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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" ]	[ "biochemistry", "microbial metabolism", "lipids", "gram negative", "sphingolipids", "gene expression", "genetics", "gene regulation", "molecular genetics", "host-pathogen interaction", "biology", "microbiology", "bacterial pathogens", "dna transcription" ]	Detection of Host-Derived Sphingosine by Pseudomonas aeruginosa Is Important for Survival in the Murine Lung	journal.ppat.1003889	null	[ [ "Pseudomonas aeruginosa is a common , Gram negative , environmental bacterium that can cause significant disease as an opportunistic pathogen , particularly in the lung .", "P . aeruginosa lung infections are prevalent in people with cystic fibrosis ( CF ) and chronic obstructive pulmonary disease ( COPD ...	[ "Pseudomonas aeruginosa is a common environmental bacterium that is also a significant opportunistic pathogen , particularly of the human lung .", "We must understand how P . aeruginosa responds to the lung environment in order to identify the regulatory changes that bacteria use to establish and maintain infecti...	[ "Many opportunistic pathogens transition from an environmental niche into the host .", "To establish an infection , these bacteria must rapidly adapt their transcriptional profile to the conditions at the site of infection .", "We used the response of Pseudomonas aeruginosa to lung surfactant as a model to disc...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Proteomic Identification of Oxidized Proteins in Entamoeba histolytica by Resin-Assisted Capture: Insights into the Role of Arginase in Resistance to Oxidative Stress	journal.pntd.0004340	null	[ [ "Amebiasis is a parasitic infection of the intestines and is mainly caused by fecal contamination [1] .", "Although 90% of infected individuals are asymptomatic , amebic dysentery affects 50 million people in India , Southeast Asia , Africa , and Latin America and amebiasis is the cause of at least 100 , ...	[ "Entamoeba histolytica is an obligate protozoan parasite of humans , and amebiasis , an infectious disease which targets the intestine and/or liver , is the second most common cause of human death due to a protozoan after malaria .", "Although amebiasis is usually asymptomatic , E . histolytica has potent pathoge...	[ "Reactive oxygen species are the most studied of environmental stresses generated by the host immune defense against pathogens .", "Although most of the studies that have investigated the effect of oxidative stress on an organism have focused on changes which occur at the protein level , only a few studies have i...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "molecular cell biology", "protozoology", "biology", "microbiology", "pathogenesis", "parasitology" ]	A Cytoplasmic New Catalytic Subunit of Calcineurin in Trypanosoma cruzi and Its Molecular and Functional Characterization	journal.pntd.0002676	null	[ [ "Chagas disease , whose etiological agent is Trypanosoma cruzi , is a neglected tropical parasitic infection .", "An estimated 10 million people are infected worldwide , predominantly in Latin America , where it is endemic , and more than 25 million people are at risk of acquiring the disease [1] .", ...	[ "Parasitological cure for Chagas disease is considered extremely difficult to achieve because of the lack of effective chemotherapeutic agents against Trypanosoma cruzi at different stages of infection .", "There are currently only two drugs available .", "These have several limitations and can produce serious ...	[ "Chagas disease is a neglected tropical parasitic infection .", "An estimated 10 million people are infected worldwide , and more than 25 million people are at risk of acquiring the disease .", "The therapeutic agents used to treat the disease may not be effective in all cases and also produce considerable side...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "invertebrates", "plant anatomy", "medicine and health sciences", "nervous system", "membrane potential", "junctional complexes", "electrophysiology", "neuroscience", "learning and memory", "animals", "gap junctions", "animal models", "drosophila melanogaster", "model ...	Electrical synapses between mushroom body neurons are critical for consolidated memory retrieval in Drosophila	journal.pgen.1008153	null	[ [ "Pavlovian olfactory learning in Drosophila melanogaster , the fruit fly , is a well-characterized behavioral paradigm in which flies are subjected to a training session of sequential exposures to two distinct odors ( conditioned stimulus , CS ) with or without electric foot shock ( unconditioned stimulus , U...	[ "Electrical synapses between neurons , also known as gap junctions , are direct cell membrane channels between adjacent neurons .", "Gap junctions play a role in the synchronization of neuronal network activity; however , their involvement in cognition has not been well characterized .", "Three-hour olfactory a...	[ "One of the most important questions in the neuroscience is how the brain process memory .", "Memory formation requires neuronal communication in the brain via synaptic transmissions , which include chemical and electrical synapses .", "Unlike the chemical synapses , the biological functions of electrical synap...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "behavioral neuroscience", "functional genomics", "developmental and pediatric neurology", "biology", "genomics", "neuroscience", "pediatrics" ]	DUF1220 Dosage Is Linearly Associated with Increasing Severity of the Three Primary Symptoms of Autism	journal.pgen.1004241	null	[ [ "Autism Spectrum Disorder ( ASD ) is a common neurodevelopmental condition characterized by impaired social reciprocity and communicative skills , as well as increased repetitive behaviors and stereotyped interests [1] .", "ASD has been frequently linked to an accelerated postnatal brain growth [2] that l...	[ "One of the three most frequently documented copy number variations associated with autism spectrum disorder ( ASD ) is a 1q21 . 1 duplication that encompasses sequences encoding DUF1220 protein domains , the dosage of which we previously implicated in increased human brain size .", "Further , individuals with AS...	[ "Autism Spectrum Disorder ( ASD ) is a common behaviorally defined condition noted by impairments in social reciprocity and communicative abilities and exaggerated repetitive behaviors and stereotyped interests .", "Individuals with ASD frequently have a larger and more rapidly growing brain than their typically ...	2014
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "cell biology", "microbiology", "molecular biology", "genetics and genomics" ]	Transcriptional Infidelity Promotes Heritable Phenotypic Change in a Bistable Gene Network	journal.pbio.1000044	RNA errors arise frequently during transcription, but with what consequence? New evidence shows that transient RNA errors can cause heritable phenotypic changes when they activate an autocatalytic positive-feedback loop in gene regulation.	[ [ "Altered proteins can result from errors incurred at any step during information transfer from DNA to protein .", "Errors in DNA , RNA , and protein synthesis occur at rates of , very roughly , 10−9 , 10−5 , and 10−4 errors per residue , respectively [1] .", "Although rare , errors in DNA synthesis ca...	[ "Bistable epigenetic switches are fundamental for cell fate determination in unicellular and multicellular organisms .", "Regulatory proteins associated with bistable switches are often present in low numbers and subject to molecular noise .", "It is becoming clear that noise in gene expression can influence ce...	[ "Errors in information transfer from DNA to RNA to protein are inevitable and ubiquitous .", "When errors that occur in DNA are not repaired and become fixed as permanent mutations , they can have heritable phenotypic consequences for cells .", "In contrast , errors that occur during RNA transcription are consi...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "immunology/immunity to infections" ]	BALB/c Mice Deficient in CD4+ T Cell IL-4Rα Expression Control Leishmania mexicana Load although Female but Not Male Mice Develop a Healer Phenotype	journal.pntd.0000930	null	[ [ "New world cutaneous leishmaniasis resulting from infection with Leishmania mexicana is under different genetic and immunoregulatory controls to those controlling L . major infection [1] .", "Also , unlike L . major , the majority of mouse strains are susceptible to L . mexicana infection [2]–[3] .", ...	[ "Immunologically intact BALB/c mice infected with Leishmania mexicana develop non-healing progressively growing lesions associated with a biased Th2 response while similarly infected IL-4Rα-deficient mice fail to develop lesions and develop a robust Th1 response .", "In order to determine the functional target ( ...	[ "Leishmania species are parasites , transmitted by sandflies which are of extensive public health importance in the tropical and subtropical regions of the world .", "A large number of distinct Leishmania species cause cutaneous disease and the vast majority of studies utilize the caustive agent of Old World cuta...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome evolution", "virulence factors and mechanisms", "virology", "molecular genetics", "biology", "genomics", "evolutionary biology", "genomic evolution", "microbiology", "computational biology", "viral evolution" ]	Viral Proteins Originated De Novo by Overprinting Can Be Identified by Codon Usage: Application to the “Gene Nursery” of Deltaretroviruses	journal.pcbi.1003162	null	[ [ "Modification of existing genes , such as by duplication or fusion , is a common and well-understood mechanism by which protein-coding genes originate [1] , [2] .", "In contrast , we have shown that viruses generate many proteins de novo ( hereafter called “de novo proteins” ) [3] , [4] .", "Prelimina...	[ "A well-known mechanism through which new protein-coding genes originate is by modification of pre-existing genes , e . g . by duplication or horizontal transfer .", "In contrast , many viruses generate protein-coding genes de novo , via the overprinting of a new reading frame onto an existing ( “ancestral” ) fra...	[ "How does novelty originate in nature ?", "It is commonly thought that new genes are generated mainly by modifications of existing genes ( the “tinkering” model ) .", "In contrast , we have shown recently that in viruses , numerous genes are generated entirely de novo ( “from scratch” ) .", "The role of these...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "biology and life sciences", "computational biology", "molecular cell biology", "biophysics" ]	Biophysical Properties of Intrinsically Disordered p130Cas Substrate Domain — Implication in Mechanosensing	journal.pcbi.1003532	null	[ [ "p130Cas ( mouse: NP_001185768; rat: NP_037063 ) is a proline-rich scaffold protein that plays an essential role in various cell functions , including motility [1] , survival [2] , apoptosis [3] and transformation [4] .", "The substrate domain , CasSD , is centrally located and contains 15 repeats of YxxP...	[ "Mechanical stretch-induced tyrosine phosphorylation in the proline-rich 306-residue substrate domain ( CasSD ) of p130Cas ( or BCAR1 ) has eluded an experimentally validated structural understanding .", "Cellular p130Cas tyrosine phosphorylation is shown to function in areas without internal actomyosin contracti...	[ "Mechanical stretching of cells causes the substrate domain of p130Cas ( CasSD ) to be phosphorylated on 15 tyrosine residues embedded along its length .", "CasSD is rich in proline and surprisingly well conserved in placental mammals .", "Stretching of CasSD by atomic force microscopy has identified that it re...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "yeast infections", "immune cells", "pathology and laboratory medicine", "vesicles", "markov models", "pathogens", "immunology", "microbiology", "organisms", "fungi", "mathematics", "phagosomes", "fungal diseases", "cellular structures and...	Macrophage activation by IFN-γ triggers restriction of phagosomal copper from intracellular pathogens	journal.ppat.1007444	null	[ [ "To successfully infect and colonize a host , pathogens must acquire sufficient nutrients from the host to enable microbe growth and proliferation .", "These metabolic resources include , but are not limited to , essential metals .", "The nutrient-limited phagosome represents a particularly challengin...	[ "Copper toxicity and copper limitation can both be effective host defense mechanisms against pathogens .", "Tolerance of high copper by fungi makes toxicity as a defense mechanism largely ineffective against fungal pathogens .", "A forward genetic screen for Histoplasma capsulatum mutant yeasts unable to replic...	[ "Control of primary pathogens that infect phagocytes often requires adaptive immunity , but the mechanisms that convert host cells from permissive to antimicrobial states are only partially understood .", "The intracellular fungal pathogen Histoplasma capsulatum resides and proliferates within the macrophage phag...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Activation and Alliance of Regulatory Pathways in C. albicans during Mammalian Infection	journal.pbio.1002076	A study of the invasive infection of a mammalian host by the pathogenic fungus Candida albicans reveals characteristic gene regulation patterns in response to the host environment, distinct from those seen when growing in vitro.	[ [ "Which genes does a pathogen express during infection ?", "Which regulatory pathways govern expression of those genes in vivo ?", "These questions are central to the study of microbial pathogenesis , and they have been addressed by diverse approaches [1–4] .", "Despite those efforts , we have a li...	[ "Gene expression dynamics have provided foundational insight into almost all biological processes .", "Here , we analyze expression of environmentally responsive genes and transcription factor genes to infer signals and pathways that drive pathogen gene regulation during invasive Candida albicans infection of a m...	[ "We have a limited understanding of how the expression of pathogens’ genes changes during infection of humans or other animal hosts , in contrast to in vitro models of infection .", "Here we profile the alteration in gene expression over time as a predictor of functional consequences during invasive growth of Can...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "rift valley fever virus", "body fluids", "pathology and laboratory medicine", "pathogens", "culicoides", "microbiology", "saliva", "animals", "viruses", "rna viruses", "insect vectors", "bunyaviruses", "infectious diseases", "aedes aegy...	Vector competence of biting midges and mosquitoes for Shuni virus	journal.pntd.0006609	null	[ [ "Arthropod-borne ( arbo ) viruses continue to pose a threat to human and animal health [1 , 2] .", "In particular the order Bunyavirales comprises emerging pathogens such as Crimean-Congo haemorrhagic fever virus ( CCHFV ) and Rift Valley fever virus ( RVFV ) [3 , 4] .", "The World Health Organization...	[ "Shuni virus ( SHUV ) is an orthobunyavirus that belongs to the Simbu serogroup .", "SHUV was isolated from diverse species of domesticated animals and wildlife , and is associated with neurological disease , abortions , and congenital malformations .", "Recently , SHUV caused outbreaks among ruminants in Israe...	[ "Arthropod-borne ( arbo ) viruses are notorious for causing unpredictable and large-scale epidemics and epizootics .", "Apart from viruses such as West Nile virus and Rift Valley fever virus that are well known to have a significant impact on human and animal health , many arboviruses remain neglected .", "Shun...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/microbial physiology and metabolism", "plant biology/plant-biotic interactions", "genetics and genomics/microbial evolution and genomics", "respiratory medicine/respiratory infections", "cell biology/cellular death and stress responses", "genetics and genomics/functional genomics", "cell b...	TmpL, a Transmembrane Protein Required for Intracellular Redox Homeostasis and Virulence in a Plant and an Animal Fungal Pathogen	journal.ppat.1000653	null	[ [ "Oxidative stress arises from a significant increase in the concentration of reactive oxygen species ( ROS ) inside the cell , and is primarily caused by either an imbalance of the cellular antioxidant capacity or a deficiency in the antioxidant system controlling ROS levels [1] .", "The damaging effects ...	[ "The regulation of intracellular levels of reactive oxygen species ( ROS ) is critical for developmental differentiation and virulence of many pathogenic fungi .", "In this report we demonstrate that a novel transmembrane protein , TmpL , is necessary for regulation of intracellular ROS levels and tolerance to ex...	[ "The critical roles of reactive oxygen species ( ROS ) in fungal development and virulence have been well established over the past half a century since the first experimental detection of hydrogen peroxide in fungal cells by Bach ( 1950 ) .", "In the cell , ROS act as signaling molecules regulating physiological...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "onchocerca volvulus", "chemical compounds", "pathology and laboratory medicine", "helminths", "methylenes", "hexanes", "tropical diseases", "parasitic diseases", "animals", "onchocerca", "toxicology", "toxicity", "medicinal plants", "ne...	Filaricidal properties of Lantana camara and Tamarindus indica extracts, and Lantadene A from L. camara against Onchocerca ochengi and Loa loa	journal.pntd.0006565	null	[ [ "Onchocerciasis ( river blindness ) is a blinding and debilitating disease caused by the parasitic nematode , Onchocerca volvulus .", "According to estimates of the World Health Organization ( WHO ) [1] , 37 million people are infected , 800 , 000 visually impaired and 270 , 000 blinded .", "Adult wor...	[ "Ivermectin is the only drug currently recommended for the treatment of onchocerciasis , the second leading infectious cause of blindness in the world .", "This drug kills only the first stage larvae—microfilariae ( mf ) of Onchocerca volvulus and is to be used cautiously in areas where Loa loa is prevalent becau...	[ "Onchocerciasis is a chronic disease of humans that affects mainly the skin and eyes .", "It is an insect-borne disease , caused by a nematode worm , Onchocerca volvulus .", "It is a public health problem and an obstacle to socio-economic development in affected communities .", "There is currently no vaccine ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "cellular structures", "neurobiology of disease and regeneration", "animal genetics", "neuroscience", "cell differentiation", "animal models", "developmental biology", "otology", "model organisms", "hearing disorders", "cytoskeleton", "proteins", "biology", "otorhinolaryngolo...	Roles of the Espin Actin-Bundling Proteins in the Morphogenesis and Stabilization of Hair Cell Stereocilia Revealed in CBA/CaJ Congenic Jerker Mice	journal.pgen.1002032	null	[ [ "A stunning example of cytoskeleton-mediated morphogenesis is the formation of hair cell stereocilia , which act as primary mechanosensory detectors in the auditory and vestibular systems [1] , [2] .", "Stereocilia are fingerlike projections that contain a specialized cytoskeletal element , the parallel a...	[ "Hearing and vestibular function depend on mechanosensory staircase collections of hair cell stereocilia , which are produced from microvillus-like precursors as their parallel actin bundle scaffolds increase in diameter and elongate or shorten .", "Hair cell stereocilia contain multiple classes of actin-bundling...	[ "Stereocilia are the fingerlike projections of inner ear hair cells that detect sound and motion .", "Stereocilia grow to specific lengths and diameters and form staircase-like arrays .", "The changes in size appear to be driven by matching alterations in the dimensions of an underlying molecular scaffold consi...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "developmental biology" ]	An Ancient Gene Network Is Co-opted for Teeth on Old and New Jaws	journal.pbio.1000031	A common gene regulatory circuit controls the development of all dentitions, from the original teeth in the throats of jawless fishes half a billion years ago, to the incisors and molars of modern vertebrates.	[ [ "Teeth are ancient vertebrate structures .", "During the early evolution of vertebrates , the appearance of a pharyngeal dentition greatly enhanced the capacity for processing food .", "Tooth-like structures located on elements of the pharyngeal series or skeleton were present in extinct jawless fishe...	[ "Vertebrate dentitions originated in the posterior pharynx of jawless fishes more than half a billion years ago .", "As gnathostomes ( jawed vertebrates ) evolved , teeth developed on oral jaws and helped to establish the dominance of this lineage on land and in the sea .", "The advent of oral jaws was facilita...	[ "During evolution , teeth originated deep in the pharynx of ancient and extinct jawless fishes .", "Later , with the evolution of bony fish , teeth appeared in the mouth , as in most current vertebrates , although some living fishes retain teeth in the posterior pharynx .", "We integrate comparative morphology ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	The Tumor Suppressor Gene Retinoblastoma-1 Is Required for Retinotectal Development and Visual Function in Zebrafish	journal.pgen.1003106	null	[ [ "Biallelic mutations in the retinoblastoma susceptibility gene rb1 are causal for intraocular childhood retinoblastomas .", "Rb1 is a member of a gene family that consists of three members , p105/Rb1 , p107/Rb-like1 , and p130/Rb-like2 , collectively known as “pocket proteins” [1] .", "The activity of...	[ "Mutations in the retinoblastoma tumor suppressor gene ( rb1 ) cause both sporadic and familial forms of childhood retinoblastoma .", "Despite its clinical relevance , the roles of rb1 during normal retinotectal development and function are not well understood .", "We have identified mutations in the zebrafish ...	[ "Before an organism can execute necessary behavioral responses to environmental stimuli , the underlying neural circuits that regulate these behaviors must be precisely wired during embryonic development .", "A properly wired neural circuit is the product of a sophisticated collaboration of multiple genetic pathw...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "computational biology/synthetic biology", "cell biology/cell signaling", "mathematics", "computer science/systems and control theory", "computer science/numerical analysis and theoretical computing", "diabetes and endocrinology", "computational biology/signaling networks", "computationa...	Optimal Experimental Design for Parameter Estimation of a Cell Signaling Model	journal.pcbi.1000558	null	[ [ "Biological cells continuously process stimuli that they receive from their inside and outside , using interconnected signaling pathways .", "Since strength , timing , and combination of inputs typically determine the output behavior in a non-linear manner , dynamic models of such signaling networks in th...	[ "Differential equation models that describe the dynamic changes of biochemical signaling states are important tools to understand cellular behavior .", "An essential task in building such representations is to infer the affinities , rate constants , and other parameters of a model from actual measurement data .",...	[ "Differential equation models of signaling processes are useful to gain a molecular and quantitative understanding of cellular information flow .", "Although these models are typically based on simple kinetic rules , they can often qualitatively describe the behavior of biological systems .", "However , in the ...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "biochemical simulations", "mathematics", "theoretical biology", "biochemistry simulations", "algebra", "linear algebra", "biology", "computational biology", "algebraic equations" ]	Characterizing the Relationship between Steady State and Response Using Analytical Expressions for the Steady States of Mass Action Models	journal.pcbi.1002901	null	[ [ "Transient activation of signaling molecules is a hallmark of the cellular response to perturbation .", "Far from acting as a simple relay , however , the dynamics of signaling molecules can encode information about the instigating stimulus [1]–[3] .", "Interestingly , these dynamics are affected by t...	[ "The steady states of cells affect their response to perturbation .", "Indeed , diagnostic markers for predicting the response to therapeutic perturbation are often based on steady state measurements .", "In spite of this , no method exists to systematically characterize the relationship between steady state an...	[ "Diagnostic markers are derived from steady state measurements , but are used to predict the cellular response to therapy .", "To develop new and better diagnostics , we would like to systematically characterize the relationship between steady state and the response to a given therapeutic .", "Mathematical mode...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Integrated Stochastic Model of DNA Damage Repair by Non-homologous End Joining and p53/p21- Mediated Early Senescence Signalling	journal.pcbi.1004246	null	[ [ "Multiple DNA lesions arise in each cell within an organism every day , caused by errors in DNA replication , by exposure to external factors such as UV light and by a variety of hydrolytic and oxidation reactions [1] .", "Most simple lesions are repaired quickly and accurately by the cellular DNA-damage ...	[ "Unrepaired or inaccurately repaired DNA damage can lead to a range of cell fates , such as apoptosis , cellular senescence or cancer , depending on the efficiency and accuracy of DNA damage repair and on the downstream DNA damage signalling .", "DNA damage repair and signalling have been studied and modelled in ...	[ "All cells are subject to damage and DNA is the most important molecule to protect .", "Cells communicate DNA damage through p53—‘the guardian of the genome’—and the dynamics of p53 signalling is one the main mechanisms that determine the outcome for the cell .", "On detection of DNA damage , p53 is activated a...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna viruses", "virology", "viral classification", "biology", "microbiology" ]	Human Monoclonal Antibodies Broadly Neutralizing against Influenza B Virus	journal.ppat.1003150	null	[ [ "Influenza virus remains a constant public health threat .", "During annual epidemics 5–15% of the worldwide population are typically infected , resulting in 3 to 5 million cases of severe illness and between 250 , 000 to 500 , 000 deaths per year [1] , [2] .", "While all age groups are affected by th...	[ "Influenza virus has the ability to evade host immune surveillance through rapid viral genetic drift and reassortment; therefore , it remains a continuous public health threat .", "The development of vaccines producing broadly reactive antibodies , as well as therapeutic strategies using human neutralizing monocl...	[ "Influenza virus is classified into types A , B and C . Influenza A virus is further divided into many subtypes , all of which exist in animals , indicating pandemic potential .", "By contrast , influenza B virus circulates almost exclusively in humans and , as there is no evidence for reassortment with influenza...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	MET18 Connects the Cytosolic Iron-Sulfur Cluster Assembly Pathway to Active DNA Demethylation in Arabidopsis	journal.pgen.1005559	null	[ [ "DNA 5-cytosine methylation ( 5mC ) is an epigenetic mark that is critical for maintaining genome integrity , regulating gene expression and responding to environmental stress in many higher eukaryotes [1–6] .", "A proper DNA methylation pattern is important for plant development and plant responses to va...	[ "DNA demethylation mediated by the DNA glycosylase ROS1 helps determine genomic DNA methylation patterns and protects active genes from being silenced .", "However , little is known about the mechanism of regulation of ROS1 enzymatic activity .", "Using a forward genetic screen , we identified an anti-silencing...	[ "DNA cytosine methylation is a major epigenetic mark that confers transcriptional regulation .", "Active removal of DNA methylation is important for plants and mammals during development and in responses to various stress conditions .", "In the model plant species Arabidopsis thaliana , active DNA demethylation...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "ears", "cell cycle and cell division", "cell processes", "cell differentiation", "endocrine physiology", "developmental biology", "organ of corti", "inner ear", "growth factors", "fibroblast growth factor", "endocrinology", "biological tissue", "head", "a...	Sox2 and FGF20 interact to regulate organ of Corti hair cell and supporting cell development in a spatially-graded manner	journal.pgen.1008254	null	[ [ "The inner ear contains six sensory organs required for the senses of hearing and balance .", "The cochlea , a snail-like coiled duct , is the auditory organ .", "It contains specialized sensory epithelia , called the organ of Corti , composed of hair cells ( HCs ) and supporting cells ( SCs ) .", ...	[ "The mouse organ of Corti , housed inside the cochlea , contains hair cells and supporting cells that transduce sound into electrical signals .", "These cells develop in two main steps: progenitor specification followed by differentiation .", "Fibroblast Growth Factor ( FGF ) signaling is important in this deve...	[ "The mammalian cochlea contains the organ of Corti , a specialized sensory epithelium populated by hair cells and supporting cells that detect sound .", "Hair cells are susceptible to injury by noise , toxins , and other insults .", "In mammals , hair cells cannot be regenerated after injury , resulting in perm...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "infectious diseases", "chicken", "in vitro", "microbiology", "evolutionary biology", "genetics and genomics", "eubacteria" ]	Genome Dynamics of Campylobacter jejuni in Response to Bacteriophage Predation	journal.ppat.0030119	null	[ [ "The Gram-negative bacterium Campylobacter jejuni is now recognised as a major cause of human gastroenteritis worldwide [1] and has been linked to serious neurological sequelae such as Guillain–Barré syndrome and Miller–Fisher syndrome [2] .", "Poultry are considered a major source of C . jejuni infection...	[ "Campylobacter jejuni is a leading cause of food-borne illness .", "Although a natural reservoir of the pathogen is domestic poultry , the degree of genomic diversity exhibited by the species limits the application of epidemiological methods to trace specific infection sources .", "Bacteriophage predation is a ...	[ "Campylobacter jejuni is the major cause of bacterial food-borne illness worldwide .", "Predation of C . jejuni by virulent bacteriophage offers the prospect of controlling bacterial populations at source in poultry .", "We report that in chickens , bacteriophage resistance is infrequent because the mutants tha...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "metabolic networks", "biology", "computational biology" ]	Predicting Network Activity from High Throughput Metabolomics	journal.pcbi.1003123	null	[ [ "Knowledge of many metabolic pathways has accumulated over the past century .", "For instance , glycolysis , citric acid cycle and oxidative phosphorylation fuel cellular processes through the generation of adenosine triphosphate; glycans and cholesterols not only serve as structural blocks but also media...	[ "The functional interpretation of high throughput metabolomics by mass spectrometry is hindered by the identification of metabolites , a tedious and challenging task .", "We present a set of computational algorithms which , by leveraging the collective power of metabolic pathways and networks , predict functional...	[ "Mass spectrometry based untargeted metabolomics can now profile several thousand of metabolites simultaneously .", "However , these metabolites have to be identified before any biological meaning can be drawn from the data .", "Metabolite identification is a challenging and low throughput process , therefore b...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "classical mechanics", "simulation and modeling", "damage mechanics", "cellular structures and organelles", "research and analysis methods", "bending", "polymer chemistry", "contractile proteins", "actins", "lipids", "proteins", "deformation", "chemistry", "biophysics", "polymerization",...	The More the Tubular: Dynamic Bundling of Actin Filaments for Membrane Tube Formation	journal.pcbi.1004982	null	[ [ "Individual cells generate tubular membrane protrusions in order to sense and interact with their environment [1] .", "The necessary work for their formation is performed by the directed polymerization of a tightly aligned parallel actin filament bundle against the load of the cell membrane [2] .", "A...	[ "Tubular protrusions are a common feature of living cells , arising from polymerization of stiff protein filaments against a comparably soft membrane .", "Although this process involves many accessory proteins in cells , in vitro experiments indicate that similar tube-like structures can emerge without them , thr...	[ "The necessary biophysical conditions for the formation of tubular membrane protrusions by polymerizing actin filament bundles have not yet been fully understood .", "For this reason we introduce a novel grand canonical simulation model that describes stochastic polymerization of filaments against a fluctuating f...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "transfection", "complement system", "medicine and health sciences", "immune physiology", "immune cells", "pathology and laboratory medicine", "hepacivirus", "pathogens", "immunology", "microbiology", "fibrosis", "viruses", "developmental biology", "rna viruses", "tcr si...	Hepatitis C virus infection inhibits a Src-kinase regulatory phosphatase and reduces T cell activation in vivo	journal.ppat.1006232	null	[ [ "Hepatitis C virus ( HCV ) persistently infects more than 120 million people globally , and chronic viremia frequently leads to cirrhosis and hepatocellular carcinoma [1–8] .", "Although numerous factors appear to contribute to viral persistence , the mechanisms by which HCV evades immune responses are in...	[ "Among human RNA viruses , hepatitis C virus ( HCV ) is unusual in that it causes persistent infection in the majority of infected people .", "To establish persistence , HCV evades host innate and adaptive immune responses by multiple mechanisms .", "Recent studies identified virus genome-derived small RNAs ( v...	[ "The mechanism by which hepatitis C virus ( HCV ) establishes persistent human infection is complex and incompletely understood .", "Recent studies identified virus-derived small RNAs ( vsRNAs ) in HCV-infected cells; however , their biological significance is unclear .", "One HCV vsRNA arising from the E2 codi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "signaling networks", "signaling in selected disciplines", "sequence assembly tools", "cell differentiation", "dna transcription", "genome sequencing", "developmental biology", "genome analysis tools", "developmental signaling", "stem cells", "sequence analysis", ...	Graded Nodal/Activin Signaling Titrates Conversion of Quantitative Phospho-Smad2 Levels into Qualitative Embryonic Stem Cell Fate Decisions	journal.pgen.1002130	null	[ [ "Morphogens are secreted signaling molecules that orchestrate the spatial distribution and sequence of cellular differentiation events throughout embryonic development .", "The specific cell types , their localization and order of induction from recipient stem cell populations are determined by the concen...	[ "Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner .", "During early embryonic development the Nodal/Activin pathway is responsible for the specification of mesoderm , endoderm , node , and mesen...	[ "Nodal and Activin are extracellular signaling molecules that diffuse from the source of secretion and induce recipient stem cells to become new cell types according to a concentration gradient .", "In the early embryo , they are important for the specification of tissues at the correct place and time , but parad...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "social and behavioral sciences", "medicine", "veterinary science", "biology" ]	Nodule Worm Infection in Humans and Wild Primates in Uganda: Cryptic Species in a Newly Identified Region of Human Transmission	journal.pntd.0002641	null	[ [ "Soil-transmitted helminths ( STHs ) are parasitic nematodes that cause infection via eggs and larvae , which are shed in feces and persist in the soils of tropical and sub-tropical countries [1] .", "STHs infect over one billion people worldwide [2] and may cause a combined disease burden as substantial ...	[ "Soil-transmitted helminths ( STHs ) are a major health concern in tropical and sub-tropical countries .", "Oesophagostomum infection is considered endemic to West Africa but has also been identified in Uganda , East Africa , among primates ( including humans ) .", "However , the taxonomy and ecology of Oesopha...	[ "Nodule worms infect the gastrointestinal tracts of a number of mammalian species , including humans and other primates .", "This study sought to identify the species of nodule worms causing infections within and around an East African national park in Uganda where monkeys and apes co-occur and overlap with peopl...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/evolutionary modeling", "developmental biology/developmental evolution", "evolutionary biology/developmental evolution" ]	Specialization Can Drive the Evolution of Modularity	journal.pcbi.1000719	null	[ [ "For our study we consider a network of genes .", "Each gene's activity state is regulated by other genes in the network .", "The genotype of an individual is defined as the set of the interactions among its genes .", "We represent this set of interactions as a matrix .", "Non-zero elements in...	[ "Organismal development and many cell biological processes are organized in a modular fashion , where regulatory molecules form groups with many interactions within a group and few interactions between groups .", "Thus , the activity of elements within a module depends little on elements outside of it .", "Modu...	[ "Throughout life's history , organisms have produced evolutionary innovations , features that are useful when facing new ecological and environmental challenges .", "A property that aids in the production of such innovations is modularity .", "Modular systems consist of groups of molecules with many interaction...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "immunology", "microbiology", "vaccines", "preventive medicine", "antibiotic resistance", "probability distribution", "mathematics", "sexually transmitted diseases", "network analysis", "pharmacology", "infectious disease control", "vaccination and immunizatio...	A dynamic power-law sexual network model of gonorrhoea outbreaks	journal.pcbi.1006748	null	[ [ "In 2017 the WHO added Neisseria gonorrhoeae to its priority list of bacterial pathogens in response to the global spread of antibiotic resistance [1] .", "The bacteria have developed resistance to every therapy used against them , from penicillin through to third-generation cephalosporins [2 , 3] .", ...	[ "Human networks of sexual contacts are dynamic by nature , with partnerships forming and breaking continuously over time .", "Sexual behaviours are also highly heterogeneous , so that the number of partners reported by individuals over a given period of time is typically distributed as a power-law .", "Both the...	[ "The formation and dissolution of sexual relationships in human populations constitute an ever-changing network of links between individuals through which sexually transmitted diseases spread .", "To study this phenomenon , we developed a dynamic simulation algorithm that can reproduce the same distribution of se...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public and occupational health", "infectious diseases", "socioeconomic aspects of health", "medicine and health sciences", "health economics", "dengue fever", "neglected tropical diseases", "tropical diseases", "viral diseases", "health care" ]	Direct Costs of Dengue Hospitalization in Brazil: Public and Private Health Care Systems and Use of WHO Guidelines	journal.pntd.0003104	null	[ [ "Dengue fever ( DF ) is an important public health concern in tropical and subtropical regions worldwide , with approximately 100 million dengue infections and 24 , 000 deaths occurring annually worldwide [1] , [2] .", "Recently , the rates of severe illness and hospitalizations related to dengue have inc...	[ "Dengue , an arboviral disease , is a public health problem in tropical and subtropical regions worldwide .", "In Brazil , epidemics have become increasingly important , with increases in the number of hospitalizations and the costs associated with the disease .", "This study aimed to describe the direct costs ...	[ "The costs of dengue outbreaks and hospitalizations have recently increased .", "Endemic in many tropical and subtropical parts of the world , dengue outbreaks occur each year and require appropriate economic studies to determine the potential financial and public health impacts of dengue management policies .", ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cardiovascular disorders/myopathies", "genetics and genomics/gene discovery", "genetics and genomics/complex traits", "genetics and genomics/genetics of disease", "cardiovascular disorders/heart failure" ]	Genetic Association Study Identifies HSPB7 as a Risk Gene for Idiopathic Dilated Cardiomyopathy	journal.pgen.1001167	null	[ [ "Dilated cardiomyopathy ( DCM ) is a common form of heart muscle disease with a prevalence of 1∶2 , 500 in the general population .", "It represents a major cause of cardiovascular morbidity and mortality and is characterized by systolic dysfunction as well as dilation and impaired contraction of the vent...	[ "Dilated cardiomyopathy ( DCM ) is a structural heart disease with strong genetic background .", "Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins .", "However , strong evidence suggests that genetic factors also affect the suscep...	[ "Dilated cardiomyopathy is a severe disease of the heart muscle and often leads to chronic heart failure , eventually with the consequence of cardiac transplantation .", "Identification of genetic disease markers in at-risk persons could play an important role in preventive health care .", "Several mutations in...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "linkage (genetics)", "trait locus", "phenotypes", "heredity", "genetics", "biology", "evolutionary biology", "quantitative traits", "cytogenetics", "evolutionary genetics", "genetics and genomics", "complex traits", "genotypes" ]	Genetic Analysis of Genome-Scale Recombination Rate Evolution in House Mice	journal.pgen.1002116	null	[ [ "Meiotic recombination fulfills dual roles in genetics and evolution .", "In many species , including mammals , the proper segregation of homologous chromosomes at the first meiotic division is contingent on the presence of at least one well-positioned crossover per homologue pair [1]–[3] .", "The imp...	[ "The rate of meiotic recombination varies markedly between species and among individuals .", "Classical genetic experiments demonstrated a heritable component to population variation in recombination rate , and specific sequence variants that contribute to recombination rate differences between individuals have r...	[ "Homologous recombination is an indispensable feature of the mammalian meiotic program and an important mechanism for creating genetic diversity .", "Despite its central significance , recombination rates vary markedly between species and among individuals .", "Although recent studies have begun to unravel the ...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "sociology", "social sciences", "physiotherapy", "health care" ]	Psychometric Properties of the Participation Scale among Former Buruli Ulcer Patients in Ghana and Benin	journal.pntd.0003254	null	[ [ "Buruli ulcer ( BU ) is a neglected tropical disease caused by Mycobacterium ulcerans ( MU ) and has been reported in more than 30 countries predominantly in tropical or subtropical areas [1] .", "Most burdened region is West Africa of which Côte d'Ivoire , Ghana and Benin have reported large number of ca...	[ "Buruli ulcer is a stigmatising disease treated with antibiotics and wound care , and sometimes surgical intervention is necessary .", "Permanent limitations in daily activities are a common long term consequence .", "It is unknown to what extent patients perceive problems in participation in social activities ...	[ "Buruli ulcer is a stigmatising condition caused by infection with Mycobacterium ulcerans .", "Besides the long term medical consequences , Buruli ulcer may lead to participation restrictions in social life .", "The Participation Scale intends to assess perceived participation restrictions; however , this instr...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "parasite groups", "immune physiology", "enzyme-linked immunoassays", "plasmodium", "immunology", "tropical diseases", "parasitic diseases", "animals", "parasitology", "vaccines", "preventive medicine", "apicomplexa", "antibodies", "vacc...	Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy	journal.pntd.0004423	null	[ [ "Malaria is a devastating parasitic disease transmitted through the bite of infected Anopheles mosquitoes .", "Outside sub-Saharan Africa , Plasmodium vivax is the most prevalent of all human malarias with approximately 2 . 48 billion people at risk [1] and an estimated 16 million cases in 2013 ( WHO Worl...	[ "A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide .", "Vivax malaria protein 1 ( VMP001 ) , a novel chimeric protein that incorporates the amino- and carboxy- termin...	[ "Plasmodium vivax malaria has several unique features .", "Two of the main features are the inability to culture this parasite in vitro and its propensity to form dormant stages within the liver , which can only be treated with a single class of drugs that are contraindicated for a proportion of the population ."...	2016
[ "Introduction", "Discussion", "Materials and methods" ]	[ "dengue virus", "medicine and health sciences", "immune physiology", "body fluids", "pathology and laboratory medicine", "enzyme-linked immunoassays", "viral transmission and infection", "pathogens", "immunology", "microbiology", "vertebrates", "animals", "mammals", "primates", "viruses"...	Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques	journal.ppat.1007766	null	[ [ "The spread of Zika virus ( ZIKV ) from Africa to Asia and the Americas has led to the co-circulation and co-infection of ZIKV with other endemic arboviruses including dengue virus ( DENV ) [1–4] .", "ZIKV exists as a single serotype while DENV consists of four antigenically similar serotypes ( DENV-1-DEN...	[ "Zika virus ( ZIKV ) and dengue virus ( DENV ) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world .", "The rapid emergence of ZIKV in the Americas in 2015 and 2016 , and its recent associations with Guillain-Barré syndrome , birth defects , a...	[ "Pre-existing immunity to one of the four DENV serotypes is known to increase the risk of severe disease upon secondary infection with a different serotype .", "Due to the antigenic similarities between ZIKV and DENV , it has been proposed that these viruses could interact in a similar fashion .", "Data from in...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "parastic protozoans", "leishmania", "immunology", "biology", "microbiology", "protozoology", "host-pathogen interaction", "immune response" ]	Leishmania major Infection in Humanized Mice Induces Systemic Infection and Provokes a Nonprotective Human Immune Response	journal.pntd.0001741	null	[ [ "Over the last decades inbred mice were used to investigate the mechanisms of adaptive and innate immune responses against the obligatory intracellular parasite Leishmania ( L . ) major .", "From these studies fundamental paradigms regarding the elimination of the parasites were generated [1] .", "It ...	[ "Leishmania ( L . ) species are the causative agent of leishmaniasis .", "Due to the lack of efficient vaccine candidates , drug therapies are the only option to deal with cutaneous leishmaniasis .", "Unfortunately , chemotherapeutic interventions show high toxicity in addition to an increased risk of dissemina...	[ "As many as 12 million people suffer from Leishmania ( L . ) infection worldwide with about one to two million newly infected people every year .", "Due to the lack of vaccine strategies , the only option is chemotherapeutic intervention which can cause serious side effects .", "Therefore , new prevention or tr...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "infectious diseases", "drug research and development", "herpes simplex", "drugs and devices", "hiv", "viral diseases", "drug discovery" ]	A Multi-targeted Drug Candidate with Dual Anti-HIV and Anti-HSV Activity	journal.ppat.1003456	null	[ [ "Human immunodeficiency virus ( HIV ) infection is commonly associated with other sexually transmitted infections such as herpes simplex virus type 2 ( HSV-2 ) .", "Such infections with HSV-2 may facilitate the risk of HIV acquisition and often worsen the clinical course of the HIV disease [1]–[5] .", ...	[ "Human immunodeficiency virus ( HIV ) infection is often accompanied by infection with other pathogens , in particular herpes simplex virus type 2 ( HSV-2 ) .", "The resulting coinfection is involved in a vicious circle of mutual facilitations .", "Therefore , an important task is to develop a compound that is ...	[ "To contain the HIV-1 epidemic , it is necessary to develop antivirals that prevent HIV-1 transmission .", "It is well known that HIV infection might be accompanied by other pathogens , which often are engaged with HIV-1 in a vicious circle of mutual facilitation .", "One of the most common of these pathogens i...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "sequencing techniques", "microbiome", "applied mathematics", "microbiology", "cloning", "random variables", "covariance", "simulation and modeling", "algorithms", "non-coding rna", "mathematics", "statistics (mathematics)", "network analysis", "shotgun sequencing", "molecular biology te...	MPLasso: Inferring microbial association networks using prior microbial knowledge	journal.pcbi.1005915	null	[ [ "Microbes play an important role both in environment and human life .", "However , the way microbes affect the human health remains largely unknown .", "Knowledge of the microbial interactions can provide a solid foundation to model the interplay between the ( host ) human body and the microbial popul...	[ "Due to the recent advances in high-throughput sequencing technologies , it becomes possible to directly analyze microbial communities in human body and environment .", "To understand how microbial communities adapt , develop , and interact with the human body and the surrounding environment , one of the fundamen...	[ "Microbial communities exhibit rich dynamics including the way they adapt , develop , and interact with the human body and the surrounding environment .", "The associations among microbes can provide a solid foundation to model the interplay between the ( host ) human body and the microbial populations .", "How...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "animal models", "model organisms", "emerging infectious diseases", "immunity", "virology", "microbial pathogens", "immunology", "biology", "microbiology", "host-pathogen interaction", "immune response" ]	IFN-γ Production Depends on IL-12 and IL-18 Combined Action and Mediates Host Resistance to Dengue Virus Infection in a Nitric Oxide-Dependent Manner	journal.pntd.0001449	null	[ [ "Dengue fever ( DF ) and its severe forms , dengue hemorrhagic fever ( DHF ) and dengue shock syndrome ( DSS ) , are mosquito-borne diseases caused by one of four serotypes of Dengue virus ( DENV-1–4 ) .", "Fifty to 100 million cases of DF are estimated annually mostly in tropical and subtropical regions ...	[ "Dengue is a mosquito-borne disease caused by one of four serotypes of Dengue virus ( DENV-1–4 ) .", "Severe dengue infection in humans is characterized by thrombocytopenia , increased vascular permeability , hemorrhage and shock .", "However , there is little information about host response to DENV infection ....	[ "Dengue fever and its severe forms , dengue hemorrhagic fever and dengue shock syndrome , are the most prevalent mosquito-borne diseases on Earth .", "It is caused by one of four serotypes of Dengue virus ( DENV-1–4 ) .", "At present , there are no vaccines or specific therapies for dengue and treatment is supp...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genomics", "genome evolution", "genome analysis", "evolutionary processes", "evolutionary modeling", "genetics", "biology and life sciences", "comparative genomics", "molecular genetics", "computational biology", "evolutionary biology", "evolutionary genetics", "evolutionary theory" ]	Inference of Transposable Element Ancestry	journal.pgen.1004482	null	[ [ "Repetitive elements may comprise two-thirds or more of most vertebrate genomes [1] , and most repeat sequence is derived from transposable elements ( TEs ) .", "To obtain an accurate picture of the structure and evolutionary history of vertebrate genomes , it is therefore necessary to have a good underst...	[ "Most common methods for inferring transposable element ( TE ) evolutionary relationships are based on dividing TEs into subfamilies using shared diagnostic nucleotides .", "Although originally justified based on the “master gene” model of TE evolution , computational and experimental work indicates that many of ...	[ "The most common entities in vertebrate genomes are transposable elements ( TEs ) , DNA sequences that have been repeatedly copied and inserted into new locations throughout the genome .", "Some TEs have been replicated hundreds of thousands of times , and their ecology and evolutionary history within a genome is...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "genome engineering", "medicine and health sciences", "breast tumors", "reproductive system", "engineering and technology", "synthetic biology", "carcinomas", "cancers and neoplasms", "cloning", "synthetic bioengineering", "crispr", "oncology", "epigenetics", "dna", "m...	The Non-coding Mammary Carcinoma Susceptibility Locus, Mcs5c, Regulates Pappa Expression via Age-Specific Chromatin Folding and Allele-Dependent DNA Methylation	journal.pgen.1006261	null	[ [ "In the United States , breast cancer is the most frequently diagnosed cancer and second leading cause of cancer death among women [1] .", "Its etiology is complex , consisting of the interaction of both genetic and environmental risk factors whose contribution to overall risk can vary depending on the de...	[ "In understanding the etiology of breast cancer , the contributions of both genetic and environmental risk factors are further complicated by the impact of breast developmental stage .", "Specifically , the time period ranging from childhood to young adulthood represents a critical developmental window in a woman...	[ "A woman’s lifetime risk of developing breast cancer is affected by both genetic and environmental risk factors that can be further exacerbated by breast developmental stage .", "Time periods conferring increased risk are referred to as Windows of Susceptibility ( WOS ) and , generally speaking , the molecular me...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "crystal structure", "pathology and laboratory medicine", "pathogens", "condensed matter physics", "microbiology", "neisseria gonorrhoeae", "physiological processes", "sequence motif analysis", "crystallography", "bacteria", "bacterial pathogens", "research an...	Structure of the Neisseria Adhesin Complex Protein (ACP) and its role as a novel lysozyme inhibitor	journal.ppat.1006448	null	[ [ "Lysozymes are ubiquitous enzymes with N-acetylmuramoyl hydrolase activities , which hydrolyse the bacterial cell wall polymer peptidoglycan ( PG ) .", "PG is the major structural component of the bacterial cell wall: its major function is to provide resistance against turgor pressure and its cleavage res...	[ "Pathogenic and commensal Neisseria species produce an Adhesin Complex Protein , which was first characterised in Neisseria meningitidis ( Nm ) as a novel surface-exposed adhesin with vaccine potential .", "In the current study , the crystal structure of a recombinant ( r ) Nm-ACP Type I protein was determined to...	[ "The genus Neisseria contains two major human pathogens: N . meningitidis ( Nm ) causes meningitis and sepsis , and N . gonorrhoeae ( Ng ) causes the sexually transmitted disease gonorrhoea .", "In addition , the genus contains a larger number of commensal organisms , including N . lactamica ( Nl ) .", "Common ...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	A Unified Model of Shoot Tropism in Plants: Photo-, Gravi- and Propio-ception	journal.pcbi.1004037	null	[ [ "Plants are constantly moving to reach the light and to maintain the architecture and posture of their aerial organs: stems , branches , leaves… These movements are active , generally powered by differential growth and are controlled by environmental signals [1] .", "Tropisms are the class of movements th...	[ "Land plants rely mainly on gravitropism and phototropism to control their posture and spatial orientation .", "In natural conditions , these two major tropisms act concurrently to create a photogravitropic equilibrium in the responsive organ .", "Recently , a parsimonious model was developed that accurately pr...	[ "Although plants are mostly seen as static , they are constantly moving to adapt to changes in their stature and to their environment .", "Gravity and light , among others , are major factors that sculpt the shapes of plants .", "Plants tend to grow in the direction of the light to get access to their energy re...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "public health and epidemiology/preventive medicine", "public health and epidemiology/global health" ]	Interactions between Global Health Initiatives and Country Health Systems: The Case of a Neglected Tropical Diseases Control Program in Mali	journal.pntd.0000798	null	[ [ "Since 2000 , global health initiatives ( GHIs ) have become a dominant international aid strategy , drawing on effective methods to control specific diseases , and accounting for a substantial increase of resources for global health [1] .", "Very soon , however , concerns emerged that , beyond anticipate...	[ "Recently , a number of Global Health Initiatives ( GHI ) have been created to address single disease issues in low-income countries , such as poliomyelitis , trachoma , neonatal tetanus , etc . .", "Empirical evidence on the effects of such GHIs on local health systems remains scarce .", "This paper explores p...	[ "Prevention of neglected tropical diseases was recently significantly scaled up in sub-Saharan Africa , protecting entire populations with mass distribution of drugs: five different diseases are now addressed simultaneously with a package of four drugs .", "Some argue however that , similarly to other major contr...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "rna interference", "parasitic cell cycles", "cell cycle and cell division", "cell processes", "parasitic diseases", "parasitic protozoans", "cell differentiation", "parasitology", "trypanosoma brucei", "developmental biology", "protozoans",...	Non-linear hierarchy of the quorum sensing signalling pathway in bloodstream form African trypanosomes	journal.ppat.1007145	null	[ [ "Cells respond to their external environment in order to regulate their proliferation , developmental fate , specialisation or death .", "This can be in response to environmental cues such as temperature , pH or light , or can be driven by chemical signals generated by other cells of the same species or f...	[ "Trypanosoma brucei , the agents of African trypanosomiasis , undergo density-dependent differentiation in the mammalian bloodstream to prepare for transmission by tsetse flies .", "This involves the generation of cell-cycle arrested , quiescent , stumpy forms from proliferative slender forms .", "The signallin...	[ "African trypanosome parasites respond to density sensing information in the bloodstream of their mammalian hosts to generate their transmission stage , the stumpy form .", "Components of this ‘quorum sensing’ signalling cascade are known but their interactions and ordering are not .", "Here we have dissected t...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "density", "influenza", "applied mathematics", "simulation and modeling", "algorithms", "seasons", "probability distribution", "mathematics", "forecasting", "statistics (mathematics)", "materials science", "materials physics", "infectious disease control", ...	Nonmechanistic forecasts of seasonal influenza with iterative one-week-ahead distributions	journal.pcbi.1006134	null	[ [ "Seasonal influenza epidemics cause widespread illness which is associated each year with an estimated 250 000 to 500 000 deaths worldwide [1] and 3000 to 56 000 deaths in the United States alone [2–4] .", "In contrast to influenza “pandemics” , which are rare global outbreaks of especially novel influenz...	[ "Accurate and reliable forecasts of seasonal epidemics of infectious disease can assist in the design of countermeasures and increase public awareness and preparedness .", "This article describes two main contributions we made recently toward this goal: a novel approach to probabilistic modeling of surveillance t...	[ "Seasonal influenza is associated with 250 000 to 500 000 deaths worldwide each year ( WHO estimates ) .", "In the United States and other temperate regions , seasonal influenza epidemics occur annually , but their timing and intensity varies significantly; accurate and reliable forecasts that quantify their unce...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "genetics and genomics/gene therapy", "genetics and genomics", "genetics and genomics/gene expression" ]	Attenuation of Zinc Finger Nuclease Toxicity by Small-Molecule Regulation of Protein Levels	journal.pgen.1000376	null	[ [ "Homologous recombination is a natural mechanism that cells use for a variety of processes including double strand break ( DSB ) repair [1] .", "To repair a DSB by homologous recombination , the cell usually uses the sister chromatid as a donor-template but can use other pieces of DNA such as extrachromos...	[ "Zinc finger nucleases ( ZFNs ) have been used successfully to create genome-specific double-strand breaks and thereby stimulate gene targeting by several thousand fold .", "ZFNs are chimeric proteins composed of a specific DNA-binding domain linked to a non-specific DNA-cleavage domain .", "By changing key res...	[ "Zinc finger nucleases ( ZFNs ) are a powerful tool to create site-specific genomic modifications in a wide variety of cell types and organisms and are about to enter human gene therapy clinical trials .", "An important aspect of using ZFNs for use in gene therapy is to minimize off-target effects .", "We made ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Adenovirus Entry From the Apical Surface of Polarized Epithelia Is Facilitated by the Host Innate Immune Response	journal.ppat.1004696	null	[ [ "Adenoviruses ( AdV ) are a common cause of upper and lower respiratory tract infections .", "Although most AdV infections are self-resolving , some may lead to acute respiratory distress syndrome , a serious and frequently fatal respiratory condition [1 , 2] .", "Epidemic AdV infections occur in clos...	[ "Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection .", "The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor ( CAR ) , a cell-cell adhesion protein normally localized at the ba...	[ "Respiratory viral infection is one of the leading causes of morbidity and mortality worldwide .", "Interventions that are able to limit viral infection will enhance human health and productivity .", "However , the mechanisms that control our susceptibility to viral infection and the factors that allow viral pa...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "body fluids", "pathology and laboratory medicine", "biopsy", "pathogens", "immunology", "microbiology", "surgical and invasive medical procedures", "viruses", "hemorrhagic fever with renal syndrome", "hantavi...	Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways	journal.ppat.1006462	null	[ [ "Hantaviruses pathogenic to humans are rodent borne , but do not cause disease in their natural hosts .", "However , transmission to humans via inhalation of aerosolized virus-contaminated rodent excreta may lead to severe disease and death , thus representing a severe threat to public health [1 , 2] .", ...	[ "Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta .", "Infection can cause severe disease with up to 40% mortality depending on the viral strain .", "The virus primarily targets the vascular endothelium without direct cytopathic effects .", "Instead , exaggerated immune responses...	[ "Inhalation of hantavirus-infected rodent droppings can cause a wide range of disease ranging from mild symptoms to deaths in humans .", "Central to hantavirus disease is vascular leakage that can manifest in different organs , including the lungs .", "Although the virus can infect endothelial cells lining the ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "parasite groups", "body fluids", "pathology and laboratory medicine", "plasmodium", "atmospheric science", "tropical diseases", "vertebrates", "parasitic diseases", "animals", "parasitology", "apicomplexa", "insect vectors", "birds", "b...	Intensive trapping of blood-fed Anopheles darlingi in Amazonian Peru reveals unexpectedly high proportions of avian blood-meals	journal.pntd.0005337	null	[ [ "The Human Blood Index ( HBI ) , formerly known as the anthropophilic index or human blood ratio , is the proportion of recently-fed mosquitoes , usually vector species that have taken a human blood-meal [1] .", "This index is a very important component of the formulae used to determine vectorial capacity...	[ "Anopheles darlingi , the main malaria vector in the Neotropics , has been considered to be highly anthropophilic .", "However , many behavioral aspects of this species remain unknown , such as the range of blood-meal sources .", "Barrier screens were used to collect resting Anopheles darlingi mosquitoes from 2...	[ "Anopheles darlingi is the major malaria vector in the Amazon .", "This species has been commonly described as highly anthropophilic throughout its geographic range , although little is known about its feeding preferences .", "Scant information is available regarding the origin of An .", "darlingi blood-meals...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "immunology", "biology", "microbiology" ]	Immune Suppression by Neutrophils in HIV-1 Infection: Role of PD-L1/PD-1 Pathway	journal.ppat.1003993	null	[ [ "Neutrophils , the most abundant leukocyte population , are traditionally recognized as essential effector cells of the innate immune system in the host defense against invading pathogens [1] .", "In recent years , a new appreciation of the role of neutrophils in interacting with and regulating the adapti...	[ "HIV-1 infection is associated with a progressive loss of T cell functional capacity and reduced responsiveness to antigenic stimuli .", "The mechanisms underlying T cell dysfunction in HIV-1/AIDS are not completely understood .", "Multiple studies have shown that binding of program death ligand 1 ( PD-L1 ) on ...	[ "Despite 30 years of intensive research , our understanding of how HIV-1 virus undermines the ability of the immune system to fight common infections is limited .", "Although we know that T cells , a key cell population that normally fights invading pathogens , lose their ability to function in HIV-1-infected ind...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	ROS-Induced JNK and p38 Signaling Is Required for Unpaired Cytokine Activation during Drosophila Regeneration	journal.pgen.1005595	null	[ [ "Tissues and organs need to function reliably regardless of adverse environmental conditions .", "Injuries , disease , infection and environmental insults are stressors causing cell damage that can be repaired via homeostatic machinery .", "Thus , optimal health is largely dependent upon tissue homeos...	[ "Upon apoptotic stimuli , epithelial cells compensate the gaps left by dead cells by activating proliferation .", "This has led to the proposal that dying cells signal to surrounding living cells to maintain homeostasis .", "Although the nature of these signals is not clear , reactive oxygen species ( ROS ) cou...	[ "Regenerative biology pursues to unveil the genetic networks triggered by tissue damage .", "Regeneration can occur after damage by cell death or by injury .", "We used the imaginal disc of Drosophila in which we genetically activated apoptosis or physically removed some parts and monitored the capacity to repa...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "rna interference", "viral transmission and infection", "molecular probe techniques", "immunology", "microbiology", "plasmid construction", "viruses", "rna viruses", "dna construction", "epigenetics", "molecular biology techniques", "bioen...	PKACs attenuate innate antiviral response by phosphorylating VISA and priming it for MARCH5-mediated degradation	journal.ppat.1006648	null	[ [ "Innate immune response is the first line of host defense against invading microbial pathogens .", "The structurally conserved components of microbes called pathogen-associated molecular patterns ( PAMPs ) are recognized by host pattern-recognition receptors ( PRRs ) , which initiates signaling pathways t...	[ "Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response , which is mediated by the central adaptor VISA .", "How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic .", "Here we identified the protein kinase A catalytic ( PKAC ) subunits...	[ "VISA is a central adaptor protein required for innate immune response to RNA virus .", "Phosphorylation of VISA by protein kinase A leads to its polyubiquitination and degradation by the E3 ligase MARCH5 at the late phase of viral infection , which provides a critical control mechanism for the host to avoid exce...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public and occupational health", "infectious diseases", "veterinary diseases", "medicine and health sciences", "diagnostic medicine", "women's health", "veterinary microbiology", "obstetrics and gynecology", "epidemiology", "biology and life sciences", "veterinary science", "pediatrics" ]	Serologic Prevalence of Toxoplasma gondii in Indian Women of Child Bearing Age and Effects of Social and Environmental Factors	journal.pntd.0002737	null	[ [ "Toxoplasma gondii ( T . gondii ) infection is a significant member of the TORCH group of diseases which cause congenital abnormalities , and even fetal loss .", "TORCH group infectious agents also consist of Rubella , Cytomegalovirus , Herpes viruses and Treponema pallidum .", "In India , awareness a...	[ "Seroprevalence and incidence of toxoplasmosis in women of child bearing age has remained a contentious issue in the Indian subcontinent .", "Different laboratories have used different patient recruitment criteria , methods and variable results , making these data difficult to compare .", "To map the point-prev...	[ "Toxoplasmosis is a protozoan parasitic disease commonly transmitted and propagated by cats as family pets .", "Infection acquired during pregnancy can lead to congenital abnormalities in the fetus , still birth or intrauterine death .", "Seroprevalence and incidence of toxoplasmosis in Indian women of child be...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "genome sequencing", "medicine", "cancer genetics", "genetics", "cancer treatment", "chemotherapy and drug treatment", "biology", "genomics", "cancers and neoplasms", "gastrointestinal tumors", "genomic medicine", "pharmacogenomics", "cholangiocarcinoma" ]	Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma	journal.pgen.1004135	null	[ [ "Biliary tract cancers ( BTC ) comprise malignant tumors of the intrahepatic and extrahepatic bile ducts .", "Known risk factors for BTC are the liver flukes O . viverrini and C . sinensis in high prevalence endemic regions in southeast Asia [1]–[3] , as well as primary sclerosing cholangitis [4]–[7] , Ca...	[ "Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited .", "During the course of a clinical trial of whole genomic sequencing seeking druggable targets , we examined six patients with advanced cholangiocarcinoma .", "Integrated genome-wide and whole tran...	[ "Cholangiocarcinoma is a cancer that affects the bile ducts .", "Unfortunately , many patients diagnosed with cholangiocarcinoma have disease that cannot be treated with surgery or has spread to other parts of the body , thus severely limiting treatment options .", "New advances in drug treatment have enabled t...	2014
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "cell biology/microbial physiology and metabolism", "biochemistry/molecular evolution", "evolutionary biology/microbial evolution and genomics", "computer science/applications", "genetics and genomics/comparative genomics", "genetics and genomics/functional genomics", "genetics and genomics/gene express...	Translational Selection Is Ubiquitous in Prokaryotes	journal.pgen.1001004	null	[ [ "Due to non-random use of synonymous codons , protein coding sequences contain a layer of information on the DNA level that is not reflected at the protein sequence level .", "The principal determinant of codon usage in prokaryotes are nucleotide substitution patterns [1] , [2] that vary greatly across ge...	[ "Codon usage bias in prokaryotic genomes is largely a consequence of background substitution patterns in DNA , but highly expressed genes may show a preference towards codons that enable more efficient and/or accurate translation .", "We introduce a novel approach based on supervised machine learning that detects...	[ "Synonymous codons are not equally common in genomes .", "The main causes of unequal codon usage are varying nucleotide substitution patterns , as manifested in the wide range of genomic nucleotide compositions .", "However , since the first E . coli and yeast genes were sequenced , it became evident that there...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "cell death", "medicine and health sciences", "reproductive system", "helminths", "cell processes", "vertebrates", "animals", "xenopus", "animal models", "germ cells", "oocytes", "model organisms", "amphibians", "integrins", "i...	Evidence for Integrin – Venus Kinase Receptor 1 Alliance in the Ovary of Schistosoma mansoni Females Controlling Cell Survival	journal.ppat.1006147	null	[ [ "Communication of cells with their environment is an essential requirement to regulate fundamental biological processes such as cell growth and differentiation .", "Different types of membrane-linked receptors mediate these communication processes , sometimes in a solitary , single receptor-mediated way ,...	[ "In metazoan integrin signaling is an important process of mediating extracellular and intracellular communication processes .", "This can be achieved by cooperation of integrins with growth factor receptors ( GFRs ) .", "Schistosoma mansoni is a helminth parasite inducing schistosomiasis , an infectious diseas...	[ "Parasites of the genus Schistosoma cause schistosomiasis , a life-threatening infectious disease for humans and animals worldwide .", "Among the remarkable biological features of schistosomes is the differentiation of the female gonads which is controlled by pairing with the male and a prerequisite for egg produ...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "microbiology/microbial evolution and genomics", "microbiology/innate immunity", "genetics and genomics", "evolutionary biology", "microbiology/microbial physiology and metabolism", "microbiology/cellular microbiolog...	Transit through the Flea Vector Induces a Pretransmission Innate Immunity Resistance Phenotype in Yersinia pestis	journal.ppat.1000783	null	[ [ "Arthropod-borne transmission of bacterial pathogens is somewhat rare but has evolved in a phylogenetically diverse group that includes the rickettsiae , Borrelia spirochetes , and the gram-negative bacteria Francisella tularensis and Yersinia pestis , the plague bacillus .", "Y . pestis circulates among ...	[ "Yersinia pestis , the agent of plague , is transmitted to mammals by infected fleas .", "Y . pestis exhibits a distinct life stage in the flea , where it grows in the form of a cohesive biofilm that promotes transmission .", "After transmission , the temperature shift to 37°C induces many known virulence facto...	[ "Bubonic plague cycles depend on the ability of Yersinia pestis to alternately infect two very different hosts—a mammal and a flea .", "Like any arthropod-borne pathogen , Y . pestis must sense host-specific environmental cues and regulate gene expression accordingly to produce a transmissible infection in the fl...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/population genetics", "evolutionary biology/evolutionary and comparative genetics", "computational biology/comparative sequence analysis", "computational biology/molecular genetics", "evolutionary biology/genomics", "computational biology/genomics", "genetics and genomics/bioinfor...	Hypermutable Non-Synonymous Sites Are under Stronger Negative Selection	journal.pgen.1000281	null	[ [ "The functional and phenotypic effects of mutations and , consequently , the strength of negative selection vary widely among nucleotide sites in any genome .", "At the opposite ends of the continuum , mutations at some sites are effectively neutral , while mutations at some other sites are lethal .", ...	[ "Mutation rate varies greatly between nucleotide sites of the human genome and depends both on the global genomic location and the local sequence context of a site .", "In particular , CpG context elevates the mutation rate by an order of magnitude .", "Mutations also vary widely in their effect on the molecula...	[ "Mutations occur in some sites in the genome more frequently than in others .", "Similarly , mutations in some sites have greater consequences than in others .", "The effect of mutations might not be independent of the frequency with which mutations occur .", "Indeed , sites where mutations happen frequently ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunity", "virology", "immunology", "biology", "microbiology" ]	Post-Translational Control of IL-1β via the Human Papillomavirus Type 16 E6 Oncoprotein: A Novel Mechanism of Innate Immune Escape Mediated by the E3-Ubiquitin Ligase E6-AP and p53	journal.ppat.1003536	null	[ [ "High-risk human papillomaviruses ( HPVs ) are causally responsible for anogenital cancer , both in women and men [1] , [2] .", "While in the latter , penile and anal carcinomas are relatively rare , HPV infection is also linked in both genders to more than 50% of all oropharyngeal squamous cell carcinoma...	[ "Infections with high-risk human papillomaviruses ( HPVs ) are causally involved in the development of anogenital cancer .", "HPVs apparently evade the innate immune response of their host cells by dysregulating immunomodulatory factors such as cytokines and chemokines , thereby creating a microenvironment that f...	[ "Persistently high-risk HPV-infected individuals have an increased risk to develop anogenital cancer .", "HPV encodes the viral proteins E6 and E7 that interact with and induce the degradation of the cell cycle regulators p53 and pRb , respectively , priming immortalized keratinocytes towards malignant transforma...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "viral transmission and infection", "virology", "genetics", "biology", "evolutionary biology", "microbiology", "genetics and genomics" ]	Two Genetic Determinants Acquired Late in Mus Evolution Regulate the Inclusion of Exon 5, which Alters Mouse APOBEC3 Translation Efficiency	journal.ppat.1002478	null	[ [ "The family of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3 ( APOBEC3 ) proteins consists of cytidine deaminases that function as cellular restriction factors against various exogenous and endogenous viruses [1]–[17] .", "Seven APOBEC3 paralogues have been identified o...	[ "Mouse apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3 ( mA3 ) , an intracellular antiviral factor , has 2 allelic variations that are linked with different susceptibilities to beta- and gammaretrovirus infections among various mouse strains .", "In virus-resistant C57BL/6 ( B6 )...	[ "Susceptibility to acutely leukemogenic Friend virus ( FV ) retrovirus infection varies among different mouse strains and is governed by several genetic factors , one of which is allelic variations at the mouse Apobec3 locus .", "FV-resistant C57BL/6 ( B6 ) mice express higher amounts of Apobec3 transcripts than ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Combinatory Microarray and SuperSAGE Analyses Identify Pairing-Dependently Transcribed Genes in Schistosoma mansoni Males, Including Follistatin	journal.pntd.0002532	null	[ [ "Schistosoma mansoni is a species of parasitic flatworms causing schistosomiasis , an infectious disease of worldwide importance for man and animals .", "Besides vertebrates as final hosts , the parasites' life cycle includes a snail intermediate host , and both are infected by aquatic larval stages .", ...	[ "Schistosomiasis is a disease of world-wide importance and is caused by parasitic flatworms of the genus Schistosoma .", "These parasites exhibit a unique reproduction biology as the female's sexual maturation depends on a constant pairing-contact to the male .", "Pairing leads to gonad differentiation in the f...	[ "Schistosomiasis is an important infectious disease caused by worm parasites of the genus Schistosoma and directly affects more than 240 million people in 78 tropical and sub-tropical countries but also animals .", "Pathogenesis is triggered by eggs that are produced by paired females and get trapped in liver and...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immune cells", "cytokines", "immunity to infections", "immunology", "immune suppression", "microbiology", "lymphoid organs", "host-pathogen interaction", "emerging infectious diseases", "immune defense", "immunoregulation", "immunomodulation", "bacterial pathogens", "inflammation", "med...	The Systemic Immune State of Super-shedder Mice Is Characterized by a Unique Neutrophil-dependent Blunting of TH1 Responses	journal.ppat.1003408	null	[ [ "Host-adapted pathogens depend on their host for transmission and dissemination within a population .", "Recent epidemiological studies have uncovered heterogeneities in infection wherein a minority of the infected individuals ( 20% ) are responsible for the majority of the infections ( 80% ) , described ...	[ "Host-to-host transmission of a pathogen ensures its successful propagation and maintenance within a host population .", "A striking feature of disease transmission is the heterogeneity in host infectiousness .", "It has been proposed that within a host population , 20% of the infected hosts , termed super-shed...	[ "Bacteria belonging to the genus Salmonella are capable of causing long-term chronic systemic infections in specific hosts where they are shed in the feces .", "These persistently infected individuals include typhoid carriers and they serve as a reservoir for disease transmission .", "Despite the importance of ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal models", "molecular neuroscience", "caenorhabditis elegans", "cellular neuroscience", "model organisms", "neurobiology of disease and regeneration", "neuronal morphology", "signaling pathways", "biology", "mouse", "neuroscience" ]	Diapause Formation and Downregulation of Insulin-Like Signaling via DAF-16/FOXO Delays Axonal Degeneration and Neuronal Loss	journal.pgen.1003141	null	[ [ "Neuronal loss constitutes an irreversible end point of several neurodegenerative conditions triggered by diverse stimuli .", "Nevertheless , early neuronal dysfunction is associated with degeneration of neuronal processes , including axons and dendrites , causing a progressive loss of neuronal function [...	[ "Axonal degeneration is a key event in the pathogenesis of neurodegenerative conditions .", "We show here that mec-4d triggered axonal degeneration of Caenorhabditis elegans neurons and mammalian axons share mechanistical similarities , as both are rescued by inhibition of calcium increase , mitochondrial dysfunc...	[ "Axonal degeneration and neuronal loss are currently considered crucial pathological factors in neurodegenerative diseases .", "Therefore , delaying or blocking these procesess is key for neuroprotection .", "In this work , we used an in vivo approach combining invertebrate ( C . elegans ) and vertebrate ( mice...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "molecular biology/chromatin structure", "genetics and genomics/gene expression", "molecular biology/chromosome structure", "genetics and genomics/chromosome biology", "genetics and genomics/epigenetics", "genetics and genomics/bioinformatics" ]	Buffering of Segmental and Chromosomal Aneuploidies in Drosophila melanogaster	journal.pgen.1000465	null	[ [ "The effects of deficiencies , duplications or chromosome losses ( e . g . somatic elimination ) on the regulation of whole chromosomes and large chromosome domains are largely unknown , although the gene dose at most specific loci generally has little effect on the development of Drosophila .", "A useful...	[ "Chromosomal instability , which involves the deletion and duplication of chromosomes or chromosome parts , is a common feature of cancers , and deficiency screens are commonly used to detect genes involved in various biological pathways .", "However , despite their importance , the effects of deficiencies , dupl...	[ "Although deletion heterozygotes and chromosomal aneuploidies have been used in genetic studies for decades , the relationships between chromosome doses and transcript outputs have been difficult to unravel .", "In other words , the effects of copy changes on the regulation of entire chromosomes or large chromoso...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "neglected tropical diseases", "syphilis" ]	Immune Evasion and Recognition of the Syphilis Spirochete in Blood and Skin of Secondary Syphilis Patients: Two Immunologically Distinct Compartments	journal.pntd.0001717	null	[ [ "Syphilis is a sexually transmitted multi-stage disease caused by the spirochetal bacterium Treponema pallidum ( Tp ) , subspecies pallidum [1] , [2] .", "Despite the existence of inexpensive and effective antibiotic treatment regimens , more than 10 . 5 million new syphilis cases are estimated to occur y...	[ "The clinical syndrome associated with secondary syphilis ( SS ) reflects the propensity of Treponema pallidum ( Tp ) to escape immune recognition while simultaneously inducing inflammation .", "To better understand the duality of immune evasion and immune recognition in human syphilis , herein we used a combinat...	[ "Syphilis , a sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum , affects close to 10 million people per year worldwide .", "Despite the robust nature of the humoral and cellular immune responses associated with the disease , weeks to months may elapse before the host gains contr...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/molecular dynamics", "biophysics/macromolecular assemblies and machines" ]	A Mechanistic View of the Role of E3 in Sumoylation	journal.pcbi.1000913	null	[ [ "Protein function is regulated by numerous mechanisms , one of which is post-translational modification .", "Covalent binding of ubiquitin ( Ub ) and ubiquitin-like ( Ubl ) modifiers to target proteins constitute a key step in cellular processes including differentiation , apoptosis , cell cycle , and str...	[ "Sumoylation , the covalent attachment of SUMO ( Small Ubiquitin-Like Modifier ) to proteins , differs from other Ubl ( Ubiquitin-like ) pathways .", "In sumoylation , E2 ligase Ubc9 can function without E3 enzymes , albeit with lower reaction efficiency .", "Here , we study the mechanism through which E3 ligas...	[ "Post-translational modifications constitute key regulatory mechanisms in the cell .", "One of these modifications is the tagging of the target protein with a smaller molecule .", "SUMO is such a ubiquitin-like tag protein , and sumoylation is the process of tagging proteins with SUMO .", "The malfunctioning ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "cellular stress responses", "rna interference", "gene regulation", "microbiology", "gene function", "escherichia coli", "cell growth", "dna recombination", "molecular genetics", "dna", "microbial growth and development", "bacterial pathogens", "gene expressio...	Single Transmembrane Peptide DinQ Modulates Membrane-Dependent Activities	journal.pgen.1003260	null	[ [ "Exposure of E . coli to DNA damaging agents induces the SOS response , which is under control of the RecA and LexA regulatory proteins .", "The SOS response upregulates gene functions involved in numerous cellular processes such as nucleotide excision repair ( NER ) , UV induced mutagenesis , recombinati...	[ "The functions of several SOS regulated genes in Escherichia coli are still unknown , including dinQ .", "In this work we characterize dinQ and two small RNAs , agrA and agrB , with antisense complementarity to dinQ .", "Northern analysis revealed five dinQ transcripts , but only one transcript ( +44 ) is activ...	[ "Exposure of the bacterium Escherichia coli to DNA damaging agents induces the SOS response , which up-regulates gene functions involved in numerous cellular processes such as DNA repair , cell division , and replication .", "Most of the SOS regulated genes in E . coli have been characterized , but still there ar...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "gene regulation", "reporter genes", "developmental biology", "immunoprecipitation", "gene types", "sequence motif analysis", "molecular biology techniques", "embryos", "research and analysis methods", "sequence analysis", "embryology", "animal cells", "gene expres...	A Maternal System Initiating the Zygotic Developmental Program through Combinatorial Repression in the Ascidian Embryo	journal.pgen.1006045	null	[ [ "In animal embryos , maternal information initiates the zygotic developmental program .", "Maternal factors are often specifically localized to set up pre-patterns .", "This mechanism has been extensively studied in embryos of invertebrates including sea urchin and flies [1 , 2] .", "In syncytium ...	[ "Maternal factors initiate the zygotic developmental program in animal embryos .", "In embryos of the chordate , Ciona intestinalis , three maternal factors—Gata . a , β-catenin , and Zic-r . a—are required to establish three domains of gene expression at the 16-cell stage; the animal hemisphere , vegetal hemisph...	[ "During animal development , transcription factors and signaling molecules transcriptionally regulate one another and constitute a gene regulatory network .", "This network is evoked by maternally provided factors .", "Many maternal factors are localized and thereby activate a set of genes in a specific region ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "viruses", "immunology", "virology" ]	Evidence of Differential HLA Class I-Mediated Viral Evolution in Functional and Accessory/Regulatory Genes of HIV-1	journal.ppat.0030094	null	[ [ "Genetic variation within the highly polymorphic human leukocyte antigen ( HLA ) class I region contributes to diversity of pathogen recognition by cytotoxic T lymphocytes ( CTLs ) [1] , and acts as a selective force shaping viral evolution within an infected host [2–6] through selection of mutations that all...	[ "Despite the formidable mutational capacity and sequence diversity of HIV-1 , evidence suggests that viral evolution in response to specific selective pressures follows generally predictable mutational pathways .", "Population-based analyses of clinically derived HIV sequences may be used to identify immune escap...	[ "One of the greatest challenges facing HIV-1 vaccine design today is the formidable capacity of the virus for mutation and adaptation , a characteristic that has contributed to the extensive worldwide genetic variability of HIV-1 strains observed today .", "On an individual basis , evolutionary selective pressure...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "invertebrates", "medicine and health sciences", "abdomen", "quantitative trait loci", "population genetics", "animals", "animal models", "drosophila melanogaster", "model organisms", "physiological parameters", "genome analysis", "experimental organism sys...	Genetic basis of thermal plasticity variation in Drosophila melanogaster body size	journal.pgen.1007686	null	[ [ "Body size has a great impact on the performance of individuals [1 , 2] , as well as that of species [3] .", "Diversity in this trait is shaped by the reciprocal interactions between the developmental processes that regulate growth , and the evolutionary forces that determine which phenotypes increase in ...	[ "Body size is a quantitative trait that is closely associated to fitness and under the control of both genetic and environmental factors .", "While developmental plasticity for this and other traits is heritable and under selection , little is known about the genetic basis for variation in plasticity that can pro...	[ "Environmental conditions can influence development and lead to the production of phenotypes adjusted to the conditions adults will live in .", "This developmental plasticity , which can help organisms cope with environmental heterogeneity , is heritable and under selection .", "Its evolution will depend on ava...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "genetic networks", "morphogenic segmentation", "molecular probe techniques", "gene regulation", "animals", "simulation and modeling", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "network analysis", "experimental organism systems",...	Dynamic patterning by the Drosophila pair-rule network reconciles long-germ and short-germ segmentation	journal.pbio.2002439	null	[ [ "Like other arthropods , the fruit fly Drosophila melanogaster has a segmented body plan .", "This segmental pattern is laid down in the embryo during the first 3 hours of development .", "During this time , the anteroposterior ( AP ) axis of the blastoderm is progressively patterned down to cellular-...	[ "Drosophila segmentation is a well-established paradigm for developmental pattern formation .", "However , the later stages of segment patterning , regulated by the “pair-rule” genes , are still not well understood at the system level .", "Building on established genetic interactions , I construct a logical mod...	[ "Segmentation in insects involves the division of the body into several repetitive units .", "In Drosophila embryos , all segments are patterned rapidly and simultaneously during early development , in a process known as “long-germ” embryogenesis .", "In contrast , many insect embryos retain an ancestral or “sh...	2017
[ "Introduction", "Results", "Discussion" ]	[ "genetics and genomics/animal genetics", "evolutionary biology/evolutionary and comparative genetics", "dermatology/hair and nail diseases", "developmental biology/developmental evolution", "genetics and genomics/disease models", "developmental biology/organogenesis", "developmental biology/developmenta...	Zebrafish eda and edar Mutants Reveal Conserved and Ancestral Roles of Ectodysplasin Signaling in Vertebrates	journal.pgen.1000206	null	[ [ "The genetic and developmental basis of the formation of organismal shape and form is a long-standing question in biology .", "The analysis of mutations has been essential in identifying the genes and regulatory networks underlying development .", "However , while the genetic basis of embryonic develo...	[ "The genetic basis of the development and variation of adult form of vertebrates is not well understood .", "To address this problem , we performed a mutant screen to identify genes essential for the formation of adult skeletal structures of the zebrafish .", "Here , we describe the phenotypic and molecular cha...	[ "A major goal of the study of developmental genetics is to understand the genes and developmental mechanisms underlying the formation of organismal complexity and diversity .", "Here , we focus on genes controlling postembryonic development and describe mutations in genes of the ectodysplasin ( Eda ) pathway in r...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "proteins", "gene expression", "genetics", "biology and life sciences", "dna repair", "dna", "dna-binding proteins", "dna transcription" ]	In TFIIH, XPD Helicase Is Exclusively Devoted to DNA Repair	journal.pbio.1001954	The DNA helicase activity of the xeroderma pigmentosum D protein, a crucial subunit of TFIID, is only needed for its role in DNA repair, not for transcription.	[ [ "The human XPD protein is a helicase with 5′–3′ polarity [1] , [2] that contains a 4Fe4S cluster ( FeS ) [3]–[6] and is organized within the context of the general transcription factor IIH ( TFIIH ) .", "TFIIH consists of a total of 10 subunits of which XPB , p62 , p52 , p44 , p34 , and p8 build the core ...	[ "The eukaryotic XPD helicase is an essential subunit of TFIIH involved in both transcription and nucleotide excision repair ( NER ) .", "Mutations in human XPD are associated with several inherited diseases such as xeroderma pigmentosum , Cockayne syndrome , and trichothiodystrophy .", "We performed a comparati...	[ "The multiprotein complex TFIIH is crucially involved in two fundamental cellular processes—the transcription of genes by RNA polymerase II and the repair of UV-induced DNA damage by a mechanism called nucleotide excision repair ( NER ) .", "The xeroderma pigmentosum complementation group D ( XPD ) helicase , whi...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "drug research and development", "drugs and devices", "african trypanosomiasis", "neglected tropical diseases", "parasitic diseases", "drug discovery" ]	Safety, Pharmacokinetic, and Efficacy Studies of Oral DB868 in a First Stage Vervet Monkey Model of Human African Trypanosomiasis	journal.pntd.0002230	null	[ [ "Human African trypanosomiasis ( HAT , sleeping sickness ) is caused by two trypanosome species that are transmitted through the bite of blood-sucking tsetse flies ( Glossina spp ) .", "Trypanosoma brucei ( T . b . ) gambiense is endemic to West and Central Africa , while T . b .", "rhodesiense is end...	[ "There are no oral drugs for human African trypanosomiasis ( HAT , sleeping sickness ) .", "A successful oral drug would have the potential to reduce or eliminate the need for patient hospitalization , thus reducing healthcare costs of HAT .", "The development of oral medications is a key objective of the Conso...	[ "Development of orally administered medicines for human African trypanosomiasis ( HAT ) would potentially reduce the need for patient hospitalization , thus lowering healthcare costs .", "In this study , we investigated the potential of a novel diamidine prodrug , DB868 ( CPD-007-10 ) , as an oral treatment for f...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry/biomacromolecule-ligand interactions", "biochemistry/biocatalysis", "virology/viral replication and gene regulation" ]	Bunyaviridae RNA Polymerases (L-Protein) Have an N-Terminal, Influenza-Like Endonuclease Domain, Essential for Viral Cap-Dependent Transcription	journal.ppat.1001101	null	[ [ "Bunyaviridae is the largest single family of mostly animal viruses comprising more than 300 species , divided into five genera: Orthobunyavirus , Phlebovirus , Nairovirus , Hantavirus and Tospovirus , the latter infecting plants .", "The viruses are mainly insect transmitted except Hantaviruses which are...	[ "Bunyaviruses are a large family of segmented RNA viruses which , like influenza virus , use a cap-snatching mechanism for transcription whereby short capped primers derived by endonucleolytic cleavage of host mRNAs are used by the viral RNA-dependent RNA polymerase ( L-protein ) to transcribe viral mRNAs .", "It...	[ "Bunyaviruses are a large family of RNA viruses that include serious human , animal and plant pathogens .", "The viral RNA-dependent RNA polymerase ( L-protein ) is responsible for replication and transcription of the viral RNA , but apart from its central polymerase domain , it is poorly characterized .", "Lik...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders/neuro-oncology" ]	Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth	journal.pbio.1000319	The A20 protein is a known inhibitor of apoptosis that here is shown to be a novel cancer stem cell-promoting factor associated with poor glioma patient survival.	[ [ "Tumors are aberrant organ systems that display a complex interplay between neoplastic cells and recruited vascular , inflammatory , and stromal elements [1] .", "Cellular heterogeneity within the neoplastic compartment has been modeled with complementary stochastic and hierarchical paradigms .", "Mol...	[ "Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioblastoma stem cells ( GSCs ) .", "GSCs are regulated by molecular pathways distinct from the bulk tumor that may be useful therapeutic targets .", "We determined that A20 ( TNFAIP3 ) , a regulator of c...	[ "Glioblastomas are the most common and aggressive primary brain tumors in adults , with a median survival of only 12–15 months .", "Glioblastomas display a cellular hierarchy with a subset of cells having stem cell–like properties , including the capacity to self-renew and propagate tumors .", "Specific ablatio...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "computational biology", "biophysics" ]	Coordinated Movement of Cytoplasmic and Transmembrane Domains of RyR1 upon Gating	journal.pbio.1000085	Three-dimensional cryo-electron microscopy of the RyR1 calcium release channel in the open and closed states reveals its mechanisms of ion gating and long-range allostery.	[ [ "Maintaining a precise intracellular Ca2+ concentration that is 10 , 000-fold lower than the surrounding environment of the cell , and the ability to dramatically increase intracellular calcium to trigger downstream events in response to specific stimulus are key for cell survival [1] .", "Ryanodine recep...	[ "Ryanodine receptor type 1 ( RyR1 ) produces spatially and temporally defined Ca2+ signals in several cell types .", "How signals received in the cytoplasmic domain are transmitted to the ion gate and how the channel gates are unknown .", "We used EGTA or neuroactive PCB 95 to stabilize the full closed or open ...	[ "Maintaining a precise intracellular calcium concentration is key for cell survival .", "In skeletal muscle , ryanodine receptor type 1 ( RyR1 ) is an intracellular calcium-release channel that is critical for contraction .", "Here , we used single-channel techniques to demonstrate the presence of functionally ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene expression", "biology", "molecular cell biology", "molecular biology" ]	Cytoplasmic Polyadenylation Element Binding Protein Deficiency Stimulates PTEN and Stat3 mRNA Translation and Induces Hepatic Insulin Resistance	journal.pgen.1002457	null	[ [ "The maintenance of glucose homeostasis requires that organisms respond to changing environmental conditions by balancing pancreatic insulin secretion with the ability of tissues , particularly liver , muscle , and fat , to respond to hormone-induced signaling by importing or secreting glucose [1] , [2] .", ...	[ "The cytoplasmic polyadenylation element binding protein CPEB1 ( CPEB ) regulates germ cell development , synaptic plasticity , and cellular senescence .", "A microarray analysis of mRNAs regulated by CPEB unexpectedly showed that several encoded proteins are involved in insulin signaling .", "An investigation ...	[ "One major hallmark of diabetes is insulin resistance in peripheral tissues that is controlled at the posttranslational level .", "For example , insulin activates a kinase cascade that leads to the phosphorylation of Akt , a centrally important molecule that regulates glucose metabolism .", "In this study , we ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genome evolution", "parasite evolution", "biology", "genomics", "microbiology", "genetics and genomics", "parasitology" ]	Multiple Mitochondrial Introgression Events and Heteroplasmy in Trypanosoma cruzi Revealed by Maxicircle MLST and Next Generation Sequencing	journal.pntd.0001584	null	[ [ "Mitochondrial genes are among the most popular markers for the reconstruction of evolutionary ancestries and resolution of phylogeographic relationships [1] .", "Their pervasive use in population genetics can be attributed to several intrinsic characteristics , notably , their high copy number , small si...	[ "Mitochondrial DNA is a valuable taxonomic marker due to its relatively fast rate of evolution .", "In Trypanosoma cruzi , the causative agent of Chagas disease , the mitochondrial genome has a unique structural organization consisting of 20–50 maxicircles ( ∼20 kb ) and thousands of minicircles ( 0 . 5–10 kb ) ....	[ "Chagas disease , caused by the protozoan parasite Trypanosoma cruzi , is an important public health problem in Latin America .", "While molecular techniques can differentiate the major T . cruzi genetic lineages , few have sufficient resolution to describe diversity among closely related strains .", "The onlin...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "viruses and cancer", "immunology", "microbiology", "tumor immunology", "epstein-barr virus infectious mononucleosis", "infectious disease immunology", "vaccination and immunization", "animal models of infection", "infectious disea...	Adoptive Transfer of EBV Specific CD8+ T Cell Clones Can Transiently Control EBV Infection in Humanized Mice	journal.ppat.1004333	null	[ [ "Epstein Barr virus ( EBV ) is a ubiquitous human γ-herpesvirus that establishes persistent infection in more than 90% of the human adult population [1] .", "Like other herpesviruses , EBV can undergo two infection programs .", "Latent infection leads to the expression of eight viral proteins and more...	[ "Epstein Barr virus ( EBV ) infection expands CD8+ T cells specific for lytic antigens to high frequencies during symptomatic primary infection , and maintains these at significant numbers during persistence .", "Despite this , the protective function of these lytic EBV antigen-specific cytotoxic CD8+ T cells rem...	[ "Epstein Barr virus persistently infects more than 90% of the human adult population .", "While fortunately carried as an asymptomatic chronic infection in most individuals , it causes B cell lymphomas and carcinomas in some patients .", "Symptomatic primary EBV infection , called infectious mononucleosis , pre...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "293t cells", "pathogens", "biological cultures", "messenger rna", "microbiology", "immunology", "retroviruses", "viruses", "immunodeficiency viruses", "rna viruses", "materials science", ...	Identifying the assembly intermediate in which Gag first associates with unspliced HIV-1 RNA suggests a novel model for HIV-1 RNA packaging	journal.ppat.1006977	null	[ [ "For released HIV-1 particles to be infectious , they must contain two copies of unspliced ( full-length ) HIV-1 RNA that are packaged during assembly of the immature HIV-1 capsid .", "Each immature capsid is composed of ~3000 copies of the HIV-1 structural protein Gag , which initially oligomerize in the...	[ "During immature capsid assembly , HIV-1 genome packaging is initiated when Gag first associates with unspliced HIV-1 RNA by a poorly understood process .", "Previously , we defined a pathway of sequential intracellular HIV-1 capsid assembly intermediates; here we sought to identify the intermediate in which HIV-...	[ "During HIV-1 immature capsid assembly , packaging of the viral genome is initiated when the HIV-1 capsid protein , Gag , first associates with unspliced HIV-1 RNA .", "Although the complex in which this association initially occurs is critical for formation of infectious virus , the identity , composition , and ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Next Generation of Transcription Factor Binding Site Prediction	journal.pcbi.1003214	null	[ [ "Transcription factors ( TFs ) and their specific binding sites act to modulate the rate of gene transcription .", "They are central to key biological processes , such as organ development and tissue differentiation , nutrient and environmental stress responses and physiological signals .", "Delineati...	[ "Finding where transcription factors ( TFs ) bind to the DNA is of key importance to decipher gene regulation at a transcriptional level .", "Classically , computational prediction of TF binding sites ( TFBSs ) is based on basic position weight matrices ( PWMs ) which quantitatively score binding motifs based on ...	[ "Transcription factors are critical proteins for sequence-specific control of transcriptional regulation .", "Finding where these proteins bind to DNA is of key importance for global efforts to decipher the complex mechanisms of gene regulation .", "Greater understanding of the regulation of transcription promi...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "mosquitoes", "pest control", "dengue fever", "neglected tropical diseases", "biology", "arboviral infections", "vectors and hosts", "infectious disease control", "agriculture" ]	Pyrethroid Resistance Reduces the Efficacy of Space Sprays for Dengue Control on the Island of Martinique (Caribbean)	journal.pntd.0001202	null	[ [ "Control of the vector Aedes aegypti remains the primary approach to reducing transmission of dengue and dengue hemorrhagic fever in human populations [1] , [2] .", "Adult control is generally implemented by spraying chemicals into the air to reduce adult populations after larval control has failed to lim...	[ "Dengue fever is reemerging on the island of Martinique and is a serious threat for the human population .", "During dengue epidemics , adult Aedes aegypti control with pyrethroid space sprays is implemented in order to rapidly reduce transmission .", "Unfortunately , vector control programs are facing operatio...	[ "The mosquito Aedes aegypti is the major vector of the Dengue virus in human populations and is responsible of serious outbreaks worldwide .", "In most countries , vector control is implemented by the use of insecticides to reduce mosquito populations .", "During epidemics , insecticides of the pyrethroid famil...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "genomics", "dna modification", "genome evolution", "gene expression", "genetics", "biology and life sciences", "dna", "comparative genomics", "computational biology", "epigenetics" ]	Methylome Diversification through Changes in DNA Methyltransferase Sequence Specificity	journal.pgen.1004272	null	[ [ "Epigenetic modifications affect gene regulation and genome maintenance [1] , [2] .", "DNA methylation is an important epigenetic modification in bacteria with functions in gene expression regulation , genome replication initiation , cell cycle regulation , anti-mutagenesis , and genome maintenance [3] , ...	[ "Epigenetic modifications such as DNA methylation have large effects on gene expression and genome maintenance .", "Helicobacter pylori , a human gastric pathogen , has a large number of DNA methyltransferase genes , with different strains having unique repertoires .", "Previous genome comparisons suggested tha...	[ "Living organisms are affected by epigenetic variation in addition to DNA sequence variation .", "DNA methylation is one of the most studied epigenetic modifications in both prokaryotes and eukaryotes .", "In prokaryotes , most DNA methylation is by DNA methyltransferases with high sequence specificity .", "H...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "homo sapiens", "oncology", "developmental biology", "mammals" ]	(A)Symmetric Stem Cell Replication and Cancer	journal.pcbi.0030053	null	[ [ "Most tissues of the body experience continuous cell turnover due to either apoptosis or loss of epithelial cells due to shedding as occurs in the gastrointestinal and respiratory tract as well as the ductal epithelium of the breast .", "This cell turnover also gives tissues the ability to repair after in...	[ "Most tissues in metazoans undergo continuous turnover due to cell death or epithelial shedding .", "Since cellular replication is associated with an inherent risk of mutagenesis , tissues are maintained by a small group of stem cells ( SCs ) that replicate slowly to maintain their own population and that give ri...	[ "In multicellular organisms , tissues such as skin , the gut , and blood undergo continuous cell turnover .", "These tissues are maintained by a small group of tightly regulated cells known as stem cells ( SCs ) that have two defining properties: they can renew themselves and give rise to more specialized cells t...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell binding", "cell physiology", "medicine and health sciences", "immune cells", "gene regulation", "immunology", "messenger rna", "micrornas", "cellular structures and organelles", "white blood cells", "animal cells", "gene expression", "ribosomes", "biochemistry", "r...	Differential Sensitivity of Target Genes to Translational Repression by miR-17~92	journal.pgen.1006623	null	[ [ "MicroRNAs ( miRNAs ) are endogenously encoded single stranded RNAs of about 22 nucleotides ( nts ) in length .", "They suppress target gene expression by translational repression and promoting mRNA degradation .", "The relative contribution of these two modes of action to miRNA regulation of its targ...	[ "MicroRNAs ( miRNAs ) are thought to exert their functions by modulating the expression of hundreds of target genes and each to a small degree , but it remains unclear how small changes in hundreds of target genes are translated into the specific function of a miRNA .", "Here , we conducted an integrated analysis...	[ "MicroRNAs ( miRNAs ) are small RNAs encoded by our genome .", "Each miRNA binds hundreds of target mRNAs and performs specific functions .", "It is thought that miRNAs exert their function by reducing the expression of all these target genes and each to a small degree .", "However , these target genes often ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "genome expression analysis", "genomics", "genetic polymorphism", "gene expression", "genetics", "epigenetics", "biology", "population genetics", "chromatin", "genetics and genomics" ]	Genetic Landscape of Open Chromatin in Yeast	journal.pgen.1003229	null	[ [ "The genetic basis of gene expression has been studied in various organisms [1]–[5] .", "For example , two different strains of Saccharomyces cerevisiae ( BY and RM ) were crossed to produce a number of different genetic recombinants , and their expression levels and genotypes were analyzed [1] , [6] .", ...	[ "Chromatin regulation underlies a variety of DNA metabolism processes , including transcription , recombination , repair , and replication .", "To perform a quantitative genetic analysis of chromatin accessibility , we obtained open chromatin profiles across 96 genetically different yeast strains by FAIRE ( forma...	[ "Quantitative trait loci ( QTL ) mapping is a genetic approach that allows the identification of genetic factors underlying a phenotype of interest .", "Genomic technologies such as DNA microarray and next-generation sequencing provide data that can be used for the analysis of multiple molecular phenotypes .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Functional Divergence in the Role of N-Linked Glycosylation in Smoothened Signaling	journal.pgen.1005473	null	[ [ "The Hedgehog ( Hh ) signaling pathway contributes to developmental patterning and adult tissue homeostasis , and when corrupted , can contribute to tumor initiation and maintenance [1–3] .", "Originally identified in Drosophila , the Smoothened ( Smo ) protein is an evolutionarily conserved G protein-cou...	[ "The G protein-coupled receptor ( GPCR ) Smoothened ( Smo ) is the requisite signal transducer of the evolutionarily conserved Hedgehog ( Hh ) pathway .", "Although aspects of Smo signaling are conserved from Drosophila to vertebrates , significant differences have evolved .", "These include changes in its acti...	[ "N-linked glycosylation is a post-translational modification occurring on membrane proteins such as G protein-coupled receptors ( GPCR ) .", "Smoothened ( Smo ) is a GPCR that functions as the signal transducer of the Hedgehog ( Hh ) pathway .", "We used a mutagenesis approach to assess the role of N-glycans in...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/molecular dynamics", "pharmacology/drug development" ]	High-Performance Drug Discovery: Computational Screening by Combining Docking and Molecular Dynamics Simulations	journal.pcbi.1000528	null	[ [ "In our screening approach , we adopted molecular docking and the MM/PB-SA method based on MD simulations as the first and second filters , respectively .", "First , we performed molecular docking by using the conformations of a target protein and the compounds contained in the compound library .", "A...	[ "Virtual compound screening using molecular docking is widely used in the discovery of new lead compounds for drug design .", "However , this method is not completely reliable and therefore unsatisfactory .", "In this study , we used massive molecular dynamics simulations of protein-ligand conformations obtaine...	[ "Lead discovery is one of the most important processes in rational drug design .", "To improve the rate of the detection of lead compounds , various technologies such as high-throughput screening and combinatorial chemistry have been introduced into the pharmaceutical industry .", "However , since these technol...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/cellular microbiology and pathogenesis" ]	A New Family of Lysozyme Inhibitors Contributing to Lysozyme Tolerance in Gram-Negative Bacteria	journal.ppat.1000019	null	[ [ "Lysozymes ( EC 3 . 2 . 1 . 17 ) hydrolyse the β- ( 1 , 4 ) glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycan , the major cell wall polymer in the Bacteria .", "Peptidoglycan forms a network that surrounds the entire bacterial cell , and its hydrolysis by lysozyme rende...	[ "Lysozymes are ancient and important components of the innate immune system of animals that hydrolyze peptidoglycan , the major bacterial cell wall polymer .", "Bacteria engaging in commensal or pathogenic interactions with an animal host have evolved various strategies to evade this bactericidal enzyme , one rec...	[ "Lysozyme is an ancient bactericidal enzyme that is part of the antibacterial defense system of vertebrate and invertebrate animals .", "Bacteria colonizing or infecting an animal host have developed various ways to overcome lysozyme action , a recently proposed mechanism being the production of lysozyme inhibito...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "phosphorylation", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "intracellular pathogens", "toxoplasma gondii", "pathogens", "immunology", "parasitic protozoans", "protozoans", "toxoplasma", "bacteria", "contractile proteins", "actin...	Toxoplasma gondii GRA7-Targeted ASC and PLD1 Promote Antibacterial Host Defense via PKCα	journal.ppat.1006126	null	[ [ "Tuberculosis ( TB ) is an infectious disease caused by Mycobacterium tuberculosis ( MTB ) [1] .", "The World Health Organization reported that in 2014 , 9 . 6 million cases and 1 . 5 million deaths were globally [2] .", "Recent developments in TB drug-development strategies ( including new and repurp...	[ "Tuberculosis is a global health problem and at least one-third of the world’s population is infected with Mycobacterium tuberculosis ( MTB ) .", "MTB is a successful pathogen that enhances its own intracellular survival by inhibiting inflammation and arresting phago-lysosomal fusion .", "We previously demonstr...	[ "We previously demonstrated that Toxoplasma gondii ( T . gondii ) dense granule antigen ( GRA ) 7 interacts with TRAF6 via MyD88 , enabling innate immune responses in macrophages and effective protection against T . gondii infection in vivo .", "However , its exact role and how it regulates host innate immune res...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "rift valley fever virus", "body fluids", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "geographical locations", "microbiology", "viral structure", "saliva", "animals", "viruses", "rna viruses", "in...	Experimental transmission of West Nile Virus and Rift Valley Fever Virus by Culex pipiens from Lebanon	journal.pntd.0005983	null	[ [ "West Nile virus ( WNV ) and Rift Valley fever virus ( RVFV ) are two important emerging mosquito-borne zoonotic agents transmitted by Culex pipiens , a complex of sibling species that includes Cx .", "pipiens s . s . , Cx .", "quinquefasciatus and possibly Cx .", "australicus [1 , 2] .", "Cx ...	[ "West Nile virus ( WNV ) and Rift Valley fever virus ( RVFV ) are two emerging arboviruses transmitted by Culex pipiens species that includes two biotypes: pipiens and molestus .", "In Lebanon , human cases caused by WNV and RVFV have never been reported .", "However , the introduction of these viruses in the c...	[ "West Nile virus ( WNV ) and Rift Valley fever virus ( RVFV ) are two emerging mosquito-borne arboviruses mainly transmitted by Culex mosquitoes .", "WNV considered one of the most important causative agent of viral encephalitis has a wide distribution in many tropical and temperate countries including the Middle...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "meiosis", "chromosome biology", "biology" ]	Variation in Genome-Wide Levels of Meiotic Recombination Is Established at the Onset of Prophase in Mammalian Males	journal.pgen.1004125	null	[ [ "Recombination is a defining event of meiosis , resulting in the physical exchange of DNA between homologous chromosomes .", "It is generally thought that this is essential for proper alignment and subsequent segregation of homologs during meiosis I and , indeed , evidence from yeast [1] , [2] , Caenorhab...	[ "Segregation of chromosomes during the first meiotic division relies on crossovers established during prophase .", "Although crossovers are strictly regulated so that at least one occurs per chromosome , individual variation in crossover levels is not uncommon .", "In an analysis of different inbred strains of ...	[ "During prophase of meiosis , homologous chromosomes exchange genetic material , in a process known as crossing-over .", "Crossovers are thought to be essential for proper separation of chromosomes during meiosis but , surprisingly , most mammalian species exhibit substantial individual variation in the number of...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "complement system", "medicine and health sciences", "immune physiology", "immune cells", "pathology and laboratory medicine", "body fluids", "pathogens", "immunology", "microbiology", "animal models", "bacterial diseases", "model organisms", "experimental organism systems",...	Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase	journal.ppat.1006493	null	[ [ "The complement cascade is crucial for clearance of invading pathogens and thus represents a key target for disruption by such organisms .", "Individual bacterial species use multiple strategies to escape the complement system , highlighting the importance of this pathway in bacterial immunity [1–7] .", ...	[ "The complement cascade is crucial for clearance and control of invading pathogens , and as such is a key target for pathogen mediated host modulation .", "C3 is the central molecule of the complement cascade , and plays a vital role in opsonization of bacteria and recruitment of neutrophils to the site of infect...	[ "The complement pathway is critical in the innate immune response to bacterial pathogens .", "It consists of a self-perpetuating proteolytic cascade initiated via three distinct pathways that converge at the central complement protein , C3 .", "Pathogens must evade complement-mediated immunity to cause disease ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious disease immunology", "medicine and health sciences", "clinical immunology", "medical microbiology", "microsporidia", "microbial pathogens", "biology and life sciences", "immunology", "microbiology", "fungal pathogens" ]	Identification of the Microsporidian Encephalitozoon cuniculi as a New Target of the IFNγ-Inducible IRG Resistance System	journal.ppat.1004449	null	[ [ "The IFNγ-inducible , immunity-related GTPases ( IRG proteins ) are a family of proteins essential for innate resistance of mice against certain intracellular pathogens .", "Until now , the protozoon Toxoplasma gondii [1] , [2] , [3] , [4] , [5] and its very close relative , Neospora caninum [6] , [7] , a...	[ "The IRG system of IFNγ-inducible GTPases constitutes a powerful resistance mechanism in mice against Toxoplasma gondii and two Chlamydia strains but not against many other bacteria and protozoa .", "Why only T . gondii and Chlamydia ?", "We hypothesized that unusual features of the entry mechanisms and intrace...	[ "For some time we have studied an intracellular resistance system essential for mice to survive infection with the intracellular protozoan , Toxoplasma gondii , that is based on a family of proteins , immunity-related GTPases or IRG proteins .", "Immediately after the parasite enters a cell , IRG proteins accumul...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "computational biology/genomics" ]	Systematic Inference of Copy-Number Genotypes from Personal Genome Sequencing Data Reveals Extensive Olfactory Receptor Gene Content Diversity	journal.pcbi.1000988	null	[ [ "Structural variants in the human genome , such as CNVs or balanced inversions , represent a major form of variation with widespread functional consequences [1] .", "Numerous surveys mapping CNVs at varying levels of resolution [2] , [3] , [4] , [5] , [6] have created a comprehensive CNV inventory , with ...	[ "Copy-number variations ( CNVs ) are widespread in the human genome , but comprehensive assignments of integer locus copy-numbers ( i . e . , copy-number genotypes ) that , for example , enable discrimination of homozygous from heterozygous CNVs , have remained challenging .", "Here we present CopySeq , a novel c...	[ "Human individual genome sequencing has recently become affordable , enabling highly detailed genetic sequence comparisons .", "While the identification and genotyping of single-nucleotide polymorphisms has already been successfully established for different sequencing platforms , the detection , quantification a...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "microbiology", "evolutionary biology", "eubacteria" ]	Recombination Speeds Adaptation by Reducing Competition between Beneficial Mutations in Populations of Escherichia coli	journal.pbio.0050225	Why there is sexual reproduction is an important question. Here the authors show that making bacteria have sex allows faster accumulation and fixation of beneficial mutations.	[ [ "Understanding the factors that contribute to the origin and maintenance of sex is an important unanswered problem in evolutionary biology [1–4] .", "A large body of research has developed several theories predicting potential advantages to sex ( reviewed in [3] ) .", "However , critical support for t...	[ "Identification of the selective forces contributing to the origin and maintenance of sex is a fundamental problem in biology .", "The Fisher–Muller model proposes that sex is advantageous because it allows beneficial mutations that arise in different lineages to recombine , thereby reducing clonal interference a...	[ "Why have sex ?", "One explanation is that sex is good because it allows beneficial mutations from different lineages to recombine .", "This reduces competition between mutations in a population and can increase the speed with which the population can adapt to environmental change .", "This explanation , know...	2007

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