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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" ]	[ "biology and life sciences", "medicine and health sciences" ]	IL-1α and Complement Cooperate in Triggering Local Neutrophilic Inflammation in Response to Adenovirus and Eliminating Virus-Containing Cells	journal.ppat.1004035	null	[ [ "Viral vectors based on adenovirus of human and animal types have been widely adapted for gene transfer applications both in vitro and in vivo .", "Adenovirus ( Ad ) is remarkably efficient at infecting both dividing and non-dividing cells and its non-enveloped capsid tolerates major modifications that ma...	[ "Inflammation is a highly coordinated host response to infection , injury , or cell stress .", "In most instances , the inflammatory response is pro-survival and is aimed at restoring physiological tissue homeostasis and eliminating invading pathogens , although exuberant inflammation can lead to tissue damage an...	[ "Adenovirus ( Ad ) induces a potent activation of pro-inflammatory cytokines and chemokines upon interaction with tissue macrophages in vivo .", "However , critical factors affecting cellular inflammatory responses to Ad and their functional significance remain unclear .", "Here we show that in the model of dis...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Suppression of Interferon Lambda Signaling by SOCS-1 Results in Their Excessive Production during Influenza Virus Infection	journal.ppat.1003845	null	[ [ "Influenza A virus ( IAV ) , a highly infectious respiratory pathogen , causes worldwide annual epidemics and occasional pandemics .", "Therefore , IAV has continued to be a top global public health threat .", "The host cytokine immune response provides the first line of defense against IAV infection ...	[ "Innate cytokine response provides the first line of defense against influenza virus infection .", "However , excessive production of cytokines appears to be critical in the pathogenesis of influenza virus .", "Interferon lambdas ( IFN-λ ) have been shown to be overproduced during influenza virus infection , bu...	[ "Influenza virus infection triggers innate immune responses .", "However , aberrant host immune responses such as excessive production of cytokines contribute to the pathogenesis of influenza virus .", "Type III interferons ( IFN-λ ) constitute the major innate immune response to influenza virus infection , but...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "medicine", "tumor physiology", "gene expression", "biology", "basic cancer research", "molecular cell biology", "dna transcription" ]	Characterization of the p53 Cistrome – DNA Binding Cooperativity Dissects p53's Tumor Suppressor Functions	journal.pgen.1003726	null	[ [ "The prominence of the p53 gene in tumor suppression is emphasized by its unsurpassed mutation rate in cancer cells [1] .", "As a master regulatory transcription factor for anti-proliferative programs , p53 can decide cell fate in response to a broad range of stress stimuli , including DNA damage and onco...	[ "p53 protects us from cancer by transcriptionally regulating tumor suppressive programs designed to either prevent the development or clonal expansion of malignant cells .", "How p53 selects target genes in the genome in a context- and tissue-specific manner remains largely obscure .", "There is growing evidenc...	[ "The tumor suppressor gene p53 counteracts tumor growth by activating genes that prevent cell proliferation or induce cell death .", "How p53 selects genes in the genome to direct cell fate specifically into one or the other direction remains unclear .", "We show that the ability of p53 molecules to interact an...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models of infection", "viral clearance", "genetic mutation", "virulence factors and mechanisms", "viral transmission and infection", "virology", "genetics", "host-pathogen interaction", "biology", "microbiology", "evolutionary biology", "viral replication", "evolutionary genetics", ...	Evolution of the Retroviral Restriction Gene Fv1: Inhibition of Non-MLV Retroviruses	journal.ppat.1003968	null	[ [ "Viruses co-evolve with their hosts , upon which they are completely dependent for replication .", "As the host acquires strategies to restrict virus infection the invaders develop counter measures to evade restriction .", "The ensuing genetic conflict can play out over an extensive timeframe [1] , [2...	[ "Fv1 is the prototypic restriction factor that protects against infection by the murine leukemia virus ( MLV ) .", "It was first identified in cells that were derived from laboratory mice and was found to be homologous to the gag gene of an endogenous retrovirus ( ERV ) .", "To understand the evolution of the h...	[ "We have followed the evolution of the retroviral restriction gene , Fv1 , by functional analysis .", "We show that Fv1 can recognize and restrict a wider range of retroviruses than previously thought including examples from the gammaretrovirus , lentivirus and foamy virus genera .", "Nearly every Fv1 tested sh...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene regulation", "rna extraction", "dna-binding proteins", "dna transcription", "epigenetics", "extraction techniques", "chromatin", "research and analysis methods", "small interfering rnas", "genome complexity", "genomics", "chromosome biology", "proteins", "gene expression", "rna spl...	A Broad Set of Chromatin Factors Influences Splicing	journal.pgen.1006318	null	[ [ "The transcribed region of almost all human genes contains introns that must be excised from the pre-mRNA for the exons to be spliced together .", "This process provides an opportunity to modify the exon content of the mature mRNA and , as such , must be regarded as a powerful source of RNA diversity .", ...	[ "Several studies propose an influence of chromatin on pre-mRNA splicing , but it is still unclear how widespread and how direct this phenomenon is .", "We find here that when assembled in vivo , the U2 snRNP co-purifies with a subset of chromatin-proteins , including histones and remodeling complexes like SWI/SNF...	[ "Splicing is an RNA editing step allowing to produce multiple transcripts from a single gene .", "The gene itself is organized in chromatin , associating DNA and multiple proteins .", "Some proteins regulating the compaction of the chromatin also affect RNA splicing .", "Yet , it was unclear whether these chr...	2016
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biophysics/theory and simulation", "biochemistry/cell signaling and trafficking structures", "biochemistry/bioinformatics", "biochemistry/theory and simulation", "computational biology/molecular dynamics", "biophysics/cell signaling and trafficking structures" ]	Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics	journal.pcbi.1000325	null	[ [ "Ras proteins are guanine nucleotide-dependent conformational switches that couple cell-surface receptors to signaling pathways that mediate cell proliferation , growth and development [1] .", "Signal propagation through Ras is mediated by a regulated GTPase cycle that induces distinct conformations with ...	[ "Ras mediates signaling pathways controlling cell proliferation and development by cycling between GTP- and GDP-bound active and inactive conformational states .", "Understanding the complete reaction path of this conformational change and its intermediary structures is critical to understanding Ras signaling .",...	[ "The Ras family of enzymes mediate signaling pathways controlling cell proliferation and development by cycling between active and inactive conformational states .", "Mutations that affect the ability to switch between states are associated with a variety of cancers .", "However , details of how the structural ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chromosome structure and function", "gene regulation", "cell cycle and cell division", "cell processes", "dna transcription", "mitosis", "fungi", "chromatin", "schizosaccharomyces", "chromosome biology", "gene expression", "schizosaccharomyces pombe", "molecular biology", "yeast", "bioc...	RNA Processing Factors Swd2.2 and Sen1 Antagonize RNA Pol III-Dependent Transcription and the Localization of Condensin at Pol III Genes	journal.pgen.1004794	null	[ [ "Mitotic chromosome condensation is essential for genome integrity .", "When defective , chromosomes often remain entangled and fail to segregate properly in anaphase .", "A key driver of chromosome condensation is the highly conserved condensin complex .", "Condensin is made of five sub-units ( S...	[ "Condensin-mediated chromosome condensation is essential for genome stability upon cell division .", "Genetic studies have indicated that the association of condensin with chromatin is intimately linked to gene transcription , but what transcription-associated feature ( s ) direct ( s ) the accumulation of conden...	[ "Failure to condense chromosomes prior to anaphase onset can lead to genome instability .", "The evolutionary-conserved condensin complex drives chromosome condensation , probably by changing the topology of chromatin around its binding sites .", "Condensin localizes to regions of high transcription , suggestin...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "developmental biology", "animal genetics", "organism development", "genome analysis", "genetics", "biology and life sciences", "molecular genetics", "computational biology", "genetics of disease", "veterinary science", "veterinary medicine" ]	A LINE-1 Insertion in DLX6 Is Responsible for Cleft Palate and Mandibular Abnormalities in a Canine Model of Pierre Robin Sequence	journal.pgen.1004257	null	[ [ "Cleft palate ( CP ) is one of the most commonly occurring craniofacial birth defects , affecting approximately 1 in 1500 live human births in the United States [1] .", "Children born with CP may develop hearing loss , difficulties with speech and eating , and may be at an increased risk for psychiatric d...	[ "Cleft palate ( CP ) is one of the most commonly occurring craniofacial birth defects in humans .", "In order to study cleft palate in a naturally occurring model system , we utilized the Nova Scotia Duck Tolling Retriever ( NSDTR ) dog breed .", "Micro-computed tomography analysis of CP NSDTR craniofacial stru...	[ "Cleft palate is one of the most commonly occurring birth defects in children , and yet its cause is not completely understood .", "In order to better understand cleft palate we have turned to man's best friend , the domestic dog .", "Common breeding practices have made the dog a unique animal model to help und...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	MAGMA: Generalized Gene-Set Analysis of GWAS Data	journal.pcbi.1004219	null	[ [ "In the past decade , genome-wide association studies ( GWAS ) have successfully identified new genetic variants for a wide variety of phenotypes [1] .", "However , despite growing sample sizes , the genetic variants discovered by GWAS generally account for only a fraction of the total heritability of a p...	[ "By aggregating data for complex traits in a biologically meaningful way , gene and gene-set analysis constitute a valuable addition to single-marker analysis .", "However , although various methods for gene and gene-set analysis currently exist , they generally suffer from a number of issues .", "Statistical p...	[ "Gene and gene-set analysis are statistical methods for analysing multiple genetic markers simultaneously to determine their joint effect .", "These methods can be used when the effects of individual markers is too weak to detect , which is a common problem when studying polygenic traits .", "Moreover , gene-se...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "histology", "functional genomics", "interstitial lung diseases", "gene regulation", "genetics", "molecular genetics", "biology", "genomics", "genetics and genomics", "respiratory medicine", "pulmonology" ]	miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1	journal.pgen.1003291	null	[ [ "Tissue fibrosis , defined as the excessive and persistent formation of non functional scar tissue in response to repeated injury and insult , is a leading cause of morbidity and mortality associated with organ failure in various chronic diseases such as those affecting the lung interstitium [1] .", "Amon...	[ "As miRNAs are associated with normal cellular processes , deregulation of miRNAs is thought to play a causative role in many complex diseases .", "Nevertheless , the precise contribution of miRNAs in fibrotic lung diseases , especially the idiopathic form ( IPF ) , remains poorly understood .", "Given the poor...	[ "Fibrosis is the final common pathway in virtually all forms of chronic organ failure , including lung , liver , and kidney , and is a leading cause of morbidity and mortality worldwide .", "Fibrosis results from the excessive activity of fibroblasts , in particular a differentiated form known as myofibroblast th...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "sexually transmitted diseases", "aids", "histoplasmosis", "neglected tropical diseases", "fungal diseases", "viral diseases", "infectious disease control", "tropical diseases" ]	HIV-Associated Histoplasmosis Early Mortality and Incidence Trends: From Neglect to Priority	journal.pntd.0003100	null	[ [ "French Guiana is a French overseas territory , located in the North-Eastern part of South America .", "The Human Immunodeficiency Virus ( HIV ) epidemic there is the most preoccupying among French territories [1] .", "During the Highly Active AntiRetroviral Therapy ( HAART ) era , disseminated histop...	[ "Histoplasmosis is an endemic fungal infection in French Guiana .", "It is the most common AIDS-defining illness and the leading cause of AIDS-related deaths .", "Diagnosis is difficult , but in the past 2 decades , it has improved in this French overseas territory which offers an interesting model of Amazonian...	[ "Histoplasmosis is an endemic fungal infection in French Guiana .", "It is the most common AIDS-defining illness and the leading cause of AIDS-related deaths .", "Diagnosis is difficult , but in the past 2 decades , it has improved .", "The objectives of the present study were to describe the temporal trends ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "borrelia infection", "medicine and health sciences", "body fluids", "enzyme-linked immunoassays", "pathology and laboratory medicine", "immune physiology", "pathogens", "immunology", "microbiology", "animal models", "bacterial diseases", "model organisms", "antibodies", "immunologic techn...	Borrelia persica Infection in Immunocompetent Mice - A New Tool to Study the Infection Kinetics In Vivo	journal.pntd.0004404	null	[ [ "Spirochetes of the genus Borrelia ( B . ) are vector-borne , spiral-shaped bacteria that can be divided into two functional groups [1] .", "One large group of spirochetes belongs to the B . burgdorferi sensu lato complex ( e . g . B . burgdorferi sensu stricto , B . afzelii , B . garinii , B . bavariensi...	[ "Borrelia persica , a bacterium transmitted by the soft tick Ornithodoros tholozani , causes tick-borne relapsing fever in humans in the Middle East , Central Asia and the Indian peninsula .", "Immunocompetent C3H/HeOuJ mice were infected intradermally with B . persica at varying doses: 1 x 106 , 1 x 104 , 1 x 10...	[ "The spirochete Borrelia persica is a tick-borne bacterium that is transmitted by the vector Ornithodoros tholozani to its vertebrate host in the Middle East , Central Asia and the Indian peninsula .", "Current migration of vast numbers of individuals from this area increases the likelihood that B . persica infec...	2016
[ "Introduction", "Results/Discussion", "Methods" ]	[ "cell biology/membranes and sorting", "neuroscience", "genetics and genomics/disease models", "neurological disorders/movement disorders" ]	The Ataxia (axJ) Mutation Causes Abnormal GABAA Receptor Turnover in Mice	journal.pgen.1000631	null	[ [ "A number of heterogeneous hereditary and non-hereditary disorders lead to ataxia characterized by coordination failures [1] , [2] , [3] .", "The spontaneous axJ mutation affects the locomotory system , causing an ataxic phenotype in mice [4] .", "The mutated gene encodes the deubiquitinating enzyme (...	[ "Ataxia represents a pathological coordination failure that often involves functional disturbances in cerebellar circuits .", "Purkinje cells ( PCs ) characterize the only output neurons of the cerebellar cortex and critically participate in regulating motor coordination .", "Although different genetic mutation...	[ "Cerebellar ataxia describes a combination of motor symptoms and uncoordinated movements that originates from various hereditary and non-hereditary diseases .", "Although functional disturbances of cerebellar inhibitory output signals are thought to cause ataxia , the underlying molecular mechanisms are barely un...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology" ]	A Global Assessment of Salmon Aquaculture Impacts on Wild Salmonids	journal.pbio.0060033	Comparing the survival of wild salmonid populations in areas near salmon farms with unexposed populations reveals a large reduction in survival in the populations reared near salmon farms.	[ [ "Since the late 1970s , salmon aquaculture has grown into a global industry , producing over 1 million tonnes of salmon per year [1] .", "The majority of this biomass is held in open net pens in coastal areas through which wild salmon migrate on their way to and from the ocean .", "A number of studies...	[ "Since the late 1980s , wild salmon catch and abundance have declined dramatically in the North Atlantic and in much of the northeastern Pacific south of Alaska .", "In these areas , there has been a concomitant increase in the production of farmed salmon .", "Previous studies have shown negative impacts on wil...	[ "The impact of salmon farming on wild salmon and trout is a hotly debated issue in all countries where salmon farms and wild salmon coexist .", "Studies have clearly shown that escaped farm salmon breed with wild populations to the detriment of the wild stocks , and that diseases and parasites are passed from far...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models of infection", "viral entry", "host cells", "viral persistence and latency", "viral transmission and infection", "virology", "neurovirulence", "biology", "microbiology" ]	Entry of Herpes Simplex Virus Type 1 (HSV-1) into the Distal Axons of Trigeminal Neurons Favors the Onset of Nonproductive, Silent Infection	journal.ppat.1002679	null	[ [ "Herpes simplex virus type 1 ( HSV-1 ) and 2 ( HSV-2 ) are prototypic members of the genus Simplexvirus within the herpesvirus subfamily Alphaherpesvirinae .", "In vitro , HSVs are pantropic , causing lytic infections in various tissues and cell types of a broad range of host species [1] .", "In vivo ...	[ "Following productive , lytic infection in epithelia , herpes simplex virus type 1 ( HSV-1 ) establishes a lifelong latent infection in sensory neurons that is interrupted by episodes of reactivation .", "In order to better understand what triggers this lytic/latent decision in neurons , we set up an organotypic ...	[ "Upon primary infection of the oronasal mucosa , herpes simplex virus type 1 ( HSV-1 ) rapidly reaches the ganglia of the peripheral nervous system via axonal transport and establishes lifelong latency in surviving neurons .", "Central to the establishment of latency is the ability of HSV-1 to reliably switch fro...	2012
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "circuit models", "computer science", "psychology", "computer modeling", "social and behavioral sciences", "cognitive psychology", "neural networks", "computational neuroscience", "memory", "biology", "computerized simulations", "neuroscience", "learning and memory", "coding mechanisms" ]	Theta Coordinated Error-Driven Learning in the Hippocampus	journal.pcbi.1003067	null	[ [ "Over the past half century the hippocampus has provided fertile ground for the work of mechanistic computational models to inform empirical research .", "From the earliest investigations into Long Term Potentiation to the complex dynamics of place cells , models of hippocampal function have enabled a gre...	[ "The learning mechanism in the hippocampus has almost universally been assumed to be Hebbian in nature , where individual neurons in an engram join together with synaptic weight increases to support facilitated recall of memories later .", "However , it is also widely known that Hebbian learning mechanisms impose...	[ "We present a novel hippocampal model based on the oscillatory dynamics of the theta rhythm , which enables the network to learn much more efficiently than the Hebbian form of learning that is widely assumed in most models .", "Specifically , two pathways , Tri-Synaptic and Mono-Synaptic , alternate in strength d...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Development of Ss-NIE-1 Recombinant Antigen Based Assays for Immunodiagnosis of Strongyloidiasis	journal.pntd.0003694	null	[ [ "Strongyloides stercoralis , an intestinal nematode that migrates through the skin and lung , is a widely distributed disease that infects 30 to 100 million people worldwide [1] .", "Unlike other helminthic parasites , S . stercoralis can complete its entire life cycle within a single human host through a...	[ "Strongyloides stercoralis is a widely distributed parasite that infects 30 to 100 million people worldwide .", "In the United States strongyloidiasis is recognized as an important infection in immigrants and refugees .", "Public health and commercial reference laboratories need a simple and reliable method for...	[ "Strongyloidiasis is a neglected tropical disease that affects millions worldwide and needs more attention and better diagnostic methods .", "Strongyloides stercoralis can undergo an autoinfection cycle and can cause hyperinfection involving the pulmonary and gastrointestinal systems and disseminated infection in...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "tropical diseases", "parasitic diseases", "parasitic protozoans", "parasitology", "parasitemia", "organisms", "protozoans", "neglected tropical diseases", "molecular biology techniques", "quantitative parasitology", "cryst...	Molecular Diagnosis of Chagas Disease in Colombia: Parasitic Loads and Discrete Typing Units in Patients from Acute and Chronic Phases	journal.pntd.0004997	null	[ [ "Chagas disease is a zoonotic parasitic disease caused by the protozoan Trypanosoma cruzi .", "It is considered a public health problem in Latin-America , where approximately 6 million people are currently infected [1] .", "The acute phase of the disease is characterised by usually mild fever that in ...	[ "The diagnosis of Chagas disease is complex due to the dynamics of parasitemia in the clinical phases of the disease .", "The molecular tests have been considered promissory because they detect the parasite in all clinical phases .", "Trypanosoma cruzi presents significant genetic variability and is classified ...	[ "Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi that shows tremendous genetic diversity evinced in at least six Discrete Typing Units and massive genetic diversity within TcI .", "Two clinical phases exist where acute phase shows high parasitemia and chronic phase shows lo...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "vesicles", "nervous system", "cell processes", "electrophysiology", "neuroscience", "motor neurons", "developmental biology", "molecular motors", "nerve fibers", "cellular structures and organelles", "motor proteins", "endosomes", "animal cells", "axons",...	Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction	journal.pgen.1007184	null	[ [ "Bidirectional communication between the neuronal cell body and distant synaptic terminals is essential for synapse formation , plasticity and neuronal survival [1 , 2] .", "This is achieved primarily through highly regulated axonal transport .", "Anterograde transport is mediated by plus-end directed...	[ "Retrograde signaling is essential for neuronal growth , function and survival; however , we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways .", "We have identified Khc-73 , a plus-end directed microtubule motor protein , as a regulator of sortin...	[ "Retrograde axonal transport is essential for normal synaptic function and neuronal survival .", "How endosomes are specifically sorted from the synaptic terminal for retrograde axonal transport is currently not known .", "At the Drosophila neuromuscular junction , receptors for the Bone Morphogenic Protein sig...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Activin Signaling Targeted by Insulin/dFOXO Regulates Aging and Muscle Proteostasis in Drosophila	journal.pgen.1003941	null	[ [ "Reduced insulin/IGF-1 signaling increases the lifespan of nematodes , flies and rodents [1] , [2] .", "In Caenorhabditis elegans , mutants in insulin-like receptor daf-2 live twice as long as wild type [3] , [4] .", "Mutation of insulin receptor InR and insulin receptor substrate ( chico ) increase a...	[ "Reduced insulin/IGF signaling increases lifespan in many animals .", "To understand how insulin/IGF mediates lifespan in Drosophila , we performed chromatin immunoprecipitation-sequencing analysis with the insulin/IGF regulated transcription factor dFOXO in long-lived insulin/IGF signaling genotypes .", "Dawdl...	[ "It is widely known that reduced insulin/IGF signaling slows aging in many contexts .", "This process requires the forkhead transcription factor ( FOXO ) .", "FOXO modulates the expression of many genes , and the list of those associated with slow aging is impressive .", "But there are few data indicating the...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Structural and Functional Characterization of the Enantiomers of the Antischistosomal Drug Oxamniquine	journal.pntd.0004132	null	[ [ "For more than 25 years , the mainstay of treatment for Schistosoma mansoni infections in Brazil was the drug oxamniquine ( OXA , ( RS ) -1 , 2 , 3 , 4-tetrahydro-2- isopropylaminomethyl-7-nitro-6-quinolylmethanol ) [1 , 2] .", "OXA is species-specific , killing S . mansoni ( 67 million cases worldwide ) ...	[ "For over two decades , a racemic mixture of oxamniquine ( OXA ) was administered to patients infected by Schistosoma mansoni , but whether one or both enantiomers exert antischistosomal activity was unknown .", "Recently , a ~30 kDa S . mansoni sulfotransferase ( SmSULT ) was identified as the target of OXA acti...	[ "Schistosomes , parasites that cause the disease schistosomiasis in humans , are blood flukes that infect an estimated 200 million people in 76 countries .", "Control of schistosomiasis is currently based on repeated doses of the drug praziquantel ( PZQ ) .", "Parasites showing reduced susceptibility to PZQ hav...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "hematopoiesis", "genetics", "genetics and genomics", "biology", "genetics of disease", "hematology" ]	Collapse of Telomere Homeostasis in Hematopoietic Cells Caused by Heterozygous Mutations in Telomerase Genes	journal.pgen.1002696	null	[ [ "At least a few hundred nucleotides of telomere repeats must “cap” each chromosome end in order to suppress DNA damage signals and avoid the activation of DNA repair pathways [1]–[3] .", "Critically short or “uncapped” telomeres may be repaired by the enzyme telomerase [4] or by recombination [5] .", ...	[ "Telomerase activity is readily detectable in extracts from human hematopoietic stem and progenitor cells , but appears unable to maintain telomere length with proliferation in vitro and with age in vivo .", "We performed a detailed study of the telomere length by flow FISH analysis in leukocytes from 835 healthy...	[ "Human blood cells all originate from a common precursor , the hematopoietic stem cell .", "Telomerase , the enzyme responsible for adding telomere repeats to chromosome ends , is active in human hematopoietic stem cells but appears unable to maintain a constant telomere length with age .", "We first document t...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Drosophila Zinc Finger Transcription Factor Ouija Board Controls Ecdysteroid Biosynthesis through Specific Regulation of spookier	journal.pgen.1005712	null	[ [ "Steroid hormones are responsible for the coordination and regulation of many biological events during development of multicellular organisms .", "In all species , steroid hormones are synthesized from cholesterol and/or other phytosterols by multiple steroidogenic enzymes , epitomized by the members of t...	[ "Steroid hormones are crucial for many biological events in multicellular organisms .", "In insects , the principal steroid hormones are ecdysteroids , which play essential roles in regulating molting and metamorphosis .", "During larval and pupal development , ecdysteroids are synthesized in the prothoracic gl...	[ "Steroid hormones are crucial for development and reproduction in multicellular organisms .", "The spatially-restricted expression of almost all steroid biosynthesis genes is key to the specialization of steroid producing cells .", "In the last decade , insects have become the focus for research on the biosynth...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "clinical research design", "virology", "clinical trials", "dengue fever", "neglected tropical diseases", "dengue", "biology", "microbiology", "viral diseases" ]	Kinetics of Viremia and NS1 Antigenemia Are Shaped by Immune Status and Virus Serotype in Adults with Dengue	journal.pntd.0001309	null	[ [ "Dengue viruses ( DENVs ) are members of the Flavivirus genus and are the most important arboviral pathogens of humans .", "The four DENVs are antigenically-related and have single-stranded , positive-sense RNA genomes that share 60–70% sequence identity between each others [1] .", "There are no licen...	[ "Dengue is a major public health problem in tropical and subtropical countries .", "Exploring the relationships between virological features of infection with patient immune status and outcome may help to identify predictors of disease severity and enable rational therapeutic strategies .", "Clinical features ,...	[ "Dengue is an acute viral disease that affects tens of millions of people annually in tropical and sub-tropical countries .", "In some cases , this infection happens to be severe and even life threatening .", "Severe cases have been associated with higher levels of virus in the blood .", "Several hypotheses h...	2011
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "animal models", "drosophila melanogaster", "model organisms", "genetics of the immune system", "immunity", "innate immunity", "genetics", "parasitology", "immunology", "biology", "zoology", "genetics and genomics", "immune response" ]	Mgat1-dependent N-glycosylation of Membrane Components Primes Drosophila melanogaster Blood Cells for the Cellular Encapsulation Response	journal.ppat.1002819	null	[ [ "Cellular encapsulation of invading organisms is a vital and conserved aspect of insect immunity [1] , [2] .", "In this immune response the invader is recognized as foreign and then surrounded by a multilayered capsule of immune cells which serves to kill or sequester it .", "Capsule formation can be ...	[ "In nature , larvae of the fruitfly Drosophila melanogaster are commonly infected by parasitoid wasps , and so have evolved a robust immune response to counter wasp infection .", "In this response , fly immune cells form a multilayered capsule surrounding the wasp egg , leading to death of the parasite .", "Man...	[ "Organisms such as the fruitfly Drosophila melanogaster have long been used as model systems to understand complex aspects of human biology .", "Work on Drosophila antimicrobial immunity has led to identification of mechanisms underlying human innate immunity , such as the use of Toll-like receptors for recognizi...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects	journal.pgen.1003926	null	[ [ "Across the entire human genome , the major histocompatibility complex ( MHC ) on chromosome 6 makes the single largest contribution to multiple sclerosis ( MS ) susceptibility .", "The classical HLA-DRB1*15:01 allele has been documented as the strongest association to MS risk , and its role has been stud...	[ "The major histocompatibility complex ( MHC ) region is strongly associated with multiple sclerosis ( MS ) susceptibility .", "HLA-DRB1*15:01 has the strongest effect , and several other alleles have been reported at different levels of validation .", "Using SNP data from genome-wide studies , we imputed and te...	[ "Multiple sclerosis ( MS ) is an inflammatory and neurodegenerative disease with a heritable component .", "Although it has been known for a long time that the strongest MS risk factor maps to the major histocompatibility complex ( MHC ) on chromosome 6 , there are still many unresolved questions as to the identi...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "crystal structure", "chemical compounds", "cd coreceptors", "condensed matter physics", "carbohydrates", "organic compounds", "materials science", "basic amino acids", "amino acids", "crystallography", "coreceptors", "oligomers", "macromolecules", "thermodynamics", "materials by structu...	Atomistic fingerprint of hyaluronan–CD44 binding	journal.pcbi.1005663	null	[ [ "Hyaluronic acid ( HA ) also known as hyaluronan is a natural carbohydrate polymer constituted by a repeating disaccharide of glucuronic acid ( GlcUA ) and N-acetylglucosamine ( GlcNAc ) ( [-β ( 1 , 4 ) -GlcUA-β ( 1 , 3 ) -GlcNAc-]n ) [1] .", "Reaching molecular weights of up to 106 Da ( i . e . , several...	[ "Hyaluronan is a polyanionic , megadalton-scale polysaccharide , which initiates cell signaling by interacting with several receptor proteins including CD44 involved in cell-cell interactions and cell adhesion .", "Previous studies of the CD44 hyaluronan binding domain have identified multiple widespread residues...	[ "Hyaluronan is a natural sugar polymer in our bodies .", "Besides acting as a space-filling agent for example in multiple connective tissues , it also functions as a cellular cue in cancer and inflammation .", "Our tissues sense hyaluronan through receptors—proteins that sit at the surface of cells and grab the...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "cardiovascular physiology", "gene regulation", "cancer treatment", "immunology", "cancers and neoplasms", "basic cancer research", "fibroblasts", "oncology", "angiogenesis", "developmental biology", ...	Reprogramming of Normal Fibroblasts into Cancer-Associated Fibroblasts by miRNAs-Mediated CCL2/VEGFA Signaling	journal.pgen.1006244	null	[ [ "Fibroblasts , a key cellular component of human tissues and tumors , can be divided into resting and activated fibroblasts [1] .", "For example , fibroblasts are highly activated at the site of healing wound [2] .", "The activated fibroblasts invade lesions and generate extracellular matrix ( ECM ) t...	[ "Cancer-associated fibroblasts ( CAFs ) , the most common constituent of the tumor stoma , are known to promote tumor initiation , progression and metastasis .", "However , the mechanism of how cancer cells transform normal fibroblasts ( NFs ) into CAFs is largely unknown .", "In this study , we determined the ...	[ "During tumorigenesis , normal fibroblasts ( NFs ) within the tumor stroma acquire a modified phenotype and become cancer-associated fibroblasts ( CAFs ) .", "CAFs provide oncogenic signals to facilitate tumor initiation , progression , and metastasis .", "Here , we set out to determine the factors that mediate...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "mammals", "physiology", "vertebrates", "neuroscience", "rattus (rat)" ]	A Burst-Based “Hebbian” Learning Rule at Retinogeniculate Synapses Links Retinal Waves to Activity-Dependent Refinement	journal.pbio.0050061	A novel learning rule describes a simple computation by which retinal wave activity robustly drives the synaptic refinement that occurs in the visual system.	[ [ "Though synaptic plasticity is a feature of most excitatory synapses in the brain , how it functions in realistic contexts is largely unclear because its effects usually only manifest on the system level .", "The synaptic refinement of retinal ganglion cell ( RGC ) axons in the developing lateral genicula...	[ "Patterned spontaneous activity in the developing retina is necessary to drive synaptic refinement in the lateral geniculate nucleus ( LGN ) .", "Using perforated patch recordings from neurons in LGN slices during the period of eye segregation , we examine how such burst-based activity can instruct this refinemen...	[ "The brain is comprised of an immense number of connections between neurons , and clever strategies are required to achieve the correct wiring during development .", "One common strategy uses neural activity itself as feedback to instruct individual connections ( synapses ) through synaptic learning rules that de...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "immunology", "microbiology", "infectious diseases" ]	Mycolic Acid Modification by the mmaA4 Gene of M. tuberculosis Modulates IL-12 Production	journal.ppat.1000081	null	[ [ "Tuberculosis ( TB ) is the second leading cause of death from an infectious disease worldwide [1] , [2] .", "Mycobacterium tuberculosis is well adapted to the human host , and possesses a variety of mechanisms that promote immune evasion and thereby permit latent infection in the presence of host innate ...	[ "Mycobacterium tuberculosis has evolved many strategies to evade elimination by the host immune system , including the selective repression of macrophage IL-12p40 production .", "To identify the M . tuberculosis genes responsible for this aspect of immune evasion , we used a macrophage cell line expressing a repo...	[ "Currently , one-third of the world's population has tuberculosis ( TB ) .", "TB , an ancient foe , has reemerged to become a threat to global public health .", "A central problem in TB research is to investigate why the host immune system cannot sterilize the infection caused by the bacterium Mycobacterium tub...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "nucleic acid synthesis", "pathology and laboratory medicine", "3' utr", "hepacivirus", "pathogens", "messenger rna", "rna extraction", "microbiology", "viruses", "rna viruses", "untranslated regions", "rna synthesis", "extraction techniques", "chemical sy...	Involvement of the 3’ Untranslated Region in Encapsidation of the Hepatitis C Virus	journal.ppat.1005441	null	[ [ "It is known that positive strand RNA viruses package their genome via replication-coupled processes [1–3] .", "Nevertheless , for several viruses , viral particle assembly occurs via recognition of particular sequences or structures termed packaging signals that are unique to the viral genes .", "The...	[ "Although information regarding morphogenesis of the hepatitis C virus ( HCV ) is accumulating , the mechanism ( s ) by which the HCV genome encapsidated remains unknown .", "In the present study , in cell cultures producing HCV , the molecular ratios of 3’ end- to 5’ end-regions of the viral RNA population in th...	[ "Although cell culture systems provide a powerful tool for deciphering the life cycle of the hepatitis C virus ( HCV ) , the mechanisms of encapsidation of the viral genome into infectious particles remain to be uncovered .", "The HCV genome is a positive RNA with one single reading frame flanked by 5’- and 3’ un...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "tropical diseases", "biomarkers", "parasitic diseases", "parasitic protozoans", "drug screening", "parasitemia", "protozoans", "pharmaceutics", "neglected tropical diseases", "pharmacology", "quantitative parasitology", "veterinary science", "veterinary par...	Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery	journal.pntd.0003451	null	[ [ "Chagas disease ( CD ) is prevalent across various countries in Central and South America , with 28 million people at risk of getting infected [1] , [2] .", "The etiological agent of CD , Trypanosoma cruzi , has two life cycle stages in the infected host , an extracellular trypomastigote form that circula...	[ "Drug discovery initiatives , aimed at Chagas treatment , have been hampered by the lack of standardized drug screening protocols and the absence of simple pre-clinical assays to evaluate treatment efficacy in animal models .", "In this study , we used a simple Enzyme Linked Aptamer ( ELA ) assay to detect T . cr...	[ "A marked decrease in incidence of Chagas Disease has been observed in the last decade achieved by vector control strategies; however , there are still geographical areas where the disease reaches endemic proportions .", "Due to high morbidity and disease burden , other avenues of Chagas control , such as vaccine...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "taxonomy", "linguistics", "social sciences", "neuroscience", "animal phylogenetics", "research design", "phylogenetics", "data management", "cognitive psychology", "phylogenetic analysis", "zoology", "research and analysis methods", "sequence analysis", "constraint relaxation", "compute...	Verbalizing phylogenomic conflict: Representation of node congruence across competing reconstructions of the neoavian explosion	journal.pcbi.1006493	null	[ [ "Three years ago , Jarvis et al . ( 2014; henceforth 2014 . JEA ) [1] published a landmark reconstruction of higher-level bird relationships .", "Within 12 months , however , another analysis by Prum et al . ( 2015; henceforth 2015 . PEA ) [2] failed to support several of the deep divergences recovered in...	[ "Phylogenomic research is accelerating the publication of landmark studies that aim to resolve deep divergences of major organismal groups .", "Meanwhile , systems for identifying and integrating the products of phylogenomic inference–such as newly supported clade concepts–have not kept pace .", "However , the ...	[ "Synthetic platforms for phylogenomic knowledge tend to manage conflict between different evolutionary reconstructions in the following way: \"If we do not agree , then it is either our view over yours , or we just collapse all conflicting node concepts into polytomies\" .", "We argue that this is not an equitabl...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "organism development", "morphogenesis", "organogenesis", "biology", "anatomy and physiology", "cardiovascular system" ]	Multiplexin Promotes Heart but Not Aorta Morphogenesis by Polarized Enhancement of Slit/Robo Activity at the Heart Lumen	journal.pgen.1003597	null	[ [ "During early development , the vertebrate heart exhibits genetic and morphological similarities to the cardiac tube ( dorsal vessel ) of the invertebrate model organism Drosophila melanogaster [1]–[3] .", "The primary genetic network that determines the heart field has been established in both vertebrate...	[ "The Drosophila heart tube represents a structure that similarly to vertebrates' primary heart tube exhibits a large lumen; the mechanisms promoting heart tube morphology in both Drosophila and vertebrates are poorly understood .", "We identified Multiplexin ( Mp ) , the Drosophila orthologue of mammalian Collage...	[ "The formation of the characteristic large heart lumen is common to all heart-containing organisms and is essential for efficient heart function; however , the structural components promoting this process are yet to be elucidated .", "The Drosophila heart represents a specific compartment within an elongated cont...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/membranes and sorting", "cardiovascular disorders/myopathies", "cardiovascular disorders/heart failure", "cell biology/cytoskeleton" ]	BIN1 Localizes the L-Type Calcium Channel to Cardiac T-Tubules	journal.pbio.1000312	Cardiac tubular-like membrane invaginations contain the membrane scaffolding protein BIN1, which tethers dynamic microtubules that deliver calcium channels directly to T-tubule membrane.	[ [ "The BAR domain superfamily is composed of proteins involved in endocytosis , organelle biogenesis , cell division , and cell migration ( review in [1] ) .", "As a member of the BAR domain superfamily , the tubulogenesis membrane scaffolding protein BIN1 ( Amphiphysin 2 ) is known to induce membrane invag...	[ "The BAR domain protein superfamily is involved in membrane invagination and endocytosis , but its role in organizing membrane proteins has not been explored .", "In particular , the membrane scaffolding protein BIN1 functions to initiate T-tubule genesis in skeletal muscle cells .", "Constitutive knockdown of ...	[ "Calcium plays a primary role in regulating heart function .", "During each heartbeat , calcium ions cross the membrane of individual cardiac muscle cells and trigger a rapid increase of calcium within the cell ( called the calcium transient ) .", "Calcium causes the muscle cells to contract and determines the ...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/genetics of the immune system", "genetics and genomics/complex traits", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "genetics and genomics/population genetics" ]	Capturing the Spectrum of Interaction Effects in Genetic Association Studies by Simulated Evaporative Cooling Network Analysis	journal.pgen.1000432	null	[ [ "Human genetics studies have been successful at identifying single-locus variants that have a large effect on Mendelian disorders , such as cystic fibrosis or neurofibromatosis .", "However , the analytical strategies appropriate for identifying Mendelian disease genes have been met with limited success w...	[ "Evidence from human genetic studies of several disorders suggests that interactions between alleles at multiple genes play an important role in influencing phenotypic expression .", "Analytical methods for identifying Mendelian disease genes are not appropriate when applied to common multigenic diseases , becaus...	[ "Susceptibility to many diseases and disorders is caused by breakdown at multiple points in the genetic network .", "Each of these points of breakdown by itself may have a very modest effect on disease risk but the points may have a much stronger effect through statistical interactions with each other .", "Geno...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Gene Fitness Landscapes of Vibrio cholerae at Important Stages of Its Life Cycle	journal.ppat.1003800	null	[ [ "The human intestinal pathogen Vibrio cholerae is a natural inhabitant of the aquatic ecosystem .", "V . cholerae is a halophile that normally resides in coastal waters and brackish estuaries , however pathogenic strains can persist in bodies of fresh water for extended periods of time in cholera endemic ...	[ "Vibrio cholerae has evolved to adeptly transition between the human small intestine and aquatic environments , leading to water-borne spread and transmission of the lethal diarrheal disease cholera .", "Using a host model that mimics the pathology of human cholera , we applied high density transposon mutagenesis...	[ "Cholera is a deadly diarrheal disease that spreads in explosive epidemics and is caused by the water-borne bacterium Vibrio cholerae .", "Pathogenic strains of V . cholerae can be found in both fresh and salt water estuaries in-between cholera outbreaks .", "Cholera infections are frequently derived from conta...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "luciferase", "enzymes", "endoplasmic reticulum", "cell processes", "enzymology", "neuroscience", "physiological processes", "homeostasis", "mitochondria", "molecular biology techniques", "bioenergetics", "cellular structures and organelles", "research and a...	Role of Mitochondrial Dynamics in Neuronal Development: Mechanism for Wolfram Syndrome	journal.pbio.1002511	Deficiency of the protein Wolframin in Wolfram syndrome triggers a stress cascade in the endoplasmic reticulum; this leads to altered calcium homeostasis, which in turn impairs mitochondrial dynamics and consequently inhibits neuronal development.	[ [ "Wolfram syndrome ( WS ) is a genetic disorder characterized by diabetes insipidus , diabetes mellitus , optical atrophy , and deafness ( DIDMOAD ) and brain atrophy that results in death in middle adulthood , typically due to brainstem atrophy-induced respiratory failure [1] .", "About 60% of patients wi...	[ "Deficiency of the protein Wolfram syndrome 1 ( WFS1 ) is associated with multiple neurological and psychiatric abnormalities similar to those observed in pathologies showing alterations in mitochondrial dynamics .", "The aim of this study was to examine the hypothesis that WFS1 deficiency affects neuronal functi...	[ "Wolfram syndrome ( WS ) is a genetic disorder characterized by diabetes insipidus , diabetes mellitus , optic atrophy , deafness , and brain atrophy .", "Brain abnormalities occur at the earliest stage of clinical symptoms , suggesting that Wolfram syndrome has a pronounced impact on early brain development .", ...	2016
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "developmental biology", "molecular biology/transcription initiation and activation", "cell biology/developmental molecular mechanisms", "genetics and genomics/disease models", "molecular biology/dna repair" ]	p8/TTDA Overexpression Enhances UV-Irradiation Resistance and Suppresses TFIIH Mutations in a Drosophila Trichothiodystrophy Model	journal.pgen.1000253	null	[ [ "The integrity of the DNA molecule can be disrupted by chemical and physical factors that cause diverse types of damage .", "The nucleotide excision repair ( NER ) pathway operates when DNA is damaged by the covalent addition of methyl groups , the formation of cyclobutane-pyrimidine dimers ( CPDs ) , or ...	[ "Mutations in certain subunits of the DNA repair/transcription factor complex TFIIH are linked to the human syndromes xeroderma pigmentosum ( XP ) , Cockayne's syndrome ( CS ) , and trichothiodystrophy ( TTD ) .", "One of these subunits , p8/TTDA , interacts with p52 and XPD and is important in maintaining TFIIH ...	[ "TFIIH participates in RNA polymerase II transcription , nucleotide excision repair , and control of the cell cycle .", "In humans , certain mutations in the XPB and XPD subunits of TFIIH generate the syndromes trichothiodystrophy ( TTD ) , xeroderma pigmentosum ( XP ) , and Cockayne's syndrome ( CS ) .", "In c...	2008
[ "Introduction", "Materials and Experimental Methods", "Experimental Results", "Model Methods", "Model Simulation Results", "Discussion" ]	[ "evolutionary ecology", "plant science", "plant viral pathogens", "ecology", "virology", "plant pathogens", "plant pathology", "biology and life sciences", "microbiology", "evolutionary biology" ]	The Relationship between Host Lifespan and Pathogen Reservoir Potential: An Analysis in the System Arabidopsis thaliana-Cucumber mosaic virus	journal.ppat.1004492	null	[ [ "Understanding the complex interplay of factors resulting in pathogen emergence has been a major goal of evolutionary ecology for the last twenty years , as emerging infectious diseases often have a high impact in human and animal health , agriculture and conservation [1]–[5] .", "Generally , emergent pat...	[ "Identification of the determinants of pathogen reservoir potential is central to understand disease emergence .", "It has been proposed that host lifespan is one such determinant: short-lived hosts will invest less in costly defenses against pathogens , so that they will be more susceptible to infection , more c...	[ "Understanding pathogen emergence is a major goal of pathology , because of the high impact of emerging diseases .", "Pathogens emerge onto a new host from a reservoir , hence the relevance of identifying the determinants of host's reservoir potential .", "Host lifespan is considered as one such determinant: sh...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "molecular probe techniques", "enzymes", "pathogens", "gene regulation", "microbiology", "enzymology", "dna-binding proteins", "nucleotides", "hepatitis b virus", "viruses", "polymera...	Flap endonuclease 1 is involved in cccDNA formation in the hepatitis B virus	journal.ppat.1007124	null	[ [ "Hepatitis B virus ( HBV ) is a major pathogenic cause of human cirrhosis and hepatocellular carcinoma [1] .", "Infectious HBV particles contain relaxed circular DNA ( rcDNA ) encapsidated by core proteins [2] .", "After entering the host hepatocyte , rcDNA is converted into covalently closed circular...	[ "Hepatitis B virus ( HBV ) is one of the major etiological pathogens for liver cirrhosis and hepatocellular carcinoma .", "Chronic HBV infection is a key factor in these severe liver diseases .", "During infection , HBV forms a nuclear viral episome in the form of covalently closed circular DNA ( cccDNA ) .", ...	[ "Hepatitis B virus ( HBV ) infection remains a worldwide health problem that affects more than 350 million people .", "HBV is one of the major etiological pathogens for liver cirrhosis and hepatocellular carcinoma .", "HBV covalently closed circular DNA ( cccDNA ) is a key viral intermediate for persistent infe...	2018
[ "Introduction", "Methods", "Results/Discussion" ]	[]	Dimensionality of Carbon Nanomaterials Determines the Binding and Dynamics of Amyloidogenic Peptides: Multiscale Theoretical Simulations	journal.pcbi.1003360	null	[ [ "The fast-developing field of nanotechnology has already had a significant impact in numerous areas of science and technology due to the ability to control the properties of nanomaterials with greater precision [1]–[3] .", "Despite the remarkable speed of developments in nanoscience , little is known abou...	[ "Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly , possibly interfering with the development of protein misfolding diseases such as Alzheimer's , Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins .", "We employ...	[ "Investigation of the effects of nanomaterials on biological systems is crucial due to the increasing exposure to nanostructured materials with the growing developments and applications of nanotechnology in everyday life .", "Nanoparticles have been shown to have an effect on protein structure and interfere with ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "model organisms", "neurological disorders", "neurology", "biology", "molecular cell biology", "neuroscience", "genetics and genomics", "clinical genetics" ]	Spastic Paraplegia Mutation N256S in the Neuronal Microtubule Motor KIF5A Disrupts Axonal Transport in a Drosophila HSP Model	journal.pgen.1003066	null	[ [ "Hereditary spastic paraplegia ( HSP ) is a group of genetically heterogeneous neurodegenerative disorders characterized by distal axonopathy that affects the longest axons in the corticospinal tract [1] , [2] .", "To date , 48 HSP loci have been described .", "The three most common causes of HSP - ac...	[ "Hereditary spastic paraplegias ( HSPs ) comprise a group of genetically heterogeneous neurodegenerative disorders characterized by spastic weakness of the lower extremities .", "We have generated a Drosophila model for HSP type 10 ( SPG10 ) , caused by mutations in KIF5A .", "KIF5A encodes the heavy chain of k...	[ "Hereditary spastic paraplegias ( HSPs ) comprise a group of inherited neurological diseases .", "The main feature of HSP is progressive stiffness of the lower limbs due to a dysfunction of nerve cells .", "We study HSP type 10 , which is caused by mutations in the neuronal motor protein KIF5A .", "HSP type 1...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/organogenesis", "cell biology/cell growth and division", "cell biology/cell signaling" ]	Zyxin Links Fat Signaling to the Hippo Pathway	journal.pbio.1000624	Using genetic and molecular analyses, the authors identify Zyx as a positive regulator of Hippo signaling and characterize its role within the pathway.	[ [ "The Hippo pathway has emerged as an important regulator of growth during metazoan development , and its dysregulation is implicated in diverse cancers [1]–[3] .", "Hippo signaling is effected by transcriptional co-activator proteins , Yorkie ( Yki ) in Drosophila and YAP and TAZ in mammals [4] .", "T...	[ "The Hippo signaling pathway has a conserved role in growth control and is of fundamental importance during both normal development and oncogenesis .", "Despite rapid progress in recent years , key steps in the pathway remain poorly understood , in part due to the incomplete identification of components .", "Th...	[ "Processes that control cell numbers are essential during normal development , when they are required to generate organs of the correct size , and during cancinogenesis , when they influence tumor growth .", "The Hippo pathway is an intercellular signaling pathway that relays information about cell-cell contact a...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "sequencing techniques", "medicine and health sciences", "plasmodium falciparum", "parasitic diseases", "parasitic protozoans", "simulation and modeling", "probability distribution", "mathematics", "protozoans", "molecular biology techniques", "research and analysis methods", "malarial parasit...	Inferring Strain Mixture within Clinical Plasmodium falciparum Isolates from Genomic Sequence Data	journal.pcbi.1004824	null	[ [ "The protozoan parasite Plasmodium falciparum ( Pf ) is the cause of the vast majority of fatal malaria cases , killing at least half a million people a year [1–3] .", "The parasite’s ability to develop resistance to drugs and the rapid spread of that resistance across geographically-separated populations...	[ "We present a rigorous statistical model that infers the structure of P . falciparum mixtures—including the number of strains present , their proportion within the samples , and the amount of unexplained mixture—using whole genome sequence ( WGS ) data .", "Applied to simulation data , artificial laboratory mixtu...	[ "Since the 1960’s researchers have observed that Plasmodium falciparum infections , the cause of most severe malaria , are frequently composed of several different strains of the parasite .", "In this work , the authors use Bayesian methods on whole genome sequence data to model the structure of these mixtures ."...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "dimers (chemical physics)", "classical mechanics", "enzymes", "cell cycle and cell division", "cell processes", "enzymology", "phosphatases", "simulation and modeling", "research and analysis methods", "proteins", "chemistry", "adenosine triphosphatase", "physics", "biochemistry", "hydr...	Regulation of Pom cluster dynamics in Myxococcus xanthus	journal.pcbi.1006358	null	[ [ "The formation of protein patterns and the intracellular positioning of proteins is a major prerequisite for many important processes in bacterial cells , such as cell division .", "In order to maintain the genetic content of the bacterial cell , the chromosome ( nucleoid ) is duplicated during the cell c...	[ "Precise positioning of the cell division site is essential for the correct segregation of the genetic material into the two daughter cells .", "In the bacterium Myxococcus xanthus , the proteins PomX and PomY form a cluster on the chromosome that performs a biased random walk to midcell and positively regulates ...	[ "In order for the rod-shaped bacterium M . xanthus to reproduce , its genetic content must be duplicated , distributed equally to the two cell halves and then the cell must divide precisely at midcell .", "Three proteins , called PomX , PomY and PomZ , are important for the localization of the cell division site ...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "biogeography", "ecology and environmental sciences", "medicine and health sciences", "population dynamics", "population genetics", "geographical locations", "tropical diseases", "ethnicities", "bacterial diseases", "population biology", "bacteria", "extraction techniques", "africa", "rese...	Mycobacterium tuberculosis complex genotypes circulating in Nigeria based on spoligotyping obtained from Ziehl-Neelsen stained slides extracted DNA	journal.pntd.0006242	null	[ [ "In 2015 , six countries , Nigeria , India , Indonesia , China , Pakistan and South-Africa , accounted for 60% of all TB cases in the world , with Nigeria having the second largest TB burden in Africa , with an estimated 586 , 000 cases in 2015 [1] .", "Nigeria is also among the ten countries with the lar...	[ "All State TB control programmes in Nigeria were requested to submit 25–50 smear-positive Ziehl-Neelsen ( ZN ) stained slides for screening during 2013–2014 .", "DNA was extracted from 929 slides for spoligotyping and drug-resistance analysis using microbead-based flow-cytometry suspension arrays .", "Spoligoty...	[ "Using a classical genotyping method designated as “spoligotyping” , which targets polymorphic repetitive DNA loci , we present a general snapshot of the genetic diversity of Mycobacterium tuberculosis complex causing tuberculosis in Nigeria .", "Our results were obtained on a collection of 549 DNAs , extracted f...	2018
[ "Introduction", "Materials and methods", "Discussion" ]	[ "cell physiology", "ion channel gating", "medicine and health sciences", "action potentials", "neural networks", "nervous system", "membrane potential", "junctional complexes", "electrophysiology", "neuroscience", "gap junctions", "ion channels", "synaptic plasticity", "electrical synapses...	Functional asymmetry and plasticity of electrical synapses interconnecting neurons through a 36-state model of gap junction channel gating	journal.pcbi.1005464	null	[ [ "In most models of neuronal networks , it is assumed that electrical synapses exhibit constant conductance , and that electric synaptic transmission is bidirectional and symmetric .", "However , experimental studies show that these assumptions are not always satisfied .", "For instance , some synapses...	[ "We combined the Hodgkin–Huxley equations and a 36-state model of gap junction channel gating to simulate electrical signal transfer through electrical synapses .", "Differently from most previous studies , our model can account for dynamic modulation of junctional conductance during the spread of electrical sign...	[ "In most computational models of neuronal networks , it is assumed that electrical synapses have a constant and ohmic conductance .", "However , numerous experimental studies demonstrate that connexin-based channels expressed in neuronal gap junctions can change their conductance in response to a transjunctional ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "united states", "bibliometrics", "sociology", "geographical locations", "social sciences", "north america", "network analysis", "social networks", "information technology", "data processing", "research and analysis methods", "computer and information sciences", "economics", "research asse...	Analysing published global Ebola Virus Disease research using social network analysis	journal.pntd.0005747	null	[ [ "The 2014/2015 West African Ebola Virus Disease ( EVD ) outbreak with more than 28 , 000 cases and 11 , 000 deaths , was a public health emergency of international concern [1 , 2] .", "Although EVD was discovered in the former Zaire ( now: Democratic Republic of Congo ) more than 40 years ago , the absenc...	[ "The 2014/2015 West African Ebola Virus Disease ( EVD ) outbreak attracted global attention .", "Numerous opinions claimed that the global response was impaired , in part because , the EVD research was neglected , although quantitative or qualitative studies did not exist .", "Our objective was to analyse how t...	[ "Ebola Virus Disease ( EVD ) research publications were used to analyse and visualise collaborations between institutions jointly publishing research results , using freely available social network analysis tools .", "Constructed co-authorship networks between author affiliated institutions showed EVD research pu...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "invertebrates", "medicine and health sciences", "immune cells", "immune physiology", "immunology", "light microscopy", "animals", "developmental biology", "nymphs", "microscopy", "confocal microscopy", "antibodies", "insect vectors", "digestive system", "research and an...	Insect tissue-specific vitellogenin facilitates transmission of plant virus	journal.ppat.1006909	null	[ [ "Rice stripe disease is a serious problem during rice production , with epidemics occurring repeatedly in China , Japan and Korea [1–3] .", "Transmission of the causative pathogen , Rice stripe virus ( RSV ) , is completely dependent on insect vectors , the most important of which is the small brown plant...	[ "Insect vitellogenin ( Vg ) has been considered to be synthesized in the fat body .", "Here , we found that abundant Vg protein is synthesized in Laodelphax striatellus hemocytes as well .", "We also determined that only the hemocyte-produced Vg binds to Rice stripe virus ( RSV ) in vivo .", "Examination of t...	[ "Rice stripe virus ( RSV ) , which is completely dependent on Laodelphax striatellus for transmission between host plants , can also be vertically transmitted from the mother insect to its offsprings .", "Passing through the insect hemolymph is an essential step for both kinds of viral transmission .", "In this...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "reaction time", "brain electrophysiology", "social sciences", "electrophysiology", "brain", "neuroscience", "cognitive neuroscience", "clinical medicine", "cognition", "brain mapping", "bioassays and physiological analysis", "vision", "event-related potenti...	Frontal cortex tracks surprise separately for different sensory modalities but engages a common inhibitory control mechanism	journal.pcbi.1006927	null	[ [ "Surprise occurs when expectations about the multi-sensory environment are violated .", "It provides an elementary cognitive and physiological process that forms the backbone of many influential theories of cognitive processing and control [1–5] .", "The rapid modification of ongoing actions after sur...	[ "The brain constantly generates predictions about the environment to guide action .", "Unexpected events lead to surprise and can necessitate the modification of ongoing behavior .", "Surprise can occur for any sensory domain , but it is not clear how these separate surprise signals are integrated to affect mot...	[ "Surprise is an elementary cognitive computation that the brain performs to guide behavior .", "We investigated how the brain tracks surprise across different senses: Do unexpected sounds make subsequent unexpected visual stimuli less surprising ?", "Or does the brain maintain separate expectations of environme...	2019
[ "Introduction", "Results & discussion", "Materials & methods" ]	[ "taxonomy", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "membrane proteins", "genomic databases", "phylogenetics", "data management", "outer membrane proteins", "phylogenetic analysis", "genome analysis", "dna", "cellular structures and...	Dynamics and impact of homologous recombination on the evolution of Legionella pneumophila	journal.pgen.1006855	null	[ [ "While all bacteria reproduce clonally , some also import DNA from other organisms into their chromosomes through processes such as recombination or horizontal gene transfer .", "The imported DNA can either replace a homologous segment of the genome ( homologous recombination ) or comprise novel genes tha...	[ "Legionella pneumophila is an environmental bacterium and the causative agent of Legionnaires’ disease .", "Previous genomic studies have shown that recombination accounts for a high proportion ( >96% ) of diversity within several major disease-associated sequence types ( STs ) of L . pneumophila .", "This sugg...	[ "Legionella pneumophila is an environmental bacterium that causes Legionnaires’ disease , a serious and potentially fatal pneumonia .", "Previous studies have shown that members of this species undergo a process called recombination , whereby DNA is imported from another bacterial cell into the recipient genome ....	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/persistence and latency", "virology/viruses and cancer", "virology" ]	A Viral microRNA Cluster Strongly Potentiates the Transforming Properties of a Human Herpesvirus	journal.ppat.1001294	null	[ [ "Epstein-Barr virus ( EBV ) establishes a clinically silent chronic infection in the large majority of the world population [1] .", "In the course of primary infection , B cells targeted by the virus initiate transient cell growth until EBV-specific CD8+ T cells mount an efficient antiviral response [2] ....	[ "Epstein-Barr virus ( EBV ) , an oncogenic human herpesvirus , induces cell proliferation after infection of resting B lymphocytes , its reservoir in vivo .", "The viral latent proteins are necessary for permanent B cell growth , but it is unknown whether they are sufficient .", "EBV was recently found to encod...	[ "To persist in their hosts , herpes viruses must avoid recognition by the host's immune system .", "Down-regulation of viral antigen production through expression of viral miRNAs is a particularly elegant mechanism as these genetic elements do not encode proteins and remain therefore invisible to the immune syste...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "plant anatomy", "quantitative trait loci", "population genetics", "cereal crops", "plant science", "rice", "model organisms", "genome analysis", "crops", "population biology", "plants", "research and analysis methods", "genome complexity", "grasses", ...	A Novel Tiller Angle Gene, TAC3, together with TAC1 and D2 Largely Determine the Natural Variation of Tiller Angle in Rice Cultivars	journal.pgen.1006412	null	[ [ "As a key factor in rice plant architecture , tiller angle determines the planting density per unit area and contributes greatly to grain yield .", "The tiller angle is defined as the angle between the main culm and the side tillers [1] .", "A favorable rice tiller angle is an important component of t...	[ "Tiller angle is one of the most important components of the ideal plant architecture that can greatly enhance rice grain yield .", "Understanding the genetic basis of tiller angle and mining favorable alleles will be helpful for breeding new plant-type varieties .", "Here , we performed genome-wide association...	[ "Tiller angle is the key component of plant architecture that greatly affect grain yield .", "However , few tiller angle-related genes that can be used for improving rice plant architecture have been isolated based on natural variation .", "Here , we identified 7 common tiller angle-related QTLs by a genome-wid...	2016
[ "Introduction", "Material and methods", "Results", "Discussion" ]	[ "invertebrates", "dengue virus", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "saliva", "animals", "viruses", "rna viruses", "insect vectors", "infectious diseases", "medical microbiology", "microbial pa...	The recently identified flavivirus Bamaga virus is transmitted horizontally by Culex mosquitoes and interferes with West Nile virus replication in vitro and transmission in vivo	journal.pntd.0006886	null	[ [ "The genus Flavivirus encompasses over 70 viral species including several human and animal pathogens , such as yellow fever virus ( YFV ) , dengue viruses ( DENV ) , Zika virus ( ZIKV ) , West Nile virus ( WNV ) and Murray Valley encephalitis virus ( MVEV ) which are transmitted by mosquitoes [1 , 2] .", ...	[ "Arthropod-borne flaviviruses such as yellow fever ( YFV ) , Zika and dengue viruses continue to cause significant human disease globally .", "These viruses are transmitted by mosquitoes when a female imbibes an infected blood-meal from a viremic vertebrate host and expectorates the virus into a subsequent host ....	[ "Mosquito-borne flaviviruses include medically significant members such as the dengue viruses , yellow fever virus and Zika virus .", "These viruses regularly cause outbreaks globally , notably in tropical regions .", "The ability of mosquitoes to transmit these viruses to vertebrate hosts plays a major role in...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbial metabolism", "medicine and health sciences", "microbial physiology", "pathology and laboratory medicine", "host-pathogen interactions", "medical microbiology", "microbial pathogens", "biology and life sciences", "microbiology", "pathogenesis", "bacterial pathogens" ]	Preferential Use of Central Metabolism In Vivo Reveals a Nutritional Basis for Polymicrobial Infection	journal.ppat.1004601	null	[ [ "The recent revival of interest in the relationship between bacterial metabolism and host-pathogen interactions has deepened our understanding of pathogen colonization and growth in vivo [1] , [2] , [3] , [4] .", "Consequently , central metabolism must be considered essential to virulence because bacteria...	[ "The human genitourinary tract is a common anatomical niche for polymicrobial infection and a leading site for the development of bacteremia and sepsis .", "Most uncomplicated , community-acquired urinary tract infections ( UTI ) are caused by Escherichia coli , while another bacterium , Proteus mirabilis , is mo...	[ "The human urinary tract is a leading source for polymicrobial infections and for the development of bacteremia and sepsis .", "Treating these potentially dangerous infections have recently become more challenging due to the appearance of uropathogenic strains that are resistant to the many of the most commonly p...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "infectious diseases/neglected tropical diseases" ]	Development and Validation of a Quantitative, High-Throughput, Fluorescent-Based Bioassay to Detect Schistosoma Viability	journal.pntd.0000759	null	[ [ "Infection with the parasitic trematode Schistosoma mansoni causes a wide range of quantifiable clinical pathologies [1] , which collectively lead to the death of approximately 200 , 000 individuals/annum [2] .", "Recent ‘first pass’ description of this parasite's genome [3] , as well as multiple reports ...	[ "Schistosomiasis , caused by infection with the blood fluke Schistosoma , is responsible for greater than 200 , 000 human deaths per annum .", "Objective high-throughput screens for detecting novel anti-schistosomal targets will drive ‘genome to drug’ lead translational science at an unprecedented rate .", "Cur...	[ "With only one effective drug , praziquantel , currently used to treat most worldwide cases of schistosomiasis , there exists a pressing need to identify alternative anthelmintics before the development of praziquantel-resistant schistosomes removes our ability to combat this neglected tropical disease .", "At pr...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "dermatology", "biology", "molecular cell biology" ]	USF-1 Is Critical for Maintaining Genome Integrity in Response to UV-Induced DNA Photolesions	journal.pgen.1002470	null	[ [ "Maintaining the integrity of the genome through cell generations is critical to ensure accurate cell function and to avoid tumor formation .", "Cells are continuously challenged by environmental insults and they are equipped with specific and efficient defense machinery to remove any DNA alterations .", ...	[ "An important function of all organisms is to ensure that their genetic material remains intact and unaltered through generations .", "This is an extremely challenging task since the cell's DNA is constantly under assault by endogenous and environmental agents .", "To protect against this , cells have evolved e...	[ "UV is responsible for DNA damage and genetic alterations of key players of the Nucleotide Excision Repair ( NER ) machinery promote the development of UV-induced skin cancers .", "The NER is the major DNA–repair process involved in the recognition and removal of UV-mediated DNA damage .", "Different factors pa...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "medicine and health sciences", "cancers and neoplasms", "diet", "habits", "oncology", "nutrition", "genome analysis", "smoking habits", "digestive system", "genetic epidemiology", "genomics", "behavior", "epidemiology", "gene expression", "adenomas",...	Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer	journal.pgen.1006296	null	[ [ "Colorectal cancer ( CRC ) is the third-most common cancer in men and the second most common cancer in women worldwide [1] .", "Both environmental and genetic factors are involved in the development of CRC [2–7] .", "Since 2007 , genome-wide association studies ( GWAS ) have identified about 50 loci a...	[ "Genome-wide association studies ( GWAS ) have identified many genetic susceptibility loci for colorectal cancer ( CRC ) .", "However , variants in these loci explain only a small proportion of familial aggregation , and there are likely additional variants that are associated with CRC susceptibility .", "Genom...	[ "Alcohol consumption and smoking are associated with CRC risk .", "We performed a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking to identify potential new genetic regions associated with CRC .", "About 8 , 000 CRC cases and 8 , 800 controls were inclu...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "in vitro", "cell biology" ]	High Incidence of Non-Random Template Strand Segregation and Asymmetric Fate Determination In Dividing Stem Cells and their Progeny	journal.pbio.0050102	Analysis of the segregation of older and younger DNA template strands in proliferating muscle stem cells provides compelling evidence of co-segregation based on template age and associated with cell fate determination.	[ [ "How stem cells maintain genetic and epigenetic constancy throughout repeated divisions is currently unknown .", "According to the “immortal strand hypothesis” [1] , as the stem cell divides asymmetrically , it selectively retains those sister chromatids containing the older template DNA strands in the da...	[ "Decades ago , the “immortal strand hypothesis” was proposed as a means by which stem cells might limit acquiring mutations that could give rise to cancer , while continuing to proliferate for the life of an organism .", "Originally based on observations in embryonic cells , and later studied in terms of stem cel...	[ "For each chromosome , the complementary DNA strands consist of a “younger” strand synthesized during the most recent round of DNA replication and an “older” strand synthesized during a previous cell division .", "When the strands separate to serve as templates for DNA synthesis during a subsequent round of repli...	2007
[ "Introduction", "Results/Discussion", "Methods" ]	[ "macromolecular complex analysis", "rna structure", "biophysic al simulations", "protein structure", "biology", "computational biology", "macromolecular structure analysis" ]	A Computational Investigation on the Connection between Dynamics Properties of Ribosomal Proteins and Ribosome Assembly	journal.pcbi.1002530	null	[ [ "Ribosomes are the macromolecular machines that synthesize proteins in all living organisms .", "They are composed of ribosomal RNA ( rRNA ) and ribosomal proteins ( r-proteins ) that self-assemble into functional units .", "The efficient and accurate self-assembly of the active ribosome in vivo is es...	[ "Assembly of the ribosome from its protein and RNA constituents has been studied extensively over the past 50 years , and experimental evidence suggests that prokaryotic ribosomal proteins undergo conformational changes during assembly .", "However , to date , no studies have attempted to elucidate these conforma...	[ "Ribosomes are complex cellular machines that synthesize new proteins in the cell .", "The accurate and efficient assembly of ribosomal proteins ( r-proteins ) and ribosomal RNA ( rRNA ) to form a functional ribosome is important for cell growth , metabolic reactions , and other cellular processes .", "Addition...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "onchocerca volvulus", "education", "helminths", "sociology", "tropical diseases", "geographical locations", "uganda", "black flies", "social sciences", "parasitic diseases", "animals", "onchocerca", "diptera", "pharmaceutics", "drug a...	Optimization and evaluation of the Esperanza Window Trap to reduce biting rates of Simulium damnosum sensu lato in Northern Uganda	journal.pntd.0007558	null	[ [ "Onchocerca volvulus , the causative agent of river blindness , remains endemic in most parts of Africa , despite mass drug campaigns with ivermectin spanning more than three decades [1 , 2] .", "There are multiple causes for this entrenchment , many of which are the result of the difficulty in eliminatin...	[ "Onchocerciasis , or river blindness , has historically been an important cause of blindness , skin disease and economic disruption in Africa and the Americas .", "It is caused by the filarial parasite Onchocerca volvulus , which is transmitted by black flies in the genus Simulium .", "Over the past decade , se...	[ "Onchocerciasis or river blindness is historically one of the most important causes of blindness and skin disease in the developing world .", "It is caused by infection with the filarial parasite Onchocerca volvulus .", "The finding that ivermectin was an effective and safe treatment for onchocerciasis and the ...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "neglected tropical diseases" ]	Tropheryma whipplei: A Common Bacterium in Rural Senegal	journal.pntd.0001403	null	[ [ "Traditionally , Tropheryma whipplei was considered to be a rare bacterium that typically caused the classic form of Whipple's disease , which is characterized by histologically periodic acid-Schiff–stained bacilli in infected small-bowel macrophages [1]–[3] .", "However , this well-known pathology , desc...	[ "Tropheryma whipplei is known as the cause of Whipple's disease , but it is also an emerging pathogen , detected in stool , that causes various chronic localized infections without histological digestive involvement and is associated with acute infections , including gastroenteritis and bacteremia .", "We conduct...	[ "Tropheryma whipplei is known as the cause of Whipple's disease .", "It is also an emerging pathogen , detected in stool that causes various chronic localized infections without histological digestive involvement and is associated with acute infections , including gastroenteritis and bacteremia .", "We have stu...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "united states", "medicine and health sciences", "parasite groups", "geographical locations", "parasitic diseases", "parasitic protozoans", "parasitology", "babesiosis", "organisms", "north america", "apicomplexa", "protozoans", "genome analysis", "mitochondria", "molecular genetics", ...	Development of a SNP barcode to genotype Babesia microti infections	journal.pntd.0007194	null	[ [ "Human babesiosis is an increasingly recognized tick-borne disease with the vast majority of cases in the United States caused by the malaria-like protozoan Babesia microti [1 , 2] .", "Infections occur predominantly through the bite of an infected Ixodes scapularis tick but can also occur via the transfu...	[ "Babesia microti is tick-borne disease that is an emerging threat to public health due to increasing prevalence and expanding geographic range .", "Detection and constant surveillance of babesiosis is imperative for predicting pathogen expansion .", "Leveraging our whole genome sequence ( WGS ) analyses of B . ...	[ "Babesia microti is an emerging tick-borne disease and is becoming a public health problem .", "Over the past two decades , the I . scapularis tick population , which is primarily responsible for human infection , has exploded , doubling the number of babesiosis and other I . scapularis-borne disease cases to app...	2019
[ "Introduction", "Method", "Results and discussion" ]	[ "medicine and health sciences", "air travel", "pathology and laboratory medicine", "viral transmission and infection", "economic analysis", "pathogens", "spatial epidemiology", "microbiology", "social sciences", "geographical locations", "human mobility", "viral vectors", "viruses", "rna v...	Inferring the risk factors behind the geographical spread and transmission of Zika in the Americas	journal.pntd.0006194	null	[ [ "The proposed model is evaluated at a country level , and therefore dependent on country level data for input .", "The socioeconomic data , epidemiological data , travel data , and vector suitability data for the principle spreading vectors species are all aggregated to the country level for all countries...	[ "An unprecedented Zika virus epidemic occurred in the Americas during 2015-2016 .", "The size of the epidemic in conjunction with newly recognized health risks associated with the virus attracted significant attention across the research community .", "Our study complements several recent studies which have map...	[ "Since May 2015 , when Zika was first reported in Brazil , the virus has spread to over 60 countries and territories , and imported cases of Zika have been increasingly reported worldwide .", "However , there is still much uncertainty behind the mechanisms which dictated the rapid emergence of the epidemic .", ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "classical mechanics", "fluid mechanics", "condensed matter physics", "vector-borne diseases", "animals", "simulation and modeling", "vaporization", "population biology", "insect vectors", "zoology", "research and analysis met...	A combined experimental-computational approach for spatial protection efficacy assessment of controlled release devices against mosquitoes (Anopheles)	journal.pntd.0007188	null	[ [ "Vector-borne diseases represent a global public health threat .", "More than 1 million people die annually of vector-borne diseases .", "Malaria alone is responsible for 400 , 000 deaths a year , and most cases are children under five years of age [1–3] .", "Current vector control techniques can ...	[ "This work describes the use of entomological studies combined with in silico models ( computer simulations derived from numerical models ) to assess the efficacy of a novel device for controlled release of spatial repellents .", "Controlled Release Devices ( CRDs ) were tested with different concentrations of me...	[ "Spatial Repellents ( SRs ) represent another tool to fight vector-borne diseases , such as malaria and dengue .", "Newly developed active ingredients were designed to repel or kill vectors in space , creating a shield effect , unlike topical repellents , such as DEET , that rely on vectors to be near or in physi...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Two-Phase Emergence of Non Pandemic HIV-1 Group O in Cameroon	journal.ppat.1005029	null	[ [ "Human Immunodeficiency Virus Type 1 ( HIV-1 ) is comprised of four groups ( M to P ) , each originating from a distinct cross species transmission event from Simian Immunodeficiency Virus ( SIV ) variants circulating in apes [1 , 2 , 3] .", "The major group ( M ) has spread worldwide from Central Africa ...	[ "Unlike the pandemic form of HIV-1 ( group M ) , group O viruses are endemic in west central Africa , especially in Cameroon .", "However , little is known about group O’s genetic evolution , and why this highly divergent lineage has not become pandemic .", "Using a unique and large set of group O sequences fro...	[ "HIV-1 group O is one of the causal agents of AIDS , together with HIV-1 groups M ( responsible for the pandemic ) , N and P ( 15 and 2 cases detected respectively , from Cameroon ) and HIV-2 groups A to I ( mostly found in West Africa ) , each group resulting from a distinct cross species transmission event from n...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology", "infectious diseases/viral infections", "nephrology/dialysis and renal transplantation" ]	Human Cytomegalovirus Induces TGF-β1 Activation in Renal Tubular Epithelial Cells after Epithelial-to-Mesenchymal Transition	journal.ppat.1001170	null	[ [ "Human cytomegalovirus ( HCMV ) has been associated with poor renal allograft outcome in numerous seroepidemiologic studies [1] , [2] , [3] , [4] .", "Evidence of active CMV infection ( DNAemia , antigenemia ) or CMV disease in renal transplant recipients is also associated with poor graft outcome [5] .",...	[ "Human cytomegalovirus ( HCMV ) infection is associated epidemiologically with poor outcome of renal allografts due to mechanisms which remain largely undefined .", "Transforming growth factor-β1 ( TGF-β1 ) , a potent fibrogenic cytokine , is more abundant in rejecting renal allografts that are infected with eith...	[ "Human cytomegalovirus ( HCMV ) is a common virus that establishes lifelong persistence in the host .", "Although asymptomatic in healthy people , HCMV can reactivate and cause disease in immunosuppressed patients , such as those undergoing kidney transplantation .", "HCMV infection is associated with inferior ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	ADAP2 Is an Interferon Stimulated Gene That Restricts RNA Virus Entry	journal.ppat.1005150	null	[ [ "The induction of innate immune signaling is critical for host defense against viral infections , and is most commonly initiated by the detection of foreign nucleic acids as non-self .", "Once this system is activated , host cells orchestrate an array of signaling pathways that culminate in the induction ...	[ "Interferon stimulated genes ( ISGs ) target viruses at various stages of their infectious life cycles , including at the earliest stage of viral entry .", "Here we identify ArfGAP with dual pleckstrin homology ( PH ) domains 2 ( ADAP2 ) as a gene upregulated by type I IFN treatment in a STAT1-dependent manner ."...	[ "The induction of antiviral innate immune signaling is a primary defense strategy employed by host cells to restrict virus infections .", "This system is triggered by the presence of ‘non-self’ components such as viral nucleic acids and culminates in the induction of type I interferons ( IFNs ) .", "Type I IFNs...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/animal genetics", "genetics and genomics/chromosome biology", "molecular biology/dna methylation", "genetics and genomics/epigenetics", "genetics and genomics/cancer genetics", "molecular biology/chromatin structure" ]	Cohesin Is Required for Higher-Order Chromatin Conformation at the Imprinted IGF2-H19 Locus	journal.pgen.1000739	null	[ [ "Cohesin is an evolutionarily conserved protein complex composed of the core subunits , SMC1 , SMC3 , SCC1/RAD21 and SCC3/SA ( reviewed in [1] ) .", "It has been proposed that cohesin mediates sister chromatid cohesion by embracing replicated DNA molecules as a ring [2] .", "Cohesin also has important...	[ "Cohesin is a chromatin-associated protein complex that mediates sister chromatid cohesion by connecting replicated DNA molecules .", "Cohesin also has important roles in gene regulation , but the mechanistic basis of this function is poorly understood .", "In mammalian genomes , cohesin co-localizes with CCCTC...	[ "Recent work has shown that cohesin , a protein best known for its role in holding sister chromatids together , and CTCF , a protein implicated in the formation of chromatin loops , localize to the same regions of DNA in mammalian genomes .", "This observation raised the intriguing possibility that cohesin might ...	2009
[ "Introduction", "Results", "Discussion", "Methods and Materials" ]	[ "viral attachment", "viral evolution", "host cells", "viral transmission and infection", "virology", "emerging viral diseases", "biology", "microbiology" ]	Evolutionary Reconstructions of the Transferrin Receptor of Caniforms Supports Canine Parvovirus Being a Re-emerged and Not a Novel Pathogen in Dogs	journal.ppat.1002666	null	[ [ "The interactions between viral pathogens and their hosts present a longstanding evolutionary challenge for both participants .", "Viruses are continuously selected for improved replication and spread in host populations , while hosts are reciprocally selected for increased resistance to infection .", ...	[ "Parvoviruses exploit transferrin receptor type-1 ( TfR ) for cellular entry in carnivores , and specific interactions are key to control of host range .", "We show that several key mutations acquired by TfR during the evolution of Caniforms ( dogs and related species ) modified the interactions with parvovirus c...	[ "Parvoviruses in cats and dogs have been studied as a model system to understand how viruses gain the ability to infect new host species .", "By studying the evolution of the transferrin receptor , which the virus uses to enter a cell , we discovered that the ancestors of dogs were likely infected by a parvovirus...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Comparative Analysis of Yeast Metabolic Network Models Highlights Progress, Opportunities for Metabolic Reconstruction	journal.pcbi.1004530	null	[ [ "Efforts to map metabolic networks—to describe the full network of anabolic and catabolic biochemical reactions occurring within a cell—have advanced from early biochemical studies of fermentation [1] to contemporary efforts to algorithmically generate pathway diagrams from genomic sequence [2] .", "Such ...	[ "We have compared 12 genome-scale models of the Saccharomyces cerevisiae metabolic network published since 2003 to evaluate progress in reconstruction of the yeast metabolic network .", "We compared the genomic coverage , overlap of annotated metabolites , predictive ability for single gene essentiality with a se...	[ "Scientists have been mapping the chemical reactions cells use to grow and manage waste since before enzymes were first identified more than 150 years ago .", "The model yeast Saccharomyces cerevisiae has one of the most extensively studied metabolic networks , including at least 25 metabolic network models publi...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "urology", "medicine and health sciences", "gut bacteria", "bacterial vaginosis", "physiological processes", "gene sequencing", "sexually transmitted diseases", "molecular biology techniques", "cellular structures and organelles", "bacteria", "wound healing", "resear...	Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract	journal.ppat.1005889	null	[ [ "Mucosal surfaces exposed to the external environment contain distinct bacterial communities that exist in relationship with the host and can contribute to health and functioning .", "These bacterial communities have been linked to several human diseases and overall health [1] , and can vary between indiv...	[ "The mechanism ( s ) by which bacterial communities impact susceptibility to infectious diseases , such as HIV , and maintain female genital tract ( FGT ) health are poorly understood .", "Evaluation of FGT bacteria has predominantly been limited to studies of species abundance , but not bacterial function .", ...	[ "The female genital tract ( FGT ) is a key mucosal surface in the context of HIV transmission .", "Lactobacillus species are beneficial to the FGT , while Garderella vaginalis and other anaerobic bacteria are detrimental .", "Bacterial vaginosis ( BV ) is an inflammatory condition characterized by an outgrowth ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "biochemistry", "computational biology", "evolutionary biology", "genetics and genomics" ]	Global Functional Atlas of Escherichia coli Encompassing Previously Uncharacterized Proteins	journal.pbio.1000096	A novel resource integrating proteomic and genome context-based tools provides a "systems-wide" functional blueprint ofE. coli, with insights into the biological and evolutionary significance of previously uncharacterized proteins.	[ [ "Because of its central position in the microbial research community , the Gram-negative bacterium Escherichia coli plays a leading role in investigations of the fundamental molecular biology of bacteria [1–8] .", "This experimentally tractable microbe is a workhorse in basic and applied research aimed at...	[ "One-third of the 4 , 225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated ( orphans ) .", "Many map to distant clades such as Archaea , suggesting involvement in basic prokaryotic traits , whereas others appear restricted to E . coli , including pathogenic strains .", "To elucidate...	[ "One goal of modern biology is to chart groups of proteins that act together to perform biological processes via direct and indirect interactions .", "Such groupings are sometimes called functional modules .", "The types of protein interactions within modules include physical interactions that generate protein ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "virology/immunodeficiency viruses", "virology/virulence factors and mechanisms", "virology/animal models of infection", "virology/host antiviral responses" ]	Association of Progressive CD4+ T Cell Decline in SIV Infection with the Induction of Autoreactive Antibodies	journal.ppat.1000372	null	[ [ "Progressive CD4+ T cell decline in human immunodeficiency virus ( HIV ) infection , the slow but persistent loss of both naïve and memory CD4+ T cells [1]–[3] , is an important marker of progression to AIDS .", "The mechanism of chronic CD4+ T cell depletion is not clear since the number of infected cell...	[ "The progressive decline of CD4+ T cells is a hallmark of disease progression in human immunodeficiency virus ( HIV ) and simian immunodeficiency virus ( SIV ) infection .", "Whereas the acute phase of the infection is dominated by virus-mediated depletion of memory CD4+ T cells , chronic infection is often assoc...	[ "Despite intensive study , the mechanisms of CD4+ T cell depletion in human immunodeficiency virus ( HIV ) infection remain elusive .", "The identification of the CD4 receptor as the primary receptor for HIV seemed initially to explain the loss of CD4+ T cell lymphocytes in AIDS .", "However , the number of inf...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "livestock", "medicine and health sciences", "dynamics", "classical mechanics", "fluid mechanics", "vertebrates", "animals", "physiological processes", "respiratory system", "breathing", "respiration", "waterfowl", "air flow", "birds", "ducks", "fluid dynamics", "fowl", "continuum ...	Robust Unidirectional Airflow through Avian Lungs: New Insights from a Piecewise Linear Mathematical Model	journal.pcbi.1004637	null	[ [ "The anatomical structure and airflow dynamics of the avian respiratory system are remarkably different to that of mammalian lungs [1] .", "The anatomical structure is complex , with multiple flexible airsacs that act like bellows to ventilate rigid tubes ( parabronchi ) in which gas exchange occurs , and...	[ "Avian lungs are remarkably different from mammalian lungs in that air flows unidirectionally through rigid tubes in which gas exchange occurs .", "Experimental observations have been able to determine the pattern of gas flow in the respiratory system , but understanding how the flow pattern is generated and dete...	[ "Birds and mammals have similar metabolic demands and cardiovascular systems , but they have evolved drastically different respiratory systems .", "A key difference in birds is that gas exchange occurs in rigid tubes , through which air flows unidirectionally during both inspiration and expiration .", "How this...	2016
[ "Introduction", "Methods", "Discussion", "Conclusions" ]	[ "animal types", "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "vertebrates", "pets and companion animals", "dogs", "animals", "mammals", "vaccines", "preventive me...	Barriers to dog rabies vaccination during an urban rabies outbreak: Qualitative findings from Arequipa, Peru	journal.pntd.0005460	null	[ [ "The city of Arequipa , Peru is in the midst of an urban rabies epidemic .", "The first rabid dog was detected in March 2015 , a rare instance of canine rabies reintroduction into an area previously declared free of transmission [1] .", "To date no human cases have been detected in Arequipa; however ,...	[ "Canine rabies was reintroduced to the city of Arequipa , Peru in March 2015 .", "The Ministry of Health has conducted a series of mass dog vaccination campaigns to contain the outbreak , but canine rabies virus transmission continues in Arequipa’s complex urban environment , putting the city’s 1 million inhabita...	[ "Canine rabies was reintroduced in Arequipa , Peru in March 2015 , a rare event in an area previously declared free of transmission .", "In Arequipa , annual mass dog vaccination is practiced as a preventive strategy , with additional campaigns being implemented since the recent detection of the virus .", "Howe...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "biochemistry", "animal genetics", "model organisms", "genetics", "biology", "mouse", "genetics and genomics" ]	Alternative Oxidase Expression in the Mouse Enables Bypassing Cytochrome c Oxidase Blockade and Limits Mitochondrial ROS Overproduction	journal.pgen.1003182	null	[ [ "In mammalian mitochondria , the terminal step of electron transfer to molecular oxygen , producing water , is exclusively mediated by the cyanide-sensitive cytochrome c oxidase ( COX ) [1] and the electron transfer is tightly coupled to proton translocation .", "Protons simultaneously accumulated on the ...	[ "Cyanide-resistant non-phosphorylating respiration is known in mitochondria from plants , fungi , and microorganisms but is absent in mammals .", "It results from the activity of an alternative oxidase ( AOX ) that conveys electrons directly from the respiratory chain ( RC ) ubiquinol pool to oxygen .", "AOX th...	[ "In mammalian mitochondria , the energy-producing machinery is powered by the electron transfer to molecular oxygen , a mechanism whose terminal step is mediated by the cyanide-sensitive cytochrome c oxidase ( COX ) .", "In plants , fungi , microorganisms , and some lower animals ( but not in mammals ) , in addit...	2013
[ "Introduction", "Results", "Discussion" ]	[]	A Unifying Probabilistic View of Associative Learning	journal.pcbi.1004567	null	[ [ "Learning to predict rewards ( or punishments ) from the occurrence of other stimuli is fundamental to the survival of animals .", "When such learning occurs , it is commonly assumed that a stimulus-reward association is stored in memory [1 , 2] .", "Two ideas have , over the last few decades , altere...	[ "Two important ideas about associative learning have emerged in recent decades: ( 1 ) Animals are Bayesian learners , tracking their uncertainty about associations; and ( 2 ) animals acquire long-term reward predictions through reinforcement learning .", "Both of these ideas are normative , in the sense that they...	[ "How do we learn about associations between events ?", "The seminal Rescorla-Wagner model provided a simple yet powerful foundation for understanding associative learning .", "However , much subsequent research has uncovered fundamental limitations of the Rescorla-Wagner model .", "One response to these limit...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell binding", "phosphorylation", "cell physiology", "medicine and health sciences", "placental growth factor", "body fluids", "vegf signaling", "endothelial cells", "epithelial cells", "endocrine physiology", "growth factors", "cellular structures and organelles", "animal cells", "protei...	A computational analysis of in vivo VEGFR activation by multiple co-expressed ligands	journal.pcbi.1005445	null	[ [ "The primary objectives of this study were: ( 1 ) to predict the distribution of VEGF and PlGF within the body , ( 2 ) to understand the effect of VEGF and PlGF on the balance of VEGFR1 and VEGFR2 ligation and VEGFR2 phosphorylation , ( 3 ) to quantify the effect of matrix-bound VEGF & PlGF binding to endothe...	[ "The splice isoforms of vascular endothelial growth A ( VEGF ) each have different affinities for the extracellular matrix ( ECM ) and the coreceptor NRP1 , which leads to distinct vascular phenotypes in model systems expressing only a single VEGF isoform .", "ECM-immobilized VEGF can bind to and activate VEGF re...	[ "Angiogenesis , the growth of new blood vessels from the existing vasculature , is critical for maintenance of health and response to injury .", "In ischemic disease , this process is impaired , but therapies targeting a key family of proteins , the vascular endothelial growth factors ( VEGF ) , have failed to tr...	2017
[ "Genome assemblies", "Gene synteny and gene composition", "Phylogenetic relationships to other", "Relationships to worldwide human", "A still uncertain origin of", "", "Conclusion", "Materials and methods" ]	[ "taxonomy", "parasite groups", "medicine and health sciences", "methods and resources", "plasmodium", "parasite evolution", "parasitic diseases", "parasitic protozoans", "parasitology", "apicomplexa", "phylogenetics", "data management", "protozoans", "phylogenetic analysis", "mammalian g...	Plasmodium vivax-like genome sequences shed new insights into Plasmodium vivax biology and evolution	journal.pbio.2006035	null	[ [ "Eleven P . vivax-like genotypes were obtained from 2 different kinds of samples: 10 infected chimpanzee blood samples collected during successive routine sanitary controls of chimpanzees living in the Park of La Lékédi ( a sanctuary in Gabon ) and 1 infected Anopheles mosquito ( An . moucheti ) collected dur...	[ "Although Plasmodium vivax is responsible for the majority of malaria infections outside Africa , little is known about its evolution and pathway to humans .", "Its closest genetic relative , P . vivax-like , was discovered in African great apes and is hypothesized to have given rise to P . vivax in humans .", ...	[ "Among the 5 species responsible for malaria in humans , Plasmodium vivax is the most prevalent outside Africa .", "It causes severe and incapacitating clinical symptoms with significant effects on human health .", "Yet little is known about its evolution , adaptation , and emergence in humans .", "The recent...	2018
[ "Introduction", "Methods", "Results and discussion" ]	[]	Clinical features and genetic background of the sympatric species Paracoccidioides brasiliensis and Paracoccidioides americana	journal.pntd.0007309	null	[ [ "Paracoccidioidomycosis ( PCM ) is a mycotic disease with a large spectrum of clinical presentations that affects both immunocompetent and immunocompromised patients from different biomes of Latin America [1] .", "The infection primarily affects the lungs and is acquired by the inhalation of Paracoccidioi...	[ "The agents of paracoccidioidomycosis , historically identified as Paracoccidioides brasiliensis , are in fact different phylogenetic species .", "This study aims to evaluate associations between Paracoccidioides phylogenetic species and corresponding clinical data .", "Paracoccidioides strains from INI/Fiocruz...	[ "Paracoccidioidomycosis ( PCM ) is a severe systemic mycosis caused by different phylogenetic species .", "According to previous studies , these species could have an impact in PCM clinical features .", "This study aims to investigate possible associations between Paracoccidioides species and corresponding clin...	2019
[ "Introduction", "Results", "Discussion", "Methods and materials" ]	[ "invertebrates", "in situ hybridization", "molecular probe techniques", "gene regulation", "regulatory proteins", "dna-binding proteins", "animals", "invertebrate genomics", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism systems...	Patterns of chromatin accessibility along the anterior-posterior axis in the early Drosophila embryo	journal.pgen.1007367	null	[ [ "During early embryogenesis all animal genomes undergo a transition from a largely quiescent to a highly active state with widespread zygotic transcription [1] .", "This process , known as the maternal-to-zygotic transition ( MZT ) , involves a major reorganization of chromatin , during which active and i...	[ "As the Drosophila embryo transitions from the use of maternal RNAs to zygotic transcription , domains of open chromatin , with relatively low nucleosome density and specific histone marks , are established at promoters and enhancers involved in patterned embryonic transcription .", "However it remains unclear ho...	[ "DNA in the nuclei of animals and other eukaryotes is not floating around freely .", "Rather it is wrapped around proteins called histones that are in turn compacted into higher order structures called chromatin .", "Highly compact chromatin can restrict which genes and regulatory regions are accessible to the ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "chemical characterization", "gene regulation", "long non-coding rnas", "cell differentiation", "developmental biology", "regulator genes", "adipocytes", "connective tissue cells", "gene types", "research and analysis methods", "adipocyte differentiation", "an...	Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators of Murine Brown Adipogenesis	journal.pgen.1006474	null	[ [ "Obesity and its associated metabolic complications such as diabetes are increasingly responsible for significant economic and social burdens in many countries worldwide .", "Physiologically , obesity develops when energy intake exceeds energy expenditure , and the current treatments of obesity have been ...	[ "Increasing energy expenditure through brown adipocyte recruitment is a promising approach to combat obesity .", "We report here the comprehensive profiling of the epigenome and transcriptome throughout the lineage commitment and differentiation of C3H10T1/2 mesenchymal stem cell line into brown adipocytes .", ...	[ "Obesity and its related metabolic diseases are growing problems worldwide .", "Brown adipose tissue ( BAT ) with its capability of burning off fat to generate heat is now at the center of research interest as target of therapeutic intervention for obesity treatment .", "In order to get a better understanding o...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Context-Dependent Role of Mitochondrial Fusion-Fission in Clonal Expansion of mtDNA Mutations	journal.pcbi.1004183	null	[ [ "Mitochondria are multi-functional organelles of eukaryotic cells .", "While their main function is to generate ATP through oxidative phosphorylation ( OXPHOS ) , mitochondria also participate in fatty acid oxidation , apoptosis , the cell cycle , and cell signaling [1] .", "Because of the importance ...	[ "The accumulation of mutant mitochondrial DNA ( mtDNA ) molecules in aged cells has been associated with mitochondrial dysfunction , age-related diseases and the ageing process itself .", "This accumulation has been shown to often occur clonally , where mutant mtDNA grow in number and overpopulate the wild-type m...	[ "Mitochondria are responsible for most energy generation in human and animal cells .", "Loss or pathological alteration of mitochondrial function is a hallmark of many age-related diseases .", "Mitochondrial dysfunction may be a central and conserved feature of the ageing process .", "As part of quality contr...	2015
[ "Introduction", "Results and Discussion", "Methods" ]	[ "cancer genetics", "gene expression", "genetics", "biology", "computational biology", "gene networks" ]	Molecular Evidence for the Inverse Comorbidity between Central Nervous System Disorders and Cancers Detected by Transcriptomic Meta-analyses	journal.pgen.1004173	null	[ [ "Epidemiological evidences point to a lower-than-expected probability of developing some types of Cancer in certain CNS disorders , including Alzheimer's disease ( AD ) , Parkinson's disease ( PD ) and Schizophrenia ( SCZ ) [1]–[6] .", "Our current understanding of such inverse comorbidities suggests that...	[ "There is epidemiological evidence that patients with certain Central Nervous System ( CNS ) disorders have a lower than expected probability of developing some types of Cancer .", "We tested here the hypothesis that this inverse comorbidity is driven by molecular processes common to CNS disorders and Cancers , a...	[ "A lower-than-expected probability of developing certain types of Cancer has been observed in patients with CNS disorders , including Alzheimer's disease , Parkinson's disease or Schizophrenia .", "Understanding such a protective effect could be the key to finding novel treatments for both types of conditions , f...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "molecular probe techniques", "membrane staining", "immunoblotting", "cloning", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "molecular biology techniques", "embryos", "cellular structures and organelles", "adp-ribosyla...	Dual Roles for Membrane Association of Drosophila Axin in Wnt Signaling	journal.pgen.1006494	null	[ [ "The Wnt/Wingless signal transduction pathway directs fundamental cellular processes during animal development and tissue homeostasis , whereas Wnt pathway deregulation results in numerous cancers and congenital disorders [1 , 2] .", "In the unstimulated state , the concentration-limiting scaffold protein...	[ "Deregulation of the Wnt signal transduction pathway underlies numerous congenital disorders and cancers .", "Axin , a concentration-limiting scaffold protein , facilitates assembly of a “destruction complex” that prevents signaling in the unstimulated state and a plasma membrane-associated “signalosome” that act...	[ "Axin is a scaffold protein with essential roles in Wnt signal transduction .", "In the classical model , the transition from the unstimulated to stimulated state is thought to be achieved by recruitment of Axin from cytosol to plasma membrane .", "We find that a pool of endogenous Drosophila Axin is localized ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "molecular biology", "biology and life sciences", "parasitology" ]	Ribose 5-Phosphate Isomerase B Knockdown Compromises Trypanosoma brucei Bloodstream Form Infectivity	journal.pntd.0003430	null	[ [ "African sleeping sickness is a vector borne disease of mammals , caused by Trypanosoma brucei ( T . brucei ) , for which the development of more effective , safe , and affordable chemotherapies remains a major goal .", "Vaccines are unlikely to be suitable [1]–[3] , and therefore disease control relies e...	[ "Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of the pentose phosphate pathway , and catalyzes the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate .", "Trypanosomatids , including the agent of African sleeping sickness namely Trypanosoma brucei , have a type B...	[ "Within the non-oxidative branch of the pentose phosphate pathway , ribose 5-phosphate isomerase catalyzes the inter-conversion of ribose 5-phosphate and ribulose 5-phosphate .", "There are two types of ribose 5-phosphate isomerase , namely A and B . The presence of type B in Trypanosoma brucei , and its absence ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	A Threshold Equation for Action Potential Initiation	journal.pcbi.1000850	null	[ [ "Spike initiation in neurons follows the all-or-none principle: a stereotypical action potential is produced and propagated when the neuron is sufficiently excited , while no spike is initiated below that threshold .", "The value of that threshold sets the firing rate and determines the way neurons comput...	[ "In central neurons , the threshold for spike initiation can depend on the stimulus and varies between cells and between recording sites in a given cell , but it is unclear what mechanisms underlie this variability .", "Properties of ionic channels are likely to play a role in threshold modulation .", "We exami...	[ "Neurons communicate primarily with stereotypical electrical impulses , action potentials , which are fired when a threshold level of excitation is reached .", "This threshold varies between cells and over time as a function of previous stimulations , which has major functional implications on the integrative pro...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/molecular dynamics", "computational biology/macromolecular structure analysis", "biophysics/theory and simulation", "biophysics/protein folding" ]	Exploring the Free Energy Landscape: From Dynamics to Networks and Back	journal.pcbi.1000415	null	[ [ "Polymers and , more specifically , proteins , show complex behavior at the cellular system level , e . g . in protein-protein interaction networks [1] , and also at the individual level , where proteins show a large degree of multistability: a single protein can fold in different conformational states [2]–[4...	[ "Knowledge of the Free Energy Landscape topology is the essential key to understanding many biochemical processes .", "The determination of the conformers of a protein and their basins of attraction takes a central role for studying molecular isomerization reactions .", "In this work , we present a novel framew...	[ "A complete description of complex polymers , such as proteins , includes information about their structure and their dynamics .", "In particular it is of utmost importance to answer the following questions: What are the structural conformations possible ?", "Is there any relevant hierarchy among these conforme...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "chemical compounds", "clinical research design", "pathology and laboratory medicine", "immunology", "tropical diseases", "neuroscience", "organic compounds", "anemia", "bacterial diseases", "research design", "cognitive neuroscience", "steroids", "signs and...	AZALEP a randomized controlled trial of azathioprine to treat leprosy nerve damage and Type 1 reactions in India: Main findings	journal.pntd.0005348	null	[ [ "Leprosy is complicated by immune–mediated reactions which affect about 30% of patients with Borderline leprosy . [1]", "These manifest clinically with inflammation of skin lesions and neuritis ( nerve inflammation ) which produces loss of sensory and motor nerve function .", "They are important becau...	[ "Leprosy Type 1 reactions are difficult to treat and only 70% of patients respond to steroid treatment .", "Azathioprine has been used as an immune-suppressant and we tested its efficacy in treating leprosy T1R .", "Randomised controlled trial adding azathioprine to steroid treatment for leprosy reactions .", ...	[ "Type 1 reactions affect leprosy patients and are due to increased inflammation in skin and nerves that can cause disfiguring skin lesions and loss of sensation and loss of power in the hands and the feet .", "These disabilities can lead to deformity and severe disability .", "It is important to improve the tre...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	The Potential for a Blood Test for Scabies	journal.pntd.0004188	null	[ [ "Scabies , caused by the mite , Sarcoptes scabiei , is a worldwide-occurring parasitic skin disease [1 , 2] .", "It was recently added to the list of neglected tropical diseases by the World Health Organization [3] .", "Estimates of the prevalence of scabies range from a small percent of the populatio...	[ "Scabies afflicts millions of people worldwide , but it is very difficult to diagnose by the usual skin scrape test , and a presumptive diagnosis is often made based on clinical signs such as rash and intense itch .", "A sensitive and specific blood test to detect scabies would allow a physician to quickly make a...	[ "Scabies , caused by the mite S . scabiei that burrows in the skin of humans , is a contagious skin disease that affects millions of people worldwide .", "It is a significant public health burden in economically disadvantaged populations , and outbreaks are common in nursing homes , daycare facilities , schools a...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "cell motility", "medicine and health sciences", "dictyostelium fruiting body", "dictyosteliomycota", "microbiology", "simulation and modeling", "fluorophotometry", "physiological processes", "developmental biology", "dictyostelium spore cells", "experimental organism system...	A critical-like collective state leads to long-range cell communication in Dictyostelium discoideum aggregation	journal.pbio.1002602	A multiscale model and imaging data show that cells of the slime mold Dictyostelium discoideum maximize their cell—cell communication range during aggregation by a critical-like state known from phase transitions in physical systems.	[ [ "Many living systems exhibit collective behavior , leading to beautiful patterns found in nature .", "Collective behavior is most obvious in animal groups with clear advantages in terms of mating , protection , foraging , and other decision-making processes [1 , 2] .", "However , how cells form collec...	[ "The transition from single-cell to multicellular behavior is important in early development but rarely studied .", "The starvation-induced aggregation of the social amoeba Dictyostelium discoideum into a multicellular slug is known to result from single-cell chemotaxis towards emitted pulses of cyclic adenosine ...	[ "Cells are often coupled to each other in cell collectives , such as aggregates during early development , tissues in the developed organism , and tumors in disease .", "How do cells communicate over macroscopic distances much larger than the typical cell—cell distance to decide how they should behave ?", "Here...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "evolutionary biology", "biochemistry/molecular evolution", "cell biology", "microbiology/parasitology" ]	Reductive Evolution of the Mitochondrial Processing Peptidases of the Unicellular Parasites Trichomonas vaginalis and Giardia intestinalis	journal.ppat.1000243	null	[ [ "The acquisition of the mitochondrial endosymbiont and its evolution into the mitochondrion were key events in the evolution of eukaryotes [1] .", "During this process , most of the protomitochondrial genome was either lost or transferred to the nucleus of the host cell [2] .", "As a consequence , mos...	[ "Mitochondrial processing peptidases are heterodimeric enzymes ( α/βMPP ) that play an essential role in mitochondrial biogenesis by recognizing and cleaving the targeting presequences of nuclear-encoded mitochondrial proteins .", "The two subunits are paralogues that probably evolved by duplication of a gene for...	[ "In classic model organisms , cleavage of signals that are required to deliver nuclear-encoded proteins to mitochondria is mediated by an enzyme comprising two different subunits , called α or β , neither of which is functional by itself .", "Here , we have characterized a novel enzyme that functions in the mitos...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "parastic protozoans", "immunopathology", "adaptive immunity", "immune cells", "leishmania", "immunity", "t cells", "immunology", "protozoology", "biology", "microbiology", "immunoregulation", "host-pathogen interaction", "immune response" ]	miR-182 and miR-10a Are Key Regulators of Treg Specialisation and Stability during Schistosome and Leishmania-associated Inflammation	journal.ppat.1003451	null	[ [ "Regulatory T ( Treg ) cells [1] employ an arsenal of non-overlapping mechanisms to maintain immunological homeostasis at environmental interfaces [2] and internal organs [3] , preventing the development of hyper-inflammatory conditions [4] , [5] .", "The suppressive functions of Treg cells are crucial , ...	[ "A diverse suite of effector immune responses provide protection against various pathogens .", "However , the array of effector responses must be immunologically regulated to limit pathogen- and immune-associated damage .", "CD4+Foxp3+ regulatory T cells ( Treg ) calibrate immune responses; however , how Treg c...	[ "The diversity of pathogens that the immune system encounters are controlled by a diverse suite of immunological effector responses .", "Preserving a well-controlled protective immune response is essential .", "Too vigorous an effector response can be as damaging as too little .", "Regulatory T cells ( Treg )...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "gastroenterology and hepatology/gastrointestinal infections", "immunology/immune response", "infectious diseases/bacterial infections", "immunology/immunity to infections", "infectious diseases/gastrointestinal infections" ]	Epithelial p38α Controls Immune Cell Recruitment in the Colonic Mucosa	journal.ppat.1000934	null	[ [ "Attaching and effacing ( A/E ) bacterial pathogens , such as the enteropathogenic Escherichia coli ( EPEC ) and enterohemorrhagic E . coli ( EHEC ) , cause debilitating disease , especially among infants and children , and are a threat to global health [1] , [2] .", "Citrobacter rodentium ( C . rodentium...	[ "Intestinal epithelial cells ( IECs ) compose the first barrier against microorganisms in the gastrointestinal tract .", "Although the NF-κB pathway in IECs was recently shown to be essential for epithelial integrity and intestinal immune homeostasis , the roles of other inflammatory signaling pathways in immune ...	[ "The cellular responses of intestinal epithelial cells ( IECs ) to microorganisms in the gastrointestinal tract are mediated by activation of a number of intracellular signaling pathways .", "It was shown that the NF-κB pathway in IECs is essential for epithelial integrity and intestinal immune homeostasis , and ...	2010
[ "Introduction", "Results", "Discussion" ]	[ "neuroscience/theoretical neuroscience", "neuroscience/sensory systems", "computational biology/computational neuroscience", "computational biology", "neuroscience", "computational biology/systems biology" ]	Representation of Time-Varying Stimuli by a Network Exhibiting Oscillations on a Faster Time Scale	journal.pcbi.1000370	null	[ [ "In recent years , there has been a growing interest in understanding how temporal information of sensory stimuli is encoded by sensory corticies ( see , e . g . , [1]–[8] ) .", "It has been shown that information about the features of the external stimulus is encoded in the fine temporal structure of the...	[ "Sensory processing is associated with gamma frequency oscillations ( 30–80 Hz ) in sensory cortices .", "This raises the question whether gamma oscillations can be directly involved in the representation of time-varying stimuli , including stimuli whose time scale is longer than a gamma cycle .", "We are inter...	[ "Sensory processing of time-varying stimuli , such as speech , is associated with high-frequency oscillatory cortical activity , the functional significance of which is still unknown .", "One possibility is that the oscillations are part of a stimulus-encoding mechanism .", "Here , we investigate a computationa...	2009
[ "Introduction" ]	[]	Ernst Rüdin’s Unpublished 1922-1925 Study “Inheritance of Manic-Depressive Insanity”: Genetic Research Findings Subordinated to Eugenic Ideology	journal.pgen.1005524	null	[ [ "At the DFA , Rüdin then worked on his second major inheritance study , on the genetic inheritance of “manic-depressive insanity” ( Zur Vererbung des manisch-depressiven Irreseins ) [28] .", "The original manuscript in the Historical Archives of the Max Planck Institute of Psychiatry in Munich is undated;...	[ "In the early 20th century , there were few therapeutic options for mental illness and asylum numbers were rising .", "This pessimistic outlook favoured the rise of the eugenics movement .", "Heredity was assumed to be the principal cause of mental illness .", "Politicians , scientists and clinicians in North...	[ "Psychiatric genetics was established as a scientific discipline in the early 20th century .", "The intention was to provide evidence for the inheritance of mental illnesses .", "This was to open up new paths in prevention , since therapeutic options at the time were meagre .", "Applying modern study designs ...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	BASiCS: Bayesian Analysis of Single-Cell Sequencing Data	journal.pcbi.1004333	null	[ [ "Current technology allows the analysis of gene expression with high resolution .", "Instead of measuring average expression levels across a bulk population , scientists can now report information at the single cell level using techniques such as single-cell RNA-sequencing ( scRNA-seq ) [1] .", "Unlik...	[ "Single-cell mRNA sequencing can uncover novel cell-to-cell heterogeneity in gene expression levels in seemingly homogeneous populations of cells .", "However , these experiments are prone to high levels of unexplained technical noise , creating new challenges for identifying genes that show genuine heterogeneous...	[ "Gene expression signatures have historically been used to generate molecular fingerprints that characterise distinct tissues .", "Moreover , by interrogating these molecular signatures it has been possible to understand how a tissue’s function is regulated at the molecular level .", "However , even between cel...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "biochemistry", "protein synthesis", "model organisms", "proteins", "gene expression", "genetics", "regulatory proteins", "biology", "mouse", "rna stability" ]	The Ribosomal Protein Rpl22 Controls Ribosome Composition by Directly Repressing Expression of Its Own Paralog, Rpl22l1	journal.pgen.1003708	null	[ [ "Protein synthesis is a major energy consuming process involving intricate coordination of translation machinery in response to nutrient availability and stress sensing signals , as well as hormonal and growth factor cues in multi-cellular organisms .", "The ribosome is comprised of two ribonucleoprotein ...	[ "Most yeast ribosomal protein genes are duplicated and their characterization has led to hypotheses regarding the existence of specialized ribosomes with different subunit composition or specifically-tailored functions .", "In yeast , ribosomal protein genes are generally duplicated and evidence has emerged that ...	[ "Translation is the process by which proteins are made within a cell .", "Ribosomes are the main macromolecular complexes involved in this process .", "Ribosomes are composed of ribosomal RNA and ribosomal proteins .", "Ribosomal proteins are generally thought to be structural components of the ribosome but r...	2013

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