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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" ]	[ "biophysics", "cell biology" ]	Force-Induced Unfolding of Fibronectin in the Extracellular Matrix of Living Cells	journal.pbio.0050268	The extracellular protein fibronectin stretches because of cell traction forces, resulting in both straightening of an initially modular structure and unfolding of fibronectin type III modules. Thus, cell signaling might be regulated by the extent to which the extracellular matrix unfolds.	[ [ "Fibronectin ( Fn ) , a major component of the extracellular matrix ( ECM ) of developing tissues and healing wounds , is a large , dimeric protein consisting of more than 50 repeating subunits ( for review see [1–6] ) .", "Fn displays a number of surface-exposed molecular recognition sites for cells , in...	[ "Whether mechanically unfolded fibronectin ( Fn ) is present within native extracellular matrix fibrils is controversial .", "Fn extensibility under the influence of cell traction forces has been proposed to originate either from the force-induced lengthening of an initially compact , folded quaternary structure ...	[ "Cells are embedded within an extracellular matrix that regulates many cellular processes , including stem cell differentiation and cancer progression .", "Yet the underlying molecular mechanisms that mediate these processes remain unknown .", "Within the extracellular matrix of cells , super-molecular assembli...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "invertebrates", "septate junctions", "medicine and health sciences", "junctional complexes", "green fluorescent protein", "cloning", "vertebrates", "animals", "cell polarity", "animal models", "developmental biology", "luminescent proteins", "model organisms", "drosop...	An alternative mode of epithelial polarity in the Drosophila midgut	journal.pbio.3000041	A developmental study in the fruit fly Drosophila melanogaster shows that apical-basal polarity in the midgut epithelium is established by a different mechanism from other Drosophila epithelia, but more akin to that of vertebrate epithelia.	[ [ "Most animal organs and tissues are composed of epithelial cells that adhere laterally to each other to form sheets that act as barriers between compartments .", "The formation of epithelial monolayers depends on the coordinated polarisation of each cell along its apical–basal axis , and this polarity und...	[ "Apical–basal polarity is essential for the formation and function of epithelial tissues , whereas loss of polarity is a hallmark of tumours .", "Studies in Drosophila have identified conserved polarity factors that define the apical ( Crumbs , Stardust , Par-6 , atypical protein kinase C [aPKC] ) , junctional ( ...	[ "The Drosophila midgut is lined by a single-layered epithelium that acts as a barrier to the environment while allowing for nutrient uptake and related physiological processes .", "To fulfil these roles , midgut epithelial cells are highly polarised , with a pronounced asymmetric distribution of cellular componen...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "death rates", "medicine and health sciences", "ecology and environmental sciences", "statistics", "physiological processes", "developmental biology", "research design", "organism development", "forecasting", "mathematics", "cohort studies", "population biology", "life expectancy", "resear...	Errors as a primary cause of late-life mortality deceleration and plateaus	journal.pbio.2006776	null	[ [ "The age-specific probability of death follows diverse , often species-specific curves .", "In several species , including humans , rates of mortality increase with age have been observed ‘flattening’ in advanced old age [1 , 2] .", "In some cases , this late-life mortality deceleration ( LLMD ) is su...	[ "Several organisms , including humans , display a deceleration in mortality rates at advanced ages .", "This mortality deceleration is sufficiently rapid to allow late-life mortality to plateau in old age in several species , causing the apparent cessation of biological ageing .", "Here , it is shown that late-...	[ "In diverse species , mortality rates increase with age at a relatively fixed rate within populations .", "However , recent discoveries have suggested this relationship breaks down in advanced old age , with mortality rate increases slowing and even reaching a plateau .", "This late-life mortality deceleration ...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "body fluids", "immune physiology", "pathology and laboratory medicine", "enzyme-linked immunoassays", "pathogens", "vibrio", "immunology", "tropical diseases", "microbiology", "vaccines", "bacterial diseases", "vibrio cholerae", "neglected tropical diseases...	Dried Blood Spots for Measuring Vibrio cholerae-specific Immune Responses	journal.pntd.0006196	null	[ [ "Despite efforts to improve access to clean water and sanitation in resource-poor settings , cholera remains a significant public health threat globally .", "Identifying key populations at the highest risk of cholera is essential to prioritize public health interventions , including vaccination and effort...	[ "Vibrio cholerae causes over 2 million cases of cholera and 90 , 000 deaths each year .", "Serosurveillance can be a useful tool for estimating the intensity of cholera transmission and prioritizing populations for cholera control interventions .", "Current methods involving venous blood draws and downstream sp...	[ "Cholera remains a major public health issue among underprivileged populations in the developing world .", "Current methods of disease surveillance are inadequate for identifying key populations at highest risk of cholera .", "Serosurveillance can provide accurate measurements of an individual or population’s e...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cadherins", "medicine", "retinal disorders", "cell biology", "synapses", "cell adhesion", "ophthalmology", "biology", "molecular cell biology", "neuroscience", "neurophysiology" ]	Celsr3 Is Required for Normal Development of GABA Circuits in the Inner Retina	journal.pgen.1002239	null	[ [ "The vertebrate retina is a well-established model system for the study of neural circuit formation within the central nervous system .", "Synaptic circuits in the retina transform light information detected by photoreceptors into signals that retinal ganglion cells send to the brain .", "Processes of...	[ "The identity of the specific molecules required for the process of retinal circuitry formation is largely unknown .", "Here we report a newly identified zebrafish mutant in which the absence of the atypical cadherin , Celsr3 , leads to a specific defect in the development of GABAergic signaling in the inner reti...	[ "Visual information is transmitted through the retina from photoreceptors to bipolars to ganglion cells , the output neurons connecting to the brain .", "This vertical transmission of information is modulated by inhibitory lateral interneurons .", "Normal vision requires the proper transmission and processing o...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious disease epidemiology", "bartonellosis", "bacterial diseases", "veterinary diagnostics", "neglected tropical diseases", "population biology", "small animal care", "veterinary science", "veterinary medicine", "infectious diseases", "veterinary diseases", "zoonoses", "...	Infection of Domestic Dogs in Peru by Zoonotic Bartonella Species: A Cross-Sectional Prevalence Study of 219 Asymptomatic Dogs	journal.pntd.0002393	null	[ [ "Bartonella species are gram-negative bacteria associated with an increasing array of disease manifestations in humans and animals .", "They are small , obligate intracellular organisms that adhere and invade erythrocytes and endothelial cells of mammalian hosts , causing long lasting bacteremia [1] , [2]...	[ "Bartonella species are emerging infectious organisms transmitted by arthropods capable of causing long-lasting infection in mammalian hosts .", "Among over 30 species described from four continents to date , 15 are known to infect humans , with eight of these capable of infecting dogs as well .", "B . bacillif...	[ "Bartonella are bacteria transmitted by fleas , ticks , sandflies and other insects capable of infecting humans , domestic animals , livestock and wildlife , including marine mammals .", "In humans , they cause diseases such as trench fever , cat scratch disease , endocarditis , fever of unknown origin and have b...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics", "mammals" ]	Regulatory Circuit of Human MicroRNA Biogenesis	journal.pcbi.0030067	null	[ [ "microRNAs ( miRNAs ) are endogenous nonprotein-coding RNAs that are thought to negatively regulate gene expression [1–4] .", "Although hundreds of human miRNAs have been discovered , the functions of most miRNAs are unknown [5–7] .", "miRNAs are present in organisms as diverse as viruses , flies , wo...	[ "miRNAs ( microRNAs ) are a class of endogenous small RNAs that are thought to negatively regulate protein production .", "Aberrant expression of many miRNAs is linked to cancer and other diseases .", "Little is known about the factors that regulate the expression of miRNAs .", "We have identified numerous re...	[ "microRNAs ( miRNAs ) are unusually small RNAs that are thought to control the production of proteins in the cell .", "Recent studies have linked miRNAs to several types of cancers .", "Several studies strongly suggest that miRNAs could be useful as diagnostic and prognostic markers of various cancers .", "Th...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/bioinformatics", "cell biology/gene expression", "computational biology/transcriptional regulation" ]	Circadian Clock Genes Contribute to the Regulation of Hair Follicle Cycling	journal.pgen.1000573	null	[ [ "Evolutionarily conserved hair follicle cycling is thought to provide mechanisms for controlling the length of hair in specific body sites , and to allow the periodic shedding of fur in response to seasonal changes in mammals [1] .", "The periodicity of the hair growth cycle ranges from approximately thre...	[ "Hair follicles undergo recurrent cycling of controlled growth ( anagen ) , regression ( catagen ) , and relative quiescence ( telogen ) with a defined periodicity .", "Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling , we discovered that , in addition to circadi...	[ "The hair follicle renews itself by repeatedly cycling among growth , regression , and rest phases .", "One function of hair follicle cycling is to allow seasonal changes in hair growth .", "Understanding the regulation of hair follicle cycling is also of interest because abnormal regulation of hair cycle contr...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Down Regulation of NO Signaling in Trypanosoma cruzi upon Parasite-Extracellular Matrix Interaction: Changes in Protein Modification by Nitrosylation and Nitration	journal.pntd.0003683	null	[ [ "Trypanosoma cruzi is the etiological agent of Chagas disease , an infectious disease affecting areas of poor socioeconomic development .", "The parasite infects a wide range of mammalian hosts , including humans , from which 7–8 million are infected and other 25 million are at risk of contamination [1] ....	[ "Adhesion of the Trypanosoma cruzi trypomastigotes , the causative agent of Chagas' disease in humans , to components of the extracellular matrix ( ECM ) is an important step in host cell invasion .", "The signaling events triggered in the parasite upon binding to ECM are less explored and , to our knowledge , th...	[ "Interaction of Trypanosoma cruzi with the extracellular matrix ( ECM ) is an essential step in the invasion of mammalian cells .", "However , the nature of the signaling triggered in the parasite is poorly understood .", "Herein the key role of nitric oxide in T . cruzi signaling is described , using an ECM pr...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "reproductive system", "chemical compounds", "maternal health", "obstetrics and gynecology", "helminths", "tropical diseases", "parasitic diseases", "animals", "organic compounds", "hydroxides", "devel...	Improvement of a tissue maceration technique for the determination of placental involvement in schistosomiasis	journal.pntd.0005551	null	[ [ "Schistosomiasis may involve the placenta of pregnant women when ova are trapped in placental tissue .", "This has been described in both Schistosoma haematobium and Schistosoma mansoni ( S . mansoni ) infections [1 , 2 , 3 , 4 , 5] .", "Lesions are predominantly located in the placental villi , the i...	[ "Schistosomiasis in pregnancy may cause low birth weight , prematurity and stillbirth of the offspring .", "The placenta of pregnant women might be involved when schistosome ova are trapped in placental tissue .", "Standard histopathological methods only allow the examination of a limited amount of placental ti...	[ "Schistosomiasis in pregnant women is associated with prematurity , low birth weight and stillbirth of the fetus .", "Schistosome eggs may be trapped in the placental tissue and , thus , contribute to fetal harm .", "As the placenta is a large organ , current microscopic histopathological examinations commonly ...	2017
[ "Introduction", "Results", "Discussion", "Materials & methods" ]	[ "sv40", "medicine and health sciences", "rift valley fever virus", "vesicular stomatitis virus", "pathology and laboratory medicine", "gene regulation", "pathogens", "microbiology", "viral structure", "viruses", "rna viruses", "dna viruses", "centrifugation", "glycoproteins", "bunyavirus...	A role for glycolipid biosynthesis in severe fever with thrombocytopenia syndrome virus entry	journal.ppat.1006316	null	[ [ "Emerging viruses pose a public health threat that is increasing with rapid global transit and continued urbanization .", "Technological advancements have made it easier to identify new viral threats and disseminate information to the public .", "However , the development of antiviral therapies and va...	[ "A novel bunyavirus was recently found to cause severe febrile illness with high mortality in agricultural regions of China , Japan , and South Korea .", "This virus , named severe fever with thrombocytopenia syndrome virus ( SFTSV ) , represents a new group within the Phlebovirus genus of the Bunyaviridae .", ...	[ "As obligate , intracellular parasites , viruses depend upon numerous host-derived factors to replicate .", "For many bunyaviruses , these pro-viral host factors are largely uncharacterized .", "In the present study , we used an unbiased genetic screening strategy to identify human genes that facilitate the ent...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "molecular biology/rna-protein interactions", "molecular biology/translation mechanisms", "physiology/cell signaling", "biochemistry/transcription and translation" ]	miR-30 Regulates Mitochondrial Fission through Targeting p53 and the Dynamin-Related Protein-1 Pathway	journal.pgen.1000795	null	[ [ "MicroRNAs ( miRNAs ) are a class of small non-coding RNAs that mediate post-transcriptional gene silencing .", "Recently , the work on miRNAs renovates our understanding about the regulation of apoptosis .", "Differential miRNAs have distinct roles with either pro- or anti-apoptosis [1] , [2] .", ...	[ "miRNAs participate in the regulation of apoptosis .", "However , it remains largely unknown as to how miRNAs are integrated into the apoptotic program .", "Mitochondrial fission is involved in the initiation of apoptosis .", "It is not yet clear whether miRNAs are able to regulate mitochondrial fission .", ...	[ "Apoptosis is related to the pathogenesis of many diseases such as tumors and neurodegenerative and cardiovascular disorders .", "Apoptosis is controlled by a variety of genes , and among them a protein called “p53” has been taken as a “death star” and is involved in the initiation of apoptosis .", "The upstrea...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "protein interactions", "applied mathematics", "dna-binding proteins", "simulation and modeling", "algorithms", "mathematics", "sequence motif analysis", "research and analysis methods", "sequence analysis", "bioinformatics", "proteins", "biophysics", "approximation methods", "physics", ...	Inherent limitations of probabilistic models for protein-DNA binding specificity	journal.pcbi.1005638	null	[ [ "The study of protein-DNA interactions has a long history and includes binding to both single- and double-stranded DNA and both non-specific and sequence-specific interactions [1] .", "Our interests are primarily in the sequence-specific interactions of transcription factors ( TFs ) that bind to DNA to re...	[ "The specificities of transcription factors are most commonly represented with probabilistic models .", "These models provide a probability for each base occurring at each position within the binding site and the positions are assumed to contribute independently .", "The model is simple and intuitive and is the...	[ "Transcription factors ( TFs ) , a class of DNA-binding proteins , play a central role in the regulation of gene expression .", "TFs control the rate of transcription by binding to the genome in a sequence-specific manner .", "Thus , one important aspect in the study of gene regulation mechanism is to model the...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "infectious diseases", "veterinary microbiology", "biology", "microbiology", "molecular cell biology", "veterinary science" ]	ATG5 Is Essential for ATG8-Dependent Autophagy and Mitochondrial Homeostasis in Leishmania major	journal.ppat.1002695	null	[ [ "Leishmania are widespread and important parasites of humans and dogs that produce a spectrum of diseases collectively called the leishmaniases .", "Differentiation between the three distinctive morphological forms , the procyclic promastigote , metacyclic promastigote and amastigote , is crucial for prog...	[ "Macroautophagy has been shown to be important for the cellular remodelling required for Leishmania differentiation .", "We now demonstrate that L . major contains a functional ATG12-ATG5 conjugation system , which is required for ATG8-dependent autophagosome formation .", "Nascent autophagosomes were found com...	[ "Leishmaniasis is a disease of humans that is of major significance throughout many parts of the world .", "It is caused by the protozoan parasite Leishmania and mammals are infected through the bite of a sand fly in which the parasite develops .", "Parasite remodelling crucial for generation of the human-infec...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/hiv infection and aids", "evolutionary biology/microbial evolution and genomics" ]	HIV-1 Transmitting Couples Have Similar Viral Load Set-Points in Rakai, Uganda	journal.ppat.1000876	null	[ [ "The severity of HIV-1 infection is thought to result from an interplay of factors in the host , the virus , and the environment ( for instance the presence of co-infections ) .", "Much work has focused on resolving host genetic factors which contribute to virulence [1] , while the possible role of viral ...	[ "It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence , and that it may be subject to natural selection in the human host population .", "A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acq...	[ "During the long period of asymptomatic infection with HIV-1 there is considerable variability in viral load set-point between infected individuals .", "Higher viral load set-points increase infectivity and decrease survival .", "Previous work has shown that the most commonly observed viral load set-points are ...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genomics", "chromosome biology", "biology", "computational biology", "structural genomics", "genetics and genomics" ]	Bayesian Inference of Spatial Organizations of Chromosomes	journal.pcbi.1002893	null	[ [ "The spatial organization of a genome plays an important role in gene regulation , DNA replication , epigenetic modification and maintenance of genome stability [1]–[5] .", "Understanding three-dimensional ( 3D ) chromosomal structures and chromatin interactions is therefore essential for decoding and int...	[ "Knowledge of spatial chromosomal organizations is critical for the study of transcriptional regulation and other nuclear processes in the cell .", "Recently , chromosome conformation capture ( 3C ) based technologies , such as Hi-C and TCC , have been developed to provide a genome-wide , three-dimensional ( 3D )...	[ "Understanding how chromosomes fold provides insights into the complex relationship among chromatin structure , gene activity and the functional state of the cell .", "Recently , chromosome conformation capture based technologies , such as Hi-C and TCC , have been developed to provide a genome-wide , high resolut...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusion" ]	[ "livestock", "medicine and health sciences", "surface water", "leptospira", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "animals", "mammals", "farms", "molecular biology techniques", "bacteria", "bacterial pathogens", "research and analysis methods", ...	Distribution and Diversity of Pathogenic Leptospira Species in Peri-domestic Surface Waters from South Central Chile	journal.pntd.0004895	null	[ [ "Each year , an estimated 1 . 03 million cases of human leptospirosis occur worldwide , resulting in 2 . 9 million disability adjusted life years lost [1 , 2] .", "Transmission of Leptospira to animal hosts and humans occurs either through direct contact with the urine of an infected animal , or indirectl...	[ "Leptospirosis is a neglected zoonosis affecting animals and humans caused by infection with Leptospira .", "The bacteria can survive outside of hosts for long periods of time in soil and water .", "While identification of Leptospira species from human cases and animal reservoirs are increasingly reported , lit...	[ "Leptospirosis is a zoonotic disease that is caused by either direct contact with the urine of animals infected with pathogenic forms of Leptospira , or indirectly , through contact with contaminated water or soil .", "Because many people become infected through the environment , where the bacteria can live for m...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Single Nucleotide Polymorphism Uncovers a Novel Function for the Transcription Factor Ace2 during Candida albicans Hyphal Development	journal.pgen.1005152	null	[ [ "Candida albicans is an opportunistic human pathogen that is able to grow in different morphological forms , including the unicellular budding yeast form , pseudohyphae or true hyphae in response to external cues ( reviewed in [1 , 2] ) .", "A key difference between yeast and hyphae is that yeast cells ac...	[ "Candida albicans is a major invasive fungal pathogen in humans .", "An important virulence factor is its ability to switch between the yeast and hyphal forms , and these filamentous forms are important in tissue penetration and invasion .", "A common feature for filamentous growth is the ability to inhibit cel...	[ "Candida albicans is a major fungal pathogen in immunologically compromised patients .", "A key virulence trait is its ability to switch between the yeast and hyphal forms .", "Whereas yeast cells are required for dissemination , the filamentous forms are important in tissue penetration and invasion .", "In o...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/environmental microbiology", "microbiology/immunity to infections", "infectious diseases/neglected tropical diseases", "microbiology/microbial evolution and genomics", "infectious diseases/bacterial infections", "infectious diseases/tropical and travel-associated diseases", "microbiology/m...	Human Leptospirosis Caused by a New, Antigenically Unique Leptospira Associated with a Rattus Species Reservoir in the Peruvian Amazon	journal.pntd.0000213	null	[ [ "Leptospirosis is a zoonotic disease of world-wide distribution caused by pathogenic spirochetes of the genus Leptospira [1]–[3] .", "The disease cannot be diagnosed on clinical grounds alone because its clinical presentations are diverse , ranging from undifferentiated fever to fulminant disease typified...	[ "As part of a prospective study of leptospirosis and biodiversity of Leptospira in the Peruvian Amazon , a new Leptospira species was isolated from humans with acute febrile illness .", "Field trapping identified this leptospire in peridomestic rats ( Rattus norvegicus , six isolates; R . rattus , two isolates ) ...	[ "Leptospirosis has emerged as a globally important infectious disease .", "Its impact on public health is often difficult to determine , sometimes because of low clinical suspicion , or , as is more common , difficulty in laboratory diagnosis .", "Gold-standard serology-based diagnosis has a number of important...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "taeniasis", "medicine", "infectious diseases", "amebiasis", "schistosomiasis", "soil-transmitted helminths", "parasitic intestinal diseases", "trichuriasis", "giardiasis", "hookworm infection", "strongyloidiasis", "neglected tropical diseases", "enterobiasis", "hookworm", "hymenolepiasi...	Mini-FLOTAC, an Innovative Direct Diagnostic Technique for Intestinal Parasitic Infections: Experience from the Field	journal.pntd.0002344	null	[ [ "Soil-transmitted helminths ( STH ) ( Ascaris lumbricoides , Trichuris trichiura , hookworm , Strongyloides stercoralis ) and intestinal protozoa ( e . g . Giardia intestinalis , Entamoeba histolytica/dispar ) are widespread in developing countries , especially where poor hygienic conditions facilitate infect...	[ "Soil-transmitted helminths and intestinal protozoa infection are widespread in developing countries , yet an accurate diagnosis is rarely performed .", "The aim of this study was to evaluate the recently developed mini–FLOTAC method and to compare with currently more widely used techniques for the diagnosis of i...	[ "The mini-FLOTAC has been recently developed as a novel direct method for the diagnosis of intestinal parasitic infections .", "Mini-FLOTAC attempts to address the challenge of using modern technology matched with high sensitivity , affordability , and appropriateness of diagnosis in resource-limited settings whe...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "primates", "urology", "mammals", "homo (human)", "genetics and genomics" ]	Genome-Wide Expression of Azoospermia Testes Demonstrates a Specific Profile and Implicates ART3 in Genetic Susceptibility	journal.pgen.0040026	null	[ [ "Spermatogenesis , a major function of mammalian testes , is complex and strictly regulated .", "While spermatogenesis is a maturation of germ cells , other cells including Sertoli , Leydig , and peritubular myoid cells also play important roles , and defects at any differentiation stage might result in i...	[ "Infertility affects about one in six couples attempting pregnancy , with the man responsible in approximately half of the cases .", "Because the pathophysiology underlying azoospermia is not elucidated , most male infertility is diagnosed as idiopathic .", "Genome-wide gene expression analyses with microarray ...	[ "Worldwide , approximately 15% of couples attempting pregnancy meet with failure .", "Male factors are thought to be responsible in 20%–50% of all infertility cases .", "Azoospermia , the absence of sperm in the ejaculate due to defects in its production or delivery is common in male infertility .", "In this ...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "histology", "model organisms", "genetics", "genetics and genomics", "biology", "neuroscience", "metabolic disorders" ]	Characterization of Inducible Models of Tay-Sachs and Related Disease	journal.pgen.1002943	null	[ [ "Two-thirds of the seventy or so inborn errors of lysosomal function affect the nervous system .", "Tay-Sachs disease [1] , [2] and Sandhoff disease [3] are GM2 gangliosidoses arising from deficiency of the lysosomal acid hydrolase , β-N-acetylhexosaminidase; they are characterized by neuronal accumulatio...	[ "Tay-Sachs and Sandhoff diseases are lethal inborn errors of acid β-N-acetylhexosaminidase activity , characterized by lysosomal storage of GM2 ganglioside and related glycoconjugates in the nervous system .", "The molecular events that lead to irreversible neuronal injury accompanied by gliosis are unknown; but ...	[ "Sandhoff and Tay-Sachs disease are devastating neurological diseases associated with developmental regression , blindness , seizures , and death in infants and young children .", "These disorders are caused by mutations in β-hexosaminidase genes , which result in neuronal accumulation of certain lipids , glycosp...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "infectious disease epidemiology", "leishmaniasis", "neglected tropical diseases", "infectious disease control" ]	Prediction Score for Antimony Treatment Failure in Patients with Ulcerative Leishmaniasis Lesions	journal.pntd.0001656	null	[ [ "Leishmaniasis is caused by protozoan parasites of the genus Leishmania sp .", "There is an estimated 2 million new cases and almost 70 000 attributable deaths worldwide every year [1] .", "Leishmaniasis includes a cluster of diseases with widely diverse clinical manifestations .", "These include ...	[ "Increased rates for failure in leishmaniasis antimony treatment have been recently recognized worldwide .", "Although several risk factors have been identified there is no clinical score to predict antimony therapy failure of cutaneous leishmaniasis .", "A case control study was conducted in Peru from 2001 to ...	[ "The manuscript is relevant because of the finding of a new risk factor for chemotherapy failure and the development of a prognosis score for cutaneous leishmaniasis .", "The proportion of patients that have multiple lesions in American Tegumentary Leishmaniasis ( ATL ) is considerable .", "Publications and our...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "radiology and medical imaging", "pet imaging", "mental health", "diagnostic radiology", "neurological disorders", "neurology", "dementia", "alzheimer disease", "nuclear medicine", "neuroimaging", "radiology", "psychiatry" ]	Generative FDG-PET and MRI Model of Aging and Disease Progression in Alzheimer's Disease	journal.pcbi.1002987	null	[ [ "Neuroimaging studies using [18F]fluorodeoxyglucose positron emission tomography ( FDG-PET ) and structural magnetic resonance imaging ( sMRI ) provide substantial evidence of high sensitivity for early detection and progression assessment in Alzheimer's disease ( AD ) at a group and single subject level [1]–...	[ "The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease ( AD ) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology ....	[ "Establishing an accurate diagnosis of Alzheimer's disease has been a major challenge in the past decades .", "With an increasing amount of studies aiming at detection and validation of imaging biomarkers for this disease , many apparently controversial findings have been reported over the time .", "The failure...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/gene discovery", "gastroenterology and hepatology/biliary tract", "genetics and genomics/gene function", "oncology/gastrointestinal cancers", "genetics and genomics/cancer genetics", "pathology/molecular pathology", "gastroenterology and hepatol...	Genomic Profiling Identifies GATA6 as a Candidate Oncogene Amplified in Pancreatobiliary Cancer	journal.pgen.1000081	null	[ [ "Pancreatic cancer has among the highest mortality rates of any cancer , pointing to a critical need for more effective therapies .", "While much progress has been made in understanding pancreatic cancer pathogenesis , a more comprehensive characterization of molecular genetic alterations is needed to def...	[ "Pancreatobiliary cancers have among the highest mortality rates of any cancer type .", "Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy .", "To catalogue genomic alterations , we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6...	[ "Pancreatic cancer is a devastating disease , having among the lowest survival rates of any cancer .", "A better understanding of the molecular basis of pancreatic cancer may lead to improved rationale therapies .", "We report here the discovery of amplification ( i . e . extra copies ) of the GATA6 gene in man...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "global health", "neglected tropical diseases", "infectious diseases", "disease ecology", "dengue fever", "biology", "vectors and hosts", "population ecology", "public health", "behavioral ecology", "mosquitoes", "ecology" ]	Oviposition Site Selection by the Dengue Vector Aedes aegypti and Its Implications for Dengue Control	journal.pntd.0001015	null	[ [ "Dengue viruses are transmitted to humans primarily by the mosquito Aedes aegypti and represent an increasing public health concern in tropical and subtropical regions worldwide .", "Because no vaccine or antiviral therapy is commercially available , controlling the mosquito vector is the only current mea...	[ "Because no dengue vaccine or antiviral therapy is commercially available , controlling the primary mosquito vector , Aedes aegypti , is currently the only means to prevent dengue outbreaks .", "Traditional models of Ae .", "aegypti assume that population dynamics are regulated by density-dependent larval compe...	[ "Controlling the mosquito Aedes aegypti is of public health importance because , at present , it is the only means to stop dengue virus transmission .", "Implementing successful mosquito control programs requires understanding what factors regulate population abundance , as well as anticipating how mosquitoes may...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "non-homologous end joining", "dna replication", "cell biology", "virology", "biology and life sciences", "dna", "dna repair", "dna recombination", "microbiology", "viral replication", "viral replication complex", "molecular biology", "viral nucleic acid", "homologous rec...	SV40 Utilizes ATM Kinase Activity to Prevent Non-homologous End Joining of Broken Viral DNA Replication Products	journal.ppat.1004536	null	[ [ "A diverse set of protein functions is required to ensure the timely , accurate duplication of the genome .", "In addition to the components of the replication machinery itself [1] , [2] , accurate replication requires the S phase checkpoint kinase , ataxia telangiectasia-mutated and rad3-related ( ATR ) ...	[ "Simian virus 40 ( SV40 ) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage .", "During SV40 DNA replication , ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevent...	[ "Viruses from both Polyomaviridae and Papillomaviridae families share several characteristics .", "These include common modes of DNA replication and an accumulation of DNA damage signaling and repair proteins at replicating viral DNA .", "Several DNA repair proteins , with unknown functions during viral DNA rep...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell biology/leukocyte signaling and gene expression", "immunology/immune response", "infectious diseases/helminth infections", "immunology/immunity to infections", "immunology/leukocyte activation" ]	IL-4Rα-Independent Expression of Mannose Receptor and Ym1 by Macrophages Depends on their IL-10 Responsiveness	journal.pntd.0000689	null	[ [ "Schistosomiasis is a severe parasitic disease with more than 200 million people infected worldwide with an estimated 280 , 000 deaths per annum in sub-Saharan Africa alone [1] , [2] .", "In the murine model , mice infected with Schistosoma mansoni develop a severe liver pathology with granulomatous infla...	[ "IL-4Rα-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis .", "Previously , we demonstrated that mice deficient for macrophage-specific IL-4Rα ( LysMcreIl4ra−/lox ) developed increased hepatotoxicity and gut inflammation; whereas inflammation was restricted t...	[ "Schistosomiasis is a tropical disease caused by one of the species of the parasitic worm Schistosoma which infects over 200 million people worldwide .", "Signalling via the IL-4 receptor alpha ( IL-4Rα ) , which is the common receptor chain for the ligands IL-4 and IL-13 , is essential for inducing protective Ty...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "neurochemistry", "enzymology", "brain", "neuroscience", "simulation and modeling", "ganglion cells", "chemical dissociation", "enzyme chemistry", "neuronal tuning", "research and analysis methods", "animal cells", "neurochemicals", "nitric oxide", "enzyme...	Competitive tuning: Competition's role in setting the frequency-dependence of Ca2+-dependent proteins	journal.pcbi.1005820	null	[ [ "Calcium ( Ca2+ ) is well-recognized as an important second messenger in cellular signaling .", "One of the most widely expressed Ca2+ binding proteins , calmodulin ( CaM ) , is a highly conserved protein in the EF-hand family [1] ( Fig 1A ) .", "CaM has over 100 reported downstream binding proteins ,...	[ "A number of neurological disorders arise from perturbations in biochemical signaling and protein complex formation within neurons .", "Normally , proteins form networks that when activated produce persistent changes in a synapse’s molecular composition .", "In hippocampal neurons , calcium ion ( Ca2+ ) flux th...	[ "Learning and memory formation are likely associated with dynamic fluctuations in the connective strength of neuronal synapses .", "These fluctuations , called synaptic plasticity , are regulated by calcium ion ( Ca2+ ) influx through ion channels localized to the post-synaptic membrane .", "Within the post-syn...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "complement system", "medicine and health sciences", "immune physiology", "body fluids", "pathology and laboratory medicine", "intracellular pathogens", "pathogens", "immunology", "vertebrates", "animals", "pulmonology", "mammals", "pneumonia", "vaccines", "infectious disease control", ...	Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi	journal.ppat.1007160	null	[ [ "Correlates of cellular and humoral immunity to major intracellular , non-viral pathogens capable of informing vaccine development are incompletely understood .", "It is unknown which ones can form the basis of a highly effective vaccine to prevent diseases such as tuberculosis ( TB ) .", "Protection ...	[ "Immune correlates of protection against intracellular bacterial pathogens are largely thought to be cell-mediated , although a reasonable amount of data supports a role for antibody-mediated protection .", "To define a role for antibody-mediated immunity against an intracellular pathogen , Rhodococcus equi , tha...	[ "Development of effective vaccines for diseases such as tuberculosis , brucellosis and others caused by intracellular pathogens has proved challenging , as data exist supporting both antibody and cellular immune effectors as mediators of protection .", "To address this problem against an important , and represent...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Border Patrol Gone Awry: Lung NKT Cell Activation by Francisella tularensis Exacerbates Tularemia-Like Disease	journal.ppat.1004975	null	[ [ "The respiratory mucosa is a major site for pathogen entry and hence , requires constant immune surveillance .", "Like other mucosal surfaces , the lungs are populated by a variety of innate cells and innate-like lymphocytes .", "One such cell type , the type I , semi-invariant natural killer T ( NKT ...	[ "The respiratory mucosa is a major site for pathogen invasion and , hence , a site requiring constant immune surveillance .", "The type I , semi-invariant natural killer T ( NKT ) cells are enriched within the lung vasculature .", "Despite optimal positioning , the role of NKT cells in respiratory infectious di...	[ "NKT cells are innate-like lymphocytes with a demonstrated role in a wide range of diseases .", "Often cited for their ability to rapidly produce a variety of cytokines upon activation , they have long been appreciated for their ability to “jump-start” the immune system and to shape the quality of both the innate...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "biology", "microbiology", "otorhinolaryngology", "otolaryngology" ]	Hemoglobin Promotes Staphylococcus aureus Nasal Colonization	journal.ppat.1002104	null	[ [ "Staphylococcus aureus is a human commensal and the causative agent of many serious acute and chronic infections [1] .", "The primary reservoir for S . aureus is the nasal cavity [2] , [3] .", "Asymptomatic colonization occurs in approximately 20% of the normal population , another 60% are transiently...	[ "Staphylococcus aureus nasal colonization is an important risk factor for community and nosocomial infection .", "Despite the importance of S . aureus to human health , molecular mechanisms and host factors influencing nasal colonization are not well understood .", "To identify host factors contributing to nasa...	[ "Staphylococcus aureus is a medically important human pathogen that is found in the nasal passages of approximately 1/3 of the population .", "The nose serves as a reservoir for spread of this pathogen and predisposes the host to potential infection .", "Factors contributing to S . aureus nasal colonization are...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "zoonoses", "neglected tropical diseases", "arboviral infections", "viral diseases", "vectors and hosts" ]	Comparison of Argentinean Saint Louis Encephalitis Virus Non-Epidemic and Epidemic Strain Infections in an Avian Model	journal.pntd.0001177	null	[ [ "The geographic distribution of St . Louis encephalitis virus ( SLEV , Flavivirus , Flaviviridae ) encompasses tropical , sub-tropical and much of the temperate-tropical zones of the Western Hemisphere and therefore , most of the populated land masses of North and South America [1] .", "In the United Stat...	[ "St . Louis encephalitis virus ( SLEV , Flavivirus , Flaviviridae ) is an emerging mosquito-borne pathogen in South America , with human SLEV encephalitis cases reported in Argentina and Brazil .", "Genotype III strains of SLEV were isolated from Culex quinquefasciatus mosquitoes in Cordoba , Argentina in 2005 , ...	[ "St . Louis encephalitis virus ( SLEV , Flavivirus , Flaviviridae ) is an emerging arbovirus in South America , with human SLEV encephalitis cases reported in Argentina and Brazil .", "Genotype III strains of SLEV were isolated from mosquitoes during the largest SLEV outbreak ever reported in South America ( Córd...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Long-Term Arthralgia after Mayaro Virus Infection Correlates with Sustained Pro-inflammatory Cytokine Response	journal.pntd.0004104	null	[ [ "Alphaviruses are pathogens responsible for endemic human diseases in various regions throughout the world [1 , 2] .", "They can be transmitted to humans by mosquitoes of the genera Ochlerotatus , Aedes , Psorophora , Mansonia , Haemagogus , and Culex , among others [3 , 4] .", "Alphavirus infection c...	[ "Mayaro virus ( MAYV ) , an alphavirus similar to chikungunya virus ( CHIKV ) , causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals .", "Currently , the immune response and its role in the development of MAYV-induced persistent art...	[ "Mayaro virus ( MAYV ) causes an acute debilitating disease which results in the development of long-term arthralgia in more than 50% of infected individuals , similarly to what has been described with CHIKV .", "In this study , we evaluated the immune response of individuals with confirmed MAYV infection in a on...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "host-pathogen interaction", "biology", "microbiology", "glycobiology", "parasitology" ]	A Nucleotide Sugar Transporter Involved in Glycosylation of the Toxoplasma Tissue Cyst Wall Is Required for Efficient Persistence of Bradyzoites	journal.ppat.1003331	null	[ [ "The Apicomplexa are a phylum of protozoan organisms , many of which are pathogens with human and veterinary relevance .", "The Apicomplexan parasites share the remarkable ability to invade and propagate within host cells .", "Among this group , Toxoplasma gondii is an exemplar of the ability to under...	[ "Toxoplasma gondii is an intracellular parasite that transitions from acute infection to a chronic infective state in its intermediate host via encystation , which enables the parasite to evade immune detection and clearance .", "It is widely accepted that the tissue cyst perimeter is highly and specifically deco...	[ "The Toxoplasma tissue cyst is essential to the persistence of the parasite during the chronic infection of an immunocompetent host .", "While significant efforts have been made to identify molecular factors that trigger and sustain parasite encystation , the role of the glycoconjugates that decorate the cyst wal...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "ecology and environmental sciences", "medicine and health sciences", "geographical locations", "social sciences", "animals", "singapore", "vaccines", "habitats", "infectious disease control", "insect vectors", "zoology", "housing", "human geography", "infectious disease...	The effectiveness of inspections on reported mosquito larval habitats in households: A case-control study	journal.pntd.0007492	null	[ [ "Dengue is an arboviral disease that imposes a substantial burden on economic development and human health across the globe .", "The annual global economic cost of this vector-borne disease has been estimated at USD$8 . 9 billion [1] .", "Global estimates place the annual number of dengue infections a...	[ "Dengue is an arboviral disease that imposes substantial health and economic burdens across the globe .", "Vector control remains a key strategy in settings where Dengvaxia ( a dengue vaccine ) has not been licenced due to safety concerns and where mass immunization programmes are not cost-effective .", "Though...	[ "Dengue is a disease that is transmitted by Aedes mosquitoes .", "In areas where the use of a dengue vaccine has not been authorized due to safety concerns and is not cost-effective , reducing the population of Aedes mosquitoes remains the key method in controlling the disease .", "One approach to mosquito popu...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation", "infectious diseases/hiv infection and aids", "infectious diseases/viral infections", "computational biology", "virology/effects of virus infection on host gene expression", "virology/host invasion and cell entry" ]	Patterns of HIV-1 Protein Interaction Identify Perturbed Host-Cellular Subsystems	journal.pcbi.1000863	null	[ [ "Acquired immunodeficiency syndrome ( AIDS ) , caused by HIV-1 , is responsible for millions of deaths every year .", "Therefore , research into HIV-1 biology is of critical importance and research efforts are significant and ongoing .", "In order to replicate , HIV-1 , like all viruses , must use hos...	[ "Human immunodeficiency virus type 1 ( HIV-1 ) exploits a diverse array of host cell functions in order to replicate .", "This is mediated through a network of virus-host interactions .", "A variety of recent studies have catalogued this information .", "In particular the HIV-1 , Human Protein Interaction Dat...	[ "HIV-1 is responsible for millions of deaths every year by causing acquired immunodeficiency syndrome ( AIDS ) .", "Therefore , research is ongoing in order to better understand and counter HIV-1 infection .", "Like any virus , HIV-1 must enter host cells and use cellular machinery to replicate .", "To do thi...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "inflammatory diseases", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "viruses", "animal models", "developmental biology", "h5n1", "model organ...	Interferon induced protein 35 exacerbates H5N1 influenza disease through the expression of IL-12p40 homodimer	journal.ppat.1007001	null	[ [ "Infections with highly pathogenic IAV , such as H5N1-IAV , are characterized by high viral titers , excessive inflammation , and increased mortality after infection [1–3]; ( WHO/GIP , 2017 ) .", "While the host innate immune response is important for limiting IAV replication and disease; an aberrant inna...	[ "Pro-inflammatory cytokinemia is a hallmark of highly pathogenic H5N1 influenza virus ( IAV ) disease yet little is known about the role of host proteins in modulating a pathogenic innate immune response .", "The host Interferon Induced Protein 35 ( Ifi35 ) has been implicated in increased susceptibility to H5N1-...	[ "Highly pathogenic influenza A viruses ( IAV ) are an important human pathogen that cause high mortality and can acquire the ability to cause pandemics .", "Following highly pathogenic H5N1-IAV infection , exaggerated inflammatory responses are detrimental to the host and lead to more disease; tipping the balance...	2018
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "medicine and health sciences", "vesicles", "pathology and laboratory medicine", "immunology", "tropical diseases", "parasitic diseases", "parasitology", "vaccines", "preventive medicine", "developmental biology", "genome analysis", "neglected tropical diseases", "vaccination and immunizatio...	Analysis on Gene Expression Profile in Oncospheres and Early Stage Metacestodes from Echinococcus multilocularis	journal.pntd.0004634	null	[ [ "Alveolar echinococcosis ( AE ) is a worldwide zoonosis that is of great public health concern in the northern hemisphere .", "Eggs of the tapeworm , which are excreted by definitive hosts , foxes and dogs , present a risk for humans [1] .", "After oral ingestion of mature oncosphere-containing eggs ,...	[ "Alveolar echinococcosis is a worldwide zoonosis of great public health concern .", "Analysis of genome data for Echinococcus multilocularis has identified antigen families that can be used in diagnostic assays and vaccine development .", "However , little gene expression data is available for antigens of the e...	[ "Humans become infected with E . multilocularis through oral ingestion of the eggs .", "Untreated alveolar echinococcosis has a fatality rate of >90% in humans , causing great public health concern in the northern hemisphere .", "The genome databases of E . multilocularis have been recently published , but stil...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biofilms", "bacteriology", "exopolysaccharides", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "fungal structure", "mutation", "fungi", "experimental organism systems", "fungal pathogens", "bacteria", "bacterial pathogens", "research a...	Candida albicans mannans mediate Streptococcus mutans exoenzyme GtfB binding to modulate cross-kingdom biofilm development in vivo	journal.ppat.1006407	null	[ [ "Candida albicans is an opportunistic fungal pathogen found in various sites of the human body causing localized and systemic infections [1–3] .", "The ability of this organism to infect and cause diseases is associated with biofilm formation [4–6] , often involving interactions with bacteria that can enh...	[ "Candida albicans is frequently detected with heavy infection by Streptococcus mutans in plaque-biofilms from children with early-childhood caries ( ECC ) .", "This cross-kingdom biofilm contains an extensive matrix of extracellular α-glucans that is produced by an exoenzyme ( GtfB ) secreted by S . mutans .", ...	[ "Early childhood caries is a severe form of tooth decay that affects toddlers and is clinically distinct from other forms of the disease .", "It is characterized by the frequent isolation of the commensal yeast Candida albicans and the bacterial pathogen Streptococcus mutans within caries-associated biofilms .", ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "invertebrates", "animals", "invertebrate genomics", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "genome analysis", "sequence motif analysis", "molecular biology techniques", "rna sequencing", "drosophila", "resea...	Numerous recursive sites contribute to accuracy of splicing in long introns in flies	journal.pgen.1007588	null	[ [ "RNA splicing is a crucial step in the mRNA lifecycle , during which pre-mRNA transcripts are processed into mature transcripts by the excision of intronic sequences .", "Introns are normally excised as a single lariat unit .", "However , some introns in the Drosophila melanogaster genome are known to...	[ "Recursive splicing , a process by which a single intron is removed from pre-mRNA transcripts in multiple distinct segments , has been observed in a small subset of Drosophila melanogaster introns .", "However , detection of recursive splicing requires observation of splicing intermediates that are inherently uns...	[ "The splicing of RNA transcripts is an essential step in the production of mature mRNA molecules , involving removal of intron sequences and joining of flanking exon sequences .", "Introns are usually removed as a single unit in a two-step catalytic reaction .", "However , a small subset of introns in flies are...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "graphical user interfaces", "action potentials", "medicine and health sciences", "engineering and technology", "membrane potential", "electrophysiology", "neuroscience", "simulation and modeling", "human factors engineering", "scientists", "bioassays and physiological analysis", "science and ...	A demonstration of modularity, reuse, reproducibility, portability and scalability for modeling and simulation of cardiac electrophysiology using Kepler Workflows	journal.pcbi.1006856	null	[ [ "Computational modeling and simulation has proven to be a powerful approach to reveal fundamental mechanisms of the cardiac rhythm in both normal and pathological conditions .", "Recent studies have expanded modeling approaches to the domain of predictive pharmacology , utilizing functional in silico appr...	[ "Multi-scale computational modeling is a major branch of computational biology as evidenced by the US federal interagency Multi-Scale Modeling Consortium and major international projects .", "It invariably involves specific and detailed sequences of data analysis and simulation , often with multiple tools and dat...	[ "We present a computational workflow as a proof of concept for integration and implementation of a reusable and reproducible cardiac multi-scale electrophysiology model that is expandable , modular and portable .", "This framework enables scientists to create intuitive , user-friendly and flexible end-to-end auto...	2019
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "molecular neuroscience", "neurochemistry", "parasite evolution", "microbiology", "neuroscience", "parasitology", "parasite physiology", "ion channels", "molecular genetics", "neurotransmitters", "proteins", "neurochemicals", "biology", "glutamate"...	Molecular Cloning and Characterization of Novel Glutamate-Gated Chloride Channel Subunits from Schistosoma mansoni	journal.ppat.1003586	null	[ [ "Schistosomiasis , a disease caused by parasitic flatworms in the genus Schistosoma , is one of the most prevalent parasitic diseases in tropical and sub-tropical areas of the world .", "S . mansoni is responsible for the majority of schistosomiasis infections in sub-Saharan Africa , the Middle East , the...	[ "Cys-loop ligand-gated ion channels ( LGICs ) mediate fast ionotropic neurotransmission .", "They are proven drug targets in nematodes and arthropods , but are poorly characterized in flatworms .", "In this study , we characterized the anion-selective , non-acetylcholine-gated Cys-loop LGICs from Schistosoma ma...	[ "Schistosomiasis is a debilitating disease caused by blood flukes in the genus Schistosoma that afflicts over 200 million people worldwide .", "Treatment relies almost exclusively on a single drug , praziquantel .", "Reports of sub-optimal efficacy of praziquantel raise concerns about the prospect of drug resis...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "nervous system", "cell cycle and cell division", "cell processes", "neuroscience", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "stem cells", "experimental organism systems", "embryos", ...	Brain expansion promoted by polycomb-mediated anterior enhancement of a neural stem cell proliferation program	journal.pbio.3000163	A study in fruit flies shows that the anterior expansion of the central nervous system, to form the brain, is driven by Polycomb-mediated repression of Hox genes, resulting in anterior enhancement of a neural stem cell program.	[ [ "During central nervous system ( CNS ) development , neural progenitor cells undergo repetitive rounds of asymmetric cell divisions , renewing themselves and generating daughter cells .", "After a certain number of cell divisions , neural progenitors subsequently exit the cell cycle .", "Daughter cell...	[ "During central nervous system ( CNS ) development , genetic programs establish neural stem cells and drive both stem and daughter cell proliferation .", "However , the prominent anterior expansion of the CNS implies anterior–posterior ( A–P ) modulation of these programs .", "In Drosophila , a set of neural st...	[ "The central nervous system displays a pronounced anterior expansion that forms the brain .", "In the fruit fly Drosophila melanogaster , this expansion is driven by enhanced anterior cell proliferation .", "Recent studies reveal that cell proliferation in the brain is promoted by the Polycomb Group Complex , a...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "cell death", "medicine and health sciences", "autophagic cell death", "immune cells", "pathology and laboratory medicine", "viral transmission and infection", "hela cells", "molecular probe techniques", "pathogens", "cell cycle and cell division", "immunology", "cell processe...	SHMT2 and the BRCC36/BRISC deubiquitinase regulate HIV-1 Tat K63-ubiquitylation and destruction by autophagy	journal.ppat.1007071	null	[ [ "The HIV-1 Tat transactivator stimulates RNAPII transcription elongation at the proviral promoter in response to increased levels of the positive transcription elongation factor-b ( P-TEFb/CDK9 ) complex in activated T cells [1–3] .", "The expression of early viral transcripts encoding Tat effectively est...	[ "HIV-1 Tat is a key regulator of viral transcription , however little is known about the mechanisms that control its turnover in T cells .", "Here we use a novel proteomics technique , called DiffPOP , to identify the molecular target of JIB-04 , a small molecule compound that potently and selectively blocks HIV-...	[ "The HIV-1 Tat protein is critical for virus expression and replication , but little is known about the factors that control its expression level in T cells .", "Here , we have investigated a small molecule compound , JIB-04 , which induces the rapid and selective destruction of the HIV-1 Tat protein in HeLa and ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "transfection", "microbial mutation", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "orthomyxoviruses", "viruses", "mutation", "substitution mutation", "rna viruses", "genome analysis", "molecular biology techniques", "microbial genomics"...	The Mutational Robustness of Influenza A Virus	journal.ppat.1005856	null	[ [ "The predictable burden of seasonal influenza and the unpredictability of the next pandemic are attributable in large part to the rapid evolution of influenza virus [1–4] .", "Like other RNA viruses , influenza viruses replicate with extremely low fidelity , with a mutation rate of roughly 2 x 10−5 substi...	[ "A virus’ mutational robustness is described in terms of the strength and distribution of the mutational fitness effects , or MFE .", "The distribution of MFE is central to many questions in evolutionary theory and is a key parameter in models of molecular evolution .", "Here we define the mutational fitness ef...	[ "Like other RNA viruses , influenza virus has a very high mutation rate .", "While high mutation rates may increase the rate at which influenza virus will adapt to a new host , acquire a new route of transmission , or escape from host immune surveillance , data from model systems suggest that most new viral mutat...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene function", "developmental biology/developmental molecular mechanisms", "cell biology/cell signaling" ]	P-Type ATPase TAT-2 Negatively Regulates Monomethyl Branched-Chain Fatty Acid Mediated Function in Post-Embryonic Growth and Development in C. elegans	journal.pgen.1000589	null	[ [ "Lipids play many critical roles in cellular function ranging from providing structural support within cell membranes to mediating signaling events .", "The importance of the particular fatty acid constituents of complex lipids is only beginning to be understood .", "While extensive analyses have been...	[ "Monomethyl branched-chain fatty acids ( mmBCFAs ) are essential for Caenorhabditis elegans growth and development .", "To identify factors acting downstream of mmBCFAs for their function in growth regulation , we conducted a genetic screen for suppressors of the L1 arrest that occurs in animals depleted of the 1...	[ "Fatty acids serve diverse functions in organisms , including roles at the cell membrane to coordinate cell signaling processes .", "Monomethyl branched-chain fatty acids ( mmBCFAs ) are a special type of fatty acid that is commonly present in animals .", "Because mmBCFAs are a small component of the total fatt...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "neurochemistry", "pathology and laboratory medicine", "pathogens", "animal models of disease", "metabolic processes", "dna-binding proteins", "microbiology", "neuroscience", "animal models", "model organisms", "experimental organism systems", "neurotransmitte...	The Klebsiella pneumoniae citrate synthase gene, gltA, influences site specific fitness during infection	journal.ppat.1008010	null	[ [ "Extended spectrum beta-lactamase ( ESBL ) -producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae ( CRE ) pose a serious public health threat due to their extensive antibiotic resistance .", "Many ESBL and CRE infections are healthcare-associated infections ( HAIs ) , meaning they occur...	[ "Klebsiella pneumoniae ( Kp ) , one of the most common causes of healthcare-associated infections , increases patient morbidity , mortality , and hospitalization costs .", "Kp must acquire nutrients from the host for successful infection; however , the host is able to prevent bacterial nutrient acquisition throug...	[ "The bacteria Klebsiella pneumoniae ( Kp ) is an important cause of infection in healthcare settings .", "These infections can be difficult to treat , as they frequently occur in chronically ill patients and the bacteria have the ability to acquire multiple antibiotic resistance markers .", "Kp is a common colo...	2019
[ "Introduction", "Methods", "Results", "Discussion", "Data availability" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "henipavirus", "pathogens", "geographical locations", "microbiology", "vertebrates", "india", "australia", "animals", "mammals", "viruses", "rna viruses", "infectious disease control", "fruit bats", "infectious diseas...	Prioritizing surveillance of Nipah virus in India	journal.pntd.0007393	null	[ [ "The henipaviruses , including Nipah virus and Hendra virus , are highly lethal , emerging , bat-borne viruses within the family Paramyxoviridae that infect humans directly or via domestic animals that function as bridging hosts [1 , 2] .", "Previous Nipah virus outbreaks were reported in Malaysia in 1998...	[ "The 2018 outbreak of Nipah virus in Kerala , India , highlights the need for global surveillance of henipaviruses in bats , which are the reservoir hosts for this and other viruses .", "Nipah virus , an emerging paramyxovirus in the genus Henipavirus , causes severe disease and stuttering chains of transmission ...	[ "Nipah virus is an emerging zoonotic virus that spills over from bats to humans causing severe disease and chains of transmission in humans .", "In May 2018 , in Kerala , India , Nipah virus infected 23 people , killing 21 .", "We reviewed and analyzed published records of Nipah virus surveillance in bats and i...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Mycolactone-Dependent Depletion of Endothelial Cell Thrombomodulin Is Strongly Associated with Fibrin Deposition in Buruli Ulcer Lesions	journal.ppat.1005011	null	[ [ "The neglected tropical disease Buruli ulcer ( BU ) , caused by subcutaneous infection with Mycobacterium ulcerans , is most common in West Africa , but has also reported from Australia and altogether more than 30 countries worldwide [1] .", "These indolent , painless , ulcers affect at least 5 , 000 pati...	[ "A well-known histopathological feature of diseased skin in Buruli ulcer ( BU ) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone .", "Since the underlying mechanism is not known , we have investigated the effect of mycolactone on endothelial cells , focussing on the expr...	[ "Buruli ulcer ( BU ) is a neglected tropical disease that is most common in West Africa and parts of Australia , but has been reported from over 30 countries worldwide .", "The symptoms are painless ulcers of the skin caused by a bacterial infection .", "The bacteria , Mycobacterium ulcerans , produce a macroli...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "animal models of infection", "model organisms", "viral transmission and infection", "virology", "biology", "microbiology", "mouse" ]	Illumination of Murine Gammaherpesvirus-68 Cycle Reveals a Sexual Transmission Route from Females to Males in Laboratory Mice	journal.ppat.1003292	null	[ [ "Herpesviruses are important pathogens which are ubiquitous in both human and animal populations .", "They establish persistent , productive infections , with virus carriers both making anti-viral immune responses that protect against disease and excreting infectious virions .", "Among herpesviruses ,...	[ "Transmission is a matter of life or death for pathogen lineages and can therefore be considered as the main motor of their evolution .", "Gammaherpesviruses are archetypal pathogenic persistent viruses which have evolved to be transmitted in presence of specific immune response .", "Identifying their mode of t...	[ "Epstein-Barr virus and the Kaposi's Sarcoma-associated Herpesvirus are two human gammaherpesviruses which are linked to the development of several cancers .", "Efficient control of these infections is therefore of major interest , particularly in some epidemiological circumstances .", "These viruses are howeve...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biogeography", "population genetics", "genome sequencing", "genome analysis tools", "effective population size", "zoology", "structural genomics", "genetic polymorphism", "chromosome biology", "comparative genomics", "biology", "population ecology", "conservation science", "haplotypes", ...	Regions of Homozygosity in the Porcine Genome: Consequence of Demography and the Recombination Landscape	journal.pgen.1003100	null	[ [ "The effect of parental relatedness on the fitness of the offspring has long been recognized .", "Consanguineous matings cause the inheritance of haplotypes that are Identical By Descent ( IBD ) , resulting in potentially long homozygous stretches across the genome of the offspring .", "These Regions ...	[ "Inbreeding has long been recognized as a primary cause of fitness reduction in both wild and domesticated populations .", "Consanguineous matings cause inheritance of haplotypes that are identical by descent ( IBD ) and result in homozygous stretches along the genome of the offspring .", "Size and position of ...	[ "Small populations have an increased risk of inbreeding depression due to a higher expression of deleterious alleles .", "This can have major consequences for the viability of these populations .", "In domesticated species like the pig that are artificially selected in breeding populations , but also in wild po...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biochemistry", "developmental biology", "computer science", "genomics", "computer modeling", "mathematics", "genetics", "applied mathematics", "biology", "computational biology", "evolutionary biology", "genetics and genomics" ]	Rearrangements of 2.5 Kilobases of Noncoding DNA from the Drosophila even-skipped Locus Define Predictive Rules of Genomic cis-Regulatory Logic	journal.pgen.1003243	null	[ [ "Understanding DNA encoding of the cis-regulatory logic responsible for controlling gene expression in metazoans is a problem at the heart of modern genomics .", "As yet , a precise and predictive decryption of this code comparable to the genetic code for protein structure has remained elusive .", "Ne...	[ "Rearrangements of about 2 . 5 kilobases of regulatory DNA located 5′ of the transcription start site of the Drosophila even-skipped locus generate large-scale changes in the expression of even-skipped stripes 2 , 3 , and 7 .", "The most radical effects are generated by juxtaposing the minimal stripe enhancers MS...	[ "Metazoan genes , including those of humans , contain large noncoding regions that are required for viability .", "Sequence variations in these regions are statistically associated with human disease , but the mechanisms underlying these associations are not well understood .", "These regions regulate transcrip...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology/breast cancer", "computational biology/systems biology", "computational biology/genomics" ]	CAERUS: Predicting CAncER oUtcomeS Using Relationship between Protein Structural Information, Protein Networks, Gene Expression Data, and Mutation Data	journal.pcbi.1001114	null	[ [ "Cancer development is a complex process driven by multiple genetic and environmental factors [1] , [2] , [3] .", "Understanding the underlying mechanism of this process and identifying related markers to assess the outcome of this process could lead to better management and treatment of this complex dise...	[ "Carcinogenesis is a complex process with multiple genetic and environmental factors contributing to the development of one or more tumors .", "Understanding the underlying mechanism of this process and identifying related markers to assess the outcome of this process would lead to more directed treatment and thu...	[ "It is widely known that cancer is a complex process in which a large number of genes appear to be involved .", "Through experimental approaches , some oncogenes and tumor suppressors have been identified as playing important roles in the signaling and the regulatory pathways .", "However , we have not fully un...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "molecular biology/rna-protein interactions", "virology/viral replication and gene regulation", "molecular biology/mrna stability", "molecular biology/mrna transport and localization", "virology/effects of virus infection on host gene e...	Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein Binds and Protects a Nuclear Noncoding RNA from Cellular RNA Decay Pathways	journal.ppat.1000799	null	[ [ "Post-transcriptional events in mRNA biogenesis are of central importance to the fidelity and regulation of gene expression .", "Cellular factors regulate nearly every step of RNA metabolism including transcription elongation , RNA splicing , 3′ end formation , nuclear export , translation , etc .", "...	[ "The control of RNA stability is a key determinant in cellular gene expression .", "The stability of any transcript is modulated through the activity of cis- or trans-acting regulatory factors as well as cellular quality control systems that ensure the integrity of a transcript .", "As a result , invading viral...	[ "In order to replicate efficiently , a virus must ensure that its genes are properly expressed in the context of an infected host cell .", "Recent work has demonstrated that eukaryotic cells have RNA quality control pathways that degrade improperly processed , aberrant RNAs .", "Our published findings using an ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "epilepsy", "synapses", "neurological disorders", "neurology", "biology", "neuroscience", "neurophysiology" ]	Enhancement of Asynchronous Release from Fast-Spiking Interneuron in Human and Rat Epileptic Neocortex	journal.pbio.1001324	Asynchronous GABA release occurs at output synapses of fast-spiking interneurons in human and rat neocortex and is elevated in epileptic tissues from both species.	[ [ "During active states in the cerebral cortex , cortical neurons receive both excitatory and inhibitory synaptic inputs .", "Proper balance of these inputs [1] , [2] is important for neuronal responsiveness to incoming inputs [3] , [4] and for sensory processing [5] , [6] .", "Disruption of this balanc...	[ "Down-regulation of GABAergic inhibition may result in the generation of epileptiform activities .", "Besides spike-triggered synchronous GABA release , changes in asynchronous release ( AR ) following high-frequency discharges may further regulate epileptiform activities .", "In brain slices obtained from surg...	[ "The balance between excitation and inhibition in the cerebral cortex is important for multiple brain functions .", "Down-regulation of GABA-induced inhibition disrupts this balance and may lead to epileptic seizures .", "Asynchronous release of GABA is known to occur at certain GABAergic synapses and represent...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "engineering and technology", "african trypanosomiasis", "angola", "tropical diseases", "geographical locations", "parasitic diseases", "parasitology", "neglected tropical diseases", "africa", "prototypes", "infectious diseases", "zoonoses", ...	Sensitivity and Specificity of a Prototype Rapid Diagnostic Test for the Detection of Trypanosoma brucei gambiense Infection: A Multi-centric Prospective Study	journal.pntd.0004608	null	[ [ "Human African trypanosomiasis ( HAT ) or sleeping sickness is a neglected tropical disease that is endemic in remote , resource-limited regions of sub-Saharan African countries [1] .", "The disease is transmitted by infected Glossina species ( tsetse fly ) and presents in two different forms caused by tw...	[ "A major challenge in the control of human African trypanosomiasis ( HAT ) is lack of reliable diagnostic tests that are rapid and easy to use in remote areas where the disease occurs .", "In Trypanosoma brucei gambiense HAT , the Card Agglutination Test for Trypanosomiasis ( CATT ) has been the reference screeni...	[ "Early diagnosis and treatment of human African trypanosomiasis is essential for safe and effective treatment .", "The tests used to screen suspected patients and populations at risk are difficult to implement in remote rural settings where the disease occurs .", "Availability of simple , easy to use , instrume...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics/theory and simulation", "cell biology/cytoskeleton" ]	Molecular Mechanics of the α-Actinin Rod Domain: Bending, Torsional, and Extensional Behavior	journal.pcbi.1000389	null	[ [ "Cytoskeletal microfilament networks contribute to the mechanical stability of the cell by dynamically arranging and rearranging actin filaments for reinforcement .", "The dynamic arrangement of actin filament requires actin filament crosslinking molecules such as α-actinin .", "α-Actinin is a 200 kDa...	[ "α-Actinin is an actin crosslinking molecule that can serve as a scaffold and maintain dynamic actin filament networks .", "As a crosslinker in the stressed cytoskeleton , α-actinin can retain conformation , function , and strength .", "α-Actinin has an actin binding domain and a calmodulin homology domain sepa...	[ "The cell interacts with its environment in both biochemical and mechanical ways .", "In this study we explore one of the ways in which the cell interacts mechanically with its environment .", "α-Actinin is a cytoskeletal crosslinker: it functions to scaffold the cytoskeletal actin filaments that provide mechan...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell walls", "plant anatomy", "vesicles", "plant cell biology", "cell processes", "brassica", "pollen", "membrane proteins", "plant cell walls", "plant science", "model organisms", "golgi apparatus", "plants", "cellular structures and organelles", "research and analysis methods", "ara...	Arabidopsis COG Complex Subunits COG3 and COG8 Modulate Golgi Morphology, Vesicle Trafficking Homeostasis and Are Essential for Pollen Tube Growth	journal.pgen.1006140	null	[ [ "In flowering plants , pollen tubes grow through the style and deliver male gametes to ovules through highly polarized growth of the tips caused by cell expansion occurring exclusively at the apex [1] .", "Pollen tubes can grow rapidly under both in vivo and in vitro conditions where actomyosin-dependent ...	[ "Spatially and temporally regulated membrane trafficking events incorporate membrane and cell wall materials into the pollen tube apex and are believed to underlie the rapid pollen tube growth .", "In plants , the molecular mechanisms and physiological functions of intra-Golgi transport and Golgi integrity mainte...	[ "In the pistils of flowering plants , pollen tubes elongate at the tips to deliver the male gametes to the egg cells for fertilization .", "The tip growth of pollen tube is due to the deposition of cell membranes and wall materials at a restricted tip area of the plasma membrane .", "Vesicle trafficking events ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "molecular biology/post-translational regulation of gene expression", "developmental biology/stem cells", "cell biology/cell growth and division", "cell biology/developmental molecular mechanisms", "developmental biology/cell differentiation", "developmental biology/m...	Cyclin E and Cdk2 Control GLD-1, the Mitosis/Meiosis Decision, and Germline Stem Cells in Caenorhabditis elegans	journal.pgen.1001348	null	[ [ "Metazoan development coordinates progression through the cell cycle with key developmental events , such as stem cell maintenance , cell fate specification and patterning .", "An emerging theme is that core cell cycle regulators can influence development in addition to their more traditional role .", ...	[ "Coordination of the cell cycle with developmental events is crucial for generation of tissues during development and their maintenance in adults .", "Defects in that coordination can shift the balance of cell fates with devastating clinical effects .", "Yet our understanding of the molecular mechanisms integra...	[ "How are cell cycle regulators coordinated with cell fate and patterning regulators during development ?", "Several studies suggest that core cell cycle regulators can influence development , but molecular mechanisms remain unknown for the most part .", "We have tackled this question in the nematode Caenorhabdi...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "trophozoites", "parasite groups", "medicine and health sciences", "pathology and laboratory medicine", "vertebrates", "parasitic protozoans", "animals", "parasitology", "mammals", "apicomplexa", "phylogenetics", "data management", "protozoans", "signs and symptoms", "phylo...	AIG1 affects in vitro and in vivo virulence in clinical isolates of Entamoeba histolytica	journal.ppat.1006882	null	[ [ "Amebiasis , a common protozoan infection in developing and developed countries , results in an estimated 40 , 600 to 73 , 800 deaths annually [1] .", "Amebiasis occurs upon ingestion of water or food contaminated with dormant cysts of Entamoeba histolytica; the cysts , then , form motile trophozoites tha...	[ "The disease state of amebiasis , caused by Entamoeba histolytica , varies from asymptomatic to severe manifestations that include dysentery and extraintestinal abscesses .", "The virulence factors of the pathogen , and host defense mechanisms , contribute to the outcomes of infection; however , the underlying ge...	[ "Comparative genomic analysis of pathogens is used to identify genes associated with disease manifestations .", "In the present study , this approach was used to identify genes , present in a strain of Entamoeba histolytica isolated from dysenteric patients , but absent in strains isolated from asymptomatic infec...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Comprehensive Meta-analysis of Ontology Annotated 16S rRNA Profiles Identifies Beta Diversity Clusters of Environmental Bacterial Communities	journal.pcbi.1004468	null	[ [ "The often quoted tenet:“Everything is everywhere , but the environment selects” by Lourens Baas Becking has been subject to intense debate [1] .", "It gave rise to a series of hypotheses , how exactly the environment selects , i . e . , which ecological rules are driving selection in which environment an...	[ "Comprehensive mapping of environmental microbiomes in terms of their compositional features remains a great challenge in understanding the microbial biosphere of the Earth .", "It bears promise to identify the driving forces behind the observed community patterns and whether community assembly happens determinis...	[ "We here set out to map the entirety of available environmental microbiomes in order to discover the underlying compositional characteristics .", "For us it is intriguing to see which environmental factors influence the assembly of microbiomes .", "We collected many diverse environmental samples and annotated t...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "vero cells", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "biological cultures", "vector-borne diseases", "microbiology", "saliva", "animals", "viral vectors", "viruses", "rna viruse...	Vector Competence of American Mosquitoes for Three Strains of Zika Virus	journal.pntd.0005101	null	[ [ "Zika virus ( ZIKV , Flaviviridae; Flavivirus ) , was first isolated from a febrile sentinel rhesus monkey in Uganda in 1947 [1] .", "Until recently , ZIKV was associated with periodic outbreaks of febrile illness in humans .", "Prior to 2007 , the geographic range was restricted to Africa and parts o...	[ "In 2015 , Zika virus ( ZIKV; Flaviviridae; Flavivirus ) emerged in the Americas , causing millions of infections in dozens of countries .", "The rapid spread of the virus and the association with disease outcomes such as Guillain-Barré syndrome and microcephaly make understanding transmission dynamics essential ...	[ "The mechanisms contributing to the explosive nature of the current ZIKV outbreak in the Americas are poorly understood .", "Therefore , we characterized the replication of three strains , one from each phylogenetic clade of ZIKV and evaluated virus strain differences in transmission efficiency by American mosqui...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell physiology", "resonance frequency", "medicine and health sciences", "action potentials", "neural networks", "nervous system", "membrane potential", "junctional complexes", "electrophysiology", "neuroscience", "gap junctions", "neuronal plasticity", "computer and information sciences", ...	Gap junction plasticity as a mechanism to regulate network-wide oscillations	journal.pcbi.1006025	null	[ [ "Oscillatory patterns of neuronal activity are reported in many brains regions with frequencies ranging from less than one Hertz to hundreds of Hertz .", "These oscillations are often associated with cognitive phenomena such as sleep or attention .", "Local field potential measurements in the neocorte...	[ "Cortical oscillations are thought to be involved in many cognitive functions and processes .", "Several mechanisms have been proposed to regulate oscillations .", "One prominent but understudied mechanism is gap junction coupling .", "Gap junctions are ubiquitous in cortex between GABAergic interneurons .", ...	[ "Oscillations of neural activity emerge when many neurons repeatedly activate together and are observed in many brain regions , particularly during sleep and attention .", "Their functional role is still debated , but could be associated with normal cognitive processes such as memory formation or with pathologies...	2018
[ "Introduction", "Methods", "Results and discussion" ]	[ "sequencing techniques", "taxonomy", "split-decomposition method", "multiple alignment calculation", "phylogenetics", "data management", "protein structure", "molecular biology techniques", "research and analysis methods", "sequence analysis", "computer and information sciences", "sequence ali...	The intrinsic dimension of protein sequence evolution	journal.pcbi.1006767	null	[ [ "Protein sequence evolution is an extremely important process in living organisms .", "During evolution , due to insertions , deletions , substitutions , a sequence can significantly change .", "Still , and most importantly , three-dimensional structures and functions are conserved , so that protein d...	[ "It is well known that , in order to preserve its structure and function , a protein cannot change its sequence at random , but only by mutations occurring preferentially at specific locations .", "We here investigate quantitatively the amount of variability that is allowed in protein sequence evolution , by comp...	[ "Protein sequence evolution is an extremely complex process , whose roles are ultimately determined by the necessity of living organisms to adapt to changes in the environment .", "We here address a fundamental question related with this process: in how many independent directions can a sequence evolve , without ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Selective Pressures to Maintain Attachment Site Specificity of Integrative and Conjugative Elements	journal.pgen.1003623	null	[ [ "Integrative and conjugative elements ( ICEs , also known as conjugative transposons ) are mobile genetic elements that encode conjugation machinery that mediates their transfer from cell to cell .", "Most characterized ICEs were identified because they carry additional genes that confer phenotypes to the...	[ "Integrative and conjugative elements ( ICEs ) are widespread mobile genetic elements that are usually found integrated in bacterial chromosomes .", "They are important agents of evolution and contribute to the acquisition of new traits , including antibiotic resistances .", "ICEs can excise from the chromosome...	[ "Integrative and conjugative elements ( ICEs ) are mobile genetic elements that transfer DNA between bacteria , driving bacterial evolution and the acquisition of new traits , including antibiotic resistances .", "ICEs normally reside integrated in a host genome , but can excise and transfer to recipient cells ."...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular probe techniques", "enzymes", "messenger rna", "rna extraction", "microbiology", "enzymology", "immunoblotting", "plasmid construction", "untranslated regions", "dna construction", "molecular biology techniques", "extraction techniques", "genetic footprinting", "research and ana...	Additive Promotion of Viral Internal Ribosome Entry Site-Mediated Translation by Far Upstream Element-Binding Protein 1 and an Enterovirus 71-Induced Cleavage Product	journal.ppat.1005959	null	[ [ "Enterovirus 71 ( EV71 ) , a cytoplasmic RNA virus of the Picornaviridae family , is known to infect both animals and humans , and can cause highly fatal neurological complications [1 , 2] .", "During the infection process , EV71 binds to P-selectin glycoprotein ligand-1 ( PSGL-1; CD162 ) [3] or scavenger...	[ "The 5' untranslated region ( 5' UTR ) of the enterovirus 71 ( EV71 ) RNA genome contains an internal ribosome entry site ( IRES ) that is indispensable for viral protein translation .", "Due to the limited coding capacity of their RNA genomes , EV71 and other picornaviruses typically recruit host factors , known...	[ "Many RNA viruses utilize internal ribosome entry sites ( IRES ) located in the 5’ untranslated region of genomic RNA to translate viral proteins in a cap-independent manner .", "Host proteins that are recruited to assist in viral IRES-driven translation are known as ITAFs ( IRES trans-acting factors ) , of which...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "antimicrobials", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "engineering and technology", "pathogens", "drugs", "immunology", "tropical diseases", "microbiology", "antifungals", "toxicology", "nanoparticles", "paracoccidioidomycos...	Antifungal Activity of Amphotericin B Conjugated to Nanosized Magnetite in the Treatment of Paracoccidioidomycosis	journal.pntd.0004754	null	[ [ "Paracoccidioidomycosis ( PCM ) is a systemic fungal infection caused by Paracoccidioides brasiliensis and Paracoccidioides lutzii [1] .", "PCM represents the most important systemic mycosis in Central and South America .", "PCM significantly affects public health primarily targeting rural workers wit...	[ "This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated ( with a double-layer of lauric acid ) magnetite nanoparticles .", "The in vitro tests compared two drugs; i ...	[ "Lung fungal infections are caused by pathogens inhaled as spores which convert into invasive yeast forms in the lungs .", "This type of infection can spread to other sites in the body through the blood and lymphatic systems , sometimes leading to ulcerations and skin lesions .", "The drug of choice for treatme...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "enzymes", "cytotoxicity assay", "cell processes", "enzymology", "immunology", "parasitic diseases", "toxicology", "organisms", "serine proteases", "fluorescence spectros...	Neutrophils kill the parasite Trichomonas vaginalis using trogocytosis	journal.pbio.2003885	null	[ [ "Trichomonas vaginalis is a unicellular , flagellated eukaryote that lives as an obligate extracellular parasite , restricted to humans [1 , 2 , 3] .", "T . vaginalis causes the most common nonviral sexually transmitted infection ( STI ) worldwide: trichomoniasis [1 , 4] .", "The World Health Organiza...	[ "T . vaginalis , a human-infective parasite , causes the most common nonviral sexually transmitted infection ( STI ) worldwide and contributes to adverse inflammatory disorders .", "The immune response to T . vaginalis is poorly understood .", "Neutrophils ( polymorphonuclear cells [PMNs] ) are the major immune...	[ "The human parasite Trichomonas vaginalis is a large unicellular , motile eukaryote that causes a highly prevalent sexually transmitted infection in humans: trichomoniasis .", "While harmful effects of trichomoniasis are associated with inflammation , the immune response to the parasite is sorely under-characteri...	2018
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biochemistry", "biophysics/protein folding", "biophysics/experimental biophysical methods", "biochemistry/protein folding", "biophysics/theory and simulation", "computational biology/molecular dynamics", "biochemistry/theory and simulation", "computational biology", "biophysics" ]	Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains	journal.pcbi.1000645	null	[ [ "The formation of contacts between pairs of residues in an unfolded polypeptide chain is one of the earliest steps in in vitro protein folding and is considered to determine the so-called protein folding speed limit [1] .", "Evidence exists for unfolded states being compact under native conditions [2]–[11...	[ "Characterization of the length dependence of end-to-end loop-closure kinetics in unfolded polypeptide chains provides an understanding of early steps in protein folding .", "Here , loop-closure in poly-glycine-serine peptides is investigated by combining single-molecule fluorescence spectroscopy with molecular d...	[ "In studies of protein folding evidence exists for early compaction in the unfolded state , although it is unclear whether these compact conformations contain specific secondary structures ( through hydrophilic interactions ) or whether compaction is a non-specific hydrophobic-driven effect .", "Here we combine s...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "medicine and health sciences", "pathology and laboratory medicine", "enzymes", "skeletal muscles", "enzymology", "parasitic diseases", "muscle proteins", "molecular motors", "molecular biology techniques", "ligases", "motor proteins", "research and analysis methods"...	Ubiquitin-Dependent Modification of Skeletal Muscle by the Parasitic Nematode, Trichinella spiralis	journal.ppat.1005977	null	[ [ "The ubiquitin ( Ub ) pathway is essential for post-translational protein regulation in eukaryotic cells , controlling many important cellular processes such as transcription , cell cycle , differentiation and apoptosis ( [1 , 2] .", "Ub is a 76 amino acid protein that , in a highly regulated fashion , is...	[ "Trichinella spiralis is a muscle-specific parasitic worm that is uniquely intracellular .", "T . spiralis reprograms terminally differentiated skeletal muscle cells causing them to de-differentiate and re-enter the cell cycle , a process that cannot occur naturally in mammalian skeletal muscle cells , but one th...	[ "Parasitic worms often establish long-lasting infections in their hosts; tightly regulating their surroundings to strike a delicate balance between host cell modulation and protection that will ensure their replication .", "This is accomplished via the active secretion of parasite glycolipids and glycoproteins in...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "trophozoites", "parasite groups", "markov models", "giardia", "parasitic protozoans", "parasitology", "apicomplexa", "fungi", "model organisms", "protozoans", "mathematics", "experimental organism systems", "saccharomyces", "giardia lamblia", "research and analysis methods", "sequence...	The single cyclic nucleotide-specific phosphodiesterase of the intestinal parasite Giardia lamblia represents a potential drug target	journal.pntd.0005891	null	[ [ "Giardia lamblia is a protozoan parasite that causes giardiasis , an intestinal disease with symptoms such as diarrhea , nausea , and malabsorption [1] .", "Trophozoites are the disease-causing stage and colonize the upper small intestine of humans and other vertebrates .", "They form cysts , which ar...	[ "Giardiasis is an intestinal infection correlated with poverty and poor drinking water quality , and treatment options are limited .", "According to the Center for Disease Control and Prevention , Giardia infections afflict nearly 33% of people in developing countries , and 2% of the adult population in the devel...	[ "Cellular signaling by the cyclic nucleotides cAMP and cGMP is ubiquitously found in organisms from human to unicellular parasites .", "Cyclic nucleotide-specific phosphodiesterases ( PDEs ) are pivotal regulators of these signaling processes and these enzymes represent important drug targets for a variety of dis...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "cancer detection and diagnosis", "biochemistry", "carcinogenesis", "physics", "medicine and health sciences", "statistical mechanics", "genetics", "biology and life sciences", "dna", "computational biology", "dna modification", "epigenetics", "epigenomics", "cancer risk fact...	The Dynamics of DNA Methylation Covariation Patterns in Carcinogenesis	journal.pcbi.1003709	null	[ [ "Cancer exhibits widespread DNA methylation ( DNAm ) changes compared to normal tissue [1]–[7] .", "As demonstrated by a number of studies , genomic sites undergoing DNA methylation changes in invasive cancers are already seen to accumulate changes in normal tissue as a function of age [8]–[11] .", "A...	[ "Recently it has been observed that cancer tissue is characterised by an increased variability in DNA methylation patterns .", "However , how the correlative patterns in genome-wide DNA methylation change during the carcinogenic progress has not yet been explored .", "Here we study genome-wide inter-CpG correla...	[ "DNA methylation is a covalent modification of DNA which can regulate how active genes are .", "DNA methylation is altered at many genomic loci in cancer cells , leading to widespread functional disruption .", "Importantly , DNA methylation alterations across the genome are seen even in early carcinogenesis .",...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biotechnology", "biochemistry", "infectious diseases", "medicine and health sciences", "cell biology", "biology and life sciences", "immunology", "microbiology", "tropical diseases", "parasitic diseases", "veterinary science", "parasitology", "agriculture" ]	Engineering Attenuated Virulence of a Theileria annulata–Infected Macrophage	journal.pntd.0003183	null	[ [ "Tropical theileriosis caused by Theileria annulata is a major parasitic disease of cattle and is endemic in North Africa , the Mediterranean basin and Asia ( India and China ) .", "Attenuated live vaccines against tropical theileriosis have been used with success in endemic countries , in spite of MHC di...	[ "Live attenuated vaccines are used to combat tropical theileriosis in North Africa , the Middle East , India , and China .", "The attenuation process is empirical and occurs only after many months , sometimes years , of in vitro culture of virulent clinical isolates .", "During this extensive culturing , attenu...	[ "Tropical theileriosis is a leukaemia-like disease of cattle caused by the Apicomplexa parasite Theileria annulata .", "Live attenuated vaccines are used to control the mortality and morbidity of tropical theileriosis and each endemic country produces its own vaccine by isolating a virulent clinical isolate and t...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "biology" ]	NADPH Phagocyte Oxidase Knockout Mice Control Trypanosoma cruzi Proliferation, but Develop Circulatory Collapse and Succumb to Infection	journal.pntd.0001492	null	[ [ "For a long time , reactive oxygen species ( ROS ) were considered the main anti-microbial radical produced by the immune system , playing a role against bacterial , fungal and protozoa infections .", "After the discovery of nitric oxide ( •NO ) , •NO found to play a major role in host defense , especiall...	[ "•NO is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infection .", "On the other hand , the microbicidal properties of reactive oxygen species ( ROS ) are well recognized , but little importance has been attributed to them during in vivo infection with T . cruzi .", "In ...	[ "When pathogens enter their hosts , they are fought by several resistance strategies , including capture by phagocytes and the production of pathogen-toxic molecules .", "Nitric oxide , a free radical , has been extensively studied as one of these toxic molecules that successfully mediates intracellular parasite ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "medicine and health sciences", "cell biology", "viral persistence and latency", "pathology and laboratory medicine", "host-pathogen interactions", "cell growth", "virology", "virulence factors", "pathogens", "biology and life sciences", "cell processes", "microbiology...	Epstein-Barr Virus Nuclear Antigen 3A Promotes Cellular Proliferation by Repression of the Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1	journal.ppat.1004415	null	[ [ "Epstein-Barr virus ( EBV ) infection of primary B cells results in sustained cellular proliferation and immortalization of infected cells in vitro , through the expression of the viral latency-associated genes: EBV nuclear antigens ( EBNAs ) 1 , 2 , 3A , 3B , 3C and LP , latent membrane proteins ( LMPs ) 1 ,...	[ "Latent infection by Epstein-Barr virus ( EBV ) is highly associated with the endemic form of Burkitt lymphoma ( eBL ) , which typically limits expression of EBV proteins to EBNA-1 ( Latency I ) .", "Interestingly , a subset of eBLs maintain a variant program of EBV latency - Wp-restricted latency ( Wp-R ) - that...	[ "Epstein-Barr virus ( EBV ) infects over 98% of the population worldwide and is associated with a variety of human cancers .", "In the healthy host , the virus represses expression of its proteins to avoid detection by the immune system to enable it to remain in the body for the lifetime of its host , a situation...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury	journal.pcbi.1004309	null	[ [ "Pressure ulcers ( PU ) affect 2 . 5 million US acute care patients and cost up to $1 billion per year [1] .", "They are a significant source of morbidity in both hospitalized patients and community-dwelling individuals with impaired mobility .", "PUs are especially common in individuals with spinal c...	[ "People with spinal cord injury ( SCI ) are predisposed to pressure ulcers ( PU ) .", "PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions .", "An agent-based model ( ABM ) of ischemia/reperfusion-induced inflammation and PU ( ...	[ "A virtual pressure ulcer was created as a platform to test therapies and determine the mechanisms most correlated with unfavorable outcomes .", "A layer of tissue fed with oxygen and diffusible molecules via blood vessels could develop an ulcer if pressure was applied , by simulating constriction of blood vessel...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "model organisms", "gene expression", "genetics", "epigenetics", "biology", "molecular genetics", "genetics and genomics" ]	Autoregulation of the Drosophila Noncoding roX1 RNA Gene	journal.pgen.1002564	null	[ [ "Some long noncoding RNAs have the ability to recruit chromatin modifying enzymes to specific genes thereby controlling their expression [1] .", "Other noncoding RNAs behave as transcriptional enhancers to flanking protein coding genes [2] .", "The two roX RNAs that participate in dosage compensation ...	[ "Most genes along the male single X chromosome in Drosophila are hypertranscribed about two-fold relative to each of the two female X chromosomes .", "This is accomplished by the MSL ( male-specific lethal ) complex that acetylates histone H4 at lysine 16 .", "The MSL complex contains two large noncoding RNAs ,...	[ "In fruit flies , the male undergoes dosage compensation to increase the transcriptional output of its single X chromosome to match that of the females' two copies .", "A large ribonucleoprotein complex that consists of two large noncoding RNA , roX1 and roX2 , and at least five MSL ( male specific lethal ) chrom...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/functional genomics", "evolutionary biology/genomics", "evolutionary biology", "genetics and genomics", "genetics and genomics/population genetics" ]	Population-Based Resequencing of Experimentally Evolved Populations Reveals the Genetic Basis of Body Size Variation in Drosophila melanogaster	journal.pgen.1001336	null	[ [ "Body size is a critical phenotype for all organisms .", "In Drosophila species , considerable evidence from natural populations indicates size is under spatially varying selection , with larger size selected in higher latitudes [1]–[4] .", "Body size is also sexually dimorphic in D . melanogaster , y...	[ "Body size is a classic quantitative trait with evolutionarily significant variation within many species .", "Locating the alleles responsible for this variation would help understand the maintenance of variation in body size in particular , as well as quantitative traits in general .", "However , successful ge...	[ "Understanding the causes and consequences of natural genetic variation is crucial to the characterization of biological evolution .", "Moreover , natural genetic variation is comprised of millions of perturbations , which are partially randomized across genotypes such that a small number of individuals can be us...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusion" ]	[ "medicine", "infectious diseases", "leishmaniasis", "neglected tropical diseases" ]	Latent Infection with Leishmania donovani in Highly Endemic Villages in Bihar, India	journal.pntd.0002053	null	[ [ "Visceral leishmaniasis ( VL ) or kala-azar is a parasitic infectious disease that is fatal if left untreated .", "Two Leishmania species are causal agents of VL: L . infantum and L . donovani .", "The first is a zoonosis and is endemic in countries around the Mediterranean basin and in Latin-America ...	[ "Asymptomatic persons infected with the parasites causing visceral leishmaniasis ( VL ) usually outnumber clinically apparent cases by a ratio of 4–10 to 1 .", "We describe patterns of markers of Leishmania donovani infection and clinical VL in relation to age in Bihar , India .", "We selected eleven villages h...	[ "In this study we assessed trends with age in the probability of being sero-positive or sero-converting for two serological markers of visceral leishmaniasis ( VL ) among asymptomatic residents of high incidence villages .", "As markers we used Direct Agglutination Test ( DAT ) and rK39 ELISA .", "We also compa...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	From Sensory Signals to Modality-Independent Conceptual Representations: A Probabilistic Language of Thought Approach	journal.pcbi.1004610	null	[ [ "While eating breakfast , you might see your coffee mug , grasp your coffee mug , or both .", "When viewing your mug , your visual system extracts and represents the shape of your mug .", "Similarly , when grasping your mug , your haptic system also extracts and represents the shape of your mug .", ...	[ "People learn modality-independent , conceptual representations from modality-specific sensory signals .", "Here , we hypothesize that any system that accomplishes this feat will include three components: a representational language for characterizing modality-independent representations , a set of sensory-specif...	[ "When viewing an object , people perceive the object’s shape .", "Similarly , when grasping the same object , they also perceive its shape .", "In general , the perceived shape is identical in these two scenarios , illustrating modality invariance , an important type of perceptual constancy .", "Modality inva...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome analysis tools", "prokaryotic models", "model organisms", "gene expression", "genetics", "molecular genetics", "biology", "genomics", "microbiology", "genetics and genomics" ]	Three Essential Ribonucleases—RNase Y, J1, and III—Control the Abundance of a Majority of Bacillus subtilis mRNAs	journal.pgen.1002520	null	[ [ "The amount of a particular mRNA in the cell is a function of the equilibrium between its synthesis and degradation .", "The pathways of RNA degradation are fairly well defined in the Gram-negative model bacterium Escherichia coli and in the eukaryotic paradigm Saccharyomyces cerevisiae .", "In E . co...	[ "Bacillus subtilis possesses three essential enzymes thought to be involved in mRNA decay to varying degrees , namely RNase Y , RNase J1 , and RNase III .", "Using recently developed high-resolution tiling arrays , we examined the effect of depletion of each of these enzymes on RNA abundance over the whole genome...	[ "RNA turnover is an important way of controlling gene expression .", "While the characterization of the pathways and enzymes for RNA degradation are well-advanced in Escherichia coli and yeast , studies in Gram-positive bacteria have lagged behind .", "This tiling array study shows that two essential enzymes , ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "zoology", "biology and life sciences", "developmental biology" ]	A Role for Taiman in Insect Metamorphosis	journal.pgen.1004769	null	[ [ "Insect metamorphosis , either through gradual morphogenesis ( hemimetaboly ) or abrupt morphogenesis mediated by the pupal stage ( holometaboly ) , is essentially regulated by two hormones , 20-hydroxyecdysone ( 20E ) and juvenile hormone ( JH ) .", "20E triggers the successive moults throughout the life...	[ "Recent studies in vitro have reported that the Methoprene-tolerant ( Met ) and Taiman ( Tai ) complex is the functional receptor of juvenile hormone ( JH ) .", "Experiments in vivo of Met depletion have confirmed this factor's role in JH signal transduction , however , there is no equivalent data regarding Tai b...	[ "Insect metamorphosis is one of the most fascinating processes of animal development .", "However , the mechanisms governing metamorphosis only started to be unveiled in the last century , when physiological research revealed that the main factor involved is juvenile hormone ( JH ) , which represses metamorphosis...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "bacterial diseases", "infectious diseases", "group b streptococcal infection", "immunology", "biology", "immune response" ]	The Pore-Forming Toxin β hemolysin/cytolysin Triggers p38 MAPK-Dependent IL-10 Production in Macrophages and Inhibits Innate Immunity	journal.ppat.1002812	null	[ [ "The pore-forming toxin ( PFT ) β hemolysin/cytolysin ( βh/c ) is a major virulence factor for Group B streptococcus ( GBS ) , which is generally attributed to its cytolytic functions that aid invasion and avoid phagocytic killing [1] .", "However , recent data have shown PFTs can act as pathogen associat...	[ "Group B Streptococcus ( GBS ) is a leading cause of invasive bacterial infections in human newborns and immune-compromised adults .", "The pore-forming toxin ( PFT ) β hemolysin/cytolysin ( βh/c ) is a major virulence factor for GBS , which is generally attributed to its cytolytic functions .", "Here we show β...	[ "Our studies show β hemolysin/cytolysin ( βh/c ) from Group B Streptococcus ( GBS ) , inhibits the activation of macrophages and the innate immune response to GBS .", "We show that βh/c triggers activation of mitogen activated protein kinase ( MAPK ) in GBS-infected macrophages leading to expression of the anti-i...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "horizontal gene transfer", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "computational biology", "microbiology", "staphylococcus aureus", "gene transfer", "methicillin-resistant staphylococcus aureus", "metagenomics", "helicobacter", "genome analysis", "...	Where did you come from, where did you go: Refining metagenomic analysis tools for horizontal gene transfer characterisation	journal.pcbi.1007208	null	[ [ "For a long time , evolution in terms of gene transfer was thought to happen only along the tree of life , i . e . from parent to offspring generation .", "The discovery of horizontal gene transfer ( HGT ) [1–4] has revolutionised this dogma , and revealed the mechanism that enables bacteria to quickly ad...	[ "Horizontal gene transfer ( HGT ) has changed the way we regard evolution .", "Instead of waiting for the next generation to establish new traits , especially bacteria are able to take a shortcut via HGT that enables them to pass on genes from one individual to another , even across species boundaries .", "The ...	[ "Evolution is traditionally viewed as a process where changes are only vertically inherited from parent to offspring across generations .", "Many principles such as phylogenetic trees and even the “tree of life” are based on that doctrine .", "The concept of horizontal gene transfer changed the way we regard ev...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biology" ]	Multiscale Modeling of Red Blood Cell Mechanics and Blood Flow in Malaria	journal.pcbi.1002270	null	[ [ "Malaria is a disease caused by a Plasmodium parasite , which infects red blood cells ( RBCs ) .", "In particular , Plasmodium falciparum ( Pf ) causes one of the most serious forms of malaria resulting in a nearly million deaths per year .", "Pf-parasitized red blood cells ( Pf-RBCs ) experience prog...	[ "Red blood cells ( RBCs ) infected by a Plasmodium parasite in malaria may lose their membrane deformability with a relative membrane stiffening more than ten-fold in comparison with healthy RBCs leading to potential capillary occlusions .", "Moreover , infected RBCs are able to adhere to other healthy and parasi...	[ "One of the most severe forms of cerebral malaria is caused by the parasite Plasmodium falciparum .", "During its development inside the host red blood cell it causes major mechanical and biochemical changes to the cell and can even alter its biconcave shape .", "The two main mechanical modifications are signif...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Drosophila bag of marbles Gene Interacts Genetically with Wolbachia and Shows Female-Specific Effects of Divergence	journal.pgen.1005453	null	[ [ "Population genetic and comparative analyses in diverse taxa have shown that many genes involved in reproduction are evolving under adaptive evolution [1–3] .", "Various selective pressures have been hypothesized to drive the adaptive evolution of those reproductive genes including sexual conflict , sexua...	[ "Many reproductive proteins from diverse taxa evolve rapidly and adaptively .", "These proteins are typically involved in late stages of reproduction such as sperm development and fertilization , and are more often functional in males than females .", "Surprisingly , many germline stem cell ( GSC ) regulatory g...	[ "Animals need to make gametes–sperm or eggs–in order to reproduce .", "Gametes are produced from a specialized tissue called the germline that is found within the testes or ovaries .", "These organs contain a small population of stem cells that are able to both self-renew and differentiate to generate gametes a...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "velocity", "ecology and environmental sciences", "classical mechanics", "social sciences", "neuroscience", "cognitive psychology", "animal behavior", "vision", "zoology", "animal sociality", "behavior", "community ecology", "physics", "psychology", "ecology", "predation", "trophic i...	A Sensory-Driven Trade-Off between Coordinated Motion in Social Prey and a Predator’s Visual Confusion	journal.pcbi.1004708	null	[ [ "Organisms are constantly challenged by the need to effectively extract and process pertinent information from uncertain and often dangerous environments .", "Many species manage to reduce their uncertainty through social information .", "When animals gather together and coordinate their activities th...	[ "Social animals are capable of enhancing their awareness by paying attention to their neighbors , and prey found in groups can also confuse their predators .", "Both sides of these sensory benefits have long been appreciated , yet less is known of how the perception of events from the perspectives of both prey an...	[ "Many social species coordinate their movements as they travel together , which is generally considered to be an adaptive behavior predominantly mediated by vision .", "Collective coordination lowers the individual’s chances of becoming separated from the group and can reduce the time spent in risky areas .", "...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "cytokines", "respiratory infections", "immunology", "pulmonology", "rhinovirus infection", "allergy and hypersensitivity", "asthma", "infectious diseases", "immune system", "clinical immunology", "immunity", "innate immunity", "viral diseases", "respiratory medicine" ]	MDA5 and TLR3 Initiate Pro-Inflammatory Signaling Pathways Leading to Rhinovirus-Induced Airways Inflammation and Hyperresponsiveness	journal.ppat.1002070	null	[ [ "Rhinovirus ( RV ) is the most frequent cause of acute respiratory tract infection in humans .", "RV infection is typically responsible for upper respiratory symptoms including rhinorrhea , sore throat , nasal congestion , sneezing , cough , and headache .", "More importantly , RV has emerged as the m...	[ "Rhinovirus ( RV ) , a single-stranded RNA picornavirus , is the most frequent cause of asthma exacerbations .", "We previously demonstrated in human bronchial epithelial cells that melanoma differentiation-associated gene ( MDA ) -5 and the adaptor protein for Toll-like receptor ( TLR ) -3 are each required for ...	[ "Rhinovirus ( RV ) is the most frequent cause of acute respiratory tract infection in humans .", "RV has emerged as the most frequent pathogen associated with exacerbations of asthma .", "However , the mechanisms by which RV causes asthma flare-ups are not precisely known .", "We studied the requirements of t...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viruses", "infectious diseases", "virology", "immunology", "mus (mouse)" ]	A Role for NKG2D in NK Cell–Mediated Resistance to Poxvirus Disease	journal.ppat.0040030	null	[ [ "Ectromelia virus ( ECTV ) , the causative agent of mousepox , is an orthopoxvirus ( OPV ) with host specificity for the mouse .", "It is genetically very similar to vaccinia virus ( VACV ) , the human pathogen variola virus ( the agent of smallpox ) , and monkeypox virus [1] , which sporadically infects ...	[ "Ectromelia virus ( ECTV ) is an orthopoxvirus ( OPV ) that causes mousepox , the murine equivalent of human smallpox .", "C57BL/6 ( B6 ) mice are naturally resistant to mousepox due to the concerted action of innate and adaptive immune responses .", "Previous studies have shown that natural killer ( NK ) cells...	[ "Ectromelia virus ( ECTV ) causes mousepox , a murine disease that is the equivalent of human smallpox .", "ECTV normally penetrates through the periphery but rapidly spreads through the lymphatic system to vital organs .", "In mousepox-sensitive strains of mice , ECTV infection culminates with either rapid dea...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "immunology", "biochemistry/theory and simulation", "computational biology/signaling networks", "computational biology", "computational biology/systems biology" ]	Identification of Potential Pathway Mediation Targets in Toll-like Receptor Signaling	journal.pcbi.1000292	null	[ [ "Toll-like receptors ( TLRs ) are a group of conserved pattern recognition receptors that activate the processes of innate and adaptive immunity [1] .", "Recent activity has focused on the characterization of the TLR network and its involvement in the apoptotic , inflammatory , and innate immune responses...	[ "Recent advances in reconstruction and analytical methods for signaling networks have spurred the development of large-scale models that incorporate fully functional and biologically relevant features .", "An extended reconstruction of the human Toll-like receptor signaling network is presented herein .", "This...	[ "The human innate immune system , as the first line of defense against pathogens , is a vital component of our survival .", "One component of the innate immune system is the Toll-like receptor signaling network , which is responsible for transmitting activation signals from the outside of the cell to molecular ma...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "veterinary diseases", "zoonoses", "medicine and health sciences", "health risk analysis", "epidemiology", "leishmaniasis", "biology and life sciences", "protozoan infections", "parasitic diseases", "veterinary science", "health care" ]	Prognostic Factors and Scoring System for Death from Visceral Leishmaniasis: An Historical Cohort Study in Brazil	journal.pntd.0003374	null	[ [ "Visceral leishmaniasis ( VL ) is a severe chronic systemic disease caused by Leishmania infantum parasites in South America , the Mediterranean region , and southwest and central Asia [1] .", "The disease is transmitted to human and animal hosts by the bite of phlebotomine sand flies , and dogs are the m...	[ "In Brazil , case-fatality rates attributable to visceral leishmaniasis ( VL ) are high and knowledge of the risk factors associated with death may help reduce mortality .", "The aim of this study was to construct and validate a scoring system for prognosis of death from VL by using all cases reported in Brazil f...	[ "Visceral leishmaniasis ( VL ) is a fatal disease if not diagnosed and treated appropriately .", "In the present study , we investigated the risk factors associated with death caused by VL identifiable at the time of clinical suspicion .", "This study was conducted using all VL cases registered in Brazil during...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "genome evolution", "cancer risk factors", "cancers and neoplasms", "cloning", "oncology", "mutation", "epigenetics", "dna", "molecular biology techniques", "dna methylation", "chromatin", "research and analysis methods", "genomics", "chromosome biology", ...	Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution	journal.pgen.1005778	null	[ [ "Cancer is a heterogeneous disease .", "Recent cancer genomics studies have revealed extensive genetic diversity among patients .", "Moreover , even a clonal tumor in one patient often harbors multiple subclones .", "This phenomenon is called intratumor heterogeneity ( ITH ) and is presumably gene...	[ "Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation .", "To this end , we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors .", "Extensive intertumor heterogeneity is observed , ...	[ "Cancer is heterogeneous disease; each tumor in different patients has different cancer genomes .", "Furthermore , another level of heterogeneity exists: even a single tumor harbors multiple genetically distinct subclones .", "This intratumor heterogeneity is presumably one of causes of therapeutic difficulty ,...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "theoretical biology", "evolutionary modeling", "biology", "evolutionary theory", "evolutionary biology", "computational biology" ]	Evolutionary Tradeoffs between Economy and Effectiveness in Biological Homeostasis Systems	journal.pcbi.1003163	null	[ [ "Biological networks have been shown to be composed of a small set of recurring interaction patterns , called network motifs [1]–[6] .", "Each motif is a small circuit element that can carry out specific dynamical functions .", "An organism often shows hundreds or thousands of instances of each networ...	[ "Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical .", "For example , regulatory systems that are designed to repair damage must be effective in reducing damage , but economical in not making too many repair proteins because making excessive pro...	[ "Many systems in the cell work to keep homeostasis , or balance .", "For example , damage repair systems make special repair proteins to resolve damage .", "These systems typically have many biochemical parameters such as biochemical rate constants , and it is not clear how much of the huge parameter space is f...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "vaccines", "preventive medicine", "bacterial diseases", "immunologic adjuvants", "enterobacteriaceae", "infectious disease contr...	Immunogenicity and efficacy following sequential parenterally-administered doses of Salmonella Enteritidis COPS:FliC glycoconjugates in infant and adult mice	journal.pntd.0006522	null	[ [ "In sub-Saharan Africa , hospital-based blood culture surveillance of febrile pediatric admissions has revealed that invasive non-typhoidal Salmonella enterica ( iNTS ) infections caused by serovars Typhimurium , I 4 , [5] , 12:i:- , and Enteritidis are widespread among children less than 5 years of age [1 , ...	[ "In sub-Saharan Africa , invasive nontyphoidal Salmonella ( iNTS ) infections with serovars S . Enteritidis , S . Typhimurium and I 4 , [5] , 12:i:- are widespread in children < 5 years old .", "Development of an efficacious vaccine would provide an important public health tool to prevent iNTS disease in this pop...	[ "Non-typhoidal Salmonella enterica ( NTS ) serovars Enteritidis and Typhimurium ( including monophasic variant I 4 , [5] , 12:i:- ) are significant causes of invasive bacterial disease amongst infants and toddlers in sub-Saharan Africa , and currently , there are no approved NTS vaccines .", "We have demonstrated...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Adaptive Protein Evolution in Animals and the Effective Population Size Hypothesis	journal.pgen.1005774	null	[ [ "Characterizing and quantifying adaptation at the molecular level is one of the major goals of evolutionary genomics .", "Recent research in this area has yielded a number of remarkable examples [1–4] .", "However , in spite of the increased size of molecular data sets and intensive methodological dev...	[ "The rate at which genomes adapt to environmental changes and the prevalence of adaptive processes in molecular evolution are two controversial issues in current evolutionary genetics .", "Previous attempts to quantify the genome-wide rate of adaptation through amino-acid substitution have revealed a surprising d...	[ "The rate at which species adapt to environmental changes is a controversial topic .", "The theory predicts that adaptation is easier in large than in small populations , and the genomic studies of model organisms have revealed a much higher adaptive rate in large population-sized flies than in small population-s...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/microbial physiology and metabolism", "microbiology/innate immunity", "biochemistry/biomacromolecule-ligand interactions", "infectious diseases/bacterial infections", "microbiology/microbial growth and development", "microbiology/cellular microbiology and pathogenesis" ]	IlsA, A Unique Surface Protein of Bacillus cereus Required for Iron Acquisition from Heme, Hemoglobin and Ferritin	journal.ppat.1000675	null	[ [ "Iron is an essential element for most organisms , including bacteria , because it is involved in many cellular processes including aerobic respiration , amino acid and nucleotide biosynthesis [1] , [2] .", "Since free iron is highly toxic for the cells , its homeostasis is strictly regulated in living or...	[ "The human opportunistic pathogen Bacillus cereus belongs to the B . cereus group that includes bacteria with a broad host spectrum .", "The ability of these bacteria to colonize diverse hosts is reliant on the presence of adaptation factors .", "Previously , an IVET strategy led to the identification of a nove...	[ "Iron is an essential compound for almost all living organisms , taking part in basic cellular homeostasis .", "Preventing access to iron sources for invading pathogens is one of the defense systems used by hosts to avoid pathogen colonization .", "To counteract this , pathogens have developed mechanisms to acq...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/bioinformatics", "molecular biology/recombination", "genetics and genomics" ]	Evidence for a Xer/dif System for Chromosome Resolution in Archaea	journal.pgen.1001166	null	[ [ "In Bacteria , homologous recombination is essential during DNA replication to resume stalled replication forks and to repair DNA double and single strand breaks .", "Odd numbers of homologous recombination events between circular chromosomes generate dimers , which need to be resolved to ensure proper se...	[ "Homologous recombination events between circular chromosomes , occurring during or after replication , can generate dimers that need to be converted to monomers prior to their segregation at cell division .", "In Escherichia coli , chromosome dimers are converted to monomers by two paralogous site-specific tyros...	[ "Bacteria with circular chromosome and active homologous recombination systems have to resolve chromosomal dimers before segregation at cell division .", "In Escherichia coli , the Xer site-specific recombination system , composed of two recombinases and a specific chromosomal site ( dif ) , is involved in the co...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/complex traits" ]	Association between Common Variation at the FTO Locus and Changes in Body Mass Index from Infancy to Late Childhood: The Complex Nature of Genetic Association through Growth and Development	journal.pgen.1001307	null	[ [ "Genome-wide association studies on body mass index ( BMI ) and adiposity have reliably identified its association with variation at the fat mass and obesity related locus ( FTO ) in adult and child populations [1]–[5] .", "In meta-analyses , the addition of each minor ( A ) allele at the single nucleotid...	[ "An age-dependent association between variation at the FTO locus and BMI in children has been suggested .", "We meta-analyzed associations between the FTO locus ( rs9939609 ) and BMI in samples , aged from early infancy to 13 years , from 8 cohorts of European ancestry .", "We found a positive association betwe...	[ "Variation at the FTO locus is reliably associated with BMI and adiposity-related traits , but little is still known about the effects of variation at this gene , particularly in children .", "We have examined a large collection of samples for which both genotypes at rs9939609 and multiple measurements of BMI are...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "velocity", "cell motility", "medicine and health sciences", "classical mechanics", "chemical compounds", "pathology and laboratory medicine", "engineering and technology", "pathogens", "biological locomotion", "biomechanics", "organic compounds", "petroleum products", "serine", "materials...	The Role of Adaptation in Bacterial Speed Races	journal.pcbi.1004974	null	[ [ "A major example of adaptation in transduction pathways is bacterial chemotaxis , where saturating stimuli are followed by a precise recovery of the cell’s pre-stimulus tumbling frequency [1 , 2] .", "The recovery is achieved by an integral feedback control [3] , which is molecularly mediated by the methy...	[ "Evolution of biological sensory systems is driven by the need for efficient responses to environmental stimuli .", "A paradigm among prokaryotes is the chemotaxis system , which allows bacteria to navigate gradients of chemoattractants by biasing their run-and-tumble motion .", "A notable feature of chemotaxis...	[ "Biological sensory pathways are presumed to evolve for the processing of environmental information , yet quantitative evidence is scant .", "Chemotaxis allows bacteria to sense chemical gradients but their ecological distribution , e . g . whether natural gradients sensed by E . coli change slowly or rapidly in ...	2016

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