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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" ]	[]	Genetic Interaction Mapping Reveals a Role for the SWI/SNF Nucleosome Remodeler in Spliceosome Activation in Fission Yeast	journal.pgen.1005074	null	[ [ "Recent work has uncovered extensive crosstalk amongst chromatin , transcription and RNA processing machineries .", "Changes to chromatin typically involve nucleosomes—histone octomers wrapped by approximately 147 nucleotides of DNA .", "We now know that nucleosomes are enriched in exons relative to i...	[ "Although numerous regulatory connections between pre-mRNA splicing and chromatin have been demonstrated , the precise mechanisms by which chromatin factors influence spliceosome assembly and/or catalysis remain unclear .", "To probe the genetic network of pre-mRNA splicing in the fission yeast Schizosaccharomyce...	[ "It has recently become apparent that most introns are removed from pre-mRNA while the transcript is still engaged with RNA polymerase II ( RNAPII ) .", "To gain insight into possible roles for chromatin in co-transcriptional splicing , we generated a genome-wide genetic interaction map in fission yeast and uncov...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell binding", "cell physiology", "chemical characterization", "gene regulation", "regulatory proteins", "dna-binding proteins", "genome analysis", "transcription factors", "genome annotation", "sequence motif analysis", "epigenetics", "chromatin", "research and analysis methods", "sequen...	Deconvolving sequence features that discriminate between overlapping regulatory annotations	journal.pcbi.1005795	null	[ [ "Many regulatory genomics analyses focus on finding DNA sequence features that are characteristic of a biological property .", "Given a set of sequences that are bound by a particular transcription factor ( TF ) , for example , we typically aim to discover short , degenerate DNA patterns that may represen...	[ "Genomic loci with regulatory potential can be annotated with various properties .", "For example , genomic sites bound by a given transcription factor ( TF ) can be divided according to whether they are proximal or distal to known promoters .", "Sites can be further labeled according to the cell types and cond...	[ "Transcription factor proteins control gene expression by recognizing and interacting with short DNA sequence patterns in regulatory regions on the genome .", "Current genomics experiments allow us to find regulatory regions associated with a particular biochemical activity over the entire genome; for example , a...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "echinococcosis", "infectious diseases", "veterinary epidemiology", "mathematics", "environmental epidemiology", "epidemiology", "statistics", "spatial epidemiology", "biostatistics", "epidemiological methods", "parasitic diseases", "veterinary science" ]	Dynamics of the Force of Infection: Insights from Echinococcus multilocularis Infection in Foxes	journal.pntd.0002731	null	[ [ "The force of infection ( FOI ) is a crucial epidemiological parameter and characterizing its dynamics is an essential part of planning cost effective control strategies for infectious diseases [1] .", "Mechanistically , disease intervention strategies are typically targeted at decreasing the per capita i...	[ "Characterizing the force of infection ( FOI ) is an essential part of planning cost effective control strategies for zoonotic diseases .", "Echinococcus multilocularis is the causative agent of alveolar echinococcosis in humans , a serious disease with a high fatality rate and an increasing global spread .", "...	[ "Human alveolar echinococcosis ( AE ) is caused by the fox tapeworm E . multilocularis and has a high fatality rate if untreated .", "The frequency of the tapeworm in foxes can be reduced through the regular distribution of anthelmintic baits and thus decrease the risk of zoonotic transmission .", "Here , we es...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "evolutionary biology", "neuroscience", "genetics and genomics" ]	Incomplete and Inaccurate Vocal Imitation after Knockdown of FoxP2 in Songbird Basal Ganglia Nucleus Area X	journal.pbio.0050321	The FoxP2 gene, which is essential for human speech and language, is also required for proper song development in songbirds, raising the possibility that songbirds and humans share molecular pathways for learned vocalizations.	[ [ "Genetic aberrations of FOXP2 cause developmental verbal dyspraxia ( DVD ) , which is characterized by impaired production of sequenced mouth movements and both expressive and receptive language deficits [1–4] .", "Brain imaging studies in adult FOXP2 patients implicate the basal ganglia as key affected r...	[ "The gene encoding the forkhead box transcription factor , FOXP2 , is essential for developing the full articulatory power of human language .", "Mutations of FOXP2 cause developmental verbal dyspraxia ( DVD ) , a speech and language disorder that compromises the fluent production of words and the correct use and...	[ "Do special “human” genes provide the biological substrate for uniquely human traits , such as language ?", "Genetic aberrations of the human FoxP2 gene impair speech production and comprehension , yet the relative contributions of FoxP2 to brain development and function are unknown .", "Songbirds are a useful ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/pattern formation", "neuroscience/neurodevelopment", "developmental biology", "neuroscience/sensory systems" ]	Positional Cues in the Drosophila Nerve Cord: Semaphorins Pattern the Dorso-Ventral Axis	journal.pbio.1000135	Positional cues target sensory axons to appropriate volumes of the developing nervous system independently of their synaptic partners.	[ [ "During the development of neural circuitry , neurons of different kinds must establish specific synaptic connections by selecting appropriate targets from large numbers of different alternatives .", "The range of these alternative targets is reduced by well organised patterns of growth , termination , an...	[ "During the development of neural circuitry , neurons of different kinds establish specific synaptic connections by selecting appropriate targets from large numbers of alternatives .", "The range of alternative targets is reduced by well organised patterns of growth , termination , and branching that deliver the ...	[ "Axons and dendrites of synaptic partners must be targeted to a common region of the developing neural network so that appropriate connections can be formed .", "The mechanisms underlying this targeting are incompletely understood .", "We showed previously that a positional cue ( Slit ) acting in the medio-late...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene regulation", "host-pathogen interaction", "microbiology", "fungal physiology", "gene function", "fungal evolution", "molecular genetics", "fungal reproduction", "mycology", "signaling in cellular processes", "transcriptional signaling", "gene expression", "biology", "pathogenesis", ...	The Transcription Factor BcLTF1 Regulates Virulence and Light Responses in the Necrotrophic Plant Pathogen Botrytis cinerea	journal.pgen.1004040	null	[ [ "Botrytis cinerea Persoon: Fries ( teleomorph Botryotinia fuckeliana ( de Bary ) Whetzel ) is a necrotrophic pathogen with a broad host range causing gray mold disease in several economically important plants including grape vine and strawberry [1]–[2] .", "Sources of infection by B . cinerea are the coni...	[ "Botrytis cinerea is the causal agent of gray mold diseases in a range of dicotyledonous plant species .", "The fungus can reproduce asexually by forming macroconidia for dispersal and sclerotia for survival; the latter also participate in sexual reproduction by bearing the apothecia after fertilization by microc...	[ "Both fungal pathogens and their host plants respond to light , which represents an important environmental cue .", "Unlike plants using light for energy generation , filamentous fungi use light , or its absence , as a general signal for orientation ( night/day , underground/on the surface ) .", "Therefore , de...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computer science/natural and synthetic vision", "neuroscience/natural and synthetic vision", "neuroscience/sensory systems" ]	A High-Throughput Screening Approach to Discovering Good Forms of Biologically Inspired Visual Representation	journal.pcbi.1000579	null	[ [ "The study of biological vision and the creation of artificial vision systems are naturally intertwined—exploration of the neuronal substrates of visual processing provides clues and inspiration for artificial systems , and artificial systems , in turn , serve as important generators of new ideas and working ...	[ "While many models of biological object recognition share a common set of “broad-stroke” properties , the performance of any one model depends strongly on the choice of parameters in a particular instantiation of that model—e . g . , the number of units per layer , the size of pooling kernels , exponents in normali...	[ "One of the primary obstacles to understanding the computational underpinnings of biological vision is its sheer scale—the visual system is a massively parallel computer , comprised of billions of elements .", "While this scale has historically been beyond the reach of even the fastest super-computing systems , r...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology", "genetics", "epigenetics", "biology", "computational biology" ]	Coordinated Cell Type–Specific Epigenetic Remodeling in Prefrontal Cortex Begins before Birth and Continues into Early Adulthood	journal.pgen.1003433	null	[ [ "Prolonged maturation of the human cerebral cortex , which extends into the third decade of life , is critical for proper development of executive functions , such as higher order problem solving and complex cognition [1] , [2] .", "Little is known about changes within the nuclei of post-mitotic neurons d...	[ "Development of prefrontal and other higher-order association cortices is associated with widespread changes in the cortical transcriptome , particularly during the transitions from prenatal to postnatal development , and from early infancy to later stages of childhood and early adulthood .", "However , the timin...	[ "Prolonged maturation of the human cerebral cortex , which extends into the third decade of life , is critical for proper development of executive functions such as higher-order problem-solving and complex cognition .", "Little is known about changes of post-mitotic neurons during this prolonged maturation period...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Bi-modal Distribution of the Second Messenger c-di-GMP Controls Cell Fate and Asymmetry during the Caulobacter Cell Cycle	journal.pgen.1003744	null	[ [ "Cyclic di-GMP is a ubiquitous second messenger that serves as key regulator of bacterial life-style decisions .", "While low intracellular concentrations of c-di-GMP promote a planktonic , single-cell life-style , where cells are generally motile and express virulence determinants , high levels of c-di-G...	[ "Many bacteria mediate important life-style decisions by varying levels of the second messenger c-di-GMP .", "Behavioral transitions result from the coordination of complex cellular processes such as motility , surface adherence or the production of virulence factors and toxins .", "While the regulatory mechani...	[ "Bacterial processes like virulence , motility or biofilm formation are governed by the second messenger c-di-GMP .", "In most bacteria , c-di-GMP is produced and degraded by a complex network comprising dozens of enzymes .", "This has hindered a comprehensive analysis of the cellular role of c-di-GMP .", "He...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "decision theory", "classical mechanics", "decision making", "engineering and technology", "thermometers", "statistics", "applied mathematics", "social sciences", "mathematical models", "neuroscience", "cognitive psychology", "mathematics", "cognition", "plants", "research and analysis m...	Sour grapes and sweet victories: How actions shape preferences	journal.pcbi.1006499	null	[ [ "Classical decision-making theory states that when facing a choice , agents consider the cost attached to potential actions and the value of their expected outcomes , and select the option that gives the maximal net benefit [1–5] .", "In this classical view , values are subjective estimates of anticipated...	[ "Classical decision theory postulates that choices proceed from subjective values assigned to the probable outcomes of alternative actions .", "Some authors have argued that opposite causality should also be envisaged , with choices influencing subsequent values expressed in desirability ratings .", "The idea i...	[ "The standard way to explain decisions is the so-called valuation/selection model , which includes", "1 ) a value function that calculates desirability for every possible outcome of alternative actions and", "2 ) a choice function that integrates outcome values and generates selection probability for every acti...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "biofilms", "medicine and health sciences", "pathology and laboratory medicine", "enzymes", "pathogens", "microbiology", "enzymology", "materials science", "glycoside hydrolases", "sequence motif analysis", "oligomers", "macromolecules", "bacteria", "bacterial pathogens",...	PgaB orthologues contain a glycoside hydrolase domain that cleaves deacetylated poly-β(1,6)-N-acetylglucosamine and can disrupt bacterial biofilms	journal.ppat.1006998	null	[ [ "A major determinant of Bordetella pathogenicity is their ability to form biofilms on biotic and abiotic surfaces [1–9] .", "Bordetella pertussis and parapertussis are the causative agents of whooping cough in humans , whereas Bordetella bronchiseptica has a broad host range , colonizing and causing respi...	[ "Poly-β ( 1 , 6 ) -N-acetyl-D-glucosamine ( PNAG ) is a major biofilm component of many pathogenic bacteria .", "The production , modification , and export of PNAG in Escherichia coli and Bordetella species require the protein products encoded by the pgaABCD operon .", "PgaB is a two-domain periplasmic protein ...	[ "From plaque on teeth to infections in the lungs of cystic fibrosis patients , biofilms are a serious health concern and difficult to eradicate .", "One of the key building blocks involved in biofilm formation are polymeric sugar compounds that are secreted by the bacteria .", "Our work focuses on the biopolyme...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "genetics and genomics/genetics of the immune system", "cell biology", "immunology/genetics of the immune system", "molecular biology" ]	A cis-Acting Diversification Activator Both Necessary and Sufficient for AID-Mediated Hypermutation	journal.pgen.1000332	null	[ [ "Vertebrate B cells are able to diversify their rearranged immunoglobulin ( Ig ) genes by hypermutation , gene conversion and class switch recombination .", "All three phenomena require expression of Activation Induced cytidine Deaminase ( AID , NC_006088 ) [1]–[3] which most likely initiates Ig gene dive...	[ "Hypermutation of the immunoglobulin ( Ig ) genes requires Activation Induced cytidine Deaminase ( AID ) and transcription , but it remains unclear why other transcribed genes of B cells do not mutate .", "We describe a reporter transgene crippled by hypermutation when inserted into or near the Ig light chain ( I...	[ "It remains an open question how AID-mediated gene diversification is targeted to the immunoglobulin loci .", "Here we define a cis-acting sequence , named DIVAC for diversification activator , which is required for hypermutation of the Ig light chain gene and sufficient to activate hypermutation at various non-I...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "dermatology", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "tropical diseases", "microbiology", "geographical locations", "alphaviruses", "headaches", "viruses", "chikungunya virus", "rna viruses", "signs and s...	First Chikungunya Outbreak in Suriname; Clinical and Epidemiological Features	journal.pntd.0004625	null	[ [ "Chikungunya fever is caused by a classical arbovirus ( genus Alphavirus , family Togaviridae ) , which is transmitted to humans primarily through Aedes aegypti and Aedes albopictus mosquitoes [1] .", "Acute onset of fever and polyarthralgia , mainly affecting the extremities ( wrists , ankles , phalanges...	[ "In June 2014 , Suriname faced the first Chikungunya outbreak .", "Since international reports mostly focus on hospitalized patients , the least affected group , a study was conducted to describe clinical characteristics of mainly outpatients including children .", "In addition , the cumulative incidence of thi...	[ "Chikungunya virus is transmitted to humans by mosquito bites and causes fever and joint pain .", "Chikungunya was first detected in Africa , but recently became a worldwide concern with outbreaks in many ( sub ) -tropical countries .", "We report the characteristics of the first outbreak in Suriname ( 2014–201...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine" ]	Regulatory T Cells Enhance Susceptibility to Experimental Trypanosoma Congolense Infection Independent of Mouse Genetic Background	journal.pntd.0001761	null	[ [ "Tse-Tse-transmitted trypanosomiasis is a complex disease in both humans and animals caused by several species of the protozoan parasite Trypanosoma [1] .", "Trypanosoma brucei gambiense and Trypanosoma brucei rhodensiense cause disease in humans ( sleeping sickness ) while trypanosomiasis in animals ( Na...	[ "BALB/c mice are highly susceptible while C57BL/6 are relatively resistant to experimental Trypanosoma congolense infection .", "Although regulatory T cells ( Tregs ) have been shown to regulate the pathogenesis of experimental T . congolense infection , their exact role remains controversial .", "We wished to ...	[ "BALB/c mice are highly susceptible while C57BL/6 is relatively resistant to experimental Trypanosoma congolense infection .", "Acute death observed in infected BALB/c mice is usually associated with the excessive production of pro-inflammatory cytokines .", "Regulatory T cells ( Tregs ) have been shown to play...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "genetics of the immune system", "genetics", "molecular genetics", "biology", "human genetics", "gene duplication", "immunology", "genetics and genomics" ]	Copy Number Variation of KIR Genes Influences HIV-1 Control	journal.pbio.1001208	The authors that the number of activating and inhibitory KIR genes varies between individuals and plays a role in the regulation of immune mechanisms that determine HIV-1 control.	[ [ "The KIR receptors are expressed mainly on the surface of lymphocyte subsets including natural killer ( NK ) cells and a small subset of T cells , and they have a unique role in fine-tuning the balance between self-tolerance and cytotoxicity .", "KIRs bind to major histocompatibility complex ( MHC ) class...	[ "A genome-wide screen for large structural variants showed that a copy number variant ( CNV ) in the region encoding killer cell immunoglobulin-like receptors ( KIR ) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry .", "This CNV encompasses the KIR3D...	[ "There is marked intrinsic variation in the extent to which individuals are able to control HIV-1 .", "We have identified a genetic copy number variable region ( CNV ) in humans that plays a significant role in the control of HIV-1 .", "This CNV is located in the genomic region that encodes the killer cell immu...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cellular stress responses", "aspergillus", "oxidative stress", "fungal genetics", "cell processes", "dna transcription", "aspergillus nidulans", "mutation", "fungi", "experimental organism systems", "mitochondria", "bioenergetics", "cellular structures and organelles", "research and analy...	Sem1 links proteasome stability and specificity to multicellular development	journal.pgen.1007141	null	[ [ "The 26S proteasome represents the major cytoplasmic and nuclear ubiquitin-dependent protein degradation machinery and is composed of a barrel-like 2 . 5 MDa 20S proteolytic core particle ( CP ) capped with one or two 19S regulatory particles ( RP ) .", "Proteins destined for degradation are unfolded , de...	[ "The transition from vegetative growth to multicellular development represents an evolutionary hallmark linked to an oxidative stress signal and controlled protein degradation .", "We identified the Sem1 proteasome subunit , which connects stress response and cellular differentiation .", "The sem1 gene encodes ...	[ "The cellular ubiquitin-proteasome pathway is essential to control cell cycle , gene expression or the response to oxidative stress .", "Sem1 is conserved in eukaryotes from single cell yeasts to humans as intrinsically disordered and multifunctional protein .", "Sem1 supports the assembly of several multiprote...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell death", "medicine and health sciences", "markov models", "cell processes", "cancers and neoplasms", "gastrointestinal tumors", "oncology", "systems science", "mathematics", "statistics (mathematics)", "epigenetics", "cancer epidemiology", "computer and information sciences", "epidemi...	Parameter estimation for multistage clonal expansion models from cancer incidence data: A practical identifiability analysis	journal.pcbi.1005431	null	[ [ "Parameter estimation is an important aspect of computational modeling in the life sciences because parameter estimates can shed light on underlying biological mechanisms and processes and provide a way to link dynamic models to real-world data .", "However , the dynamics of many living systems have evolv...	[ "Many cancers are understood to be the product of multiple somatic mutations or other rate-limiting events .", "Multistage clonal expansion ( MSCE ) models are a class of continuous-time Markov chain models that capture the multi-hit initiation–promotion–malignant-conversion hypothesis of carcinogenesis .", "Th...	[ "Parameter estimation from data is an important part of mathematical modeling , and structural identifiability is the study of what parametric information exists , for a given model , in ideal data .", "Unfortunately , for a variety of reasons , there is often less information available in our real data sets .", ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell motility", "medicine and health sciences", "swimming", "pathology and laboratory medicine", "pathogens", "microbiology", "sand flies", "flagellar motility", "parasitic diseases", "protozoan life cycles", "parasitic protozoans", "biological locomotion", "developmental biology", "proto...	Genetic dissection of a Leishmania flagellar proteome demonstrates requirement for directional motility in sand fly infections	journal.ppat.1007828	null	[ [ "Eukaryotic flagella / cilia are complex multifunctional organelles conserved from protists to humans [1] .", "Protists use flagella for swimming , feeding , cell-to-cell communication , adherence to substrates and morphogenesis [2] .", "Single-celled organisms , most prominently among them the green ...	[ "The protozoan parasite Leishmania possesses a single flagellum , which is remodelled during the parasite’s life cycle from a long motile flagellum in promastigote forms in the sand fly to a short immotile flagellum in amastigotes residing in mammalian phagocytes .", "This study examined the protein composition a...	[ "Leishmania are protozoan parasites , transmitted between mammals by the bite of phlebotomine sand flies .", "Promastigote forms in the sand fly have a long flagellum , which is motile and used for anchoring the parasites to prevent clearance with the digested blood meal remnants .", "To dissect flagellar funct...	2019
[ "Introduction", "Results/Discussion", "Methods" ]	[ "computational biology/systems biology", "computational biology/transcriptional regulation", "cell biology/cellular death and stress responses", "genetics and genomics/functional genomics", "genetics and genomics/gene expression", "computational biology/genomics", "genetics and genomics/bioinformatics" ...	Genome-Wide Fitness and Expression Profiling Implicate Mga2 in Adaptation to Hydrogen Peroxide	journal.pgen.1000488	null	[ [ "Oxidative stress is caused by a number of reactive oxygen species ( ROS ) generated as a result of aerobic metabolism or chemical exposure .", "These compounds damage a variety of cellular products , including DNA , proteins , and lipid membranes , and are associated with a number of human pathologies ."...	[ "Caloric restriction extends lifespan , an effect once thought to involve attenuation of reactive oxygen species ( ROS ) generated by aerobic metabolism .", "However , recent evidence suggests that caloric restriction may in fact raise ROS levels , which in turn provides protection from acute doses of oxidant thr...	[ "Reactive oxygen species ( ROS ) damage a variety of structures within the cell , resulting in disease and aging .", "In a seemingly paradoxical effect termed adaptation , it is possible to prevent damage caused by ROS by pre-treating the cell with a small amount of oxidant .", "We studied this process in order...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biotechnology", "medicine", "drug research and development", "science policy", "technology development", "drugs and devices", "pharmacology", "biology", "zoology", "drug discovery", "helminthology" ]	Whole Organism High-Content Screening by Label-Free, Image-Based Bayesian Classification for Parasitic Diseases	journal.pntd.0001762	null	[ [ "Infection with parasitic worms ( helminths ) causes a huge burden of human disease [1] and economic loss to the livestock industry [2] .", "Currently the major control strategy for the human diseases is by large scale drug administration to schools or by mass drug administration [3] .", "However , th...	[ "Sole reliance on one drug , Praziquantel , for treatment and control of schistosomiasis raises concerns about development of widespread resistance , prompting renewed interest in the discovery of new anthelmintics .", "To discover new leads we designed an automated label-free , high content-based , high throughp...	[ "Schistosomiasis is a severe helminth infection affecting an estimated 600 million people .", "The one drug widely available , praziquantel ( PZQ ) , is not ideal .", "PZQ kills the adult worms but not the developing juveniles so the treated patient may not be cured long-term .", "In addition , use of repeate...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "children", "medicine and health sciences", "ecology and environmental sciences", "ecological niches", "maternal health", "obstetrics and gynecology", "neuroscience", "endocrine physiology", "age groups", "women's health", "theoretical ecology", "population biology", "evolutionary emergence"...	Grandmothering and cognitive resources are required for the emergence of menopause and extensive post-reproductive lifespan	journal.pcbi.1005631	null	[ [ "Menopause , the permanent cessation of ovulation , occurs in women well before the end of their expected lifespan; reproductive senescence occurs substantially earlier than somatic senescence , leading to a particularly long post-reproductive life [1] .", "This is a rather uniform pattern across traditio...	[ "Menopause , the permanent cessation of ovulation , occurs in humans well before the end of the expected lifespan , leading to an extensive post-reproductive period which remains a puzzle for evolutionary biologists .", "All human populations display this particularity; thus , it is difficult to empirically evalu...	[ "In all human populations , regardless of environmental and socioeconomic conditions , menopause occurs in women well before the end of their expected lifespan .", "Conversely , extensive post-reproductive life-span is rare in other species; except in some cetaceans .", "Evolutionary theory predicts that menopa...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal models of infection", "immunodeficiency viruses", "mechanisms of resistance and susceptibility", "model organisms", "viral immune evasion", "virology", "genetics", "viral structure", "biology", "microbiology", "evolutionary biology", "viral evolution" ]	Gain-of-Sensitivity Mutations in a Trim5-Resistant Primary Isolate of Pathogenic SIV Identify Two Independent Conserved Determinants of Trim5α Specificity	journal.ppat.1003352	null	[ [ "The anti-retroviral activity of Trim5α was discovered in a screen to identify rhesus macaque cDNAs conferring resistance to HIV-1 replication [1] .", "Antiretroviral activity has since been demonstrated for a large number of primate Trim5 orthologs , including prosimians , as well as homologs from cow an...	[ "Retroviral capsid recognition by Trim5 blocks productive infection .", "Rhesus macaques harbor three functionally distinct Trim5 alleles: Trim5αQ , Trim5αTFP and Trim5CypA .", "Despite the high degree of amino acid identity between Trim5αQ and Trim5αTFP alleles , the Q/TFP polymorphism results in the different...	[ "TRIM5α is an intrinsic immunity protein that blocks retrovirus infection through a specific interaction with the viral capsid .", "Uniquely among primates , rhesus macaques harbor three functionally distinct kinds of Trim5 alleles: rhTrim5αTFP , rhTrim5αQ and rhTrim5CypA .", "SIVmac239 , a simian immunodeficie...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fourier analysis", "medicine and health sciences", "membrane potential", "social sciences", "light", "electrophysiology", "neuroscience", "electromagnetic radiation", "systems science", "mathematics", "luminance", "visible light", "vision", "research and analysis methods", "computer and...	A novel mechanism of cone photoreceptor adaptation	journal.pbio.2001210	null	[ [ "A natural environment is an ever-changing sensory landscape .", "Sensory systems adapt to these changes , increasing an animal’s ability to extract important information and survive under a wide range of conditions .", "In the natural world , the mean luminance and variations around the mean luminanc...	[ "An animal’s ability to survive depends on its sensory systems being able to adapt to a wide range of environmental conditions , by maximizing the information extracted and reducing the noise transmitted .", "The visual system does this by adapting to luminance and contrast .", "While luminance adaptation can b...	[ "An animal’s ability to survive depends on its ability to adapt to a wide range of light conditions , by maximizing the information flow through the retina .", "Here , we show a new form of adaptation in cone photoreceptors that helps them optimize the information they transmit by adjusting their response kinetic...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genomics", "model organisms", "biology", "computational biology" ]	On the Use of Gene Ontology Annotations to Assess Functional Similarity among Orthologs and Paralogs: A Short Report	journal.pcbi.1002386	null	[ [ "The Gene Ontology ( GO ) Consortium has , over the last 10 years , revolutionized the use of structured , controlled vocabularies in biology , and provides GO annotations of gene products that describe biological function from the molecular to organism level [1] , [2] .", "During this time , the biocurat...	[ "A recent paper ( Nehrt et al . , PLoS Comput . Biol . 7:e1002073 , 2011 ) has proposed a metric for the “functional similarity” between two genes that uses only the Gene Ontology ( GO ) annotations directly derived from published experimental results .", "Applying this metric , the authors concluded that paralog...	[ "Understanding gene function—how individual genes contribute to the biology of an organism at the molecular , cellular and organism levels—is one of the primary aims of biomedical research .", "It has been a longstanding tenet of model organism research that experimental knowledge obtained in one organism is ofte...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "drosophila", "cell biology", "developmental biology", "molecular biology" ]	Developmental Role and Regulation of cortex, a Meiosis-Specific Anaphase-Promoting Complex/Cyclosome Activator	journal.pgen.0030202	null	[ [ "Developmental regulation of meiosis is crucial for generating viable eggs and sperm and , thus , a successful fertilization event .", "Meiosis is a modified cell cycle in which segregation of homologous chromosomes is followed by segregation of sister chromatids without an intervening S phase .", "Th...	[ "During oogenesis in metazoans , the meiotic divisions must be coordinated with development of the oocyte to ensure successful fertilization and subsequent embryogenesis .", "The ways in which the mitotic machinery is specialized for meiosis are not fully understood .", "cortex , which encodes a putative female...	[ "Meiosis is a modified cell cycle that generates four gametes , each containing half the genetic content of the parent cell , through a reductional division followed by an equational division without an intervening DNA synthesis phase .", "During oogenesis of multicellular organisms , proper coordination of the m...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "cellular stress responses", "cell division", "cell biology", "gene expression", "biology", "molecular cell biology", "molecular biology" ]	The Fission Yeast Stress-Responsive MAPK Pathway Promotes Meiosis via the Phosphorylation of Pol II CTD in Response to Environmental and Feedback Cues	journal.pgen.1002387	null	[ [ "The cell cycle programs for mitosis and meiosis appear to be strictly segregated from each other , although they are likely to have molecular mechanisms in common .", "Analyses in lower eukaryotes have shown that factors required exclusively for meiosis , generated through the transcriptional activation ...	[ "The RRM-type RNA-binding protein Mei2 is a master regulator of meiosis in fission yeast , in which it stabilizes meiosis-specific mRNAs by blocking their destruction .", "Artificial activation of Mei2 can provoke the entire meiotic process , and it is suspected that Mei2 may do more than the stabilization of mei...	[ "Hundreds of genes are newly expressed during meiosis , a process to form gametes , and the control of meiosis-specific gene expression is not simple .", "The master regulator of meiosis in fission yeast , Mei2 , blocks an RNA destruction system that selectively degrades meiosis-specific mRNAs , highlighting the ...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "rna-binding proteins", "medicine and health sciences", "rna sequences", "pathology and laboratory medicine", "pathogens", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "enthalpy", "rna viruses", "sequence motif analysis", "thermodynamics", "research and analysis m...	The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV	journal.ppat.1006221	null	[ [ "The assembly of the HIV particle is orchestrated by the HIV-1 Gag precursor protein ( Pr55Gag ) .", "As the major structural protein forming the virus , it is essential that Pr55Gag packs tightly with other Pr55Gag molecules to shape the virus shell while also encapsulating the genomic RNA required for i...	[ "The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packaging are essential elements that facilitate HIV assembly .", "However , mechanistic details of these interactions are not clearly defined .", "Here , we overcome previous limitations in producing large quantities of full-length...	[ "Formation of any virus particle will require energy , yet the precise biophysical properties that drive the formation of HIV particles remain undefined .", "Isothermal titration calorimetry ( ITC ) is a biophysical technique that is the gold standard to reveal parameters governing biochemical and biophysical rea...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "molecular biology/histone modification", "cell biology/gene expression", "computational biology/transcriptional regulation", "molecular biology/transcription elongation", "genetics and genomics/epigenetics", "molecular biology/chromatin structure" ]	Evidence for Gene-Specific Rather Than Transcription Rate–Dependent Histone H3 Exchange in Yeast Coding Regions	journal.pcbi.1000282	null	[ [ "The nucleosome is the basic repeating unit of the chromatin and comprises 147 bp of DNA wrapped around an octamer of histone proteins ( two copies of H2A , H2B , H3 and H4 ) .", "Nucleosome disassembly and reassembly is tightly coupled with replication , transcription , DNA repair and heterochromatin sil...	[ "In eukaryotic organisms , histones are dynamically exchanged independently of DNA replication .", "Recent reports show that different coding regions differ in their amount of replication-independent histone H3 exchange .", "The current paradigm is that this histone exchange variability among coding regions is ...	[ "During nucleosome disassembly and reassembly , evicted histones are exchanged with newly synthesized histones .", "Histone exchange occurs in several DNA metabolism processes , including replication , transcription , and repair .", "Recent reports from several labs show that replication-independent histone H3 ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "developmental biology/developmental molecular mechanisms", "molecular biology/dna methylation", "genetics and genomics/gene expression" ]	Inter- and Intra-Individual Variation in Allele-Specific DNA Methylation and Gene Expression in Children Conceived using Assisted Reproductive Technology	journal.pgen.1001033	null	[ [ "Several epidemiological studies have reported a higher incidence of rare disorders involving imprinted genes ( Angelman syndrome [1]–[3] and Beckwith-Wiedemann syndrome [4]–[8] ) among children conceived using assisted reproductive technologies ( ART ) .", "Studies on imprinted gene expression and parent...	[ "Epidemiological studies have reported a higher incidence of rare disorders involving imprinted genes among children conceived using assisted reproductive technology ( ART ) , suggesting that ART procedures may be disruptive to imprinted gene methylation patterns .", "We examined intra- and inter-individual varia...	[ "We have screened a population of children conceived in vitro for epigenetic alterations at two loci that carry parent-of-origin specific methylation marks .", "We made the observation that epigenetic variability was greater in extraembryonic tissues than embryonic tissues in both groups , as has also been demons...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Borna Disease Virus Phosphoprotein Impairs the Developmental Program Controlling Neurogenesis and Reduces Human GABAergic Neurogenesis	journal.ppat.1004859	null	[ [ "Upon entrance in the brain , viruses most often induce inflammation , fever , and brain injury , all signs symptomatic of acute encephalitis .", "A strong immunological response is typically triggered and generally limits viral dissemination and resolves infection .", "In some cases , however , virus...	[ "It is well established that persistent viral infection may impair cellular function of specialized cells without overt damage .", "This concept , when applied to neurotropic viruses , may help to understand certain neurologic and neuropsychiatric diseases .", "Borna disease virus ( BDV ) is an excellent exampl...	[ "When a virus enters the brain , it most often induces inflammation , fever , and brain injury , all signs that are indicative of acute encephalitis .", "Under certain conditions , however , some neurotropic viruses may cause disease in a subtler manner .", "The Borna disease virus ( BDV ) is an excellent examp...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/macromolecular structure analysis" ]	Beauty Is in the Eye of the Beholder: Proteins Can Recognize Binding Sites of Homologous Proteins in More than One Way	journal.pcbi.1000821	null	[ [ "Protein-protein interaction is the basis of numerous biological functions , such as immune response , supra-molecular assembly , enzymatic reactions , and many more .", "Understanding the way proteins interact is thus a fundamental challenge .", "The collection of all protein-protein interactions , t...	[ "Understanding the mechanisms of protein–protein interaction is a fundamental problem with many practical applications .", "The fact that different proteins can bind similar partners suggests that convergently evolved binding interfaces are reused in different complexes .", "A set of protein complexes composed ...	[ "Interaction between proteins is a fundamental process , generic to most biological pathways .", "The increasing number of protein–protein complexes with atomic data should help us to understand the major factors that guide protein interactions .", "In particular , a number of examples are available of similar ...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "linguistics", "diagnostic radiology", "pathology and laboratory medicine", "nervous system", "brain", "social sciences", "neuroscience", "magnetic resonance imaging", "brain morphometry", "signs and symptoms", "temporal lobe", "artificial intelligence", "br...	Semantic representation in the white matter pathway	journal.pbio.2003993	null	[ [ "One of the most challenging questions in cognitive neuroscience is how abstract knowledge emerges from more basic dimensions of information , such as visual shapes and patterns of motor action .", "How do we proceed from the visual shape of a pair of scissors to the knowledge that they can be used to cut...	[ "Object conceptual processing has been localized to distributed cortical regions that represent specific attributes .", "A challenging question is how object semantic space is formed .", "We tested a novel framework of representing semantic space in the pattern of white matter ( WM ) connections by extending th...	[ "One of the most challenging questions in cognitive neuroscience is how semantic knowledge , for example , that “scissors” and “knives” are related in meaning , can emerge from primary sensory dimensions such as visual forms .", "It is often assumed that in the human brain , semantics are stored in regions of the...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "glycolipids", "immune cells", "viral transmission and infection", "sphingolipids", "antigen-presenting cells", "immunity to infections", "immunology", "microbiology", "host-pathogen interaction", "viral structure", "viral attachment", "viruslike particles", "lipids", "viral immune evasion...	Siglec-1 Is a Novel Dendritic Cell Receptor That Mediates HIV-1 Trans-Infection Through Recognition of Viral Membrane Gangliosides	journal.pbio.1001448	The novel dendritic cell receptor Siglec-1 binds sialyllactose moieties on HIV-1 membrane gangliosides, thereby enhancing HIV-1 transinfection.	[ [ "HIV-1 can infect CD4+ cells of the lymphoid and myeloid lineage with a strong preference for CD4+ T cells .", "Myeloid DCs exhibit innate resistance against HIV-1 infection .", "HIV-2 , on the other hand , efficiently infects myeloid DCs due to its accessory viral protein Vpx , not present in HIV-1 ,...	[ "Dendritic cells ( DCs ) are essential antigen-presenting cells for the induction of immunity against pathogens .", "However , HIV-1 spread is strongly enhanced in clusters of DCs and CD4+ T cells .", "Uninfected DCs capture HIV-1 and mediate viral transfer to bystander CD4+ T cells through a process termed tra...	[ "Mature dendritic cells ( mDCs ) capture and store infectious HIV-1 and subsequently infect neighboring CD4+ T cells in lymphoid organs .", "This process , known as trans-infection , is a key contributor to HIV pathogenesis , but the precise mechanism and the identity of the receptor on the mDC surface that recog...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "invertebrates", "caenorhabditis", "invertebrate genomics", "animals", "animal models", "nucleosome mapping", "caenorhabditis elegans", "drosophila melanogaster", "model organisms", "sequence motif analysis", "epigenetics", "molecular biology techniques", "chromati...	Influence of Rotational Nucleosome Positioning on Transcription Start Site Selection in Animal Promoters	journal.pcbi.1005144	null	[ [ "An essential step in gene regulation is the recruitment of RNA-Pol-II ( Pol-II ) to the transcription start sites ( TSS ) at gene promoters [1–3] .", "This is often facilitated by the presence of conserved sequence motifs known as core promoter elements ( CPEs ) , which are found at a fixed or nearly fix...	[ "The recruitment of RNA-Pol-II to the transcription start site ( TSS ) is an important step in gene regulation in all organisms .", "Core promoter elements ( CPE ) are conserved sequence motifs that guide Pol-II to the TSS by interacting with specific transcription factors ( TFs ) .", "However , only a minority...	[ "Gene transcription is a complex process that starts with the recruitment and positioning of Pol-II enzyme at the transcription start site ( TSS ) .", "Specific promoter sequences , known as core promoter elements ( CPEs ) facilitate this process .", "Surprisingly , only a fraction of promoters contain them .",...	2016
[ "Introduction", "Results", "Discussion", "Models" ]	[ "biophysics/theory and simulation", "computational biology" ]	Axial and Radial Forces of Cross-Bridges Depend on Lattice Spacing	journal.pcbi.1001018	null	[ [ "Radial forces are the same order of magnitude as axial forces in contracting muscles [1]–[3] .", "These forces , along with axial force acting in the direction of muscle contraction , depend on myofilament lattice spacing [4] , [5] .", "At the same time , structural information about myosin cross-bri...	[ "Nearly all mechanochemical models of the cross-bridge treat myosin as a simple linear spring arranged parallel to the contractile filaments .", "These single-spring models cannot account for the radial force that muscle generates ( orthogonal to the long axis of the myofilaments ) or the effects of changes in fi...	[ "The molecular motor myosin drives the contraction of muscle , but doesn't just produce force in the axis of shortening .", "Models of muscle contraction have primarily treated myosin as a simple spring oriented parallel to its direction of movement .", "This assumption does not allow prediction of the relation...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "leptospira", "pathology and laboratory medicine", "pathogens", "tropical diseases", "microbiology", "vertebrates", "animals", "mammals", "bacterial diseases", "urban environments", "neglected tropical diseases", "bacter...	Association of rodent-borne Leptospira spp. with urban environments in Malaysian Borneo	journal.pntd.0007141	null	[ [ "Leptospirosis is the most widespread zoonotic disease globally , with over a million cases of severe disease and around 60 , 000 deaths reported annually [1] .", "Occurring in a wide variety of environmental settings , and with the greatest impact on public health in tropical and subtropical regions , it...	[ "Although leptospirosis is traditionally considered a disease of rural , agricultural and flooded environments , Leptospira spp .", "are found in a range of habitats and infect numerous host species , with rodents among the most significant reservoirs and vectors .", "To explore the local ecology of Leptospira ...	[ "Leptospirosis is a significant zoonotic disease that is found in a range of environments worldwide , most notably tropical regions prone to flooding .", "The bacterial agents of this disease , Leptospira spp .", ", are most often associated with rodents , including species frequently found in urban areas .", ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/viral infections", "virology/virulence factors and mechanisms", "virology/host invasion and cell entry" ]	Immature Dengue Virus: A Veiled Pathogen?	journal.ppat.1000718	null	[ [ "Dengue virus ( DENV ) represents a major emerging arthropod-borne pathogen .", "There are four distinct serotypes of DENV which , according to WHO estimates , infect about 50-100 million individuals annually , mostly in the ( sub ) tropical regions of the world .", "While most DENV infections are asy...	[ "Cells infected with dengue virus release a high proportion of immature prM-containing virions .", "In accordance , substantial levels of prM antibodies are found in sera of infected humans .", "Furthermore , it has been recently described that the rates of prM antibody responses are significantly higher in pat...	[ "Dengue virus represents a major emerging arboviral pathogen circulating in the ( sub ) tropical regions of the world , putting 2 . 5 billion people at risk of infection .", "Each of the four circulating serotypes can cause disease ranging from febrile illness to devastating manifestations including dengue hemorr...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "saccharomyces", "homo (human)", "computational biology" ]	Capturing Heterogeneity in Gene Expression Studies by Surrogate Variable Analysis	journal.pgen.0030161	null	[ [ "Large-scale gene expression studies allow one to characterize transcriptional variation with respect to measured variables of interest , such as differing environments , treatments , time points , phenotypes , or clinical outcomes .", "However , a number of unmeasured or unmodeled factors may also influe...	[ "It has unambiguously been shown that genetic , environmental , demographic , and technical factors may have substantial effects on gene expression levels .", "In addition to the measured variable ( s ) of interest , there will tend to be sources of signal due to factors that are unknown , unmeasured , or too com...	[ "In scientific and medical studies , great care must be taken when collecting data to understand the relationship between two variables , such as a drug and its effect on a disease .", "In any given study there will be many other variables at play , such as the effects of age and sex on the disease .", "We show...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/viral infections", "virology/new therapies, including antivirals and immunotherapy", "microbiology/immunity to infections", "virology/vaccines" ]	Broadly Protective Monoclonal Antibodies against H3 Influenza Viruses following Sequential Immunization with Different Hemagglutinins	journal.ppat.1000796	null	[ [ "Under non-pandemic conditions , the global mortality attributed to influenza virus infection is considerable , with 200 , 000–500 , 000 associated deaths occurring each year [1] .", "In the setting of the 1918 influenza pandemic , the global mortality reached 50 million people in one year , equivalent to...	[ "As targets of adaptive immunity , influenza viruses are characterized by the fluidity with which they respond to the selective pressure applied by neutralizing antibodies .", "This mutability of structural determinants of protective immunity is the obstacle in developing universal influenza vaccines .", "Towar...	[ "Influenza viruses remain a formidable public health threat .", "Because of a dramatic increase in drug resistant strains of influenza viruses and due to the semi-regular emergence of pandemic virus strains , the development of novel antibody-based therapies and influenza vaccine constructs is of great interest ....	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Loss of Glycosaminoglycan Receptor Binding after Mosquito Cell Passage Reduces Chikungunya Virus Infectivity	journal.pntd.0004139	null	[ [ "Chikungunya virus ( CHIKV ) is a mosquito-transmitted , single-stranded RNA virus belonging to the genus Alphavirus of the family Togaviridae .", "In humans , CHIKV infection can cause fever , headache , maculopapular rashes , myalgia , acute joint swelling , persistent arthritis , and even life-threaten...	[ "Chikungunya virus ( CHIKV ) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans .", "CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins , which may affect its replication and virulence .", "Herein , we compare replica...	[ "Chikungunya virus ( CHIKV ) is a chronic arthritis-causing pathogen in humans , for which no licensed vaccine or specific antiviral drug is currently available .", "Due to the global spread of its mosquito vectors , CHIKV is now becoming a public health threat worldwide .", "CHIKV can replicate in both mammali...	2015
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "bacteriology", "microbial metabolism", "ecology and environmental sciences", "environmental impacts", "population dynamics", "microbiology", "computerized simulations", "developmental biology", "population modeling", "population biology", "microbial growth and development", "bacteria", "pse...	Low Probability of Initiating nirS Transcription Explains Observed Gas Kinetics and Growth of Bacteria Switching from Aerobic Respiration to Denitrification	journal.pcbi.1003933	null	[ [ "Denitrification is a key process in the global nitrogen cycle and is also a major source of atmospheric N2O [2] .", "A plethora of biogeochemical models have been developed for understanding the ecosystem controls of denitrification and N2O emissions [3] .", "A common feature of these models is that ...	[ "In response to impending anoxic conditions , denitrifying bacteria sustain respiratory metabolism by producing enzymes for reducing nitrogen oxyanions/-oxides ( NOx ) to N2 ( denitrification ) .", "Since denitrifying bacteria are non-fermentative , the initial production of denitrification proteome depends on en...	[ "In response to oxygen-limiting conditions , denitrifying bacteria produce a set of enzymes to convert / to N2 via NO and N2O .", "The process ( denitrification ) helps generate energy for survival and growth during anoxia .", "Denitrification is imperative for the nitrogen cycle and has far-reaching consequenc...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "infectious diseases/fungal infections", "genetics and genomics/complex traits", "oncology/hematological malignancies" ]	Plasminogen Alleles Influence Susceptibility to Invasive Aspergillosis	journal.pgen.1000101	null	[ [ "Invasive infection with Aspergillus fumigatus ( AF ) is a common and life-threatening infection among severely immunocompromised individuals .", "Despite aggressive surveillance and prophylaxis , the incidence of invasive aspergillosis ( IA ) in hematopoietic stem cell transplant ( HSCT ) recipients rema...	[ "Invasive aspergillosis ( IA ) is a common and life-threatening infection in immunocompromised individuals .", "A number of environmental and epidemiologic risk factors for developing IA have been identified .", "However , genetic factors that affect risk for developing IA have not been clearly identified .", ...	[ "Invasive aspergillosis ( IA ) is the most common invasive mould infection among highly immune compromised hosts .", "While exogenous immune suppression is the greatest risk factor for infection acquisition , polymorphic variation in key immune effector genes likely contributes to disease susceptibility as well ....	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Application of RNAi to Genomic Drug Target Validation in Schistosomes	journal.pntd.0003801	null	[ [ "Schistosomiasis is a parasitic disease caused by a trematode of the genus Schistosoma , affecting around 200 million people in the poorest areas of the world and despite progress in development of a vaccine against schistosomiasis , none is yet available [1–3] .", "Therefore , currently , both treatment ...	[ "Concerns over the possibility of resistance developing to praziquantel ( PZQ ) , has stimulated efforts to develop new drugs for schistosomiasis .", "In addition to the development of improved whole organism screens , the success of RNA interference ( RNAi ) in schistosomes offers great promise for the identific...	[ "Schistosomiasis is a neglected tropical disease affecting 200 million people in the poorest areas of the world .", "To date no vaccine exists against this parasitosis , and the only possible cure relies on the use of the one available drug , praziquantel .", "Praziquantel is a safe and effective drug active ag...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cellular stress responses", "enzymes", "plant cell biology", "gene regulation", "regulatory proteins", "brassica", "enzymology", "dna-binding proteins", "chloroplasts", "cell processes", "pigments", "plant science", "model organisms", "materials science", "experimental organism systems"...	Interference with plastome gene expression and Clp protease activity in Arabidopsis triggers a chloroplast unfolded protein response to restore protein homeostasis	journal.pgen.1007022	null	[ [ "Endosymbiotic organelles such as mitochondria and chloroplasts play fundamental roles in eukaryotic organisms .", "They both contain their own genome but most of their proteins are encoded by the nuclear genome .", "As a consequence , mechanisms to adjust nuclear gene expression to particular organel...	[ "Disruption of protein homeostasis in chloroplasts impairs the correct functioning of essential metabolic pathways , including the methylerythritol 4-phosphate ( MEP ) pathway for the production of plastidial isoprenoids involved in photosynthesis and growth .", "We previously found that misfolded and aggregated ...	[ "Chloroplasts are central metabolic factories for plant cells .", "Yet , they are constantly challenged by stress episodes that alter protein homeostasis and disrupt normal chloroplast functions .", "To deal with this problem , protein quality control pathways involving particular chaperones and proteases promo...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genetics and genomics", "biology", "genomics", "metabolic disorders" ]	Genomic Convergence among ERRα, PROX1, and BMAL1 in the Control of Metabolic Clock Outputs	journal.pgen.1002143	null	[ [ "In most living organisms , metabolic and behavioral processes are orchestrated in a timely fashion approximating a 24 hr daily cycle .", "In mammals , light/dark ( LD ) cycles regulate the diurnal activity of the master pacemaker within the suprachiasmatic nuclei ( SCN ) and in turn synchronize autonomou...	[ "Metabolic homeostasis and circadian rhythms are closely intertwined biological processes .", "Nuclear receptors , as sensors of hormonal and nutrient status , are actively implicated in maintaining this physiological relationship .", "Although the orphan nuclear receptor estrogen-related receptor α ( ERRα , NR...	[ "The molecular basis for coordinated control of circadian rhythms and metabolism is not well understood .", "Although integral components of the molecular clock such as the transcription factor BMAL1 can directly regulate some metabolic genes , the output from the circadian oscillator is believed to be in large p...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "gene identification and analysis", "genetics", "molecular genetics", "biology", "genomics", "comparative genomics", "microbiology", "bacterial biochemistry", "microbial growth and development", "genetics and genomics", "gene function" ]	Identification of Functional Toxin/Immunity Genes Linked to Contact-Dependent Growth Inhibition (CDI) and Rearrangement Hotspot (Rhs) Systems	journal.pgen.1002217	null	[ [ "Many bacteria lead social lives in communities where they cooperate and compete with members of their own species , as well as those of other species [1] .", "One mechanism of bacterial communication is quorum sensing , in which small signaling molecules are released to coordinate group behavior when a c...	[ "Bacterial contact-dependent growth inhibition ( CDI ) is mediated by the CdiA/CdiB family of two-partner secretion proteins .", "Each CdiA protein exhibits a distinct growth inhibition activity , which resides in the polymorphic C-terminal region ( CdiA-CT ) .", "CDI+ cells also express unique CdiI immunity pr...	[ "Recent work from our laboratories has shown that many bacteria express contact-dependent growth inhibition ( CDI ) systems in which stick-like proteins on the cell surface deliver toxic tips into target cells .", "Over 60 distinct toxic tips have been identified in bacteria , and our data indicate that each CDI+...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene regulation", "neuroscience", "alternative splicing", "animal models", "model organisms", "mammalian genomics", "epigenetics", "dna", "chromatin", "dna methylation", "research and analysis methods", "genomic signal processing", "animal cells", "chromosome biology", "gene expression"...	Misregulation of Alternative Splicing in a Mouse Model of Rett Syndrome	journal.pgen.1006129	null	[ [ "Rett syndrome ( RTT ) is a progressive neurodevelopmental disorder that predominantly affects females[1 , 2] .", "Classic RTT patients develop normally in the first 6–18 months , and then undergo a rapid regression of higher brain functions that eventually leads to the loss of speech and purposeful hand ...	[ "Mutations in the human MECP2 gene cause Rett syndrome ( RTT ) , a severe neurodevelopmental disorder that predominantly affects girls .", "Despite decades of work , the molecular function of MeCP2 is not fully understood .", "Here we report a systematic identification of MeCP2-interacting proteins in the mouse...	[ "Rett syndrome ( RTT ) is a debilitating neurodevelopmental disorder with no cure or effective treatment .", "To fully understand the disease mechanism and develop therapies , it is necessary to study all aspects of the molecular function of methyl-CpG binding protein 2 ( MeCP2 ) , mutations in which have been id...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mitogenic signaling", "protein interactions", "regulatory proteins", "dna transcription", "histone modification", "membrane receptor signaling", "cell growth", "chromatin", "signaling in cellular processes", "proteins", "gene expression", "membranes and sorting", "biology", "molecular bio...	The ING1a Tumor Suppressor Regulates Endocytosis to Induce Cellular Senescence Via the Rb-E2F Pathway	journal.pbio.1001502	An age-associated isoform of ING1, ING1a, induces cell senescence by altering endocytosis, subsequently activating the retinoblastoma tumor suppressor.	[ [ "Cellular senescence was first described as a consequence of the limited replicative capacity of human diploid fibroblasts by Hayflick in the early 1960s [1] .", "It was later characterized as an intrinsic tumor-suppressive mechanism that acts to limit the proliferative capacity of precancerous cells .", ...	[ "The INhibitor of Growth ( ING ) proteins act as type II tumor suppressors and epigenetic regulators , being stoichiometric members of histone acetyltransferase and histone deacetylase complexes .", "Expression of the alternatively spliced ING1a tumor suppressor increases >10-fold during replicative senescence ."...	[ "Alternative splicing of several genes including the p16 and p53 tumor suppressors has been reported to increase during replicative senescence of normal diploid cells , but the biological functions of most alternative transcripts are unknown .", "We have found that a splicing product of the ING1 epigenetic regula...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "face", "tropical diseases", "parasitic diseases", "health care", "global health", "neglected tropical diseases", "mood disorders", "public and occupational health", "infectious diseases", "zoonoses", "protozoan infections", "head", "mental health and psychi...	Cutaneous leishmaniasis and co-morbid major depressive disorder: A systematic review with burden estimates	journal.pntd.0007092	null	[ [ "Cutaneous leishmaniasis ( CL ) is the most prevalent form of leishmaniasis and 1 of 22 highly prevalent neglected tropical diseases ( NTD ) [1] .", "Current disease classifications differentiate aspects of the active ( nodular , ulcerative or plaque ) CL lesion in terms of its transmission route ( “zoono...	[ "Major depressive disorder ( MDD ) associated with chronic neglected tropical diseases ( NTDs ) has been identified as a significant and overlooked contributor to overall disease burden .", "Cutaneous leishmaniasis ( CL ) is one of the most prevalent and stigmatising NTDs , with an incidence of around 1 million n...	[ "Cutaneous leishmaniasis is a highly prevalent vector-borne disease affecting large parts of Latin America and the Middle East , as well as parts of Northern Africa .", "There are several types of Cutaneous leishmaniasis , almost all of which have an active phase characterized by a disfiguring lesion ( typically ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Substrate-Driven Mapping of the Degradome by Comparison of Sequence Logos	journal.pcbi.1003353	null	[ [ "The degradome , the complete set of proteolytic enzymes [1] ( herein excluding their binding partners , although this term has also been used for proteases and their substrates and inhibitors together ) , comprises more than 500 proteases in humans , where every single one is linked to a particular cleavage ...	[ "Sequence logos are frequently used to illustrate substrate preferences and specificity of proteases .", "Here , we employed the compiled substrates of the MEROPS database to introduce a novel metric for comparison of protease substrate preferences .", "The constructed similarity matrix of 62 proteases can be u...	[ "We present a novel approach to intuitively map the degradome , the set of proteolytic enzymes , based on their substrates rather than on the protease sequences .", "Information stored in cleavage site sequence logos is extracted and transferred into a metric for similarity in protease substrate recognition .", ...	2013
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Plasticity Regulators Modulate Specific Root Traits in Discrete Nitrogen Environments	journal.pgen.1003760	null	[ [ "Nitrogen is a limiting nutrient in plant growth that is typically taken up from the soil by the root system [1] .", "However , because the soil environment often varies over space and time , a single genotype needs to adjust its root architecture in response to different soil conditions , an example of d...	[ "Plant development is remarkably plastic but how precisely can the plant customize its form to specific environments ?", "When the plant adjusts its development to different environments , related traits can change in a coordinated fashion , such that two traits co-vary across many genotypes .", "Alternatively ...	[ "Plants can dramatically alter their development in order to cope with new environmental conditions .", "Such plasticity is especially evident in the root system since it adopts a particular architecture under one condition , but can change architecture by altering the extent of lateral root branching in a differ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "influenza", "pathogens", "microbiology", "orthomyxoviruses", "alleles", "genetic mapping", "viruses", "linkage disequilibrium", "rna viruses", "microbial evolution", "infectious diseases", "medi...	The effective rate of influenza reassortment is limited during human infection	journal.ppat.1006203	null	[ [ "Genome sequencing has provided multiple insights into the evolution of the influenza virus .", "At the global level , sequences collected from circulating strains of the virus have enabled the identification of codons in the virus evolving under positive selection [1 , 2] , and demonstrated the importanc...	[ "We characterise the evolutionary dynamics of influenza infection described by viral sequence data collected from two challenge studies conducted in human hosts .", "Viral sequence data were collected at regular intervals from infected hosts .", "Changes in the sequence data observed across time show that the w...	[ "The influenza virus is an important cause of disease in the human population .", "During the course of an infection the virus can evolve rapidly .", "An important mechanism of viral evolution is reassortment , whereby different segments of the influenza genome are shuffled with other segments , producing new v...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "hydrology", "people and places", "public and occupational health", "geography", "ecology and environmental sciences", "medicine and health sciences", "social sciences", "ecology", "science policy", "epidemiology", "earth sciences", "atmospheric science", "biology and life sciences", "spec...	Spatio-Temporal Distribution of Dengue and Lymphatic Filariasis Vectors along an Altitudinal Transect in Central Nepal	journal.pntd.0003035	null	[ [ "Dengue fever ( DF ) is a mosquito-borne viral disease which has become a major international public health concern in recent years .", "Dengue virus ( DENV ) , the causative agent of this disease , belongs to the genus Flavivirus , family Flaviviridae , and is transmitted by Aedes mosquitoes , especially...	[ "Rapidly increasing temperatures in the mountain region of Nepal and recent reports of dengue fever and lymphatic filariasis cases from mountainous areas of central Nepal prompted us to study the spatio-temporal distribution of the vectors of these two diseases along an altitudinal transect in central Nepal .", "...	[ "Dengue fever , a viral disease transmitted by the bites of infected Aedes aegypti and Aedes albopictus mosquitoes , has been rapidly spreading in Nepal since it was first reported in this country in 2004 .", "Similarly , lymphatic filariasis , a parasitic disease transmitted by Culex quinquefasciatus mosquitoes ...	2014
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "evolutionary biology/human evolution", "molecu...	Clusters of Nucleotide Substitutions and Insertion/Deletion Mutations Are Associated with Repeat Sequences	journal.pbio.1000622	The authors propose that short repeat sequences may play an important role in causing the pervasive clustering of mutations across diverse genomes from prokaryotes to humans.	[ [ "A major challenge of evolutionary genetics is to determine the mechanisms underlying cryptic patterns of mutation rate variation and how they influence evolutionary outcomes [1] .", "One of the most striking of these trends is the association between indel mutations and nucleotide substitutions [2]–[7] ....	[ "The genome-sequencing gold rush has facilitated the use of comparative genomics to uncover patterns of genome evolution , although their causal mechanisms remain elusive .", "One such trend , ubiquitous to prokarya and eukarya , is the association of insertion/deletion mutations ( indels ) with increases in the ...	[ "An intriguing observation made during the comparison of genomes is that insertion and deletion mutations ( indels ) cluster together with nucleotide substitutions .", "Two ( not mutually exclusive ) hypotheses have been proposed to explain this phenomenon .", "The first postulates that an indel mutation causes...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "viral transmission and infection", "microbiology", "vertebrates", "animals", "mammals", "primates", "animal models", "experimental organism systems", "microbial genetics", "viral load", "old world monkeys", "research and analysis methods", ...	Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy	journal.ppat.1006359	null	[ [ "A major obstacle to developing a cure for HIV is the establishment in early infection of long-lived viral reservoirs , defined as sources of virus that can persist over extended periods despite seemingly effective suppressive combination antiretroviral therapy ( cART ) , that can cause recrudescent viremia i...	[ "HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads .", "However , this total viral load value represents the sum of many individual infection events , which are difficult to independently track using conventional sequencing approaches .", "To overcome this challenge , we g...	[ "Elucidation of HIV dynamics is essential for a thorough understanding of viral transmission , therapeutic interventions , pathogenesis , and immune evasion .", "The complex dynamics of reservoir establishment and viral recrudescence upon therapy removal present the primary obstacles to developing a functional cu...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "cell death", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "cell processes", "immunology", "microbiology", "bone marrow cells", "animal models", "streptococcus pyogenes", "model organisms", "bacteria", "bacterial pathoge...	The Influence of Programmed Cell Death in Myeloid Cells on Host Resilience to Infection with Legionella pneumophila or Streptococcus pyogenes	journal.ppat.1006032	null	[ [ "Pathogen clearance and host resilience/tolerance are both important in surviving a given infection [1 , 2] [3] [4] [5] .", "A main purpose of the immune response is to identify and clear invading pathogens .", "However , highly resilient hosts can survive infection with a given pathogen , independent...	[ "Pathogen clearance and host resilience/tolerance to infection are both important factors in surviving an infection .", "Cells of the myeloid lineage play important roles in both of these processes .", "Neutrophils , monocytes , macrophages , and dendritic cells all have important roles in initiation of the imm...	[ "Multicellular organisms are constantly interacting with microbes .", "Pathogens are microbes that can cause harm to the host if not properly controlled , therefore pathogen clearance is an essential part of survival of all multi-cellular organisms .", "Equally important factors in survival are host resilience ...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "invertebrates", "microbiology", "animals", "invertebrate genomics", "viruses", "phylogenetics", "data management", "rna viruses", "phylogenetic analysis", "genome analysis", "planarians", "microbial genomics", "viral genomics", "computer and information sciences", "protein...	A planarian nidovirus expands the limits of RNA genome size	journal.ppat.1007314	null	[ [ "Radiation of primitive life as it took hold on earth was likely accompanied by genome expansion , which was associated with increased complexity and a proposed progression from RNA-based through RNA-protein to DNA-based life [1] .", "The feasibility of an autonomous ancient RNA genome , and the mechanism...	[ "RNA viruses are the only known RNA-protein ( RNP ) entities capable of autonomous replication ( albeit within a permissive host environment ) .", "A 33 . 5 kilobase ( kb ) nidovirus has been considered close to the upper size limit for such entities; conversely , the minimal cellular DNA genome is in the 100–300...	[ "RNA viruses are the only known RNA-protein ( RNP ) entities capable of autonomous replication .", "The upper genome size for such entities was assumed to be <35 kb; conversely , the minimal cellular DNA genome is in the 100–300 kilobase ( kb ) range .", "This large difference presents a daunting gap for the pr...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Structure Analysis Uncovers a Highly Diverse but Structurally Conserved Effector Family in Phytopathogenic Fungi	journal.ppat.1005228	null	[ [ "Pathogenic microorganisms have to cope with the immune system of their host and therefore deploy measures to hide their presence , disturb host immunity or inactivate defense responses .", "In all these strategies , proteins secreted by the pathogen during infection and acting on host proteins and cellul...	[ "Phytopathogenic ascomycete fungi possess huge effector repertoires that are dominated by hundreds of sequence-unrelated small secreted proteins .", "The molecular function of these effectors and the evolutionary mechanisms that generate this tremendous number of singleton genes are largely unknown .", "To get ...	[ "Fungal plant pathogens are of outstanding economic and ecological importance and cause destructive diseases on many cultivated and wild plants .", "Effector proteins that are secreted during infection to manipulate the host and to promote disease are a key element in fungal virulence .", "Phytopathogenic fungi...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schoolchildren", "children", "medicine and health sciences", "pathology and laboratory medicine", "education", "chlamydia trachomatis", "pathogens", "sociology", "tropical diseases", "microbiology", "geographical locations", "social sciences", "bacterial diseases", "age groups", "eye di...	Prevalence of trachoma in school children in the Marajó Archipelago, Brazilian Amazon, and the impact of the introduction of educational and preventive measures on the disease over eight years	journal.pntd.0006282	null	[ [ "Trachoma , an eye disease caused by Chlamydia trachomatis ( serotypes A , B , Ba , and C ) , continues to be the leading infectious cause of blindness in the world [1 , 2] .", "The clinical presentation of trachoma is characterized by follicular and papillary hyperplasia in the conjunctiva , forming gray...	[ "Trachoma is the leading infectious cause of blindness in the world and is associated with precarious living conditions in developing countries .", "The aim of the present study was to evaluate the prevalence of trachoma in three municipalities of the Marajó Archipelago , located in the state of Pará , Brazil .",...	[ "Trachoma is one of the main neglected infectious diseases and carry a considerable burden to human health as a consequence of the clinical severity of the disease which may evolve to blindness .", "The lack of hygiene , education and other indicators of low social and economic markers occurring in developing and...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "helminths", "enzymes", "tropical diseases", "enzymology", "parasitic diseases", "animals", "parasitology", "parasite physiology", "neglected tropical diseases", "digestive enzymes", "soil-transmitted helminthiases", "veterinary parasitology...	Peptidases Compartmentalized to the Ascaris suum Intestinal Lumen and Apical Intestinal Membrane	journal.pntd.0003375	null	[ [ "Parasitic nematodes cause major diseases of humans , directly affecting more than two billion people on a global scale [1] .", "Diseases they cause in food animal species also pose significant constraints to agricultural production and thus , indirectly impact human health in regions of the world where n...	[ "The nematode intestine is a tissue of interest for developing new methods of therapy and control of parasitic nematodes .", "However , biological details of intestinal cell functions remain obscure , as do the proteins and molecular functions located on the apical intestinal membrane ( AIM ) , and within the int...	[ "Past research has demonstrated that the nematode intestine has value for developing new methods of therapy and control of parasitic nematodes , as related to both vaccines and other anthelmintics .", "Yet , information related to basic intestinal cell biology is very limited .", "Research progress reported her...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genetics and genomics/genomics", "microbiology/immunity to infections", "genetics and genomics/disease models", "genetics and genomics/gene function", "public health and epidemiology/infectious diseases", "infectious diseases/bacterial infections", "genetics and genomics/bioinformatics" ]	Comprehensive Identification of Salmonella enterica Serovar Typhimurium Genes Required for Infection of BALB/c Mice	journal.ppat.1000529	null	[ [ "Salmonella enterica serovar Typhimurium ( S . Typhimurium ) infection of mice is well established as a model of systemic typhoid fever in humans [1] .", "The system is particularly useful for identifying the genetic determinants of Salmonella virulence , usually by comparing the in vivo growth of mutants...	[ "Genes required for infection of mice by Salmonella Typhimurium can be identified by the interrogation of random transposon mutant libraries for mutants that cannot survive in vivo .", "Inactivation of such genes produces attenuated S . Typhimurium strains that have potential for use as live attenuated vaccines ....	[ "Salmonella Typhimurium infection of mice is an established model of systemic typhoid fever in humans .", "Mutations that inactivate genes that are important for virulence produce attenuated S . Typhimurium bacteria that have potential for use as live vaccines .", "To investigate the infection process we have p...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Staphylococcus aureus ArlRS Two-Component System Is a Novel Regulator of Agglutination and Pathogenesis	journal.ppat.1003819	null	[ [ "Staphylococcus aureus is a Gram-positive opportunistic pathogen that exists as part of the normal human microflora in approximately one third of the human population [1] .", "This pathogen is responsible for causing a wide range of acute and chronic infections resulting in significant morbidity and morta...	[ "Staphylococcus aureus is a prominent bacterial pathogen that is known to agglutinate in the presence of human plasma to form stable clumps .", "There is increasing evidence that agglutination aids S . aureus pathogenesis , but the mechanisms of this process remain to be fully elucidated .", "To better define t...	[ "Staphylococcus aureus is a bacterial pathogen that is responsible for causing significant disease in humans .", "The development of antibiotic resistant strains has made these infections more difficult to treat , and an improved understanding of how this pathogen causes infections will facilitate the development...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "flow cytometry", "medicine and health sciences", "pathology and laboratory medicine", "endothelial cells", "protein interaction networks", "pathogens", "microbiology", "epithelial cells", "viruses", "dna viruses", "network analysis", "peroxisomes", "cellular structures and organelles", "h...	Integrated systems biology analysis of KSHV latent infection reveals viral induction and reliance on peroxisome mediated lipid metabolism	journal.ppat.1006256	null	[ [ "Viruses have evolved functions to reprogram the proteomic landscape of their host and modulate cellular signaling pathways to adjust the regulation of cellular machinery .", "These cellular alterations support the survival of infected cells to allow replication and spread of the virus .", "Many virus...	[ "Kaposi’s Sarcoma associated Herpesvirus ( KSHV ) , an oncogenic , human gamma-herpesvirus , is the etiological agent of Kaposi’s Sarcoma the most common tumor of AIDS patients world-wide .", "KSHV is predominantly latent in the main KS tumor cell , the spindle cell , a cell of endothelial origin .", "KSHV modu...	[ "Kaposi’s Sarcoma herpesvirus ( KSHV ) is the etiologic agent of Kaposi’s Sarcoma , the most common tumor of AIDS patients .", "KSHV modulates host cell signaling and metabolism to maintain a life-long latent infection .", "To unravel the underlying cellular mechanisms modulated by KSHV , we used multiple globa...	2017
[ "Introduction", "Methods", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "helminths", "tropical diseases", "hookworms", "parasitic diseases", "animals", "mathematics", "pharmaceutics", "drug administration", "neglected tropical diseases", "pharmacology", "extraction techniques", "discrete mathematics", "combina...	Comprehensive evaluation of stool-based diagnostic methods and benzimidazole resistance markers to assess drug efficacy and detect the emergence of anthelmintic resistance: A Starworms study protocol	journal.pntd.0006912	null	[ [ "Currently , the reduction in number of eggs excreted in stool after drug administration ( egg reduction rate , ERR ) is the recommended method for monitoring the efficacy of anthelmintic drugs against STHs [27] .", "In contrast to other available assays , it allows for the assessment of the efficacy of a...	[ "To work towards reaching the WHO goal of eliminating soil-transmitted helminth ( STH ) infections as a public health problem , the total number of children receiving anthelmintic drugs has strongly increased over the past few years .", "However , as drug pressure levels rise , the development of anthelmintic dru...	[ "Soil-transmitted helminths ( STHs ) affect 1 . 4 billion people worldwide and cause significant morbidity when the intensity of infection is high .", "Currently , these infections are controlled in school-aged children by preventive chemotherapy with the benzimidazole drugs albendazole ( ALB ) or mebendazole ( M...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "hiv", "genetics", "biology", "genomics", "viral diseases" ]	Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 Controls	journal.ppat.1003515	null	[ [ "Variation in infection susceptibility and severity is a hallmark of infectious disease biology .", "This natural variation can be attributed to a variety of host , pathogen and environmental factors , including host genetics .", "Several genome-wide association studies ( GWAS ) of HIV-1 outcomes have...	[ "Multiple genome-wide association studies ( GWAS ) have been performed in HIV-1 infected individuals , identifying common genetic influences on viral control and disease course .", "Similarly , common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS , although in general...	[ "Comparing the frequency differences between common DNA variants in disease-affected cases and in unaffected controls has been successful in uncovering the genetic component of multiple diseases .", "This approach is most effective when large samples of cases and controls are available .", "Here we combine info...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Mass-Longevity Triangle: Pareto Optimality and the Geometry of Life-History Trait Space	journal.pcbi.1004524	null	[ [ "Mammals can have very different lifespans , and it is of great interest to understand why longevity differs between species .", "Recent studies use comparative approaches to understand mechanisms for longevity in diverse mammalian species , especially species which are long lived [1–3] .", "In order ...	[ "When organisms need to perform multiple tasks they face a fundamental tradeoff: no phenotype can be optimal at all tasks .", "This situation was recently analyzed using Pareto optimality , showing that tradeoffs between tasks lead to phenotypes distributed on low dimensional polygons in trait space .", "The ve...	[ "Understanding why some mammals live longer than others is of crucial interest .", "Here we study how longevity relates to other life-history traits , using data on about 2000 species of mammals and birds .", "In contrast to the tradition in which traits fall on a line in logarithmic coordinates , called allome...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene expression", "genetics", "epigenetics", "biology and life sciences", "molecular genetics" ]	A System for Genome-Wide Histone Variant Dynamics In ES Cells Reveals Dynamic MacroH2A2 Replacement at Promoters	journal.pgen.1004515	null	[ [ "All genomic transactions in eukaryotes occur in the context of chromatin .", "While histones are generally among the most stably-associated DNA-binding proteins known [1] , a subset of histones exhibit dynamic replication-independent exchange with the soluble pool of nucleoplasmic histones [2]–[4] .", ...	[ "Dynamic exchange of a subset of nucleosomes in vivo plays important roles in epigenetic inheritance of chromatin states , chromatin insulator function , chromosome folding , and the maintenance of the pluripotent state of embryonic stem cells .", "Here , we extend a pulse-chase strategy for carrying out genome-w...	[ "The ability of cells to remember the correct cell fate is at least partly dependent on how the genome is packaged .", "Embryonic stem ( ES ) cells , which have the ability to become any cell type in the body , are a particularly well-studied system for understanding how the packaging of the genome – chromatin – ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "mus (mouse)", "oncology", "genetics and genomics", "immunology" ]	A Mechanism Misregulating p27 in Tumors Discovered in a Functional Genomic Screen	journal.pgen.0030219	null	[ [ "p27KIP1 binds to and thereby prevents cyclin-CDK complexes from phosphorylating their protein substrates [1] .", "The biological consequence of this molecular interaction in cultured cells is cell cycle arrest , primarily in the G1 phase .", "Analysis of p27−/− mice provides further evidence that p27...	[ "The cyclin-dependent kinase inhibitor p27KIP1 is a tumor suppressor gene in mice , and loss of p27 protein is a negative prognostic indicator in human cancers .", "Unlike other tumor suppressors , the p27 gene is rarely mutated in tumors .", "Therefore misregulation of p27 , rather than loss of the gene , is r...	[ "Many human cancers express abnormally low amounts of the p27 protein , and this is associated with aggressive tumor behavior and a poor clinical outcome .", "Surprisingly , the p27 gene is rarely mutated in these tumors and retains the potential to produce normal amounts of p27 protein .", "Therefore , underst...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Parasitological, Hematological and Biochemical Characteristics of a Model of Hyper-microfilariaemic Loiasis (Loa loa) in the Baboon (Papio anubis)	journal.pntd.0004202	null	[ [ "Loa loa is a parasitic filarial nematode of humans , and a member the super family Filariodea which includes infections that are targeted for elimination , such as lymphatic filariasis ( Wuchereria bancrofti , Brugia sp ) , and onchocerciasis ( Onchocerca volvulus ) .", "L . loa is found in the tropics [...	[ "Loiasis , a filarial infection caused by Loa loa usually thought to cause relatively minor morbidity , can cause serious and often fatal reactions in patients carrying very high levels of circulating Loa loa microfilariae ( mf ) following administration of microfilaricidal drugs .", "An experimental model of thi...	[ "Loiasis is a filarial infection of humans that , in addition to causing severe direct clinical effects , is of concern to the global community’s efforts to eliminate the important filarial diseases , onchocerciasis and lymphatic filariasis , through causing interruption to mass drug distribution activities .", "...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Snakebite is Under Appreciated: Appraisal of Burden from West Africa	journal.pntd.0004088	null	[ [ "Snakebite envenoming ( SBE ) is a major public health problem among communities of the savanna region of West Africa , notably in Benin , Burkina-Faso , Cameroon , Chad , Ghana , Nigeria , Senegal and Togo [1 , 2 , 3 , 4] .", "The precise incidence of snakebite is difficult to determine and is often gros...	[ "Snakebite envenoming ( SBE ) is a major problem in rural areas of West Africa ( WA ) .", "Compared to other Neglected Tropical Diseases ( NTD ) , the public health burden of SBE has not been well characterized .", "We estimated the impact of snakebite mortality and morbidity using the Disability Adjusted Life ...	[ "Snakebite envenoming ( SBE ) is a major problem in rural West Africa ( WA ) .", "However , despite the high incidence of SBE in this region , government funding for the prevention or treatment of SBE is generally limited .", "In this analysis , we attempted to estimate how the public health burden of SBE compa...	2015
[ "Introduction", "Results", "Discussion", "Materials & methods" ]	[ "flow cytometry", "medicine and health sciences", "nose", "face", "pathology and laboratory medicine", "pathogens", "canine distemper virus", "microbiology", "vertebrates", "light microscopy", "orthomyxoviruses", "animals", "mammals", "viruses", "confocal laser microscopy", "respirator...	Delineating morbillivirus entry, dissemination and airborne transmission by studying in vivo competition of multicolor canine distemper viruses in ferrets	journal.ppat.1006371	null	[ [ "Morbilliviruses are enveloped , non-segmented , negative strand RNA viruses that belong to the family Paramyxoviridae [1] .", "They are highly contagious , spread via the respiratory route , cause profound immune suppression but also elicit lifelong immunity in surviving hosts , and have a propensity to ...	[ "Identification of cellular receptors and characterization of viral tropism in animal models have vastly improved our understanding of morbillivirus pathogenesis .", "However , specific aspects of viral entry , dissemination and transmission remain difficult to recapitulate in animal models .", "Here , we used ...	[ "Canine distemper virus ( CDV ) infection of ferrets is a tractable animal model for measles .", "Ferrets are highly susceptible to CDV , and inoculation with a low dose leads to lethal disease .", "We performed in vivo competition experiments to study virus entry , dissemination and transmission .", "Ferrets...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "genetics and genomics", "microbiology" ]	The Properties of Adaptive Walks in Evolving Populations of Fungus	journal.pbio.1000250	A novel method to infer the number and fitness effect of beneficial mutations reveals that the bulk of adaptive evolution is attributable to a few mutations with variable effects on fitness.	[ [ "The rate and extent of adaptive evolution over long time periods depends ultimately on the sequential substitution of beneficial mutations by natural selection , a process termed an adaptive walk .", "Although recent work with microbial populations has shed light on the properties of a single bout of ada...	[ "The rarity of beneficial mutations has frustrated efforts to develop a quantitative theory of adaptation .", "Recent models of adaptive walks , the sequential substitution of beneficial mutations by selection , make two compelling predictions: adaptive walks should be short , and fitness increases should become ...	[ "Adaptation is one of the least understood processes in biology because it relies on beneficial mutations , which are often too rare to study .", "We developed a method to infer the number and size of beneficial mutations substituted during adaptation , a process called an adaptive walk , and used this to test pr...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunodeficiency viruses", "infectious diseases", "medicine and health sciences", "medical microbiology", "hiv", "viral pathogens", "microbial pathogens", "biology and life sciences", "immunology", "microbiology", "viral diseases" ]	Antibody to gp41 MPER Alters Functional Properties of HIV-1 Env without Complete Neutralization	journal.ppat.1004271	null	[ [ "Advances in both vaccine development and immunoprophylaxis are needed to combat HIV/AIDS [1]–[3] .", "Both of these strategies target the viral envelope glycoprotein spike ( Env ) , which is a trimer of gp120-gp41 heterodimers .", "HIV-1 Env is functionally labile [4] , [5] , heterogeneously glycosyl...	[ "Human antibody 10E8 targets the conserved membrane proximal external region ( MPER ) of envelope glycoprotein ( Env ) subunit gp41 and neutralizes HIV-1 with exceptional potency .", "Remarkably , HIV-1 containing mutations that reportedly knockout 10E8 binding to linear MPER peptides are partially neutralized by...	[ "As vaccination , immunoprophylaxis and immunotherapies are becoming increasingly feasible approaches to combat HIV/AIDS , understanding the activity of relevant anti-HIV antibodies is crucial .", "Antibody 10E8 defines a key vulnerability on the envelope spikes of a vast majority of HIV isolates but mechanisms o...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell walls", "protein interactions", "chemical compounds", "membrane staining", "vertebrates", "carbohydrates", "organic compounds", "glucose", "animals", "mammals", "xenarthra", "cell signaling", "fungi", "cellular structures and organelles", "mapk signaling cascades", "research and ...	Hsp70-nucleotide exchange factor (NEF) Fes1 has non-NEF roles in degradation of gluconeogenic enzymes and cell wall integrity	journal.pgen.1008219	null	[ [ "Fbp1 and other gluconeogenic enzymes that are highly expressed when cells are starved of glucose are rapidly inactivated and degraded when glucose is restored .", "Restoring glucose after starving one day causes Fbp1 to be degraded by the proteasome [1 , 2] , but when cells are starved three days before ...	[ "Fes1 is a conserved armadillo repeat-containing Hsp70 nucleotide exchange factor important for growth at high temperature , proteasomal protein degradation and prion propagation .", "Depleting or mutating Fes1 induces a stress response and causes defects in these processes that are ascribed solely to disruption ...	[ "Fes1 , a yeast homolog of human nucleotide exchange factor HspBP1 , binds and regulates Hsp70 , a universally conserved protein that helps maintain health of proteins in cells .", "Fes1 is believed to function only by helping Hsp70 release ADP and substrates and cells lacking Fes1 are sick .", "We find Fes1 is...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "computational biology" ]	An Information Theoretic Characterisation of Auditory Encoding	journal.pbio.0050288	A part of the auditory cortex (planum temporale) encodes the information content of pitch sequences.	[ [ "We are constantly required to perceive , distinguish , and identify signals in our acoustic environment .", "A critical first stage of these processes is the encoding of the information into a robust neural code that allows efficient subsequent processing in the auditory system [1] .", "We investigat...	[ "The entropy metric derived from information theory provides a means to quantify the amount of information transmitted in acoustic streams like speech or music .", "By systematically varying the entropy of pitch sequences , we sought brain areas where neural activity and energetic demands increase as a function o...	[ "Understanding how the brain makes sense of our acoustic environment remains a major challenge .", "One way to describe the complexity of our acoustic environment is in terms of information entropy: acoustic signals with high entropy convey large amounts of information , whereas low entropy signifies redundancy ....	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "bacterial diseases", "infectious diseases" ]	Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity	journal.ppat.1002632	null	[ [ "The epidemic form of hemolytic uremic syndrome ( HUS ) , has been associated with enterohemorrhagic infections caused by Shiga toxin ( Stx ) -producing Escherichia coli ( STEC ) [1] .", "HUS is the most common cause of acute renal failure in children and is related to endothelial damage of kidney glomeru...	[ "The hemolytic uremic syndrome ( HUS ) is characterized by hemolytic anemia , thrombocytopenia and renal dysfunction .", "The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin ( Stx ) -producing Escherichia coli ( STEC ) .", "Endothelial dysfunction induced by Stx is centr...	[ "Hemolytic-uremic syndrome ( HUS ) is generally caused by Shiga toxin ( Stx ) -producing Escherichia coli but bacterial lipopolysaccharide ( LPS ) and neutrophils ( PMN ) contribute to the pathophysiology .", "Acute renal failure is the main feature of HUS , but in severe cases , patients develop neurological com...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene function", "genetics and genomics/cancer genetics" ]	BRIT1/MCPH1 Is Essential for Mitotic and Meiotic Recombination DNA Repair and Maintaining Genomic Stability in Mice	journal.pgen.1000826	null	[ [ "The repair of DNA double-strand breaks ( DSBs ) is critical for maintaining genomic integrity [1] , [2] .", "DSBs can arise from exogenous agents such as ionizing radiation ( IR ) [3] and endogenous factors such as stalled replication forks [4] .", "In addition , DSBs can form in a programmed manner ...	[ "BRIT1 protein ( also known as MCPH1 ) contains 3 BRCT domains which are conserved in BRCA1 , BRCA2 , and other important molecules involved in DNA damage signaling , DNA repair , and tumor suppression .", "BRIT1 mutations or aberrant expression are found in primary microcephaly patients as well as in cancer pati...	[ "The repair of DNA breaks in cells is critical for maintaining genomic integrity and suppressing tumor development .", "DNA breaks can arise from exogenous agents such as ionizing radiation ( IR ) or can form during the process of germ cell ( sperm and egg ) generation .", "BRIT1 protein ( also known as MCPH1 )...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna interference", "gene regulation", "reporter genes", "fungi", "model organisms", "gene types", "epigenetics", "chromatin", "schizosaccharomyces", "heterochromatin", "research and analysis methods", "small interfering rnas", "chromosome biology", "genetic interference", "gene expressi...	A Novel Epigenetic Silencing Pathway Involving the Highly Conserved 5’-3’ Exoribonuclease Dhp1/Rat1/Xrn2 in Schizosaccharomyces pombe	journal.pgen.1005873	null	[ [ "In eukaryotic cells , DNA coils around histones to form nucleosomes , which are packaged into chromatin .", "Various post-translational modifications ( PTMs ) of histones , histone variants , and nucleosome remodeling factors confer distinct chromatin states on genes and facilitate the organization of la...	[ "Epigenetic gene silencing plays a critical role in regulating gene expression and contributes to organismal development and cell fate acquisition in eukaryotes .", "In fission yeast , Schizosaccharomyces pombe , heterochromatin-associated gene silencing is known to be mediated by RNA processing pathways includin...	[ "Epigenetic mechanisms regulate when , where , and how an organism uses the genetic information stored in its genome .", "They are essential to many cellular processes , such as the regulation of gene expression , genome organization , and cell-fate determination .", "They also govern growth , development , and...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "dermatology", "invertebrates", "schistosoma", "schistosoma mansoni", "medicine and health sciences", "cell death", "immune cells", "helminths", "immunology", "cell processes", "animals", "skin infections", "phagocytes", "infectious diseases", "white blood cells", "ani...	Alternatively Activated Mononuclear Phagocytes from the Skin Site of Infection and the Impact of IL-4Rα Signalling on CD4+T Cell Survival in Draining Lymph Nodes after Repeated Exposure to Schistosoma mansoni Cercariae	journal.pntd.0004911	null	[ [ "Schistosomiasis is a debilitating disease that develops following percutaneous infection with the parasitic helminth Schistosoma spp [1 , 2] .", "The disease affects approximately 230 million people worldwide with infection occurring when the skin is exposed to the free-swimming tissue invasive cercariae...	[ "In a murine model of repeated exposure of the skin to infective Schistosoma mansoni cercariae , events leading to the priming of CD4 cells in the skin draining lymph nodes were examined .", "The dermal exudate cell ( DEC ) population recovered from repeatedly ( 4x ) exposed skin contained an influx of mononuclea...	[ "In areas endemic for schistosomiasis , repeated exposure to infective cercariae is a frequent occurrence , and repeated exposure of murine skin to Schistosoma mansoni resulted in CD4+ T cells becoming hypo-responsive .", "Here potential contributory mechanisms were investigated .", "In the skin infection site ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "biology and life sciences", "parasitic diseases", "molecular biology", "parasitology" ]	Golgi-Located NTPDase1 of Leishmania major Is Required for Lipophosphoglycan Elongation and Normal Lesion Development whereas Secreted NTPDase2 Is Dispensable for Virulence	journal.pntd.0003402	null	[ [ "Leishmania parasites cause a spectrum of diseases in humans , ranging from localized cutaneous lesions to disseminated mucocutaneous and lethal visceral infections .", "It is estimated that 1 . 5 to 2 million new cases of leishmaniasis occur annually and that more than 350 million people are at risk worl...	[ "Parasitic protozoa , such as Leishmania species , are thought to express a number of surface and secreted nucleoside triphosphate diphosphohydrolases ( NTPDases ) which hydrolyze a broad range of nucleoside tri- and diphosphates .", "However , the functional significance of NTPDases in parasite virulence is poor...	[ "Nucleoside triphosphate diphosphohydrolases ( NTPDases ) are a family of enzymes expressed in many eukaryotes , ranging from single-celled parasites to mammals .", "In mammals , NTPDases can have an immunomodulatory role , while in pathogenic protists cell-surface and secreted NTPDases are thought to be importan...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "cell biology/gene expression", "cell biology/nuclear structure and function" ]	Restricting Dosage Compensation Complex Binding to the X Chromosomes by H2A.Z/HTZ-1	journal.pgen.1000699	null	[ [ "Many species- such as humans , mice , flies , and worms- utilize a chromosome-based mechanism to establish sex .", "This results in a difference in sex chromosome number between the sexes that , left uncorrected , puts one sex at a great selective disadvantage .", "In order to combat this , these org...	[ "Dosage compensation ensures similar levels of X-linked gene products in males ( XY or XO ) and females ( XX ) , despite their different numbers of X chromosomes .", "In mammals , flies , and worms , dosage compensation is mediated by a specialized machinery that localizes to one or both of the X chromosomes in o...	[ "In organisms where females have two X chromosomes and males only have one , a mechanism called dosage compensation ensures that both sexes receive the same amount of information from their X chromosomes .", "Disruption of dosage compensation leads to lethality in the affected sex .", "While the precise mechani...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Concurrent Infections of Giardia duodenalis, Enterocytozoon bieneusi, and Clostridium difficile in Children during a Cryptosporidiosis Outbreak in a Pediatric Hospital in China	journal.pntd.0002437	null	[ [ "Cryptosporidium is a significant cause of diarrhea in humans worldwide [1] .", "Humans can acquire Cryptosporidium infections through the fecal-oral route via direct person-to-person or animal-to-person contact , or ingestion of contaminated water or food [2] .", "Thus far , over 200 waterborne , foo...	[ "Over 200 cryptosporidiosis outbreaks have been reported , but little is known if other enteric pathogens were also involved in some of these outbreaks .", "Recently , an outbreak of cryptosporidiosis linked to poor hygiene by two Cryptosporidium hominis subtypes occurred in a pediatric hospital ward ( Ward A ) i...	[ "The transmission of Giardia duodenalis , Enterocytozoon bieneusi , and Clostridium difficile is poorly understood in developing countries despite their wide occurrence .", "Because they are transmitted by the same fecal-oral route as Cryptosporidium , in this study , we have examined the occurrence of these ente...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/bacterial infections" ]	Cost-Effectiveness of Blood Agar for Isolation of Mycobacteria	journal.pntd.0000083	null	[ [ "Specific media , such as egg-based media ( e . g . Lowenstein Jensen medium ) , agar-based media ( e . g . Middlebrook media ) and liquid media ( e . g . Middlebrook and BACTEC broths ) are recommended for culturing Mycobacterium species [1] .", "Such requirements pose logistic and economic problems , es...	[ "Mycobacterium species are grown using specific media that increase laboratory cost , thus hampering their diffusion in resource-limited countries .", "Preliminary data suggested that versatile blood agar may be also used for mycobacterial culture .", "We examined the growth of 41 different Mycobacterium specie...	[ "Mycobacteria are organisms responsible for animal and human infections comprising tuberculosis due to Mycobacterium tuberculosis and other opportunistic infections .", "Such infections require specific antibiotic treatment and prevention of secondary cases in the occurrence of pulmonary tuberculosis .", "The a...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/sequence motif analysis", "molecular biology/bioinformatics", "biophysics/biomacromolecule-ligand interactions", "biochemistry/bioinformatics", "biochemistry/drug discovery" ]	Accurate Prediction of Peptide Binding Sites on Protein Surfaces	journal.pcbi.1000335	null	[ [ "Protein–protein interactions are vital for all cellular processes , including signaling , DNA repair , trafficking , replication , gene-expression and metabolism .", "These interactions can vary substantially in how they are mediated .", "What perhaps most often comes to mind are interactions involvi...	[ "Many important protein–protein interactions are mediated by the binding of a short peptide stretch in one protein to a large globular segment in another .", "Recent efforts have provided hundreds of examples of new peptides binding to proteins for which a three-dimensional structure is available ( either known e...	[ "An important class of protein interactions in critical cellular processes , such as signaling pathways , involves a domain from one protein binding to a linear peptide stretch of another .", "Many methods identify peptides mediating such interactions but without details of how the interactions occur , even when ...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	A Field Study in Benin to Investigate the Role of Mosquitoes and Other Flying Insects in the Ecology of Mycobacterium ulcerans	journal.pntd.0003941	null	[ [ "Buruli ulcer , which is caused by M . ulcerans , is a neglected tropical disease affecting mostly poor rural communities in West and Central Africa .", "In 2013 , 75% of all new cases of Buruli ulcer worldwide were declared by Ivory Coast , Ghana and Benin .", "This skin disease , which mostly affect...	[ "Buruli ulcer , the third mycobacterial disease after tuberculosis and leprosy , is caused by the environmental mycobacterium M . ulcerans .", "There is at present no clear understanding of the exact mode ( s ) of transmission of M . ulcerans .", "Populations affected by Buruli ulcer are those living close to h...	[ "Buruli ulcer is a neglected tropical disease due to M . ulcerans , an environmental mycobacteria .", "Modes of transmission to human remain unclear and water bugs and mosquitoes had been incriminated with more or less experimental laboratory evidences and filed studies .", "In this context , we have investigat...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "cell biology", "computational biology", "evolutionary biology", "molecular biology", "genetics and genomics" ]	Network Hubs Buffer Environmental Variation in Saccharomyces cerevisiae	journal.pbio.0060264	A genome-wide screen inSaccharomyces cerevisiae identifies over 300 gene products that buffer environmental variation--dubbed phenotypic capacitors--and function as hubs in protein-protein and synthetic-lethal interaction networks.	[ [ "The relationship between genotype and phenotype is a central concern of many fields , from developmental biology to human genetics to evolutionary biology .", "Although in most cases this relationship is poorly understood , some general properties do seem to be shared across diverse systems .", "Chie...	[ "Regulatory and developmental systems produce phenotypes that are robust to environmental and genetic variation .", "A gene product that normally contributes to this robustness is termed a phenotypic capacitor .", "When a phenotypic capacitor fails , for example when challenged by a harsh environment or mutatio...	[ "Most species maintain abundant genetic variation and experience a wide range of environmental conditions , yet phenotypic differences between individuals are usually small .", "This phenomenon , known as phenotypic robustness , presents an apparent contradiction: if biological systems are so resistant to variati...	2008
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "alleles", "animal models", "genomic databases", "model organisms", "drug design", "experimental organism systems", "genome analysis", "pharmacology", "computer-aided drug design", "research and analysis methods", "biologic...	Semantic prioritization of novel causative genomic variants	journal.pcbi.1005500	null	[ [ "Since the first successful identification of disease-causing variation From whole exome sequencing in 2010 [1] , impressive advances have been made in the field of next generation sequencing and its related analysis , with the aim of fulfilling the promise of whole exome ( WES ) and whole genome ( WGS ) sequ...	[ "Discriminating the causative disease variant ( s ) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today .", "Computational approaches for variant prioritization include machine learning methods utilizing a large number of features ...	[ "We address the problem of how to distinguish which of the many thousands of DNA sequence variants carried by an individual with a rare disease is responsible for the disease phenotypes .", "This can help clinicians arrive at a diagnosis , but also can be instrumental in improving our understanding of the pathobi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene expression", "genetics", "epigenetics", "biology", "molecular genetics", "genetics and genomics" ]	The ISWI Chromatin Remodeler Organizes the hsrω ncRNA–Containing Omega Speckle Nuclear Compartments	journal.pgen.1002096	null	[ [ "ISWI , the catalytic subunit of several ATP-dependent chromatin remodeling complexes , is highly conserved during evolution and is essential for cell viability [1] .", "ISWI-containing complexes play central roles in DNA replication , gene expression and chromosome organization [2] .", "ISWI uses ATP...	[ "The complexity in composition and function of the eukaryotic nucleus is achieved through its organization in specialized nuclear compartments .", "The Drosophila chromatin remodeling ATPase ISWI plays evolutionarily conserved roles in chromatin organization .", "Interestingly , ISWI genetically interacts with ...	[ "Chromatin structure and function are regulated by the concerted activity of covalent modifiers of chromatin , nucleosome remodeling factors , and several emerging classes of non-coding RNAs .", "ISWI is an evolutionarily conserved ATP-dependent chromatin remodeler playing essential roles in chromosome condensati...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant anatomy", "medicine and health sciences", "fusarium", "barley", "pathology and laboratory medicine", "fungal genetics", "gene regulation", "pathogens", "microbiology", "fusarium graminearum", "cereal crops", "fungi", "plant science", "crops", "plant pathology", "fungal diseases"...	An RNAi-Based Control of Fusarium graminearum Infections Through Spraying of Long dsRNAs Involves a Plant Passage and Is Controlled by the Fungal Silencing Machinery	journal.ppat.1005901	null	[ [ "According to the FAO [1] , more than half of the world’s harvested area is allotted to cereals such as rice , maize and wheat ( ca . 2 . 3 billion tons in 2010 ) .", "Diseases of cereal crops such as Fusarium head blight ( FHB ) and Fusarium seedling blight ( FSB ) , caused by necrotrophic fungi of the g...	[ "Meeting the increasing food and energy demands of a growing population will require the development of ground-breaking strategies that promote sustainable plant production .", "Host-induced gene silencing has shown great potential for controlling pest and diseases in crop plants .", "However , while delivery o...	[ "RNA interference has emerged as a powerful genetic tool for scientific research .", "The demonstration that agricultural pests , such as insects and nematodes , are killed by exogenously supplied RNA targeting their essential genes has raised the possibility that plant predation can be controlled by lethal RNA s...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal genetics", "cancer genetics", "immune cells", "genetic screens", "genetics", "t cells", "immunology", "biology", "genetics and genomics" ]	Cadm1 Is a Metastasis Susceptibility Gene That Suppresses Metastasis by Modifying Tumor Interaction with the Cell-Mediated Immunity	journal.pgen.1002926	null	[ [ "Metastatic disease remains a major problem for the clinical treatment of many different malignancies .", "Metastases can appear years after treatment of the primary tumor and is frequently refractory to therapy [1] .", "It has been estimated that approximately 90% of cancer-related deaths are directl...	[ "Metastasis is a complex process utilizing both tumor-cell-autonomous properties and host-derived factors , including cellular immunity .", "We have previously shown that germline polymorphisms can modify tumor cell metastatic capabilities through cell-autonomous mechanisms .", "However , how metastasis suscept...	[ "Metastasis , the dissemination and growth of tumor cells in organs distinct from which they originated , is the most common cause of cancer-related death .", "Accumulating evidence indicates that an individual's genetic background , the heritable complement of genetic variations that distinguish individuals , no...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/epigenetics", "nutrition" ]	A Sustained Dietary Change Increases Epigenetic Variation in Isogenic Mice	journal.pgen.1001380	null	[ [ "Epigenetic modifications lie at the interface between genes and the environment , and", "thus have the potential to create functional diversity in response to environmental", "cues .", "There is mounting evidence that the establishment of epigenetic states during", "mammalian development can ...	[ "Epigenetic changes can be induced by adverse environmental exposures , such as", "nutritional imbalance , but little is known about the nature or extent of these", "changes .", "Here we have explored the epigenomic effects of a sustained nutritional", "change , excess dietary methyl donors , by assessing g...	[ "Epigenetic changes to gene expression that do not involve changes to DNA sequence", "can be influenced by the environment and provide one candidate mechanism by", "which early nutrition can influence adult disease risk .", "Here , we examined", "epigenetic changes across the genome in response to short- an...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/population genetics", "genetics and genomics/microbial evolution and genomics", "evolutionary biology/sexual behavior", "computational biology/evolutionary modeling", "genetics and genomics/population genetics" ]	Optimal Strategy for Competence Differentiation in Bacteria	journal.pgen.1001108	null	[ [ "Bacteria mainly reproduce asexually , which has strong implications for the degree and patterns of intraspecific genetic diversity .", "However , three quasi-sexual mechanisms operate to combine genetic information between different lineages: conjugation , transduction , and transformation .", "Among...	[ "A phylogenetically diverse subset of bacterial species are naturally competent for transformation by DNA .", "Transformation entails recombination of genes between different lineages , representing a form of bacterial sex that increases standing genetic variation .", "We first assess whether homologous recombi...	[ "In certain environmental conditions , populations of the bacterium Bacillus subtilis split into two physiologically distinct phenotypes .", "While some cells continue to grow and divide , a minority become “competent” for transformation by extracellular DNA .", "This differentiation process is driven not by ge...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells	journal.pgen.1005555	null	[ [ "MIcrophthalmia-associated Transcription Factor ( MITF ) is a basic helix-loop-helix leucine zipper ( bHLH-Zip ) factor playing an essential role in the differentiation , survival , and proliferation of normal melanocytes , and in controlling the melanoma cell physiology [1–4] .", "Quiescent murine adult ...	[ "MIcrophthalmia-associated Transcription Factor ( MITF ) regulates melanocyte and melanoma physiology .", "We show that MITF associates the NURF chromatin-remodelling factor in melanoma cells .", "ShRNA-mediated silencing of the NURF subunit BPTF revealed its essential role in several melanoma cell lines and in...	[ "The melanocytes pigmenting the coat of adult mice derive from the melanocyte stem cell population residing in the permanent bulge area of the hair follicle .", "At each angen phase , melanocyte stem cells are stimulated to generate proliferative transient amplifying cells that migrate to the bulb of the follicle...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "physics", "biochemistry", "developmental biology", "biology", "molecular cell biology", "biophysics" ]	Spire and Formin 2 Synergize and Antagonize in Regulating Actin Assembly in Meiosis by a Ping-Pong Mechanism	journal.pbio.1001795	An in vitro study reveals how the three actin binding proteins profilin, formin 2, and Spire functionally cooperate by a ping-pong mechanism to regulate actin assembly during reproductive cell division.	[ [ "In mouse meiosis I , translocation of the spindle toward a cortical site that defines polar body extrusion is the first step in establishment of oocyte polarity [1] , [2] .", "This process is driven by assembly of cytoplasmic actin filaments in which formin 2 ( Fmn2 ) plays a pivotal role [3]–[8] .", ...	[ "In mammalian oocytes , three actin binding proteins , Formin 2 ( Fmn2 ) , Spire , and profilin , synergistically organize a dynamic cytoplasmic actin meshwork that mediates translocation of the spindle toward the cortex and is required for successful fertilization .", "Here we characterize Fmn2 and elucidate the...	[ "Mammalian reproduction requires successful meiosis , which consists of two strongly asymmetric cell divisions .", "In meiosis I , movement of the spindle ( the subcellular structure that segregates chromosomes during division ) toward the oocyte cortex ( the outer layer of the egg ) is essential for fertility ."...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "flow cytometry", "lysosomes", "rna interference", "membrane proteins", "immunoprecipitation", "epigenetics", "cellular structures and organelles", "research and analysis methods", "sequence analysis", "specimen preparation and treatment", "staining", "sequence alignment", "genetic interfere...	Controlling transferrin receptor trafficking with GPI-valence in bloodstream stage African trypanosomes	journal.ppat.1006366	null	[ [ "Many eukaryotic secretory proteins such as surface antigens , adhesion proteins , and receptors are attached to the external leaflet of the plasma membrane by glycosylphosphatidylinositol ( GPI ) anchors [1 , 2] .", "GPI anchors function as vesicular transport signals for ER export , for post-Golgi sorti...	[ "Bloodstream-form African trypanosomes encode two structurally related glycosylphosphatidylinositol ( GPI ) -anchored proteins that are critical virulence factors , variant surface glycoprotein ( VSG ) for antigenic variation and transferrin receptor ( TfR ) for iron acquisition .", "Both are transcribed from the...	[ "African trypanosomes , protozoan parasites that cause African Sleeping Sickness , have two structurally related secretory proteins that are critical for their success as pathogens: variant surface glycoprotein ( VSG ) , which is responsible for evasion of host immune responses , and transferrin receptor ( TfR ) , ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Alternatively Spliced Homologous Exons Have Ancient Origins and Are Highly Expressed at the Protein Level	journal.pcbi.1004325	null	[ [ "Studies have estimated that alternative splicing can produce differently spliced messenger RNA ( mRNA ) transcripts for practically all multi-exon human genes [1 , 2] .", "These mRNA variants have the potential to expand the cellular protein repertoire far beyond the one gene–one protein model that forme...	[ "Alternative splicing of messenger RNA can generate a wide variety of mature RNA transcripts , and these transcripts may produce protein isoforms with diverse cellular functions .", "While there is much supporting evidence for the expression of alternative transcripts , the same is not true for the alternatively ...	[ "Alternative splicing is thought to be one means for generating the protein diversity necessary for the whole range of cellular functions .", "While the presence of alternatively spliced transcripts in the cell has been amply demonstrated , the same cannot be said for alternatively spliced proteins .", "The que...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "trachoma" ]	Antibody Signature of Spontaneous Clearance of Chlamydia trachomatis Ocular Infection and Partial Resistance against Re-challenge in a Nonhuman Primate Trachoma Model	journal.pntd.0002248	null	[ [ "The obligate intracellular bacterial parasite Chlamydia trachomatis is the causative agent of blinding trachoma and sexually transmitted diseases .", "C . trachomatis utilizes a unique biphasic developmental cycle alternating between infectious elementary bodies ( EB ) and metabolically active reticulate...	[ "Chlamydia trachomatis is the etiological agent of trachoma the world's leading cause of infectious blindness .", "Here , we investigate whether protracted clearance of a primary infection in nonhuman primates is attributable to antigenic variation or related to the maturation of the anti-chlamydial humoral immun...	[ "Chlamydia trachomatis is the etiological agent of trachoma the world's leading cause of infectious blindness .", "In this study , we investigated whether delayed clearance of a primary infection in nonhuman primates was attributable to antigenic variation or related to gradual changes in the humoral immune respo...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "animal types", "children", "medicine and health sciences", "zoonotic pathogens", "animal pathogens", "pathology and laboratory medicine", "pathogens", "diet", "vertebrates", "animals", "mammals", "animal products", "age groups", "nutrition", "animal behavior", "meat", "zoology", "...	Participation of women and children in hunting activities in Sierra Leone and implications for control of zoonotic infections	journal.pntd.0005699	null	[ [ "Recent occurrences of infectious disease outbreaks involving pathogens such as Lassa virus , Ebola virus and simian retroviruses have led to increasing concern about emerging zoonoses [1] .", "The probability of a zoonotic infection depends in part upon the frequency and nature of contact between animal ...	[ "The emergence of infectious diseases of zoonotic origin highlights the need to understand social practices at the animal-human interface .", "This study provides a qualitative account of interactions between humans and wild animals in predominantly Mende villages of southern Sierra Leone .", "We conducted fiel...	[ "Studying how and why humans interact with animals is important to understand the transmission of zoonotic diseases ( infectious diseases transmitted from animals to humans ) and how to prevent and control them .", "We conducted a qualitative study to understand how and why people come into contact with wild anim...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell biology/cell growth and division", "genetics and genomics/chromosome biology", "genetics and genomics/functional genomics" ]	Identification of Drosophila Mitotic Genes by Combining Co-Expression Analysis and RNA Interference	journal.pgen.1000126	null	[ [ "RNA interference ( RNAi ) in Drosophila cell cultures is a powerful tool for the identification of proteins involved in mitotic cell division .", "The addition of a double stranded RNA ( dsRNA ) to the cell medium leads to rapid downregulation of the corresponding mitotic protein , resulting in a specifi...	[ "RNAi screens have , to date , identified many genes required for mitotic divisions of Drosophila tissue culture cells .", "However , the inventory of such genes remains incomplete .", "We have combined the powers of bioinformatics and RNAi technology to detect novel mitotic genes .", "We found that Drosophil...	[ "Mitosis is the evolutionarily conserved process that enables a dividing cell to equally partition its genetic material between the two daughter cells .", "The fidelity of mitotic division is crucial for normal development of multicellular organisms and to prevent cancer or birth defects .", "Understanding the ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Meiotic Crossover Control by Concerted Action of Rad51-Dmc1 in Homolog Template Bias and Robust Homeostatic Regulation	journal.pgen.1003978	null	[ [ "During meiosis , haploid gametes are formed from diploid precursor cells via two successive rounds of chromosome segregation .", "By a program of events unique to meiosis , parental chromosomes ( homologs ) associate into homologous pairs and then disjoin from one another at the first division of meiosis...	[ "During meiosis , repair of programmed DNA double-strand breaks ( DSBs ) by recombination promotes pairing of homologous chromosomes and their connection by crossovers .", "Two DNA strand-exchange proteins , Rad51 and Dmc1 , are required for meiotic recombination in many organisms .", "Studies in budding yeast ...	[ "Meiosis is the specialized cell division that produces gametes by precisely reducing the chromosome copy number from two to one .", "Accurate segregation of homologous chromosome pairs requires they be connected by crossing-over , the precise breakage and exchange of chromosome arms that is carried out by a proc...	2013

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