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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" ]	[ "infectious diseases/hiv infection and aids", "immunology/immunity to infections", "virology/animal models of infection", "virology/host antiviral responses" ]	Critical Loss of the Balance between Th17 and T Regulatory Cell Populations in Pathogenic SIV Infection	journal.ppat.1000295	null	[ [ "Progressive disease caused by the human immunodeficiency virus , type 1 ( HIV ) is marked by systemic inflammation and immune dysregulation , most notably CD4+ T cell depletion [1] , [2] , [3] , [4] .", "Insights into HIV-induced pathogenesis have been provided by studying SIV infection of non-human prim...	[ "Chronic immune activation and progression to AIDS are observed after SIV infection in macaques but not in natural host primate species .", "To better understand this dichotomy , we compared acute pathogenic SIV infection in pigtailed macaques ( PTs ) to non-pathogenic infection in African green monkeys ( AGMs ) ...	[ "Natural infection by the simian immunodeficiency virus ( SIV ) in over 40 different species of African non-human primates is not accompanied by progression to acquired immunodeficiency syndrome ( AIDS ) .", "To understand this phenomenon , we have performed a detailed virologic , immunologic , and gene expressio...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "engineering and technology", "signal processing", "brain", "brain electrophysiology", "electrophysiology", "neuroscience", "surgical and invasive medical procedures", "transcranial alternating current stimulation", "functional electrical stimulation", "membrane e...	Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent	journal.pbio.1002424	This study presents mathematical models that explain the effect of temporally patterned electrical stimulation on cortical oscillations and provides supporting evidence using data recorded directly from human cortex during transcranial electrical stimulation.	[ [ "Oscillations in a wide range of frequencies represent a ubiquitous organizational pattern of cortical network dynamics [1] .", "In particular , oscillations in the alpha frequency band are pronounced activity patterns routinely observed in posterior leads of electroencephalograms ( EEGs ) of healthy huma...	[ "Cortical oscillations play a fundamental role in organizing large-scale functional brain networks .", "Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation ( rTMS ) and transcranial alternating current stimulation ( tACS ) have been proposed to mo...	[ "Rhythms in the brain are believed to play an important role in cognition .", "Disruptions in these oscillations are associated with a number of neurological and psychiatric disorders .", "Therefore , noninvasive brain stimulation techniques that target these oscillations offer promise as therapeutic tools .", ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "reverse transcriptase-polymerase chain reaction", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "body fluids", "pathogens", "immunology", "microbiology", "bacterial diseases", "molecular biology techniques", "antibodies...	Succinyl-CoA Synthetase: New Antigen Candidate of Bartonella bacilliformis	journal.pntd.0004989	null	[ [ "Bartonella bacilliformis is the etiological agent of Carrion’s disease , a neglected endemic illness in Peru which has also been reported in Ecuador and Colombia [1] .", "Two well-established phases have been described in this infection .", "In the acute phase , also called Oroya Fever , B . bacillif...	[ "Bartonella bacilliformis is the causative agent of Carrion’s disease , a neglected illness with mortality rates of 40–85% in the absence of treatment .", "The lack of a diagnostic technique to overcome misdiagnosis and treat asymptomatic carriers is of note .", "This study aimed to identify new B . bacilliform...	[ "B . bacilliformis is a neglected pathogen causing Carrion’s disease , a febrile illness with two distinct phases , the acute so-called Oroya fever that can be life-threatening , and the chronic so-called Peruvian wart .", "This illness is currently limited to poor inhabitants of Andean valleys of Ecuador , Colom...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "immune cells", "proteins", "immunity", "immunology", "biology", "microbiology", "protozoology" ]	KSAC, a Defined Leishmania Antigen, plus Adjuvant Protects against the Virulence of L. major Transmitted by Its Natural Vector Phlebotomus duboscqi	journal.pntd.0001610	null	[ [ "Leishmaniasis is a neglected disease endemic in 98 countries with an estimated 350 million people at risk and an estimated burden of 2 , 357 , 000 disability-adjusted life years [1] .", "Visceral leishmaniasis is fatal if left untreated , and the morbidity and stigma caused by cutaneous leishmaniasis is ...	[ "Recombinant KSAC and L110f are promising Leishmania vaccine candidates .", "Both antigens formulated in stable emulsions ( SE ) with the natural TLR4 agonist MPL® and L110f with the synthetic TLR4 agonist GLA in SE protected BALB/c mice against L . major infection following needle challenge .", "Considering th...	[ "Leishmaniasis is a neglected disease caused by the Leishmania parasite and transmitted by the bite of an infective sand fly .", "Despite the importance of this disease there is no vaccine available for humans .", "Studies have shown that vector-transmitted infections are more virulent , promoting parasite esta...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "microbiology/microbial physiology and metabolism", "microbiology/microbial evolution and genomics", "microbiology", "microbiology/microbial growth and development" ]	Structural Alterations in a Component of Cytochrome c Oxidase and Molecular Evolution of Pathogenic Neisseria in Humans	journal.ppat.1001055	null	[ [ "The genus Neisseria comprises Gram-negative , oxidase-positive diplococci that are frequently isolated from the mucosal surfaces of humans and two closely related species are important pathogens of man [1] .", "Neisseria gonorrhoeae is the etiologic agent of gonorrhea that remains one of the most common ...	[ "Three closely related bacterial species within the genus Neisseria are of importance to human disease and health .", "Neisseria meningitidis is a major cause of meningitis , while Neisseria gonorrhoeae is the agent of the sexually transmitted disease gonorrhea and Neisseria lactamica is a common , harmless comme...	[ "The closely related bacterial species N . meningitidis , N . gonorrhoeae and N . lactamica exclusively colonise mucosal surfaces in humans .", "While N . gonorrhoeae leads to gonorrhea , the other two species persist mainly in their host in the absence of disease .", "N . meningitidis does occasionally cause s...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "homo (human)", "genetics and genomics", "neurological disorders" ]	Genome-Wide Association Identifies a Common Variant in the Reelin Gene That Increases the Risk of Schizophrenia Only in Women	journal.pgen.0040028	null	[ [ "Schizophrenia ( 181500 ) is a common psychiatric disorder of unknown aetiology .", "Individual twin studies and meta-analyses of twin studies [1] estimate that the heritability of schizophrenia is approximately 80% .", "Analysis of family , adoption and twin data indicate that inheritance acts in a c...	[ "Sex differences in schizophrenia are well known , but their genetic basis has not been identified .", "We performed a genome-wide association scan for schizophrenia in an Ashkenazi Jewish population using DNA pooling .", "We found a female-specific association with rs7341475 , a SNP in the fourth intron of the...	[ "Schizophrenia is a complex mental disease , which includes symptoms of delusions , hallucinations , disorganized speech , aberrant behavior , lack of emotional expression , diminished motivation , and social withdrawal .", "The cause of schizophrenia is unknown , but there is extensive evidence that genetics pla...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "biology", "biophysics" ]	Crystal Structures Reveal the Multi-Ligand Binding Mechanism of Staphylococcus aureus ClfB	journal.ppat.1002751	null	[ [ "Staphylococcus aureus ( S . aureus ) , an important opportunistic pathogen , is a major threat to humans and animals causing high morbidity and mortality worldwide .", "It is responsible for a variety of infections ranging from mild superficial infections to severe infections such as infective endocardit...	[ "Staphylococcus aureus ( S . aureus ) pathogenesis is a complex process involving a diverse array of extracellular and cell wall components .", "ClfB , an MSCRAMM ( Microbial Surface Components Recognizing Adhesive Matrix Molecules ) family surface protein , described as a fibrinogen-binding clumping factor , is ...	[ "Staphylococcus aureus ( S . aureus ) , an important opportunistic pathogen , is a major threat to humans and animals , causing high morbidity and mortality worldwide .", "It is responsible for a variety of infections ranging from mild superficial infections to severe infections such as infective endocarditis , s...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "chemical compounds", "dwarfism", "nucleotides", "organic compounds", "animal models", "model organisms", "methylation", "experimental organism systems", "pyrimidines", "epigenetics", "dna", "mammalian genomics", "dna methylation", "chromatin", "research...	Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity	journal.pgen.1007766	null	[ [ "Dietary , genetic and pharmacological interventions can extend health- and lifespan in diverse model organisms whilst delaying the onset of age-related pathologies [1–3] .", "Understanding the underlying mechanisms holds the prospect of harnessing these benefits for prevention of age-related diseases in ...	[ "Dietary , pharmacological and genetic interventions can extend health- and lifespan in diverse mammalian species .", "DNA methylation has been implicated in mediating the beneficial effects of these interventions; methylation patterns deteriorate during ageing , and this is prevented by lifespan-extending interv...	[ "Dietary , genetic and pharmacological interventions can extend lifespan in diverse organisms and represent good models for developing therapies against age-related diseases in humans .", "However , whether these longevity interventions act by slowing down the effects of ageing , or inducing novel phenotypes to c...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "dna-binding proteins", "limbs (anatomy)", "thumbs", "somites", "animal models", "developmental biology", "model organisms", "organism development", "experimental organism systems", "embryos", "research and analysis methods", "embryology", "musculoskeletal s...	Tbx5 Buffers Inherent Left/Right Asymmetry Ensuring Symmetric Forelimb Formation	journal.pgen.1006521	null	[ [ "The external body plan of most metazoans is bilaterally symmetric .", "How this symmetry is achieved has fascinated biologists for centuries and is exemplified by Leonardo Da Vinci’s description of the “Vitruvian Man” that describes some of the uniform proportions of the human body .", "In vertebrate...	[ "The forelimbs and hindlimbs of vertebrates are bilaterally symmetric .", "The mechanisms that ensure symmetric limb formation are unknown but they can be disrupted in disease .", "In Holt-Oram Syndrome ( HOS ) , caused by mutations in TBX5 , affected individuals have left-biased upper/forelimb defects .", "W...	[ "Externally , the human form appears bilaterally symmetric .", "For example , each of our pairs of arms and legs are the same length .", "This external symmetry masks many asymmetries found in internal organs .", "In most people the heart is found on the left side of the chest .", "The stomach , liver and s...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Disruption of Transcriptional Coactivator Sub1 Leads to Genome-Wide Re-distribution of Clustered Mutations Induced by APOBEC in Active Yeast Genes	journal.pgen.1005217	null	[ [ "Faithful replication of genomes and accurate repair of damaged DNA ensures the low mutation rates necessary for the functionality of living cells and organisms .", "An elevated mutation rate leads to cancer .", "On the other hand , mutations provide the raw material for evolution on the population le...	[ "Mutations in genomes of species are frequently distributed non-randomly , resulting in mutation clusters , including recently discovered kataegis in tumors .", "DNA editing deaminases play the prominent role in the etiology of these mutations .", "To gain insight into the enigmatic mechanisms of localized hype...	[ "Genomes of tumors are heavily enriched with mutations .", "Some of these mutations are distributed non-randomly , forming mutational clusters .", "Editing cytosine deaminases from APOBEC superfamily are responsible for the formation of many of these clusters .", "We have expressed APOBEC enzyme in diploid ye...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology and environmental sciences", "biodiversity", "marine biology", "age groups", "developmental biology", "adults", "fisheries", "coral reefs", "marine and aquatic sciences", "life cycles", "reefs", "agriculture", "conservation science", "people and places", "ecology", "earth scie...	Marine Reserve Targets to Sustain and Rebuild Unregulated Fisheries	journal.pbio.2000537	null	[ [ "Overfishing and other anthropogenic impacts threaten the sustainability of coastal marine biodiversity and ecosystem functioning worldwide [1 , 2] .", "To counter this problem , nearly 200 governments have committed to protecting 10% of all coastal and marine areas “effectively” by 2020 ( Aichi Target 11...	[ "Overfishing threatens the sustainability of coastal marine biodiversity , especially in tropical developing countries .", "To counter this problem , about 200 governments worldwide have committed to protecting 10%–20% of national coastal marine areas .", "However , associated impacts on fisheries productivity ...	[ "Marine reserves are an important tool to conserve biodiversity but increasingly are relied upon also to benefit fisheries , specifically in diverse , unassessed , and otherwise unregulated systems .", "Whether the globally adopted Aichi Target 11 ( 10% “effective” protection of national coastal marine areas ) ca...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "telomeres", "genome evolution", "chromosome biology", "centromeres", "biology", "genomics", "comparative genomics", "genetics and genomics" ]	Mechanisms of Chromosome Number Evolution in Yeast	journal.pgen.1002190	null	[ [ "Centromeres and telomeres are essential genetic and structural elements of eukaryotic chromosomes .", "To maintain the accurate transmission of the genome to the next generation , each chromosome must have exactly one centromere and two telomeres .", "Evolutionary changes in an organism's number of c...	[ "The whole-genome duplication ( WGD ) that occurred during yeast evolution changed the basal number of chromosomes from 8 to 16 .", "However , the number of chromosomes in post-WGD species now ranges between 10 and 16 , and the number in non-WGD species ( Zygosaccharomyces , Kluyveromyces , Lachancea , and Ashbya...	[ "The number of chromosomes in organisms often changes over evolutionary time .", "To study how the number changes , we compare several related species of yeast that share a common ancestor roughly 150 million years ago and have varying numbers of chromosomes .", "By inferring ancestral genome structures , we ex...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "molecular cell biology", "cell division", "cell biology", "genetics", "yeast and fungal models", "biology", "saccharomyces cerevisiae", "microbiology", "genetics and genomics", "cyclins" ]	F-Box Protein Specificity for G1 Cyclins Is Dictated by Subcellular Localization	journal.pgen.1002851	null	[ [ "The ubiquitin-proteasome system plays an essential role in controlling passage through the eukaryotic cell cycle [1] .", "A significant fraction of cell cycle-regulated ubiquitination is carried out by SCF ( Skp1-Cullin-F-box protein ) family ubiquitin ligases , which target numerous cell cycle regulator...	[ "Levels of G1 cyclins fluctuate in response to environmental cues and couple mitotic signaling to cell cycle entry .", "The G1 cyclin Cln3 is a key regulator of cell size and cell cycle entry in budding yeast .", "Cln3 degradation is essential for proper cell cycle control; however , the mechanisms that control...	[ "Most cells only divide when they receive the proper cues .", "When a cell receives a signal to divide , levels of G1 cyclin proteins increase and drive entry into the cell division cycle .", "Overexpression of G1 cyclins can drive cells into the cell cycle inappropriately and thus may contribute to the hyperpr...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "neural networks", "computational neuroscience", "biology", "neuroscience" ]	Stimulus-Dependent State Transition between Synchronized Oscillation and Randomly Repetitive Burst in a Model Cerebellar Granular Layer	journal.pcbi.1002087	null	[ [ "The cerebellar granular layer is one of the stations receiving external stimuli for information processing of the cerebellar cortex .", "The granular layer is thought to transform spatial patterns of mossy fibers ( MFs ) input signals into a population of active granule cells ( grcs ) [1] , [2] .", "...	[ "Information processing of the cerebellar granular layer composed of granule and Golgi cells is regarded as an important first step toward the cerebellar computation .", "Our previous theoretical studies have shown that granule cells can exhibit random alternation between burst and silent modes , which provides a...	[ "Intensive studies of Pavlovian delay eyelid conditioning suggest that the cerebellum can memorize a passage-of-time ( POT ) from the onset of an external stimulus .", "To account for possible mechanisms of such POT representation , some network models have been proposed to show that granule cells ( grcs ) in the...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal genetics", "genomics", "genetic polymorphism", "genome evolution", "chromosomal inheritance", "heredity", "genetics", "biology and life sciences", "population genetics", "molecular evolution", "computational biology", "evolutionary biology", "mammalian genetics", "epigenetics", "...	PRDM9 Drives Evolutionary Erosion of Hotspots in Mus musculus through Haplotype-Specific Initiation of Meiotic Recombination	journal.pgen.1004916	null	[ [ "Genetic recombination increases variability by facilitating selection for new , favorable combinations of alleles and against deleterious mutations .", "In many eukaryotes , including humans and mice , recombination is restricted to short ( 1- to 2-kb ) regions known as hotspots [reviewed in 1] , [2] .",...	[ "Meiotic recombination generates new genetic variation and assures the proper segregation of chromosomes in gametes .", "PRDM9 , a zinc finger protein with histone methyltransferase activity , initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand ...	[ "Sexually reproducing creatures need to produce germ cells , notably sperm and egg , and do so using a specialized cell division , termed meiosis .", "A hallmark of meiosis is the process of recombination , in which pieces of maternal and paternal genetic material are exchanged , creating new combinations that ar...	2015
[ "Introduction", "Methods", "Results/Discussion" ]	[]	Analyzing and Synthesizing Phylogenies Using Tree Alignment Graphs	journal.pcbi.1003223	null	[ [ "Evolutionary biologists use phylogenetic trees to conceptualize , visualize , and analyze the relationships among biological lineages .", "However , when examining trees from individual datasets ( e . g . , posterior distribution of trees , bootstrapped trees , individual gene trees ) or multiple partial...	[ "Phylogenetic trees are used to analyze and visualize evolution .", "However , trees can be imperfect datatypes when summarizing multiple trees .", "This is especially problematic when accommodating for biological phenomena such as horizontal gene transfer , incomplete lineage sorting , and hybridization , as w...	[ "Phylogenetic trees are the most common datatype by which we examine evolutionary patterns .", "However , biological and practical considerations require the exploration of other models .", "Here , we address a problem concerning the representation of conflicting and partially overlapping datasets in phylogenet...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "medicine", "immune cells", "immunity to infections", "immunology", "cytomegalovirus infection", "epstein-barr virus infectious mononucleosis", "adaptive immunity", "vaccination", "infectious diseases", "t cells", "clinical immunology", "immunity", "vaccine development", "viral diseases" ]	Deep Sequencing of Antiviral T-Cell Responses to HCMV and EBV in Humans Reveals a Stable Repertoire That Is Maintained for Many Years	journal.ppat.1002889	null	[ [ "The selection and maintenance of CD8+ T-cell clones is pivotal in antiviral immune responses .", "CD8+ T-cell responses can be divided in 3 different phases .", "After detection of a viral peptide , high-affinity CD8+ T-cells will clonally expand and acquire effector functions to clear the infected c...	[ "CD8+ T-cell responses against latent viruses can cover considerable portions of the CD8+ T-cell compartment for many decades , yet their initiation and maintenance remains poorly characterized in humans .", "A key question is whether the clonal repertoire that is raised during the initial antiviral response can ...	[ "Several viruses have found ways to evade the human immune system and cause latent infections .", "Examples include HIV and herpes-viruses .", "Most humans carry these herpes-viruses .", "The human immune system mounts continuous responses against these viruses to prevent them from causing disease .", "If t...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Development of an Immunochromatographic Test for Diagnosis of Visceral Leishmaniasis Based on Detection of a Circulating Antigen	journal.pntd.0003902	null	[ [ "Visceral leishmaniasis ( VL ) , or kala-azar , is a vector-borne disease caused by protozoan parasites belonging to the Leishmania donovani complex , which includes L . donovani , L . infantum and L . chagasi .", "The parasites infect and multiply preferentially in macrophages of the spleen , liver , bon...	[ "Visceral leishmaniasis ( VL ) is a life-threatening disease caused by protozoan parasites of the Leishmania donovani complex .", "Early case detection followed by adequate treatment is essential to the control of VL .", "However , the available diagnostic tests are either invasive and require considerable expe...	[ "Visceral leishmaniasis is a neglected disease caused by different species of protozoan parasites of the genus Leishmania .", "The disease is endemic in 61 countries , and in many of them it poses a serious public health issue .", "As visceral leishmaniasis is fatal if left untreated , early diagnosis is essent...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "blood cells", "medicine and health sciences", "immune cells", "vesicular stomatitis virus", "pathology and laboratory medicine", "molecular probe techniques", "293t cells", "pathogens", "biological cultures", "immunology", "microbiology", "immunoblotting", "plasmid constr...	Multiple UBXN family members inhibit retrovirus and lentivirus production and canonical NFκΒ signaling by stabilizing IκBα	journal.ppat.1006187	null	[ [ "The UBX family member proteins are thought to regulate diverse cellular processes , including protein stability and degradation .", "Members of the gene family include UBXN2a ( also termed UBXD4 ) , UBXN2b ( p37 ) , UBXN2c ( UBXD10 , p47 , or UBX1 ) , UBXN3a ( FAF1 or UBXD12 ) , UBXN3b ( FAF2 or UBXD8 ) ...	[ "UBXN proteins likely participate in the global regulation of protein turnover , and we have shown that UBXN1 interferes with RIG-I-like receptor ( RLR ) signaling by interacting with MAVS and impeding its downstream effector functions .", "Here we demonstrate that over-expression of multiple UBXN family members ...	[ "A family of human genes termed UBXN is thought to control many cellular processes , including protein destruction .", "While working with these proteins , we noticed several profoundly blocked the production of human immunodeficiency virus ( HIV ) and other , similar viruses .", "We delved into the how this oc...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/cellular microbiology and pathogenesis", "microbiology/parasitology" ]	Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis	journal.ppat.1001286	null	[ [ "Phosphoinositides are phosphorylated derivatives of the structural membrane lipid phosphatidylinositol and function both as signalling molecules and as compartment specific localization signals for phosphoinositide-binding proteins .", "PI3-kinases produce derivatives phosphorylated at the D-3 position o...	[ "Apicomplexan parasites cause devastating diseases including malaria and toxoplasmosis .", "They harbour a plastid-like , non-photosynthetic organelle of algal origin , the apicoplast , which fulfils critical functions for parasite survival .", "Because of its essential and original metabolic pathways , the api...	[ "Phosphatidyinositol 3-monophosphate ( PI3P ) is important for endocytic fusion events in eukaryotic cells .", "Despite the importance of this lipid in cell biology , its localization and function in apicomplexan parasites has not yet been extensively explored .", "In this study , we attribute for the first tim...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Epidemic Reconstruction in a Phylogenetics Framework: Transmission Trees as Partitions of the Node Set	journal.pcbi.1004613	null	[ [ "The increasing availability of faster and cheaper sequencing technologies is making it possible to acquire genetic data on the pathogens involved in outbreaks and epidemics at a very fine resolution .", "It is likely that in future outbreaks where most or all clinical cases can be identified , pathogen n...	[ "The use of genetic data to reconstruct the transmission tree of infectious disease epidemics and outbreaks has been the subject of an increasing number of studies , but previous approaches have usually either made assumptions that are not fully compatible with phylogenetic inference , or , where they have based in...	[ "With sequence data becoming available in increasing high volumes and at decreasing costs , there has been substantial recent interest in the possibility of using pathogen genome sequences as a means to retrace the spread of disease amongst the infected hosts in an epidemic .", "While several such methods exist ,...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacterial diseases", "infectious diseases", "tuberculosis", "medicine and health sciences" ]	LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis	journal.ppat.1004376	null	[ [ "Mycobacterium tuberculosis is a human pathogen that has infected one-third of world's population and causes 8 million new cases and over one million deaths each year [1] .", "In the absence of a protective vaccine and the global prevalence of drug resistant strains , a greater understanding of virulence ...	[ "Mycobacterium tuberculosis employs various virulence strategies to subvert host immune responses in order to persist and cause disease .", "Interaction of M . tuberculosis with mannose receptor on macrophages via surface-exposed lipoarabinomannan ( LAM ) is believed to be critical for cell entry , inhibition of ...	[ "Mycobacterium tuberculosis is among the leading infectious causes of human death .", "A better understanding of its virulence mechanisms is needed to facilitate development of novel therapeutics and a preventative vaccine .", "Lipoarabinomannan ( LAM ) , an abundant surface-exposed lipoglycan , is believed to ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "genetics and genomics/gene expression", "infectious diseases/neglected tropical diseases", "microbiology/parasitology", "genetics and genomics/epigenetics", "molecular biology/translational regulation" ]	H2A.Z Demarcates Intergenic Regions of the Plasmodium falciparum Epigenome That Are Dynamically Marked by H3K9ac and H3K4me3	journal.ppat.1001223	null	[ [ "Plasmodium falciparum , the deadly protozoan parasite , causes malaria via the invasion of erythrocytes .", "During its ∼48 h asexual reproductive cycle within human red blood cells ( RBC ) , the parasite exploits and remodels the host cell , multiplies and finally ruptures the RBC to invade fresh erythr...	[ "Epigenetic regulatory mechanisms and their enzymes are promising targets for malaria therapeutic intervention; however , the epigenetic component of gene expression in P . falciparum is poorly understood .", "Dynamic or stable association of epigenetic marks with genomic features provides important clues about t...	[ "Plasmodium falciparum is a unicellular pathogen that is responsible for the most severe form of malaria .", "Similar to other eukaryotic organisms , its genome is organized into chromosomes by proteins called histones .", "Modification or replacement of these histones has marked effects on the packaging grade ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	IRF-4-Mediated CIITA Transcription Is Blocked by KSHV Encoded LANA to Inhibit MHC II Presentation	journal.ppat.1003751	null	[ [ "Major histocompatibility complex ( MHC ) class II is known to play critical roles in the induction and regulation of adaptive immune responses to pathogenic agents [1] .", "In human , there are at least six major MHC II molecules: HLA-DRα , HLA-DRβ , HLA-DPα , HLA-DPβ , HLA-DQα and HLA-DQβ .", "Durin...	[ "Peptides presentation to T cells by MHC class II molecules is of importance in initiation of immune response to a pathogen .", "The level of MHC II expression directly influences T lymphocyte activation and is often targeted by various viruses .", "Kaposi's sarcoma-associated herpesvirus ( KSHV ) encoded LANA ...	[ "Major histocompatibility complex ( MHC ) class II is critical for eliciting specific adaptive immune responses against a wide range of pathogenic agents .", "KSHV as a member of the herpesvirus family has been shown to encode viral proteins for deregulation of the MHC II signaling pathway .", "In this study , ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis	journal.pgen.1005561	null	[ [ "According to Greek mythology , Odysseus was forced to carefully navigate his ship between two dangers—Scylla and Charybdis—whereby passing too close to either one would lead to destruction .", "Likewise , in metabolic regulation , the liver strikes a difficult balance between glucose and lipid homeostasi...	[ "In mammals , the liver plays a central role in maintaining carbohydrate and lipid homeostasis by acting both as a major source and a major sink of glucose and lipids .", "In particular , when dietary carbohydrates are in excess , the liver converts them to lipids via de novo lipogenesis .", "The molecular chec...	[ "After a meal , dietary glucose travels through the hepatic portal vein to the liver .", "A substantial part of this glucose is taken up by liver , which converts it to glycogen which is stored , and lipids which are in part stored and in part secreted as VLDL particles .", "The rest of the organs receive whate...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "inflammatory diseases", "medicine and health sciences", "body fluids", "diagnostic radiology", "pathology and laboratory medicine", "neurocysticercosis", "nervous system", "tropical diseases", "parasitic diseases", "migraine", "headaches", "magnetic resonance imaging", "signs and symptoms",...	Clinical Symptoms, Imaging Features and Cyst Distribution in the Cerebrospinal Fluid Compartments in Patients with Extraparenchymal Neurocysticercosis	journal.pntd.0005115	null	[ [ "Neurocysticercosis is the most common parasitic disease of the central nervous system ( CNS ) worldwide .", "It is caused by the accidental ingestion of eggs of the tapeworm Taenia solium .", "After hatching from the eggs , some of the larvae lodge themselves in the CNS , where they induce inflammato...	[ "Extraparenchymal neurocysticercosis has an aggressive course because cysts in the cerebrospinal fluid compartments induce acute inflammatory reactions .", "The relationships between symptoms , imaging findings , lesion type and location remain poorly understood .", "In this retrospective clinical records-based...	[ "Neurocysticercosis is caused by the accidental ingestion of eggs from Taenia solium whose larvae lodge in the central nervous system .", "In this study we found that cysts within the cerebrospinal fluid leaded to high rates of raised intracranial pressure , meningitis , seizures and headache .", "Imaging studi...	2016
[ "Introduction", "Materials and Methods", "Results" ]	[]	Decoding Structural Properties of a Partially Unfolded Protein Substrate: En Route to Chaperone Binding	journal.pcbi.1004496	null	[ [ "Properly folded proteins is a prerequisite in nearly every cellular process .", "Several proteins fold spontaneously while others rely on molecular chaperones to reach their native states [1] .", "GroEL , an indispensable chaperone of Escherichia coli , selectively binds with unfolded proteins to ass...	[ "Many proteins comprising of complex topologies require molecular chaperones to achieve their unique three-dimensional folded structure .", "The E . coli chaperone , GroEL binds with a large number of unfolded and partially folded proteins , to facilitate proper folding and prevent misfolding and aggregation .", ...	[ "Several non-native proteins require molecular chaperones for proper folding .", "Many unfolded proteins if not folded accurately , become causal factors in various types of misfolding or aggregation induced diseases such as Alzheimer′s , Huntington′s and several other neurodegenerative disorders .", "However ,...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neurotoxicology", "dengue virus", "medicine and health sciences", "flaviviruses", "viral transmission and infection", "medical microbiology", "virology", "viral pathogens", "entomology", "microbial pathogens", "epidemiology", "biology and life sciences", "vector biology", "microbiology", ...	A Single Crossing-Over Event in Voltage-Sensitive Na+ Channel Genes May Cause Critical Failure of Dengue Mosquito Control by Insecticides	journal.pntd.0003085	null	[ [ "Aedes aegypti is the major mosquito vector of dengue fever ( DF ) , yellow fever , and chikungunya fever .", "DF causes more illness and death in humans than any other arboviral disease [1] .", "Mosquito control is mainly achieved by pyrethroids because of the high and rapid activity of this class of...	[ "The voltage-sensitive sodium ( Na+ ) channel ( Vssc ) is the target site of pyrethroid insecticides .", "Pest insects develop resistance to this class of insecticide by acquisition of one or multiple amino acid substitution ( s ) in this channel .", "In Southeast Asia , two major Vssc types confer pyrethroid r...	[ "Pyrethroids are one of the major classes of insecticides that is widely used to control mosquito vectors .", "The target site of pyrethroids is found in the voltage-sensitive Na+ channel ( Vssc ) consisting of about 2100 amino acid residues .", "In this study we generated several types of Vssc with a single or...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell signaling", "developmental biology/cell differentiation", "nephrology/hereditary, genetic, and development nephrology", "developmental biology/organogenesis", "developmental biology/developmental molecular mechanisms", "cell biology/gene expression" ]	Gata3 Acts Downstream of β-Catenin Signaling to Prevent Ectopic Metanephric Kidney Induction	journal.pgen.1000316	null	[ [ "In human , urinary tract anomalies rank among the most common birth defects , with an estimated occurrence of 1 in 250 live births [1] .", "Most of these ontogenic malformations are classified as Congenital Anomalies of the Kidney and Urinary Tract ( CAKUT ) [2] , which is a highly heterogenous condition...	[ "Metanephric kidney induction critically depends on mesenchymal–epithelial interactions in the caudal region of the nephric ( or Wolffian ) duct .", "Central to this process , GDNF secreted from the metanephric mesenchyme induces ureter budding by activating the Ret receptor expressed in the nephric duct epitheli...	[ "In humans , kidney development originates during embryonic development by the sprouting of an epithelial bud—called the ureteric bud—from a simple epithelial structure—the nephric duct .", "The ureteric bud quickly grows and branches in a treelike fashion to form the kidney collecting duct system , while the eme...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "chemical compounds", "enzymes", "immunology", "microbiology", "enzymology", "parasitic diseases", "protozoan life cycles", "organic compounds", "parasitic protozoans", "developmental biology", "protozoans", "leishmania", "...	An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion	journal.ppat.1005494	null	[ [ "Protozoan parasites of the genus Leishmania are causative agents of a wide spectrum of human and veterinary diseases , with clinical manifestations ranging from lesions of the skin and mucous membranes to lethal visceral disease [1] .", "Leishmania species cause morbidity and mortality throughout large a...	[ "Amino acid sensing is an intracellular function that supports nutrient homeostasis , largely through controlled release of amino acids from lysosomal pools .", "The intracellular pathogen Leishmania resides and proliferates within human macrophage phagolysosomes .", "Here we describe a new pathway in Leishmani...	[ "Protozoa of the genus Leishmania are the causative agents of leishmaniasis in humans .", "These parasites cycle between promastigotes in the sand fly mid-gut and amastigotes in phagolysosome of mammalian macrophages .", "During infection , host cells up-regulate nitric oxide while/or parasites induce expressio...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "parastic protozoans", "developmental biology", "molecular cell biology", "chromosome biology", "chromosome structure and function", "gene expression", "parasitology", "protozoology", "microbial growth and development", "biology", "microbiology", "cell differentiation", "dna transcription" ]	DNA Topoisomerase II Is Involved in Regulation of Cyst Wall Protein Genes and Differentiation in Giardia lamblia	journal.pntd.0002218	null	[ [ "Giardia lamblia is an intestinal protozoan parasite causing outbreaks of infectious diarrheal diseases worldwide with an estimated 280 million cases of giardiasis yearly [1] , [2] , [3] .", "It has been isolated from various other animals that may act as reservoirs for human infection [4] .", "Giardi...	[ "The protozoan Giardia lamblia differentiates into infectious cysts within the human intestinal tract for disease transmission .", "Expression of the cyst wall protein ( cwp ) genes increases with similar kinetics during encystation .", "However , little is known how their gene regulation shares common mechanis...	[ "Giardia lamblia becomes infective by differentiation into water-resistant cysts .", "During encystation , cyst wall proteins ( CWPs ) are highly synthesized and are targeted to the cyst wall .", "However , little is known about the regulation mechanisms of these genes .", "DNA topoisomerases can resolve the ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "theoretical biology", "virology", "emerging viral diseases", "biology", "evolutionary biology", "microbiology", "host-pathogen interaction", "evolutionary genetics", "viral evolution" ]	Effect of Host Species on the Distribution of Mutational Fitness Effects for an RNA Virus	journal.pgen.1002378	null	[ [ "The emergence of new epidemic viruses is a critical issue for public health and economic welfare [1]–[7] .", "Virus emergence is a complex , multilevel problem that results from a combination of ecological and genetic factors [5]–[8] .", "The increasing threats imposed by emerging and re-emerging vir...	[ "Knowledge about the distribution of mutational fitness effects ( DMFE ) is essential for many evolutionary models .", "In recent years , the properties of the DMFE have been carefully described for some microorganisms .", "In most cases , however , this information has been obtained only for a single environme...	[ "Mutations are the raw material on which natural selection operates to optimize the fitness of populations .", "The occurrence of selection and its strength depend on the effect that mutations may have on the survival and reproduction of individuals: mutations can be lethal , deleterious , neutral , or beneficial...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/sensory systems", "neuroscience/motor systems" ]	A Cholinergic-Regulated Circuit Coordinates the Maintenance and Bi-Stable States of a Sensory-Motor Behavior during Caenorhabditis elegans Male Copulation	journal.pgen.1001326	null	[ [ "Male copulation is the most complex behavior for C . elegans [1] .", "The nervous system must integrate sensory cues from the hermaphrodite to generate instructions for each step of mating .", "In addition , the sex-specific mating circuits monitor the progress , and then determine whether to retain ...	[ "Penetration of a male copulatory organ into a suitable mate is a conserved and necessary behavioral step for most terrestrial matings; however , the detailed molecular and cellular mechanisms for this distinct social interaction have not been elucidated in any animal .", "During mating , the Caenorhabditis elega...	[ "Animal behaviors are generated when a sequence of muscle movements is coordinated by neural circuits .", "In complex invertebrates or lab-studied vertebrates , due to the large number of cells in their nervous systems and the complexities of their behaviors , it is difficult to address how circuits process infor...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "rna-binding proteins", "chemical characterization", "gene regulation", "messenger rna", "regulator genes", "micrornas", "post-transcriptional gene regulation", "gene types", "sequence motif analysis", "research and analysis methods", "sequence analysis", "bioinformatics", "proteins", "gen...	Highly accessible AU-rich regions in 3’ untranslated regions are hotspots for binding of regulatory factors	journal.pcbi.1005460	null	[ [ "Post-transcriptional regulation is the set of mechanisms and processes that control gene expression at the RNA level and affect the properties and the amount of RNA transcribed and translated into proteins .", "This regulation is performed mainly by RNA binding proteins ( RBPs ) and miRNAs , which primar...	[ "Post-transcriptional regulation is regarded as one of the major processes involved in the regulation of gene expression .", "It is mainly performed by RNA binding proteins and microRNAs , which target RNAs and typically affect their stability .", "Recent efforts from the scientific community have aimed at unde...	[ "All the cells in a given organism contain the same genome , yet their phenotype can be very diverse .", "The vast majority of this diversity arises from the differences in the expression of genes and proteins in them .", "One of the main mechanisms involved in controlling the protein and mRNA repertoire in cel...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "rna", "transposons", "retrotransposons", "dna replication", "nucleic acids", "genetics", "molecular genetics", "dna", "biology", "molecular cell biology", "rna stability" ]	Genetic and Biochemical Assays Reveal a Key Role for Replication Restart Proteins in Group II Intron Retrohoming	journal.pgen.1003469	null	[ [ "Mobile group II introns are non-long-terminal-repeat ( non-LTR ) retroelements that are commonly found in prokaryotes and in organellar genomes of eukaryotes and are thought to be evolutionary ancestors of splicesomal introns and retrotransposons in higher organisms [1] .", "They consist of an autocataly...	[ "Mobile group II introns retrohome by an RNP-based mechanism in which the intron RNA reverse splices into a DNA site and is reverse transcribed by the associated intron-encoded protein .", "The resulting intron cDNA is then integrated into the genome by cellular mechanisms that have remained unclear .", "Here ,...	[ "Mobile group II introns are bacterial retrotransposons that are evolutionarily related to introns and retroelements in higher organisms .", "They spread within and between genomes by a mechanism termed “retrohoming” in which the intron RNA inserts directly into a DNA site and is reverse transcribed by an intron-...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics", "haplotype", "cladistic analysis", "case control studies" ]	Incorporating Single-Locus Tests into Haplotype Cladistic Analysis in Case-Control Studies	journal.pgen.0030046	null	[ [ "Recent advances in biotechnology such as high-throughput single nucleotide polymorphism ( SNP ) genotyping have provided useful tools to improve our understanding of the genetic basis of human complex diseases .", "With these advances , an intense and comprehensive evaluation of candidate genes , linkage...	[ "In case-control studies , genetic associations for complex diseases may be probed either with single-locus tests or with haplotype-based tests .", "Although there are different views on the relative merits and preferences of the two test strategies , haplotype-based analyses are generally believed to be more pow...	[ "Methods of haplotype-based analysis and single-locus analysis are widely used in genetic association studies .", "There is no consensus as to the best strategy for the performance of the two methods .", "Although haplotype-based analysis is a powerful tool , the large number of distinct haplotypes may reduce i...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "nuclear staining", "pathology and laboratory medicine", "pathogens", "microbiology", "viral structure", "viruses", "dna replication", "dna viruses", "molecular biology techniques", "dna", "microbial genomics", "research and analysis methods", "cell labeling...	Localization of adenovirus morphogenesis players, together with visualization of assembly intermediates and failed products, favor a model where assembly and packaging occur concurrently at the periphery of the replication center	journal.ppat.1006320	null	[ [ "AdV virions consist of a 95 nm , icosahedral pseudoT = 25 protein shell enclosing a non-icosahedral DNA-protein core .", "Each capsid facet has 12 trimers of the major coat protein , hexon .", "A pentamer of penton base associated with a fiber trimer sits at each vertex .", "The most studied AdV ...	[ "Adenovirus ( AdV ) morphogenesis is a complex process , many aspects of which remain unclear .", "In particular , it is not settled where in the nucleus assembly and packaging occur , and whether these processes occur in a sequential or a concerted manner .", "Here we use immunofluorescence and immunoelectron ...	[ "Viruses assemble in particular locations inside infected cells where newly replicated genomes and capsids proteins meet , called viral factories .", "Virus genomes are packaged inside capsids by one of two mechanisms: concerted , where a protein shell is built around the genome , or sequential , where the genome...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	NK4 Antagonizes Tbx1/10 to Promote Cardiac versus Pharyngeal Muscle Fate in the Ascidian Second Heart Field	journal.pbio.1001725	Cross inhibition between NK4 and TBX1 transcription factors specifies heart versus pharyngeal muscle fates by promoting the activation of tissue-specific regulators in distinct precursors within the cardiopharyngeal lineage of the ascidian, Ciona intestinalis.	[ [ "The combined cardiac and craniofacial malformations observed in Cardio-Velo-Facial/Di George Syndrome patients arise from complex sets of defects in the development of the pharyngeal apparatus [1]–[4] .", "Developmental studies focused on amniote model systems have documented the ontogenetic proximity of...	[ "The heart and head muscles share common developmental origins and genetic underpinnings in vertebrates , including humans .", "Parts of the heart and cranio-facial musculature derive from common mesodermal progenitors that express NKX2-5 , ISL1 , and TBX1 .", "This ontogenetic kinship is dramatically reflected...	[ "Mutations in the regulatory genes encoding the transcription factors NKX2-5 and TBX1 , which govern heart and head muscle development , cause prevalent congenital defects .", "Recent studies using vertebrate models have shown that the heart and pharyngeal head muscle cells derive from common progenitors in the e...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biotechnology", "biochemistry", "cell biology", "physiology", "immunology" ]	Nanosensor Detection of an Immunoregulatory Tryptophan Influx/Kynurenine Efflux Cycle	journal.pbio.0050257	Genetically encoded FRET nanosensors were developed to measure cytosolic tryptophan steady-state levels and flux in real time.	[ [ "l-tryptophan is an essential amino acid necessary for protein synthesis in mammalian cells .", "Moreover , tryptophan is the precursor for the neurotransmitter serotonin , for the hormone melatonin , and contributes to the synthesis of the coenzymes NADH and NADPH .", "Degradation products of tryptop...	[ "Mammalian cells rely on cellular uptake of the essential amino acid tryptophan .", "Tryptophan sequestration by up-regulation of the key enzyme for tryptophan degradation , indoleamine 2 , 3-dioxygenase ( IDO ) , e . g . , in cancer and inflammation , is thought to suppress the immune response via T cell starvat...	[ "Although regulated suppression of the immune system prevents autoimmunity and is important during pregnancy to protect the fetus or after organ transplant to block graft rejection , it can be harmful if co-opted by tumors to escape detection .", "T cells of the immune system normally recognize and destroy abnorm...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mathematics", "biophysics/theory and simulation", "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Action Potential Energy Efficiency Varies Among Neuron Types in Vertebrates and Invertebrates	journal.pcbi.1000840	null	[ [ "Electrical signaling within neurons dominates the energy consumption of mammalian brains [1] , [2] and action potentials ( APs ) make a significant contribution to overall usage [1] .", "The energy consumption of APs is due to the influx of Na+ ions and efflux of K+ ions through voltage-gated ion channel...	[ "The initiation and propagation of action potentials ( APs ) places high demands on the energetic resources of neural tissue .", "Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients , thus consuming more energy .", "Here , we ask whether the ionic currents underlying ...	[ "Neurons produce a myriad of action potentials with different shapes and varying heights and widths; underlying these action potentials are highly nonlinear , voltage-dependent ionic conductances with varying biophysical properties .", "Each action potential comes at a cost: the brain uses a substantial portion o...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Mu Insertions Are Repaired by the Double-Strand Break Repair Pathway of Escherichia coli	journal.pgen.1002642	null	[ [ "Transposable elements drive genome evolution in many ways – increasing DNA content , rearranging and mutating genes , as well as altering gene regulation [1] .", "Temperate phage Mu has played a pivotal role in our current understanding of how movable elements move [2] .", "A unique aspect of Mu is t...	[ "Mu is both a transposable element and a temperate bacteriophage .", "During lytic growth , it amplifies its genome by replicative transposition .", "During infection , it integrates into the Escherichia coli chromosome through a mechanism not requiring extensive DNA replication .", "In the latter pathway , t...	[ "Transposon activity shapes genome structure and evolution .", "The movement of these elements generates target site duplications as a result of staggered cuts in the target made initially by the transposase .", "For replicative transposons , the single-stranded gaps generated after the initial strand transfer ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Cryptococcus neoformans Alkaline Response Pathway: Identification of a Novel Rim Pathway Activator	journal.pgen.1005159	null	[ [ "To survive the harsh environment of the infected host , microorganisms must be able to sense their external environment and adaptively alter their cellular processes .", "For example , microorganisms often encounter changes in extracellular pH when moving between different microenvironments .", "For ...	[ "The Rim101/PacC transcription factor acts in a fungal-specific signaling pathway responsible for sensing extracellular pH signals .", "First characterized in ascomycete fungi such as Aspergillus nidulans and Saccharomyces cerevisiae , the Rim/Pal pathway maintains conserved features among very distantly related ...	[ "Microorganisms that cause human disease use various cues to determine when they encounter a host .", "One of these signals is the slightly alkaline pH of human tissues .", "We have defined components of a pH-responsive signaling pathway in the human fungal pathogen Cryptococcus neoformans .", "This particula...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "mycobacterium leprae", "medicine and health sciences", "immune cells", "chemical compounds", "immunology", "tropical diseases", "organic compounds", "bacterial diseases", "neglected tropical diseases", "bacteria", "infectious diseases", "white blood cells", "animal cells", ...	Intrinsic activation of the vitamin D antimicrobial pathway by M. leprae infection is inhibited by type I IFN	journal.pntd.0006815	null	[ [ "The ability of macrophages ( MΦ ) to kill intracellular pathogens is critical to the outcome of infection .", "Addition of exogenous ligands derived from the pathogen such as a Toll-like receptor 2 ligand ( TLR2L ) or from human immune cells , such as IFN-γ , provides an extrinsic signal to activate a vi...	[ "Following infection , virulent mycobacteria persist and grow within the macrophage , suggesting that the intrinsic activation of an innate antimicrobial response is subverted by the intracellular pathogen .", "For Mycobacterium leprae , the intracellular bacterium that causes leprosy , the addition of exogenous ...	[ "Our macrophages are equipped with the ability to detect and kill invading pathogens , and yet , these cells of the innate immune system are still subject to infection by intracellular bacterium .", "In particular , mycobacterium , the type of intracellular bacteria responsible for diseases such as tuberculosis a...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "crystal structure", "pathology and laboratory medicine", "enzymes", "pathogens", "condensed matter physics", "microbiology", "enzymology", "staphylococcus aureus", "pseudomonas aeruginosa", "materials science", "protein structure", "crystallography", "oligo...	Inhibition of the Staphylococcus aureus c-di-AMP cyclase DacA by direct interaction with the phosphoglucosamine mutase GlmM	journal.ppat.1007537	null	[ [ "For pathogenic bacteria , the ability to rapidly adapt to the host cell environment or different host cell niches is essential for their infectivity .", "Nucleotide second-messenger molecules are critical components involved in such adaptive responses , allowing bacteria to simultaneously regulate multip...	[ "c-di-AMP is an important second messenger molecule that plays a pivotal role in regulating fundamental cellular processes , including osmotic and cell wall homeostasis in many Gram-positive organisms .", "In the opportunistic human pathogen Staphylococcus aureus , c-di-AMP is produced by the membrane-anchored Da...	[ "c-di-AMP has recently emerged as an essential molecule in Gram-positive bacteria , controlling osmotic stress resistance and virulence .", "The molecule has also been linked to antibiotic resistance/sensitivity , as alterations in its levels have been shown to modulate the effect of cell wall-targeting antibioti...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "evolutionary biology", "insects" ]	Transition-Transversion Bias Is Not Universal: A Counter Example from Grasshopper Pseudogenes	journal.pgen.0030022	null	[ [ "While evolutionary theory assumes that mutations are random with regard to their adaptive value , it has long been recognized that this does not necessarily imply randomness in other respects .", "For example , some nucleotides are more mutable than others [1] .", "For the time being , studies of mut...	[ "Comparisons of the DNA sequences of metazoa show an excess of transitional over transversional substitutions .", "Part of this bias is due to the relatively high rate of mutation of methylated cytosines to thymine .", "Postmutation processes also introduce a bias , particularly selection for codon-usage bias i...	[ "Some mutations occur more frequently than others .", "We need to understand these biases if we are to interpret the differences that have accumulated between species and individuals .", "Applications include estimating the time since evolutionary lineages diverged and detecting the signature of natural selecti...	2007
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine", "bacterial diseases", "infectious diseases", "oral medicine", "biology", "microbiology", "bacterial pathogens" ]	The Exopolysaccharide Matrix Modulates the Interaction between 3D Architecture and Virulence of a Mixed-Species Oral Biofilm	journal.ppat.1002623	null	[ [ "Virulent biofilms formed on surfaces are prime biological phenomena that are associated with many illnesses and infections in humans , including oral diseases , native valve endocarditis , and a number of nosocomial infections [1] .", "Human dental plaque is one of the most complex biofilm systems in nat...	[ "Virulent biofilms are responsible for a range of infections , including oral diseases .", "All biofilms harbor a microbial-derived extracellular-matrix .", "The exopolysaccharides ( EPS ) formed on tooth-pellicle and bacterial surfaces provide binding sites for microorganisms; eventually the accumulated EPS en...	[ "Virulent biofilms formed on surfaces are associated with many human infections .", "The disease dental caries , expressed as cavities , is a prime example of the consequences arising from interactions between bacteria and sugars on tooth-surfaces .", "When Streptococcus mutans metabolize sugars , they produce ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Protein Domain-Level Landscape of Cancer-Type-Specific Somatic Mutations	journal.pcbi.1004147	null	[ [ "Cancer is caused in large part by the accumulation of mutations in oncogenes and tumor suppressor genes .", "Previous analyses of well-studied cancers , such as colorectal cancer and retinoblastoma , have suggested that as few as three mutations are sufficient for cancer initiation [1–3] .", "Thousan...	[ "Identifying driver mutations and their functional consequences is critical to our understanding of cancer .", "Towards this goal , and because domains are the functional units of a protein , we explored the protein domain-level landscape of cancer-type-specific somatic mutations .", "Specifically , we systemat...	[ "Extensive tumor genome sequencing has provided raw material to understand mutational processes and identify cancer-associated somatic variants .", "However , fundamental problems remain to:", "i ) separate ‘driver’ from ‘passenger’ mutations ,", "ii ) further understand the functional mechanisms and conseque...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "evolutionary biology/microbial evolution and genomics", "genetics and genomics/functional genomics", "evolutionary biology/genomics", "evolutionary biology/bioinformatics" ]	Pervasive and Persistent Redundancy among Duplicated Genes in Yeast	journal.pgen.1000113	null	[ [ "Gene duplication is the primary source of new genes [1] and provides essential raw material for the evolution of functional novelty .", "Upon duplication , the two gene copies are generally assumed to be entirely redundant and either of the gene copies is thus susceptible to loss through inactivating mut...	[ "The loss of functional redundancy is the key process in the evolution of duplicated genes .", "Here we systematically assess the extent of functional redundancy among a large set of duplicated genes in Saccharomyces cerevisiae .", "We quantify growth rate in rich medium for a large number of S . cerevisiae str...	[ "Gene duplication is the primary source of new genes .", "To persist , duplicated genes must lose some of the original redundancy either by partitioning the ancestral function ( subfunctionalization ) or by gaining new non-redundant functions ( neofunctionalization ) .", "The extent to which these processes sha...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "dermatology", "infectious diseases", "immunology", "microbiology" ]	Proteolysis of Human Thrombin Generates Novel Host Defense Peptides	journal.ppat.1000857	null	[ [ "The innate immune system , largely based on antimicrobial peptides , provides a first line of defense against invading microbes [1] , [2] , [3] , [4] , [5] .", "During recent years it has become increasingly evident that many cationic and amphipathic antimicrobial peptides , such as defensins and catheli...	[ "The coagulation system is characterized by the sequential and highly localized activation of a series of serine proteases , culminating in the conversion of fibrinogen into fibrin , and formation of a fibrin clot .", "Here we show that C-terminal peptides of thrombin , a key enzyme in the coagulation cascade , c...	[ "Wounding of the skin and other epithelial barriers represents an ever-present challenge and poses a potential threat for invasive infection and sepsis .", "Therefore , it is not surprising that evolutionary pressure has maintained and developed multiple host defense systems , involving initial hemostasis and fib...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Asymmetric Nerve Enlargement: A Characteristic of Leprosy Neuropathy Demonstrated by Ultrasonography	journal.pntd.0004276	null	[ [ "Neurological involvement is present throughout the leprosy clinical spectrum , and nerve impairment is responsible for the most feared consequences of the disease; therefore , some authors advocate that leprosy should be regarded as a chronic neurological condition rather than a skin disease [1–5] .", "S...	[ "Neurological involvement occurs throughout the leprosy clinical spectrum and is responsible for the most feared consequences of the disease .", "Ultrasonography ( US ) provides objective measurements of nerve thickening and asymmetry .", "We examined leprosy patients before beginning multi-drug therapy aiming ...	[ "Leprosy is an infectious disease that affects the peripheral nerves , leading to nerve thickening , asymmetry and dysfunction; therefore , early detection of leprosy neuropathy is important for preventing deformities and disabilities .", "We examined peripheral nerve involvement using ultrasonography ( US ) in 9...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "blood cells", "cell physiology", "flow cytometry", "medicine and health sciences", "immune cells", "immunology", "epithelial cells", "granulocytes", "glycoproteins", "digestive system", "research and analysis methods", "specimen preparation and treatment", "staining", "w...	GM1 ganglioside-independent intoxication by Cholera toxin	journal.ppat.1006862	null	[ [ "The disease cholera is well known for the acute diarrhea that if left untreated can be lethal within hours .", "The World Health Organization ( WHO ) estimates that over 100 000 people die every year from cholera infection and children under five are the most susceptible .", "The vast majority of pat...	[ "Cholera toxin ( CT ) enters and intoxicates host cells after binding cell surface receptors via its B subunit ( CTB ) .", "We have recently shown that in addition to the previously described binding partner ganglioside GM1 , CTB binds to fucosylated proteins .", "Using flow cytometric analysis of primary human...	[ "The disease cholera , caused by cholera toxin produced by Vibrio cholerae , is responsible for over 100 000 deaths every year .", "When taken up by cells in the intestine , the toxin causes diarrhea , and the ganglioside GM1 ( a glycolipid ) has long been considered the main receptor for cholera toxin .", "We ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "veterinary epidemiology", "epidemiology", "public health", "veterinary science" ]	Global Burden of Human Brucellosis: A Systematic Review of Disease Frequency	journal.pntd.0001865	null	[ [ "Brucellosis is one of the most common zoonotic infections globally [1] , transmitted to humans through consumption of unpasteurised dairy products or through direct contact with infected animals , placentas or aborted foetuses .", "This bacterial disease causes a severely debilitating and disabling illne...	[ "This report presents a systematic review of scientific literature published between 1990–2010 relating to the frequency of human brucellosis , commissioned by WHO .", "The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and , ultimatel...	[ "Brucellosis is a bacterial disease transmitted to humans by consumption of infected , unpasteurised animal milk or through direct contact with infected animals , particularly aborted foetuses .", "The livestock production losses resulting from these abortions have a major economic impact on individuals and commu...	2012
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "population genetics", "vertebrates", "animals", "mammals", "simulation and modeling", "developmental biology", "morphometry", "molecular development", "population biology", "morphogenesis", "pattern formation", "research and analysis methods", "imaging techniques", "genetic polymorphism",...	Isolating and quantifying the role of developmental noise in generating phenotypic variation	journal.pcbi.1006943	null	[ [ "Vertebrates show a wide variety of integumentary colors and patterns both within and among species .", "Variation in vertebrate coloration represents a model to understand the link between genetic basis , developmental patterns , and phenotype ( e . g . , [12–15] ) .", "Furthermore , variation in col...	[ "Genotypic variation , environmental variation , and their interaction may produce variation in the developmental process and cause phenotypic differences among individuals .", "Developmental noise , which arises during development from stochasticity in cellular and molecular processes when genotype and environme...	[ "The observable characteristics of an organism make up its phenotype .", "Variation among phenotypes is due to genetic differences , environmental factors and developmental noise ( effects due to inherent stochasticity ) during development .", "We used mathematical models to investigate the contributions of var...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "mathematics", "computer science", "computational biology" ]	Probing the Extent of Randomness in Protein Interaction Networks	journal.pcbi.1000114	null	[ [ "Degree-weighted behavior , simply put , implies that the higher the degree of a node is the more likely it is to have an edge with any other node .", "Thus , the likelihood of an edge between two nodes is proportional to the product of their degrees , where the exact probability can be given by Pij = γ (...	[ "Protein–protein interaction ( PPI ) networks are commonly explored for the identification of distinctive biological traits , such as pathways , modules , and functional motifs .", "In this respect , understanding the underlying network structure is vital to assess the significance of any discovered features .", ...	[ "A protein–protein interaction network represents the set of pair-wise associations that have been discerned between the constituent proteins of an organism .", "There are three main types of such networks:", "( i ) those determined from a single high-throughput experiment;", "( ii ) curated , where interacti...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "embryology", "developmental biology", "biology and life sciences", "morphogenesis", "cell differentiation" ]	Fat-Dachsous Signaling Coordinates Cartilage Differentiation and Polarity during Craniofacial Development	journal.pgen.1004726	null	[ [ "What are the mechanisms of cell-cell communication that mediate organ morphogenesis ?", "Bones , for example , have many different sizes and shapes yet the individual and collective cell behaviors necessary to assemble these shapes remain largely unknown .", "During development , cartilage serves as ...	[ "Organogenesis requires coordinated regulation of cellular differentiation and morphogenesis .", "Cartilage cells in the vertebrate skeleton form polarized stacks , which drive the elongation and shaping of skeletal primordia .", "Here we show that an atypical cadherin , Fat3 , and its partner Dachsous-2 ( Dchs...	[ "Little is known about the mechanisms of cell-cell communication necessary to assemble skeletal elements of appropriate size and shape .", "In this study , we investigate the roles of genetic factors belonging to a developmental pathway that affects skeletal progenitor behavior: the atypical cadherins Fat3 and Da...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Secondary Structure across the Bacterial Transcriptome Reveals Versatile Roles in mRNA Regulation and Function	journal.pgen.1005613	null	[ [ "The primary role of mRNA in cellular physiology is to act as an informational molecule for translating ribosomes .", "Yet , emerging evidence places mRNA more centrally in regulating biogenesis of the encoded protein , including cotranslational folding and insertion and interactions with auxiliary factor...	[ "Messenger RNA acts as an informational molecule between DNA and translating ribosomes .", "Emerging evidence places mRNA in central cellular processes beyond its major function as informational entity .", "Although individual examples show that specific structural features of mRNA regulate translation and tran...	[ "Messenger RNA ( mRNA ) is intrinsically prone to form higher order structures which is optimized for mRNA stability in the cell .", "We took advantage of recent developments in high throughput sequencing technologies and coupled them with RNA structure-probing approaches to provide a high resolution view of the ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome-Wide Analysis of PAPS1-Dependent Polyadenylation Identifies Novel Roles for Functionally Specialized Poly(A) Polymerases in Arabidopsis thaliana	journal.pgen.1005474	null	[ [ "The poly ( A ) tail is an essential modification found at the 3’ ends of virtually all eukaryotic mRNAs [1 , 2 , 3] .", "After transcription of the pre-mRNA , sequences in the 3’ UTR recruit two protein complexes , Cleavage and Polyadenylation Specificity Factor ( CPSF ) and Cleavage Stimulation Factor (...	[ "The poly ( A ) tail at 3’ ends of eukaryotic mRNAs promotes their nuclear export , stability and translational efficiency , and changes in its length can strongly impact gene expression .", "The Arabidopsis thaliana genome encodes three canonical nuclear poly ( A ) polymerases , PAPS1 , PAPS2 and PAPS4 .", "As...	[ "The poly ( A ) tail of eukaryotic mRNAs promotes export from the nucleus , translation in the cytoplasm and stability of the mRNA , and changes in poly ( A ) -tail length can strongly impact on gene expression .", "The Arabidopsis thaliana genome encodes three nuclear canonical poly ( A ) polymerases ( PAPS1 , P...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "microbiology", "evolutionary biology" ]	Genetic Pathway in Acquisition and Loss of Vancomycin Resistance in a Methicillin Resistant Staphylococcus aureus (MRSA) Strain of Clonal Type USA300	journal.ppat.1002505	null	[ [ "The extensive use of antibiotics in the clinical environment has led to the appearance of a wide variety of drug resistance mechanisms among all bacterial pathogens , including S . aureus .", "While most of these resistance mechanisms are associated with the acquisition of “foreign” genetic elements – ot...	[ "An isolate of the methicillin-resistant Staphylococcus aureus ( MRSA ) clone USA300 with reduced susceptibility to vancomycin ( SG-R ) ( i . e , vancomycin-intermediate S . aureus , VISA ) and its susceptible “parental” strain ( SG-S ) were recovered from a patient at the end and at the beginning of an unsuccessfu...	[ "The extensive use of antibiotics has led to the selection of methicillin-resistant S . aureus ( MRSA ) strains that are resistant to most antimicrobial agents and a treatment of choice against such strains is vancomycin .", "However , during the last decade reports of treatment failure with vancomycin non-suscep...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational neuroscience", "single neuron function", "sensory systems", "biology", "neuroscience" ]	Characteristic Effects of Stochastic Oscillatory Forcing on Neural Firing: Analytical Theory and Comparison to Paddlefish Electroreceptor Data	journal.pcbi.1003170	null	[ [ "Oscillatory activity is common in neural systems .", "Mechanical oscillations form an important class of sensory stimuli , for instance , in hearing , but may also be generated autonomously by mechanosensory hair cells [1] .", "In single neurons , periodicities may occur in the form of subthreshold m...	[ "Stochastic signals with pronounced oscillatory components are frequently encountered in neural systems .", "Input currents to a neuron in the form of stochastic oscillations could be of exogenous origin , e . g . sensory input or synaptic input from a network rhythm .", "They shape spike firing statistics in a...	[ "We explore how a neuron responds to a special type of input signal which is oscillatory but noisy ( narrow-band noise ) .", "These fluctuations could be due to sensory input , due to oscillatory activity of a surrounding network , or due to a natural stimulus .", "We study theoretically the effects of noisy os...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Peridomestic Infection as a Determining Factor of Dengue Transmission	journal.pntd.0004296	null	[ [ "Dengue is the most important vector-borne viral disease in the world due to its morbidity and economic impact [1] .", "Because there are no vaccines available to date , the interruption of dengue transmission is based on the vector control .", "However , despite control programs in endemic countries ...	[ "The study of endemic dengue transmission is essential for proposing alternatives to impact its burden .", "The traditional paradigm establishes that transmission starts around cases , but there are few studies that determine the risk .", "To assess the association between the peridomestic dengue infection and ...	[ "The study of dengue transmission is essential for proposing alternatives to diminish the cases and the cost of dengue treatment and control .", "The traditional paradigm establishes that transmission chain starts around a case , but there are few studies that determine the risk , therefore , we studied if to liv...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "auditory cortex", "acoustics", "medicine and health sciences", "linguistics", "brain", "vertebrates", "social sciences", "neuroscience", "animals", "mammals", "primates", "computational neuroscience", "old world monkeys", "research and analysis methods", "sequence analysis", "sensory ...	Sequence learning modulates neural responses and oscillatory coupling in human and monkey auditory cortex	journal.pbio.2000219	null	[ [ "Natural environments are dynamic and constantly changing , yet certain sensory events can predict the occurrence of others .", "For any animal to adapt and survive in its environment requires that its brain establish and monitor the predictability of ordering relationships between sensory events , a proc...	[ "Learning complex ordering relationships between sensory events in a sequence is fundamental for animal perception and human communication .", "While it is known that rhythmic sensory events can entrain brain oscillations at different frequencies , how learning and prior experience with sequencing relationships a...	[ "While natural environments constantly change , certain events can predict the future occurrence of others .", "Learning ordering relationships is vital for animal perception and human communication , yet how such learning and prior experience affect the brain remains poorly understood .", "We set out to unders...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders", "mus (mouse)", "radiology and medical imaging", "neuroscience", "hematology", "cardiovascular disorders" ]	Imaging the Impact of Cortical Microcirculation on Synaptic Structure and Sensory-Evoked Hemodynamic Responses In Vivo	journal.pbio.0050119	High-resolution structural and functional imaging of the effects of targeted strokes on individual synapses in somatosensory cortex reveals that blood flow from surrounding intact tissue can aid in the immediate post-stroke recovery.	[ [ "Previous magnetic resonance imaging and histological studies have provided valuable information on the histopathology and the development of ischemic brain damage [1–4] .", "Based on insight from these macroscopic imaging approaches , therapeutic strategies for stroke involve not saving the ischemic core...	[ "In vivo two-photon microscopy was used to image in real time dendrites and their spines in a mouse photothrombotic stroke model that reduced somatosensory cortex blood flow in discrete regions of cortical functional maps .", "This approach allowed us to define relationships between blood flow , cortical structur...	[ "The brain is critically dependent on an adequate supply of energy as it consumes up to 20% of the oxygen we breathe .", "Here we determine the distance scale over which interruptions in blood flow affect synaptic hard wiring and brain function .", "High-resolution microscopy of live mice was used to image cere...	2007
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "infectious diseases/neglected tropical diseases" ]	Protease Activated Receptor Signaling Is Required for African Trypanosome Traversal of Human Brain Microvascular Endothelial Cells	journal.pntd.0000479	null	[ [ "Human African trypanosomiasis ( HAT ) , commonly called sleeping sickness , is a vector-borne disease for which death is inevitable if the patient is untreated [1] , [2] , [3] .", "HAT is caused by two subspecies of African trypanosomes , Trypanosoma brucei rhodesiense and T . b .", "gambiense causin...	[ "Using human brain microvascular endothelial cells ( HBMECs ) as an in vitro model for how African trypanosomes cross the human blood-brain barrier ( BBB ) we recently reported that the parasites cross the BBB by generating calcium activation signals in HBMECs through the activity of parasite cysteine proteases , p...	[ "Human African trypanosomiasis , or sleeping sickness , occurs when single-cell trypanosome protozoan parasites spread from the blood to brain over the blood-brain barrier ( BBB ) .", "This barrier is composed of brain microvascular endothelial cells ( BMECs ) especially designed to keep pathogens out .", "Safe...	2009
[ "Introduction", "Results", "Discussion", "Methods", "Data access" ]	[ "blood cells", "t helper cells", "medicine and health sciences", "immune cells", "gene regulation", "immunology", "cell differentiation", "optimization", "developmental biology", "regulator genes", "mathematics", "genome analysis", "gene types", "small interfering rnas", "white blood cel...	LASSIM—A network inference toolbox for genome-wide mechanistic modeling	journal.pcbi.1005608	null	[ [ "The ‘omics’ era of molecular biology has generated enormous amounts of potentially informative molecular data .", "However , without new methods for data analysis , this tends to drown researchers in data , rather than provide clear and useful insights .", "Such methods are considered within systems ...	[ "Recent technological advancements have made time-resolved , quantitative , multi-omics data available for many model systems , which could be integrated for systems pharmacokinetic use .", "Here , we present large-scale simulation modeling ( LASSIM ) , which is a novel mathematical tool for performing large-scal...	[ "There are excellent methods to mathematically model time-resolved biological data on a small scale using accurate mechanistic models .", "Despite the rapidly increasing availability of such data , mechanistic models have not been applied on a genome-wide level due to excessive runtimes and the non-identifiabilit...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "vaccines", "public and occupational health", "preventive medicine", "population metrics", "infectious diseases", "medicine and health sciences", "cholera vaccines", "immunity", "epidemiology", "disease dynamics", "biology and life sciences", "immunology", "population biology", "vaccinatio...	Logistical constraints lead to an intermediate optimum in outbreak response vaccination	journal.pcbi.1006161	null	[ [ "In applied epidemiology , models are increasingly used to inform management decisions on effective responses to a variety of outbreaking diseases , e . g . cholera [1] , smallpox [2] , influenza [3] , Ebola [4] , measles [5] , and Zika fever [6] .", "In general , these epidemic dynamic models are designe...	[ "Dynamic models in disease ecology have historically evaluated vaccination strategies under the assumption that they are implemented homogeneously in space and time .", "However , this approach fails to formally account for operational and logistical constraints inherent in the distribution of vaccination to the ...	[ "It has long been recognized that an epidemic of infectious disease can be prevented if a sufficient proportion of the susceptible population is vaccinated in advance .", "This logic also holds for vaccine-based outbreak response to stop an outbreak of a novel , or re-emerging pathogen , but with an important cav...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "classical mechanics", "fluid mechanics", "population genetics", "social sciences", "neuroscience", "isomerism", "developmental biology", "mutation", "population biology", "embryos", "cellular structures and organelles", "embryology", "chemistry", "fluid dynamics", "continuum mechanics",...	Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination	journal.pgen.1006070	null	[ [ "The internal organs and vasculature of vertebrates are highly asymmetrical between left and right .", "For example , the heart and stomach become positioned towards the left side while the lungs undergo asymmetric branching , giving rise to different numbers of lobes on the left and right sides .", "...	[ "During mammalian development , left-right ( L-R ) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node .", "This ‘nodal flow’ is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD...	[ "Vertebrates exhibit left-right ( L-R ) asymmetry in positioning and patterning their internal organs and associated vasculature; abnormal L-R asymmetry can result in birth defects such as congenital heart disease .", "The earliest known event in mammalian L-R patterning is a leftward fluid flow across a transien...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "taxonomy", "parasite groups", "medicine and health sciences", "plasmodium", "tropical diseases", "geographical locations", "vertebrates", "india", "parasitic diseases", "parasitic protozoans", "animals", "mammals", "parasitology", "primates", "apicomplexa", "phylogenetics", "data ma...	Reinvestigating the status of malaria parasite (Plasmodium sp.) in Indian non-human primates	journal.pntd.0006801	null	[ [ "In the last two decades much work has been done to understand the evolutionary origin of human malarial parasite .", "Molecular phylogeny of Plasmodium infecting primates suggests that the principal malaria causing pathogens in humans ( P . falciparum , P . vivax , P . malariae , and P . ovale ) are rela...	[ "Many human parasites and pathogens have closely related counterparts among non-human primates .", "For example , non-human primates harbour several species of malaria causing parasites of the genus Plasmodium .", "Studies suggest that for a better understanding of the origin and evolution of human malaria para...	[ "Non-human primates are our closest relatives and with them we share many of our disease-causing pathogens .", "Malaria is one such example where the parasite ( Plasmodium ) causing malaria in humans has originated from non-human primate populations .", "To understand origin and evolution of human malaria paras...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology", "cell biology", "molecular biology", "drosophila", "genetics and genomics" ]	Drosophila brca2 Is Required for Mitotic and Meiotic DNA Repair and Efficient Activation of the Meiotic Recombination Checkpoint	journal.pgen.0040031	null	[ [ "The genomic stability of eukaryotic cells is constantly challenged by exogenous and endogenous stresses that can lead to the loss or alteration of genetic material .", "Genomic stability is maintained through robust DNA repair and checkpoint pathways that are tightly coordinated with each other and the d...	[ "Heterozygous mutations in the tumor suppressor BRCA2 confer a high risk of breast and other cancers in humans .", "BRCA2 maintains genome stability in part through the regulation of Rad51-dependent homologous recombination .", "Much about its precise function in the DNA damage responses is , however , not yet ...	[ "Breast cancer can arise due to inherited mutations in a few well-defined breast cancer susceptibility genes .", "BRCA2 is one of two known human genes in which common mutations are associated with high breast cancer risk .", "A known function of BRCA2 is the repair of damaged DNA using the homologous recombina...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/cellular microbiology and pathogenesis" ]	Helicobacter pylori Usurps Cell Polarity to Turn the Cell Surface into a Replicative Niche	journal.ppat.1000407	null	[ [ "In order to cause infection bacteria have to colonize a specialized niche within the host .", "This implies adaptations that allow bacteria to reach , extract nutrients from , and replicate within particular anatomical and physiological environments in the host .", "Bacteria that colonize mucosal sur...	[ "Helicobacter pylori ( Hp ) intimately interacts with the gastric epithelial surface and translocates the virulence factor CagA into host cells in a contact-dependent manner .", "To study how Hp benefits from interacting with the cell surface , we developed live-cell microscopy methods to follow the fate of indiv...	[ "Helicobacter pylori ( Hp ) is a bacterium that chronically infects the human stomach , in some cases leading to diseases such as stomach cancer and ulcers .", "The bacteria live in close proximity to the epithelial lining and can adhere directly to the host cell membrane and deliver toxins .", "We utilized liv...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "oncology", "medicine", "infectious diseases", "basic cancer research", "virology", "oncology agents", "biology", "microbiology", "host-pathogen interaction", "viral diseases" ]	Hsp90 Inhibitors Are Efficacious against Kaposi Sarcoma by Enhancing the Degradation of the Essential Viral Gene LANA, of the Viral Co-Receptor EphA2 as well as Other Client Proteins	journal.ppat.1003048	null	[ [ "Heat shock protein 90 ( Hsp90 ) is a conserved molecular chaperone that facilitates the maturation of a wide range of proteins and assists in the correct folding and productive assembly of cellular proteins and multimeric protein complexes in normally growing cells [1] , [2] .", "Hsp90 also has important...	[ "Heat-shock protein 90 ( Hsp90 ) inhibitors exhibit activity against human cancers .", "We evaluated a series of new , oral bioavailable , chemically diverse Hsp90 inhibitors ( PU-H71 , AUY922 , BIIB021 , NVP-BEP800 ) against Kaposi sarcoma ( KS ) .", "All Hsp90 inhibitors exhibited nanomolar EC50 in culture an...	[ "Heat shock proteins , such as Hsp90 , aid the folding of proteins .", "They seem to be essential to sustain the growth of cancer cells .", "Hsp90 inhibitors are in clinical trials for many cancers but with mixed results , presumably since these proteins have many clients .", "The mechanism for drug efficacy ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna interference", "viral transmission and infection", "immunology", "microbiology", "host-pathogen interaction", "viral vectors", "biology", "pathogenesis", "molecular biology", "immune response", "biochemistry", "rna", "mosquitoes", "nucleic acids", "vector biology", "virology", "...	Production of Virus-Derived Ping-Pong-Dependent piRNA-like Small RNAs in the Mosquito Soma	journal.ppat.1002470	null	[ [ "In plants and invertebrate animals the double stranded RNA ( dsRNA ) formed during the replication of RNA viruses is a potent inducer of an antiviral immune response directed by short interfering RNAs ( siRNAs ) [1] .", "In flies , exogenous dsRNA is processed by an RNase III enzyme , Dicer 2 ( Dcr-2 ) [...	[ "The natural maintenance cycles of many mosquito-borne pathogens require establishment of persistent non-lethal infections in the invertebrate host .", "The mechanism by which this occurs is not well understood , but we have previously shown that an antiviral response directed by small interfering RNAs ( siRNAs )...	[ "Mosquitoes defend themselves against viral infection with an innate immune response .", "Thus , mosquito-borne viral diseases like West Nile fever , dengue fever , and chikungunya fever are transmitted to humans only when the pathogen overcomes these defenses .", "Despite this , relatively little is known abou...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "cardiovascular anatomy", "biological cultures", "collagens", "animal models", "model organisms", "experimental organism systems", "cell cultures", "cellular structures and organelles", "elastin", "research and analysis methods", "specimen preparation and treatm...	Roles of fibronectin isoforms in neonatal vascular development and matrix integrity	journal.pbio.2004812	null	[ [ "Fibronectin ( FN ) is an abundant and ubiquitously expressed protein in the extracellular matrix ( ECM ) of various connective tissues as well as in blood of vertebrates [1 , 2] .", "Even though coded by a single gene [3] , it exists in multiple isoforms as a result of alternate splicing [4] .", "Eac...	[ "Fibronectin ( FN ) exists in two forms—plasma FN ( pFN ) and cellular FN ( cFN ) .", "Although the role of FN in embryonic blood vessel development is well established , its function and the contribution of individual isoforms in early postnatal vascular development are poorly understood .", "Here , we employe...	[ "Fibronectin is a protein that exists in vertebrates in two distinct forms: one present in the blood and the other in blood vessel walls .", "In mammals , fibronectin is important for the development of blood vessels before birth , but whether it is continuously required for blood vessel homeostasis from birth to...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "nervous system", "population genetics", "vertebrates", "neuroscience", "animals", "gene pool", "motor neurons", "animal models", "osteichthyes", "developmental biology", "model organisms", "experimental organism systems", "nerve fibers", "mitochondria", ...	Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy	journal.pgen.1006744	null	[ [ "Spinal Muscular Atrophy ( SMA ) is an autosomal recessive childhood neuromuscular disorder .", "The disease is characterized by muscle weakness and paralysis , resulting from early neuromuscular junction ( NMJ ) breakdown occurring prior to a widespread loss of lower motor neurons ( MN ) from the ventral...	[ "Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy ( SMA ) , resulting from low levels of ubiquitously-expressed survival motor neuron ( SMN ) protein .", "One remarkable , yet unresolved , feature of SMA is that not all motor neurons are equally affected ,...	[ "Selective vulnerability of particular cell types is a prominent , unresolved feature of many neurodegenerative diseases .", "In SMA , motor neurons are the most affected cell type , but not all motor neuron pools are affected at the same rate .", "Some pools degenerate early in disease and others remain resist...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "cell physiology", "enzymes", "cell cycle and cell division", "cell processes", "enzymology", "phosphatases", "biochemical analysis", "mitosis", "in vitro kinase assay", "enzyme assays", "immunoprecipitation", "bioassays and physiological analysis", "research and analysi...	Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint	journal.pgen.1006310	null	[ [ "The activity of Cdk1/cyclin B is essential for cells to enter and complete mitosis .", "As recently shown in Xenopus and Drosophila , the phosphatase activity that dephosphorylates Cdk1 substrates is inhibited simultaneously with the peak of Cdk1 activity when cells enter mitosis to ensure maximal phosph...	[ "The Greatwall kinase/Mastl is an essential gene that indirectly inhibits the phosphatase activity toward mitotic Cdk1 substrates .", "Here we show that although Mastl knockout ( MastlNULL ) MEFs enter mitosis , they progress through mitosis without completing cytokinesis despite the presence of misaligned chromo...	[ "Cdk1 phosphorylates many substrates in mitosis and simultaneoulsy reduces the activity of the corresponding phosphatase PP2A through the Greatwall kinase/Mastl .", "When Mastl is deleted , cells progress through mitosis with missegregated chromosomes , which become unraveled .", "However , the molecular mechan...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Localized DNA Demethylation at Recombination Intermediates during Immunoglobulin Heavy Chain Gene Assembly	journal.pbio.1001475	The dynamics of DNA methylation during the complex genomic rearrangement of antigen receptor genes in developing B lymphocytes reveal localized demethylation of the first recombination product that may serve as a mark necessary for the second step of rearrangement.	[ [ "Tissue-specific gene expression requires multiple epigenetic changes .", "These include nuclear location , chromatin remodeling , covalent histone modifications , and DNA methylation [1]–[4] .", "Recent genome-wide analyses reveal several important correlations between gene activity and epigenetic mo...	[ "Multiple epigenetic marks have been proposed to contribute to the regulation of antigen receptor gene assembly via V ( D ) J recombination .", "Here we provide a comprehensive view of DNA methylation at the immunoglobulin heavy chain ( IgH ) gene locus prior to and during V ( D ) J recombination .", "DNA methy...	[ "DNA methylation at CpG dinucleotides is implicated in the regulation of gene expression in mammals .", "However , the regulation of DNA methylation itself is less clear despite recent advances in identifying enzymes that add or remove methyl groups .", "We have investigated the dynamics of DNA methylation duri...	2013
[ "Introduction", "Discussion", "Materials and Methods" ]	[ "protein interactions", "engineering and technology", "rna analysis", "experimental design", "research design", "industrial engineering", "quality control", "bioassays and physiological analysis", "molecular biology techniques", "research and analysis methods", "specimen preparation and treatmen...	AuPairWise: A Method to Estimate RNA-Seq Replicability through Co-expression	journal.pcbi.1004868	null	[ [ "Recent analyses of RNA-seq have emphasized the value added by experimental designs with more samples , permitting better estimation of biological and technical variability [1–4] .", "Unfortunately , this does not automatically translate into an experimental design decision for more replicates ( biologica...	[ "In addition to detecting novel transcripts and higher dynamic range , a principal claim for RNA-sequencing has been greater replicability , typically measured in sample-sample correlations of gene expression levels .", "Through a re-analysis of ENCODE data , we show that replicability of transcript abundances wi...	[ "RNA-sequencing has become a popular means to detect the expression levels of genes .", "However , quality control is still challenging , requiring both extreme measures and rules which are set in stone from extensive previous analysis .", "Instead of relying on these rules , we show that co-expression can be u...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "chromosome 5", "medicine and health sciences", "body fluids", "alleles", "animal models", "model organisms", "research and analysis methods", "epilepsy", "chromosome biology", "mouse models", "chromosome pairs", "blood plasma", "genetic loci", "hematology", "blood", "anatomy", "cell...	Fine Mapping of a Dravet Syndrome Modifier Locus on Mouse Chromosome 5 and Candidate Gene Analysis by RNA-Seq	journal.pgen.1006398	null	[ [ "Epilepsy is one of the most common neurological disorders , affecting approximately 50 million people worldwide .", "Approximately two-thirds of human epilepsies are presumed to have a genetic basis .", "Voltage-gated sodium channel gene mutations are the most common cause of monogenic epilepsy .", ...	[ "A substantial number of mutations have been identified in voltage-gated sodium channel genes that result in various forms of human epilepsy .", "SCN1A mutations result in a spectrum of severity ranging from mild febrile seizures to Dravet syndrome , an infant-onset epileptic encephalopathy .", "Dravet syndrome...	[ "Epilepsy is a neurological disorder affecting approximately 3 million Americans and 1% of the worldwide population .", "Approximately 70% of patients diagnosed with epilepsy have a genetic basis for their disease .", "The same genetic mutation can result in epilepsy with varying clinical severity in some indiv...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Immune Adaptor ADAP Regulates Reciprocal TGF-β1-Integrin Crosstalk to Protect from Influenza Virus Infection	journal.ppat.1004824	null	[ [ "H5N1 influenza viruses are highly pathogenic avian influenza ( HPAI ) virus , which also infect humans and cause fatal human respiratory diseases [1 , 2] .", "Numerous animal or clinical studies have indicated that virus-induced cytokine dysregulation is one central reason for H5N1 pathogenesis and disea...	[ "Highly pathogenic avian influenza virus ( HPAI , such as H5N1 ) infection causes severe cytokine storm and fatal respiratory immunopathogenesis in human and animal .", "Although TGF-β1 and the integrin CD103 in CD8+ T cells play protective roles in H5N1 virus infection , it is not fully understood which key sign...	[ "Infection of avian influenza virus , especially the highly pathogenic strain H5N1 , is a serious threat to public health worldwide , which causes severe fatal respiratory disease and excessive levels of inflammation .", "It has been reported that both transforming growth factor-beta 1 ( TGF-β1 ) and the integrin...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "invertebrates", "meiosis", "medicine and health sciences", "reproductive system", "nuclear staining", "pathology and laboratory medicine", "cell cycle and cell division", "cell processes", "animals", "spermatogonia", "reproductive physiology", "animal models", "germ cells", ...	p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis	journal.pgen.1007024	null	[ [ "Cell death can occur as part of a physiological program; for example , during development and tissue homeostasis , and can also be induced in pathologies when adaptive cellular responses to adversity fail .", "Necrosis has long been considered an accidental process , but it has become increasingly clear ...	[ "The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized .", "However , the physiological relevance of regulated necrosis remains unclear .", "Here , we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian sperma...	[ "Cell death allows elimination of supernumerary cells during development or of abnormal cells throughout life .", "Physiological cell death is tightly regulated to prevent pathologies such as degenerative diseases or cancers , which often occur due to excessive or absent cell death , respectively .", "Understan...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Dynamically Allocated Hub in Task-Evoked Network Predicts the Vulnerable Prefrontal Locus for Contextual Memory Retrieval in Macaques	journal.pbio.1002177	Patterns of whole-brain activity while macaques perform a memory retrieval task show that the task-specific functional hub in the dynamic cortical network predicts the task-specific consequences of brain damage better than a task-invariant structural hub does.	[ [ "The prefrontal cortex ( PFC ) supports cognitive control of memory [1–6] .", "As shown using functional neuroimaging in humans , multiple PFC areas are activated in response to memory demands [4 , 6] .", "However , patients with typically broad cortical damage that includes a portion of these areas d...	[ "Neuroimaging and neurophysiology have revealed that multiple areas in the prefrontal cortex ( PFC ) are activated in a specific memory task , but severity of impairment after PFC lesions is largely different depending on which activated area is damaged .", "The critical relationship between lesion sites and impa...	[ "Patients with lesions in the front part of the brain’s frontal lobe—the prefrontal cortex—suffer from severe memory deficits .", "Neuroimaging and neurophysiology studies have revealed that multiple areas in the prefrontal cortex are activated during a specific memory task .", "However , the severity of the me...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "ecology and environmental sciences", "medicine and health sciences", "surface water", "pathology and laboratory medicine", "vertebrates", "parasitic diseases", "animals", "freshwater fish", "gastropods", "aquatic environments", "fresh water", "bodies of water", "snails", ...	Seasonal and Spatial Environmental Influence on Opisthorchis viverrini Intermediate Hosts, Abundance, and Distribution: Insights on Transmission Dynamics and Sustainable Control	journal.pntd.0005121	null	[ [ "Opisthorchis viverrini ( Ov ) , the Southeast Asian liver fluke , is a fish-borne complex life cycle trematode endemic in Thailand , Lao PDR , Cambodia and southern parts of Vietnam where an under-estimate of 10 million people are reported to be at risk of Ov infection [1 , 2] .", "While most infections ...	[ "Opisthorchis viverrini ( Ov ) is a complex-life-cycle trematode affecting 10 million people in SEA ( Southeast Asia ) .", "Human infection occurs when infected cyprinid fish are consumed raw or undercooked .", "Ov requires three hosts and presents two free-living parasitic stages .", "As a consequence Ov tra...	[ "Opisthorchis viverrini ( Ov ) is a fish-borne parasite infecting humans when they consume raw or undercooked fish .", "Ov is endemic in Southeast Asia , particularly in rural parts of Northeast Thailand , Lao PDR , Cambodia and Vietnam .", "The Ov lifecycle includes three different hosts: snails , fish and hum...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "water resources", "surface water", "pathology and laboratory medicine", "rivers", "atmospheric science", "geographical locations", "health care", "diarrhea", "seasons", "signs and symptoms", "aquatic environments", "gas...	Hydrological Regime and Water Shortage as Drivers of the Seasonal Incidence of Diarrheal Diseases in a Tropical Montane Environment	journal.pntd.0005195	null	[ [ "The global burden of diarrhea is a leading cause of morbidity and mortality worldwide .", "Acute diarrhea , which is defined as 3 or more loose watery stools within a 24-hour period [1] , threatens the linear growth of children [2] , increases school absenteeism and contributes to loss of productivity [3...	[ "The global burden of diarrhea is a leading cause of morbidity and mortality worldwide .", "In montane areas of South-East Asia such as northern Laos , recent changes in land use have induced increased runoff , soil erosion and in-stream suspended sediment loads , and potential pathogen dissemination .", "To ou...	[ "Aiming to identify the most critical drivers of diarrhea epidemics in montane areas of South-East Asia , we conducted a retrospective time series analysis of diarrhea reported cases and of hydro-meteorological variables measured in two contrasted river basins in northern Laos , together with socio-behavioral pract...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "functional genomics", "fungal genomes", "quantitative trait loci", "fungal genetics", "population genetics", "alleles", "genome analysis", "trait locus analysis", "genetic interactions", "genetic loci", "signal transduction", "fungal genomics", "cell biology", "genetic screens", "gene r...	Genetic Mapping of MAPK-Mediated Complex Traits Across S. cerevisiae	journal.pgen.1004913	null	[ [ "Cellular survival is dependent on the ability to sense and respond to changing environmental conditions .", "Mitogen-activated protein kinase ( MAPK ) signaling cascades are ubiquitous in eukaryotic organisms and enable them to react to extracellular stimuli [1] .", "MAPK cascades are composed of thr...	[ "Signaling pathways enable cells to sense and respond to their environment .", "Many cellular signaling strategies are conserved from fungi to humans , yet their activity and phenotypic consequences can vary extensively among individuals within a species .", "A systematic assessment of the impact of naturally o...	[ "Wild yeast strains differ in phenotypes that are controlled by highly conserved signaling pathways .", "Yet it remains unknown how naturally occurring genetic variants influence signaling pathways in yeast .", "We have developed an approach to facilitate the mapping of genetic variants that underlie these phen...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics" ]	New Evidence Confirms That the Mitochondrial Bottleneck Is Generated without Reduction of Mitochondrial DNA Content in Early Primordial Germ Cells of Mice	journal.pgen.1000756	null	[ [ "Mammalian mitochondrial genome shows a 5 to 10 times greater mutation rate than the nuclear genome [1] , [2] .", "This elevated mutation rate coupled with clonal maternal transmission leads to the high mtDNA polymorphism in populations .", "However , despite the prevalence of genetic variance within ...	[ "In mammals , observations of rapid shifts in mitochondrial DNA ( mtDNA ) variants between generations have led to the creation of the bottleneck theory for the transmission of mtDNA .", "The bottleneck could be attributed to a marked decline of mtDNA content in germ cells giving rise to the next generation , to ...	[ "Mutations of mtDNA are responsible for many types of mitochondrial diseases in humans , including myopathy and neurological disorders .", "Females carrying a mixture of mutant and wild-type mtDNA variants transmit a variable amount of mutant mtDNA to each offspring .", "The proportion of mutated mtDNA inherite...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "action potentials", "medicine and health sciences", "membrane potential", "brain", "electrophysiology", "neuroscience", "materials science", "cerebellum", "neuronal dendrites", "research and analysis methods", "curve fitting", "mathematical functions", "animal cells", "cerebral cortex", ...	Inverse Stochastic Resonance in Cerebellar Purkinje Cells	journal.pcbi.1005000	null	[ [ "Understanding the way neurons integrate synaptic inputs and provide appropriate outputs are crucial steps in the process of understanding neural circuits and relating their function to the function of specific brain areas .", "The cerebellar circuit is believed to be involved in ongoing motor control and...	[ "Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures .", "They have complex internal dynamics , which allow them to fire spontaneously , display bistability , and also to be involved in network pheno...	[ "How neurons generate output spikes in response to various combinations of inputs is a central issue in contemporary neuroscience .", "Due to their large dendritic tree and complex intrinsic properties , cerebellar Purkinje cells are an important model system to study this input-output transformation .", "Here ...	2016
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "deletion mutation", "medicine and health sciences", "pathology and laboratory medicine", "chemical compounds", "pathogens", "vibrio", "tropical diseases", "microbiology", "geographical locations", "organic compounds", "north america", "bacterial diseases", "mutation", "vibrio cholerae", ...	Major Shift of Toxigenic V. cholerae O1 from Ogawa to Inaba Serotype Isolated from Clinical and Environmental Samples in Haiti	journal.pntd.0005045	null	[ [ "After being absent for 100 years , cholera was introduced into Haiti in October , 2010 by Nepalese Peace-Keeping troops providing assistance to Haiti following the 2010 earthquake [1] .", "The initial cholera epidemic was caused by a single clone of toxigenic V . cholerae O1 biotype El Tor , serotype Oga...	[ "In October of 2010 , an outbreak of cholera was confirmed in Haiti for the first time in more than a century .", "A single clone of toxigenic Vibrio cholerae O1 biotype El Tor serotype Ogawa strain was implicated as the cause .", "Five years after the onset of cholera , in October , 2015 , we have discovered a...	[ "For the first time in 100 years , in October 2010 , cholera caused by toxigenic strains of V . cholerae was introduced in Haiti .", "Conventional and genetic analysis revealed that a single clone of V . cholerae O1 biotype El Tor , serotype Ogawa strain was brought to Haiti by Nepalese Peace-Keeping troops .", ...	2016
[ "Introduction", "Methods", "Results", "Discussion", "Disclaimers" ]	[ "bacteriology", "antimicrobials", "taxonomy", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "drugs", "microbiology", "genomic databases", "data management", "antibiotics", "genome analysis", "pharmacology", "bacteria", "bacterial patho...	Identification of Gram negative non-fermentative bacteria: How hard can it be?	journal.pntd.0007729	null	[ [ "The non-fermentative Gram-negative bacteria are widely distributed in the environment and have become increasingly common isolates in the clinical laboratory .", "Being ubiquitous in nature , they are often disregarded as contaminants .", "Medically , their pathogenic potential has been proved beyond...	[ "The prevalence of bacteremia caused by Gram negative non-fermentative ( GNNF ) bacteria has been increasing globally over the past decade .", "Many studies have investigated their epidemiology but focus on the common GNNF including Pseudomonas aeruginosa and Acinetobacter baumannii .", "Knowledge of the uncomm...	[ "Infections caused by Gram negative non fermentative bacteria ( GNNF ) , other than the more commonly described Pseudomonas aeruginosa and Acinetobacter baumannii , constitute an emerging problem .", "They are not only isolated in nosocomial settings , mainly affecting immunocomprised hosts , but also are opportu...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases of the nervous system", "infectious diseases", "neurology", "neurodegenerative diseases", "prion diseases" ]	Defining the Conformational Features of Anchorless, Poorly Neuroinvasive Prions	journal.ppat.1003280	null	[ [ "Prions are pathogenic protein aggregates that cause progressive neurodegenerative disease in humans and animals [1] , [2] .", "Most infectious prions spread from peripheral entry sites into the central nervous system ( CNS ) , and can also spread from the CNS to extracerebral sites , such as muscle [3] ,...	[ "Infectious prions cause diverse clinical signs and form an extraordinary range of structures , from amorphous aggregates to fibrils .", "How the conformation of a prion dictates the disease phenotype remains unclear .", "Mice expressing GPI-anchorless or GPI-anchored prion protein exposed to the same infectiou...	[ "Prions cause fatal neurodegenerative disease in humans and animals and there is currently no treatment available .", "The cellular prion protein is normally tethered to the outer leaflet of the plasma membrane by a glycophosphatidyl inositol ( GPI ) anchor .", "A rare stop codon mutation in the PRNP gene leads...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/immunization" ]	BCG Revaccination Does Not Protect Against Leprosy in the Brazilian Amazon: A Cluster Randomised Trial	journal.pntd.0000167	null	[ [ "BCG vaccination is given routinely to neonates to prevent tuberculosis in Brazil and in most of the world .", "BCG also protects against leprosy , with estimates of protection ranging from 20% to 90% [1] , [2] .", "In Brazil , in addition to routine BCG vaccination at birth to prevent tuberculosis , ...	[ "Although BCG has been found to impart protection against leprosy in many populations , the utility of repeat or booster BCG vaccinations is still unclear .", "When a policy of giving a second BCG dose to school children in Brazil was introduced , a trial was conducted to assess its impact against tuberculosis , ...	[ "BCG is a vaccine developed and used to protect against tuberculosis , but it can also protect against leprosy .", "In Brazil , children receive BCG at birth , and since 1996 a trial has been conducted to find out if a second dose of BCG administered to schoolchildren gives additional protection against tuberculo...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine" ]	Impact of Aetiological Treatment on Conventional and Multiplex Serology in Chronic Chagas Disease	journal.pntd.0001314	null	[ [ "The chronic form of Chagas disease , now considered to be globalized is prevalent in Latin America as well as in countries where T . cruzi-infection is not endemic [1]–[3] .", "In Argentina , T . cruzi infection is diagnosed by the conventional serologic tests indirect immunofluorescence assay ( IFI ) , ...	[ "The main criterion for treatment effectiveness in Chagas Disease has been the seronegative conversion , achieved many years post-treatment .", "One of the main limitations in evaluating treatment for chronic Chagas disease is the lack of reliable tests to ensure parasite clearance and to examine the effects of t...	[ "The main criterion for treatment effectiveness in Chagas Disease has been the seronegative conversion of previously reactive serology , generally achieved many years post-treatment .", "The lack of reliable tests to ensure parasite clearance and to examine the effect of treatment is the main difficulty in evalua...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "action potentials", "dendritic structure", "nervous system", "membrane potential", "electrophysiology", "neuroscience", "ganglion cells", "neuronal dendrites", "animal cells", "biophysics", "physics", "cellular neuroscience", "cell biology", "anatomy", ...	Heterogeneous firing responses predict diverse couplings to presynaptic activity in mice layer V pyramidal neurons	journal.pcbi.1005452	null	[ [ "The specific activation of subpopulations within neocortical networks appears to be the core mechanism for the cortical representation of sensory features .", "The details of how such specific activations happen are therefore key questions in systems neuroscience .", "As a primary source for specific...	[ "In this study , we present a theoretical framework combining experimental characterizations and analytical calculus to capture the firing rate input-output properties of single neurons in the fluctuation-driven regime .", "Our framework consists of a two-step procedure to treat independently how the dendritic in...	[ "Neocortical processing of sensory input relies on the specific activation of subpopulations within the cortical network .", "Though specific circuitry is thought to be the primary mechanism underlying this functional principle , we explore here a putative complementary mechanism: whether diverse biophysical feat...	2017
[ "Introduction", "Results and Discussion", "Methods" ]	[]	Coarse-Grained Simulations of Topology-Dependent Mechanisms of Protein Unfolding and Translocation Mediated by ClpY ATPase Nanomachines	journal.pcbi.1004675	null	[ [ "Protein quality control mechanisms , which include folding assistance or degradation of abnormal proteins , are critical for maintaining cell viability and function and for preventing protein aggregation pathways that underlie neurodegenerative diseases .", "In bacteria and eukaryotic organelles , protei...	[ "Clp ATPases are powerful ring shaped nanomachines which participate in the degradation pathway of the protein quality control system , coupling the energy from ATP hydrolysis to threading substrate proteins ( SP ) through their narrow central pore .", "Repetitive cycles of sequential intra-ring ATP hydrolysis ev...	[ "Cell survival is critically dependent on tightly regulated protein quality control , which includes chaperone-mediated folding and degradation .", "In the degradation pathway , AAA+ nanomachines , such as bacterial Clp proteases , use ATP-driven mechanisms to mechanically unfold , translocate , and destroy exces...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology", "biology" ]	Bacteria-Induced Dscam Isoforms of the Crustacean, Pacifastacus leniusculus	journal.ppat.1002062	null	[ [ "The immunoglobulin super family ( IgSF ) is composed of proteins that contain at least one immunoglobulin domain [1] .", "Several members of IgSF are expressed on the cell surface and there serve as receptors for diverse ligands , and contribute to a variety of cellular activities [2] .", "In vertebr...	[ "The Down syndrome cell adhesion molecule , also known as Dscam , is a member of the immunoglobulin super family .", "Dscam plays an essential function in neuronal wiring and appears to be involved in innate immune reactions in insects .", "The deduced amino acid sequence of Dscam in the crustacean Pacifastacus...	[ "Invertebrate animals lack an adaptive immune system and have no antibodies .", "Vertebrate antibodies belong to the immunoglobulin super family of proteins , and one other member of this large family is the Down syndrome cell adhesion molecule or Dscam .", "Of specific interest is that Dscam proteins in invert...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunomodulation", "infectious diseases/protozoal infections" ]	Parasite-Dependent Expansion of TNF Receptor II–Positive Regulatory T Cells with Enhanced Suppressive Activity in Adults with Severe Malaria	journal.ppat.1000402	null	[ [ "Infection with Plasmodium falciparum causes over 1 million deaths each year and an effective malaria vaccine remains elusive .", "The cellular immune responses controlling parasite replication and disease severity in falciparum malaria are not fully understood .", "Natural Treg cells characterized by...	[ "Severe Plasmodium falciparum malaria is a major cause of global mortality , yet the immunological factors underlying progression to severe disease remain unclear .", "CD4+CD25+ regulatory T cells ( Treg cells ) are associated with impaired T cell control of Plasmodium spp infection .", "We investigated the rel...	[ "Malaria is a major global health problem responsible for more than 1 million deaths annually .", "Severity of malaria disease is associated with the inability of host immune cells to efficiently eliminate malaria parasites from the blood .", "Little is known about immune regulatory factors controlling the onse...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "centrosomes", "nuclear staining", "gene regulation", "cell cycle and cell division", "cell processes", "immunoprecipitation", "cellular structures and organelles", "research and analysis methods", "small interfering rnas", "specimen preparation and treatment", "staining", "proteins", "gene ...	USP9X counteracts differential ubiquitination of NPHP5 by MARCH7 and BBS11 to regulate ciliogenesis	journal.pgen.1006791	null	[ [ "Primary cilia , microtubule-based protrusions found on the surface of most eukaryotic cells , are derived from centrosomes and possess sensory function such as chemosensation and mechanosensation[1 , 2] .", "Formation of primary cilia is tightly regulated during the cell cycle: they assemble primarily du...	[ "Ciliogenesis is a fundamental biological process central to human health .", "Precisely how this process is coordinated with the cell cycle remains an open question .", "We report that nephrocystin-5 ( NPHP5/IQCB1 ) , a positive regulator of ciliogenesis , is a stable and low turnover protein subjected to cycl...	[ "Centrosomes are non-membrane bound organelles that modulate a variety of cellular processes including cell division and formation of hair-like protrusions called primary cilia .", "Primary cilia function as cellular antennae to sense a wide variety of signals important for growth , development and differentiatio...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody	journal.ppat.1003684	null	[ [ "Henipaviruses , Hendra virus ( HeV ) and Nipah virus ( NiV ) [1] , are recently emerged , highly pathogenic paramyxovirus zoonoses whose major reservoirs in nature are several species of pteropid fruit bats [2] , [3] .", "HeV causes lethal respiratory disease and encephalitis in horses and severe respira...	[ "The henipaviruses , represented by Hendra ( HeV ) and Nipah ( NiV ) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia , Southeast Asia , India and Bangladesh .", "The high morbidity and mortality rates associated with infectio...	[ "Since their initial emergence , henipaviruses have continued to cause spillover events in both human and livestock populations , posing significant biothreats .", "Currently there are no licensed or approved therapies for treatment of henipavirus infection and the human case mortality rates average >70% .", "W...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal genetics", "biochemical analysis", "in vitro kinase assay", "enzyme assays", "mitochondria", "molecular genetics", "bioenergetics", "bioassays and physiological analysis", "cellular structures and organelles", "mitochondrial membrane", "protein kinase signaling cascade", "research and ...	Phosphorylation of Mitochondrial Polyubiquitin by PINK1 Promotes Parkin Mitochondrial Tethering	journal.pgen.1004861	null	[ [ "Parkin ( Gene ID: 5071 ) is an RBR ( RING-in-between-RING ) E3 Ub ligase with a Ubl domain at its N-terminus , and an atypical RING domain , RING0 , has been newly identified in the linker region between the Ubl and the RBR domains [1] , [2] .", "Mutations in parkin genes cause early-onset Parkinson's di...	[ "The kinase PINK1 and the E3 ubiquitin ( Ub ) ligase Parkin participate in mitochondrial quality control .", "The phosphorylation of Ser65 in Parkin's ubiquitin-like ( UBl ) domain by PINK1 stimulates Parkin activation and translocation to damaged mitochondria , which induces mitophagy generating polyUb chain .",...	[ "Parkinson's disease is a neurodegenerative disorder caused by degeneration of the midbrain dopaminergic system in addition to other nervous systems .", "PINK1 and parkin , which encode mitochondrial protein kinase and cytosolic Ub ligase , respectively , were identified as the genes responsible for the autosomal...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "atmospheric science", "geographical locations", "animals", "viruses", "animal behavior", "infectious disease control", "insect vectors", "zoology", "climate change", "infectious diseases", "south america", "behavior", "epidemiology", "a...	Impact of environmental factors on neglected emerging arboviral diseases	journal.pntd.0005959	null	[ [ "The Oropouche virus ( Orthobunyavirus genus ) was first isolated in 1955 from a febrile human patient and Coquillettidia venezuelensis mosquitoes in Trinidad and Tobago [8] .", "Five years later , the virus was detected in a Brazilian territory in a sloth ( Bradypus tridactylus ) and in Ochlerotatus serr...	[ "Brazil is a tropical country that is largely covered by rainforests and other natural ecosystems , which provide ideal conditions for the existence of many arboviruses .", "However , few analyses have examined the associations between environmental factors and arboviral diseases .", "Thus , based on the hypoth...	[ "The Oropouche , Mayaro , Saint Louis , and Rocio viruses are neglected emerging mosquito-borne viruses that are spreading and causing wide-scale epidemics in South America .", "However , under-reporting of these cases is possible , as the symptoms are shared with other endemic diseases .", "Moreover , little i...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "agriculture", "biology" ]	The Role of Rice HEI10 in the Formation of Meiotic Crossovers	journal.pgen.1002809	null	[ [ "Reduction division is unique to eukaryotic cells undergoing meiosis .", "It requires specific mechanisms to pair the homologous chromosomes in their proper orientation and for correct separation [1] .", "In most organisms , a stable connection is established by crossovers ( COs ) .", "COs not onl...	[ "HEI10 was first described in human as a RING domain-containing protein that regulates cell cycle and cell invasion .", "Mice HEI10mei4 mutant displays no obvious defect other than meiotic failure from an absence of chiasmata .", "In this study , we characterize rice HEI10 by map-based cloning and explore its f...	[ "Meiosis is a specialized cell division that is essential for sexual reproduction .", "Errors in meiosis are the leading cause of both infertility and birth defects .", "Most meiotic genes and their functions seem to be highly conserved among different species .", "HEI10 was first identified to regulate cell ...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "ocular anatomy", "neuroscience", "glaucoma", "ganglion cells", "eye diseases", "mammalian genomics", "eyes", "genomics", "animal cells", "head", "animal genomics", "genetic loci", "cellular neuroscience", "retina", "anatomy", "cell biology", "cornea...	Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma	journal.pgen.1007145	null	[ [ "Since the early Ocular Hypertension Treatment Studies ( OHTS ) [1] and subsequent independent findings of others [2 , 3] , central corneal thickness ( CCT ) was identified as a factor related to the risk for developing primary open angle glaucoma ( POAG ) .", "In these studies , CCT was a powerful predic...	[ "Central corneal thickness ( CCT ) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma ( POAG ) .", "The present study uses the BXD Recombinant Inbred ( RI ) strains to identify novel quantitative trait loci ( QTLs ) modulating CCT in the mouse with t...	[ "Glaucoma is a complex group of diseases with several known causal mutations and many known risk factors .", "One well-known risk factor for developing primary open angle glaucoma is the thickness of the central cornea .", "The present study leverages a unique blend of systems biology methods using BXD recombin...	2018

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