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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" ]	[ "neurological disorders/prion diseases" ]	Abnormal Brain Iron Homeostasis in Human and Animal Prion Disorders	journal.ppat.1000336	null	[ [ "Imbalance of brain iron homeostasis is considered an important contributing factor of neurotoxicity in several neurodegenerative disorders including Parkinson's disease , Alzheimer's disease , and Huntington's disease [1]–[4] .", "Recent evidence suggests a similar alteration of iron homeostasis in prion...	[ "Neurotoxicity in all prion disorders is believed to result from the accumulation of PrP-scrapie ( PrPSc ) , a β-sheet rich isoform of a normal cell-surface glycoprotein , the prion protein ( PrPC ) .", "Limited reports suggest imbalance of brain iron homeostasis as a significant associated cause of neurotoxicity...	[ "Prion disorders are neurodegenerative conditions of humans and animals that are invariably fatal .", "The main agent responsible for neurotoxicity in all prion disorders is PrP-scrapie ( PrPSc ) , a β-sheet rich isoform of a normal cell-surface glycoprotein , the prion protein ( PrPC ) .", "Deposits of PrPSc i...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/comparative genomics", "genetics and genomics/chromosome biology", "evolutionary biology/genomics" ]	Comparative Genomic Hybridization (CGH) Reveals a Neo-X Chromosome and Biased Gene Movement in Stalk-Eyed Flies (Genus Teleopsis)	journal.pgen.1001121	null	[ [ "The origin and evolution of sex chromosomes have long been of interest to geneticists and evolutionary biologists [1]–[3] .", "Besides their essential role in sex-determination , sex chromosomes are distinct from autosomes in their gene content , pattern of gene expression , rate of gene duplication and ...	[ "Chromosomal location has a significant effect on the evolutionary dynamics of genes involved in sexual dimorphism , impacting both the pattern of sex-specific gene expression and the rate of duplication and protein evolution for these genes .", "For nearly all non-model organisms , however , knowledge of chromos...	[ "The distribution and organization of genes on chromosomes vary widely among animals .", "Chromosomes can change in number and size , as well as gene composition , over short evolutionary time scales .", "Furthermore , chromosome location can influence how genes are expressed in various tissues and how they evo...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "yeast infections", "pathology and laboratory medicine", "immune physiology", "cytokines", "pathogens", "immunology", "microbiology", "cell differentiation", "developmental biology", "fungi", "molecula...	Caspase-11-dependent IL-1α release boosts Th17 immunity against Paracoccidioides brasiliensis	journal.ppat.1007990	null	[ [ "During pulmonary Paracoccidioides brasiliensis infection , the granulomatous inflammation is a crucial process to control dissemination and prevent systemic chronic paracoccidioidomycosis ( PCM ) .", "Concerted efforts of both innate and adaptive immune cells are necessary for fungal recognition and elim...	[ "The granulomatous lesion resulting from infection with the fungus Paracoccidioides brasiliensis is characterized by a compact aggregate of mature cells , surrounded by a fibroblast- and collagen-rich content .", "Granuloma formation requires signaling elicited by inflammatory molecules such as members of the int...	[ "After infectious insults , the release of intracellular molecules from dying cells , such as IL-1α , provokes a local inflammation as an alert of tissue damage .", "In this study , we investigated the steps necessary for IL-1α-mediated inflammation and its implications after fungal infection .", "We identified...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biology" ]	Quantitative Proteomics of Intracellular Campylobacter jejuni Reveals Metabolic Reprogramming	journal.ppat.1002562	null	[ [ "Campylobacter jejuni is the leading cause of bacterial food-borne disease in the USA and Europe and a major cause of diarrheal disease in developing countries [1] , [2] .", "The typical route of C . jejuni transmission is through handling and ingesting contaminated food , milk , or water [3] .", "In ...	[ "Campylobacter jejuni is the major cause of bacterial food-borne illness in the USA and Europe .", "An important virulence attribute of this bacterial pathogen is its ability to enter and survive within host cells .", "Here we show through a quantitative proteomic analysis that upon entry into host cells , C . ...	[ "Campylobacter jejuni is one of the most common causes of food-borne illness in the United States and a major cause of diarrheal diseases in developing countries .", "This pathogen can invade intestinal epithelial cells , which is very important for its ability to cause disease .", "Once it gains access to epit...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology", "emerging viral diseases", "biology", "microbiology", "viral structure" ]	The Enterovirus 71 A-particle Forms a Gateway to Allow Genome Release: A CryoEM Study of Picornavirus Uncoating	journal.ppat.1003240	null	[ [ "Enterovirus 71 ( EV71 ) is an emerging pathogen with pandemic potential [1] .", "First isolated in 1969 , EV71 is classified as a member of the family Picornaviridae , genus Enterovirus [2] , [3] .", "This single-stranded positive-sense RNA virus is a causative agent of hand , foot , and mouth diseas...	[ "Since its discovery in 1969 , enterovirus 71 ( EV71 ) has emerged as a serious worldwide health threat .", "This human pathogen of the picornavirus family causes hand , foot , and mouth disease , and also has the capacity to invade the central nervous system to cause severe disease and death .", "Upon binding ...	[ "In a picornavirus capsid structural integrity must not be compromised until a key mechanism triggers genome release into a permissive cell .", "It has long been established that the majority of members of the picornavirus family solve this dilemma with a two-step uncoating process initiated by receptor recogniti...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/cancer genetics", "pathology/molecular pathology" ]	Lactic Acidosis Triggers Starvation Response with Paradoxical Induction of TXNIP through MondoA	journal.pgen.1001093	null	[ [ "Human cancers are extremely heterogeneous due to multiple mutations in oncogenes and tumor suppressor genes , a range of inherited germline variations and varying degrees of microenvironmental stresses .", "These tumor microenvironmental stresses include tumor hypoxia , accumulation of lactic acid ( lact...	[ "Although lactic acidosis is a prominent feature of solid tumors , we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells .", "We compared global transcriptional responses of breast cancer cells in response to three distinct tumor microenviro...	[ "Solid tumors usually have many differences in their chemical environments , such as low oxygen , depletion of glucose , high acidity ( low pH ) , and accumulation of lactate , from normal tissues .", "These changes are usually called tumor microenvironmental stresses .", "In this study , we have used microarra...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "vesicles", "cell processes", "social sciences", "neuroscience", "membrane proteins", "golgi apparatus", "eyes", "cellular structures and organelles", "endosomes", "research and analysis methods", "specimen preparation and treatment", "staining", "animal cel...	Rab6 Is Required for Multiple Apical Transport Pathways but Not the Basolateral Transport Pathway in Drosophila Photoreceptors	journal.pgen.1005828	null	[ [ "Many cells that make up animal bodies have multiple plasma membrane domains , which are the basis of their specific functions .", "Polarized vesicle transport is essential for establishing and maintaining these domains .", "However , the underlying mechanisms are not well elucidated .", "The Dros...	[ "Polarized membrane trafficking is essential for the construction and maintenance of multiple plasma membrane domains of cells .", "Highly polarized Drosophila photoreceptors are an excellent model for studying polarized transport .", "A single cross-section of Drosophila retina contains many photoreceptors wit...	[ "Cells in animal bodies have multiple plasma membrane domains; this polarized characteristic of cells is essential for their specific functions .", "Selective membrane transport pathways play key roles in the construction and maintenance of polarized structures .", "Drosophila photoreceptors with multiple plasm...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "cryptosporidiosis", "helminth infections", "infectious diseases", "medicine and health sciences", "amebiasis", "parasitic intestinal diseases", "giardiasis", "neglected tropical diseases", "tropical diseases", "protozoan infections", "soil-transmitted helminthiases", "parasitic diseases" ]	Epidemiology of Intestinal Polyparasitism among Orang Asli School Children in Rural Malaysia	journal.pntd.0003074	null	[ [ "Intestinal parasitic infections ( IPI ) are still public health problems in many communities , particularly among children in rural areas of developing countries .", "It is estimated that more than 2 billion people worldwide are infected with IPI and more than half of the world's population are at risk o...	[ "This cross-sectional study aimed to investigate the current prevalence and risk factors associated with intestinal polyparasitism ( the concurrent infection with multiple intestinal parasite species ) among Orang Asli school children in the Lipis district of Pahang state , Malaysia .", "Fecal samples were collec...	[ "Intestinal parasitic infections ( IPI ) are still a major public health problem worldwide , with more than 2 billion people infected with at least one parasite species .", "Despite efforts to improve the quality of life of the Orang Asli population in rural Malaysia , IPI are still highly prevalent and of seriou...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "gene regulation", "regulatory proteins", "dna-binding proteins", "alleles", "dna transcription", "mathematics", "genome analysis", "transcription factors", "epigenetics", "dna", "dna methylation", "chromatin", "discrete mathematics", "combinatorics", ...	Genetic variants influence on the placenta regulatory landscape	journal.pgen.1007785	null	[ [ "Functional genomic approaches using combinations of genomic , epigenomic and transcriptomic data can define regulatory landscapes and provide a basis for biomarker discovery and insights into disease etiology .", "Advances in sequencing technologies have resulted in a surge in the number and complexity o...	[ "From genomic association studies , quantitative trait loci analysis , and epigenomic mapping , it is evident that significant efforts are necessary to define genetic-epigenetic interactions and understand their role in disease susceptibility and progression .", "For this reason , an analysis of the effects of ge...	[ "The placenta is a critical organ playing multiple roles including oxygen and metabolite transfer from mother to fetus , hormone production , and vascular perfusion .", "With this study , we aimed to deliver a placenta-specific regulatory map based on a combination of publicly available and newly generated data ....	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "plant anatomy", "microtubules", "pavement cells", "cell cycle and cell division", "plant cell biology", "cell processes", "brassica", "condensed matter physics", "plant science", "model organisms", "experimental organism systems", "plants", "flowering plants", "cellular structures and org...	A computational framework for cortical microtubule dynamics in realistically shaped plant cells	journal.pcbi.1005959	null	[ [ "It is well known that the cortical microtubule ( hereafter abbreviated to MT ) cytoskeleton in plant cells plays a decisive role in controlled cell expansion and oriented cell division , which together drive the plant morphogenesis [1] .", "In the absence of MT organizing centers like centrosomes [2] , h...	[ "Plant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells .", "It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes .", "This ordered structure emerges as the collective result of stoc...	[ "In contrast to animal cells , plant cells are encased in a rigid cell wall providing among others the necessary rigidity to contain the turgor pressure that allows the plant as a whole to raise itself against gravity .", "In order to maintain this mechanical integrity while growing requires plant cells to rigoro...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "crystal structure", "markov models", "condensed matter physics", "multivariate analysis", "mutation", "mathematics", "statistics (mathematics)", "mutation databases", "crystallography", "research and analysis methods", "solid state physics", "mathematical and...	Assessment of mutation probabilities of KRAS G12 missense mutants and their long-timescale dynamics by atomistic molecular simulations and Markov state modeling	journal.pcbi.1006458	null	[ [ "The small GTPase protein KRAS is a signal-transducing protein , which binds GDP in its inactive state and GTP in its active state [1] .", "The gene KRAS is frequently mutated in various human cancers .", "The mutation is most often , in about 86% of the cases [2] , found at G12 .", "In fact , eve...	[ "A mutated KRAS protein is frequently observed in human cancers .", "Traditionally , the oncogenic properties of KRAS missense mutants at position 12 ( G12X ) have been considered as equal .", "Here , by assessing the probabilities of occurrence of all KRAS G12X mutations and KRAS dynamics we show that this ass...	[ "The oncogene KRAS is frequently mutated in various cancers .", "When the amino acid glycine 12 is mutated , KRAS protein acquires oncogenic properties that result in tumor cell-growth and cancer progression .", "These mutations prevail especially in the pancreatic ductal adenocarcinoma , which is a cancer with...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "epigenetics", "biology", "genetics of disease", "genetics and genomics" ]	The [PSI+] Prion Exists as a Dynamic Cloud of Variants	journal.pgen.1003257	null	[ [ "Prions in yeast are a new form of gene , composed of proteins instead of nucleic acids [1] .", "As such , their inheritance , mutation and segregation are not expected to follow the same rules as the majority DNA/RNA genes .", "The [PSI+] prion was first recognized as a non-chromosomal genetic elemen...	[ "[PSI+] is an amyloid-based prion of Sup35p , a subunit of the translation termination factor .", "Prion “strains” or “variants” are amyloids with different conformations of a single protein sequence , conferring different phenotypes , but each relatively faithfully propagated .", "Wild Saccharomyces cerevisiae...	[ "The [PSI+] prion ( infectious protein ) of yeast is a self-propagating amyloid ( filamentous protein polymer ) of the Sup35 protein , a subunit of the translation termination factor .", "A single protein can form many biologically distinct prions , called prion variants .", "Wild yeast strains have three group...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/microbial evolution and genomics", "genetics and genomics/comparative genomics", "genetics and genomics/functional genomics", "genetics and genomics/chromosome biology", "genetics and genomics", "genetics and genomics/bioinformatics" ]	A Comprehensive Genome-Wide Map of Autonomously Replicating Sequences in a Naive Genome	journal.pgen.1000946	null	[ [ "The first step in the initiation of DNA synthesis in eukaryotes is the binding of the Origin Recognition Complex ( ORC ) to the replication origin [1] .", "However , replication origins have very different characteristics depending on the organism and sometimes the locale within the genome of an organism...	[ "Eukaryotic chromosomes initiate DNA synthesis from multiple replication origins .", "The machinery that initiates DNA synthesis is highly conserved , but the sites where the replication initiation proteins bind have diverged significantly .", "Functional comparative genomics is an obvious approach to study the...	[ "DNA replication is an evolutionarily conserved , cell cycle–regulated , spatially and temporally coordinated mechanism in eukaryotes .", "It is initiated by the binding of the Origin Recognition Complex ( ORC ) to multiple replication origins .", "While the ORC is highly conserved , its DNA binding specificity...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "genome engineering", "medicine and health sciences", "engineering and technology", "synthetic biology", "crispr", "synthetic bioengineering", "oncology", "immunoprecipitation", "stem cells", "induced pluripotent stem cells", "genome analysis", "epigenetics", "molecular bi...	Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis	journal.ppat.1006668	null	[ [ "Merkel cell carcinoma ( MCC ) is an aggressive skin cancer with a high rate of mortality .", "Risk factors for developing MCC include immunosuppression and UV-induced DNA damage from excessive exposure to sunlight [1] .", "Recognition of the immunosuppressive risk for MCC prompted a search to identif...	[ "Merkel cell carcinoma ( MCC ) frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen ( LT ) and an intact Small T antigen ( ST ) .", "While LT binds RB and inactivates its tumor suppressor function , it is less clear how ST contributes to MCC tumori...	[ "Merkel cell carcinoma ( MCC ) is a highly aggressive , neuroendocrine cancer of the skin .", "MCC frequently contains integrated copies of Merkel cell polyomavirus DNA and expresses two viral transcripts including a truncated form of Large T antigen ( LT ) and an intact Small T antigen ( ST ) .", "While LT bin...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "arabidopsis (thale cress)", "plant biology" ]	Mechanical Stress Induces Biotic and Abiotic Stress Responses via a Novel cis-Element	journal.pgen.0030172	null	[ [ "Plants are persistently challenged with numerous biotic and abiotic environmental stresses .", "To cope with environmental stresses plants have evolved phytohormones such as jasmonic acid , salicylic acid , ethylene , and abscisic acid , which are utilized to regulate plant responses to both abiotic and ...	[ "Plants are continuously exposed to a myriad of abiotic and biotic stresses .", "However , the molecular mechanisms by which these stress signals are perceived and transduced are poorly understood .", "To begin to identify primary stress signal transduction components , we have focused on genes that respond rap...	[ "Plants are sessile organisms constantly challenged by a wide spectrum of biotic and abiotic stresses .", "These stresses cause considerable losses in crop yields worldwide , while the demand for food and energy is on the rise .", "Understanding the molecular mechanisms driving stress responses is crucial to de...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "genome expression analysis", "innate immune system", "medicine and health sciences", "animal genetics", "pathology and laboratory medicine", "immunology", "microbiology", "vertebrates", "animals", "mammals", "parasitology", "animal models", "genome sequencing", ...	A Highly Conserved Toxo1 Haplotype Directs Resistance to Toxoplasmosis and Its Associated Caspase-1 Dependent Killing of Parasite and Host Macrophage	journal.ppat.1004005	null	[ [ "Toxoplasma gondii is a widespread obligate intracellular protozoan parasite .", "One preeminent aspect of its life cycle is the establishment of a chronic infection in humans and many other vertebrate hosts [1] .", "Toxoplasmosis is most often asymptomatic depending on the parasite's ability to elici...	[ "Natural immunity or resistance to pathogens most often relies on the genetic make-up of the host .", "In a LEW rat model of refractoriness to toxoplasmosis , we previously identified on chromosome 10 the Toxo1 locus that directs toxoplasmosis outcome and controls parasite spreading by a macrophage-dependent mech...	[ "Toxoplasmosis is a ubiquitous parasitic infection causing a wide spectrum of diseases .", "It is usually asymptomatic but can lead to severe ocular and neurological disorders .", "The host factors that determine natural resistance to toxoplasmosis are yet poorly characterized .", "Among the animal models to ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Checkpoint Activation of an Unconventional DNA Replication Program in Tetrahymena	journal.pgen.1005405	null	[ [ "A major challenge of the cell cycle is to faithfully transmit chromosomes to daughter cells .", "This is accomplished through the replication and segregation of chromosomes during the respective S and M phases .", "The integrity of chromosomes is under constant assault from extrinsic and intrinsic so...	[ "The intra-S phase checkpoint kinase of metazoa and yeast , ATR/MEC1 , protects chromosomes from DNA damage and replication stress by phosphorylating subunits of the replicative helicase , MCM2-7 .", "Here we describe an unprecedented ATR-dependent pathway in Tetrahymena thermophila in which the essential pre-rep...	[ "DNA damage and replication stress activate cell cycle checkpoint responses that protect the integrity of eukaryotic chromosomes .", "A well-conserved response involves the reversible phosphorylation of the replicative helicase , MCM2-7 , which together with the origin recognition complex ( ORC ) dictates when an...	2015
[ "Introduction", "Model", "Results", "Discussion" ]	[ "ecology/theoretical ecology", "computational biology/population genetics", "genetics and genomics/microbial evolution and genomics", "mathematics/statistics" ]	First Principles Modeling of Nonlinear Incidence Rates in Seasonal Epidemics	journal.pcbi.1001079	null	[ [ "A plethora of deterministic epidemic models involving susceptible , infected and recovered individuals have been proposed [1] , [2] , carefully analyzed [3]–[8] and confronted with data sets in the biomathematics and ecology literatures [9]–[12] .", "A well defined topic within this mathematical ecology ...	[ "In this paper we used a general stochastic processes framework to derive from first principles the incidence rate function that characterizes epidemic models .", "We investigate a particular case , the Liu-Hethcote-van den Driessche's ( LHD ) incidence rate function , which results from modeling the number of su...	[ "Nonlinearity in the infection incidence is one of the main components that shape seasonal epidemics .", "Here , we revisit classical incidence and propose a first principles derivation of the infection incidence rate .", "A qualitative analysis of the SIRS model with both the classical and the proposed inciden...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Human Papillomaviruses Activate and Recruit SMC1 Cohesin Proteins for the Differentiation-Dependent Life Cycle through Association with CTCF Insulators	journal.ppat.1004763	null	[ [ "Human papillomaviruses are the causative agents of cervical and other anogenital malignancies .", "HPV-16 , 18 , 31 along with at least ten other types are referred to as high-risk as they are associated with the development of genital cancers[1] [2] .", "These high-risk viruses infect squamous epith...	[ "Human papillomaviruses infect stratified epithelia and link their productive life cycle to the differentiation state of the host cell .", "Productive viral replication or amplification is restricted to highly differentiated suprabasal cells and is dependent on the activation of the ATM DNA damage pathway .", "...	[ "Over 120 types of human papillomavirus ( HPV ) have been identified , and approximately one-third of these infect epithelial cells of the genital mucosa .", "Infection by a subset of HPV types is responsible for the development of cervical and other anogenital cancers .", "The infectious life cycle of HPV is d...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "tissue mechanics", "medicine", "mechanics", "classical mechanics", "dynamics (mechanics)", "neuroscience", "biomechanics", "biophysics simulations", "neuroimaging", "biology", "head injury", "biophysics", "continuum mechanics", "connectomics", "physics", "neuroanatomy", "biophysic a...	Combining the Finite Element Method with Structural Connectome-based Analysis for Modeling Neurotrauma: Connectome Neurotrauma Mechanics	journal.pcbi.1002619	null	[ [ "The finite element method is often used to study neurotrauma [1]–[9] and continues to emerge as a useful tool in the field of neuroscience [10]–[13] .", "Models continue to advance in biofidelity by incorporating an increased level of anatomic detail [4] , [13] , [14] , improved representation of the mat...	[ "This article presents the integration of brain injury biomechanics and graph theoretical analysis of neuronal connections , or connectomics , to form a neurocomputational model that captures spatiotemporal characteristics of trauma .", "We relate localized mechanical brain damage predicted from biofidelic finite...	[ "According to the Centers for Disease Control and Prevention in the United States , approximately 1 . 7 million people , on average , sustain a traumatic brain injury annually .", "During the last few decades , brain neurotrauma biomechanics has been an active area of research involving medical clinicians and a b...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "developmental biology", "caenorhabditis elegans", "developmental neuroscience", "model organisms", "biology", "neuroscience", "cell fate determination" ]	The MicroRNA mir-71 Inhibits Calcium Signaling by Targeting the TIR-1/Sarm1 Adaptor Protein to Control Stochastic L/R Neuronal Asymmetry in C. elegans	journal.pgen.1002864	null	[ [ "Cell fate determination during development requires both the induction of cell type specific genes and the suppression of genes that promote an alternative cell fate [1]–[4] .", "For example , both inductive signaling , mediated by an EGFR-Ras-MAPK pathway , and lateral inhibition , mediated by LIN-12/No...	[ "The Caenorhabditis elegans left and right AWC olfactory neurons communicate to establish stochastic asymmetric identities , AWCON and AWCOFF , by inhibiting a calcium-mediated signaling pathway in the future AWCON cell .", "NSY-4/claudin-like protein and NSY-5/innexin gap junction protein are the two parallel si...	[ "Cell identity determination requires a competition between the induction of cell type–specific genes and the suppression of genes that promote an alternative cell type .", "In the nematode C . elegans , a specific sensory neuron pair communicates to establish stochastic asymmetric identities by inhibiting a calc...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "microbiology/plant-biotic interactions", "microbiology/microbial growth and development", "microbiology/microbial evolution and genomics" ]	Fungicide-Driven Evolution and Molecular Basis of Multidrug Resistance in Field Populations of the Grey Mould Fungus Botrytis cinerea	journal.ppat.1000696	null	[ [ "Synthetic fungicides are used worldwide that provide protection of major crops from destruction by fungal plant pathogens [1] .", "As a result of repeated fungicide treatments , however , resistant strains of the pathogens are being selected [2] .", "Different resistance mechanisms have been reported...	[ "The grey mould fungus Botrytis cinerea causes losses of commercially important fruits , vegetables and ornamentals worldwide .", "Fungicide treatments are effective for disease control , but bear the risk of resistance development .", "The major resistance mechanism in fungi is target protein modification resu...	[ "Bacterial and fungal pathogens cause diseases in humans and plants alike .", "Antibiotics and fungicides are used for disease control , but the microbes are able to adapt quickly to these drugs by mutation .", "Multiple drug resistance ( MDR ) is well investigated in human pathogens and causes increasing probl...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "animal types", "medicine and health sciences", "animal pathogens", "immune cells", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "population genetics", "animals", "clinical medicine", "population biology", "antibodies", "zoology", ...	The ecology of immune state in a wild mammal, Mus musculus domesticus	journal.pbio.2003538	null	[ [ "Immune systems protect animals from infection and disease .", "The mammalian immune system reacts to antigenic exposure with a multitude of cellular and humoral responses , including cytotoxicity , phagocytosis , and the production of cytokines and antibodies .", "The ultimate result of these respons...	[ "The immune state of wild animals is largely unknown .", "Knowing this and what affects it is important in understanding how infection and disease affects wild animals .", "The immune state of wild animals is also important in understanding the biology of their pathogens , which is directly relevant to explaini...	[ "The immune state of wild animals—and the factors that affect this—is largely unknown .", "Knowing this is important in understanding how infection and disease affects wild animals , and the biology of their pathogens .", "The paucity of knowledge about wild animals' immune state is in stark contrast to our exq...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "immunodeficiency viruses", "infectious diseases", "medicine and health sciences", "medical microbiology", "hiv", "viral pathogens", "genetics", "microbial pathogens", "biology and life sciences", "immunology", "microbiology", "computational biology", "viral diseases" ]	The Fitness Landscape of HIV-1 Gag: Advanced Modeling Approaches and Validation of Model Predictions by In Vitro Testing	journal.pcbi.1003776	null	[ [ "The ideal way to combat the spread of HIV-1 is with an effective prophylactic or therapeutic vaccine [1] , [2] .", "One of the greatest challenges hindering the achievement of this goal is the incredible sequence diversity and mutability of HIV-1 [3] , which can limit the effectiveness of the immune resp...	[ "Viral immune evasion by sequence variation is a major hindrance to HIV-1 vaccine design .", "To address this challenge , our group has developed a computational model , rooted in physics , that aims to predict the fitness landscape of HIV-1 proteins in order to design vaccine immunogens that lead to impaired vir...	[ "At least 70 million people have been infected with HIV since the beginning of the epidemic and an effective vaccine remains elusive .", "The high mutation rate and diversity of HIV strains enables the virus to effectively evade host immune responses , presenting a significant challenge for HIV vaccine design .",...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genetics and genomics/microbial evolution and genomics", "cell biology/microbial growth and development", "microbiology/parasitology", "infectious diseases/protozoal infections", "infectious diseases/tropical and travel-associated diseases" ]	Three Members of the 6-cys Protein Family of Plasmodium Play a Role in Gamete Fertility	journal.ppat.1000853	null	[ [ "Sexual reproduction is an obligate process in the Plasmodium life cycle and is required for transmission of the parasites between the vertebrate and mosquito hosts .", "The sexual phase is initiated by the formation of male and female cells ( gametocytes ) in the blood of the vertebrate host .", "Gam...	[ "The process of fertilization is critically dependent on the mutual recognition of gametes and in Plasmodium , the male gamete surface protein P48/45 is vital to this process .", "This protein belongs to a family of 10 structurally related proteins , the so called 6-cys family .", "To identify the role of addit...	[ "Sexual reproduction for malaria parasites is an essential process and is necessary for parasite transmission between hosts .", "Fertilisation between female and male gametes occurs in the midgut of the mosquito and proteins on the surface of gametes are principle targets in transmission blocking strategies .", ...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "antimicrobials", "medicine and health sciences", "classical mechanics", "pathology and laboratory medicine", "fluid mechanics", "pathogens", "drugs", "microbiology", "antibiotic resistance", "pharmaceutics", "antibiotics", "enterococcus", "pharmacology", "population biology", "bacteria"...	Population Density Modulates Drug Inhibition and Gives Rise to Potential Bistability of Treatment Outcomes for Bacterial Infections	journal.pcbi.1005098	null	[ [ "The inhibitory effects of antibiotics often decrease with increasing density of the starting microbial population , a phenomenon known as the inoculum effect [1] .", "While the IE is commonly attributed to enzymatic degradation of the drug [2 , 3]—with the classical example being the degradation of β-lac...	[ "The inoculum effect ( IE ) is an increase in the minimum inhibitory concentration ( MIC ) of an antibiotic as a function of the initial size of a microbial population .", "The IE has been observed in a wide range of bacteria , implying that antibiotic efficacy may depend on population density .", "Such density...	[ "The pace of antibiotic discovery has rapidly slowed in the last few decades , creating an urgent need to reevaluate and optimize therapies based on current drugs .", "In this work , we combine quantitative laboratory experiments on bacterial populations with mathematical models of antimicrobial therapies to demo...	2016
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[]	Skin-Derived C-Terminal Filaggrin-2 Fragments Are Pseudomonas aeruginosa-Directed Antimicrobials Targeting Bacterial Replication	journal.ppat.1005159	null	[ [ "Human skin and mucosal surfaces harbor and encounter a high number of diverse microorganisms [1 , 2] , but are rarely infected .", "Apart from the physical skin barrier of the stratum corneum ( reviewed in ref . [3] ) , a “chemical barrier” , consisting of various antimicrobial peptides and proteins ( AM...	[ "Soil- and waterborne bacteria such as Pseudomonas aeruginosa are constantly challenging body surfaces .", "Since infections of healthy skin are unexpectedly rare , we hypothesized that the outermost epidermis , the stratum corneum , and sweat glands directly control the growth of P . aeruginosa by surface-provid...	[ "Pseudomonas aeruginosa is able to cause severe infections that increasingly threaten patients with cystic fibrosis and burns .", "The emerging antibiotic resistance of those bacteria exigently necessitates the development of new effective drugs .", "Since healthy skin is unexpectedly resistant towards P . aeru...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "statistical mechanics", "muscle tissue", "fibroblasts", "connective tissue cells", "waves", "cellular structures and organelles", "cytoskeleton", "cardiology", "contractile proteins", "actins", "computer and information sciences", "arrhythmia", "animal cell...	Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fraction of non-conducting cells	journal.pcbi.1006597	null	[ [ "The contraction of the heart is controlled by propagating waves of excitation .", "Abnormal regimes of the wave propagation may cause cardiac arrhythmia , asynchronous contractions of the heart and even lead to cardiac arrest and sudden cardiac death .", "Cardiac arrhythmias often originate from bloc...	[ "Cardiac fibrosis occurs in many forms of heart disease and is considered to be one of the main arrhythmogenic factors .", "Regions with a high density of fibroblasts are likely to cause blocks of wave propagation that give rise to dangerous cardiac arrhythmias .", "Therefore , studies of the wave propagation t...	[ "Cardiac arrhythmias are one of the major causes of death in the industrialized world .", "The most dangerous ones are often caused by the blocks of propagation of electrical signals .", "One of the common factors that contribute to the likelihood of these blocks , is a condition called cardiac fibrosis .", "...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "medicine and health sciences", "solomon islands", "pathology and laboratory medicine", "chlamydia trachomatis", "pathogens", "immunology", "tropical diseases", "geographical locations", "microbiology", "bacterial diseases", "signs and symptoms", "eye diseases", "s...	Low Prevalence of Conjunctival Infection with Chlamydia trachomatis in a Treatment-Naïve Trachoma-Endemic Region of the Solomon Islands	journal.pntd.0004863	null	[ [ "Trachoma , caused by ocular strains of Chlamydia trachomatis ( Ct ) , is the leading infectious cause of blindness worldwide [1] .", "Ocular infection with Ct is associated with a characteristic follicular conjunctivitis , known as “trachomatous inflammation—follicular” ( TF ) [2] , which can persist for...	[ "Trachoma is endemic in several Pacific Island states .", "Recent surveys across the Solomon Islands indicated that whilst trachomatous inflammation—follicular ( TF ) was present at levels warranting intervention , the prevalence of trachomatous trichiasis ( TT ) was low .", "We set out to determine the relatio...	[ "Trachoma is the most common infectious cause blindness worldwide , and the target of a global elimination initiative .", "A package of community-wide interventions is recommended to treat trachoma , which aim to reduce transmission of the causative agent Chlamydia trachomatis .", "These interventions require s...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "gene regulation", "radii", "geometry", "animals", "simulation and modeling", "animal models", "drosophila melanogaster", "model organisms", "mathematics", "materials science", "experimental organism systems", "epigenetics", "macromolecules", "drosophila", "chromatin",...	A Looping-Based Model for Quenching Repression	journal.pcbi.1005337	null	[ [ "Polymer looping is a phenomenon that is critical for the understanding of many chemical and biological processes .", "In particular , DNA looping has been implicated in transcriptional regulation across many organisms , and as a result plays a crucial role in how organisms develop and respond to their en...	[ "We model the regulatory role of proteins bound to looped DNA using a simulation in which dsDNA is represented as a self-avoiding chain , and proteins as spherical protrusions .", "We simulate long self-avoiding chains using a sequential importance sampling Monte-Carlo algorithm , and compute the probabilities fo...	[ "Biological regulation-at-a-distance , whereby a transcription factor ( TF ) is able to generate susbstantial regulatory effects on gene expression even though it may be bound a large distance away from its target ( 500 bp–1 Mbp ) , is only partially understood .", "Using a biophysical model and a computer simula...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Macrophage and T Cell Produced IL-10 Promotes Viral Chronicity	journal.ppat.1003735	null	[ [ "The functional down regulation of antiviral T cells , also termed T cell exhaustion , is a major hurdle inhibiting the control or even clearance of chronic infections .", "T cell exhaustion is characterized by a gradual loss of cytokine producing antiviral CD8+ T cells [1] .", "The host-derived anti-...	[ "Chronic viral infections lead to CD8+ T cell exhaustion , characterized by impaired cytokine secretion .", "Presence of the immune-regulatory cytokine IL-10 promotes chronicity of Lymphocytic Choriomeningitis Virus ( LCMV ) Clone 13 infection , while absence of IL-10/IL-10R signaling early during infection resul...	[ "Chronic viral infections like Hepatitis B and C Virus ( HBV and HCV ) and Human Immunodeficiency Virus ( HIV ) in humans affect more than 500 million people worldwide .", "While a robust T cell response is a hallmark of many acute infections one hurdle inhibiting the clearance of chronic viral infections is that...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry", "infectious diseases", "virology", "in vitro", "chemistry", "chemical biology" ]	Structural Basis of PP2A Inhibition by Small t Antigen	journal.pbio.0050202	The crystal structure of full-length SV40 small t antigen (ST) in complex with the A subunit of its target, protein phosphatase 2A, contributes to our understanding of the oncogenic functions of ST.	[ [ "Simian virus 40 ( SV40 ) is a DNA tumor virus in the polyomavirus family .", "SV40 may play a role in a subset of human cancers , and the study of transformation induced by SV40 has led to many insights into the pathways involved in spontaneously arising cancers [1] .", "The Early Region of SV40 is e...	[ "The SV40 small t antigen ( ST ) is a potent oncoprotein that perturbs the function of protein phosphatase 2A ( PP2A ) .", "ST directly interacts with the PP2A scaffolding A subunit and alters PP2A activity by displacing regulatory B subunits from the A subunit .", "We have determined the crystal structure of f...	[ "The study of how DNA tumor viruses induce malignant transformation has led to the identification of key pathways that also play a role in spontaneously arising cancers .", "One such virus , simian virus 40 ( SV40 ) , produces two proteins , the large T and small t antigens , that bind and inactivate tumor suppre...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "laboratory equipment", "engineering and technology", "social sciences", "sand flies", "light", "neuroscience", "animals", "electromagnetic radiation", "reproductive physiology", "artificial light", "filter paper", "vision", "insect vector...	Diel periodicity and visual cues guide oviposition behavior in Phlebotomus papatasi, vector of old-world cutaneous leishmaniasis	journal.pntd.0007165	null	[ [ "Phlebotomine sand flies ( Diptera: Psychodidae ) transmit protozoan parasites ( Leishmania spp . ) , as well as pathogenic bacteria ( Bartonella bacilliformis ) and viruses [1–3] .", "Most significant are the human leishmaniases that , following malaria and dengue , are the most pervasive vector-borne di...	[ "Phlebotomine sand flies are vectors of human leishmaniases , important neglected tropical diseases .", "In this study , we investigated diel patterns of oviposition behavior , effects of visual cues on oviposition-site selection , and whether these affect the attraction of gravid Phlebotomus papatasi ( Scopoli )...	[ "Sand flies are vectors of human leishmaniases , an important neglected tropical disease .", "An alternative approach to the conventional delivery of an insecticide to the vector is to bring the vector to the insecticide using oviposition ( egg-laying ) -site attractants .", "Olfactory cues originating from org...	2019
[ "Introduction", "Discussion", "Material and Methods" ]	[ "evolutionary biology/evolutionary and comparative genetics", "evolutionary biology/human evolution", "nutrition", "computational biology/molecular genetics", "computational biology/evolutionary modeling" ]	The Origins of Lactase Persistence in Europe	journal.pcbi.1000491	null	[ [ "Lactase persistence ( LP ) is an autosomal dominant trait enabling the continued production of the enzyme lactase throughout adult life .", "Lactase non-persistence is the ancestral condition for humans , and indeed for all mammals [1] .", "Production of lactase in the gut is essential for the digest...	[ "Lactase persistence ( LP ) is common among people of European ancestry , but with the exception of some African , Middle Eastern and southern Asian groups , is rare or absent elsewhere in the world .", "Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans ( −13 , 910...	[ "Most adults worldwide do not produce the enzyme lactase and so are unable to digest the milk sugar lactose .", "However , most people in Europe and many from other populations continue to produce lactase throughout their life ( lactase persistence ) .", "In Europe , a single genetic variant , −13 , 910*T , is ...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "gene regulation", "messenger rna", "dna-binding proteins", "cloning", "long non-coding rnas", "dna transcription", "molecular biology techniques", "research and analysis methods", "transcriptional control", "proteins", "gene expression", "histones", "molecular biology", "biochemistry", ...	Regulation of the cohesin-loading factor NIPBL: Role of the lncRNA NIPBL-AS1 and identification of a distal enhancer element	journal.pgen.1007137	null	[ [ "Genetic information needs to be inherited without any changes over numerous cell generations and from parents to offspring .", "This process crucially depends on the cohesin complex that ensures genome stability during cell divisions , DNA damage repair and is involved in the three-dimensional organisati...	[ "Cohesin is crucial for genome stability , cell division , transcription and chromatin organization .", "Its functions critically depend on NIPBL , the cohesin-loader protein that is found to be mutated in >60% of the cases of Cornelia de Lange syndrome ( CdLS ) .", "Other mutations are described in the cohesin...	[ "The most frequent mutations in the human developmental disorder Cornelia de Lange Syndrome ( CdLS ) occur in the NIPBL gene .", "NIPBL is critical for chromatin-association of the cohesin complex and has a dual role as transcription factor .", "The regulation of the NIPBL gene is of great interest since organi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "sheep", "none", "vertebrates", "animals", "mammals" ]	Diversity in Neuroanatomical Distribution of Abnormal Prion Protein in Atypical Scrapie	journal.ppat.0030082	null	[ [ "Transmissible spongiform encephalopathies ( TSEs ) are fatal neurodegenerative diseases that are caused by prions [1] and include , among others , Creutzfeldt-Jakob and Gerstmann-Sträussler-Scheinker disease ( GSS ) in humans , bovine spongiform encephalopathy ( BSE ) in cattle , and scrapie in small ruminan...	[ "Scrapie is a transmissible spongiform encephalopathy ( TSE ) in sheep and goats .", "In recent years , atypical scrapie cases were identified that differed from classical scrapie in the molecular characteristics of the disease-associated pathological prion protein ( PrPsc ) .", "In this study , we analyze the ...	[ "In the view of concerns that bovine spongiform encephalopathy has entered the small ruminant population , comprehensive active surveillance programs for transmissible spongiform encephalopathies ( TSEs ) in sheep and goats were implemented worldwide .", "In these , previously unrecognized atypical scrapie cases ...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "hela cells", "biological cultures", "microbiology", "viral structure", "viruses", "rna viruses", "cell cultures", "rhinovirus infection", "microbial genomics", "research and analysis methods", "infectious diseases", "viral genomics", "genomics", "proteins...	Cellular N-myristoyltransferases play a crucial picornavirus genus-specific role in viral assembly, virion maturation, and infectivity	journal.ppat.1007203	null	[ [ "The family Picornaviridae encompasses 35 genera of small non-enveloped RNA viruses that include numerous animal and human pathogens ( www . picornaviridae . com ) .", "They are causative agents of diseases with huge impact on health care and economy ranging from the relatively harmless common cold typica...	[ "In nearly all picornaviruses the precursor of the smallest capsid protein VP4 undergoes co-translational N-terminal myristoylation by host cell N-myristoyltransferases ( NMTs ) .", "Curtailing this modification by mutation of the myristoylation signal in poliovirus has been shown to result in severe assembly def...	[ "Picornaviruses are important human and animal pathogens .", "Protective vaccines are only available against very few representatives .", "Furthermore , antiviral drugs have not made it to the market because of serious side effects and viral mutational escape .", "We here show that pharmacological inhibition ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "developmental biology", "homo (human)", "drosophila", "molecular biology", "genetics and genomics" ]	Drosophila Brakeless Interacts with Atrophin and Is Required for Tailless-Mediated Transcriptional Repression in Early Embryos	journal.pbio.0050145	Co-repressor activity of Brakeless with Tailless in Drosophila regulates segmentation genes Krüppel and knirps. Interactions between Brakeless and Atrophin may be important in developmental processes including the human neurodegenerative disease dentatorubral-pallidoluysian atrophy.	[ [ "The generation of complex spatial and temporal gene expression patterns during embryo development is achieved through gene regulatory networks in which broadly distributed transcriptional activators act in combination with repressors with a more restricted distribution ( reviewed in [1] ) .", "Repressors...	[ "Complex gene expression patterns in animal development are generated by the interplay of transcriptional activators and repressors at cis-regulatory DNA modules ( CRMs ) .", "How repressors work is not well understood , but often involves interactions with co-repressors .", "We isolated mutations in the brakel...	[ "Nuclear receptors play important roles in embryonic development and cellular differentiation by regulating gene expression at the level of transcription .", "The functions of transcriptional repressors , including nuclear receptors , are often mediated by other proteins , so-called co-repressors .", "We perfor...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutation", "genetics", "biology and life sciences", "human genetics", "genetics of disease" ]	A Gain-of-Function Mutation in Tnni2 Impeded Bone Development through Increasing Hif3a Expression in DA2B Mice	journal.pgen.1004589	null	[ [ "Distal arthrogryposis type 2B ( DA2B ) ( also called Sheldon-Hall syndrome , or SHS ) is an autosomal dominant genetic disorder with marked genetic heterogeneity .", "The typical clinical phenotypes of DA2B patients include hand and/or foot contracture malformation and shortness of stature [1]–[3] .", ...	[ "Distal arthrogryposis type 2B ( DA2B ) is an important genetic disorder in humans .", "However , the mechanisms governing this disease are not clearly understood .", "In this study , we generated knock-in mice carrying a DA2B mutation ( K175del ) in troponin I type 2 ( skeletal , fast ) ( TNNI2 ) , which encod...	[ "Distal arthrogryposis type 2B ( DA2B ) is an autosomal dominant genetic disorder .", "The typical clinical features of DA2B include hand and/or foot contracture and shortness of stature in patients .", "To date , mutations in TNNI2 can explain approximately 20% of familial incidences of DA2B .", "TNNI2 encod...	2014
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biotechnology", "biomacromolecule-ligand interactions", "sequencing techniques", "medicine and health sciences", "functional genomics", "small molecules", "molecular biology techniques", "pharmacology", "sequence analysis", "genome complexity", "proteins", "molecular biology", "drug discove...	Analysis of the Protein Domain and Domain Architecture Content in Fungi and Its Application in the Search of New Antifungal Targets	journal.pcbi.1003733	null	[ [ "There has been a significant rise in the incidence of fungal infection over the last few years .", "This has been partially due to an increase in the susceptible population as the result of blood cancer , intensive care , solid organ transplantation , or chronic granulomatous disease , in addition to a g...	[ "Over the past several years fungal infections have shown an increasing incidence in the susceptible population , and caused high mortality rates .", "In parallel , multi-resistant fungi are emerging in human infections .", "Therefore , the identification of new potential antifungal targets is a priority .", ...	[ "Some fungi have become pathogenic to plants and in a lesser extent to animals .", "Under certain conditions their presence in the human body can prove a threat for human health , especially for immunocompromised patients .", "Yet , some fungi can also infect healthy individuals .", "The low sensitivity of th...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "oxidative stress", "neurodegenerative diseases", "neuroscience", "animals", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "genome analysis", "mitochondria", "bioenergetics", "cellular struct...	Isocitrate protects DJ-1 null dopaminergic cells from oxidative stress through NADP+-dependent isocitrate dehydrogenase (IDH)	journal.pgen.1006975	null	[ [ "Parkinson’s disease ( PD ) is the second most common neurodegenerative disease and is characterized by typical movement disorders and selective loss of dopaminergic ( DA ) neurons in the substantia nigra pars compacta ( SNpc ) [1] .", "Accumulated evidence has firmly linked the death of these neurons to ...	[ "DJ-1 is one of the causative genes for early onset familiar Parkinson’s disease ( PD ) and is also considered to influence the pathogenesis of sporadic PD .", "DJ-1 has various physiological functions which converge on controlling intracellular reactive oxygen species ( ROS ) levels .", "In RNA-sequencing anal...	[ "The molecular pathogenesis of Parkinson’s disease ( PD ) is still elusive even though many causative genes for the disease have been identified .", "In this study , we demonstrated that isocitrate dehydrogenase ( IDH ) , the enzyme responsible for converting isocitrate into α-ketoglutarate , is critical for the ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "signal transduction", "signal inhibition", "computer and information sciences", "cell motility", "developmental biology", "cell biology", "simulation and modeling", "network analysis", "cell migration", "chemokines", "biology and life sciences", "signaling networks", "wnt signaling cascade"...	Polarization and migration in the zebrafish posterior lateral line system	journal.pcbi.1005451	null	[ [ "In this section , we describe additional biological background for our investigation .", "The PLLP consists of more than 100 cells ( ≈4-5 cells wide ) when migration is initiated , which migrate about 2 . 3 mm down the horizontal myoseptum during the time interval 22-48 hours post-fertilization [1] .", ...	[ "Collective cell migration plays an important role in development .", "Here , we study the posterior lateral line primordium ( PLLP ) a group of about 100 cells , destined to form sensory structures , that migrates from head to tail in the zebrafish embryo .", "We model mutually inhibitory FGF-Wnt signalling ne...	[ "Collective migration of a group of cells plays an important role in the development of an organism .", "Here we study a specific example in the zebrafish embryo , where a group of about 100 cells ( the posterior lateral line primordium , PLLP ) , destined to form sensory structures , migrates from head to tail ....	2017
[ "Introduction", "Results/Discussion", "Methods" ]	[]	On the Role of Aggregation Prone Regions in Protein Evolution, Stability, and Enzymatic Catalysis: Insights from Diverse Analyses	journal.pcbi.1003291	null	[ [ "Irreversible β-strand driven protein aggregation and amyloidogenesis is a tremendous burden to biological organisms .", "Protein loss-of function due to aggregation causes stress to the cell and metabolic energy is lost on the expression , synthesis , and degradation of proteins which aggregate .", "...	[ "The various roles that aggregation prone regions ( APRs ) are capable of playing in proteins are investigated here via comprehensive analyses of multiple non-redundant datasets containing randomly generated amino acid sequences , monomeric proteins , intrinsically disordered proteins ( IDPs ) and catalytic residue...	[ "Biotechnology requires the large-scale expression , yield , and storage of recombinant proteins .", "Each step in protein production has the potential to cause aggregation as proteins , not evolved to exist outside the cell , endure the various steps involved in commercial manufacturing processes .", "Mechanis...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Pathogen Recognition Receptor Signaling Accelerates Phosphorylation-Dependent Degradation of IFNAR1	journal.ppat.1002065	null	[ [ "Cytokines that belong to the family of Type I interferons ( IFNs , including IFNα/β ) , play an important role in innate immunity [1] , [2] , [3] , [4] .", "These cytokines are produced by various cell types including dendritic cells ( DCs ) , which are equipped with a diverse set of specialized pathogen...	[ "An ability to sense pathogens by a number of specialized cell types including the dendritic cells plays a central role in host's defenses .", "Activation of these cells through the stimulation of the pathogen-recognition receptors induces the production of a number of cytokines including Type I interferons ( IFN...	[ "We have previously observed and reported that the activation of unfolded protein responses during infection with some viruses such as vesicular stomatitis virus and hepatitis C virus compromises the cellular responses to the cytokines that belong to family of Type I interferons ( IFNα/β ) .", "These effects appa...	2011
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "invertebrates", "medicine and health sciences", "natural antisense transcripts", "gene regulation", "neuroscience", "biological locomotion", "animals", "circadian oscillators", "animal models", "micrornas", "model organisms", "drosophila melanogaster", "experimental organism systems", "ch...	miR-210 controls the evening phase of circadian locomotor rhythms through repression of Fasciclin 2	journal.pgen.1007655	null	[ [ "The circadian locomotor rhythms of flies are generated by a neuronal network , which consists of ~150 brain circadian neurons expressing core pacemaker genes [1–4] .", "These neurons can be further divided into 7 clusters based on their cell localization and neurotransmitters they express [4] .", "Th...	[ "Circadian clocks control the timing of animal behavioral and physiological rhythms .", "Fruit flies anticipate daily environmental changes and exhibit two peaks of locomotor activity around dawn and dusk .", "microRNAs are small non-coding RNAs that play important roles in post-transcriptional regulation .", ...	[ "Circadian clocks control the timing of animal physiology .", "Drosophila has been a powerful model in understanding the mechanisms of circadian regulation .", "Fruit flies anticipate daily environmental changes and exhibit two peaks of locomotor activity around dawn and dusk .", "Here we identify miR-210 as ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "cell biology/cellular death and stress responses", "neurological disorders", "biochemistry/cell signaling and trafficking structures", "biochemistry/macromolecular assemblies and machines", "computational biology/systems biology" ]	Experimental and Computational Analysis of Polyglutamine-Mediated Cytotoxicity	journal.pcbi.1000944	null	[ [ "A hallmark feature of human neurodegenerative diseases is the accumulation of misfolded or otherwise abnormal proteins which become concentrated into large aggregates .", "Inclusion bodies are large nuclear or cytoplasmic protein aggregates whose predominant constituents may be characteristic of particul...	[ "Expanded polyglutamine ( polyQ ) proteins are known to be the causative agents of a number of human neurodegenerative diseases but the molecular basis of their cytoxicity is still poorly understood .", "PolyQ tracts may impede the activity of the proteasome , and evidence from single cell imaging suggests that t...	[ "Neurodegenerative diseases feature concentration of misfolded or damaged proteins into inclusion bodies .", "There is controversy over whether these entities are protective , detrimental , or relatively benign .", "The formation of inclusion bodies may be accelerated by inefficient protein degradation and may ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/animal models of infection", "pathology/immunology", "virology/effects of virus infection on host gene expression", "immunology/immunity to infections", "pathology/molecular pathology" ]	Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection	journal.ppat.1001347	null	[ [ "Although liver transplantation has emerged as an effective therapeutic approach for treating fulminant virus hepatitis ( FH ) , mortality rates associated with FH remain very high worldwide [1] .", "The recent development of a mouse FH model , based upon infection with the murine hepatitis virus strain-3...	[ "The inhibitory receptor programmed death-1 ( PD-1 ) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however , its precise role in fulminant viral hepatitis ( FH ) has yet to be described .", "Here , we investigated the functional mechanisms of PD-1 as related to FH pathogen...	[ "The principal characteristic of fulminant viral hepatitis ( FH ) induced by the murine hepatitis virus strain-3 ( MHV-3 ) is severe hepatocellular necrosis , which is mediated by the fibrinogen-like protein 2 ( FGL2 ) , a molecule that has the capacity to promote fibrinogen deposition and activate the coagulation ...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune physiology", "immune cells", "spleen", "drugs", "immunology", "pulmonology", "immunosuppressives", "animal models", "pneumonia", "routes of administration", "model organisms", "experimental organism systems", "pha...	Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia	journal.ppat.1006955	null	[ [ "Macrolides have immunomodulatory properties in addition to their antibacterial effects [1 , 2] .", "Indeed , previous clinical trials have shown that macrolides exhibit clinical benefits for various pulmonary diseases , including diffuse panbronchiolitis [3] , chronic obstructive pulmonary disease [4] , ...	[ "Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however , little is known about their precise mechanism of action .", "In this study , we investigated the functional significance of the expansion of myeloid-derived suppressor cell ( MDSC ) -like CD11b+Gr-1+ ...	[ "Myeloid-derived suppressor cells ( MDSCs ) are a heterogeneous population of anti-inflammatory myeloid progenitors that expand in response to acute and chronic inflammation as well as in various diseases , such as autoimmune diseases and cancer .", "The macrolide antibiotic clarithromycin has immunomodulatory ef...	2018
[ "Introduction", "Results/Discussion", "Methods" ]	[]	Conformational Changes in Talin on Binding to Anionic Phospholipid Membranes Facilitate Signaling by Integrin Transmembrane Helices	journal.pcbi.1003316	null	[ [ "Integrins are cell surface receptors involved in many essential cellular processes , such as cell migration , and in pathological defects , such as thrombosis and cancer [1] .", "Integrins are αβ heterodimers .", "Each subunit has a large ectodomain , a single transmembrane ( TM ) helix and a short f...	[ "Integrins are heterodimeric ( αβ ) cell surface receptors that are activated to a high affinity state by the formation of a complex involving the α/β integrin transmembrane helix dimer , the head domain of talin ( a cytoplasmic protein that links integrins to actin ) , and the membrane .", "The talin head domain...	[ "Transmission of signals across the cell membrane is an essential process for all living organisms .", "Integrins are one example of cell surface receptors ( αβ ) which , uniquely , form a bidirectional signalling pathway across the membrane .", "Integrins are crucial for many cellular processes and play key ro...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "transfer rna", "rna-binding proteins", "mitochondrial dna", "gene regulation", "population genetics", "non-coding rna", "forms of dna", "mitochondria", "dna", "bioenergetics", "population biology", "molecular biology techniques", "rna sequencing", "cellular stru...	Ancient Out-of-Africa Mitochondrial DNA Variants Associate with Distinct Mitochondrial Gene Expression Patterns	journal.pgen.1006407	null	[ [ "Genetic variants in the nuclear and mitochondrial genomes have been traditionally used to trace the ancient global migration paths of different human populations [1 , 2] .", "Such studies assumed most variants to be neutral and hence merely reflective of the age of the populations studied .", "Howeve...	[ "Mitochondrial DNA ( mtDNA ) variants have been traditionally used as markers to trace ancient population migrations .", "Although experiments relying on model organisms and cytoplasmic hybrids , as well as disease association studies , have served to underline the functionality of certain mtDNA SNPs , only littl...	[ "The mitochondrion is an organelle found in all cells of our body and plays a significant role in the energy and heat production .", "This is the only organelle in animal cells harboring its own genome outside of the nucleus .", "Mitochondrial DNA ( mtDNA ) variants have been traditionally used as neutral marke...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/functional genomics", "genetics and genomics/gene expression", "computational biology/genomics", "computational biology/transcriptional regulation" ]	Functional Characterization of Variations on Regulatory Motifs	journal.pgen.1000018	null	[ [ "The regulation of gene expression is mediated mainly through specific interactions of TF proteins with DNA promoter elements .", "TF binding sites ( TFBS ) are short ( typically of length 6–20 bases ) and imprecise; unlike restriction enzymes which recognize unique nucleotide sequences , a single TF prot...	[ "Transcription factors ( TFs ) regulate gene expression through specific interactions with short promoter elements .", "The same regulatory protein may recognize a variety of related sequences .", "Moreover , once they are detected it is hard to predict whether highly similar sequence motifs will be recognized ...	[ "A prime mode of control of transcription is the binding of transcription factors to promoter elements .", "These elements are often imprecise – often more than one , yet typically not all , of the nucleotides may be tolerated .", "In another field of protein structures , only some of the amino acid substitutio...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "rna-binding proteins", "rna interference", "gene regulation", "rna extraction", "brassica", "plant physiology", "plant science", "model organisms", "experimental organism systems", "epigenetics", "plants", "extraction techniques", "research and analysis methods", "arabi...	Cucumber mosaic virus coat protein modulates the accumulation of 2b protein and antiviral silencing that causes symptom recovery in planta	journal.ppat.1006522	null	[ [ "RNA silencing is a well-established plant antiviral response triggered by viral double-stranded RNAs or highly structured single-stranded RNAs in host plants .", "Host Dicer-like ( DCL ) enzymes cleave both RNA types into 21 to 24 nucleotide ( nt ) small interfering RNAs ( siRNAs ) that are subsequently ...	[ "Shoot apical meristems ( SAM ) are resistant to most plant viruses due to RNA silencing , which is restrained by viral suppressors of RNA silencing ( VSRs ) to facilitate transient viral invasion of the SAM .", "In many cases chronic symptoms and long-term virus recovery occur , but the underlying mechanisms are...	[ "In many virus-infected plants , the development of viral symptoms on the upper leaves gradually decline , until finally the top leaves appear normal and become resistant to secondary infection .", "Many documented cases suggest that symptom recovery is accompanied with antiviral RNA silencing .", "Most plant v...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans	journal.pgen.1005040	null	[ [ "In eukaryotes , cytoplasmic genes are generally inherited from the mother .", "The mechanisms responsible for this appear to differ between organisms .", "The elimination of mitochondrial DNA ( mtDNA ) during spermatogenesis prevents paternal transmission in Drosophila melanogaster [1] .", "Conve...	[ "Recent reports have questioned the accepted dogma that mammalian mitochondrial DNA ( mtDNA ) is strictly maternally inherited .", "In humans , the argument hinges on detecting a signature of inter-molecular recombination in mtDNA sequences sampled at the population level , inferring a paternal source for the mix...	[ "Emerging evidence raises the possibility that human mitochondrial DNA ( mtDNA ) is not strictly maternally inherited , but it has not been technically possible to test this hypothesis directly .", "We identified trios with discordant mtDNA haplotypes , parent-offspring trios were validated using polymorphic micr...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "gene regulation", "regulatory proteins", "precursor cells", "social sciences", "dna-binding proteins", "cloning", "neuroscience", "dna transcription", "gene function", "transcription factors", "molecular biology techniques", "eyes", "research and analysis m...	R7 Photoreceptor Specification in the Developing Drosophila Eye: The Role of the Transcription Factor Deadpan	journal.pgen.1006159	null	[ [ "Development proceeds in a stepwise manner in which cells pass through a series of interim states in the progression from a pluripotent precursor to a fully-specified and final cell fate .", "Positional signals play a prominent role in this mechanism , with the receipt of the signals promoting the cells t...	[ "As cells proceed along their developmental pathways they make a series of sequential cell fate decisions .", "Each of those decisions needs to be made in a robust manner so there is no ambiguity in the state of the cell as it proceeds to the next stage .", "Here we examine the decision made by the Drosophila R...	[ "Animals are made from a vast diversity of different cell types , and understanding how they are specified is a major goal of developmental biology .", "In this study we use the Drosophila R7 photoreceptor as a model system for understanding how cell fate specification occurs .", "We examine the step when the R...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Plasmodium Infection Is Associated with Impaired Hepatic Dimethylarginine Dimethylaminohydrolase Activity and Disruption of Nitric Oxide Synthase Inhibitor/Substrate Homeostasis	journal.ppat.1005119	null	[ [ "Current estimates of world-wide mortality due to malaria range from 367 , 000 to 755 , 000 deaths per year , mostly in African children [1 , 2] .", "Prompt treatment with parenteral artesunate improves survival in children with severe malaria but mortality remains high in those presenting with complicati...	[ "Inhibition of nitric oxide ( NO ) signaling may contribute to pathological activation of the vascular endothelium during severe malaria infection .", "Dimethylarginine dimethylaminohydrolase ( DDAH ) regulates endothelial NO synthesis by maintaining homeostasis between asymmetric dimethylarginine ( ADMA ) , an e...	[ "During a malaria infection , the vascular endothelium becomes more adhesive , permeable , and prone to trigger blood clotting .", "These changes help the parasite adhere to blood vessels , but endanger the host by obstructing blood flow through small vessels .", "Endothelial nitric oxide ( NO ) would normally ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "physiology", "biology", "anatomy and physiology", "biophysics", "computational biology", "cardiovascular" ]	Effects of Electrical and Structural Remodeling on Atrial Fibrillation Maintenance: A Simulation Study	journal.pcbi.1002390	null	[ [ "Atrial fibrillation ( AF ) is a cardiac arrhythmia characterized by rapid and irregular atrial activation .", "Such desynchronized activation may occur when multiple waves circulate the atria .", "Unlike ventricular fibrillation , where unsynchronized activation of the ventricles ( the main pumping c...	[ "Atrial fibrillation , a common cardiac arrhythmia , often progresses unfavourably: in patients with long-term atrial fibrillation , fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls .", "This is due to electrical , structural , and contractile remo...	[ "Atrial fibrillation is an abnormal heart rhythm characterized by rapid and irregular activation of the upper chambers of the heart .", "Atrial fibrillation often shows a natural progression towards longer and more frequently occurring episodes and often occurs in patients with existing heart disease ( s ) .", ...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Random Wiring, Ganglion Cell Mosaics, and the Functional Architecture of the Visual Cortex	journal.pcbi.1004602	null	[ [ "Processing high-dimensional external stimuli and efficiently communicating their essential features to higher brain areas is a fundamental function of any sensory system .", "For many sensory modalities , this task is implemented via convergent and divergent neural pathways in which information from a la...	[ "The architecture of iso-orientation domains in the primary visual cortex ( V1 ) of placental carnivores and primates apparently follows species invariant quantitative laws .", "Dynamical optimization models assuming that neurons coordinate their stimulus preferences throughout cortical circuits linking millions ...	[ "In the primary visual cortex of primates and carnivores , local visual stimulus features such as edge orientation are processed by neurons arranged in arrays of iso-orientation domains .", "Large-scale comparative studies have uncovered that the spatial layout of these domains and their topological defects follo...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission	journal.pntd.0004052	null	[ [ "With 3 . 6 billion people at risk and nearly 400 million infections annually [1 , 2] , dengue has become the most important mosquito-borne viral disease affecting humans today .", "Dengue virus ( DENV ) is a positive-sense , single-stranded RNA virus of the family Flaviviridae , genus Flavivirus .", ...	[ "Dengue virus ( DENV ) infection of an individual human or mosquito host produces a dynamic population of closely-related sequences .", "This intra-host genetic diversity is thought to offer an advantage for arboviruses to adapt as they cycle between two very different host species , but it remains poorly charact...	[ "Dengue virus ( DENV ) is transmitted between humans through the bite of infected female Aedes aegypti mosquitoes .", "Virus populations experience significant drops in size and are subject to differing selection pressures as they cycle between human and mosquito hosts .", "Subsequent changes in viral intra-hos...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "cell biology", "computational biology" ]	Endothelial Cell Capture of Heparin-Binding Growth Factors under Flow	journal.pcbi.1000971	null	[ [ "The bioavailability of molecules as they circulate through the bloodstream is a crucial factor in their signaling capability .", "Half-life in circulation can determine the effectiveness of a drug simply by regulating the opportunities a molecule has to interact with the vessel wall .", "Although in ...	[ "Circulation is an important delivery method for both natural and synthetic molecules , but microenvironment interactions , regulated by endothelial cells and critical to the molecule's fate , are difficult to interpret using traditional approaches .", "In this work , we analyzed and predicted growth factor captu...	[ "In this work we have investigated the role of a family of cell surface molecules , proteoglycans , in blood vessel capture of proteins important to normal and diseased states under flow conditions .", "We developed a computer model to analyze and predict these events and , using an experimental system incorporat...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "second messenger system", "mechanisms of signal transduction", "cgmp signaling", "host-pathogen interaction", "microbiology", "parasitology", "parasite physiology", "phosphoinositide signal transduction", "crosstalk", "cell movement signaling", "signaling pathways", "calcium signaling", "pr...	Phosphoinositide Metabolism Links cGMP-Dependent Protein Kinase G to Essential Ca2+ Signals at Key Decision Points in the Life Cycle of Malaria Parasites	journal.pbio.1001806	Chemical genetics and a global comparative analysis of phosphorylation and phospholipids in vivo shows that PKG is the upstream regulator that induces calcium signals that enables Plasmodium to progress through its complex life cycle.	[ [ "Malaria is caused by vector-born protozoan parasites of the genus Plasmodium , which cycle between mosquitoes and humans .", "Waves of fever arise from the synchronised egress of merozoites from erythrocytes , an event that must be followed by the invasion of fresh red blood cells ( RBCs ) for the asexua...	[ "Many critical events in the Plasmodium life cycle rely on the controlled release of Ca2+ from intracellular stores to activate stage-specific Ca2+-dependent protein kinases .", "Using the motility of Plasmodium berghei ookinetes as a signalling paradigm , we show that the cyclic guanosine monophosphate ( cGMP ) ...	[ "Malaria , caused by Plasmodium spp .", "parasites , is a profound human health problem .", "Plasmodium parasites progress through a complex life cycle as they move between infected humans and blood-feeding mosquitoes .", "We know that tight regulation of calcium ion levels within the cytosol of the parasite ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "neurobiology of disease and regeneration", "functional genomics", "retrovirology and hiv immunopathogenesis", "microbiology", "neuroscience", "infectious diseases", "hiv", "biology", "dementia", "virology", "neurology", "neurological disorders", "viral diseases", "genomics",...	Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders	journal.ppat.1002213	null	[ [ "HAND is a common complication of HIV-1 infection in the nervous system presenting a varied spectrum of clinical manifestations with cognitive , motor and behavioral symptoms .", "Currently three conditions of increasing severity are recognized as components of HAND: HIV-1-associated asymptomatic neurocog...	[ "Antiretroviral therapy ( ART ) has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders ( HAND ) persist despite treatment .", "The reasons for the limited efficacy of ART in the brain are unknown .", "Here we used functional genomics to determine ART effectiven...	[ "HAND is a common complication of HIV-1 infection in the nervous system presenting a varied spectrum of clinical manifestations with cognitive , motor and behavioral symptoms .", "Introduction of ART has greatly reduced morbidity and mortality in HIV-1 infection; however HAND persists and its overall prevalence a...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "milk", "reproductive system", "body fluids", "maternal health", "nucleases", "enzymes", "gene regulation", "dna-binding proteins", "enzymology", "diet", "reproductive physiology", "endocrine physiology", "epithelial cells", "nutrition", "women's health"...	A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation	journal.pgen.1007072	null	[ [ "The oligoadenylate synthetase ( OAS ) enzymes are activated by detection of double stranded RNA produced during the viral life cycle , and in response polymerize ATP into 2´-5´ linked oligoadenylates ( 2-5A ) of various lengths .", "The 2-5As then bind and activate latent RNase L , which degrades viral a...	[ "We identified a non-synonymous mutation in Oas2 ( I405N ) , a sensor of viral double-stranded RNA , from an ENU-mutagenesis screen designed to discover new genes involved in mammary development .", "The mutation caused post-partum failure of lactation in healthy mice with otherwise normally developed mammary gla...	[ "Using ENU-mutagenesis in mice we discovered a pedigree with lactation failure .", "Mammary development through puberty and pregnancy appeared normal in mutant animals , but the activation of lactation failed in the immediate post partum period and no milk reached the pups .", "Failure of lactation was accompan...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cancer genomics", "sequencing techniques", "medicine and health sciences", "chemical compounds", "cancers and neoplasms", "basic cancer research", "organic compounds", "oncology", "genome sequencing", "mutation", "pyrimidines", "sequence motif analysis", "dna", "molecular biology techniqu...	Elevated pyrimidine dimer formation at distinct genomic bases underlies promoter mutation hotspots in UV-exposed cancers	journal.pgen.1007849	null	[ [ "Whole genome analysis of cancer genomes has the potential to reveal non-coding somatic mutations that drive tumor development , but it remains a major challenge to separate these events from non-functional passengers .", "The main principle for identifying drivers is recurrence across independent tumors ...	[ "Sequencing of whole cancer genomes has revealed an abundance of recurrent mutations in gene-regulatory promoter regions , in particular in melanoma where strong mutation hotspots are observed adjacent to ETS-family transcription factor ( TF ) binding sites .", "While sometimes interpreted as functional driver ev...	[ "Cancer is caused by somatic mutations that typically occur in protein-coding genes .", "However , the advent of whole genome sequencing has made it possible to venture beyond protein-coding DNA in search of non-coding mutations with putative cancer driver roles .", "Indeed , recent studies , in particular in s...	2018
[ "Introduction", "Results and discussions", "Materials and methods" ]	[ "protons", "medicine and health sciences", "metabolic networks", "physiological processes", "metabolites", "network analysis", "genome analysis", "bioenergetics", "thermodynamics", "research and analysis methods", "computer and information sciences", "genomics", "biological databases", "nu...	Erroneous energy-generating cycles in published genome scale metabolic networks: Identification and removal	journal.pcbi.1005494	null	[ [ "Constraint-based analysis , in particular flux-balance analysis ( FBA ) , is the current state of the art in genome-scale metabolic modeling [1] .", "Constraint-based modeling assumes a steady state ( i . e . , every internal metabolite that is produced must be consumed at the same rate ) and imposes low...	[ "Energy metabolism is central to cellular biology .", "Thus , genome-scale models of heterotrophic unicellular species must account appropriately for the utilization of external nutrients to synthesize energy metabolites such as ATP .", "However , metabolic models designed for flux-balance analysis ( FBA ) may ...	[ "Genome-scale metabolic models are routinely used to simulate the growth of unicellular organisms , and are likely to become an important tool in the medical sciences .", "The most popular method employed for this task is flux balance analysis ( FBA ) , a simplified mathematical description able to describe the s...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical bonding", "medicine and health sciences", "manganese", "hela cells", "biological cultures", "cell processes", "vertebrates", "animals", "biological locomotion", "animal models", "osteichthyes", "organisms", "developmental biology", "model organisms", "experimental organism syst...	Zebrafish slc30a10 deficiency revealed a novel compensatory mechanism of Atp2c1 in maintaining manganese homeostasis	journal.pgen.1006892	null	[ [ "Manganese ( Mn ) is an essential element required for the catalytic activity of numerous cellular enzymes [1] .", "The mammalian divalent metal ion influx transporter SLC39A8 has high affinity for Mn [2 , 3] , and mutations are associated with low blood Mn levels and impaired function of Mn-dependent enz...	[ "Recent studies found that mutations in the human SLC30A10 gene , which encodes a manganese ( Mn ) efflux transporter , are associated with hypermanganesemia with dystonia , polycythemia , and cirrhosis ( HMDPC ) .", "However , the relationship between Mn metabolism and HMDPC is poorly understood , and no specifi...	[ "Impaired function of the manganese transporter SLC30A10 has been implicated in HMDPC ( hypermanganesemia with dystonia , polycythemia , and cirrhosis ) , an early-onset metabolic disorder clinically characterized by increased systemic Mn levels , neurological impairment , polycythemia , and hepatic injury .", "N...	2017
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "molecular biology", "evolutionary biology" ]	Concatenated Analysis Sheds Light on Early Metazoan Evolution and Fuels a Modern “Urmetazoon” Hypothesis	journal.pbio.1000020	Total evidence analyses reveal a surprise: Higher animals did not evolve from any known lower animal group.	[ [ "Mainly because of misinterpretation of life cycle stages between Trichoplax adhaerens and the hydrozoan Eleutheria dichotoma , Placozoa lost their predominant role as the key model system for studying the origin of metazoan life [5 , 17] .", "This outcome was nourished by molecular studies based on a var...	[ "For more than a century , the origin of metazoan animals has been debated .", "One aspect of this debate has been centered on what the hypothetical “urmetazoon” bauplan might have been .", "The morphologically most simply organized metazoan animal , the placozoan Trichoplax adhaerens , resembles an intriguing ...	[ "Following one of the basic principles in evolutionary biology that complex life forms derive from more primitive ancestors , it has long been believed that the higher animals , the Bilateria , arose from simpler ( diploblastic ) organisms such as the cnidarians ( corals , polyps , and jellyfishes ) .", "A large ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Activin-Like Kinase 2 Functions in Peri-implantation Uterine Signaling in Mice and Humans	journal.pgen.1003863	null	[ [ "The tunica mucosa of the uterus , called the endometrium , must undergo significant changes to become receptive to implantation of the blastocyst .", "The endometrium consists of glandular and luminal epithelium and stroma , and when the endometrium is receptive , the embryos can attach to the endometria...	[ "Implantation of a blastocyst in the uterus is a multistep process tightly controlled by an intricate regulatory network of interconnected ovarian , uterine , and embryonic factors .", "Bone morphogenetic protein ( BMP ) ligands and receptors are expressed in the uterus of pregnant mice , and BMP2 has been shown ...	[ "A couple is defined as infertile when failing to become pregnant after one year of regular , unprotected intercourse .", "Infertility affects more than 10% of couples .", "The implantation of the embryo in the uterus is one of the most critical steps of pregnancy , and it has been estimated that 75% of pregnan...	2013
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "caenorhabditis", "fungal genetics", "rna extraction", "parasitic diseases", "animals", "nematode infections", "animal models", "fungi", "caenorhabditis elegans", "model organisms", "experimental organism systems", "extraction techniques", ...	Intercellular communication is required for trap formation in the nematode-trapping fungus Duddingtonia flagrans	journal.pgen.1008029	null	[ [ "A predatory lifestyle is typically associated with animals like lions , tigers or snakes .", "Dramatic hunts or attacks out of a hiding place are typical scenes in reportage movies .", "No less dramatic is the situation when some nematode-trapping fungi ( NTF ) catch their prey using sophisticated tr...	[ "Nematode-trapping fungi ( NTF ) are a large and diverse group of fungi , which may switch from a saprotrophic to a predatory lifestyle if nematodes are present .", "Different fungi have developed different trapping devices , ranging from adhesive cells to constricting rings .", "After trapping , fungal hyphae ...	[ "Nematode-trapping fungi are fascinating microorganisms , because they are able to switch from saprotrophic growth to a predatory lifestyle .", "Duddingtonia flagrans forms adhesive trap systems and conidia and resistant chlamydospores .", "Chlamydospores are ideal for dissemination in the environment to contro...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "cell biology", "computational biology", "molecular biology" ]	The Signal Sequence Coding Region Promotes Nuclear Export of mRNA	journal.pbio.0050322	Signal sequences, which target newly synthesized secretory proteins to the endoplasmic reticulum, are encoded by adenine-depleted nucleotide sequences that promote the nuclear export of the mRNAs.	[ [ "In eukaryotes , mRNAs are synthesized and processed in the nucleus before they are transported through the nuclear pores into the cytoplasm , where they are translated into proteins .", "Nuclear export of most mRNAs is mediated by the conserved transcription export ( TREX ) complex that is comprised of t...	[ "In eukaryotic cells , most mRNAs are exported from the nucleus by the transcription export ( TREX ) complex , which is loaded onto mRNAs after their splicing and capping .", "We have studied in mammalian cells the nuclear export of mRNAs that code for secretory proteins , which are targeted to the endoplasmic re...	[ "In eukaryotic cells , precursors of messenger RNAs ( mRNAs ) are synthesized and processed in the nucleus .", "During processing , noncoding introns are spliced out , and a cap and poly-adenosine sequence are added to the beginning and end of the transcript , respectively .", "The resulting mature mRNA is expo...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "circuit models", "connectomics", "calcium imaging", "developmental neuroscience", "computer science", "neuroanatomy", "neural networks", "computational neuroscience", "biology", "computerized simulations", "neuroscience", "neural circuit formation", "neuroimaging" ]	Model-Free Reconstruction of Excitatory Neuronal Connectivity from Calcium Imaging Signals	journal.pcbi.1002653	null	[ [ "The identification of the topological features of neuronal circuits is an essential step towards understanding neuronal computation and function .", "Despite considerable progress in neuroanatomy , electrophysiology and imaging [1]–[8] , the detailed mapping of neuronal circuits is already a difficult ta...	[ "A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically infeasible , even in simpler systems like dissociated neuronal cultures .", "We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct structural connecti...	[ "Unraveling the general organizing principles of connectivity in neural circuits is a crucial step towards understanding brain function .", "However , even the simpler task of assessing the global excitatory connectivity of a culture in vitro , where neurons form self-organized networks in absence of external sti...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "borrelia infection", "zoonoses", "neglected tropical diseases" ]	Multispacer Sequence Typing Relapsing Fever Borreliae in Africa	journal.pntd.0001652	null	[ [ "In Africa , relapsing fevers ( RF ) are arthropod-borne diseases caused by four cultured species Borrelia crocidurae , Borrelia duttonii , Borrelia hispanica and Borrelia recurrentis [1] .", "Transmission is by the bite of Ornithodoros soft ticks for the first three species whereas Pediculus humanus lous...	[ "In Africa , relapsing fevers are neglected arthropod-borne infections caused by closely related Borrelia species .", "They cause mild to deadly undifferentiated fever particularly severe in pregnant women .", "Lack of a tool to genotype these Borrelia organisms limits knowledge regarding their reservoirs and t...	[ "In Africa , relapsing fevers are caused by four cultured species: Borrelia crocidurae , Borrelia duttonii , Borrelia hispanica and Borrelia recurrentis .", "These borreliae are transmitted by the bite of Ornithodoros soft ticks except for B . recurrentis which is transmitted by louse Pediculus humanus .", "The...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology", "biology", "computational biology" ]	Structural Consensus among Antibodies Defines the Antigen Binding Site	journal.pcbi.1002388	null	[ [ "Antibody-Antigen ( Ab-Ag ) interactions are based on non-covalent binding between the antibody ( Ab ) and the antigen ( Ag ) .", "Correct identification of the residues that mediate Ag recognition and binding would improve our understanding of antigenic interactions and may permit the modification and ma...	[ "The Complementarity Determining Regions ( CDRs ) of antibodies are assumed to account for the antigen recognition and binding and thus to contain also the antigen binding site .", "CDRs are typically discerned by searching for regions that are most different , in sequence or in structure , between different anti...	[ "Antibodies are a primary adaptive defence mechanism against infection , and function by recognizing and binding to non-self antigens .", "While most of the sequence of all antibodies of a given individual is identical , relatively small variations turn each antibody into a specific binder of one antigen .", "I...	2012
[ "Introduction", "Results and Discussion", "Conclusions", "Methods" ]	[]	Biofilm Formation As a Response to Ecological Competition	journal.pbio.1002191	Mixing natural isolates of the pathogenic bacterium Pseudomonas aeruginosa shows that the formation of biofilm is a response to antibiotic stress from competing genotypes.	[ [ "While the traditional model for bacterial life was one of cells swimming in liquid , it is now realized that bacteria commonly live in surface-associated communities known as biofilms [1–4] .", "These groups of bacteria carry significant medical and economic importance that includes a role in chronic dis...	[ "Bacteria form dense surface-associated communities known as biofilms that are central to their persistence and how they affect us .", "Biofilm formation is commonly viewed as a cooperative enterprise , where strains and species work together for a common goal .", "Here we explore an alternative model: biofilm ...	[ "Bacteria often attach to each other and to surfaces and make biofilms .", "These dense communities occur everywhere , including on us and inside us , where they are central to both health and disease .", "Biofilm formation is often viewed as the coordinated action of multiple strains that work together in orde...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	A Conserved Endoplasmic Reticulum Membrane Protein Complex (EMC) Facilitates Phospholipid Transfer from the ER to Mitochondria	journal.pbio.1001969	Tethering of the endoplasmic reticulum to mitochondria by a conserved endoplasmic reticulum complex is needed for the transfer of phospholipids between these organelles.	[ [ "Mitochondria are critical cellular components that are needed for energy production , lipid metabolism , calcium regulation , and apoptosis .", "Most proteins and lipids necessary for mitochondrial biogenesis are not synthesized in mitochondria and must be imported .", "Although protein import into m...	[ "Mitochondrial membrane biogenesis and lipid metabolism require phospholipid transfer from the endoplasmic reticulum ( ER ) to mitochondria .", "Transfer is thought to occur at regions of close contact of these organelles and to be nonvesicular , but the mechanism is not known .", "Here we used a novel genetic ...	[ "Mitochondrial membrane biogenesis and lipid metabolism depend on the transfer of phospholipid from the endoplasmic reticulum to mitochondria .", "This transfer is thought to occur at regions where these organelles are in close contact , and , although the process is thought not to involve vesicles , the mechanis...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "pathology and laboratory medicine", "cell processes", "genomic library screening", "animals", "wolbachia", "invertebrate genomics", "animal models", "drosophila melanogaster", "model organisms", "experimental organism syst...	Whole genome screen reveals a novel relationship between Wolbachia levels and Drosophila host translation	journal.ppat.1007445	null	[ [ "Insects are common vectors for devastating human viruses such as Zika , Yellow Fever , and Dengue .", "A novel preventative strategy has emerged to combat vector-borne diseases that exploits the consequences of vector-insect infection with the bacteria Wolbachia pipientis [1–4] .", "Wolbachia is a ve...	[ "Wolbachia is an intracellular bacterium that infects a remarkable range of insect hosts .", "Insects such as mosquitos act as vectors for many devastating human viruses such as Dengue , West Nile , and Zika .", "Remarkably , Wolbachia infection provides insect hosts with resistance to many arboviruses thereby ...	[ "Insects such as mosquitos act as vectors to spread devastating human diseases such as Dengue , West Nile , and Zika .", "It is critical to develop control strategies to prevent the transmission of these diseases to human populations .", "A novel strategy takes advantage of an endosymbiotic bacterium Wolbachia ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "hepatitis c", "infectious diseases", "medicine and health sciences", "infectious hepatitis", "simulation and modeling", "population modeling", "gastroenterology and hepatology", "biology and life sciences", "infectious disease modeling", "computational biology", "viral diseases", "liver disea...	Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes	journal.pcbi.1003934	null	[ [ "Around 170 million people worldwide are chronically infected with hepatitis C virus ( HCV ) , representing a major public health problem [1] .", "Chronic HCV infection can lead to liver cirrhosis , hepatocellular carcinoma and liver failure , and it represents the leading cause for liver transplantation ...	[ "Chronic liver infection by hepatitis C virus ( HCV ) is a major public health concern .", "Despite partly successful treatment options , several aspects of intrahepatic HCV infection dynamics are still poorly understood , including the preferred mode of viral propagation , as well as the proportion of infected h...	[ "Around 170 million people worldwide are chronically infected with the hepatitis C virus ( HCV ) .", "Although partly successful treatment options are available , several aspects of HCV infection dynamics within the liver are still poorly understood .", "How many hepatocytes are infected during chronic HCV infe...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	High-Throughput Genetic and Gene Expression Analysis of the RNAPII-CTD Reveals Unexpected Connections to SRB10/CDK8	journal.pgen.1003758	null	[ [ "The largest subunit of RNA polymerase II , Rpb1 , has a unique C-terminal domain ( CTD ) composed of the repeated sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser ( Y1 S2 P3 T4 S5 P6 S7 ) [1] , [2] .", "Although the CTD is highly conserved across species , the number of repeats varies in a manner resembling genomic ...	[ "The C-terminal domain ( CTD ) of RNA polymerase II ( RNAPII ) is composed of heptapeptide repeats , which play a key regulatory role in gene expression .", "Using genetic interaction , chromatin immunoprecipitation followed by microarrays ( ChIP-on-chip ) and mRNA expression analysis , we found that truncating t...	[ "RNA Polymerase II ( RNAPII ) is the enzyme responsible for the transcription of all protein-coding genes .", "It has a unique extended domain called the C-terminal domain ( CTD ) .", "This domain is highly conserved across species and is composed of repeats of a seven amino acid sequence .", "The CTD functio...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunomodulation", "infectious diseases/tropical and travel-associated diseases", "immunology/immunity to infections", "infectious diseases/protozoal infections" ]	Distinct Roles for FOXP3+ and FOXP3− CD4+ T Cells in Regulating Cellular Immunity to Uncomplicated and Severe Plasmodium falciparum Malaria	journal.ppat.1000364	null	[ [ "The clinical spectrum of P . falciparum infection ranges from asymptomatic parasite carriage to a febrile disease that may develop into a severe , life-threatening illness .", "The factors that determine disease severity are not completely understood but are likely to include both parasite and host compo...	[ "Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to pathogenesis of severe malaria .", "To determine whether this balance is maintained by classical regulatory T cells ( CD4+ FOXP3+ CD127−/low; Tregs ) we compared cellular responses between...	[ "While Tregs have been implicated in regulation of the immune response to chronic infections , their potential in determining disease outcome in acute infections is unclear .", "In this study we have found that Tregs are unable to control the florid inflammation during acute , severe P . falciparum malaria infect...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome sequencing", "genomics", "genetic mutation", "genetics", "biology", "human genetics", "genetics of disease", "genetics and genomics" ]	Predicting Mendelian Disease-Causing Non-Synonymous Single Nucleotide Variants in Exome Sequencing Studies	journal.pgen.1003143	null	[ [ "Since the first successful application of exome sequencing in finding the causal mutation for a Mendelian disease [1] , many such studies have been conducted to identify other Mendelian disease-causing ( or pathogenic ) variants .", "Compared to genetic linkage studies of Mendelian diseases , exome seque...	[ "Exome sequencing is becoming a standard tool for mapping Mendelian disease-causing ( or pathogenic ) non-synonymous single nucleotide variants ( nsSNVs ) .", "Minor allele frequency ( MAF ) filtering approach and functional prediction methods are commonly used to identify candidate pathogenic mutations in these ...	[ "Sequencing the coding regions of the human genome is becoming a standard approach in identifying causal genes for human Mendelian diseases .", "Researchers often rely on multiple functional prediction methods/tools to separate the candidate causal mutation ( s ) from other rare mutations in these studies .", "...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "biochemical simulations", "cell death", "signal transduction", "mathematics", "cell biology", "apoptosis", "gene expression", "genetics", "biology and life sciences", "cell processes", "physical sciences", "computational biology", "stochastic processes", "probability the...	Modeling Dynamics of Cell-to-Cell Variability in TRAIL-Induced Apoptosis Explains Fractional Killing and Predicts Reversible Resistance	journal.pcbi.1003893	null	[ [ "TNF-Related Apoptosis Inducing-Ligand ( TRAIL ) is a promising therapeutic agent against cancer because it induces apoptosis specifically in tumor cells [1]–[3] .", "This motivated dozens of clinical trials based on TRAIL-related therapies .", "However , efficiency was usually limited [4] .", "Mo...	[ "Isogenic cells sensing identical external signals can take markedly different decisions .", "Such decisions often correlate with pre-existing cell-to-cell differences in protein levels .", "When not neglected in signal transduction models , these differences are accounted for in a static manner , by assuming r...	[ "TRAIL induces apoptosis selectively in cancer cells and is currently tested in clinics .", "Having a mechanistic understanding of TRAIL resistance could help to limit its apparition .", "Several observations suggested that protein level fluctuations play an important role in TRAIL resistance and its acquisitio...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Parent-of-Origin Effects of the APOB Gene on Adiposity in Young Adults	journal.pgen.1005573	null	[ [ "Genome-wide association studies ( GWAS ) have identified multiple loci associated with cardio-metabolic risk ( CMR ) phenotypes and traits , such as adiposity and glycemic traits ( e . g [1–4] ) .", "GWAS are conducted , very largely , in unrelated individuals .", "In general , the magnitudes of thes...	[ "Loci identified in genome-wide association studies ( GWAS ) of cardio-metabolic traits account for a small proportion of the traits' heritability .", "To date , most association studies have not considered parent-of-origin effects ( POEs ) .", "Here we report investigation of POEs on adiposity and glycemic tra...	[ "To date , genetic variants identified in large-scale genetic studies using recent technical and methodological advances explain only a small proportion of the genetic basis of obesity , diabetes and other cardiovascular risk factors .", "These studies were typically conducted in samples of unrelated individuals ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood serum", "dengue virus", "medicine and health sciences", "chemical characterization", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "body fluids", "pathogens", "immunology", "microbiology", "viruses", "vaccines", "preventive medicine", "rna...	Human dengue virus serotype 2 neutralizing antibodies target two distinct quaternary epitopes	journal.ppat.1006934	null	[ [ "Dengue virus ( DENV ) is a single stranded positive sense RNA virus that is transmitted by the Aedes mosquito [1] .", "There are four distinct DENV serotypes ( DENV1-4 ) , and infection results in a range of symptoms , from fever and rash to the more serious dengue hemorrhagic fever and dengue shock synd...	[ "Dengue virus ( DENV ) infection causes dengue fever , dengue hemorrhagic fever and dengue shock syndrome .", "It is estimated that a third of the world’s population is at risk for infection , with an estimated 390 million infections annually .", "Dengue virus serotype 2 ( DENV2 ) causes severe epidemics , and ...	[ "Dengue viruses ( DENV ) are flaviviruses transmitted by mosquitos .", "There are approximately 390 million DENV infections every year , making dengue virus a major global public health concern .", "While there is a recently licensed DENV vaccine , it has low efficacy against preventing DENV2 infections .", "...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "mycobacterium leprae", "medicine and health sciences", "enzyme-linked immunoassays", "pathology and laboratory medicine", "laboratory equipment", "engineering and technology", "tropical diseases", "geographical locations", "biomarkers", "bacterial diseases", "neglected tropical diseases", "fi...	Longitudinal assessment of anti-PGL-I serology in contacts of leprosy patients in Bangladesh	journal.pntd.0006083	null	[ [ "Leprosy is an infectious disease caused by Mycobacterium leprae ( M . leprae ) , which causes damage to the skin and peripheral nerves[1] .", "The highest numbers of new leprosy cases are detected in India ( 127 , 326 in 2015 ) , Brazil ( 26 , 395 in 2015 ) and Indonesia ( 17 , 202 in 2015 ) [2] .", ...	[ "Despite elimination efforts , the number of Mycobacterium leprae ( M . leprae ) infected individuals who develop leprosy , is still substantial .", "Solid evidence exists that individuals living in close proximity to patients are at increased risk to develop leprosy .", "Early diagnosis of leprosy in endemic a...	[ "Leprosy is an infectious disease caused by the bacterium Mycobacterium leprae , which causes skin and nerve damage .", "Despite worldwide efforts to eliminate leprosy , the number of infected individuals who develop leprosy , is still substantial .", "Household contacts of new leprosy patients are especially a...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Computational Identification of Mechanistic Factors That Determine the Timing and Intensity of the Inflammatory Response	journal.pcbi.1004460	null	[ [ "Prolonged inflammation is a recognized contributor to a multitude of pathological conditions , including cardiovascular , metabolic , and neurodegenerative diseases , as well as chronic injuries [1 , 2] .", "Timely resolution of inflammation is essential for tissue homeostasis .", "Inflammation resol...	[ "Timely resolution of inflammation is critical for the restoration of homeostasis in injured or infected tissue .", "Chronic inflammation is often characterized by a persistent increase in the concentrations of inflammatory cells and molecular mediators , whose distinct amount and timing characteristics offer an ...	[ "A recent approach to quantitatively characterize the timing and intensity of the inflammatory response relies on the use of four quantities termed inflammation indices .", "The values of the inflammation indices may reflect the differences between normal and pathological inflammation , and may be used to gauge t...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "mathematics", "statistics", "biology", "computational biology" ]	Near-Native Protein Loop Sampling Using Nonparametric Density Estimation Accommodating Sparcity	journal.pcbi.1002234	null	[ [ "Starting from a known structural homolog , template based modeling ( TBM ) of protein structure provides the most accurate predictions of protein sequences with unknown structure [1] , [2] .", "However , even with close structural homologs , structurally variable regions ( SVRs ) , commonly referred to a...	[ "Unlike the core structural elements of a protein like regular secondary structure , template based modeling ( TBM ) has difficulty with loop regions due to their variability in sequence and structure as well as the sparse sampling from a limited number of homologous templates .", "We present a novel , knowledge-...	[ "A protein's structure consists of elements of regular secondary structure connected by less regular stretches of loop segments .", "The irregularity of the loop structure makes loop modeling quite challenging .", "More accurate sampling of these loop conformations has a direct impact on protein modeling , desi...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "organismal evolution", "genome evolution", "population genetics", "microbiology", "parallel evolution", "mutation", "microbial evolution", "forms of evolution", "comparative genomics", "biology", "evolutionary theory", "evolutionary genetics", "viral evolution", "natural selection", "vi...	Intrasubtype Reassortments Cause Adaptive Amino Acid Replacements in H3N2 Influenza Genes	journal.pgen.1004037	null	[ [ "The genome of influenza A virus consists of 8 segments , each represented by an RNA molecule .", "Coinfection of a cell by viruses of different genotypes occasionally leads to reassortments , i .", "e .", "formation of genotypes containing molecules from different sources .", "Most of the maj...	[ "Reassortments and point mutations are two major contributors to diversity of Influenza A virus; however , the link between these two processes is unclear .", "It has been suggested that reassortments provoke a temporary increase in the rate of amino acid changes as the viral proteins adapt to new genetic environ...	[ "Influenza A is a rapidly evolving virus with genome composed of eight distinct RNA molecules called segments .", "This genetic structure allows formation of new combinations of segments when a cell is coinfected by multiple viral strains , in a process called reassortment .", "While “antigenic drift” – the pro...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	UFBP1, a Key Component of the Ufm1 Conjugation System, Is Essential for Ufmylation-Mediated Regulation of Erythroid Development	journal.pgen.1005643	null	[ [ "The Ufm1 ( Ubiquitin-fold modifier 1 ) conjugation system is a novel ubiquitin-like ( Ubl ) modification system that mediates protein modification by a small protein modifier Ufm1 [1] .", "Ufmylation is catalyzed by a series of enzymes , consisting of Ufm1-activating E1 enzyme ( Uba5 ) , Ufm1-conjugating...	[ "The Ufm1 conjugation system is an ubiquitin-like modification system that consists of Ufm1 , Uba5 ( E1 ) , Ufc1 ( E2 ) , and less defined E3 ligase ( s ) and targets .", "The biological importance of this system is highlighted by its essential role in embryogenesis and erythroid development , but the underlying ...	[ "Protein modification by Ubiquitin ( Ub ) and Ubiquitin-like proteins ( Ubl ) plays pivotal roles in a wide range of cellular functions and signaling pathways .", "The Ufm1 conjugation system is a novel ubiquitin-like system , yet its biological functions and working mechanism remains poorly understood .", "UFB...	2015
[ "Introduction", "Materials and methods", "Results and discussion" ]	[ "taxonomy", "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "vertebrates", "animals", "mammals", "genetic mapping", "viruses", "phylogenetics", "data management", "rna viruses", "phyloge...	First cases of European bat lyssavirus type 1 in Iberian serotine bats: Implications for the molecular epidemiology of bat rabies in Europe	journal.pntd.0006290	null	[ [ "Rabies is caused by viruses of the genus Lyssavirus , which includes so far fourteen species recognized by the International Committee on Taxonomy of Viruses ( ICTV ) , plus the recently proposed Lleida bat Lyssavirus ( LLEBV ) [1] and Gannoruwa bat lyssavirus ( GBLV ) [2] .", "Three of the viruses of th...	[ "Previous studies have shown that EBLV-1 strains exclusively hosted by Eptesicus isabellinus bats in the Iberian Peninsula cluster in a specific monophyletic group that is related to the EBLV-1b lineage found in the rest of Europe .", "More recently , enhanced passive surveillance has allowed the detection of the...	[ "Rabies is caused by at least fourteen different viruses of the genus Lyssavirus .", "Although the classical rabies virus transmitted by the dog accounts for most human cases , most lyssaviruses are hosted by bats , which are able to transmit the disease to humans .", "The European bat lyssaviruses 1 ( EBLV-1 )...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "brain", "vertebrates", "social sciences", "neuroscience", "animals", "mammals", "magnetic resonance imaging", "primates", "brain mapping", "animal management", "animal performance", "neuroim...	Areal differences in depth cue integration between monkey and human	journal.pbio.2006405	null	[ [ "Visual environments provide a range of cues that allow the brain to extract depth structure from the ambiguous images projected onto the two-dimensional ( 2D ) retinas .", "A fundamental challenge in visual neuroscience is to understand how this 2D information is processed and integrated , to allow the v...	[ "Electrophysiological evidence suggested primarily the involvement of the middle temporal ( MT ) area in depth cue integration in macaques , as opposed to human imaging data pinpointing area V3B/kinetic occipital area ( V3B/KO ) .", "To clarify this conundrum , we decoded monkey functional MRI ( fMRI ) responses ...	[ "In everyday life , we interact with a three-dimensional world that we perceive via our two-dimensional retinas .", "Our brain can reconstruct the third dimension from these flat retinal images using multiple sources of visual information , or cues .", "The horizontal displacement of the two retinal images , kn...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "innate immune system", "medicine and health sciences", "reproductive system", "immune physiology", "cytokines", "pathology and laboratory medicine", "viral transmission and infection", "spleen", "immunology", "microbiology", "vertebrates", "cytomegalovirus infection", "animals", "mammals"...	Roles of GP33, a guinea pig cytomegalovirus-encoded G protein-coupled receptor homolog, in cellular signaling, viral growth and inflammation in vitro and in vivo	journal.ppat.1007487	null	[ [ "Congenital infection of human cytomegalovirus ( HCMV ) occurs in 0 . 2–1% of all births and causes birth defects and developmental abnormalities , including neurological sequela [1–4] .", "In contrast to murine CMV ( MCMV ) and rat CMV ( RCMV ) , guinea pig CMV ( GPCMV ) causes infection in utero and pat...	[ "Cytomegaloviruses ( CMVs ) encode cellular homologs to evade host immune functions .", "In this study , we analyzed the roles of GP33 , a guinea pig CMV ( GPCMV ) -encoded G protein-coupled receptor ( GPCR ) homolog , in cellular signaling , viral growth and pathogenesis .", "The cDNA structure of GP33 was det...	[ "Cytomegalovirus ( CMV ) is a major pathogen that causes congenital diseases , including birth defects and developmental abnormalities in newborns .", "Better understanding of the immune evasion mechanisms may open the way to the development of new types of live attenuated vaccines for congenital CMV infection ."...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "ecology/evolutionary ecology", "infectious diseases/nosocomial and healthcare-associated infections", "microbiology/microbial evolution and genomics", "microbiology", "infectious diseases/respiratory infections", "infectious diseases/bacterial in...	Quorum Sensing Inhibition Selects for Virulence and Cooperation in Pseudomonas aeruginosa	journal.ppat.1000883	null	[ [ "Anti-virulence therapies have been recently suggested as alternative strategies to circumvent the growing problem of antibiotic resistance [1] , [2] .", "In P . aeruginosa inhibition of Quorum-Sensing ( QS ) seems particularly attractive as QS regulates many virulence determinants of this pathogen [3] ."...	[ "With the rising development of bacterial resistance the search for new medical treatments beyond conventional antimicrobials has become a key aim of public health research .", "Possible innovative strategies include the inhibition of bacterial virulence .", "However , consideration must be given to the evoluti...	[ "With the rising development of antibiotic resistance and rapid spread of nosocomial pathogens , the search for new treatments beyond conventional antibiotics becomes a key aim of public health research .", "As such , anti-virulence therapies might be alternative antimicrobial strategies .", "However , consider...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "algorithms", "systems biology", "medicine", "infectious diseases", "computer science", "bacterial diseases", "mycobacterium", "diagnostic medicine", "tuberculosis", "global health", "biology", "computational biology", "malaria", "parasitic diseases", "hematology" ]	Biomarker Discovery by Sparse Canonical Correlation Analysis of Complex Clinical Phenotypes of Tuberculosis and Malaria	journal.pcbi.1003018	null	[ [ "The aim of biomarker discovery is to find small subsets of measurements in ‘omics data that correlate with the clinical syndromes or phenotypes of interest .", "Despite the fact that most clinical phenotypes ( e . g . diseases ) are characterized by a complex set of clinical parameters , with a variable ...	[ "Biomarker discovery aims to find small subsets of relevant variables in ‘omics data that correlate with the clinical syndromes of interest .", "Despite the fact that clinical phenotypes are usually characterized by a complex set of clinical parameters , current computational approaches assume univariate targets ...	[ "Many infectious diseases such as tuberculosis and malaria are challenging both for scientists trying to understand the biochemical basis of the diseases and for medical doctors making diagnosis .", "The challenges arise both from the dependence of the diseases on sets of proteins and from the complexity of the s...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "systems biology", "biology", "genetics and genomics" ]	Modeling Cortisol Dynamics in the Neuro-endocrine Axis Distinguishes Normal, Depression, and Post-traumatic Stress Disorder (PTSD) in Humans	journal.pcbi.1002379	null	[ [ "PTSD is an anxiety disorder that results from exposure to traumatic events .", "According to the Diagnostic and Statistical Manual of Mental Disorders ( DSM-IV ) , the core symptoms are impaired concentration , emotional numbing , recurrent flashes of traumatic memories , social withdrawal , and hyperaro...	[ "Cortisol , secreted in the adrenal cortex in response to stress , is an informative biomarker that distinguishes anxiety disorders such as major depression and post-traumatic stress disorder ( PTSD ) from normal subjects .", "Yehuda et al . proposed a hypothesis that , in humans , the hypersensitive hypothalamus...	[ "PTSD is an anxiety disorder that occurs among persons exposed to a traumatic event involving life threat and injury .", "This is a co-morbid psychiatric disorder that occurs along with depression .", "Cortisol is an informative endocrine biomarker that can distinguish PTSD from other co-morbid disorders .", ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "kala-azar", "medicine and health sciences", "immunology", "tropical diseases", "geographical locations", "india", "age distribution", "sand flies", "parasitic diseases", "geoinformatics", "age groups", "neglected tropical diseases", "population biology", "insect vectors", "infectious di...	Visceral leishmaniasis: Spatiotemporal heterogeneity and drivers underlying the hotspots in Muzaffarpur, Bihar, India	journal.pntd.0006888	null	[ [ "Visceral leishmaniasis ( VL ) –also known as kala-azar—is the deadliest vector-borne parasitic disease after malaria worldwide and is transmitted by female sand flies [1–3] .", "On the Indian subcontinent ( ISC ) , VL is caused by Leishmania donovani and humans are considered the only host .", "Here ...	[ "Despite the overall decrease in visceral leishmaniasis ( VL ) incidence on the Indian subcontinent , there remain spatiotemporal clusters or ‘hotspots’ of new cases .", "The characteristics of these hotspots , underlying transmission dynamics , and their importance for shaping control strategies are not yet full...	[ "Visceral leishmaniasis ( VL ) is the deadliest vector-borne parasitic disease after malaria worldwide and is one of the neglected tropical diseases targeted for elimination and control by the World Health Organization .", "Despite the overall decrease in VL incidence in Bihar , India , a region previously highly...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "protein chemistry", "drugs and devices", "influenza", "pharmacology", "biology", "viral diseases", "drug interactions", "biophysics" ]	H1N1 2009 Pandemic Influenza Virus: Resistance of the I223R Neuraminidase Mutant Explained by Kinetic and Structural Analysis	journal.ppat.1002914	null	[ [ "Strategies to combat the burden of disease caused by influenza mainly rely on vaccination [1] .", "However , in cases when vaccine efficacy is low or vaccine is unavailable , for instance during the first months of a pandemic , antiviral drugs are an important line of defense .", "For individual pati...	[ "Two classes of antiviral drugs , neuraminidase inhibitors and adamantanes , are approved for prophylaxis and therapy against influenza virus infections .", "A major concern is that antiviral resistant viruses emerge and spread in the human population .", "The 2009 pandemic H1N1 virus is already resistant to ad...	[ "Recently , a pandemic A/H1N1 influenza virus was isolated from an immune compromised patient with a novel antiviral resistance pattern to the neuraminidase inhibitor class of drugs .", "This virus had an amino acid change in the viral neuraminidase enzyme; an isoleucine at position 223 was substituted by an argi...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "immune cells", "immunity", "immunology", "biology", "parasitic diseases", "immune system" ]	The CTLA-4 and PD-1/PD-L1 Inhibitory Pathways Independently Regulate Host Resistance to Plasmodium-induced Acute Immune Pathology	journal.ppat.1002504	null	[ [ "The outcome of microbial infections is dependent on the balance between pro-inflammatory and regulatory immune responses .", "Priming of naïve T cells and their differentiation into effector cells needs to be balanced by switching off these cells , at an appropriate stage of infection , in order to preve...	[ "The balance between pro-inflammatory and regulatory immune responses in determining optimal T cell activation is vital for the successful resolution of microbial infections .", "This balance is maintained in part by the negative regulators of T cell activation , CTLA-4 and PD-1/PD-L , which dampen effector respo...	[ "T cells are part of the body's defense system in response to infection .", "However , once the infection has been suitably controlled , these T cells must be switched off .", "Inhibitory pathways , such as CTLA-4 and PD-1 , are known to send the ‘turn off’ signal to T cells during chronic infections .", "How...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion", "Data reporting" ]	[ "acoustics", "medicine and health sciences", "neural networks", "engineering and technology", "audio signal processing", "applied mathematics", "signal processing", "vertebrates", "neuroscience", "animals", "mammals", "animal signaling and communication", "simulation and modeling", "algori...	Bat detective—Deep learning tools for bat acoustic signal detection	journal.pcbi.1005995	null	[ [ "There is a critical need for robust and accurate tools to scale up biodiversity monitoring and to manage the impact of anthropogenic change [1 , 2] .", "Modern hardware for passive biodiversity sensing such as camera trapping and audio recording now enables the collection of vast quantities of data relat...	[ "Passive acoustic sensing has emerged as a powerful tool for quantifying anthropogenic impacts on biodiversity , especially for echolocating bat species .", "To better assess bat population trends there is a critical need for accurate , reliable , and open source tools that allow the detection and classification ...	[ "There is a critical need for robust and accurate tools to scale up biodiversity monitoring and to manage the impact of anthropogenic change .", "For example , the monitoring of bat species and their population dynamics can act as an important indicator of ecosystem health as they are particularly sensitive to ha...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "body fluids", "population dynamics", "blood counts", "integrative physiology", "blood volume", "mathematics", "population modeling", "population biology", "stochastic processes", "theoretical biology", "biophysics", "hematology", "probability theory", "sy...	In Vivo Volume and Hemoglobin Dynamics of Human Red Blood Cells	journal.pcbi.1003839	null	[ [ "A typical red blood cell loses 30% of its volume and 20% of its intracellular hemoglobin ( Hb ) over the course of its 100-day lifespan in the circulation [1]–[6] .", "These physical characteristics control the RBC's ability to fulfill its main function of delivering oxygen to the tissues .", "With s...	[ "Human red blood cells ( RBCs ) lose ∼30% of their volume and ∼20% of their hemoglobin ( Hb ) content during their ∼100-day lifespan in the bloodstream .", "These observations are well-documented , but the mechanisms for these volume and hemoglobin loss events are not clear .", "RBCs shed hemoglobin-containing ...	[ "Red blood cell concentration ( RBC ) , mean volume ( MCV ) , and hemoglobin content ( MCH ) are routinely measured in the complete blood count , a fundamental clinical test essential for the screening , diagnosis , and management of most diseases .", "Variation in MCV and MCH is associated with many important cl...	2014
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "saccharomyces", "computational biology" ]	Not All Scale-Free Networks Are Born Equal: The Role of the Seed Graph in PPI Network Evolution	journal.pcbi.0030118	null	[ [ "In the past few years , protein–protein interaction ( PPI ) networks of several organisms have been derived and made publicly available .", "Some of these networks have interesting topological properties ( e . g . , the degree distribution of the yeast PPI network is heavy-tailed; that is , there are a f...	[ "The ( asymptotic ) degree distributions of the best-known “scale-free” network models are all similar and are independent of the seed graph used; hence , it has been tempting to assume that networks generated by these models are generally similar .", "In this paper , we observe that several key topological featu...	[ "The interactions among proteins in an organism can be represented as a protein–protein interaction ( PPI ) network , where each protein is represented with a node , and each interaction is represented with an edge between two nodes .", "As PPI networks of several model organisms become available , their topologi...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "evolutionary biology/human evolution", "genetics and genomics/functional genomics", "immunology/innate immunity", "molecular biology/bioinformatics", "immunology/genetics of the immune system", ...	Death and Resurrection of the Human IRGM Gene	journal.pgen.1000403	null	[ [ "Immunity Related GTPases ( IRG ) , a family of genes induced by interferons , are one of the strongest resistance systems to intracellular pathogens [1]–[4] .", "The IRGM gene has been shown to have a role in the autophagy-targeted destruction of Mycobacterium bovis BCG [5] .", "Recently , whole geno...	[ "Immunity-related GTPases ( IRG ) play an important role in defense against intracellular pathogens .", "One member of this gene family in humans , IRGM , has been recently implicated as a risk factor for Crohn's disease .", "We analyzed the detailed structure of this gene family among primates and showed that ...	[ "The IRG gene family plays an important role in defense against intracellular bacteria , and genome-wide association studies have implicated structural variants of the single-copy human IRGM locus as a risk factor for Crohn's disease .", "We reconstruct the evolutionary history of this region among primates and s...	2009

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