Caused by Dosage Imbalance in Regulation of the Budding Yeast Cell Cycle	journal.pgen.1000919	null	[ [ "Intracellular biochemical parameters , such as gene expression levels and protein activities , are highly optimized in order to maximize the performance of biological systems [1]–[4] .", "On the other hand , these parameters operate within certain limitations to maintain the function of the system agains...	[ "Cells can maintain their functions despite fluctuations in intracellular parameters , such as protein activities and gene expression levels .", "This commonly observed biological property of cells is called robustness .", "On the other hand , these parameters have different limitations , each reflecting the pr...	[ "Normal cell functioning is dependent on balance between protein interactions and gene regulations .", "Although the balance is often perturbed by environmental changes , mutations , and noise in biochemical reactions , cellular systems can maintain their function despite these perturbations .", "This property ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "model organisms", "genetics", "biology", "genomics", "microbiology", "genetics and genomics" ]	E. coli Fis Protein Insulates the cbpA Gene from Uncontrolled Transcription	journal.pgen.1003152	null	[ [ "Bacterial chromosomes are organised into a nucleoid by an integrated network of supercoiling , transcription and nucleoid associated DNA binding proteins [1] .", "This network is highly dynamic and responsive to changes in the extracellular environment .", "In Escherichia coli , a particularly notabl...	[ "The Escherichia coli curved DNA binding protein A ( CbpA ) is a poorly characterised nucleoid associated factor and co-chaperone .", "It is expressed at high levels as cells enter stationary phase .", "Using genetics , biochemistry , and genomics , we have examined regulation of , and DNA binding by , CbpA .",...	[ "Compaction of chromosomal DNA is a fundamental process that impacts on all aspects of cellular biology .", "However , our understanding of chromosome organisation in bacteria is poorly developed .", "Since bacteria are amongst the most abundant living organisms on the planet , this represents a startling gap i...	2013
[ "Introduction", "Methods", "Discussion" ]	[ "cell biology/cell signaling", "computational biology/transcriptional regulation", "mathematics", "computational biology/metabolic networks", "computational biology/signaling networks", "computational biology/molecular dynamics", "computational biology/systems biology" ]	Dynamic Analysis of Integrated Signaling, Metabolic, and Regulatory Networks	journal.pcbi.1000086	null	[ [ "Intracellular biochemical networks are comprised of signaling , metabolic , and regulatory processes .", "( Note that here we use “regulation” to refer specifically to transcriptional regulatory and protein synthesis networks , and “signaling” to describe intracellular reactions that drive responses to t...	[ "Extracellular cues affect signaling , metabolic , and regulatory processes to elicit cellular responses .", "Although intracellular signaling , metabolic , and regulatory networks are highly integrated , previous analyses have largely focused on independent processes ( e . g . , metabolism ) without considering ...	[ "Cellular systems comprise many diverse components and component interactions spanning signal transduction , transcriptional regulation , and metabolism .", "Although signaling , metabolic , and regulatory activities are often investigated independently of one another , there is growing evidence that considerable...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "mathematics", "statistics", "biology", "computational biology", "neuroscience", "probability theory" ]	A Self-Organizing State-Space-Model Approach for Parameter Estimation in Hodgkin-Huxley-Type Models of Single Neurons	journal.pcbi.1002401	null	[ [ "Among several tools at the disposal of neuroscientists today , data-driven computational models have come to hold an eminent position for studying the electrical activity of single neurons and the significance of this activity for the operation of neural circuits [1]–[4] .", "Typically , these models dep...	[ "Traditional approaches to the problem of parameter estimation in biophysical models of neurons and neural networks usually adopt a global search algorithm ( for example , an evolutionary algorithm ) , often in combination with a local search method ( such as gradient descent ) in order to minimize the value of a c...	[ "Parameter estimation is a problem of central importance and , perhaps , the most laborious task in biophysical modeling of neurons and neural networks .", "An emerging trend is to treat parameter estimation in this context as yet another statistical inference problem , which can be tackled using well-established...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "rna-binding proteins", "radiochemistry", "messenger rna", "animals", "invertebrate genomics", "dna transcription", "nuclear decay", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "epigenetics", "chromatin", "drosophila", ...	Comprehensive analysis of nucleocytoplasmic dynamics of mRNA in Drosophila cells	journal.pgen.1006929	null	[ [ "The production , nuclear export and degradation of mRNA are key steps in the control of cytoplasmic mRNA levels .", "Steady-state levels of transcripts in the cytoplasm are determined by the rates of these three processes .", "Hence , our understanding of gene regulatory systems requires quantitative...	[ "Eukaryotic mRNAs undergo a cycle of transcription , nuclear export , and degradation .", "A major challenge is to obtain a global , quantitative view of these processes .", "Here we measured the genome-wide nucleocytoplasmic dynamics of mRNA in Drosophila cells by metabolic labeling in combination with cellula...	[ "All mRNAs start from production in the nucleus , undergo exportation through nuclear pores and finally are degraded in the cytoplasm .", "A comprehensive characterization of the kinetic rates of all mRNAs is an important prerequisite for a global understanding of the regulation of the transcriptome and the cell ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cancer detection and diagnosis", "medicine and health sciences", "chromosome structure and function", "insertion mutation", "cancers and neoplasms", "oncology", "telomeres", "mutation", "nonsense mutation", "frameshift mutation", "chromosome biology", "leiomyosarcoma", "sarcomas", "cell b...	Exome Sequencing of Uterine Leiomyosarcomas Identifies Frequent Mutations in TP53, ATRX, and MED12	journal.pgen.1005850	null	[ [ "Uterine leiomyosarcoma ( ULMS ) is a rare , highly malignant tumor that originates from the smooth muscle layer of the uterus , the myometrium .", "It is the most common subtype of uterine sarcoma and accounts for 1–2% of all uterine malignancies with an estimated incidence of 0 . 4/100 , 000 women per y...	[ "Uterine leiomyosarcomas ( ULMSs ) are aggressive smooth muscle tumors associated with poor clinical outcome .", "Despite previous cytogenetic and molecular studies , their molecular background has remained elusive .", "To examine somatic variation in ULMS , we performed exome sequencing on 19 tumors .", "Alt...	[ "Uterine leiomyosarcomas are rare , malignant smooth muscle tumors with a poor 5-year survival and high recurrence rate .", "They account for 1–2% of all uterine malignancies with an estimated incidence of 0 . 4/100 , 000 women per year .", "The symptoms and signs of this tumor type widely overlap with those of...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	The DEAD-Box Protein Dhh1 Promotes Decapping by Slowing Ribosome Movement	journal.pbio.1001342	The highly conserved translational control protein Dhh1 promotes mRNA decapping by regulating a late step in translation in yeast.	[ [ "Messenger RNA ( mRNA ) is targeted for destruction in a precise and regulated fashion .", "In eukaryotic cells , the digestion of the 3′ polyadenosine tail ( deadenylation ) is the first step , followed predominantly by removal of the mRNA cap and 5′→3′ exonucleolytic digestion or , rarely , 3′→5′ degrad...	[ "Translational control and messenger RNA ( mRNA ) decay represent important control points in the regulation of gene expression .", "In yeast , the major pathway for mRNA decay is initiated by deadenylation followed by decapping and 5′–3′ exonucleolytic digestion of the mRNA .", "Proteins that activate decappin...	[ "Translation of mRNA into protein and turnover of mRNA are two points at which cells can exert regulatory control of gene expression , thereby ensuring that the protein products are present in cells and tissues at the appropriate time and place .", "The DDX6 family of DEAD box helicases , exemplified by the yeast...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/macromolecular structure analysis", "pharmacology/drug resistance", "pharmacology/drug development", "biotechnology/small molecule chemistry", "infectious diseases/bacterial infections", "pharmacology/adverse reactions", "computational biology/systems biology" ]	Drug Discovery Using Chemical Systems Biology: Repositioning the Safe Medicine Comtan to Treat Multi-Drug and Extensively Drug Resistant Tuberculosis	journal.pcbi.1000423	null	[ [ "Tuberculosis , which is caused by the bacterial pathogen Mycobacterium tuberculosis ( M . tuberculosis ) , is a leading cause of mortality among infectious diseases .", "It has been estimated by the World Health Organization ( WHO ) that almost one-third of the world's population , around 2 billion peopl...	[ "The rise of multi-drug resistant ( MDR ) and extensively drug resistant ( XDR ) tuberculosis around the world , including in industrialized nations , poses a great threat to human health and defines a need to develop new , effective and inexpensive anti-tubercular agents .", "Previously we developed a chemical s...	[ "The rise of multi-drug resistant ( MDR ) and extensively drug resistant ( XDR ) tuberculosis around the world , including in industrialized nations , poses a great threat to human health .", "This resistance highlights the need to develop new , effective and inexpensive anti-tubercular agents .", "Unfortunatel...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dermatology", "medicine and health sciences", "clinical research design", "tropical diseases", "geographical locations", "australia", "group a streptococcal infection", "parasitic diseases", "research design", "bacterial diseases", "age groups", "skin infections", "ectoparasitic infections"...	Scabies and risk of skin sores in remote Australian Aboriginal communities: A self-controlled case series study	journal.pntd.0006668	null	[ [ "Remote Aboriginal communities in northern Australia have the world’s highest prevalence of skin sores with more than 80% of children affected by their first birthday[1] .", "Skin sores , also known as impetigo , are commonly caused by Group A Streptococcus ( GAS ) infections in these populations and can ...	[ "Skin sores caused by Group A streptococcus ( GAS ) infection are a major public health problem in remote Aboriginal communities .", "Skin sores are often associated with scabies , which is evident in scabies intervention programs where a significant reduction of skin sores is seen after focusing solely on scabie...	[ "Skin sores , also known as impetigo , are highly contagious bacterial skin infections , which are found commonly in school children and occasionally in adults .", "Skin sores are prevalent in disadvantaged or resource-poor settings .", "In Australia , about two thirds of Aboriginal children suffer from skin so...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "virology/virulence factors and mechanisms", "virology/virus evolution and symbiosis", "virology/immunodeficiency viruses", "virology/mechanisms of resistance and susceptibility, including host genetics", "virology/immune evasion" ]	Inefficient Nef-Mediated Downmodulation of CD3 and MHC-I Correlates with Loss of CD4+ T Cells in Natural SIV Infection	journal.ppat.1000107	null	[ [ "Although all primate lentiviruses are referred to as human and simian “immunodeficiency” viruses ( HIV and SIV , respectively ) , SIVs do generally not cause disease in their natural monkey hosts [1] , [2] .", "This is in contrast to HIV-1-infected humans and SIVmac-infected macaques , who develop immuno...	[ "Recent data suggest that Nef-mediated downmodulation of TCR-CD3 may protect SIVsmm-infected sooty mangabeys ( SMs ) against the loss of CD4+ T cells .", "However , the mechanisms underlying this protective effect remain unclear .", "To further assess the role of Nef in nonpathogenic SIV infection , we cloned n...	[ "The accessory Nef protein is commonly considered a “pathogenicity” factor of primate lentiviruses .", "However , SIVs do not cause disease in their natural hosts , although they all encode nef genes and sustain high levels of viremia .", "To better understand the role of Nef in natural nonpathogenic SIV infect...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "action potentials", "medicine and health sciences", "neural networks", "depolarization", "membrane potential", "electrophysiology", "neuroscience", "simulation and modeling", "computational neuroscience", "research and analysis methods", "excitatory postsynaptic potentials", "computer and inf...	Adaptive Spike Threshold Enables Robust and Temporally Precise Neuronal Encoding	journal.pcbi.1004984	null	[ [ "The essential computation performed by neurons is the ( non-linear ) integration of synaptic inputs and subsequent generation of a spike .", "This summation is determined by multiple factors , including the passive membrane properties , active currents , and the neuronal geometry [1–3] .", "The curre...	[ "Neural processing rests on the intracellular transformation of information as synaptic inputs are translated into action potentials .", "This transformation is governed by the spike threshold , which depends on the history of the membrane potential on many temporal scales .", "While the adaptation of the thres...	[ "A neuron is a tiny computer that transforms electrical inputs into electrical outputs .", "While neurons have been investigated and modeled for many decades , some aspects remain elusive .", "Recently , it was demonstrated that the membrane ( voltage ) state of a neuron determines its threshold to spiking .", ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Cell-Type Specific Features of Circular RNA Expression	journal.pgen.1003777	null	[ [ "Recently , we were surprised to find that the predominant RNA isoform from hundreds of human genes is a circle , and that circular RNAs were transcribed from thousands of genes in both human and mouse [1] .", "Circular RNA transcripts had been reported previously for a handful of genes .", "With the ...	[ "Thousands of loci in the human and mouse genomes give rise to circular RNA transcripts; at many of these loci , the predominant RNA isoform is a circle .", "Using an improved computational approach for circular RNA identification , we found widespread circular RNA expression in Drosophila melanogaster and estima...	[ "Last year , we reported that circular RNA isoforms , previously thought to be very rare , are actually a pervasive feature of eukaryotic gene expression programs; indeed , the major RNA isoform from hundreds of human genes is a circle .", "Previous novel RNA species that initially appeared to be special cases , ...	2013
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "biotechnology", "cell biology", "biology and life sciences", "molecular cell biology" ]	A Nucleic-Acid Hydrolyzing Single Chain Antibody Confers Resistance to DNA Virus Infection in HeLa Cells and C57BL/6 Mice	journal.ppat.1004208	null	[ [ "Viruses are pathogenic agents that cause potentially devastating diseases such as the flu , hepatitis , poliomyelitis , acquired immunodeficiency syndrome ( AIDS ) , severe acute respiratory syndrome ( SARS ) , avian influenza , and foot-and-mouse disease [1] , [2] , [3] .", "Many antiviral drug studies ...	[ "Viral protein neutralizing antibodies have been developed but they are limited only to the targeted virus and are often susceptible to antigenic drift .", "Here , we present an alternative strategy for creating virus-resistant cells and animals by ectopic expression of a nucleic acid hydrolyzing catalytic 3D8 si...	[ "Most strategies for developing virus-resistant transgenic cells and animals are based on the concept of virus-derived resistance , in which dysfunctional virus-derived products are expressed to interfere with the pathogenic process of the virus in transgenic cells or animals .", "However , these viral protein ta...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "children", "medicine and health sciences", "tropical diseases", "parasitic diseases", "pediatrics", "vaccines", "age groups", "neglected tropical diseases", "infectious disease control", "onchocerciasis", "families", "public and occupational health", "infectious diseases", "agrochemicals"...	Strategies to improve treatment coverage in community-based public health programs: A systematic review of the literature	journal.pntd.0006211	null	[ [ "The health impact of community-based public health programs is dependent upon the proportion of the targeted population that is reached with the preventative health services , also known as treatment coverage .", "The World Health Organization ( WHO ) , country governments , and other institutions typica...	[ "Community-based public health campaigns , such as those used in mass deworming , vitamin A supplementation and child immunization programs , provide key healthcare interventions to targeted populations at scale .", "However , these programs often fall short of established coverage targets .", "The purpose of t...	[ "Many public health platforms provide decentralized interventions outside of health facilities , including mass drug administration for neglected tropical diseases , immunizations , vitamin supplementation , and others .", "The purpose of these community-based public health platforms is to reach large proportions...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "medicine and health sciences", "animals", "wolbachia", "seasons", "mathematics", "statistics (mathematics)", "population biology", "insect vectors", "bacteria", "infectious diseases", "geography", "aedes aegypti", "disease vectors", "insects", "arthropoda", "approxi...	Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes aegypti	journal.pbio.2001894	null	[ [ "Dengue fever is the most common arboviral disease affecting humans [1] .", "Over 2 , 500 , 000 , 000 people live in dengue-afflicted regions , and dengue incidence is increasing at an alarming rate in tropical and subtropical countries [2] .", "A number of other arboviruses also represent emerging di...	[ "Dengue-suppressing Wolbachia strains are promising tools for arbovirus control , particularly as they have the potential to self-spread following local introductions .", "To test this , we followed the frequency of the transinfected Wolbachia strain wMel through Ae .", "aegypti in Cairns , Australia , followin...	[ "Wolbachia are bacteria that live inside insect cells .", "In insects that act as viral vectors , Wolbachia can suppress virus transmission to new hosts .", "Wolbachia have been experimentally introduced into Aedes aegypti mosquito populations to reduce the transmission of dengue , Zika , and other arboviruses ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biophysics", "none", "computational biology" ]	Design of Multi-Specificity in Protein Interfaces	journal.pcbi.0030164	null	[ [ "Proteins have evolved to operate within the context of crowded cellular milieus and complex functional networks [1] .", "It is not well understood how and to what extent protein sequences and structures are optimized for multiple and likely interdependent properties such as stability and efficiency of fo...	[ "Interactions in protein networks may place constraints on protein interface sequences to maintain correct and avoid unwanted interactions .", "Here we describe a “multi-constraint” protein design protocol to predict sequences optimized for multiple criteria , such as maintaining sets of interactions , and apply ...	[ "Computational methods have recently led to remarkable successes in the design of molecules with novel functions .", "These approaches offer great promise for creating highly selective molecules to accurately control biological processes .", "However , to reach these goals modeling procedures are needed that ar...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "bacterial diseases", "infectious diseases", "veterinary diseases", "medicine and health sciences", "biology and life sciences", "veterinary bacteriology", "q fever", "veterinary science" ]	Epidemiology of Coxiella burnetii Infection in Africa: A OneHealth Systematic Review	journal.pntd.0002787	null	[ [ "Coxiella burnetii , a zoonotic bacterial pathogen found worldwide except in New Zealand , is transmitted to humans through direct contact with milk , urine , feces , or semen from infected animals as well as inhalation of aerosolized particles from animal placentas , parturient fluids , aborted fetuses , and...	[ "Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings .", "Coxiella burnetii , the causative pathogen , is transmitted among varied host species , but the epidemiology of the organism in Africa is poorly understood .", "We conducted a systematic review of C ...	[ "Coxiella burnetii is a bacterium that can cause acute and chronic fever illness and pneumonia in humans .", "It is also a known cause of abortion in livestock species , and is principally transmitted to humans through contact with infected animal birth products .", "With growing awareness of the over-diagnosis...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "biochemistry", "hemodynamics", "protein metabolism", "proteins", "plasma proteins", "biocatalysis", "vascular biology", "regulatory proteins", "biology", "hypertension", "metabolism", "cardiovascular" ]	Serine Carboxypeptidase SCPEP1 and Cathepsin A Play Complementary Roles in Regulation of Vasoconstriction via Inactivation of Endothelin-1	journal.pgen.1004146	null	[ [ "Vascular resistance of the mammalian circulation system is tightly regulated by many endogenous agents that influence the blood volume , and diverse functions of endothelium , vascular smooth muscle and myocardium .", "When the balance of these agents is disturbed , persistent systemic hypertension devel...	[ "The potent vasoconstrictor peptides , endothelin 1 ( ET-1 ) and angiotensin II control adaptation of blood vessels to fluctuations of blood pressure .", "Previously we have shown that the circulating level of ET-1 is regulated through its proteolytic cleavage by secreted serine carboxypeptidase , cathepsin A ( C...	[ "Arterial blood pressure is regulated by small peptide hormones ( vasoactive peptides ) that cause contraction or relaxation of the arterial wall .", "The blood and tissue levels of these peptides are controlled by two mechanisms: through their synthesis and through their inactivation by the enzymes that are capa...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "socioeconomic aspects of health", "public health and epidemiology", "epidemiological methods", "epidemiology", "global health", "dengue fever", "neglected tropical diseases", "spatial epidemiology", "economic epidemiology", "public health" ]	Use of Expansion Factors to Estimate the Burden of Dengue in Southeast Asia: A Systematic Analysis	journal.pntd.0002056	null	[ [ "Dengue has become a major public health problem in many tropical and subtropical regions , with an estimate of 100–200 million dengue infections occurring each year in more than 100 countries , resulting in approximately 20 , 000 deaths [1] .", "It represents a significant economic burden to communities ...	[ "Dengue virus infection is the most common arthropod-borne disease of humans and its geographical range and infection rates are increasing .", "Health policy decisions require information about the disease burden , but surveillance systems usually underreport the total number of cases .", "These may be estimate...	[ "Dengue is the most common disease transmitted by a mosquito , with about 100–200 million infections occurring each year in more than 100 tropical and subtropical countries .", "Policy-makers require accurate information about the number of symptomatic dengue episodes to make informed decisions concerning dengue ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organisms", "biochemistry", "rna-binding proteins", "rna", "fungi", "proteins", "gene regulatory networks", "genetics", "schizosaccharomyces pombe", "biology and life sciences", "molecular genetics", "computational biology", "schizosaccharomyces", "rna stability", "yeast" ]	Systematic Analysis of the Role of RNA-Binding Proteins in the Regulation of RNA Stability	journal.pgen.1004684	null	[ [ "The steady state levels of messenger RNAs ( mRNAs ) are determined by both their synthesis and decay rates [1] .", "Moreover , decay rates determine the time required for a new steady state to be reached after changes in transcription , and thus contribute to shaping dynamic changes of mRNA levels [2]–[5...	[ "mRNA half-lives are transcript-specific and vary over a range of more than 100-fold in eukaryotic cells .", "mRNA stabilities can be regulated by sequence-specific RNA-binding proteins ( RBPs ) , which bind to regulatory sequence elements and modulate the interaction of the mRNA with the cellular RNA degradation...	[ "Messenger RNAs ( mRNAs ) are the molecules that relay the information from genes ( DNA ) to proteins .", "Cells contain different amounts of each mRNA type depending on their function and their situation .", "The quantity of each mRNA depends on the balance between its production ( transcription ) and its degr...	2014
[ "Introduction", "Models", "Results", "Discussion" ]	[ "computational biology/evolutionary modeling", "evolutionary biology", "chemical biology/directed molecular evolution" ]	Multilevel Selection in Models of Prebiotic Evolution II: A Direct Comparison of Compartmentalization and Spatial Self-Organization	journal.pcbi.1000542	null	[ [ "Consideration of selection acting on multiple levels of biotic organization is important for understanding of biological evolution in general [1]–[6] .", "In the studies of prebiotic evolution , it has been shown that some form of multilevel selection is even necessary for the maintenance and evolution o...	[ "Multilevel selection has been indicated as an essential factor for the evolution of complexity in interacting RNA-like replicator systems .", "There are two types of multilevel selection mechanisms: implicit and explicit .", "For implicit multilevel selection , spatial self-organization of replicator populatio...	[ "The origin of life has ever been attracting scientific inquiries .", "The RNA world hypothesis suggests that , before the evolution of DNA and protein , primordial life was based on RNA-like molecules both for information storage and chemical catalysis .", "In the simplest form , an RNA world consists of RNA m...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virion structure, assembly, and egress", "virology" ]	NS2 Protein of Hepatitis C Virus Interacts with Structural and Non-Structural Proteins towards Virus Assembly	journal.ppat.1001278	null	[ [ "The hepatitis C virus ( HCV ) has a high propensity to establish a persistent infection in the human liver .", "Approximately 170 million people suffer from chronic hepatitis C and are at risk to develop cirrhosis and hepatocellular carcinoma [1] .", "Current antiviral therapy is based on the use of ...	[ "Growing experimental evidence indicates that , in addition to the physical virion components , the non-structural proteins of hepatitis C virus ( HCV ) are intimately involved in orchestrating morphogenesis .", "Since it is dispensable for HCV RNA replication , the non-structural viral protein NS2 is suggested t...	[ "Hepatitis C virus ( HCV ) causes major health problems worldwide .", "Understanding the major steps of the life cycle of this virus is essential to developing new and more efficient antiviral molecules .", "Virus assembly is the least understood step of the HCV life cycle .", "Growing experimental evidence i...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Cyclin A Degradation by Primate Cytomegalovirus Protein pUL21a Counters Its Innate Restriction of Virus Replication	journal.ppat.1003825	null	[ [ "Human cytomegalovirus ( HCMV ) , a widespread β-herpesvirus that establishes a lifelong infection , is capable of causing severe complications in immuno-naïve populations and immuno-compromised patients [1] .", "HCMV is known to use a number of mechanisms to manipulate the host cell cycle so that infecte...	[ "Cyclin A is critical for cellular DNA synthesis and S phase progression of the cell cycle .", "Human cytomegalovirus ( HCMV ) can reduce cyclin A levels and block cellular DNA synthesis , and cyclin A overexpression can repress HCMV replication .", "This interaction has only been previously observed in HCMV as...	[ "Cyclins are evolutionarily conserved proteins that associate with cyclin-dependent kinases ( CDKs ) to regulate phosphorylation of multiple substrates to promote cell-cycle progression .", "Many viruses manipulate the cell cycle in order to create an environment suitable for replication; however , only few examp...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "yeast and fungi", "infectious diseases", "genetics and genomics", "microbiology" ]	Transcriptional Regulation by Protein Kinase A in Cryptococcus neoformans	journal.ppat.0030042	null	[ [ "Cryptococcus neoformans is a basidiomycete fungal pathogen that infects both immunocompromised and immunocompetent individuals to cause meningioencephalitis [1] .", "A variety of virulence factors have been characterized , including the formation of a polysaccharide capsule , the production of the pigmen...	[ "A defect in the PKA1 gene encoding the catalytic subunit of cyclic adenosine 5′-monophosphate ( cAMP ) –dependent protein kinase A ( PKA ) is known to reduce capsule size and attenuate virulence in the fungal pathogen Cryptococcus neoformans .", "Conversely , loss of the PKA regulatory subunit encoded by pkr1 re...	[ "The ability of pathogens to regulate the export of proteins and other macromolecules is an important aspect of the infection process .", "The fungal pathogen Cryptococcus neoformans causes life-threatening infections in individuals with AIDS and delivers several virulence factors to the cell surface .", "These...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "gene expression and vector techniques", "biochemistry", "veterinary parasitology", "proteins", "biology and life sciences", "molecular biology techniques", "recombinant proteins", "molecular biology", "parasitology", "molecular biology assays and analysis techniques" ]	Novel Recombinant Multiepitope Proteins for the Diagnosis of Asymptomatic Leishmania infantum-Infected Dogs	journal.pntd.0003429	null	[ [ "Visceral leishmaniasis is caused by a protozoan parasite and affects approximately 500 , 000 million individuals annually worldwide [1] .", "Dogs are the main domestic reservoir of the causative agent of zoonotic visceral leishmaniasis , Leishmania infantum ( = L . chagasi ) [2] , [3] .", "Measures e...	[ "Visceral leishmaniasis is the most severe form of leishmaniasis .", "Worldwide , approximately 20% of zoonotic human visceral leishmaniasis is caused by Leishmania infantum , also known as Leishmania chagasi in Latin America .", "Current diagnostic methods are not accurate enough to identify Leishmania-infecte...	[ "Visceral leishmaniasis is the most severe form among leishmaniasis , being a neglected disease caused by a protozoan parasite .", "Its transmission through phlebotominae bites , between dogs and humans , classifies it as a zoonotic disease .", "It is caused by the specie Leishmania infantum ( = L . chagasi ) a...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental neuroscience", "cellular neuroscience", "neuronal morphology", "biology", "neuroscience", "neural circuit formation" ]	Bimodal Control of Dendritic and Axonal Growth by the Dual Leucine Zipper Kinase Pathway	journal.pbio.1001572	The dual leucine zipper kinase pathway acts on two separate transcriptional programs to dichotomously control dendritic and axonal growth.	[ [ "The separation of the dendritic and axonal compartments in neurons is prerequisite to the function of neural circuits .", "Although the difference between dendrites and axons is a cornerstone of modern neuroscience , as theorized in the “neuron doctrine” by Ramon y Cajal [1] , our molecular understanding...	[ "Knowledge of the molecular and genetic mechanisms underlying the separation of dendritic and axonal compartments is not only crucial for understanding the assembly of neural circuits , but also for developing strategies to correct defective dendrites or axons in diseases with subcellular precision .", "Previous ...	[ "Dendrites and axons are the input and output compartments of a neuron , respectively .", "Understanding how dendrites and axons are separated during neuronal development may help in developing strategies to correct defective neurons in neurological disorders and injuries .", "We show here that an evolutionaril...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "vertebrates", "rickettsia", "mammals", "animals", "marsupials", "clinical medicine", "fleas", "infectious disease control", "bacteria", "ba...	A 2015 outbreak of flea-borne rickettsiosis in San Gabriel Valley, Los Angeles County, California	journal.pntd.0006385	null	[ [ "Acute febrile flea-borne rickettsial diseases are caused by intracellular gram-negative bacteria Rickettsia typhi and Rickettsia felis , which are known to be transmitted to humans by the bite of Xenopsylla cheopis ( oriental rat flea ) and Ctenocephalides felis ( cat flea ) ; both fleas are found on many do...	[ "Although flea-borne rickettsiosis is endemic in Los Angeles County , outbreaks are rare .", "In the spring of 2015 three human cases of flea-borne rickettsiosis among residents of a mobile home community ( MHC ) prompted an investigation .", "Fleas were ubiquitous in common areas due to presence of flea-infest...	[ "Outbreaks of flea-borne rickettsiosis are rare despite the endemic status in Los Angeles County .", "In the spring of 2015 three human cases of flea-borne rickettsiosis among residents of a mobile home community ( MHC ) prompted an investigation .", "Fleas were found in all common areas at the MHC due to prese...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "engineering and technology", "pathogens", "signal processing", "immunology", "microbiology", "dna transcription", "retroviruses", "viruses", "immunodeficiency viruses", "immune receptor sig...	Strength of T cell signaling regulates HIV-1 replication and establishment of latency	journal.ppat.1007802	null	[ [ "HIV-1 persists in a transcriptionally silent latent state in long-lived memory T cells .", "Although antiretroviral therapies ( ART ) suppress HIV-1 replication , interruption of treatment results in rapid viral rebound .", "Therefore , HIV-1 patients must remain on ART indefinitely , despite long-te...	[ "A major barrier to curing HIV-1 is the long-lived latent reservoir that supports re-emergence of HIV-1 upon treatment interruption .", "Targeting this reservoir will require mechanistic insights into the establishment and maintenance of HIV-1 latency .", "Whether T cell signaling at the time of HIV-1 infection...	[ "Activation of CD4+ T cells facilitates HIV-1 infection; however , whether there are minimal signals required for the establishment of infection , replication , and latency has not been explored .", "To determine how T cell signaling influences HIV-1 infection and the generation of latently infected cells , we us...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "cell motility", "medicine and health sciences", "phytoplankton", "chemical compounds", "animals", "nitrates", "nutrition", "materials science", "materials physics", "sedimentation", "plants", "chemistry", "algae", "physics", "stoichiometry", "eukaryota", "cell bio...	Effects of growth rate, cell size, motion, and elemental stoichiometry on nutrient transport kinetics	journal.pcbi.1006118	null	[ [ "Nutrient transport ( e . g . , of NO3- , NH4+ , PO43- ) typically occurs via secondary active porters that are either matched for a specific nutrient molecule type , or for similar types [12]; thus a transporter for NO3- will not transport NH4+ , while similar amino acids such as the cationic group arginine ...	[ "Nutrient acquisition is a critical determinant for the competitive advantage for auto- and osmohetero- trophs alike .", "Nutrient limited growth is commonly described on a whole cell basis through reference to a maximum growth rate ( Gmax ) and a half-saturation constant ( KG ) .", "This empirical application ...	[ "Relating environmental nutrient concentration and nutrient acquisition to cell growth is an important feature of numerical simulations describing ecological systems of microbes .", "Here we investigate the critical role of the combined effects of maximum growth rate , cell size , motion , and elemental stoichiom...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	STING-Dependent Type I IFN Production Inhibits Cell-Mediated Immunity to Listeria monocytogenes	journal.ppat.1003861	null	[ [ "Cell-mediated immunity ( CMI ) is a critical component for protection against intracellular pathogens .", "Upon infection , the innate immune response provides resistance and initiates the development of antigen-specific lymphocytes including cytotoxic CD8+ T cells , which ultimately kill host cells harb...	[ "Infection with Listeria monocytogenes strains that enter the host cell cytosol leads to a robust cytotoxic T cell response resulting in long-lived cell-mediated immunity ( CMI ) .", "Upon entry into the cytosol , L . monocytogenes secretes cyclic diadenosine monophosphate ( c-di-AMP ) which activates the innate ...	[ "Current vaccines are successful at generating neutralizing antibodies , however there is a pressing medical need to find adjuvants that yield long-lived memory T cells .", "Immunization with the bacterium Listeria monocytogenes induces a robust protective immune response mediated by cytotoxic lymphocytes that ar...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "genetics", "biology", "metabolism", "genetics and genomics" ]	Insulin/IGF-1 and Hypoxia Signaling Act in Concert to Regulate Iron Homeostasis in Caenorhabditis elegans	journal.pgen.1002498	null	[ [ "In order to survive in a changing environment , organisms have evolved abilities to sense their surroundings and adaptively adjust their physiology .", "For example , the nematode Caenorhabditis elegans is capable of postponing reproduction if conditions are unsuitable for growth and reproduction by form...	[ "Iron plays an essential role in many biological processes , but also catalyzes the formation of reactive oxygen species ( ROS ) , which can cause molecular damage .", "Iron homeostasis is therefore a critical determinant of fitness .", "In Caenorhabditis elegans , insulin/IGF-1 signaling ( IIS ) promotes growt...	[ "Iron plays a role in many biological processes , including energy generation and DNA replication .", "But to maintain health , levels of cellular iron must be just right: too much or too little iron can cause illnesses , such as anemia and hemochromatosis , respectively .", "Animals therefore carefully control...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "psychology", "social and behavioral sciences", "behavior", "biology", "computational biology", "neuroscience", "neuroimaging" ]	Decoding Unattended Fearful Faces with Whole-Brain Correlations: An Approach to Identify Condition-Dependent Large-Scale Functional Connectivity	journal.pcbi.1002441	null	[ [ "Faces with a fearful expression are thought to signal the presence of a significant , yet undetermined source of danger within the environment , or ‘ambiguous threat’ [1] .", "Evidence from fMRI and evoked potentials ( ERPs ) suggest that fearful face processing can strongly affect brain systems responsi...	[ "Processing of unattended threat-related stimuli , such as fearful faces , has been previously examined using group functional magnetic resonance ( fMRI ) approaches .", "However , the identification of features of brain activity containing sufficient information to decode , or “brain-read” , unattended ( implici...	[ "Brain activity is increasingly characterized by patterns of pair-wise correlations ( large-scale functional connectivity ) across the whole brain obtained from Blood Oxygen Level Dependent ( BOLD ) functional magnetic resonance imaging ( fMRI ) .", "Typically this is done during resting states ( i . e . no prese...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "infectious disease epidemiology", "population dynamics", "parasitic diseases", "neglected tropical diseases", "population biology", "infectious disease control", "infectious diseases", "epidemiology", "biology", "infectious disease modeling", "d...	Visceral Leishmaniasis in the Indian Subcontinent: Modelling Epidemiology and Control	journal.pntd.0001405	null	[ [ "VL , also called Kala-azar ( KA ) , causes more than 50 , 000 deaths each year worldwide [5] .", "The name ‘Kala-azar’ ( ‘black-fever’ ) originates from India; it refers to the hyperpigmentation of the skin during the course of the disease .", "In contrast to CL and MCL , where the parasites are loca...	[ "In the Indian subcontinent , about 200 million people are at risk of developing visceral leishmaniasis ( VL ) .", "In 2005 , the governments of India , Nepal and Bangladesh started the first regional VL elimination program with the aim to reduce the annual incidence to less than 1 per 10 , 000 by 2015 .", "A m...	[ "Visceral Leishmaniasis is a neglected , life-threatening disease affecting the poorest of the poor .", "It has received more attention in light of the regional VL elimination program .", "A deterministic compartmental model was developed to estimate parameters for L . donovani transmission and to optimise inte...	2011
[ "Introduction", "Results", "Material and methods", "Discussion" ]	[ "information entropy", "ecology and environmental sciences", "gene regulation", "experimental design", "research design", "regulator genes", "probability distribution", "mathematics", "gene types", "research and analysis methods", "computer and information sciences", "gene expression", "soil...	An information theoretic treatment of sequence-to-expression modeling	journal.pcbi.1006459	null	[ [ "Cellular processes are determined by the response of regulatory sequences in DNA to signals from specific proteins called transcription factors ( TFs ) , leading to up- or down-regulation of gene expression [1] .", "A major class of regulatory sequences is that of cis-regulatory modules ( CRMs , also cal...	[ "Studying a gene’s regulatory mechanisms is a tedious process that involves identification of candidate regulators by transcription factor ( TF ) knockout or over-expression experiments , delineation of enhancers by reporter assays , and demonstration of direct TF influence by site mutagenesis , among other approac...	[ "In-depth studies of gene regulatory mechanisms employ a variety of experimental approaches such as identifying a gene’s enhancer ( s ) and testing its variants through reporter assays , followed by transcription factor mis-expression or knockouts , site mutagenesis , etc .", "The biologist is often faced with th...	2018

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