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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" ]	[ "systems biology", "genomics", "theoretical biology", "biology", "computational biology", "molecular cell biology", "genetics and genomics" ]	Transcriptome Kinetics Is Governed by a Genome-Wide Coupling of mRNA Production and Degradation: A Role for RNA Pol II	journal.pgen.1002273	null	[ [ "The dynamics of the transcriptome in response to environmental changes is chiefly governed by two opposing processes – RNA production , namely transcription , and RNA degradation .", "Despite this fact , most of the attention has been given to the study of transcription .", "Recently genome-wide tech...	[ "Transcriptome dynamics is governed by two opposing processes , mRNA production and degradation .", "Recent studies found that changes in these processes are frequently coordinated and that the relationship between them shapes transcriptome kinetics .", "Specifically , when transcription changes are counter-act...	[ "Organisms alter genes expression programs in response to changes in their environment .", "Such programs can specify fast induction , slow relaxation , oscillations , etc .", "Conceivably these kinetic outputs may depend on proper orchestration of the various phases of gene expression , including transcription...	2011
[ "Introduction", "Results/Discussion", "Methods" ]	[ "macromolecular complex analysis", "sequence analysis", "protein structure", "biology", "computational biology", "macromolecular structure analysis" ]	Intrinsic Disorder in the Human Spliceosomal Proteome	journal.pcbi.1002641	null	[ [ "In eukaryotic cells and certain viruses that infect them , the coding sequences ( exons ) of most protein-coding genes are interrupted by noncoding regions ( introns ) .", "Following the transcription of an entire gene into a precursor messenger RNA ( pre-mRNA ) , the introns are excised and the exons ar...	[ "The spliceosome is a molecular machine that performs the excision of introns from eukaryotic pre-mRNAs .", "This macromolecular complex comprises in human cells five RNAs and over one hundred proteins .", "In recent years , many spliceosomal proteins have been found to exhibit intrinsic disorder , that is to l...	[ "In eukaryotic cells , introns are spliced out of proteincoding mRNAs by a highly dynamic and extraordinarily plastic molecular machine called the spliceosome .", "In recent years , multiple regions of intrinsic structural disorder were found in spliceosomal proteins .", "Intrinsically disordered regions lack s...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "ecology and environmental sciences", "neurochemistry", "brassica", "plant physiology", "neuroscience", "plant biotechnology", "plant science", "model organisms", "luminescent proteins", "genetically modified plants", "yellow fluorescent protein", "plant pathology", "seedl...	Arabidopsis CaM1 and CaM4 Promote Nitric Oxide Production and Salt Resistance by Inhibiting S-Nitrosoglutathione Reductase via Direct Binding	journal.pgen.1006255	null	[ [ "Soil salinization is one of the most important ecological crises today .", "High salinity alters normal plant growth and development via osmotic stress and ion toxicity .", "Elucidation of the mechanisms by which plants recognize and respond to salt stress is of great interest to plant biologists see...	[ "Salt is a major threat to plant growth and crop productivity .", "Calmodulin ( CaM ) , the most important multifunctional Ca2+ sensor protein in plants , mediates reactions against environmental stresses through target proteins; however , direct proof of the participation of CaM in salt tolerance and its corresp...	[ "Calmodulins ( CaMs ) are a highly conserved protein family in eukaryotes .", "They are known to be important for plant tolerance against external stimuli .", "Here we described a new molecular function of the Arabidopsis thaliana CaMs in response to salinity .", "We reported that two CaM isoforms AtCaM1 and ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Emergence of a New Lineage of Dengue Virus Type 2 Identified in Travelers Entering Western Australia from Indonesia, 2010-2012	journal.pntd.0003442	null	[ [ "Dengue is the most rapidly spreading mosquito-borne viral disease of humans .", "An estimated 390 million dengue virus infections occur annually , of which approximately one quarter result in clinical disease [1] .", "Dengue transmission is predicted to be ubiquitous throughout the tropics , with the...	[ "Dengue virus ( DENV ) transmission is ubiquitous throughout the tropics .", "More than 70% of the current global dengue disease burden is borne by people who live in the Asia-Pacific region .", "We sequenced the E gene of DENV isolated from travellers entering Western Australia between 2010–2012 , most of whom...	[ "Dengue is currently the most rapidly spreading mosquito-borne viral disease of humans , and is endemic in most tropical and sub-tropical countries .", "An estimated 390 million infections occur annually , and over 70% of the current global dengue disease burden is borne by people who live in Southeast Asia and t...	2015
[ "Introduction", "Model", "Results", "Discussion" ]	[ "biophysics/theory and simulation", "computational biology/signaling networks", "genetics and genomics/population genetics" ]	Epistasis in a Model of Molecular Signal Transduction	journal.pcbi.1001134	null	[ [ "Molecular genetics and systems biology have taught us that cells and organisms function as interacting molecular networks [1] , [2] Yet , population genetics studies of correlations between phenotypic traits and genotypes find that phenotypic variation is to a surprising degree attributable to alleles acting...	[ "Biological functions typically involve complex interacting molecular networks , with numerous feedback and regulation loops .", "How the properties of the system are affected when one , or several of its parts are modified is a question of fundamental interest , with numerous implications for the way we study an...	[ "Heritable phenotypic properties are often defined by complex pathways and therefore dependent on multiple polymorphisms affecting different genes .", "Mapping phenotypic consequences of such genetic variation is central to our understanding of disease susceptibility and is fundamental to understanding evolutiona...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Ablating Adult Neurogenesis in the Rat Has No Effect on Spatial Processing: Evidence from a Novel Pharmacogenetic Model	journal.pgen.1003718	null	[ [ "Adult neurogenesis occurs in the olfactory bulb and the hippocampus , where stem-cell like progenitor cells proliferate throughout adult life to generate functionally active neurons [1] , [2] , [3] , [4] , [5] , [6] , [7] .", "Whether this cellular population has a specific role in hippocampal processing...	[ "The function of adult neurogenesis in the rodent brain remains unclear .", "Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments .", "One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation , allowing animals to disting...	[ "Adult neurogenesis occurs in the rodent brain , but its function remains unclear .", "Current theories support the view that adult neurogenesis in the hippocampus supports pattern separation in the hippocampus , thereby allowing animals to distinguish between similar , overlapping inputs .", "However the effec...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "reproductive system", "liver", "nucleases", "cardiovascular anatomy", "enzymes", "dna-binding proteins", "enzymology", "animal models", "mutation", "model organisms", "heart", "experimental organism systems", "molecular biology techniques", "genotyping", ...	MutLγ promotes repeat expansion in a Fragile X mouse model while EXO1 is protective	journal.pgen.1007719	null	[ [ "The 5’ end of the human FMR1 gene ( MIM* 309550 ) contains an unstable CGG/CCG-repeat tract .", "This instability shows a strong expansion bias , with alleles having 55–200 repeats , known as Premutation ( PM ) alleles , being as much as 10 times more likely to expand than contract [1] .", "The likel...	[ "The Fragile X-related disorders ( FXDs ) are Repeat Expansion Diseases resulting from an expansion of a CGG-repeat tract at the 5’ end of the FMR1 gene .", "The mechanism responsible for this unusual mutation is not fully understood .", "We have previously shown that mismatch repair ( MMR ) complexes , MSH2/MS...	[ "The Fragile X-related disorders arise from expansion of a tandem repeat or microsatellite consisting of CGG-repeat units .", "The expansion mutation is not well understood , but our previous data suggests that MutSα and MutSβ , mismatch repair ( MMR ) proteins that normally protect the genome against microsatell...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "molecular biology/recombination", "infectious diseases/gastrointestinal infections" ]	Tissue Invasion by Entamoeba histolytica: Evidence of Genetic Selection and/or DNA Reorganization Events in Organ Tropism	journal.pntd.0000219	null	[ [ "Entamoeba histolytica , the causative agent of human amebiasis , is endemic in many tropical countries .", "It is well established that E . histolytica infections result in variable clinical outcomes .", "Most infections remain asymptomatic , some develop diarrhea and dysentery , and only a few devel...	[ "Entamoeba histolytica infection may have various clinical manifestations .", "Nine out of ten E . histolytica infections remain asymptomatic , while the remainder become invasive and cause disease .", "The most common form of invasive infection is amebic diarrhea and colitis , whereas the most common extra-int...	[ "The parasite Entamoeba histolytica can cause serious disease by invading the lining of the large intestine and spreading to other organs of the body .", "However , most infected individuals never develop symptoms , and it is not clear what determines the different outcomes of infection .", "Factors that might ...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model	journal.pntd.0004265	null	[ [ "Buruli Ulcer ( BU ) is a necrotizing skin disease caused by Mycobacterium ulcerans .", "M . ulcerans pathogenesis is mediated by mycolactone , a potent polyketide-derived macrolide that triggers apoptotic cell death [1 , 2] .", "Initial pre-ulcerative BU lesions are indolent with no systemic symptoms...	[ "Buruli Ulcer ( BU ) is a necrotizing skin disease caused by Mycobacterium ulcerans infection .", "BU is characterized by a wide range of clinical forms , including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated .", "Nevertheless , spontaneous healing has been reported to ...	[ "Buruli Ulcer ( BU ) is a devastating skin disease caused by Mycobacterium ulcerans .", "BU usually starts off as a non-ulcerative lesion , but if lesions are left untreated they can evolve into ulcers or may even affect the bone .", "Nevertheless , spontaneous healing of active lesions has been reported in som...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/signaling networks" ]	Plato's Cave Algorithm: Inferring Functional Signaling Networks from Early Gene Expression Shadows	journal.pcbi.1000828	null	[ [ "A major goal of systems biology is to elucidate the molecular networks that underlie cellular decision-making and predict emergent properties of the system .", "Knowledge of molecular networks provides novel insight into the mechanisms underlying both physiological and pathological cellular processes .",...	[ "Improving the ability to reverse engineer biochemical networks is a major goal of systems biology .", "Lesions in signaling networks lead to alterations in gene expression , which in principle should allow network reconstruction .", "However , the information about the activity levels of signaling proteins con...	[ "Elucidating the biochemical interactions in living cells is essential to understanding their behavior under various external conditions .", "Some of these interactions occur between signaling components with many active states , and their activity levels may be difficult to measure directly .", "However , most...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/immunodeficiency viruses", "virology", "infectious diseases/hiv infection and aids", "virology/host antiviral responses", "virology/host invasion and cell entry" ]	Tetherin Restricts Productive HIV-1 Cell-to-Cell Transmission	journal.ppat.1000955	null	[ [ "HIV and many other viruses move not only as free viral particles diffusing in the extracellular environment , but also directly between cells [1] .", "Cell-to-cell spread accelerates viral dissemination , and likely influences pathogenesis and immune evasion [1] .", "Various modes of cell-to-cell HIV...	[ "The IFN-inducible antiviral protein tetherin ( or BST-2/CD317/HM1 . 24 ) impairs release of mature HIV-1 particles from infected cells .", "HIV-1 Vpu antagonizes the effect of tetherin .", "The fate of virions trapped at the cell surface remains poorly understood .", "Here , we asked whether tetherin impairs...	[ "Tetherin is a cell surface “restriction factor” that acts as an innate antiviral defense .", "Tetherin prevents newly produced particles of HIV-1 and other enveloped viruses from escaping the surface of infected cells .", "HIV-1 encodes the protein Vpu to counteract this host defense .", "We have studied her...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biotechnology", "molecular probe techniques", "marker genes", "cloning", "codons", "dna sequences", "complementary rna", "dna construction", "dna", "molecular biology techniques", "genetic engineering", "promoter regions", "plasmid vectors", "cell labeling", "small interfering rnas", ...	New Developments of RNAi in Paracoccidioides brasiliensis: Prospects for High-Throughput, Genome-Wide, Functional Genomics	journal.pntd.0003173	null	[ [ "Paracoccidioides brasiliensis is a thermo-dimorphic Ascomycota phylogenetically related to Blastomyces dermatitidis , Coccidioides immitis and Histoplasma capsulatum .", "Likewise these human-pathogen fungi , inhaled conidia from the saprophytic mycelia form of P . brasiliensis undergo a most remarkable ...	[ "The Fungal Genome Initiative of the Broad Institute , in partnership with the Paracoccidioides research community , has recently sequenced the genome of representative isolates of this human-pathogen dimorphic fungus: Pb18 ( S1 ) , Pb03 ( PS2 ) and Pb01 .", "The accomplishment of future high-throughput , genome-...	[ "Diverse eukaryotes , including various fungi , utilize RNA interference ( RNAi ) pathways to regulate genome-wide gene expression .", "Since the initial characterization of these pathways and the demonstration of its artificial induction in the filamentous ascomycete Neurospora crassa , RNAi has emerged as the m...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/infectious diseases of the nervous system", "pathology/neuropathology", "molecular biology/nucleolus and nuclear bodies", "virology/virion structure, assembly, and egress", "neurological disorders/infectious diseases of the nervous system", "microbiology/innate immunity", "infectiou...	Entrapment of Viral Capsids in Nuclear PML Cages Is an Intrinsic Antiviral Host Defense against Varicella-Zoster Virus	journal.ppat.1001266	null	[ [ "Promyelocytic leukemia protein ( PML ) is a major organizing component of structures that are referred to as PML nuclear bodies ( PML-NBs ) or nuclear domain 10 ( ND10 ) bodies [1]–[3] .", "These nuclear bodies are heterogenous in size , shape and molecular composition [4]–[6] , are prominent in most mam...	[ "The herpesviruses , like most other DNA viruses , replicate in the host cell nucleus .", "Subnuclear domains known as promyelocytic leukemia protein nuclear bodies ( PML-NBs ) , or ND10 bodies , have been implicated in restricting early herpesviral gene expression .", "These viruses have evolved countermeasure...	[ "Many DNA viruses , including varicella-zoster virus ( VZV ) , a herpesvirus that causes varicella ( chickenpox ) and zoster ( shingles ) , replicate in the host cell nucleus .", "Here , we have identified an intrinsic antiviral mechanism that specifically targets newly assembled VZV capsids and contains these es...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "gastroenterology and hepatology/colon and rectum", "infectious diseases/gastrointestinal infections", "immunology/innate immunity" ]	Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa	journal.ppat.1000902	null	[ [ "The attaching and effacing ( A/E ) bacteria Enteropathogenic Escherichia coli ( EPEC ) and Enterohemorrhagic E . coli ( EHEC ) are major contributors to the global disease burden caused by enteric bacterial pathogens [1] .", "EPEC infects the small bowel causing acute watery diarrhea , fever and nausea [...	[ "Despite recent advances in our understanding of the pathogenesis of attaching and effacing ( A/E ) Escherichia coli infections , the mechanisms by which the host defends against these microbes are unclear .", "The goal of this study was to determine the role of goblet cell-derived Muc2 , the major intestinal sec...	[ "Enteropathogenic E . coli ( EPEC ) and Enterohemorrhagic E . coli ( EHEC ) are important causes of diarrheal disease and other serious complications worldwide .", "Despite many studies addressing the pathogenic strategies used by these microbes , how the host protects itself from these pathogens is poorly unders...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "mathematics", "computer science", "computational biology" ]	Taking the Lag out of Jet Lag through Model-Based Schedule Design	journal.pcbi.1000418	null	[ [ "Endogenous circadian ( ∼24 hour ) rhythms are important physiological regulators of sleep quality and duration , hormone levels , mood ( including alertness ) , and cognitive neurobehavioral performance in humans [1] .", "The significant effect of circadian timing ( phase ) on performance has been shown ...	[ "Travel across multiple time zones results in desynchronization of environmental time cues and the sleep–wake schedule from their normal phase relationships with the endogenous circadian system .", "Circadian misalignment can result in poor neurobehavioral performance , decreased sleep efficiency , and inappropri...	[ "Traveling across several times zones can cause an individual to experience “jet lag , ” which includes trouble sleeping at night and trouble remaining awake during the day .", "A major cause of these effects is the desynchronization between the body's internal circadian clock and local environmental cues .", "...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology/human evolution", "evolutionary biology/genomics", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics" ]	Adaptive Evolution in Zinc Finger Transcription Factors	journal.pgen.1000325	null	[ [ "Coordinated evolution of complex characters can occur by altering regulatory genes that control large suites of effector genes [1] .", "A small number of changes in these regulatory genes can result in conspicuous and harmonious changes in developmental pattern , reproduction , or physiology , because th...	[ "The majority of human genes are conserved among mammals , but some gene families have undergone extensive expansion in particular lineages .", "Here , we present an evolutionary analysis of one such gene family , the poly–zinc-finger ( poly-ZF ) genes .", "The human genome encodes approximately 700 members of ...	[ "Gene families , arising by the repeated duplication and diversification of existing genes , are a pervasive feature of the genomes of higher organisms .", "In this study , we analyze the evolutionary history of one of the largest gene families in humans , the poly–zinc-finger genes .", "Each poly–zinc-finger g...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Supporting Information" ]	[ "evolutionary biology", "viruses", "virology", "computational biology" ]	An Evolutionary-Network Model Reveals Stratified Interactions in the V3 Loop of the HIV-1 Envelope	journal.pcbi.0030231	null	[ [ "The human immunodeficiency virus type 1 ( HIV-1 ) possesses a highly variable envelope comprising the glycoproteins gp120 and gp41 , which mediate the binding and entry of the virus into a host cell .", "The viral envelope is also a potent antigen for neutralizing antibodies [1–4] and cytotoxic and helpe...	[ "The third variable loop ( V3 ) of the human immunodeficiency virus type 1 ( HIV-1 ) envelope is a principal determinant of antibody neutralization and progression to AIDS .", "Although it is undoubtedly an important target for vaccine research , extensive genetic variation in V3 remains an obstacle to the develo...	[ "The third variable loop ( V3 ) of the human immunodeficiency virus type 1 ( HIV-1 ) envelope is a principal determinant of viral growth characteristics and an important target for the immune system .", "Interactions between residues of V3 allow the virus to shift between combinations of residues to escape the im...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Notch Is Required in Adult Drosophila Sensory Neurons for Morphological and Functional Plasticity of the Olfactory Circuit	journal.pgen.1005244	null	[ [ "Appropriate behavioral responses to changing environments are essential for an organism’s survival .", "Odors are key environmental signals .", "In response to chronic odor exposure , depending on the valence of the conditioning odor and the context of odor delivery , an animal will either exhibit de...	[ "Olfactory receptor neurons ( ORNs ) convey odor information to the central brain , but like other sensory neurons were thought to play a passive role in memory formation and storage .", "Here we show that Notch , part of an evolutionarily conserved intercellular signaling pathway , is required in adult Drosophil...	[ "Appropriate behavioral responses to changing environmental signals , such as odors , are essential for an organism’s survival .", "In Drosophila odors are detected by olfactory receptor neurons ( ORNs ) that synapse with second order projection neurons ( PNs ) and local interneurons in morphologically identifiab...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "hospitalizations", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "respiratory infections", "pathogens", "tropical diseases", "microbiology", "geographical locations", "alphaviruses", "pulmonology", "health care", "viruses", ...	Risk factors for hospitalization of patients with chikungunya virus infection at sentinel hospitals in Puerto Rico	journal.pntd.0007084	null	[ [ "Chikungunya is an acute febrile illness ( AFI ) characterized by potentially debilitating arthralgia [1] and is the result of infection with chikungunya virus ( CHIKV ) , which is transmitted to humans primarily through the bite of infected Aedes ( Stegomyia ) species mosquitoes [2] .", "Previous reports...	[ "Hospitalization of patients during outbreaks of chikungunya virus has been reported to be uncommon ( 0 . 5–8 . 7% ) , but more frequent among infants and the elderly .", "CHIKV was first detected in Puerto Rico in May 2014 .", "We enrolled patients with acute febrile illness ( AFI ) presenting to two hospital ...	[ "Chikungunya is an emerging infectious disease caused by a virus ( chikungunya virus , CHIKV ) transmitted through the bite of infected mosquitos; typical symptoms are fever and joint pain .", "After CHIKV was first detected in Puerto Rico in 2014 , an epidemic quickly spread across the island .", "Because prev...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/membranes and sorting" ]	Endocytic Sorting and Recycling Require Membrane Phosphatidylserine Asymmetry Maintained by TAT-1/CHAT-1	journal.pgen.1001235	null	[ [ "In eukaryotic cells , internalized cargoes are transported to early endosomes where they are sorted to be recycled back to the plasma membrane , degraded in lysosomes or delivered to the trans-Golgi network .", "Early endosomes display a complex and pleiomorphic organization with many tubular processes e...	[ "Endocytic sorting is achieved through the formation of morphologically and functionally distinct sub-domains within early endosomes .", "Cargoes destined for recycling are sorted to and transported through newly-formed tubular membranes , but the processes that regulate membrane tubulation are poorly understood ...	[ "The process by which cells take up nutrients and other large molecules from the extracellular environment is known as endocytosis .", "At the cell surface , external molecules become enclosed in membrane spheres called endosomes .", "Early endosomes serve as a sorting station , directing the contents ( cargo m...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/persistence and latency", "virology/viruses and cancer", "cell biology/cell signaling" ]	KSHV Reactivation from Latency Requires Pim-1 and Pim-3 Kinases to Inactivate the Latency-Associated Nuclear Antigen LANA	journal.ppat.1000324	null	[ [ "Kaposi's sarcoma herpesvirus ( KSHV ) is an etiological agent of three types of malignancies: Kaposi's sarcoma ( KS ) , multicentric Castleman disease , and primary effusion lymphoma ( PEL ) [1] .", "The KSHV genome encodes homologs of cellular proteins , which deregulate signaling pathways , govern cell...	[ "Host signal-transduction pathways are intimately involved in the switch between latency and productive infection of herpes viruses .", "As with other herpes viruses , infection by Kaposi's sarcoma herpesvirus ( KSHV ) displays these two phases .", "During latency only few viral genes are expressed , while in t...	[ "The switch from latency to productive viral replication ( reactivation ) is a crucial decision in the viral life cycle , and recent clinico-epidemiological studies support the importance of lytic replication in the development and progression of Kaposi's sarcoma .", "Hence , cellular signaling pathways operative...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "sequencing techniques", "database searching", "sequence assembly tools", "plant science", "metagenomics", "genome analysis", "molecular biology techniques", "photosynthesis", "ribulose-1,5-bisphosphate carboxylase oxygenase", "sequence similarity searching", "research and analysis methods", "...	A Graph-Centric Approach for Metagenome-Guided Peptide and Protein Identification in Metaproteomics	journal.pcbi.1005224	null	[ [ "Microbiome studies have produced massive metagenomic data , and more recently other meta-omics including metatranscriptomic and metaproteomic data [1] .", "Analyses of these data reveal insights into the composition , function and regulatory characteristics of the microbial communities associated with di...	[ "Metaproteomic studies adopt the common bottom-up proteomics approach to investigate the protein composition and the dynamics of protein expression in microbial communities .", "When matched metagenomic and/or metatranscriptomic data of the microbial communities are available , metaproteomic data analyses often e...	[ "In recent years , meta-omic ( including metatranscriptomic and metaproteomic ) techniques have been adopted as complementary approaches to metagenomic sequencing to study functional characteristics and dynamics of microbial communities , aiming at a holistic understanding of a community to respond to the changes i...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "plant science", "infectious disease epidemiology", "epidemiology", "plant pathology", "biology and life sciences" ]	Protection Motivation Theory in Predicting Intention to Engage in Protective Behaviors against Schistosomiasis among Middle School Students in Rural China	journal.pntd.0003246	null	[ [ "Prevention of schistosomiasis has been a significant public health challenge in tropical and subtropical regions of the world .", "Schistosomiasis epidemic has been recorded in 80 countries , and more than 240 million people are infected and 700 million are susceptible [1] , [2] .", "The global disab...	[ "Among millions of people who suffer from schistosomiasis in China , adolescents are at increased risk to be infected .", "However , there is a lack of theory-guided behavioral prevention intervention programs to protect these adolescents .", "This study attempted to apply the Protection Motivation Theory ( PMT...	[ "In China , millions of population suffer from schistosomiasis infection and adolescents tend to have higher infection rates than adults .", "The Knowledge-Attitude-Practice ( KAP ) Theory has traditionally been used as guidance to schistosomiasis prevention in China .", "However , despite increases in knowledg...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Epigenetic Aging Signatures Are Coherently Modified in Cancer	journal.pgen.1005334	null	[ [ "Age is the strongest demographic risk factor for cancer , indicating that molecular changes upon aging trigger malignant transformation .", "Somatic mutations are usually considered as tumor-initiating events [1] .", "However , aging is also accompanied by specific epigenetic modifications , which ma...	[ "Aging is associated with highly reproducible DNA methylation ( DNAm ) changes , which may contribute to higher prevalence of malignant diseases in the elderly .", "In this study , we analyzed epigenetic aging signatures in 5 , 621 DNAm profiles of 25 cancer types from The Cancer Genome Atlas ( TCGA ) .", "Over...	[ "Our genome harbors epigenetic marks , such as DNA methylation ( DNAm ) at cytosine residues , which govern cellular differentiation .", "Some epigenetic modifications accumulate throughout life in a highly reproducible manner–they may contribute to the aging process and facilitate reliable age-predictions .", ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "infectious diseases", "biochemistry/macromolecular assemblies and machines", "microbiology" ]	Topology and Organization of the Salmonella typhimurium Type III Secretion Needle Complex Components	journal.ppat.1000824	null	[ [ "One of the most exciting recent developments in the field of bacterial pathogenesis is the discovery that many bacterial pathogens utilize supramolecular nanomachines to deliver bacterial proteins into eukaryotic cells .", "These proteins , which are collectively referred to as effectors , have the capac...	[ "The correct organization of single subunits of multi-protein machines in a three dimensional context is critical for their functionality .", "Type III secretion systems ( T3SS ) are molecular machines with the capacity to deliver bacterial effector proteins into host cells and are fundamental for the biology of ...	[ "Many Gram negative pathogens such as Salmonella , Yersinia , or Shigella use the type III secretion system ( T3SS ) to initiate infection in eukaryotic cells , resulting in well known clinical symptoms ranging from mild headaches and diarrhea to life-threatening diseases such as typhoid fever or bubonic plague .",...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "connectomics", "neuroanatomy", "anatomy", "computational neuroscience", "nervous system", "biology and life sciences", "computational biology", "neuroscience" ]	A Network Convergence Zone in the Hippocampus	journal.pcbi.1003982	null	[ [ "The hippocampal formation is among the most studied areas of the brain .", "Along with adjacent cortical structures , such as the entorhinal , perirhinal and parahippocampal cortices , the hippocampus is thought to facilitate memory function , particularly the initial encoding of memories [1]–[4] .", ...	[ "The hippocampal formation is a key structure for memory function in the brain .", "The functional anatomy of the brain suggests that the hippocampus may be a convergence zone , as it receives polysensory input from distributed association areas throughout the neocortex .", "However , recent quantitative graph-...	[ "The hippocampus is a key structure in the brain , particularly for memory function .", "The functional anatomy of brain networks suggests that the hippocampus should be a hub in the large-scale connectome , yet so far quantitative network analyses have failed to find any evidence of such a role .", "Here we sh...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "transfer rna", "mitochondrial dna", "gene regulation", "rna extraction", "vertebrates", "nucleotides", "animals", "forms of dna", "mitochondria", "dna", "bioenergetics", "cellular structures and organelles", "extraction techniques", "research and analysis methods", "small interfering rn...	Mitochondrial 16S rRNA Is Methylated by tRNA Methyltransferase TRMT61B in All Vertebrates	journal.pbio.1002557	Two solutions were selected during evolution to allow proper function of the vertebrate mitochondrial 16S ribosomal RNAeither RNA methylation by a tRNA methyltransferase or ancient evolutionary mutation.	[ [ "Most RNAs are enzymatically modified after transcription .", "To date , more than 100 different species of chemical modifications have been identified in various RNA molecules from all domains of life [1] .", "Historically , analyses of RNA modifications have been limited to abundant RNA molecules su...	[ "The mitochondrial ribosome , which translates all mitochondrial DNA ( mtDNA ) -encoded proteins , should be tightly regulated pre- and post-transcriptionally .", "Recently , we found RNA-DNA differences ( RDDs ) at human mitochondrial 16S ( large ) rRNA position 947 that were indicative of post-transcriptional m...	[ "RNA modifications constitute an important layer of information , with functional implications that are not written in the underlying DNA sequence .", "Recently , we observed an apparent RNA-DNA difference ( RDD ) at position 947 of the human mitochondrial 16S ribosomal RNA ( rRNA ) , but its nature and mechanism...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/plant-biotic interactions", "evolutionary biology/microbial evolution and genomics", "virology/virus evolution and symbiosis", "virology", "plant biology", "evolutionary biology", "virology/host invasion and cell entry" ]	Large Bottleneck Size in Cauliflower Mosaic Virus Populations during Host Plant Colonization	journal.ppat.1000174	null	[ [ "The main forces driving changes of the frequencies of alleles within populations are selection ( deterministic ) and genetic drift ( stochastic ) .", "While both forces obviously act concomitantly in most cases , the balance of their respective action is governed by a number of factors , one of the most ...	[ "The effective size of populations ( Ne ) determines whether selection or genetic drift is the predominant force shaping their genetic structure and evolution .", "Despite their high mutation rate and rapid evolution , this parameter is poorly documented experimentally in viruses , particularly plant viruses .", ...	[ "Whether selection or stochastic genetic drift is the major force driving the evolution of a virus depends largely on the size of the viral population , with the former being predominant in large populations and the latter taking over when population sizes are transiently or durably reduced .", "This question has...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemical biology", "microbiology/applied microbiology" ]	Cleavage of Phosphorothioated DNA and Methylated DNA by the Type IV Restriction Endonuclease ScoMcrA	journal.pgen.1001253	null	[ [ "The sequence of the DNA bases contains the genetic information that is copied with great accuracy and inherited by successive generations .", "DNA may also carry so called epigenetic modifications that are added by host enzymes after replication .", "These modifications are lost or changed after tran...	[ "Many taxonomically diverse prokaryotes enzymatically modify their DNA by replacing a non-bridging oxygen with a sulfur atom at specific sequences .", "The biological implications of this DNA S-modification ( phosphorothioation ) were unknown .", "We observed that simultaneous expression of the dndA-E gene clus...	[ "Bacteria frequently exchange genetic information among themselves .", "DNA from one species can be transferred efficiently to unrelated microbes .", "Bacteria have developed systems that restrict gene transfer .", "Many restriction systems recognize and destroy foreign DNA entering the cells , but there are ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "systems biology", "biophysics theory", "biology", "computational biology", "metabolic networks", "biophysics" ]	A Scalable Algorithm to Explore the Gibbs Energy Landscape of Genome-Scale Metabolic Networks	journal.pcbi.1002562	null	[ [ "Constraint-based models of cellular metabolism are important tools to analyze and predict the chemical activity and response to perturbations of cells without relying on kinetic details that are often unavailable .", "In such frameworks , the metabolic capabilities of a cell are inferred from the overall...	[ "The integration of various types of genomic data into predictive models of biological networks is one of the main challenges currently faced by computational biology .", "Constraint-based models in particular play a key role in the attempt to obtain a quantitative understanding of cellular metabolism at genome s...	[ "The operation of biological systems is constrained under all circumstances by the laws of physics .", "Thermodynamics , in particular , dictates preferential directions in which biochemical reactions should flow at stationarity .", "When applied to cellular reaction systems ( like metabolic networks ) , it fav...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "enzymes", "parasitology", "immunology", "host-pathogen interaction", "biology", "microbiology", "immune response", "immunoglobulins" ]	The Secreted Triose Phosphate Isomerase of Brugia malayi Is Required to Sustain Microfilaria Production In Vivo	journal.ppat.1003930	null	[ [ "Continued survival of parasitic helminths within their mammalian host requires that they neutralise potentially protective immune responses , generate energy and reproduce .", "Filarial nematodes are particularly long-lived , tissue-dwelling parasites which evade immunity and maintain transmission over m...	[ "Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects .", "Microfilariae are produced by long-lived adult parasites , which also release a suite of excretory-secretory products that have recently been sub...	[ "Triose phosphate isomerase ( TPI ) is a ubiquitous and highly conserved enzyme in intracellular glucose metabolism .", "Surprisingly , the human lymphatic filariai nematode parasite Brugia malayi , releases TPI into the extracellular environment , suggesting a role in helminth survival in the mammalian host .", ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "veterinary immunology", "veterinary diseases", "veterinary parasitology", "zoonotic diseases", "leishmaniasis", "immunology", "veterinary science", "veterinary medicine" ]	Use of a LiESP/QA-21 Vaccine (CaniLeish) Stimulates an Appropriate Th1-Dominated Cell-Mediated Immune Response in Dogs	journal.pntd.0001683	null	[ [ "Canine leishmaniasis , a vector-borne disease of dogs , is caused by Leishmania infantum in the Mediterranean basin and is a significant problem for the canine population of endemic areas [1] .", "It is transmitted in the Mediterranean area by the bite of certain species of sand flies of the Phlebotomus ...	[ "Canine leishmaniasis is an important zoonotic disease of dogs .", "The clinical outcome of infection is variable , with the efficiency of the immune response being the key determining factor .", "There is now a general consensus that a predominant Th1 immune profile in an overall mixed Th1/Th2 response is asso...	[ "The dog is the principle reservoir of Leishmania infantum , a parasite spread from dog to dog by a sandfly vector .", "The reduction of canine leishmaniasis is therefore a key factor in the overall management of the epidemiology of this parasite .", "There is also a need for effective prevention on welfare gro...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "fluorescence imaging", "medicine and health sciences", "immune physiology", "immunology", "microbiology", "viral structure", "membrane proteins", "viruses", "rna viruses", "antibodies", "cellular structures and organelles", "research and analysis methods", "immune system proteins", "imagi...	The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites	journal.ppat.1005428	null	[ [ "Positive-strand RNA viruses account for a significant portion of the total viral diseases affecting humans around the world .", "Within this class of viruses is the Flaviviridae family , consisting of four viral genera , including Flavivirus and Hepacivirus .", "HCV is a Hepacivirus that is estimated...	[ "Hepatitis C virus ( HCV ) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide .", "HCV replicates in the cytoplasm , and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures , collectively termed the membra...	[ "Hepatitis C virus ( HCV ) is a positive-strand RNA virus and it is a major cause of liver disease worldwide affecting more than 170 million individuals .", "Infection of cells with HCV leads to rearrangement of cytoplasmic host cell membranes and the formation of the membranous web ( MW ) containing viral replic...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "chemical compounds", "disaccharides", "pathology and laboratory medicine", "pathogens", "carbohydrates", "animals", "organic compounds", "muscle contraction", "animal models", "physiological processes", "drosophila melanogaster", "model org...	The DH31/CGRP enteroendocrine peptide triggers intestinal contractions favoring the elimination of opportunistic bacteria	journal.ppat.1007279	null	[ [ "The intestinal mucosa is endowed with several systems of defense to fight against the bacteria that are swallowed along with food .", "First of all , the gut epithelium is a sealed barrier preventing aggressors from crossing the epithelial layer [1] .", "Secondly , the gut lining is covered by mucus ...	[ "The digestive tract is the first organ affected by the ingestion of foodborne bacteria .", "While commensal bacteria become resident , opportunistic or virulent bacteria are eliminated from the gut by the local innate immune system .", "Here we characterize a new mechanism of defense , independent of the immun...	[ "The intestine is the first barrier to fight non-commensal bacteria ingested along with the food .", "The innate immune system is the main mean mounted by the gut lining in response to ill-causing bacteria to avoid detrimental impact .", "Intestinal cells produce chlorine bleach and antimicrobial peptides that ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "innate immune system", "medicine and health sciences", "viral vaccines", "immune physiology", "cytokines", "pathology and laboratory medicine", "immunology", "tropical diseases", "microbiology", "vaccines", "preventive medicine", "phase iii clinical investigation", "developmental biology", ...	Cytokine Profile of Children Hospitalized with Virologically-Confirmed Dengue during Two Phase III Vaccine Efficacy Trials	journal.pntd.0004830	null	[ [ "Dengue virus ( DENV ) is the most important mosquito-borne pathogen threatening approximately half of the world’s population , mostly in tropical and subtropical areas including Latin America and Southeast Asia [1 , 2] .", "Infection with any of the four DENV serotypes can be asymptomatic or cause a spec...	[ "Two large-scale efficacy studies with the recombinant yellow fever-17D–dengue virus , live-attenuated , tetravalent dengue vaccine ( CYD-TDV ) candidate undertaken in Asia ( NCT01373281 ) and Latin America ( NCT01374516 ) demonstrated significant protection against dengue disease during two years’ active surveilla...	[ "A live-attenuated , tetravalent dengue vaccine ( CYD-TDV ) has been shown to provide protection against dengue disease in two large-scale , placebo-controlled , phase III efficacy studies .", "Continued surveillance of study participants was subsequently undertaken to better define longer term vaccine efficacy a...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "genome analysis tools", "gene expression", "genetics", "biology", "genomics", "genetics and genomics", "genetic maps" ]	Rare and Common Regulatory Variation in Population-Scale Sequenced Human Genomes	journal.pgen.1002144	null	[ [ "Deeper characterization of genetic variation is becoming increasingly available with advances in DNA sequencing technology [1]–[5] .", "This improves our ability to pinpoint protein-coding variants which disrupt protein structure , and has already begun to provide insight into the genetic basis of diseas...	[ "Population-scale genome sequencing allows the characterization of functional effects of a broad spectrum of genetic variants underlying human phenotypic variation .", "Here , we investigate the influence of rare and common genetic variants on gene expression patterns , using variants identified from sequencing d...	[ "The recent availability of almost fully sequenced human genomes by the 1000 genomes project allows the direct study of genetic variants that influence levels of gene expression in the cell .", "In this study , we explore the effect of rare and common variants on levels of gene expression .", "We show that the ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "visual system", "biology", "sensory systems", "neuroscience" ]	Synaptic Transmission from Horizontal Cells to Cones Is Impaired by Loss of Connexin Hemichannels	journal.pbio.1001107	null	[ [ "In the vertebrate retina , photoreceptors project to horizontal cells and bipolar cells .", "Horizontal cells are mediating lateral inhibition in the outer retina , a process that is thought to be involved in contrast enhancement .", "Horizontal cells are electrically coupled by gap-junctions , thus ...	[ "In the vertebrate retina , horizontal cells generate the inhibitory surround of bipolar cells , an essential step in contrast enhancement .", "For the last decades , the mechanism involved in this inhibitory synaptic pathway has been a major controversy in retinal research .", "One hypothesis suggests that con...	[ "Contrast enhancement is a fundamental feature of our visual system , initiated at the first synaptic connections in the retina .", "These are the synapses between photoreceptors ( rods and cones ) and their targets , horizontal cells and bipolar cells .", "Horizontal cells receive input from many cones and sub...	2011
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "infectious diseases/respiratory infections", "genetics and genomics/comparative genomics", "genetics and genomics/gene expression" ]	Analysis of the Legionella longbeachae Genome and Transcriptome Uncovers Unique Strategies to Cause Legionnaires' Disease	journal.pgen.1000851	null	[ [ "Legionella longbeachae is one species of the family Legionellaceae that causes legionellosis , an atypical pneumonia that can be fatal if not promptly treated .", "While Legionella pneumophila is the leading cause of legionellosis in the USA and Europe , and is associated with around 91% of the cases wor...	[ "Legionella pneumophila and L . longbeachae are two species of a large genus of bacteria that are ubiquitous in nature .", "L . pneumophila is mainly found in natural and artificial water circuits while L . longbeachae is mainly present in soil .", "Under the appropriate conditions both species are human pathog...	[ "Legionella longbeachae , found in potting soil , and L . pneumophila , present in aquatic environments , are opportunistic human pathogens that cause Legionnaires' disease , a severe and often fatal pneumonia .", "The analysis and comparison of the genome sequences of four L . longbeachae genomes together with t...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "microbiology" ]	The DEAD-box RNA Helicase DDX6 is Required for Efficient Encapsidation of a Retroviral Genome	journal.ppat.1002303	null	[ [ "Foamy viruses , the only genus in the retrovirus subfamily Spumaretrovirinae , are complex retroviruses that infect all non-human primates , cats , cows , and horses .", "Humans are not natural hosts but can acquire primate foamy viruses as zoonotic infections [1] .", "The genome of foamy virus encod...	[ "Viruses have to encapsidate their own genomes during the assembly process .", "For most RNA viruses , there are sequences within the viral RNA and virion proteins needed for high efficiency of genome encapsidation .", "However , the roles of host proteins in this process are not understood .", "Here we find ...	[ "Foamy viruses are complex retroviruses that infect non-human primates , cats , cows , and horses .", "Humans are not natural hosts but can acquire primate foamy viruses as zoonotic infections .", "During foamy virus assembly process , viral RNAs and Gag capsid proteins are targeted to a discrete intra-cytoplas...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Xenosurveillance: A Novel Mosquito-Based Approach for Examining the Human-Pathogen Landscape	journal.pntd.0003628	null	[ [ "Over the last half century infectious diseases have emerged with increasing frequency [1] .", "Emerging infectious diseases ( EIDs ) have profound public health and economic consequences as highlighted by the ongoing epidemics of Ebola virus in West Africa [2] , MERS coronavirus in the Middle East [3] , ...	[ "Globally , regions at the highest risk for emerging infectious diseases are often the ones with the fewest resources .", "As a result , implementing sustainable infectious disease surveillance systems in these regions is challenging .", "The cost of these programs and difficulties associated with collecting , ...	[ "The emergence of infectious diseases can have devastating public health and economic consequences .", "Being able to identify such events at early stages could significantly mitigate some of these outcomes .", "In many resource poor regions of the world , current surveillance methods are hindered by the costs ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "aging", "developmental biology", "animal genetics", "invertebrate genetics", "organism development", "genetics", "biology and life sciences" ]	Gene Pathways That Delay Caenorhabditis elegans Reproductive Senescence	journal.pgen.1004752	null	[ [ "Age-associated reproductive decline is one of the first aging phenotypes to manifest in humans .", "As women age , they experience both a decline in fertility and an increased risk of miscarriage and birth defects [1] , [2] , and completely cease reproduction ( reproductive senesce ) after menopause .", ...	[ "Reproductive senescence is a hallmark of aging .", "The molecular mechanisms regulating reproductive senescence and its association with the aging of somatic cells remain poorly understood .", "From a full genome RNA interference ( RNAi ) screen , we identified 32 Caenorhabditis elegans gene inactivations that...	[ "Female reproductive senescence is one hallmark of human aging , and as the germline ages , there is increased incidence of chromosome non-dysjunction and DNA damage .", "Delayed childbearing is a general feature in modern society , resulting in high risk of infertility , miscarriage and birth defects .", "Thus...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "geography", "social and behavioral sciences", "epidemiology", "global health", "public health", "toxicology" ]	Using Geographical Information Systems to Identify Populations in Need of Improved Accessibility to Antivenom Treatment for Snakebite Envenoming in Costa Rica	journal.pntd.0002009	null	[ [ "The primary aim of the present study is to provide information to assist decision-making concerning for which primary health care facilities ( EBAIS ) it is suitable to have antivenom , i . e . those that serve a population with a high risk of snakebites and long transport times to hospitals or clinics where...	[ "Snakebite accidents are an important health problem in rural areas of tropical countries worldwide , including Costa Rica , where most bites are caused by the pit-viper Bothrops asper .", "The treatment of these potentially fatal accidents is based on the timely administration of specific antivenom .", "In man...	[ "Snakebite accidents are a neglected cause of much death and suffering worldwide .", "The situation is especially severe in rural areas of low income tropical countries , where long distances to well-equipped health care facilities mean that the time needed to reach antivenom treatment is often long .", "Delays...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "genomics", "evolutionary biology", "population biology", "genetics and genomics" ]	Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies	journal.pgen.1002641	null	[ [ "The term ‘Pygmy’ is applied to human populations whose adult males exhibit an average height of ∼150 cm or less , although thresholds between 140 and 160 cm have been employed [1] .", "Such groups are found all over the world including Africa , Asia , and the Americas , tend to live in tropical environme...	[ "African Pygmy groups show a distinctive pattern of phenotypic variation , including short stature , which is thought to reflect past adaptation to a tropical environment .", "Here , we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricul...	[ "Africa is thought to be the location of origin of modern humans within the past 200 , 000 years and the source of our dispersion across the globe within the past 100 , 000 years .", "Africa is also a region of extreme environmental , cultural , linguistic , and phenotypic diversity , and human populations living...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders/alzheimer disease", "biochemistry", "infectious diseases/prion diseases", "cell biology/membranes and sorting", "neurological disorders/prion diseases" ]	Glypican-1 Mediates Both Prion Protein Lipid Raft Association and Disease Isoform Formation	journal.ppat.1000666	null	[ [ "Creutzfeldt-Jakob ( CJD ) disease of humans , bovine spongiform encephalopathy of cattle and scrapie of sheep are all examples of prion diseases .", "These diseases propagate through the misfolding of the normal cellular form of the prion protein ( PrPC ) into the disease-associated isoform ( PrPSc ) [1]...	[ "In prion diseases , the cellular form of the prion protein , PrPC , undergoes a conformational conversion to the infectious isoform , PrPSc .", "PrPC associates with lipid rafts through its glycosyl-phosphatidylinositol ( GPI ) anchor and a region in its N-terminal domain which also binds to heparan sulfate prot...	[ "The prion diseases are unique in that their infectious nature is not dependent on nucleic acid but is instead attributed to a misfolded protein , the prion protein .", "This misfolded prion protein is capable of inducing the misfolding of the normal form of the prion protein that is present on the surface of neu...	2009
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "children", "medicine and health sciences", "pathology and laboratory medicine", "maternal health", "obstetrics and gynecology", "cardiovascular anatomy", "nervous system", "pathogens", "geographical locations", "microbiology", "viruses", "ventricular septal defects", "age groups", "develo...	Cardiac findings in infants with in utero exposure to Zika virus- a cross sectional study	journal.pntd.0006362	null	[ [ "Zika virus ( ZIKV ) is an arbovirus of the Flavivirus genus like Dengue virus ( DENV ) and Yellow Fever virus ( YFV ) [1] .", "In response to the search for the causative agent of a “dengue-like” exanthematous disease in 2015 , ZIKV was identified for the first time in Brazil by reverse transcriptase pol...	[ "Antenatal exposure to Zika virus ( ZIKV ) is related to severe neurological manifestations .", "A previous study in Brazil reported an increased incidence of non-severe congenital heart defects in infants with diagnosis of congenital Zika syndrome but without laboratory confirmation of ZIKV infection in the moth...	[ "We performed cardiologic assessment of 120 infants born between November 2015 and January 2017 with confirmed vertical exposure to Zika virus ( ZIKV ) .", "The diagnosis of ZIKV exposure was confirmed by PCR in maternal blood specimens and/or amniotic fluid during pregnancy and/or infant specimens including PCR ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbial metabolism", "microbial physiology", "microbial pathogens", "biology", "microbiology", "host-pathogen interaction", "pathogenesis" ]	Glucose Phosphorylation Is Required for Mycobacterium tuberculosis Persistence in Mice	journal.ppat.1003116	null	[ [ "Mycobacterium tuberculosis ( Mtb ) is the causative agent of tuberculosis , a disease that killed 1 . 5 million people in 2010 worldwide [1] .", "The development of new and effective antimycobacterial drugs hinges on our ability to understand how Mtb establishes and maintains chronic infections .", "...	[ "Mycobacterium tuberculosis ( Mtb ) is thought to preferentially rely on fatty acid metabolism to both establish and maintain chronic infections .", "Its metabolic network , however , allows efficient co-catabolism of multiple carbon substrates .", "To gain insight into the importance of carbohydrate substrates...	[ "The development of new drugs targeting Mycobacterium tuberculosis ( Mtb ) will benefit from a better understanding of the mechanisms by which this pathogen establishes and maintains chronic infections .", "Mtb has to adapt its metabolic needs to the nutritional environment in the host .", "We investigated the ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Dual Model for Prioritizing Cancer Mutations in the Non-coding Genome Based on Germline and Somatic Events	journal.pcbi.1004583	null	[ [ "Since the onset of cancer genomics , the search for cancer genes and cancer-causing mutations has largely focused on protein-coding genes and , more specifically , their coding exons , where the damaging effect of mutations is best understood .", "Among 572 human genes considered as cancer drivers [1 , 2...	[ "We address here the issue of prioritizing non-coding mutations in the tumoral genome .", "To this aim , we created two independent computational models .", "The first ( germline ) model estimates purifying selection based on population SNP data .", "The second ( somatic ) model estimates tumor mutation densi...	[ "Cancer cells undergo a mutation/selection process that resembles that of any living cell .", "Most mutations in cancer cell DNA occur in the so-called \"non-coding\" regions that represent 98 . 5% of the genome length .", "Pinning down which of these mutations contribute to the fitness of cancer cells would be...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/neurodevelopment", "biophysics/theory and simulation", "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Shunting Inhibition Controls the Gain Modulation Mediated by Asynchronous Neurotransmitter Release in Early Development	journal.pcbi.1000973	null	[ [ "Gain control of synapses regulates the flow of information through neural circuits [1] .", "The neurophysiological mechanisms that modulate neuronal transfer functions have been the focus of several studies [2]–[6] .", "In particular , background noise and shunting inhibition have a divisive effect o...	[ "The sensitivity of a neuron to its input can be modulated in several ways .", "Changes in the slope of the neuronal input-output curve depend on factors such as shunting inhibition , background noise , frequency-dependent synaptic excitation , and balanced excitation and inhibition .", "However , in early deve...	[ "Computation in a single neuron is regulated by gain control – the change in the sensitivity of a neuron to different patterns of stimulation .", "Hence , it is important to understand the different mechanisms underlying gain modulation .", "Earlier work focused on gain modulation in mature networks with functi...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/computational neuroscience" ]	Divisive Gain Modulation with Dynamic Stimuli in Integrate-and-Fire Neurons	journal.pcbi.1000365	null	[ [ "Gain modulation ( or gain control ) is an adjustment of the input-output response of neurons , and is widely observed during neural processing [1] .", "Gaze direction sets the response gain in primary visual [2] , posterior parietal cortex [3] , and auditory brainstem [4] .", "In specific species , g...	[ "The modulation of the sensitivity , or gain , of neural responses to input is an important component of neural computation .", "It has been shown that divisive gain modulation of neural responses can result from a stochastic shunting from balanced ( mixed excitation and inhibition ) background activity .", "Th...	[ "Many neural computations , including sensory and motor processing , require neurons to control their sensitivity ( often termed ‘gain’ ) to stimuli .", "One common form of gain manipulation is divisive gain control , where the neural response to a specific stimulus is simply scaled by a constant .", "Most prev...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "veterinary diseases", "veterinary parasitology", "zoonotic diseases", "immunology", "biology", "veterinary science", "immunoglobulins" ]	High-Throughput Analysis of Synthetic Peptides for the Immunodiagnosis of Canine Visceral Leishmaniasis	journal.pntd.0001310	null	[ [ "Leishmaniasis , which is one of the major parasitic diseases recognized by the World Health Organization , affects approximately 1–2 million individuals annually .", "Dogs are considered the main domestic reservoir of Leishmania infantum ( also known as L . chagasi ) [1] , which is the causative agent of...	[ "Visceral leishmaniasis is the most severe form of leishmaniasis .", "Approximately 20% of zoonotic human visceral leishmaniasis worldwide is caused by Leishmania infantum , which is also known as Leishmania chagasi in Latin America , and disease incidence is increasing in urban and peri-urban areas of the tropic...	[ "Globally , the number of new human cases of visceral leishmaniasis ( VL ) is estimated to be approximately 500 , 000 per year .", "This is the most severe of all forms of leishmaniasis , and the zoonotic form of VL , caused by Leishmania infantum ( also known as Leishmania chagasi ) , represents 20% of human vis...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biogeography", "organismal evolution", "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "pathogens", "population genetics", "geographical locations", "microbiology", "vertebrates", "animals", "mammals", "viruses", "rna viruses", ...	The Global Phylogeography of Lyssaviruses - Challenging the 'Out of Africa' Hypothesis	journal.pntd.0005266	null	[ [ "Determining the evolutionary history of viruses is fundamental to our understanding of the patterns and processes occurring during viral emergence and spread .", "Emergence and spread of viral diseases is a permanent threat in animal and public health and special attention has been given to fast-evolving...	[ "Rabies virus kills tens of thousands of people globally each year , especially in resource-limited countries .", "Yet , there are genetically- and antigenically-related lyssaviruses , all capable of causing the disease rabies , circulating globally among bats without causing conspicuous disease outbreaks .", "...	[ "Rabies virus kills tens of thousands of people globally each year and causes indescribable misery and family disturbance , especially in developing countries .", "Yet in much of the world there are related viruses , called lyssaviruses , which circulate among bats without causing conspicuous outbreaks .", "The...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "influenza", "amides", "organic compounds", "aromatic hydrocarbons", "rhinovirus infection", "infectious disease control", "infectious diseases", "enterovirus infection", "membranes and sorting", "chemistry", "biology", "organic chemistry", "cell biology", "common cold", "v...	Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects	journal.ppat.1002976	null	[ [ "The discovery of antibiotics against microbes in the early 20th century has had a major impact on society and saved countless lives [1] .", "Yet , broad range inhibitors against viral pathogens are presently not available .", "Classical antiviral strategies have targeted viral structural or enzymatic...	[ "Viruses use a limited set of host pathways for infection .", "These pathways represent bona fide antiviral targets with low likelihood of viral resistance .", "We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes .", "Niclosamide is approved for human us...	[ "Current antiviral approaches are directed against specific viral targets but are limited in their broad-spectrum potential .", "Targeting host pathways , on the other hand can have broad antiviral effects , albeit with possible side effects .", "Here , we report the mode of antiviral action of a small chemical...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "biology and life sciences", "computational biology" ]	SANTA: Quantifying the Functional Content of Molecular Networks	journal.pcbi.1003808	null	[ [ "The roadmap for functional analysis of networks provided by Costanzo et al . [7] relies on assessing the clustering of selected nodes on the network .", "However , their analysis was done by eye and depends not only on the gene set and the network but also on the visualisation algorithm used .", "Clu...	[ "Linking networks of molecular interactions to cellular functions and phenotypes is a key goal in systems biology .", "Here , we adapt concepts of spatial statistics to assess the functional content of molecular networks .", "Based on the guilt-by-association principle , our approach ( called SANTA ) quantifies...	[ "Molecular networks are maps of the tens of thousands of interactions that occur between the components of biological systems .", "Types of interactions include physical , genetic and functional interactions between genes , gene products and metabolites .", "Network-based approaches to molecular biology are inc...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "textbooks", "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "ecology and environmental sciences", "surface water", "body fluids", "education", "helminths", "sociology", "tropical diseases", "social sciences", "parasitic diseases", "animals", "hea...	Is there a gap between health education content and practice toward schistosomiasis prevention among schoolchildren along the shores of Lake Victoria in Kenya?	journal.pntd.0007572	null	[ [ "Schistosomiasis is a parasitic disease caused by Schistosoma species .", "The parasite infects humans through skin penetration during contact with water that is contaminated with schistosome cercariae .", "Schistosomiasis is listed as a neglected tropical disease ( NTD ) by the World Health Organizat...	[ "Despite provision of preventive measures against schistosomiasis such as mass drug administration ( MDA ) , the prevalence of Schistosoma mansoni remains high in communities living near Lake Victoria .", "This study aimed to analyse the status of schistosomiasis , including its prevalence , health education , kn...	[ "According to WHO , it is estimated that at least 206 million people required preventive treatment for schistosomiasis in 2016 and of those at least 90% live in Africa .", "Moreover , school-age children are most affected by this worm .", "In Kenya , despite preventive measures against schistosomiasis such as m...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genetic Regulation of Caenorhabditis elegans Lysosome Related Organelle Function	journal.pgen.1003908	null	[ [ "Lysosomes are ubiquitous , dynamic , membrane-bound organelles that serve a major degradative role within cells .", "Lysosomes receive material through the endocytic pathway and are its terminal compartment [1]–[3] .", "Lysosomes also receive material via the secretory pathway and directly from the c...	[ "Lysosomes are membrane-bound organelles that contain acid hydrolases that degrade cellular proteins , lipids , nucleic acids , and oligosaccharides , and are important for cellular maintenance and protection against age-related decline .", "Lysosome related organelles ( LROs ) are specialized lysosomes found in ...	[ "Lysosome related organelles ( LROs ) are specialized , membrane-bound organelles that share many common features of canonical lysosomes .", "Mutations in critical components of LRO biogenesis lead to human diseases of immunity , blood clotting , and pigmentation .", "In Caenorhabditis elegans , LROs are the si...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "enzyme-linked immunoassays", "immunology", "tropical diseases", "sand flies", "parasitic diseases", "saliva", "neglected tropical diseases", "immunologic techniques", "insect vectors", "antibody response", "digestive system", "research and an...	Human cellular and humoral immune responses to Phlebotomus papatasi salivary gland antigens in endemic areas differing in prevalence of Leishmania major infection	journal.pntd.0005905	null	[ [ "Leishmaniasis caused by protozoan parasites of the genus Leishmania transmitted by phlebotomine sand fly vectors has one of the largest diseases burden among the neglected tropical diseases [1 , 2] .", "These infections cause a broad clinical spectrum including cutaneous , mucocutaneous or visceral forms...	[ "Sand fly saliva compounds are able to elicit specific immune responses that have a significant role in Leishmania parasite establishment and disease outcome .", "Characterizing anti-saliva immune responses in individuals living in well defined leishmaniasis endemic areas would provide valuable insights regarding...	[ "During murine experimental leishmaniasis sand fly saliva components modulate the host immune response and facilitate infection while pre-exposition to uninfected sand fly bites is associated with a protective cellular response against subsequent infection .", "Human anti-saliva immune responses are not well defi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	DNA Polymerase ζ-Dependent Lesion Bypass in Saccharomyces cerevisiae Is Accompanied by Error-Prone Copying of Long Stretches of Adjacent DNA	journal.pgen.1005110	null	[ [ "Genomic stability is continuously threatened by endogenous and exogenous DNA-damaging factors .", "Unrepaired lesions stall the replication machinery , because the highly selective active sites of replicative DNA polymerases cannot accept abnormally shaped nucleotides [1 , 2] .", "The bypass of repli...	[ "Translesion synthesis ( TLS ) helps cells to accomplish chromosomal replication in the presence of unrepaired DNA lesions .", "In eukaryotes , the bypass of most lesions involves a nucleotide insertion opposite the lesion by either a replicative or a specialized DNA polymerase , followed by extension of the resu...	[ "Genomic instability is associated with multiple genetic diseases .", "Endogenous and exogenous DNA-damaging factors constitute a major source of genomic instability .", "Mutations occur when DNA lesions are bypassed by specialized translesion synthesis ( TLS ) DNA polymerases that are less accurate than the no...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "physical sciences" ]	Epistatic Adaptive Evolution of Human Color Vision	journal.pgen.1004884	null	[ [ "The chance of survival of novel mutations is affected strongly by the molecular background in which they appear [1]–[3] .", "To understand the evolutionary dynamics of these mutations , it is necessary to characterize the phenotypic variation they generate .", "For vertebrates , however , understandi...	[ "Establishing genotype-phenotype relationship is the key to understand the molecular mechanism of phenotypic adaptation .", "This initial step may be untangled by analyzing appropriate ancestral molecules , but it is a daunting task to recapitulate the evolution of non-additive ( epistatic ) interactions of amino...	[ "Mapping the genotype-phenotype relationship is necessary to understand how variable phenotypes have evolved in nature .", "The blue-sensitive visual pigment in human ( human S1 ) evolved from the UV-sensitive pigment in the Boreoeutherian ( or Boreotherian ) ancestor ( AncBoreotheria S1 ) by seven mutations .", ...	2014
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "biology", "microbiology" ]	The Single-Nucleotide Resolution Transcriptome of Pseudomonas aeruginosa Grown in Body Temperature	journal.ppat.1002945	null	[ [ "The outcomes of the broad spectrum of diseases caused by the opportunistic pathogen Pseudomonas aeruginosa are determined by several factors related to the predisposing conditions of the infected individual [1] , the mechanism of entry [2] and consequences of interaction with the innate defense mechanisms [3...	[ "One of the hallmarks of opportunistic pathogens is their ability to adjust and respond to a wide range of environmental and host-associated conditions .", "The human pathogen Pseudomonas aeruginosa has an ability to thrive in a variety of hosts and cause a range of acute and chronic infections in individuals wit...	[ "Identifying coordinately regulated genes and their control by environmentally-initiated signal transduction pathways is important for understanding bacterial virulence mechanisms .", "The work reported here provides a comprehensive , high resolution , transcriptome map of the opportunistic pathogen Pseudomonas a...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "plant science", "genomics", "genome evolution", "plant evolution", "genetics", "biology and life sciences", "comparative genomics", "computational biology", "evolutionary biology" ]	Recurrent Loss of Specific Introns during Angiosperm Evolution	journal.pgen.1004843	null	[ [ "Spliceosomal introns ( called introns hereafter ) are noncoding DNA segments within eukaryotic genes that are removed after transcription .", "Although the presence of introns is one of the universal features of eukaryotes , and a large number of intron positions are highly conserved in orthologous genes...	[ "Numerous instances of presence/absence variations for introns have been documented in eukaryotes , and some cases of recurrent loss of the same intron have been suggested .", "However , there has been no comprehensive or phylogenetically deep analysis of recurrent intron loss .", "Of 883 cases of intron presen...	[ "The spliceosomal introns are nucleotide sequences that interrupt coding regions of eukaryotic genes and are removed by RNA splicing after transcription .", "Recent studies have reported several examples of possible recurrent intron loss or gain , i . e . , introns that are independently removed from or inserted ...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "bacteriology", "biofilms", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "chemical compounds", "cellulose", "pathogens", "immunology", "microbiology", "organic compounds", "autoantibodies", "bacterial diseases", ...	Bacterial amyloid curli acts as a carrier for DNA to elicit an autoimmune response via TLR2 and TLR9	journal.ppat.1006315	null	[ [ "Amyloid proteins , such as human amyloid beta and serum amyloid A , self-assemble into a cross-beta sheet quaternary structure , in which the individual strands of the beta sheets are oriented perpendicularly to the fiber axis [1 , 2] .", "Like humans , bacteria also produce amyloids .", "It is estim...	[ "Bacterial biofilms are associated with numerous human infections .", "The predominant protein expressed in enteric biofilms is the amyloid curli , which forms highly immunogenic complexes with DNA .", "Infection with curli-expressing bacteria or systemic exposure to purified curli-DNA complexes triggers autoim...	[ "Bacterial amyloids are conserved proteins expressed by many bacteria in biofilms .", "Bacterial amyloid curli and DNA form highly immunogenic complexes that stimulate autoimmunity and accelerate the progression of systemic lupus erythematosus .", "Here , we show that the innate immune receptors TLR2 and TLR9 a...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/environmental microbiology", "infectious diseases/neglected tropical diseases", "ecology/environmental microbiology", "infectious diseases/bacterial infections", "microbiology/applied microbiology", "infectious diseases/tropical and travel-associated diseases", "microbiology/medical microb...	Coxiella burnetii in Humans and Ticks in Rural Senegal	journal.pntd.0000654	null	[ [ "Q fever is a worldwide zoonotic disease caused by Coxiella burnetii [1] .", "The disease can be acute or chronic and exhibits a wide spectrum of clinical manifestations .", "The reported prevalence of Q fever is continuously increasing due to both true prevalence and improved quality of diagnostic to...	[ "Q fever is a worldwide zoonotic disease caused by Coxiella burnetii .", "Epidemiologically , animals are considered reservoirs and humans incidental hosts .", "We investigated Q fever in rural Senegal .", "Human samples ( e . g . , sera , saliva , breast milk , feces ) were screened in the generally healthy ...	[ "Q fever is a zoonotic disease known since 1937 .", "The disease may be severe , causing pneumonia , hepatitis and endocarditis .", "Q fever agent has been described as a possible biological weapon .", "Animals—especially domestic cows , goats and sheep—are considered reservoirs for this infection .", "They...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "ecology and environmental sciences", "medicine and health sciences", "rna interference", "pathology and laboratory medicine", "plant science", "rice", "genetically modified plants", "experimental organism systems", "plant pathology", "epigenetics", "glycosylation", "plants"...	A novel Meloidogyne graminicola effector, MgGPP, is secreted into host cells and undergoes glycosylation in concert with proteolysis to suppress plant defenses and promote parasitism	journal.ppat.1006301	null	[ [ "Root-knot nematodes ( RKNs ) are one of the most economically important plant-parasitic nematodes ( PPNs ) , infecting more than 5500 plant species [1 , 2] .", "The soil-borne RKNs devastate varieties of crop plants , resulting in about $70 billion losses in worldwide agriculture annually [3] .", "Ge...	[ "Plant pathogen effectors can recruit the host post-translational machinery to mediate their post-translational modification ( PTM ) and regulate their activity to facilitate parasitism , but few studies have focused on this phenomenon in the field of plant-parasitic nematodes .", "In this study , we show that th...	[ "Post-translational modification ( PTM ) is a tool used by prokaryotic and eukaryotic cells to regulate protein activity , and many unique and important functions of proteins depend on appropriate PTMs .", "Evidence is emerging that plant pathogen effectors can utilize the host post-translational machinery to med...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "virology/virus evolution and symbiosis", "evolutionary biology/genomics", "infectious diseases/viral infections", "evolutionary biology" ]	Mosquitoes Put the Brake on Arbovirus Evolution: Experimental Evolution Reveals Slower Mutation Accumulation in Mosquito Than Vertebrate Cells	journal.ppat.1000467	null	[ [ "Arthropod-borne RNA viruses ( arboviruses ) pose an especially high risk of emergence from reservoir hosts into humans [1] , [2] , due to the genetic plasticity of the viral RNA genome coupled with the dispersal potential of arthropod vectors and some amplification hosts .", "Paradoxically , vector-borne...	[ "Like other arthropod-borne viruses ( arboviruses ) , mosquito-borne dengue virus ( DENV ) is maintained in an alternating cycle of replication in arthropod and vertebrate hosts .", "The trade-off hypothesis suggests that this alternation constrains DENV evolution because a fitness increase in one host usually di...	[ "Dengue virus ( DENV ) is an arthropod-borne virus of immense public health concern .", "Recent studies suggest that the rate of DENV evolution has accelerated , as well as the disease severity ( virulence ) , most likely driven by the increased transmission and selection by the vector , Aedes aegypti , over the ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "sequencing techniques", "plant anatomy", "gene regulation", "regulatory proteins", "dna-binding proteins", "plant science", "genetically modified plants", "transcription factors", "sequence motif analysis", "molecular biology techniques", "plants", "flowering plants", "ge...	MicroProtein-Mediated Recruitment of CONSTANS into a TOPLESS Trimeric Complex Represses Flowering in Arabidopsis	journal.pgen.1005959	null	[ [ "The formation of higher order protein complexes greatly expands the matrix of physiological responses and is crucial for the adjustment of developmental processes in regard to environmental changes .", "MicroProteins are important modulators , because they are able to prevent larger , multi-domain protei...	[ "MicroProteins are short , single domain proteins that act by sequestering larger , multi-domain proteins into non-functional complexes .", "MicroProteins have been identified in plants and animals , where they are mostly involved in the regulation of developmental processes .", "Here we show that two Arabidops...	[ "MicroProteins are short single-domain proteins that possess the ability to interfere with larger multi-domain proteins .", "These protein species can be identified in plants and animals where they evolved from large proteins by successive domain-loss .", "MicroProteins often act as decoys thus interaction with...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "epilepsy", "medicine and health sciences", "physiology", "neurology", "biology and life sciences", "electrophysiology", "neuroscience" ]	Action Potential Initiation in Neocortical Inhibitory Interneurons	journal.pbio.1001944	Sodium channels add variety to inhibitory interneurons Different populations of inhibitory interneurons in the cerebral cortex express distinct subtypes of sodium channels, resulting in diverse action potential thresholds and network excitability.	[ [ "In general , synaptic inputs that arrive at the dendrites and the cell body of a neuron interact with intrinsic membrane properties and cause the generation of the main output signal , the action potential ( AP ) , at the axon initial segment ( AIS ) [1]–[5] .", "Previous modeling , immunostaining , and ...	[ "Action potential ( AP ) generation in inhibitory interneurons is critical for cortical excitation-inhibition balance and information processing .", "However , it remains unclear what determines AP initiation in different interneurons .", "We focused on two predominant interneuron types in neocortex: parvalbumi...	[ "Inhibitory interneurons in the cerebral cortex are diverse in many respects .", "Here , we examine whether this diversity extends to the composition of ion channels along the axon , which might determine the neurons' excitability .", "We performed patch-clamp recordings from cortical interneuron axons in brain...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell death", "medicine and health sciences", "immune cells", "yeast infections", "pathology and laboratory medicine", "intracellular pathogens", "gene regulation", "pathogens", "regulatory proteins", "immunology", "cell processes", "microbiology", "dna-binding proteins", ...	The transcription factor CHOP, an effector of the integrated stress response, is required for host sensitivity to the fungal intracellular pathogen Histoplasma capsulatum	journal.ppat.1006589	null	[ [ "Death of the host cell has profound consequences for an intracellular pathogen .", "It may eliminate the pathogen’s replicative niche , or it may promote pathogen spread .", "The specific form of cell death can impact immune activation of the host: pyroptosis and necroptosis are highly inflammatory t...	[ "The ability of intracellular pathogens to manipulate host-cell viability is critical to successful infection .", "Some pathogens promote host-cell survival to protect their replicative niche , whereas others trigger host-cell death to facilitate release and dissemination of the pathogen after intracellular repli...	[ "Histoplasma capsulatum is the causative agent of histoplasmosis , a fungal infection that can be fatal in a wide range of mammalian hosts , including otherwise healthy , immunocompetent individuals .", "Histoplasma cells replicate to very high levels within host macrophages , eventually causing macrophage death ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "vesicles", "crystal structure", "chemical compounds", "built structures", "engineering and technology", "condensed matter physics", "electrophysiology", "neuroscience", "organic compounds", "membrane proteins", "ion channels", "membrane structures", "amino ...	Dissecting the Molecular Mechanism of Nucleotide-Dependent Activation of the KtrAB K+ Transporter	journal.pbio.1002356	This study reveals how structural changes triggered by the exchange of bound ADP for ATP activate KtrAB, a potassium ion transporter involved in osmotic adaption in bacteria.	[ [ "KtrAB belongs to the Trk/Ktr/HKT superfamily of monovalent cation ( K+ and Na+ ) transport proteins that are found ubiquitously in nonanimal cells [1–3] .", "The Trk/Ktr/HKT superfamily comprises uniporters ( K+ or Na+ ) and symporters ( K+/Na+ or K+/H+ ) and underlies a plethora of cellular functions in...	[ "KtrAB belongs to the Trk/Ktr/HKT superfamily of monovalent cation ( K+ and Na+ ) transport proteins that closely resemble K+ channels .", "These proteins underlie a plethora of cellular functions that are crucial for environmental adaptation in plants , fungi , archaea , and bacteria .", "The activation mechan...	[ "Animals have organs that regulate the balance of water and ions in the fluids bathing their cells .", "In contrast , the cells of plants , bacteria , and fungi have little or no control over those fluids and , thus , they have to cope with changes in the local environment .", "These cells have therefore evolve...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "taxonomy", "horizontal gene transfer", "organismal evolution", "microbiology", "gene transfer", "optimization", "phylogenetics", "data management", "mathematics", "phylogenetic analysis", "network analysis", "microbial evolution", "computer and information sciences", "evolutionary systema...	Rearrangement moves on rooted phylogenetic networks	journal.pcbi.1005611	null	[ [ "A recent trend in evolutionary biology is the growing appreciation of reticulate evolution—which occurs when the history of a set of taxa ( e . g . , species , populations or genes ) cannot be accurately represented as a phylogenetic tree [1 , 2] , because of events causing inheritance from more than one anc...	[ "Phylogenetic tree reconstruction is usually done by local search heuristics that explore the space of the possible tree topologies via simple rearrangements of their structure .", "Tree rearrangement heuristics have been used in combination with practically all optimization criteria in use , from maximum likelih...	[ "Phylogenetic networks are used to represent reticulate evolution , that is , cases in which the tree-of-life metaphor for evolution breaks down , because some of its branches have merged at one or several points in the past .", "This may occur , for example , when some organisms in the phylogeny are hybrids .", ...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Epidemiology and Molecular Characterization of Cryptosporidium spp. in Humans, Wild Primates, and Domesticated Animals in the Greater Gombe Ecosystem, Tanzania	journal.pntd.0003529	null	[ [ "Cryptosporidium is one of the most important parasitic diarrheal agents in humans in the world , is among the top four causes of moderate-to-severe diarrheal disease in young children in developing nations , and is problematic as an opportunistic co-infection with HIV due to increased morbidity and mortality...	[ "Cryptosporidium is an important zoonotic parasite globally .", "Few studies have examined the ecology and epidemiology of this pathogen in rural tropical systems characterized by high rates of overlap among humans , domesticated animals , and wildlife .", "We investigated risk factors for Cryptosporidium infec...	[ "Cryptosporidium is a common zoonotic gastrointestinal parasite .", "In a cross-sectional survey of humans , non-human primates ( chimpanzees and baboons ) and livestock in the Greater Gombe Ecosystem , Tanzania , Cryptosporidium infection rate was 4 . 3% , 16 . 0% and 9 . 6% respectively .", "Infection was not...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "fish", "cell cycle and cell division", "cell processes", "ocular anatomy", "vertebrates", "geometry", "animals", "aspect ratio", "animal models", "osteichthyes", "developmental biology", "model organisms", "mathematics", "experimental organism systems", ...	A non-cell-autonomous actin redistribution enables isotropic retinal growth	journal.pbio.2006018	null	[ [ "Acquiring the correct size and shape during development is a crucial prerequisite for tissue and organ function .", "In diverse tissues , such as the Drosophila salivary gland [1] or the vertebrate retina [2] , shape characteristics are established early in development and need to be retained throughout ...	[ "Tissue shape is often established early in development and needs to be scaled isotropically during growth .", "However , the cellular contributors and ways by which cells interact tissue-wide to enable coordinated isotropic tissue scaling are not yet understood .", "Here , we follow cell and tissue shape chang...	[ "As the shape of a tissue or organ is usually important for its function , it is critical to understand both how tissues form with the correct size and how their shape is maintained during development .", "However , so far , most studies have focused on how the shape of tissues changes during morphogenesis , whil...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "flow cytometry", "phosphorylation", "medicine and health sciences", "immune cells", "immunology", "animal models", "model organisms", "stem cells", "experimental organism systems", "research and analysis methods", "immune system proteins", "contractile proteins", "actins", ...	The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development	journal.pbio.2005380	null	[ [ "One requirement for T-cell–mediated immune surveillance is the permanent reshaping of the cell body .", "Here , a functional remodeling of the actin cytoskeleton is important for changes of the cell shape during migration or immune synapse ( IS ) formation with antigen presenting cells ( APCs ) or target...	[ "Cofilin is an essential actin remodeling protein promoting depolymerization and severing of actin filaments .", "To address the relevance of cofilin for the development and function of T cells in vivo , we generated knock-in mice in which T-cell–specific nonfunctional ( nf ) cofilin was expressed instead of wild...	[ "T cells are produced in the thymus and are critical to fighting infections and combating cancer .", "To move through the body and to fulfill their specific functions , T cells need to dynamically reshape their cell body .", "This requires remodeling the actin cytoskeleton using a plethora of actin-binding prot...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "immune cells", "enzyme-linked immunoassays", "pathogens", "animal models of disease", "immunology", "tropic...	Dysregulated TGF-β Production Underlies the Age-Related Vulnerability to Chikungunya Virus	journal.ppat.1005891	null	[ [ "Chikungunya virus ( CHIKV ) is a re-emerging mosquito-borne alphavirus endemic to West Africa , with outbreaks in many Asian and African countries [1] , that causes a febrile illness characterized by rash and arthralgia that is often debilitating [2 , 3] .", "The distinctive severity of the joint pain ca...	[ "Chikungunya virus ( CHIKV ) is a re-emerging global pathogen with pandemic potential , which causes fever , rash and debilitating arthralgia .", "Older adults over 65 years are particularly susceptible to severe and chronic CHIKV disease ( CHIKVD ) , accounting for >90% of all CHIKV-related deaths .", "There a...	[ "Chikungunya virus ( CHIKV ) causes an acute febrile syndrome and severe acute and chronic joint disease that , for unknown reasons , especially affects older adults .", "CHIKV has recently reached the Americas and is threatening the Southeastern USA .", "At the present there is no approved vaccine or antiviral...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood serum", "genome-wide association studies", "medicine and health sciences", "body fluids", "ulcerative colitis", "colitis", "physiological processes", "developmental biology", "organism development", "gastroenterology and hepatology", "genome analysis", "inflammatory bowel disease", "p...	High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors	journal.pgen.1006565	null	[ [ "The study of molecular mechanisms is of great importance for understanding the etiology of disease .", "Genome wide association studies ( GWAS ) help to identify genetic loci that are likely to contain causal variants for human diseases .", "Investigation of molecular phenotypes and how they relate t...	[ "To date , no large scale , systematic description of the blood serum proteome has been performed in inflammatory bowel disease ( IBD ) patients .", "By using microarray technology , a more complete description of the blood proteome of IBD patients is feasible .", "It may help to achieve a better understanding ...	[ "GWAS have resulted in greater than one hundred susceptibility loci for inflammatory bowel disease ( Crohn’s Disease and Ulcerative Colitis ) .", "However , the molecular etiology of these diseases is not completely understood .", "In this study we profiled serum protein levels in IBD and control subjects and d...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell physiology", "medicine and health sciences", "breast tumors", "metabolic networks", "cancers and neoplasms", "cell metabolism", "neuroscience", "oncology", "metabolites", "artificial intelligence", "network analysis", "computer and information sciences", "metabolic pathways", "gene e...	Data-Driven Metabolic Pathway Compositions Enhance Cancer Survival Prediction	journal.pcbi.1005125	null	[ [ "In recent years the study of cancer metabolism gained renewed interest as means to understand cancer’s emergence , pathophysiology , and for finding candidate targets for therapeutics [1–6] .", "Metabolism is universally conceptualized through the abstraction of pathways , which are groups of enzymatic r...	[ "Altered cellular metabolism is an important characteristic and driver of cancer .", "Surprisingly , however , we find here that aggregating individual gene expression using canonical metabolic pathways fails to enhance the classification of noncancerous vs . cancerous tissues and the prediction of cancer patient...	[ "Cancer proliferating cells adapt their metabolism to support the conversion of available nutrients into biomass , which often involves an increased rate of specific metabolic pathways , such as glycolysis .", "Surprisingly , however , we observe that aggregating individual gene expression using canonical human m...	2016
[ "Introduction", "Results", "Discussions", "Methods" ]	[]	A Virtual Mixture Approach to the Study of Multistate Equilibrium: Application to Constant pH Simulation in Explicit Water	journal.pcbi.1004480	null	[ [ "Chemical and thermodynamic equilibrium of multiple states is a fundamental phenomenon in biological systems .", "Typical examples of multiple state equilibria are protonation equilibrium , ligand binding equilibrium , and phosphorylation equilibrium .", "For example , through the equilibrium of diffe...	[ "Chemical and thermodynamic equilibrium of multiple states is a fundamental phenomenon in biology systems and has been the focus of many experimental and computational studies .", "This work presents a simulation method to directly study the equilibrium of multiple states .", "This method constructs a virtual m...	[ "Computer simulation plays an important role to understand molecular systems and has been applied to problems of increasing complexity .", "Multistate equilibrium is a fundamental concept behind the structure and function of biological systems .", "Due to the limit in computing resources and lack of good altern...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biophysics/transcription and translation", "genetics and genomics/gene expression", "computational biology/transcriptional regulation" ]	Combinatorial Gene Regulation Using Auto-Regulation	journal.pcbi.1000813	null	[ [ "Many transcription factors ( TFs ) in Escherichia coli regulate the transcription rate of their own gene .", "In fact , 59% of the TFs are known to auto-regulate and the list is growing [1] , [2] .", "Negative auto-regulation ( auto-repression ) occurs more frequently than positive auto-regulation ( ...	[ "As many as 59% of the transcription factors in Escherichia coli regulate the transcription rate of their own genes .", "This suggests that auto-regulation has one or more important functions .", "Here , one possible function is studied .", "Often the transcription rate of an auto-regulator is also controlled...	[ "Bacteria adjust which proteins they make , and how many copies of each kind , depending on their environment .", "The production rate of each regulated protein is controlled by a special class of proteins called transcription factors .", "The rate at which a certain protein is produced usually depends on the c...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Intracellular Bacterium Wolbachia Uses Parasitoid Wasps as Phoretic Vectors for Efficient Horizontal Transmission	journal.ppat.1004672	null	[ [ "Vertically transmitted intracellular bacteria often live in symbioses with their arthropod hosts [1] .", "These endosymbionts may be obligate ( essential for host survival ) or facultative , in which case they can increase or decrease host fitness [1–3] .", "When endosymbionts are obligate they typic...	[ "Facultative bacterial endosymbionts are associated with many arthropods and are primarily transmitted vertically from mother to offspring .", "However , phylogenetic affiliations suggest that horizontal transmission must also occur .", "Such horizontal transfer can have important biological and agricultural co...	[ "Vertically-transmitted facultative bacterial endosymbionts are common in invertebrates , and affect traits as diverse as the mode of sexual reproduction , speciation , and susceptibility to pathogens .", "Horizontal transmission of endosymbionts is thought to be infrequent in most species , and not to contribute...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virulence factors and mechanisms", "respiratory medicine/respiratory infections", "virology/vaccines", "infectious diseases/viral infections", "infectious diseases/respiratory infections", "respiratory medicine/respiratory pediatrics", "microbiology/medical microbiology", "virology/host inva...	The Synthetic Bacterial Lipopeptide Pam3CSK4 Modulates Respiratory Syncytial Virus Infection Independent of TLR Activation	journal.ppat.1001049	null	[ [ "Human respiratory syncytial virus ( RSV ) is a major cause of respiratory tract disease in infants , immunocompromised subjects and the elderly [1] .", "The virus is a member of the family Paramyxoviridae , which also includes human metapneumovirus ( HMPV ) and measles virus ( MV ) .", "RSV owes its ...	[ "Respiratory syncytial virus ( RSV ) is an important cause of acute respiratory disease in infants , immunocompromised subjects and the elderly .", "However , it is unclear why most primary RSV infections are associated with relatively mild symptoms , whereas some result in severe lower respiratory tract infectio...	[ "Respiratory syncytial virus ( RSV ) infections are an important cause of hospitalization of infants during the winter season .", "However , RSV is often not the only detectable pathogen , but co-infections with respiratory bacteria are common .", "It has been hypothesized that this results from epithelial dama...	2010
[ "Introduction", "Methods", "Results", "Discussion", "Supporting Information" ]	[ "infectious diseases", "homo (human)", "immunology", "microbiology", "mus (mouse)", "molecular biology", "eubacteria" ]	TBK1 Protects Vacuolar Integrity during Intracellular Bacterial Infection	journal.ppat.0030029	null	[ [ "Host organisms employ a multitude of innate defense mechanisms against invading microbial pathogens .", "Functions of the innate immune system include control and destruction of pathogens and instruction of the developing adaptive immune response through expression of cytokines , chemokines , and other p...	[ "TANK-binding kinase-1 ( TBK1 ) is an integral component of Type I interferon induction by microbial infection .", "The importance of TBK1 and Type I interferon in antiviral immunity is well established , but the function of TBK1 in bacterial infection is unclear .", "Upon infection of murine embryonic fibrobla...	[ "Early control of invading microbial pathogens is an essential function of the host response to infection .", "Previous studies have shown that upon viral infection , a protein called TANK-binding kinase-1 ( TBK1 ) signals the induction of a program of protection that results in inhibition of viral replication ."...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "medicine and health sciences", "water resources", "body fluids", "melioidosis", "geographical locations", "ponds", "bacterial diseases", "plant science", "rice", "experimental organism systems", "bodies of water", "plant ecology", "plants", "researc...	Prevalence and genetic diversity of Burkholderia pseudomallei isolates in the environment near a patient’s residence in Northeast Thailand	journal.pntd.0007348	null	[ [ "Melioidosis is a fatal infectious disease caused by the Gram-negative bacterium Burkholderia pseudomallei .", "The disease is endemic to Southeast Asia and Northern Australia; however , it is also increasingly recognised in other tropical areas throughout Africa , America and South Asia [1] .", "Appr...	[ "Burkholderia pseudomallei is the causative agent of melioidosis , a severe infectious disease in tropical regions .", "It is necessary to understand the risk of acquiring this infection from the environment .", "The prevalence , concentration and genetic diversity of B . pseudomallei isolates collected from tw...	[ "Burkholderia pseudomallei , an environmental bacterium , causes melioidosis , a serious but neglected infectious disease that is endemic in many tropical regions .", "Infection routes include inoculation , ingestion and inhalation .", "Several environmental sources serve as niches for persistence , providing a...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "molecular biology", "biology and life sciences", "microbiology" ]	A New Family of Secreted Toxins in Pathogenic Neisseria Species	journal.ppat.1004592	null	[ [ "The growing number of sequenced bacterial genomes has led to the computer-based prediction of numerous novel bacterial factors possibly involved in virulence .", "As a result , many novel putative bacterial toxins have been identified by sequence-homology criteria .", "However , very few of these bac...	[ "The genus Neisseria includes both commensal and pathogenic species which are genetically closely related .", "However , only meningococcus and gonococcus are important human pathogens .", "Very few toxins are known to be secreted by pathogenic Neisseria species .", "Recently , toxins secreted via type V secr...	[ "Many bacteria are able to secrete toxins targeted against neighboring cells .", "In order to protect themselves against their own toxin , they also express an “immunity” protein .", "In silico analysis of bacterial genomes predicts that numerous genes could encode potential new toxin-immunity systems .", "Th...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "genomic library construction", "sequence assembly tools", "genome analysis", "dna construction", "molecular biology techniques", "research and analysis methods", "sequence analysis", "genomic libraries", "sequence alignment", "chromosome biology", "comparative genomic...	Chromosomal-Level Assembly of the Asian Seabass Genome Using Long Sequence Reads and Multi-layered Scaffolding	journal.pgen.1005954	null	[ [ "The Asian seabass ( Lates calcarifer; Bloch , 1790 ) is a highly fecund , robust , tropical species; immensely popular as a food fish in the Asia-Pacific and beyond .", "The species , which is also known as barramundi ( Australia ) , pla kapong ( Thailand ) , ikan siakap ( Malaysia ) , and 75 other local...	[ "We report here the ~670 Mb genome assembly of the Asian seabass ( Lates calcarifer ) , a tropical marine teleost .", "We used long-read sequencing augmented by transcriptomics , optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a co...	[ "We describe the genome assembly of Asian seabass ( Lates calcarifer ) , a marine teleost with aquaculture relevance .", "Though >500 eukaryotic genome sequences are available in public repositories , the majority are highly fragmented with incomplete assemblies , which explains why considerable effort and resour...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "developmental biology", "histology", "model organisms", "physiology", "genetics", "immunology", "biology", "anatomy and physiology", "molecular cell biology", "proteomics", "genetics and genomics" ]	Acute Multiple Organ Failure in Adult Mice Deleted for the Developmental Regulator Wt1	journal.pgen.1002404	null	[ [ "Although much is known about the mechanisms that govern cellular differentiation during development , we know less about the processes that regulate cell turnover and homeostasis in the adult .", "Perhaps the exceptions to this rule are rapidly turning over tissues such as intestine , skin and haematopoi...	[ "There is much interest in the mechanisms that regulate adult tissue homeostasis and their relationship to processes governing foetal development .", "Mice deleted for the Wilms' tumour gene , Wt1 , lack kidneys , gonads , and spleen and die at mid-gestation due to defective coronary vasculature .", "Wt1 is vit...	[ "It is important to understand the cellular and molecular pathways that regulate the maintenance and turnover of adult tissues .", "These processes often go awry in diseases and are likely to deteriorate with ageing .", "Here we show that removal of a single gene , the Wilms' Tumour gene , Wt1 , in the adult mo...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "rivers", "tropical diseases", "geographical locations", "vertebrates", "parasitic diseases", "animals", "mammals", "age groups", "signs and symptoms", "aquatic environments", "bodies...	High prevalence of epilepsy in onchocerciasis endemic regions in the Democratic Republic of the Congo	journal.pntd.0005732	null	[ [ "A high prevalence of epilepsy ( >1% ) has been reported in many onchocerciasis endemic regions .", "In Africa , a special form of epilepsy referred to as “nodding syndrome” has been reported solely in onchocerciasis endemic areas [1] .", "The Democratic Republic of the Congo ( DRC ) is the country wi...	[ "An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas .", "The objective of this study was to determine the prevalence of epilepsy in onchocerciasis endemic areas in the Democratic Republic of the Congo ( DRC ) and investigate whether a higher annual intake of Ivermectin was ...	[ "An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas .", "Between July 2014 and February 2016 , house-to-house epilepsy prevalence surveys were carried out in the Bas-Uele , Tshopo and Ituri province of the Democratic Republic of the Congo , in areas with a high level of onc...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry/molecular evolution", "evolutionary biology/microbial evolution and genomics", "biochemistry/rna structure", "virology/viral replication and gene regulation", "evolutionary biology/genomics", "virology", "biochemistry/structural genomics" ]	A Discontinuous RNA Platform Mediates RNA Virus Replication: Building an Integrated Model for RNA–based Regulation of Viral Processes	journal.ppat.1000323	null	[ [ "Plus-strand RNA viruses infect a wide variety of organisms and are responsible for causing significant diseases in plants , animals , and humans .", "A key step in the reproduction of these pathogens is replication of their single-stranded RNA genomes .", "This process occurs in the cytosol of host c...	[ "Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes .", "The traditional view of these elements is that of local RNA structures .", "This perspective , however , is changing due to increasing discoveries of functional viral RNA elements that a...	[ "Plus-strand ( i . e . messenger-sensed ) RNA viruses are responsible for significant diseases in plants and animals .", "The single-stranded RNA genomes of these viruses serve as templates for translation of viral proteins and perform other essential functions that generally involve local RNA structures , such a...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "bacteriology", "medicine and health sciences", "gut bacteria", "body fluids", "chemical compounds", "pathology and laboratory medicine", "aliphatic amino acids", "pathogens", "bacillus", "microbiology", "bile", "organic compounds", "plasmid construction", "mutation", "prokaryotic models...	The requirement for co-germinants during Clostridium difficile spore germination is influenced by mutations in yabG and cspA	journal.ppat.1007681	null	[ [ "Clostridioides difficile ( formerly Clostridium difficile ) [1–3] is a Gram-positive , spore-forming pathogenic bacterium , and has become a leading cause of nosocomial diarrhea in the United States [4 , 5] .", "C . difficile infection ( CDI ) is commonly the result of disruption to the gut microflora ca...	[ "Clostridium difficile spore germination is critical for the transmission of disease .", "C . difficile spores germinate in response to cholic acid derivatives , such as taurocholate ( TA ) , and amino acids , such as glycine or alanine .", "Although the receptor with which bile acids are recognized ( germinant...	[ "Germination by C . difficile spores is one of the very first steps in the pathogenesis of this organism .", "The transition from the metabolically dormant spore form to the actively-growing , toxin-producing vegetative form is initiated by certain host-derived bile acids and amino acid signals .", "Despite nea...	2019
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[]	Detecting Horizontal Gene Transfer between Closely Related Taxa	journal.pcbi.1004408	null	[ [ "Most microbial genomes have experienced extensive gene mobility between lineages during their evolution , a phenomenon known as horizontal gene transfer ( HGT ) .", "This process has been critical in shaping microbial genome evolution both in terms of functional repertoires and of genome architecture [1 ...	[ "Horizontal gene transfer ( HGT ) , the transfer of genetic material between organisms , is crucial for genetic innovation and the evolution of genome architecture .", "Existing HGT detection algorithms rely on a strong phylogenetic signal distinguishing the transferred sequence from ancestral ( vertically derive...	[ "The transfer of genetic material between organisms , usually denoted as horizontal ( or lateral ) gene transfer ( HGT or LGT ) , is a prime mechanism in microbial evolution and responsible for genetic innovation and the evolution of genome architecture .", "Detecting HGT between closely related species or strain...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cancer detection and diagnosis", "medicine and health sciences", "breast tumors", "cancers and neoplasms", "oncology", "dna damage", "mutation", "dna", "mutation databases", "research and analysis methods", "ovarian cancer", "chromosome biology", "chromosomal aberrations", "breast cancer"...	Targeted Next-Generation Sequencing Identifies a Recurrent Mutation in MCPH1 Associating with Hereditary Breast Cancer Susceptibility	journal.pgen.1005816	null	[ [ "Breast cancer is the most common malignancy among women , and the contribution of hereditary susceptibility to its development has been well recognized .", "Numerous breast cancer susceptibility genes are involved in the DNA damage response , strongly indicating that certain pathways of DNA repair and ch...	[ "Breast cancer is strongly influenced by hereditary risk factors , a majority of which still remain unknown .", "Here , we performed a targeted next-generation sequencing of 796 genes implicated in DNA repair in 189 Finnish breast cancer cases with indication of hereditary disease susceptibility and focused the a...	[ "Although the contribution of hereditary susceptibility to breast cancer is well-established , the majority of predisposing factors still remain unidentified .", "Here , we have taken advantage of recent technical and methodological advances and performed a massive parallel sequencing of hundreds of DNA damage re...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "children", "medicine and health sciences", "maternal health", "obstetrics and gynecology", "helminths", "tropical diseases", "hookworms", "geographical locations", "parasitic diseases", "animals", "age groups", "adults", "women's health", "pharmaceutics", "pregnancy",...	Estimation of the number of women of reproductive age in need of preventive chemotherapy for soil-transmitted helminth infections	journal.pntd.0006269	null	[ [ "Soil-transmitted helminth ( STH ) are infections caused by the nematodes Ascaris lumbricoides ( roundworm ) , Ancylostoma duodenale and Necator americanus ( hookworms ) , and Trichuris trichiura ( whipworm ) .", "Humans acquire these infections from soil contaminated by faeces of STH-infected individuals...	[ "Soil-transmitted helminth infections are among the most common infections in developing countries .", "Globally , as many as 2 billion people are considered to be at risk for soil-transmitted-helminth ( STH ) infections .", "Preschool children ( PSAC ) , school-age children ( SAC ) and women of reproductive ag...	[ "Soil-transmitted helminths ( STH ) are intestinal worms that cause morbidity in many people worldwide; children and women of reproductive-age ( WRA ) are the group most at risk of these infections .", "The primary control strategy is the periodic anthelminthic treatment of people at risk of STH .", "Over the l...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pig models", "influenza", "pathogens", "immunology", "microbiology", "vertebrates", "cloning", "orthomyxoviruses", "animals", "mammals", "animal models", "viruses", "rna viruses", "...	Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig	journal.ppat.1007017	null	[ [ "Infection with influenza A virus is a major cause of human morbidity and mortality globally .", "Influenza is highly infectious , constantly mutating and infects a range of host species including humans , pigs and birds .", "Human influenza infection places a large burden on health care resources and...	[ "There is increasing evidence that induction of local immune responses is a key component of effective vaccines .", "For respiratory pathogens , for example tuberculosis and influenza , aerosol delivery is being actively explored as a method to administer vaccine antigens .", "Current animal models used to stud...	[ "Influenza virus infection in pigs represents a significant problem to industry and also carries substantial risks to human health .", "Pigs can be infected with both bird and human forms of influenza where these viruses can mix with swine influenza viruses to generate new pandemic strains that can spread quickly...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "ecology and environmental sciences", "genome evolution", "population genetics", "conservation genetics", "computational biology", "evolutionary adaptation", "population biology", "extinct genomes", "conservation biology", "genetic polymorphism", "molecular evolution", "evolutionary genetics",...	Genomic variation predicts adaptive evolutionary responses better than population bottleneck history	journal.pgen.1008205	null	[ [ "Evolutionary theory predicts reduced capacity for adaptation in populations with small effective population size ( Ne ) [1–4] .", "Causes include loss of genetic variation due to genetic drift limiting the potential for genetic adaptation [5–12] as well as an increased risk of deleterious alleles being l...	[ "The relationship between population size , inbreeding , loss of genetic variation and evolutionary potential of fitness traits is still unresolved , and large-scale empirical studies testing theoretical expectations are surprisingly scarce .", "Here we present a highly replicated experimental evolution setup wit...	[ "Genetic variation is a prerequisite for evolution to occur .", "Quantifying , utilizing and understanding the role of this variation for the survival and persistence of populations is central to several research disciplines including evolutionary biology , animal and plant breeding and conservation genetics .", ...	2019
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "chemistry/biochemistry", "infectious diseases/neglected tropical diseases", "biophysics/theory and simulation", "computer science/numerical analysis and theoretical computing", "biophysics/protein chemistry and proteomics", "chemical biology/protein chemistry and proteomics" ]	Functional and Structural Insights Revealed by Molecular Dynamics Simulations of an Essential RNA Editing Ligase in Trypanosoma brucei	journal.pntd.0000068	null	[ [ "The existence and widespread occurrence of several devastating trypanosomal tropical diseases , such as Chagas' disease and African sleeping sickness , cause an estimated 1 million deaths each year in developing countries [1] .", "In 2005 , the completely sequenced genomes of Trypanosoma brucei , the cau...	[ "RNA editing ligase 1 ( TbREL1 ) is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei , the parasite responsible for the devastating tropical disease African sleeping sickness .", "The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes , and no clos...	[ "RNA editing ligase 1 ( TbREL1 ) is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei , the parasite responsible for the devastating tropical disease African sleeping sickness .", "The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes , and no clos...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physiology/neuronal signaling mechanisms", "biophysics/theory and simulation", "computational biology/computational neuroscience" ]	How To Record a Million Synaptic Weights in a Hippocampal Slice	journal.pcbi.1000098	null	[ [ "The neuronal wiring diagram of many mammalian brain regions is known in a statistical sense , but not at the level of individual neurons [1] .", "The hippocampal CA3 to CA1 region is a particularly simple circuit with considerable functional relevance in memory , and is therefore an interesting test case...	[ "A key step toward understanding the function of a brain circuit is to find its wiring diagram .", "New methods for optical stimulation and optical recording of neurons make it possible to map circuit connectivity on a very large scale .", "However , single synapses produce small responses that are difficult to...	[ "The circuitry of the brain is defined by the connections ( synapses ) between its cells .", "Synapses are very small , so it is difficult to identify more than a few at a time using standard methods like electron microscopy or high-precision electrical recordings from cells .", "This study shows that it is pos...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gram negative", "microbial pathogens", "biology", "microbiology", "host-pathogen interaction", "microbial growth and development", "bacterial pathogens" ]	The Lipid Transfer Protein CERT Interacts with the Chlamydia Inclusion Protein IncD and Participates to ER-Chlamydia Inclusion Membrane Contact Sites	journal.ppat.1002092	null	[ [ "Chlamydia species are obligate intracellular Gram-negative bacterial pathogens that infect genital , ocular and pulmonary epithelial surfaces .", "Chlamydia are characterized by a biphasic developmental cycle that occurs exclusively in the host cell .", "The bacteria alternate between an infectious ,...	[ "Bacterial pathogens that reside in membrane bound compartment manipulate the host cell machinery to establish and maintain their intracellular niche .", "The hijacking of inter-organelle vesicular trafficking through the targeting of small GTPases or SNARE proteins has been well established .", "Here , we show...	[ "The obligate intracellular bacterial pathogen Chlamydia has developed strategies to invade , survive and replicate within the host genital , ocular and pulmonary epithelial surfaces .", "Chlamydia developmental cycle occurs in a membrane bound vacuole , the inclusion .", "The Chlamydia-dependent remodeling of ...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell motility", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "cell-mediated immunity", "microbiology", "bacterial diseases", "helicobacter", "gastroenterology and hepatology", "cytotoxic t cells", "bacteria"...	BATF3-dependent dendritic cells drive both effector and regulatory T-cell responses in bacterially infected tissues	journal.ppat.1007866	null	[ [ "Mononuclear phagocytes ( MPs ) residing in the lamina propria ( LP ) of the gastrointestinal ( GI ) tract comprise populations of resident macrophages that are replenished from Ly6Chi blood monocytes , and of dendritic cells ( DCs ) that originate from a pre-DC-progenitor and require FLT3L for their developm...	[ "The gastric lamina propria of mice that have been experimentally infected with the pathobiont Helicobacter pylori hosts a dense network of myeloid cells that includes BATF3-dependent CD103+ dendritic cells ( DCs ) .", "We show here that CD103+ DCs are strictly required for gastric Th1 responses to H . pylori and...	[ "In this work , Arnold & Zhang et al report that CD103+ DCs are required for protective Th1 responses , infection control of mucosal and systemic bacterial pathogens , and anti-tumor immunity driven by CD4+ Th1 cells and CD8+ T cells .", "CD103+ DCs further specifically promote the recruitment of Tbet+ peripheral...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "cell cycle and cell division", "cell processes", "trypanosoma congolense", "microbiology", "parasitic protozoans", "protozoan life cycles", "trypanosoma brucei", "developmental biology", "protozoans", "epimast...	Shape-shifting trypanosomes: Flagellar shortening followed by asymmetric division in Trypanosoma congolense from the tsetse proventriculus	journal.ppat.1007043	null	[ [ "Trypanosomatids such as Leishmania and Trypanosoma are digenetic , single-celled , parasitic flagellates that undergo complex life cycles involving morphological and metabolic changes to fit them for survival in different environments within their hosts .", "While metabolic changes are brought about by c...	[ "Trypanosomatids such as Leishmania and Trypanosoma are digenetic , single-celled , parasitic flagellates that undergo complex life cycles involving morphological and metabolic changes to fit them for survival in different environments within their mammalian and insect hosts .", "According to current consensus , ...	[ "Tsetse-transmitted trypanosomes are parasitic protists that cause severe human and livestock diseases in tropical Africa .", "During their developmental cycle in the tsetse fly , these trypanosomes undergo complex cycles of differentiation and proliferation .", "Here we have investigated part of the developmen...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "reactive oxygen species", "immune cells", "respiratory infections", "parasite replication", "immunology", "microbiology", "parasitic diseases", "parasitic protozoans", "pulmonology", "parasitology", "protozoan life cycles", "developmental bio...	Trypanosoma cruzi Needs a Signal Provided by Reactive Oxygen Species to Infect Macrophages	journal.pntd.0004555	null	[ [ "Macrophages are one of the first lines of defense against intracellular pathogens [1] .", "During Trypanosoma cruzi infection , these cells are activated to produce ROS , a process called respiratory burst [2–4] .", "The detection of infectious agents leads to activation of the membrane bound NADPH o...	[ "During Trypanosoma cruzi infection , macrophages produce reactive oxygen species ( ROS ) in a process called respiratory burst .", "Several works have aimed to elucidate the role of ROS during T . cruzi infection and the results obtained are sometimes contradictory .", "T . cruzi has a highly efficiently regul...	[ "The parasite Trypanosoma cruzi is the causative agent of Chagas’ disease , which affects 10 million people , mainly in Latin American .", "Macrophages are one of the first cellular actors facing the invasion of pathogens and during T . cruzi infection , produce reactive oxygen species ( ROS ) .", "To deal with...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Protein-Protein Interactions in a Crowded Environment: An Analysis via Cross-Docking Simulations and Evolutionary Information	journal.pcbi.1003369	null	[ [ "Protein-protein interactions ( PPI ) are at the heart of the molecular processes governing life and constitute an increasingly important target for drug design [1]–[4] .", "Given their importance , it is clearly vital to characterize PPIs and notably to determine which protein interactions are likely to ...	[ "Large-scale analyses of protein-protein interactions based on coarse-grain molecular docking simulations and binding site predictions resulting from evolutionary sequence analysis , are possible and realizable on hundreds of proteins with variate structures and interfaces .", "We demonstrated this on the 168 pro...	[ "Protein-protein interactions ( PPI ) are at the heart of the molecular processes governing life and constitute an increasingly important target for drug design .", "Given their importance , it is vital to determine which protein interactions have functional relevance and to characterize the protein competition i...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "antigen processing and recognition", "biology and life sciences", "immunology", "evolutionary biology", "evolutionary genetics" ]	An Evolutionary Analysis of Antigen Processing and Presentation across Different Timescales Reveals Pervasive Selection	journal.pgen.1004189	null	[ [ "Cell mediated immune responses are initiated by the recognition of an MHC/antigen complex on the surface of an APC ( antigen presenting cell ) by a T cell receptor ( TcR ) .", "MHC class I and II molecules present peptides to T cells that express the CD8 or CD4 molecules , respectively .", "Non-conve...	[ "The antigenic repertoire presented by MHC molecules is generated by the antigen processing and presentation ( APP ) pathway .", "We analyzed the evolutionary history of 45 genes involved in APP at the inter- and intra-species level .", "Results showed that 11 genes evolved adaptively in mammals .", "Several ...	[ "Antigen-presenting cells digest intracellular and extracellular proteins and display the resulting antigenic repertoire on cell surface molecules for recognition by T cells .", "This process initiates cell-mediated immune responses and is essential to detect infections .", "The antigenic repertoire is generate...	2014

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