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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", "Methods", "Results", "Discussion" ]	[ "evolutionary ecology", "medicine and health sciences", "ecology", "population modeling", "epidemiology", "biology and life sciences", "population biology", "spatial epidemiology", "computational biology", "evolutionary biology" ]	Evolution of Pathogen Specialisation in a Host Metapopulation: Joint Effects of Host and Pathogen Dispersal	journal.pcbi.1003633	null	[ [ "In spatially structured populations , habitat spatial heterogeneity plays a crucial role in determining the potential for species and genotypes to coexist [1] , [2] and in shaping the evolution of populations and species [3] , [4] .", "However , environments are not static and temporal fluctuations in ha...	[ "Metapopulation processes are important determinants of epidemiological and evolutionary dynamics in host-pathogen systems , and are therefore central to explaining observed patterns of disease or genetic diversity .", "In particular , the spatial scale of interactions between pathogens and their hosts is of prim...	[ "Relatively little is known about actual patterns of generalisation and specialisation in natural plant-pathogen systems largely because many fewer studies have focused on the pathogenicity structure of pathogen populations than on the resistance structure of their host populations .", "The spatial scale of inter...	2014
[ "Introduction", "Results and Discussion", "Methods" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "helminths", "computational biology", "animals", "trematodes", "genome analysis", "research and analysis methods", "fasciola hepatica", "proteins", "flatworms", "fasciola", "biological databases", "comp...	Genomes of Fasciola hepatica from the Americas Reveal Colonization with Neorickettsia Endobacteria Related to the Agents of Potomac Horse and Human Sennetsu Fevers	journal.pgen.1006537	null	[ [ "Food borne trematodes ( FBTs ) are an assemblage of platyhelminth parasites that are transmitted through the food chain [1] .", "Among the four major groups of FBT infections recognized as neglected tropical diseases ( NTDs ) by the World Health Organization [2] , fascioliasis stands out due to its zoono...	[ "Food borne trematodes ( FBTs ) are an assemblage of platyhelminth parasites transmitted through the food chain , four of which are recognized as neglected tropical diseases ( NTDs ) .", "Fascioliasis stands out among the other NTDs due to its broad and significant impact on both human and animal health , as Fasc...	[ "This report presents novel findings revealing", "( a ) the genome sequence of the food-borne trematode Fasciola hepatica ( the liver fluke ) isolated from sheep , which stands out among neglected tropical diseases due to its zoonotic impact on both human and animal health and", "( b ) the first instance ( and ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "viral vaccines", "emerging infectious diseases", "virology", "neglected tropical diseases", "biology", "microbiology", "arboviral infections", "infectious disease control", "viral evolution" ]	Random Codon Re-encoding Induces Stable Reduction of Replicative Fitness of Chikungunya Virus in Primate and Mosquito Cells	journal.ppat.1003172	null	[ [ "Many emerging infectious diseases are caused by arthropod-borne viruses ( arboviruses ) , almost all of which are single strand RNA viruses .", "The major outbreaks of dengue fever [1] , West Nile encephalitis [2] , Chikungunya fever [3] , and Rift Valley fever [4] that have occurred in recent decades , ...	[ "Large-scale codon re-encoding represents a powerful method of attenuating viruses to generate safe and cost-effective vaccines .", "In contrast to specific approaches of codon re-encoding which modify genome-scale properties , we evaluated the effects of random codon re-encoding on the re-emerging human pathogen...	[ "Emerging arthropod-borne viruses ( arboviruses ) are a major cause of human and animal morbidity and mortality .", "Climatic and anthropological activities are responsible for the dispersal of arbovirus transmission vectors into new territories .", "Chikungunya virus ( CHIKV ) is an important example of a re-e...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genetics and genomics/epigenetics", "genetics and genomics/gene discovery", "genetics and genomics/genetics of disease", "genetics and genomics/medical genetics" ]	Germline Mutation in NLRP2 (NALP2) in a Familial Imprinting Disorder (Beckwith-Wiedemann Syndrome)	journal.pgen.1000423	null	[ [ "Genomic imprinting is an epigenetic modification that causes genes to be expressed according to their parent of origin .", "Although less than 100 imprinted genes have been identified in human and mice , many imprinted genes appear to have a critical role in prenatal growth and development [1] .", "M...	[ "Beckwith-Wiedemann syndrome ( BWS ) is a fetal overgrowth and human imprinting disorder resulting from the deregulation of a number of genes , including IGF2 and CDKN1C , in the imprinted gene cluster on chromosome 11p15 . 5 .", "Most cases are sporadic and result from epimutations at either of the two 11p15 . 5...	[ "A small set of genes ( imprinted genes ) are expressed in a “parent-of-origin” manner , a phenomenon known as genomic imprinting .", "Research in human disorders associated with aberrant genomic imprinting provided insights into the molecular mechanisms of genomic imprinting and the role of imprinted genes in no...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "cell biology", "microbiology", "infectious diseases/bacterial infections", "molecular biology" ]	Inhibition of Host Vacuolar H+-ATPase Activity by a Legionella pneumophila Effector	journal.ppat.1000822	null	[ [ "The delivery of newly formed phagosomes to the lysosomal system by the endocytic pathway is essential for the digestion of phagocytosed materials .", "To evade such destruction , successful intracellular bacterial pathogens have evolved various mechanisms , including inhibition of phagolysosomal fusion ,...	[ "Legionella pneumophila is an intracellular pathogen responsible for Legionnaires' disease .", "This bacterium uses the Dot/Icm type IV secretion system to inject a large number of bacterial proteins into host cells to facilitate the biogenesis of a phagosome permissive for its intracellular growth .", "Like ma...	[ "One hallmark of the lysosome is a low luminal pH that is important for its maturation as well as the activity of many hydrolyzing enzymes responsible for efficient digestion of phagocytosed contents .", "To survive and replicate in phagocytes , successful intracellular pathogens have evolved various mechanisms t...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "phosphorylation", "medicine and health sciences", "cell cycle inhibitors", "immune cells", "pathology and laboratory medicine", "cell cycle and cell division", "pathogens", "immunology", "cell processes", "microbiology", "cell differentiation", "retroviruses", "viruses", ...	The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells	journal.ppat.1005829	null	[ [ "Macrophages are a highly heterogeneous cell population that plays a prominent role in innate immune system as key effector cells for the elimination of pathogens , infected cells and cancer cells [1 , 2] .", "Macrophages also play an essential role in maintaining tissue homeostasis by supporting tissue d...	[ "Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases ( CDK ) .", "Here , we have used primary human monocyte-derived macrophages differentiated thro...	[ "Macrophages are a heterogeneous population of immune cells that provide crucial innate immune defense against pathogens , including HIV-1 .", "The molecular biology of HIV-1 infection in macrophages is influenced by the presence of the host cell restriction factor SAMHD1 , which is regulated by phosphorylation b...	2016
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "plant science", "microbial evolution", "plant pathogens", "plant pathology", "plant biology", "biology", "microbiology" ]	The Stealth Episome: Suppression of Gene Expression on the Excised Genomic Island PPHGI-1 from Pseudomonas syringae pv. phaseolicola	journal.ppat.1002010	null	[ [ "The exchange of genomic pathogenicity islands by horizontal gene transfer is recognised as a key factor in the development of new more virulent bacterial pathogens of both animals and plants [1] , [2] , [3] , [4] .", "Pseudomonas syringae is a bacterial species sub-divided into pathovars based on host ra...	[ "Pseudomonas syringae pv .", "phaseolicola is the causative agent of halo blight in the common bean , Phaseolus vulgaris .", "P . syringae pv .", "phaseolicola race 4 strain 1302A contains the avirulence gene avrPphB ( syn . hopAR1 ) , which resides on PPHGI-1 , a 106 kb genomic island .", "Loss of PPHGI-1 ...	[ "Bacterial pathogens evolve rapidly through the transfer of large segments , or genomic islands ( GIs ) , of DNA .", "We study the mobility of an island named PPHGI-1 in Pseudomonas syringae pv .", "phaseolicola that causes halo-blight disease of bean .", "The exposure of P . syringae pv .", "phaseolicola t...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Plasma Membrane Profiling Defines an Expanded Class of Cell Surface Proteins Selectively Targeted for Degradation by HCMV US2 in Cooperation with UL141	journal.ppat.1004811	null	[ [ "HCMV is the prototype betaherpesvirus and an important human pathogen .", "Following primary infection , HCMV persists for the lifetime of the host under constant control by the host immune system .", "In the face of this selective pressure , HCMV has evolved multiple mechanisms to evade immune detec...	[ "Human cytomegalovirus ( HCMV ) US2 , US3 , US6 and US11 act in concert to prevent immune recognition of virally infected cells by CD8+ T-lymphocytes through downregulation of MHC class I molecules ( MHC-I ) .", "Here we show that US2 function goes far beyond MHC-I degradation .", "A systematic proteomic study ...	[ "As the largest human herpesvirus , HCMV is a paradigm of viral immune evasion and has evolved multiple mechanisms to evade immune detection and enable survival .", "The HCMV genes US2 , US3 , US6 and US11 promote virus persistence by their ability to downregulate cell surface MHC .", "We developed ‘Plasma Memb...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genome-wide association studies", "medicine and health sciences", "protein interactions", "protein interaction networks", "variant genotypes", "bipolar disorder", "alleles", "genetic mapping", "coronary heart disease", "network analysis", "genome analysis", "mood disorders", "cardiology", ...	PoCos: Population Covering Locus Sets for Risk Assessment in Complex Diseases	journal.pcbi.1005195	null	[ [ "Genome-wide association studies ( GWAS ) have a transformative effect on the search for genetic variants that are associated with complex traits , since they enable screening of hundreds of thousands of genomic variants for their association with traits of interest [1] .", "Recently published GWAS lead t...	[ "Susceptibility loci identified by GWAS generally account for a limited fraction of heritability .", "Predictive models based on identified loci also have modest success in risk assessment and therefore are of limited practical use .", "Many methods have been developed to overcome these limitations by incorpora...	[ "Several studies try to predict the individual disease risk using genetic data obtained from genome wide association studies ( GWAS ) .", "Earlier studies only focus on individual genetic variants .", "However , studies on disease mechanisms suggest the aggregation of genomic variants may contribute to diseases...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/theoretical neuroscience", "neuroscience/sensory systems" ]	Pairwise Maximum Entropy Models for Studying Large Biological Systems: When They Can Work and When They Can't	journal.pcbi.1000380	null	[ [ "Many fundamental questions in biology are naturally treated in a probabilistic", "setting .", "For instance , deciphering the neural code requires knowledge of the", "probability of observing patterns of activity in response to stimuli [1];", "determining which features of a protein are impor...	[ "One of the most critical problems we face in the study of biological systems is", "building accurate statistical descriptions of them .", "This problem has been", "particularly challenging because biological systems typically contain large", "numbers of interacting elements , which precludes the use of sta...	[ "Biological systems are exceedingly complicated: They consist of a large number of", "elements , those elements interact in nonlinear and highly unpredictable ways ,", "and collective interactions typically play a critical role .", "It would seem", "surprising , then , that one could build a quantitative de...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics", "biology", "genetics and genomics" ]	Multiple Wnts Redundantly Control Polarity Orientation in Caenorhabditis elegans Epithelial Stem Cells	journal.pgen.1002308	null	[ [ "For tissues and organs to be properly organized , it is often essential that cell polarity be coordinated among cell groups .", "In the Drosophila wing , for example , cells are polarized in the same proximal-to-distal orientation to produce hairs pointing distally [1] .", "Similarly , in the mammali...	[ "During development , cell polarization is often coordinated to harmonize tissue patterning and morphogenesis .", "However , how extrinsic signals synchronize cell polarization is not understood .", "In Caenorhabditis elegans , most mitotic cells are polarized along the anterior-posterior axis and divide asymme...	[ "Proper functions and development of organs often require the synchronized polarization of entire cell groups .", "How cells coordinate their polarity is poorly understood .", "One plausible model is that individual cells recognize extrinsic signal gradients that orient their polarity , although this has not be...	2011
[ "Introduction", "Results/Discussion", "Methods" ]	[ "molecular biology/bioinformatics", "genetics and genomics/bioinformatics", "computational biology" ]	Prediction by Graph Theoretic Measures of Structural Effects in Proteins Arising from Non-Synonymous Single Nucleotide Polymorphisms	journal.pcbi.1000135	null	[ [ "The introduction of large-scale genome sequencing technologies has dramatically increased the number of single nucleotide polymorphisms ( SNPs ) in public databases .", "For example , the NCBI ( National Center for Biotechnology Information ) dbSNP database [1] , which is a major repository of human SNPs...	[ "Recent analyses of human genome sequences have given rise to impressive advances in identifying non-synonymous single nucleotide polymorphisms ( nsSNPs ) .", "By contrast , the annotation of nsSNPs and their links to diseases are progressing at a much slower pace .", "Many of the current approaches to analysin...	[ "Non-synonymous single nucleotide polymorphisms ( nsSNPs ) are single base differences between individual genomes that lead to amino acid changes in protein sequences .", "They may influence an individual's susceptibility to disease or response to drugs through their impacts on a protein's structure and hence cau...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "humoral immunity", "antibody-producing cells", "white blood cells", "immune cells", "cell biology", "animal cells", "b cells", "immunity", "immunity to infections", "biology and life sciences", "cellular types", "immunology", "immune response" ]	Establishment of Murine Gammaherpesvirus Latency in B Cells Is Not a Stochastic Event	journal.ppat.1004269	null	[ [ "The murid γ-herpesvirus-4 ( MuHV-4 , also known as MHV-68 or γHV-68 ) has led to valuable insights in understanding human γ-herpesvirus related diseases caused by Epstein-Barr virus ( EBV ) and Kaposi's sarcoma associated herpesvirus ( KSHV ) [1] .", "Whereas primo infection by γ-herpesviruses can be res...	[ "Murid γ-herpesvirus-4 ( MuHV-4 ) promotes polyclonal B cell activation and establishes latency in memory B cells via unclear mechanisms .", "We aimed at exploring whether B cell receptor specificity plays a role in B cell susceptibility to viral latency and how this is related to B cell activation .", "We firs...	[ "Murid γ-herpesvirus-4 ( MuHV-4 ) is a good model to study infectious mononucleosis in mice , in which the virus ultimately establishes life-long latency in B cells .", "Whereas several viral proteins have been shown to modulate B cell behavior , in the present study we aimed at clarifying the parameters that dic...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics of disease", "medicine", "model organisms", "otorhinolaryngology", "drugs and devices", "gene expression", "genetics", "biology", "otolaryngology", "gene networks", "genetics and genomics" ]	HIF–VEGF Pathways Are Critical for Chronic Otitis Media in Junbo and Jeff Mouse Mutants	journal.pgen.1002336	null	[ [ "Chronic middle ear effusion without the symptoms of acute infection is termed otitis media ( OM ) with effusion and can be sequel to acute bacterial otitis media .", "Otitis media with effusion ( OME ) is the most common cause of hearing impairment in children potentially causing language delays , learni...	[ "Otitis media with effusion ( OME ) is the commonest cause of hearing loss in children , yet the underlying genetic pathways and mechanisms involved are incompletely understood .", "Ventilation of the middle ear with tympanostomy tubes is the commonest surgical procedure in children and the best treatment for chr...	[ "Otitis media with effusion ( OME ) is the commonest cause of hearing loss in children , and treatment using grommets remains the commonest surgical procedure in children .", "Chronic forms of OM are known from human population studies to have a significant genetic component , but little is known of the underlyin...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "united states", "evolutionary biology", "population genetics", "geographical locations", "census", "genetic mapping", "ethnicities", "north america", "research design", "latin american people", "population biology", "research and analysis methods", "genomics", "comparative genomics", "n...	Native American admixture recapitulates population-specific migration and settlement of the continental United States	journal.pgen.1008225	null	[ [ "Native Americans inhabited the area that now makes up the continental US for thousands of years prior to the arrival of the first European settlers .", "The ancestors of modern Native Americans are thought have arrived in the Americas from Asia , by way of the Bering Strait , in several successive waves ...	[ "European and African descendants settled the continental US during the 17th-19th centuries , coming into contact with established Native American populations .", "The resulting admixture among these groups yielded a significant reservoir of Native American ancestry in the modern US population .", "We analyzed ...	[ "The post-Colombian settling of North America brought African , European , and Native American populations into close proximity for the first time .", "The inevitable admixture among these groups resulted a reservoir of Native American ancestry in modern US populations , outside of traditional Native American gro...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "biogeography", "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "intracellular pathogens", "pathogens", "immunology", "population genetics", "clinical medicine", "molecular biology techniques", "population biol...	Pathogen diversity drives the evolution of generalist MHC-II alleles in human populations	journal.pbio.3000131	Whereas specialist major histocompatibility complex (MHC) molecules initiate immune response against only relatively few pathogens, generalists provide protection against a broad range. Accordingly, this study shows that the geographical distribution of generalist MHC alleles in human populations reflects exposure to d...	[ [ "The major histocompatibility complex ( MHC ) genes in vertebrates encode cell surface proteins and are essential components of adaptive immune recognition [1] .", "MHC proteins are endowed with highly variable peptide-binding domains that bind short protein fragments .", "The MHC region is one of the...	[ "Central players of the adaptive immune system are the groups of proteins encoded in the major histocompatibility complex ( MHC ) , which shape the immune response against pathogens and tolerance to self-peptides .", "The corresponding genomic region is of particular interest , as it harbors more disease associat...	[ "Variation in the human genome influences our susceptibility to infectious diseases , but the causal link between disease and underlying mutation often remains enigmatic .", "Major histocompatibility complex II ( MHC class II ) molecules shape both our immune response against pathogens and our tolerance of self-p...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "developmental biology", "model organisms", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	Stress-Induced PARP Activation Mediates Recruitment of Drosophila Mi-2 to Promote Heat Shock Gene Expression	journal.pgen.1002206	null	[ [ "The activity of eukaryotic genomes is regulated by dynamic changes in chromatin structure .", "A multitude of nucleosome remodeling enzymes , histone modifying activities and chromatin binding proteins cooperate to establish , maintain and reprogram chromatin structures that determine genome activity .",...	[ "Eukaryotic cells respond to genomic and environmental stresses , such as DNA damage and heat shock ( HS ) , with the synthesis of poly-[ADP-ribose] ( PAR ) at specific chromatin regions , such as DNA breaks or HS genes , by PAR polymerases ( PARP ) .", "Little is known about the role of this modification during ...	[ "Cells respond to elevated temperatures with the rapid activation of heat shock genes to ensure cellular survival .", "Heat shock gene activation involves the synthesis of poly-[ADP-ribose] ( PAR ) at heat shock loci , the opening of chromatin structure , and the coordinated recruitment of transcription factors a...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genetics", "genetics and genomics", "biology", "genomics", "respiratory medicine", "pulmonology" ]	Lung eQTLs to Help Reveal the Molecular Underpinnings of Asthma	journal.pgen.1003029	null	[ [ "Recent genome-wide association studies ( GWAS ) have identified loci that harbor susceptibility genes for asthma and other pulmonary conditions [1]–[16] .", "Many of the genes at these loci have unknown function and have not previously been considered biologically plausible candidates for disease pathoge...	[ "Genome-wide association studies ( GWAS ) have identified loci reproducibly associated with pulmonary diseases; however , the molecular mechanism underlying these associations are largely unknown .", "The objectives of this study were to discover genetic variants affecting gene expression in human lung tissue , t...	[ "Recent genome-wide association studies ( GWAS ) have identified genetic variants associated with lung diseases .", "The challenge now is to find the causal genes in GWAS–nominated chromosomal regions and to characterize the molecular function of disease-associated genetic variants .", "In this paper , we descr...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation", "molecular biology/rna-protein interactions", "virology/antivirals, including modes of action and resistance", "virology", "biochemistry/replication and repair" ]	Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture	journal.ppat.1001176	null	[ [ "Zinc ions are involved in many different cellular processes and have proven crucial for the proper folding and activity of various cellular enzymes and transcription factors .", "Zn2+ is probably an important cofactor for numerous viral proteins as well .", "Nevertheless , the intracellular concentra...	[ "Increasing the intracellular Zn2+ concentration with zinc-ionophores like pyrithione ( PT ) can efficiently impair the replication of a variety of RNA viruses , including poliovirus and influenza virus .", "For some viruses this effect has been attributed to interference with viral polyprotein processing .", "...	[ "Positive-stranded RNA ( +RNA ) viruses include many important pathogens .", "They have evolved a variety of replication strategies , but are unified in the fact that an RNA-dependent RNA polymerase ( RdRp ) functions as the core enzyme of their RNA-synthesizing machinery .", "The RdRp is commonly embedded in a...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemical bonding", "chemical compounds", "enzymes", "enzymology", "organic compounds", "mutation", "substitution mutation", "amino acid substitution", "network analysis", "amino acids", "hydrogen bonding", "physical chemistry", "computer and information sciences", "proteins", "chemistry...	Application of Rigidity Theory to the Thermostabilization of Lipase A from Bacillus subtilis	journal.pcbi.1004754	null	[ [ "Thermostability is a crucial factor for a wealth of biotechnological enzyme applications [1 , 2] .", "Protein engineering aimed at improving thermostability is thus an important field of research in biotechnology [3 , 4] .", "There , methods of directed evolution are usually applied , which mimic nat...	[ "Protein thermostability is a crucial factor for biotechnological enzyme applications .", "Protein engineering studies aimed at improving thermostability have successfully applied both directed evolution and rational design .", "However , for rational approaches , the major challenge remains the prediction of m...	[ "Protein thermostability is a crucial factor for biotechnological enzyme applications .", "However , performance studies of computational approaches for predicting effects of mutations on protein ( thermo ) stability have suggested that there is still room for improvement .", "We describe and validate a novel a...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "chemical characterization", "pathology and laboratory medicine", "gene regulation", "regulatory proteins", "dna-binding proteins", "dna transcription", "transcription factors", "genetic elements", "dna", "research and analysis methods", "dna binding assay", "...	Transcription Factors Encoded on Core and Accessory Chromosomes of Fusarium oxysporum Induce Expression of Effector Genes	journal.pgen.1006401	null	[ [ "Plant pathogenic fungi are genetically adapted to infect their host plant , but are also in a constant arms race with that host to stay virulent .", "For this , pathogens need to allow accelerated evolution of pathogenicity-related genes , without affecting the function of housekeeping genes .", "One...	[ "Proteins secreted by pathogens during host colonization largely determine the outcome of pathogen-host interactions and are commonly called ‘effectors’ .", "In fungal plant pathogens , coordinated transcriptional up-regulation of effector genes is a key feature of pathogenesis and effectors are often encoded in ...	[ "Eukaryotic genomes are organised .", "Genomic regions may differ in spatial organisation , chromatin condensation , rate of evolution , GC content , gene expression and transposon density .", "Many plant pathogenic fungi maintain genomic subcompartments containing specialized genes to facilitate host colonisat...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "chemical compounds", "oxides", "oxidative stress", "cell disruption", "mutation", "hydrogen peroxide", "cellular structures and organelles", "cytoskeleton", "research and analysis methods", "contractile proteins", "infectious diseases", "actins", "mutant st...	Disrupting the cortical actin cytoskeleton points to two distinct mechanisms of yeast [PSI+] prion formation	journal.pgen.1006708	null	[ [ "Prions are infectious agents composed of misfolded proteins .", "They are associated with a group of neurodegenerative diseases in animals and humans that have common pathological hallmarks , typified by human Creutzfeldt-Jakob Disease ( CJD ) .", "The presence of the misfolded prion protein ( PrPSc ...	[ "Mammalian and fungal prions arise de novo; however , the mechanism is poorly understood in molecular terms .", "One strong possibility is that oxidative damage to the non-prion form of a protein may be an important trigger influencing the formation of its heritable prion conformation .", "We have examined the ...	[ "Prions are infectious agents which are composed of misfolded proteins and have been implicated in progressive neurodegenerative diseases such as Creutzfeldt Jakob Disease ( CJD ) .", "Most prion diseases occur sporadically and are then propagated in a protein-only mechanism via induced protein misfolding .", "...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "viral hemorrhagic fevers", "infectious diseases", "venezuelan hemorrhagic fever", "neglected tropical diseases", "argentine hemorrhagic fever", "viral diseases", "lassa fever" ]	Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever	journal.pntd.0001342	null	[ [ "A limited number of phylogenetically distinct viruses that belong to the Arenaviridae , Bunyaviridae , Filoviridae , and Flaviviridae families can cause a severe hemorrhagic fever syndrome that often results in death .", "Among the arenaviruses , two Old World ( Lassa and Lujo ) and several New World ( J...	[ "Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever , respectively .", "At present , ribavirin is the only antiviral drug indicated for use in treatment of these diseases , but becaus...	[ "Several viruses in the Arenaviridae family cause severe life-threatening hemorrhagic fever syndromes , which are considered neglected tropical diseases in endemic areas of Africa and South America .", "Ribavirin , the only licensed antiviral indicated for use has limited efficacy when treating advanced cases of ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Macrophage Activation Associated with Chronic Murine Cytomegalovirus Infection Results in More Severe Experimental Choroidal Neovascularization	journal.ppat.1002671	null	[ [ "Angiogenesis , the formation of blood vessels , plays a critical role in embryonic development , wound healing , and normal physiologic processes associated with natural growth and development .", "On the other hand , new blood vessel growth ( neovascularization ) contributes to a number of pathologic co...	[ "The neovascular ( wet ) form of age-related macular degeneration ( AMD ) leads to vision loss due to choroidal neovascularization ( CNV ) .", "Since macrophages are important in CNV development , and cytomegalovirus ( CMV ) -specific IgG serum titers in patients with wet AMD are elevated , we hypothesized that c...	[ "Neovascular age-related macular degeneration ( AMD ) is the leading cause of vision loss in the elderly .", "Onset of AMD is due to local production of vascular endothelial growth factor ( VEGF ) that promotes formation of new blood vessels in the retina , thereby leading to retinal tissue destruction and blindn...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "infectious diseases/neglected tropical diseases", "microbiology/parasitology" ]	Trypanosoma brucei Modifies the Tsetse Salivary Composition, Altering the Fly Feeding Behavior That Favors Parasite Transmission	journal.ppat.1000926	null	[ [ "Tsetse flies ( Diptera: Glossinidae ) are obligate blood feeding insects that are important disease vectors given their involvement in the transmission of different pathogenic trypanosome species that cause human sleeping sickness and livestock trypanosomiasis in Africa .", "Trypanosomes of the Trypanoso...	[ "Tsetse flies are the notorious transmitters of African trypanosomiasis , a disease caused by the Trypanosoma parasite that affects humans and livestock on the African continent .", "Metacyclic infection rates in natural tsetse populations with Trypanosoma brucei , including the two human-pathogenic subspecies , ...	[ "Human African Trypanosomiasis , or sleeping sickness , is a devastating parasitic disease that is fatal if left untreated .", "Infections are acquired via the bite of an obligate blood feeding fly , the tsetse fly , that is exclusively present on the African continent .", "In this insect vector , the trypanoso...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/genetics of disease", "rheumatology/rheumatoid arthritis", "genetics and genomics/genetics of the immune system" ]	An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans	journal.pgen.1000424	null	[ [ "Cytotoxic T-lymphocyte associated protein 4 ( CTLA4 , CD152 ) is a negative regulator of T-cell activation .", "As the T-cell activation signal propagates due to costimulatory B7 molecule ( CD80 , CD86 ) binding of CD28 , cell surface expression of CTLA4 increases to compete with CD28 [1] .", "CTLA4 ...	[ "Cytotoxic T-lymphocyte associated protein 4 ( CTLA4 ) is a negative regulator of T-cell proliferation .", "Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis ( RA ) in populations of European ancestry but have not been examined in African Americans .", "The p...	[ "Rheumatoid arthritis ( RA ) is a systemic autoimmune condition affecting the synovial membranes of diarthrodial joints .", "The etiology of RA is unclear but is thought to result from an environmental trigger in the context of genetic predisposition .", "We report that a single nucleotide polymorphism ( SNP ) ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "gene regulation", "regulatory proteins", "immunology", "dna-binding proteins", "cell differentiation", "bone marrow cells", "developmental biology", "micrornas", "transcription factors", "molecular biology techniques", "resear...	The miR-23a~27a~24-2 microRNA cluster buffers transcription and signaling pathways during hematopoiesis	journal.pgen.1006887	null	[ [ "Non-coding RNAs , including microRNAs ( miRNAs ) , play a critical role in regulating hematopoietic gene expression networks .", "MiRNAs are ~22 nucleotide long RNA molecules that negatively regulate gene expression post-transcriptionally by binding to the 3’ untranslated region ( UTR ) of target mRNAs[1...	[ "MicroRNA cluster mirn23a has previously been shown to promote myeloid development at the expense of lymphoid development in overexpression and knockout mouse models .", "This polarization is observed early in hematopoietic development , with an increase in common lymphoid progenitors ( CLPs ) and a decrease in a...	[ "MicroRNAs ( miRNAs ) are small ~22 nucleotide long RNA molecules that are involved in regulating multiple cellular processes through inhibiting the expression of target proteins .", "We previously identified a gene ( mirn23a ) that codes for 3 miRNAs that control the development of immune cells in the bone marro...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Tracking Proliferative History in Lymphocyte Development with Cre-Mediated Sister Chromatid Recombination	journal.pgen.1003887	null	[ [ "Cell proliferation is a tightly regulated process in tissue development and maintenance of tissue functions .", "Knowing the frequency and history of cell division is not only important in the study of normal tissue development but also in the investigation of tissue regeneration and tumorogenesis .", ...	[ "Tracking and isolating live cells based on their proliferative history in live animals remains a technical challenge in animal studies .", "We have designed a genetic marking system for tracking the proliferative frequency and history of lymphocytes during their development and homeostatic maintenance .", "Thi...	[ "Identification and isolation of live cells based on their proliferative history remains a technical challenge in genetic analysis of animal models .", "We have designed a novel genetic tool for tracking dividing cells in live animals .", "The experimental system is based on a fluorescent reporter , whose expre...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Host Reticulocytes Provide Metabolic Reservoirs That Can Be Exploited by Malaria Parasites	journal.ppat.1004882	null	[ [ "The malaria-causing apicomplexan parasites Plasmodium spp .", "have a dynamic life cycle which is reflected in stage-specific morphologies , transcriptomes , proteomes and metabolomes [1–8] .", "These changes , particularly in their metabolome , reflect the nutritional needs and biological processes ...	[ "Human malaria parasites proliferate in different erythroid cell types during infection .", "Whilst Plasmodium vivax exhibits a strong preference for immature reticulocytes , the more pathogenic P . falciparum primarily infects mature erythrocytes .", "In order to assess if these two cell types offer different ...	[ "Malaria , caused by the Apicomplexan parasites Plasmodium spp .", ", is a deadly disease which poses a huge health and economic burden over many populations in the world , mostly in sub-Saharan Africa and Asia .", "To design new intervention strategies and to improve upon existing drugs against malaria , it is...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Mutations in RECQL Gene Are Associated with Predisposition to Breast Cancer	journal.pgen.1005228	null	[ [ "Breast cancer is the most common malignancy disease in women world wide .", "Among these , approximately 10% of breast cancer patients have a family history of breast cancer ( referred as familial breast cancer ) , but only 10–15% of familial breast cancer is owing to germline mutations in one of the two...	[ "The genetic cause for approximately 80% of familial breast cancer patients is unknown .", "Here , by sequencing the entire exomes of nine early-onset familial breast cancer patients without BRCA1/2 mutations ( diagnosed with breast cancer at or before the age of 35 ) we found that two index cases carried a poten...	[ "In this study , we aimed to find novel breast cancer susceptibility genes by whole-exome sequencing in nine early-onset familial breast cancer patients without BRCA1/2 mutations .", "We found that two index cases carried a potentially deleterious mutation in the RECQL gene ( RecQ helicase-like ) .", "We furthe...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "reproductive system", "gonads", "caenorhabditis", "gene regulation", "animals", "animal models", "germ cells", "developmental biology", "caenorhabditis elegans", "model organisms", "experimental organism systems", "sperm", "research and a...	Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans	journal.pgen.1007219	null	[ [ "Phenotypic plasticity in response to environmental stress is a critical component of organismal fitness .", "Environmentally-induced phenotypic variation is thought to result , in part , from programmed changes in gene expression inherited through cell divisions or transgenerationally via epigenetic mech...	[ "Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression .", "Using the nematode C . elegans , we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by difference...	[ "Environmental stress during early development in animals can have profound effects on adult behavior and physiology due to programmed changes in gene expression .", "However , whether different stresses result in distinct changes in traits that allow stressed animals to better survive and reproduce in future adv...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "nuclear staining", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "australia", "saliva", "animals", "viruses", "rna viruses", "insect vectors", "digestive system", "research an...	Vector competence of Australian Aedes aegypti and Aedes albopictus for an epidemic strain of Zika virus	journal.pntd.0007281	null	[ [ "Over the past decade , Zika virus ( ZIKV ) has caused unprecedented epidemics in the Western Pacific and the Americas .", "ZIKV is a mosquito-borne , single-stranded RNA virus that belongs to the Flavivirus genus within the Flaviviridae family [1] .", "First discovered in Uganda in 1947 [2] , ZIKV sp...	[ "Recent epidemics of Zika virus ( ZIKV ) in the Pacific and the Americas have highlighted its potential as an emerging pathogen of global importance .", "Both Aedes ( Ae . ) aegypti and Ae .", "albopictus are known to transmit ZIKV but variable vector competence has been observed between mosquito populations fr...	[ "Zika virus ( ZIKV ) is a mosquito-borne pathogen that generally causes a mild febrile illness but mostly remains asymptomatic in 50–80% of infections .", "Infection during pregnancy can cause congenital malformations , notably microcephaly .", "In adults , it can cause Guillain-Barré syndrome .", "The recent...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "global health", "neglected tropical diseases", "onchocerciasis", "infectious disease control" ]	Validation of a Remote Sensing Model to Identify Simulium damnosum s.l. Breeding Sites in Sub-Saharan Africa	journal.pntd.0002342	null	[ [ "Onchocerciasis , or river blindness , has historically been one of the most important causes of blindness worldwide [1] , [2] .", "The disease is caused by the filarial parasite Onchocerca volvulus .", "It is estimated that 37 million individuals worldwide are at risk for O . volvulus infection , wit...	[ "Recently , most onchocerciasis control programs have begun to focus on elimination .", "Developing an effective elimination strategy relies upon accurately mapping the extent of endemic foci .", "In areas of Africa that suffer from a lack of infrastructure and/or political instability , developing such accurat...	[ "Onchocerciasis , or river blindness , represents a major cause of socio-economic disruption throughout much of Africa .", "The discovery that Mectizan ( ivermectin ) was effective in treating onchocerciasis , together with the decision of Merck Sharpe and Dohme to donate this drug for the treatment of this disea...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "medicine", "protein interactions", "viral transmission and infection", "viral classification", "macromolecular assemblies", "host-pathogen interaction", "microbiology", "viral structure", "protein structure", "infectious diseases", "zoonoses", "viral ...	A Unique Spumavirus Gag N-terminal Domain with Functional Properties of Orthoretroviral Matrix and Capsid	journal.ppat.1003376	null	[ [ "Spuma- or foamy viruses ( FVs ) are complex retroviruses and constitute the only members of the Spumaretrovirinae subfamily within the Retroviridae family .", "They have been isolated from a variety of primate hosts [1] , [2] , [3] , [4] as well as from cats [5] , [6] , [7] , cattle [8] , horses [9] and ...	[ "The Spumaretrovirinae , or foamyviruses ( FVs ) are complex retroviruses that infect many species of monkey and ape .", "Although FV infection is apparently benign , trans-species zoonosis is commonplace and has resulted in the isolation of the Prototypic Foamy Virus ( PFV ) from human sources and the potential ...	[ "Foamyviruses ( FVs ) or spuma-retroviruses derive their name from the cytopathic effects they cause in cell culture .", "By contrast , infection in humans is benign and FVs have entered the human population through zoonosis from apes resulting in the emergence of Prototypic Foamyvirus ( PFV ) .", "Like all ret...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "immune cells", "toxoplasma gondii", "immunology", "parasitic diseases", "parasitic protozoans", "developmental biology", "protozoans", "toxoplasma", "molecular development", "immune ...	The lectin-specific activity of Toxoplasma gondii microneme proteins 1 and 4 binds Toll-like receptor 2 and 4 N-glycans to regulate innate immune priming	journal.ppat.1007871	null	[ [ "Toxoplasma gondii is a coccidian parasite belonging to the phylum Apicomplexa and is the causative agent of toxoplasmosis .", "This protozoan parasite infects a variety of vertebrate hosts , including humans with about one-third of the global population being chronically infected [1] .", "Toxoplasmos...	[ "Infection of host cells by Toxoplasma gondii is an active process , which is regulated by secretion of microneme ( MICs ) and rhoptry proteins ( ROPs and RONs ) from specialized organelles in the apical pole of the parasite .", "MIC1 , MIC4 and MIC6 assemble into an adhesin complex secreted on the parasite surfa...	[ "Toxoplasmosis is caused by the protozoan Toxoplasma gondii , belonging to the Apicomplexa phylum .", "This phylum comprises important parasites able to infect a broad diversity of animals , including humans .", "A particularity of T . gondii is its ability to invade virtually any nucleated cell of all warm-blo...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "plant anatomy", "gene regulation", "regulatory proteins", "brassica", "dna-binding proteins", "dna transcription", "plant science", "model organisms", "luminescent proteins", "genetically modified plants", "yellow fluorescent protein", "experimental organism systems", "tr...	MicroRNA319-regulated TCPs interact with FBHs and PFT1 to activate CO transcription and control flowering time in Arabidopsis	journal.pgen.1006833	null	[ [ "Flowering is a transition from the vegetative to the reproductive phase in the plant life cycle , which is crucial for successful reproduction .", "Genetic approaches in the model plant Arabidopsis , in which flowering is often promoted under long-day ( LD ) but is delayed during short-day ( SD ) conditi...	[ "The transcription factor CONSTANS ( CO ) is a central component that promotes Arabidopsis flowering under long-day conditions ( LDs ) .", "Here , we show that the microRNA319-regulated TEOSINTE BRANCHED/CYCLOIDEA/PCF ( TCP ) transcription factors promote photoperiodic flowering through binding to the CO promoter...	[ "Plants monitor day-length changes ( photoperiod ) throughout the year to precisely align their flowering time , which is crucial for successful reproduction .", "In Arabidopsis , some components , such as CONSTANS ( CO ) , have been proved to play central roles in promoting the photoperiodic flowering under long...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "plant anatomy", "medicine and health sciences", "geographical locations", "tropical diseases", "animals", "developmental biology", "plant science", "neglected tropical diseases", "insect vectors", "africa", "infectious diseases", "geography", "aedes aegypti", "dengue fe...	Assessment of risk of dengue and yellow fever virus transmission in three major Kenyan cities based on Stegomyia indices	journal.pntd.0005858	null	[ [ "Dengue ( DEN ) and yellow fever ( YF ) are re-emerging diseases of public health importance caused by arboviral pathogens [1–4] .", "Both diseases share a common ecological niche including non-human primates as reservoir hosts and are vectored primarily by Aedes ( Stegomyia ) species [5] .", "Dengue ...	[ "Dengue ( DEN ) and yellow fever ( YF ) are re-emerging in East Africa , with contributing drivers to this trend being unplanned urbanization and increasingly adaptable anthropophilic Aedes ( Stegomyia ) vectors .", "Entomological risk assessment of these diseases remains scarce for much of East Africa and Kenya ...	[ "Despite the growing problem of dengue ( DEN ) and yellow fever ( YF ) evidenced from recent outbreaks in East Africa , risk assessment for their transmission and establishment through surveys of populations of the Aedes mosquito vectors , remain scarce .", "By estimating standard indices for the potential vector...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "china", "atmospheric science", "tropical diseases", "geographical locations", "animals", "health care", "mathematics", "statistics (mathematics)", "neglected tropical diseases", "infectious disease control", "humidity", "insect vectors", ...	Community Involvement in Dengue Outbreak Control: An Integrated Rigorous Intervention Strategy	journal.pntd.0004919	null	[ [ "Dengue fever , a mosquito-borne viral disease caused by any of the four dengue virus serotypes , is regarded as one of the most important arboviral diseases globally [1] .", "At present , no specific antiviral treatment or vaccine against dengue fever is available .", "It was estimated that about 2 ,...	[ "An explosive outbreak of dengue fever occurred in Guangdong Province , China in 2014 .", "A community-based integrated intervention was applied to control this outbreak in the capital city Guangzhou , where dengue epidemic was mainly caused by imported cases .", "We used a time series generalized additive mode...	[ "Dengue fever , caused by any of the four dengue virus serotypes , is regarded as one of the most important arboviral diseases globally .", "Guangdong Province in south China has the highest dengue infestation level in mainland China .", "An explosive outbreak occurred in this province in 2014 , with a total of...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational neuroscience", "neuroscience", "biology and life sciences", "computational biology" ]	Oscillation-Induced Signal Transmission and Gating in Neural Circuits	journal.pcbi.1003940	null	[ [ "The ground state of cortical networks is characterized by irregular and asynchronous spiking activity [1]–[4] and its dynamics are highly sensitive to perturbations , e . g . , missing or additional spikes [2] , [3] , [5]–[8] .", "Yet , reliable transmission of information in the presence of such perturb...	[ "Reliable signal transmission constitutes a key requirement for neural circuit function .", "The propagation of synchronous pulse packets through recurrent circuits is hypothesized to be one robust form of signal transmission and has been extensively studied in computational and theoretical works .", "Yet , alt...	[ "Rhythmic activity in the brain is ubiquitous , its functions are debated .", "Here we show that it may contribute to the reliable transmission of information within brain areas .", "We find that its effect is particularly strong if we take nonlinear coupling into account .", "This experimentally found neuron...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "natural antisense transcripts", "cancer treatment", "immunology", "histone modification", "oncology", "micrornas", "signs and symptoms", "bioassays and physiological analysis", "epigenetics", "chromatin"...	Downregulation of ERG and FLI1 expression in endothelial cells triggers endothelial-to-mesenchymal transition	journal.pgen.1007826	null	[ [ "Reciprocal interactions between tumor cells and stromal cells have a profound impact on tumor progression .", "Among tumor stromal cells , endothelial cells ( ECs ) and blood vessels are important components , as they supply nutrients and oxygen , and act as an entrance into systemic circulation , leadin...	[ "Endothelial cell ( EC ) plasticity in pathological settings has recently been recognized as a driver of disease progression .", "Endothelial-to-mesenchymal transition ( EndMT ) , in which ECs acquire mesenchymal properties , has been described for a wide range of pathologies , including cancer .", "However , t...	[ "Differentiated cells possess unique characteristics to maintain vital activities .", "However , cells occasionally show abnormal behavior in pathological settings due to dysregulated gene expression .", "Endothelial-to-mesenchymal transition ( EndMT ) is a phenomenon in which endothelial cells lose their chara...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "parasite groups", "plasmodium", "drugs", "microbiology", "parasitology", "genetic mapping", "antimalarials", "apicomplexa", "genome analysis", "pharmacology", "molecular genetics", "genomic signal processing", "antimicrobial resistance", "genomics", "mo...	Identity-by-descent analyses for measuring population dynamics and selection in recombining pathogens	journal.pgen.1007279	null	[ [ "Two alleles are identical by state ( IBS ) if they have the same nucleotide sequence .", "These alleles can be further classified as identical by descent ( IBD ) if they have been inherited from a common ancestor [1] .", "While a genomic region that is IBD must also be IBS , the converse of this stat...	[ "Identification of genomic regions that are identical by descent ( IBD ) has proven useful for human genetic studies where analyses have led to the discovery of familial relatedness and fine-mapping of disease critical regions .", "Unfortunately however , IBD analyses have been underutilized in analysis of other ...	[ "There are growing concerns over the emergence of antimicrobial drug resistance , which threatens the efficacy of treatments for infectious diseases such as malaria .", "As such , it is important to understand the dynamics of resistance by investigating population structure , natural selection and disease transmi...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "virology/mechanisms of resistance and susceptibility, including host genetics", "virology/host antiviral responses", "evolutionary biology/evolutionary and comparative genetics" ]	Adaptive Evolution of Mus Apobec3 Includes Retroviral Insertion and Positive Selection at Two Clusters of Residues Flanking the Substrate Groove	journal.ppat.1000974	null	[ [ "Species susceptible to infectious retroviruses have evolved numerous constitutively expressed antiviral factors that target various stages of the retroviral life cycle .", "The factors responsible for this intrinsic immunity include 3 that act at post-entry stages of virus replication: Fv1 , APOBEC3 and ...	[ "Mouse APOBEC3 ( mA3 ) is a cytidine deaminase with antiviral activity .", "mA3 is linked to the Rfv3 virus resistance factor , a gene responsible for recovery from infection by Friend murine leukemia virus , and mA3 allelic variants differ in their ability to restrict mouse mammary tumor virus .", "We sequence...	[ "APOBEC3 ( mA3 ) is a cytidine deaminase with antiretroviral activity .", "Genetic variants of mA3 are associated with the restriction factor Rfv3 ( recovery from Friend leukemia virus ) and with resistance to mouse mammary tumor virus .", "We sequenced mA3 from laboratory strains and wild mouse species to exam...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "rubella virus", "pathology and laboratory medicine", "togaviruses", "pathogens", "microbiology", "nucleocapsids", "viral structure", "viruses", "rna viruses", "glycoproteins", "infectious diseases", "medical microbiology", "microbial pathogens", "viral pa...	Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus	journal.ppat.1006377	null	[ [ "Rubella virus is an airborne human pathogen that causes a contagious disease with measles-like symptoms in children and adults .", "Rubella infection in pregnant women can lead to fetal death or severe life-long disabilities such as mental retardation , deafness , cataracts and heart defects in the new-b...	[ "Viral infections during pregnancy are a significant cause of infant morbidity and mortality .", "Of these , rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects .", "However , structural information about the rubella virus has been lacking due to the pleomo...	[ "Rubella virus ( RV ) causes serious fetal defects when contracted during pregnancy .", "Despite its medical importance , due to the irregular shapes and different sizes of the virions , the RV structure has remained unknown .", "Using cryo-electron tomography , we have determined the RV structure , which shows...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	IFIT1 Differentially Interferes with Translation and Replication of Alphavirus Genomes and Promotes Induction of Type I Interferon	journal.ppat.1004863	null	[ [ "The Alphavirus genus in the Togaviridae family contains 30 species and has a worldwide distribution [1] .", "Most alphaviruses are transmitted by mosquito vectors between amplifying vertebrate hosts [2] .", "In vertebrates , alphaviruses cause acute infections , characterized by high titer viremia th...	[ "Alphaviruses are a group of widely distributed human and animal pathogens .", "It is well established that their replication is sensitive to type I IFN treatment , but the mechanism of IFN inhibitory function remains poorly understood .", "Using a new experimental system , we demonstrate that in the presence o...	[ "Alphaviruses represent a group of highly important human pathogens , which are transmitted by mosquito vectors between vertebrate hosts .", "Alphavirus replication in vertebrates depends on their ability to interfere with host antiviral responses on both cellular and organismal levels .", "The identification o...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "rna interference", "pathology and laboratory medicine", "pathogens", "parasitic protozoans", "membrane proteins", "trypanosoma brucei", "protozoans", "mitochondria", "energy-producing organelles", "bioenergetics", "epigenetics", "cellular structures and organ...	Biogenesis of the mitochondrial DNA inheritance machinery in the mitochondrial outer membrane of Trypanosoma brucei	journal.ppat.1006808	null	[ [ "Mitochondria are a hallmark of eukaryotic cells [1] .", "They derive from an endosymbiotic event between an archaeal host cell and an α-proteobacterium .", "The bacterial symbiont was subsequently converted into an organelle .", "Continued evolution since the origin of the mitochondrion , approxi...	[ "Mitochondria cannot form de novo but require mechanisms that mediate their inheritance to daughter cells .", "The parasitic protozoan Trypanosoma brucei has a single mitochondrion with a single-unit genome that is physically connected across the two mitochondrial membranes with the basal body of the flagellum ."...	[ "Trypanosoma brucei and its relatives are important human and animal pathogens .", "Unlike most other eukaryotes trypanosomes have a single mitochondrion with a single unit mitochondrial genome , termed the kinetoplast DNA ( kDNA ) .", "During each cell cycle the kDNA is replicated and subsequently segregated i...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "learning", "medicine and health sciences", "neurochemistry", "chemical compounds", "decision making", "applied mathematics", "dopaminergics", "brain", "social sciences", "neuroscience", "organic compounds", "learning and memory", "hormones", "simulation and modeling", "algorithms", "c...	Predictive representations can link model-based reinforcement learning to model-free mechanisms	journal.pcbi.1005768	null	[ [ "Here , we briefly review the formalism of reinforcement learning in a Markov decision process ( MDP ) , which provides the foundation for our simulations ( see [25] or [26] for a fuller presentation ) .", "An MDP is defined by a set of states , a set of actions , a reward function R ( s , a ) over state/...	[ "Humans and animals are capable of evaluating actions by considering their long-run future rewards through a process described using model-based reinforcement learning ( RL ) algorithms .", "The mechanisms by which neural circuits perform the computations prescribed by model-based RL remain largely unknown; howev...	[ "According to standard models , when confronted with a choice , animals and humans rely on two separate , distinct processes to come to a decision .", "One process deliberatively evaluates the consequences of each candidate action and is thought to underlie the ability to flexibly come up with novel plans .", "...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biochemistry", "medicinal chemistry", "chemistry", "biology", "computational biology" ]	Naphthoquinone Derivatives Exert Their Antitrypanosomal Activity via a Multi-Target Mechanism	journal.pntd.0002012	null	[ [ "Among the tropical diseases , there are maladies whose etiological agents belong to the Trypanosomatidae family of the Protista , order Kinetoplastea , that are responsible for infections concentrated in the poorest , mainly rural areas of the planet , and that are grouped under the name of “most neglected d...	[ "Recently , we reported on a new class of naphthoquinone derivatives showing a promising anti-trypanosomatid profile in cell-based experiments .", "The lead of this series ( B6 , 2-phenoxy-1 , 4-naphthoquinone ) showed an ED50 of 80 nM against Trypanosoma brucei rhodesiense , and a selectivity index of 74 with re...	[ "The multitarget approach can represent a promising strategy for the discovery of innovative drug candidates against neglected tropical diseases .", "However , multitarget drug discovery can be very demanding , because of the highly time-consuming step related to the fine balancing of the biological activities ag...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusion" ]	[ "heme", "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "animals", "toxicology", "ddt", "genome analysis", "bioassays and physiological analysis", "insect vectors", "research and analysis methods", "agrochemicals", "aedes aegypti", "proteins", "epide...	Pyrethroid Resistance in Malaysian Populations of Dengue Vector Aedes aegypti Is Mediated by CYP9 Family of Cytochrome P450 Genes	journal.pntd.0005302	null	[ [ "The mosquito Aedes aegypti Linnaeus , 1762 ( Diptera: Culicidae ) is the most important vector of dengue , Zika , yellow fever [1 , 2] and chikungunya [3 , 4] viruses to human throughout the tropical world .", "This domestic mosquito usually bites during daylight , feeding predominantly on humans , matin...	[ "Dengue control and prevention rely heavily on insecticide-based interventions .", "However , insecticide resistance in the dengue vector Aedes aegypti , threatens the continued effectiveness of these tools .", "The molecular basis of the resistance remains uncharacterised in many endemic countries including Ma...	[ "Aedes aegypti is the major vector of emerging or re-emerging arboviruses such as dengue , chikungunya and Zika viruses worldwide .", "As there is still no vaccine or specific treatment for these diseases , their prevention relies mainly on insecticide-based interventions .", "Unfortunately , vector control pro...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "finland", "medicine and health sciences", "infectious disease epidemiology", "influenza", "immunology", "geographical locations", "preventive medicine", "age groups", "seasons", "infectious disease control", "vaccination and immunization", "public and occupational health", "infectious disea...	Revealing the True Incidence of Pandemic A(H1N1)pdm09 Influenza in Finland during the First Two Seasons — An Analysis Based on a Dynamic Transmission Model	journal.pcbi.1004803	null	[ [ "The threat of the pandemic influenza A strain , A ( H1N1 ) pdm09 ( ‘swine flu’ ) , imposed a huge burden on the public health system in Finland in 2009 [1] .", "The first A ( H1N1 ) pdm09 season was part of the global pandemic and occurred from September 2009 through January 2010 with a major outbreak in...	[ "The threat of the new pandemic influenza A ( H1N1 ) pdm09 imposed a heavy burden on the public health system in Finland in 2009-2010 .", "An extensive vaccination campaign was set up in the middle of the first pandemic season .", "However , the true number of infected individuals remains uncertain as the surve...	[ "In 2009 , the threat of the new pandemic influenza A ( H1N1 ) pdm09 ( referenced in media as ‘swine flu’ ) created a heavy burden to the public health systems wordwide .", "In Finland , an extensive vaccination campaign was set up in the middle of the first pandemic season 2009/2010 .", "However , the true num...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome sequencing", "genomics", "gustatory system", "gene expression", "genetics", "olfactory system", "molecular genetics", "comparative genomics", "biology", "gene duplication", "evolutionary biology", "genomic evolution", "neuroscience", "sensory systems" ]	Female Behaviour Drives Expression and Evolution of Gustatory Receptors in Butterflies	journal.pgen.1003620	null	[ [ "Nearly 50 years ago Ehrlich and Raven proposed that butterflies and their host-plants co-evolve [1] .", "Based on field observations of egg-laying in adult female butterflies , feeding behavior of caterpillars , and studies of systematics and taxonomy of plants and butterflies themselves , they outlined ...	[ "Secondary plant compounds are strong deterrents of insect oviposition and feeding , but may also be attractants for specialist herbivores .", "These insect-plant interactions are mediated by insect gustatory receptors ( Grs ) and olfactory receptors ( Ors ) .", "An analysis of the reference genome of the butte...	[ "Insects and their chemically-defended hostplants engage in a co-evolutionary arms race but the genetic basis by which suitable host plants are identified by insects is poorly understood .", "Host plant specializations require specialized sensors by the insects to exploit novel ecological niches .", "Adult male...	2013
[ "Introduction", "Models", "Results", "Discussion" ]	[]	A Model of Drosophila Larva Chemotaxis	journal.pcbi.1004606	null	[ [ "It is well established that Drosophila larvae perform chemotaxis towards a wide range of odourants ( e . g . [1] ) .", "Our aim in this paper is to examine what sensorimotor mechanism ( s ) account for larval chemotaxis , looking for a minimal model that captures observed phenomena .", "This will all...	[ "Detailed observations of larval Drosophila chemotaxis have characterised the relationship between the odour gradient and the runs , head casts and turns made by the animal .", "We use a computational model to test whether hypothesised sensorimotor control mechanisms are sufficient to account for larval behaviour...	[ "The larvae of the fruitfly are attracted to many odours .", "We use a computational model in which simulated larvae stop , start and redirect their crawling behaviour in response to their experience of changes in odour .", "We show that three simple rules for switching between behaviours are sufficient to prod...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Ecological Model to Predict Potential Habitats of Oncomelania hupensis, the Intermediate Host of Schistosoma japonicum in the Mountainous Regions, China	journal.pntd.0004028	null	[ [ "Schistosomiasis japonica , caused by Schistosoma japonicum , is transmitted by the snail intermediate host Oncomelania hupensis [1 , 2] .", "A reference group from the World Health Organization ( WHO ) reported that the disease burden associated with schistosomiasis was estimated to be 3 . 309 million di...	[ "Schistosomiasis japonica is a parasitic disease that remains endemic in seven provinces in the People’s Republic of China ( P . R . China ) .", "One of the most important measures in the process of schistosomiasis elimination in P . R . China is control of Oncomelania hupensis , the unique intermediate host snai...	[ "Schistosomiasis japonica is a parasitic disease caused by the infection of Schistosoma japonicum .", "Oncomelania hupensis , serving as the unique intermediate host of S . japonicum , has a distribution highly correlated with schistosomiasis epidemic .", "At present , elimination of O . hupensis is still an im...	2015
[ "Results", "Discussion", "Methods" ]	[ "taxonomy", "medicine and health sciences", "fish", "chemical compounds", "nervous system", "vertebrates", "electrophysiology", "neuroscience", "organic compounds", "animals", "animal models", "osteichthyes", "phylogenetics", "ion channels", "data management", "model organisms", "ami...	Rapid evolution of a voltage-gated sodium channel gene in a lineage of electric fish leads to a persistent sodium current	journal.pbio.2004892	null	[ [ "To identify Nav channels expressed in the EMNs , we generated transcriptomes from the posterior spinal cords ( where EMNs are abundant ) and trunk muscle of adults of 3 species of Apteronotids ( A . albifrons , A . leptorhynchus , and Parapteronotus hasemani ) , one myogenic electric gymnotiform ( Eigenmanni...	[ "Most weakly electric fish navigate and communicate by sensing electric signals generated by their muscle-derived electric organs .", "Adults of one lineage ( Apteronotidae ) , which discharge their electric organs in excess of 1 kHz , instead have an electric organ derived from the axons of specialized spinal ne...	[ "The electrical properties of excitable cells , such as those in muscle and nervous tissue , were enabled in large part by the evolution of voltage-gated ion channel genes .", "The regulated conduction of ions through these channels results in the propagation of electrical signals , facilitating communication bet...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "split-decomposition method", "marker genes", "database searching", "next-generation sequencing", "multiple alignment calculation", "gene sequencing", "genome analysis", "molecular biology techniques", "research and analysis methods", "sequence analysis", "genomics", ...	NINJA-OPS: Fast Accurate Marker Gene Alignment Using Concatenated Ribosomes	journal.pcbi.1004658	null	[ [ "The advent of next-generation sequencing technologies , combined with major advances in molecular and bioinformatics techniques , have enabled rapid growth in the culture-independent sequencing of amplified marker genes ( amplicons ) from environmental microbial communities .", "The major benefit of ampl...	[ "The explosion of bioinformatics technologies in the form of next generation sequencing ( NGS ) has facilitated a massive influx of genomics data in the form of short reads .", "Short read mapping is therefore a fundamental component of next generation sequencing pipelines which routinely match these short reads ...	[ "The analysis of the microbial communities in and around us is a growing field of study , partly because of its major implications for human health , and partly because high-throughput DNA sequencing technology has only recently emerged to enable us to quantitatively study them .", "One of the most fundamental st...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Competence of non-human primates to transmit Leishmania infantum to the invertebrate vector Lutzomyia longipalpis	journal.pntd.0007313	null	[ [ "Visceral leishmaniasis is a zoonotic disease caused by obligate intracellular protozoa of the genus Leishmania ( order Kinetoplasta: family Trypanosomatidae ) , which infect macrophages of several mammalian species , including man [1] .", "There are different species of Leishmania that can cause visceral...	[ "Leishmaniasis is a zoonotic disease of worldwide relevance .", "Visceral leishmaniasis is endemic in Brazil , where it is caused by Leishmania infantum with Lutzomyia longipalpis being the most important invertebrate vector .", "Non-human primates are susceptible to L . infantum infection .", "However , litt...	[ "Visceral leishmaniasis is a zoonotic disease with worldwide distribution .", "The disease is endemic in several Brazilian regions , including the city of Belo Horizonte , where visceral leishmaniasis is caused by Leishmania infantum and transmitted by Lutzomyia longipalpis .", "This study evaluated the compete...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "antibody engineering", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "viral transmission and infection", "engineering and technology", "pathogens", "synthetic biology", "immunology", "geographical locations", "microbiology", "vert...	Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections	journal.ppat.1006860	null	[ [ "The World Health Organization estimated that in 2015 , approximately two-thirds of the 2 million new HIV-1 infections globally , were in sub-Saharan Africa .", "Since HIV-1 infection cannot be cured , effective vaccines or other prevention measures are needed to mitigate the impact of HIV/AIDS on global ...	[ "There is great interest in passive transfer of broadly neutralizing antibodies ( bnAbs ) and engineered bispecific antibodies ( Abs ) for prevention of HIV-1 infections due to their in vitro neutralization breadth and potency against global isolates and long in vivo half-lives .", "We compared the potential of e...	[ "In the absence of effective vaccines , the use of passive transfer of conventional and engineered antibodies to prevent HIV-1 infection is being considered .", "This approach is promising because of broad efficacy and long in vivo lifetimes of antibodies .", "We analyzed the potential of leading antibody candi...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "virology/virus evolution and symbiosis" ]	The Effect of Vaccination on the Evolution and Population Dynamics of Avian Paramyxovirus-1	journal.ppat.1000872	null	[ [ "Live attenuated virus vaccines have been successfully employed in veterinary medicine to prevent the economic impact of many diseases in poultry and livestock .", "However , the role of vaccination with attenuated viruses on the evolution of wild type strains is not often considered .", "Antigenic es...	[ "Newcastle Disease Virus ( NDV ) is a pathogenic strain of avian paramyxovirus ( aPMV-1 ) that is among the most serious of disease threats to the poultry industry worldwide .", "Viral diversity is high in aPMV-1; eight genotypes are recognized based on phylogenetic reconstruction of gene sequences .", "Modifie...	[ "Modified live virus ( MLV ) vaccines have been effective in reducing disease burden and economic loss caused by Newcastle Disease ( ND ) in domestic poultry .", "Because the vaccine is a live virus , it is transmissible among birds .", "Thus , vaccination strategies have the potential to impact the evolutionar...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Assessing Mitochondrial DNA Variation and Copy Number in Lymphocytes of ~2,000 Sardinians Using Tailored Sequencing Analysis Tools	journal.pgen.1005306	null	[ [ "As the “cellular power plant” , each mitochondrion encodes some of its constituent proteins in resident mitochondrial DNA ( mtDNA ) .", "Human mtDNA is a circular molecule of 16 , 569 bases , and mutations that have become fixed in the sequence of every mtDNA may cause several genetic diseases .", "A...	[ "DNA sequencing identifies common and rare genetic variants for association studies , but studies typically focus on variants in nuclear DNA and ignore the mitochondrial genome .", "In fact , analyzing variants in mitochondrial DNA ( mtDNA ) sequences presents special problems , which we resolve here with a gener...	[ "We present a new program that provides a general solution for the analysis of variation of mtDNA ( the small circular genome in mitochondria , separate from the DNA in the nucleus ) .", "This is needed because many large-scale genetic studies are using new DNA sequencing technologies to help assess genetic varia...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes	journal.pntd.0002497	null	[ [ "Dengue is a member of the genus Flavivirus with a positive sense , single stranded RNA genome of ∼10 kb .", "The genome encodes for a polyprotein that is co- and post-translationally cleaved into 10 proteins: three structural ( capsid , precursor membrane and envelope ) , which constitute the virus parti...	[ "Anti-dengue T-cell responses have been implicated in both protection and immunopathology .", "However , most of the T-cell studies for dengue include few epitopes , with limited knowledge of their inter-serotype variation and the breadth of their human leukocyte antigen ( HLA ) affinity .", "In order to expand...	[ "Although there is an increased recognition of the role of T-cells in both dengue pathogenesis and protection , comprehensive analysis of T-cell activation during dengue infection is hampered by the small repertoire of known human dengue T-cell epitopes .", "Although dengue serotype 3 ( DENV3 ) is responsible for...	2013
[ "Introduction", "Results and discussion", "Methods" ]	[ "cell motility", "glycosylamines", "chemical compounds", "chromosome structure and function", "dictyosteliomycota", "carbohydrates", "organic compounds", "glucose", "telomeres", "model organisms", "experimental organism systems", "molecular biology techniques", "adenosine", "research and a...	A telomerase with novel non-canonical roles: TERT controls cellular aggregation and tissue size in Dictyostelium	journal.pgen.1008188	null	[ [ "Each time a chromosome replicates , it loses some DNA from each of its ends .", "This is not necessarily problematic , because the chromosome is initially capped at each end by a sacrificial strand of non-coding DNA , a telomere [1–3] .", "Further instances of replication , however , can expose the c...	[ "Telomerase , particularly its main subunit , the reverse transcriptase , TERT , prevents DNA erosion during eukaryotic chromosomal replication , but also has poorly understood non-canonical functions .", "Here , in the model social amoeba Dictyostelium discoideum , we show that the protein encoded by tert has te...	[ "When cells divide , their chromosomes are prone to shrinkage .", "This risk is reduced by an enzyme that repairs protective caps on each chromosome after cell division .", "This enzyme , telomerase , also has several other important but unrelated roles in human health .", "Most importantly , via one or other...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "legs", "health services research", "behavioral and social aspects of health", "tropical diseases", "limbs (anatomy)", "parasitic diseases", "herbs", "health care", "farms", "neglected tropical diseases", "patients", "plants", "public and occupational health...	Using Qualitative Methods to Explore Lay Explanatory Models, Health-Seeking Behaviours and Self-Care Practices of Podoconiosis Patients in North-West Ethiopia	journal.pntd.0004878	null	[ [ "Podoconiosis ( endemic non-filiarial elephantiasis ) is a chronic non-infectious disease affecting individuals whose feet have been exposed to red clay soil found in the tropical highland areas . [1]", "A very recent study from Molla et al . demonstrates the importance of phyllosilicate clay minerals , p...	[ "Podoconiosis ( endemic non-filarial elephantiasis ) is a chronic , non-infectious disease resulting from exposure of bare feet to red-clay soil in tropical highlands .", "This study examined lay beliefs about three under-researched aspects of podoconiosis patients’ care: explanatory models , health-seeking behav...	[ "Podoconiosis is a disease that is caused by long-term exposure to red clay soil found in tropical highland areas .", "This causes swelling of the legs , episodes of intense pain and severe disability .", "Sufferers of the condition experience stigma and exclusion from the community .", "Previous work has dem...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	A Systematic Review on the Epidemiological Data of Erythema Nodosum Leprosum, a Type 2 Leprosy Reaction	journal.pntd.0002440	null	[ [ "Erythema Nodosum Leprosum ( ENL ) , the main symptom of a type-2 reaction in leprosy , is caused by a humoral immune response to Mycobacterium Leprae [1] .", "Patients develop fever and tender/painful subcutaneous nodules , often in the face or extensor surfaces of the limbs [2]–[4] .", "ENL may also...	[ "Erythema Nodosum Leprosum ( ENL ) is a humoral immunological response in leprosy that leads to inflammatory skin nodules which may result in nerve and organ damage , and may occur years after antibiotic treatment .", "Multiple episodes are frequent and suppression requires high doses of immunosuppressive drugs ....	[ "This systematic review addresses an underpublicized and yet highly significant leprosy topic .", "Erythema Nodosum Leprosum ( ENL ) is a serious complication in multi-bacillary ( MB ) leprosy that may lead to severe disability .", "Inflammatory skin nodules may result in nerve and organ damage and require high...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genetics of the immune system", "evolutionary biology/human evolution", "immunology/immune response", "virology/mechanisms of resistance and susceptibility, including host genetics", "infectious diseases/viral infections", "virology/host antiviral responses", "immunology/immunity ...	Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach	journal.pgen.1000849	null	[ [ "Infectious diseases represent one of the major threats to human populations , are still the first cause of death in developing countries [1] , and are therefore a powerful selective force .", "In particular , viruses have affected humans before they emerged as a species , as testified by the fact that ro...	[ "Viruses have exerted a constant and potent selective pressure on human genes throughout evolution .", "We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants .", "Virus diversity ( the number of different viruses in a geographic region ) was used to ...	[ "Viruses have represented a constant threat to human communities throughout their history , therefore , human genes involved in anti-viral response can be thought of as targets of virus-driven selective pressure .", "Here we utilized the marks left by selection to identify viral infection-associated allelic varia...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection	journal.ppat.1005276	null	[ [ "For most viral vaccines in clinical use today , neutralizing antibodies ( nAbs ) represent the main correlate of protection [1 , 2] .", "However , viral immune evasion strategies such as antigenic variation and so-called “glycan shields” on viral envelope proteins [3–8] can undermine the protective , neu...	[ "Arenaviruses such as Lassa virus ( LASV ) can cause severe hemorrhagic fever in humans .", "As a major impediment to vaccine development , delayed and weak neutralizing antibody ( nAb ) responses represent a unifying characteristic of both natural infection and all vaccine candidates tested to date .", "To inv...	[ "Neutralizing antibodies ( nAbs ) represent a key principle of antiviral immunity .", "Protective vaccines aim at inducing nAbs to prevent viral infection , and infusion of nAbs in convalescent patient serum can offer a potent antiviral therapy .", "Certain viruses , however , have found ways to evade nAb contr...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Identifying and Tracking Simulated Synaptic Inputs from Neuronal Firing: Insights from In Vitro Experiments	journal.pcbi.1004167	null	[ [ "Neural computation requires fast , structured transformations from presynaptic input to postsynaptic spiking [1–3] .", "Changes in these transformations underlie learning , memory , and recovery from injury [4 , 5] .", "Tools for identifying synaptic weights and tracking their changes , thus , play a...	[ "Accurately describing synaptic interactions between neurons and how interactions change over time are key challenges for systems neuroscience .", "Although intracellular electrophysiology is a powerful tool for studying synaptic integration and plasticity , it is limited by the small number of neurons that can b...	[ "Synapses play a central role in neural information processing – weighting individual inputs in different ways allows neurons to perform a range of computations , and the changing of synaptic weights over time allows learning and recovery from injury .", "Intracellular recordings provide the most detailed view of...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "cytokines", "pathology and laboratory medicine", "immunity to infections", "immunology", "tropical diseases", "parasitic diseases", "developmental biology", "molecular development", "neglected tropical diseases", "infectious diseases", "pathogenesis", "immune...	Cytokine Responses to Schistosoma mansoni and Schistosoma haematobium in Relation to Infection in a Co-endemic Focus in Northern Senegal	journal.pntd.0003080	null	[ [ "Schistosomiasis is a parasitic disease of major public health importance .", "Schistosoma mansoni and S . haematobium are the main human species .", "Both species are endemic in Africa , where their distributions show a great overlap [1] .", "Schistosomes are known to down-regulate host immune re...	[ "In Africa , many areas are co-endemic for the two major Schistosoma species , S . mansoni and S . haematobium .", "Epidemiological studies have suggested that host immunological factors may play an important role in co-endemic areas .", "As yet , little is known about differences in host immune responses and p...	[ "In the developing world , over 207 million people are infected with blood-dwelling parasitic Schistosoma worms .", "Schistosoma haematobium and S . mansoni are the most widespread species .", "In Africa , they often occur together in the same area , with many people carrying both species .", "Yet , little is...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "gene expression", "drug discovery", "biology", "microbiology", "molecular cell biology", "parasitology", "histone modification" ]	Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets	journal.pntd.0002428	null	[ [ "The current strategy for the treatment and control of schistosomiasis is the mass-treatment of populations in endemic areas using the only available drug , Praziquantel .", "Notably , the Schistosomiasis Control Initiative [1] in sub-Saharan Africa had dispensed more than 40 million doses of Praziquantel...	[ "The chemotherapy of schistosomiasis currently depends on the use of a single drug , praziquantel .", "In order to develop novel chemotherapeutic agents we are investigating enzymes involved in the epigenetic modification of chromatin .", "Sirtuins are NAD+ dependent lysine deacetylases that are involved in a w...	[ "Schistosomiasis is a disease affecting more than 200 million people in tropical and sub-tropical countries caused by parasitic flatworms of the genus Schistosoma .", "The current reliance on a single drug , Praziquantel , for the treatment and control of the disease renders urgent the development of new therapeu...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "action potentials", "membrane potential", "ocular anatomy", "electrophysiology", "light", "neuroscience", "electromagnetic radiation", "surgical and invasive medical procedures", "eigenvalues", "mathematics", "functional electrical stimulation", "ganglion cel...	Electrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons	journal.pcbi.1005997	null	[ [ "Implantable neural stimulation devices have demonstrated clinical efficacy , from the facilitation of hearing for deaf people using cochlear implants [1] to the treatment of neurological disorders such as epilepsy , Parkinson's disease , and depression using deep brain stimulation [2] .", "Additionally ,...	[ "Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases .", "Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation .", "Due to these complexities , most existing...	[ "Implantable neural stimulation devices are being widely used and clinically tested for the restoration of lost function ( e . g . cochlear implants ) and the treatment of neurological disorders .", "Smart devices that can combine sensing and stimulation will dramatically improve future patient outcomes .", "To...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "medicine and health sciences", "parasite groups", "pathology and laboratory medicine", "chemical compounds", "plasmodium", "pathogens", "diet", "carbohydrates", "animals", "wolbachia", "parasitology", "organic compounds", "apicomplexa", "nutrition", "insect vectors", ...	Diet-Induced Nutritional Stress and Pathogen Interference in Wolbachia-Infected Aedes aegypti	journal.pntd.0005158	null	[ [ "Wolbachia pipientis ( Rickettsiaceae ) is an obligate bacterial endosymbiont that shows great potential as a natural control agent for a range of clinically important mosquito-transmitted pathogens , including those responsible for diseases such as malaria and dengue in humans [1 , 2] .", "Wolbachia natu...	[ "The pathogen interference phenotype greatly restricts infection with dengue virus ( DENV ) and other pathogens in Wolbachia-infected Aedes aegypti , and is a vital component of Wolbachia-based mosquito control .", "Critically , the phenotype’s causal mechanism is complex and poorly understood , with recent evide...	[ "Mosquito-transmitted disease severely impacts human health around the world .", "One novel form of control involves infecting medically important mosquito species with the naturally occurring bacterium Wolbachia , which restricts dengue and malaria transmission through a process called pathogen interference .", ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics/replication and repair", "biochemistry/replication and repair", "biophysics/macromolecular assemblies and machines", "biochemistry/macromolecular assemblies and machines" ]	DNA Structure Modulates the Oligomerization Properties of the AAV Initiator Protein Rep68	journal.ppat.1000513	null	[ [ "Adeno-associated virus ( AAV ) is a non-pathogenic human parvovirus that has evolved a unique mechanism of persistence in human cells by integrating its genome site-specifically into a defined locus of human chromosome 19 [1] .", "The single-stranded AAV DNA genome contains two open reading frames ( ORFs...	[ "Rep68 is a multifunctional protein of the adeno-associated virus ( AAV ) , a parvovirus that is mostly known for its promise as a gene therapy vector .", "In addition to its role as initiator in viral DNA replication , Rep68 is essential for site-specific integration of the AAV genome into human chromosome 19 ."...	[ "Adeno-associated virus ( AAV ) is a parvovirus with a linear single-stranded DNA genome .", "Thus far , it is the only eukaryotic virus known to integrate its genome in human cells in a specific region of chromosome 19 .", "Because no pathologies have been associated with AAV , there is great interest in using...	2009
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "biophysics", "infectious diseases", "eubacteria" ]	Crystal Structure of the P Pilus Rod Subunit PapA	journal.ppat.0030073	null	[ [ "Urinary tract infections , which include infections of the bladder ( cystitis ) and kidney ( pyelonephritis ) , are some of the most common bacterial infections .", "These infections are caused mainly by uropathogenic Escherichia coli [1] .", "Once uropathogenic E . coli is introduced , survival and ...	[ "P pili are important adhesive fibres involved in kidney infection by uropathogenic Escherichia coli strains .", "P pili are assembled by the conserved chaperone–usher pathway , which involves the PapD chaperone and the PapC usher .", "During pilus assembly , subunits are incorporated into the growing fiber via...	[ "Bacterial adhesion to a host is a crucial step that determines the onset of bacterial infection .", "It is mediated through recognition of a receptor on the host cell surface by a protein called an adhesin displayed on the surface of the bacterium .", "Many adhesins are displayed at the tip of specialized orga...	2007
[ "Introduction", "Results" ]	[ "sequencing", "biochemistry", "antigen processing and recognition", "immunity", "peptide mapping", "immunity to infections", "immunology", "biology", "proteomics", "immune response" ]	Kinetics of Antigen Expression and Epitope Presentation during Virus Infection	journal.ppat.1003129	null	[ [ "The presentation of virus peptides ( epitopes ) to CD8+ T cells plays a pivotal role in anti-viral immunity .", "Recognition of these epitopes presented on MHC class I drives CD8+ T cell priming following interactions with professional antigen presenting cells ( APC ) and subsequently allows control of i...	[ "Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity .", "Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus...	[ "A major mechanism for the detection of virus infection is the recognition by T cells of short peptide fragments ( epitopes ) derived from the degradation of intracellular proteins presented at the cell surface in a complex with class I MHC .", "Whilst the mechanics of antigen degradation and the loading of pepti...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	The HILDA Complex Coordinates a Conditional Switch in the 3′-Untranslated Region of the VEGFA mRNA	journal.pbio.1001635	The HILDA complex coordinates three regulatory elements located in the 3′ UTR of the VEGFA mRNA in a RNA switch that controls translation in response to inflammation and hypoxia.	[ [ "Mammalian cells integrate diverse , and sometimes conflicting , environmental signals to generate appropriate , condition-dependent responses .", "Tissue myeloid cells are exposed to a plethora of stimulatory and inhibitory signals , and thus its integrated response is particularly complex .", "This ...	[ "Cell regulatory circuits integrate diverse , and sometimes conflicting , environmental cues to generate appropriate , condition-dependent responses .", "Here , we elucidate the components and mechanisms driving a protein-directed RNA switch in the 3′UTR of vascular endothelial growth factor ( VEGF ) -A .", "We...	[ "Many cells of our body , particularly cells such as monocyte/macrophages involved in host immunity , are exposed to diverse and constantly changing environments .", "These cells require mechanisms by which they can rapidly respond to multiple , sometimes conflicting , environmental cues to generate appropriate r...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Ultra-Deep Sequencing of Intra-host Rabies Virus Populations during Cross-species Transmission	journal.pntd.0002555	null	[ [ "Rabies virus ( RABV ) is one of the most deadly pathogens known and is able to infect a wide variety of mammalian hosts .", "RABV is present on all continents except for Antarctica and has reservoirs in terrestrial species as well as bats ( Chiroptera ) .", "Although vaccination and antibody therapy ...	[ "One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission ( CST ) events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale .", "In 2009 , the California Department of ...	[ "Understanding the role of genetic variants within a viral population is a necessary step toward predicting and treating emerging infectious diseases .", "The high mutation rate of RNA viruses increases the ability of these viruses to adapt to diverse hosts and cause new human and zoonotic diseases .", "The gen...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal models", "molecular neuroscience", "caenorhabditis elegans", "behavioral neuroscience", "model organisms", "cellular neuroscience", "gustatory system", "olfactory system", "genetics", "membranes and sorting", "molecular genetics", "signaling pathways", "biology", "sensory systems",...	An ER Complex of ODR-4 and ODR-8/Ufm1 Specific Protease 2 Promotes GPCR Maturation by a Ufm1-Independent Mechanism	journal.pgen.1004082	null	[ [ "Molecular chaperones ensure the correct folding , assembly , quality control , traffic , and sub-cellular targeting of newly made proteins .", "Failure of these processes results in protein aggregation , with potential pathological consequences [1] .", "In the nervous system a growing number of chape...	[ "Despite the importance of G-protein coupled receptors ( GPCRs ) their biogenesis is poorly understood .", "Like vertebrates , C . elegans uses a large family of GPCRs as chemoreceptors .", "A subset of these receptors , such as ODR-10 , requires the odr-4 and odr-8 genes to be appropriately localized to sensor...	[ "Despite the importance of G-protein coupled receptors ( GPCRs ) , we know little about their biogenesis .", "Olfactory receptors form a large and divergent group of GPCRs .", "We investigate their biogenesis in C . elegans .", "We show that maturation of a subset of these GPCRs , including the diacetyl recep...	2014
[ "Introduction", "Results", "Discussion", "Methods", "Supplemental data" ]	[ "blood cells", "genome-wide association studies", "quantitative trait loci", "alleles", "red blood cells", "genome analysis", "hemoglobin", "sex chromosomes", "animal cells", "proteins", "chromosome biology", "x chromosomes", "genetic loci", "biochemistry", "cell biology", "genetics", ...	Genome-wide association study of red blood cell traits in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos	journal.pgen.1006760	null	[ [ "Red blood cell ( RBC ) development and maintenance are critical for transport of oxygen to tissues throughout the body .", "Several parameters commonly measured in clinical blood count evaluations are used to characterize RBC: hematocrit ( HCT ) , hemoglobin ( HGB ) , RBC count , mean corpuscular hemoglo...	[ "Prior GWAS have identified loci associated with red blood cell ( RBC ) traits in populations of European , African , and Asian ancestry .", "These studies have not included individuals with an Amerindian ancestral background , such as Hispanics/Latinos , nor evaluated the full spectrum of genomic variation beyon...	[ "Red blood cells ( RBC ) are important for transport of oxygen to tissues throughout the body .", "Distribution of RBC traits differs by ethnicity and gender , and both genetic and acquired factors likely contribute to these differences .", "Prior genetic studies have identified physical regions of the genome a...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "recreation", "children", "medicine and health sciences", "salaries", "pathology and laboratory medicine", "sports", "cutaneous larva migrans", "geographical locations", "tropical diseases", "social sciences", "vertebrates", "parasitic diseases", "animals", "mammals", "dogs", "age grou...	Prevalence and Risk Factors of Hookworm-Related Cutaneous Larva Migrans (HrCLM) in a Resource-Poor Community in Manaus, Brazil	journal.pntd.0004514	null	[ [ "Hookworm-related cutaneous larva migrans ( HrCLM ) is a parasitic skin disease caused by the penetration of feline or canine hookworm larvae into the human epidermis .", "The most frequent species are Ancylostoma braziliense , Ancylostoma caninum and Uncinaria stenocephala [1–3] .", "In humans , the ...	[ "Hookworm-related cutaneous larva migrans ( HrCLM ) is a neglected tropical skin disease associated with significant clinical pathology .", "Little knowledge exists about prevalence and risk factors of HrCLM in endemic regions .", "To understand the epidemiology of HrCLM in Amazonia , we conducted a cross-secti...	[ "Hookworm-related cutaneous larva migrans ( HrCLM ) is a parasitic skin disease caused by the penetration of animal hookworm larvae into the human skin .", "In this compartment the larvae cannot pass the basal membrane and reproduce , but migrate in the outer skin layer for several weeks , causing skin inflammati...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Ongoing Spillover of Hantaan and Gou Hantaviruses from Rodents Is Associated with Hemorrhagic Fever with Renal Syndrome (HFRS) in China	journal.pntd.0002484	null	[ [ "Hantaviruses are important zoonotic pathogens .", "Although they can establish a persistent and asymptomatic infection in their natural rodent reservoirs [1] , in humans hantaviruses can cause two severe diseases: hemorrhagic fever with renal syndrome ( HFRS ) and hantavirus ( cardio ) pulmonary syndrome...	[ "Longquan City , Zhejiang province , China , has been seriously affected by hemorrhagic fever with renal syndrome ( HFRS ) since the first cases were registered in 1974 .", "To understand the epidemiology and emergence of HFRS in Longquan , which may be indicative of large parts of rural China , we studied long-t...	[ "Hemorrhagic fever with renal syndrome ( HFRS ) is a major public health problem in China despite human vaccination .", "We investigated the epidemiology and emergence of HFRS in Longquan ( Zhejiang Province ) , a rural area with a high incidence of HFRS .", "During 1974–2011 , a total of 1866 cases of HFRS wer...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "learning", "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "neural networks", "social sciences", "neuroscience", "learning and memory", "magnetic resonance imaging", "multivariate analysis", "cognitive psychology", "mathematics", "statistics ...	Formal Models of the Network Co-occurrence Underlying Mental Operations	journal.pcbi.1004994	null	[ [ "There is uncertainty about pertinent concepts of functional brain architecture .", "Systems neuroscience has established the existence of a set of fluctuating yet robust brain networks in humans [1 , 2] .", "It however remains elusive how these neurophysiological phenomena relate to the repertoire of...	[ "Systems neuroscience has identified a set of canonical large-scale networks in humans .", "These have predominantly been characterized by resting-state analyses of the task-unconstrained , mind-wandering brain .", "Their explicit relationship to defined task performance is largely unknown and remains challengi...	[ "Assuming the central importance of canonical brain networks for realizing human cognitive processes , the present work demonstrates the quantifiability of relative neural networks involvements during psychological tasks .", "This is achieved by a machine-learning approach that combines exploratory network discov...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mammals", "eukaryotes", "computational biology", "molecular biology", "genetics and genomics" ]	Pre-mRNA Secondary Structures Influence Exon Recognition	journal.pgen.0030204	null	[ [ "RNA molecules can adopt various conformations in solution by base pairings and hydrophobic interactions .", "For example , transfer RNA ( tRNA ) adopts a defined secondary and tertiary structure [1] , whereas most messenger RNAs ( mRNAs ) exhibit only local structures [2] .", "Defined RNA structures ...	[ "The secondary structure of a pre-mRNA influences a number of processing steps including alternative splicing .", "Since most splicing regulatory proteins bind to single-stranded RNA , the sequestration of RNA into double strands could prevent their binding .", "Here , we analyzed the secondary structure contex...	[ "Almost all human protein-coding genes contain several exons and introns .", "Prior to translation , introns have to be removed and exons have to be joined , which happens in a processing step called splicing that generates the mature mRNA .", "For most genes , certain exons can be either included or excluded f...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "veterinary diseases", "zoonoses", "medicine and health sciences", "diagnostic medicine", "biology and life sciences", "vector-borne diseases", "protozoan infections", "trypanosomiasis", "parasitic diseases", "veterinary science" ]	Evaluation of the Diagnostic Accuracy of Prototype Rapid Tests for Human African Trypanosomiasis	journal.pntd.0003373	null	[ [ "Human African trypanosomiasis ( HAT ) , otherwise known as sleeping sickness , is caused by infection with the haemoflagellate parasites Trypanosoma brucei gambiense ( in west and central Africa ) and T . b .", "rhodesiense ( in east and southern Africa ) [1] .", "Infection is initiated after the bit...	[ "Diagnosis of human African trypanosomiasis ( HAT ) remains a challenge both for active screening , which is critical in control of the disease , and in the point-of-care scenario where early and accurate diagnosis is essential .", "Recently , the first field deployment of a lateral flow rapid diagnostic test ( R...	[ "The most prevalent species of trypanosome causing human African trypanosomiasis ( HAT ) , Trypanosoma brucei gambiense , presents a diagnostic challenge .", "While early diagnosis is essential for effective treatment and also to control transmission , symptoms are non-specific and parasitological diagnosis is la...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "genetics and genomics", "microbiology", "eubacteria" ]	Expression Profiles Reveal Parallel Evolution of Epistatic Interactions Involving the CRP Regulon in Escherichia coli	journal.pgen.0040035	null	[ [ "Epistatic interactions are revealed when the contribution of a mutation to an organism's phenotype depends on the genetic background in which it occurs .", "Epistasis plays an important role in many evolutionary theories , including those seeking to explain speciation [1] , the evolution of sex [2–5] , a...	[ "The extent and nature of epistatic interactions between mutations are issues of fundamental importance in evolutionary biology .", "However , they are difficult to study and their influence on adaptation remains poorly understood .", "Here , we use a systems-level approach to examine epistatic interactions tha...	[ "The effect of a genetic mutation can depend on the genotype of the organism in which it occurs .", "For example , a mutation that is beneficial in one genetic background might be neutral or even deleterious in another .", "The interactions between genes that cause this dependence—known as epistasis—play an imp...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Cattle Sex-Specific Recombination and Genetic Control from a Large Pedigree Analysis	journal.pgen.1005387	null	[ [ "In eukaryotes , meiotic recombination through reciprocal crossovers is an essential biological process that ensures the proper segregation of homologous chromosomes during meiosis [1–4] .", "Any mistakes or aberrations during this process can result in aneuploidy , a potentially deleterious outcome [5 , ...	[ "Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis .", "From a large USDA dairy cattle pedigree with over half a million genotyped animals , we extracted 186 , 927 three-generation families , identified over 8 . 5...	[ "Previous studies on cattle recombination largely focused on males .", "Using a large Holstein sample from the USDA national database , we studied both male and female recombination by assembling paternal and maternal recombination events in at least three generations .", "This unique data set provides unpreced...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "antimicrobials", "medicine and health sciences", "vesicular stomatitis virus", "pathology and laboratory medicine", "chemical compounds", "pathogens", "drugs", "microbiology", "viral structure", "organic compounds", "viruses", "tyrosine", "rna viruses", "tetracyclines...	The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles	journal.ppat.1005501	null	[ [ "Arenaviruses are a family of rodent-borne viruses with a worldwide distribution .", "These viruses typically establish persistent , asymptomatic infections in rodent reservoir species [1] .", "In contrast , arenaviruses cause severe and often fatal diseases in humans .", "Several arenaviruses , i...	[ "Arenaviruses cause severe diseases in humans but establish asymptomatic , lifelong infections in rodent reservoirs .", "Persistently-infected rodents harbor high levels of defective interfering ( DI ) particles , which are thought to be important for establishing persistence and mitigating virus-induced cytopath...	[ "Arenaviruses cause severe and often fatal diseases in humans yet typically establish lifelong , asymptomatic infections in their rodent reservoirs .", "Several families of enveloped RNA viruses , including the arenaviruses , encode short amino acid motifs , called late domains , to hijack host proteins in the en...	2016
[ "Introduction", "Methods", "Results and discussion" ]	[ "taxonomy", "medicine and health sciences", "pathology and laboratory medicine", "geographical locations", "tropical diseases", "sand flies", "parasitic diseases", "parasitic protozoans", "phylogenetics", "data management", "protozoans", "signs and symptoms", "leishmania", "phylogenetic an...	An outbreak of Leishmania major from an endemic to a non-endemic region posed a public health threat in Iraq from 2014-2017: Epidemiological, molecular and phylogenetic studies	journal.pntd.0006255	null	[ [ "Leishmaniasis is considered to be a neglected tropical and zoonotic disease that spreads via phlebotomine sandfly vectors [1] .", "Leishmaniasis is a parasitic disease caused by intracellular protozoa which in humans has four clinical forms including cutaneous ( CL ) , diffuse cutaneous ( DCL ) , viscera...	[ "Cutaneous leishmaniasis ( CL ) is a neglected worldwide , zoonotic , vector-borne , tropical disease that is a threat to public health .", "This threat may spread from endemic to non-endemic areas .", "Current research has exploited epidemiological , molecular and phylogenetical studies to determine the danger...	[ "Leishmaniasis refers to a disease with three main types of clinical manifestation in infected individuals including cutaneous , mucocutaneous and visceral forms .", "It is caused by several species of a parasite belonging to the genus Leishmania and is transmitted by a small blood-sucking insect called a sandfly...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "skin", "cell binding", "cell physiology", "mycobacterium leprae", "keratinocytes", "medicine and health sciences", "integumentary system", "tropical diseases", "macroglial cells", "collagens", "epithelial cells", "bacterial diseases", "dermis", "schwann cells", "epidermis", "neglected...	M. leprae interacts with the human epidermal keratinocytes, neonatal (HEKn) via the binding of laminin-5 with α-dystroglycan, integrin-β1, or -β4	journal.pntd.0007339	null	[ [ "Leprosy , Hansen’s disease , is a chronic granulomatous disease caused by the intracellular bacterium Mycobacterium leprae ( M . leprae ) .", "It mainly affects both the skin and peripheral nerves , resulting in the development of skin lesions , such as macules , plaques or nodules , and peripheral neuro...	[ "Although Mycobacterium leprae ( M . leprae ) is usually found in macrophages and nerves of the dermis of patients with multibacillary leprosy , it is also present in all layers of the epidermis , basal , suprabasal , prickle cells , and keratin layers .", "However , the mechanism by which M . leprae invades the ...	[ "In the current study , we investigated the issue of how M . leprae is phagocytosed by human epidermal keratinocytes , neonatal ( HEKn ) .", "We focused on the role of LN-5 , a predominant form of laminin of the epidermis , in the interaction of M . leprae with keratinocytes .", "Our results show that M . lepra...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "mammalogy", "zoology", "ecology", "vector biology", "epidemiology", "global health", "biology", "microbiology", "host-pathogen interaction", "public health", "bacterial pathogens", "parasitology" ]	Endemic Foci of the Tick-Borne Relapsing Fever Spirochete Borrelia crocidurae in Mali, West Africa, and the Potential for Human Infection	journal.pntd.0001924	null	[ [ "The epidemiology of tick-borne relapsing fever was founded on the works of several independent investigators working across central Africa during the first decade of the 20th century .", "David Livingstone is credited with the first written account in 1857 of a malady associated with the bite of soft tic...	[ "Tick-borne relapsing fever spirochetes are maintained in endemic foci that involve a diversity of small mammals and argasid ticks in the genus Ornithodoros .", "Most epidemiological studies of tick-borne relapsing fever in West Africa caused by Borrelia crocidurae have been conducted in Senegal .", "The risk f...	[ "Tick-borne relapsing fever is a spirochete-caused , recurrent illness acquired by the bite of fast-feeding ticks .", "In Mali , the potential for people to acquire relapsing fever is unknown although a few human cases have been reported there .", "Human malaria is also abundant in Mali , and could be complicat...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "algorithms", "computer and information sciences", "cancer genetics", "mathematics", "evolutionary modeling", "genetics", "applied mathematics", "biology and life sciences", "physical sciences", "computational biology", "evolutionary biology", "evolutionary processes" ]	Algorithms to Model Single Gene, Single Chromosome, and Whole Genome Copy Number Changes Jointly in Tumor Phylogenetics	journal.pcbi.1003740	null	[ [ "In this paper , we develop new methods to advance the theory of phylogenetic inference for reconstructing evolutionary histories of cell populations in solid tumors .", "The work is specifically designed for use in tracking tumor evolution by gain and loss of genomic regions as assessed by multicolor flu...	[ "We present methods to construct phylogenetic models of tumor progression at the cellular level that include copy number changes at the scale of single genes , entire chromosomes , and the whole genome .", "The methods are designed for data collected by fluorescence in situ hybridization ( FISH ) , an experimenta...	[ "Cancer is an evolutionary system whose growth and development is attributed to aberrations in well-known genes and to cancer-type specific genomic imbalances .", "Here , we present methods for reconstructing the evolution of individual tumors based on cell-to-cell variations between copy numbers of targeted regi...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutagenesis", "biochemistry", "model organisms", "genetic mutation", "dna replication", "nucleic acids", "genetics", "dna", "dna repair", "biology", "yeast and fungal models", "saccharomyces cerevisiae" ]	In Vivo Bypass of 8-oxodG	journal.pgen.1003682	null	[ [ "All DNA bases are subject to a variety of different types of damage due to reactive oxygen species ( ROS ) [1] .", "Among the most common and most mutagenic is 7 , 8-dihydro-8-oxoguanine , or 8-oxoG , which is mutagenic because of its tendency to pair with adenine and thus create GC to TA transversion mu...	[ "8-oxoG is one of the most common and mutagenic DNA base lesions caused by oxidative damage .", "However , it has not been possible to study the replication of a known 8-oxoG base in vivo in order to determine the accuracy of its replication , the influence of various components on that accuracy , and the extent ...	[ "In the course of normal cellular functions , many types of reactive oxygen species are produced that can lead to oxidative damage in the cell .", "DNA bases are subject to the formation of various oxidative lesions; one of the most common is the production of 8-oxoG which can pair relatively well with A instead ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Extrapolating Weak Selection in Evolutionary Games	journal.pcbi.1003381	null	[ [ "In evolutionary theory , weak selection means that differences in reproductive success are small .", "If fitness differences are close enough to zero , perturbation analysis allows to derive analytical results in models of population dynamics .", "This approach has a long standing history in populati...	[ "In evolutionary games , reproductive success is determined by payoffs .", "Weak selection means that even large differences in game outcomes translate into small fitness differences .", "Many results have been derived using weak selection approximations , in which perturbation analysis facilitates the derivati...	[ "In evolutionary game dynamics in finite populations , selection intensity plays a key role in determining the impact of the game on reproductive success .", "Weak selection is often employed to obtain analytical results in evolutionary game theory .", "We investigate the validity of weak selection predictions ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "innate immune system", "medicine and health sciences", "liver", "immune cells", "immune physiology", "cytokines", "helminths", "granulomas", "spleen", "immunology", "fibrosis", "animals", "developmental biology", "molecular deve...	Single-sex infection with female Schistosoma mansoni cercariae mitigates hepatic fibrosis after secondary infection	journal.pntd.0005595	null	[ [ "The blood flukes of the genus Schistosoma spp .", "are among the world's most prevalent human helminthic parasites .", "According to the WHO over 258 million people are currently receiving preventive therapy , mostly to avoid severe long-term liver damage [1] .", "During their life-span of up to ...	[ "Infection with Schistosoma spp .", "affects more than 258 million people worldwide .", "Current treatment strategies are mainly based on the anthelmintic Praziquantel , which is effective against adult worms but neither prevents re-infection nor cures severe liver damage .", "The best long-term strategy to c...	[ "Schistosomiasis remains a major cause of morbidity and mortality , and in the tropics and subtropics in particular , infection rates are high .", "The efficacy of anthelmintic therapy is limited since it has no effect on immature parasite stages and does not prevent re-infection .", "The root cause of disease ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "learning", "medicine and health sciences", "vertebrates", "social sciences", "limbs (anatomy)", "neuroscience", "theory of mind", "mammals", "learning and memory", "animals", "primates", "cognitive psychology", "animal behavior", "cognition", "animal management", "zoology", "animal ...	Reading wild minds: A computational assay of Theory of Mind sophistication across seven primate species	journal.pcbi.1005833	null	[ [ "How do you know what others think or feel ?", "Theory of Mind ( ToM ) , i . e . the ability to identify covert mental states from others’ overt behaviour , is a crucial component of human social intelligence .", "Although ToM endows humans with highly adaptive skills such as bonding , teaching or dec...	[ "Theory of Mind ( ToM ) , i . e . the ability to understand others' mental states , endows humans with highly adaptive social skills such as teaching or deceiving .", "Candidate evolutionary explanations have been proposed for the unique sophistication of human ToM among primates .", "For example , the Machiave...	[ "The contribution of Theory of Mind ( ToM ) , i . e . the ability to understand others' mental states , to the cognitive toolkit of non-human animal species ( including primates ) , is fiercely disputed .", "We contribute to this debate by", "( i ) proposing a computational definition of ToM sophistication that...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Conoid Associated Motor MyoH Is Indispensable for Toxoplasma gondii Entry and Exit from Host Cells	journal.ppat.1005388	null	[ [ "The phylum of Apicomplexa includes numerous human and animal pathogens that have adopted an obligate intracellular life style and consequently critically depend on active invasion and egress from the infected cells to ensure survival and propagation .", "Host cell entry is initiated by the attachment and...	[ "Many members of the phylum of Apicomplexa have adopted an obligate intracellular life style and critically depend on active invasion and egress from the infected cells to complete their lytic cycle .", "Toxoplasma gondii belongs to the coccidian subgroup of the Apicomplexa , and as such , the invasive tachyzoite...	[ "The Apicomplexa phylum groups important pathogens that infect humans and animals .", "Host cell invasion and egress from infected cells are key events in the lytic cycle of these obligate intracellular parasites .", "Host cell entry is powered by gliding motility and initiated by the discharge of apical secret...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dengue virus", "glycosylamines", "microbial mutation", "medicine and health sciences", "pathology and laboratory medicine", "nucleobases", "pathogens", "microbiology", "nucleotides", "viruses", "rna viruses", "viral genome", "microbial genomics", "viral genomics", "medical microbiology"...	Nucleobases and corresponding nucleosides display potent antiviral activities against dengue virus possibly through viral lethal mutagenesis	journal.pntd.0006421	null	[ [ "Dengue virus ( DENV ) is a worldwide health threat , with hundreds of millions of people infected yearly in more than 100 countries [1] .", "There are four known DENV serotypes and a first infection with one serotype followed by a second infection with another serotype may result in severe disease [2 , 3...	[ "Dengue virus affects millions of people worldwide each year .", "To date , there is no drug for the treatment of dengue-associated disease .", "Nucleosides are effective antivirals and work by inhibiting the accurate replication of the viral genome .", "Nucleobases offer a cheaper alternative to nucleosides ...	[ "Dengue virus is a world-wide public health menace estimated to infect hundreds of millions of people per year .", "Vaccines to prevent dengue virus infection have had limited success due in part to the requirement to elicit effective immune responses against the four dengue serotypes .", "There is an urgent un...	2018
[ "Introduction", "Design and implementation", "Results", "Discussion", "Materials and methods", "Availability and future directions" ]	[ "wavelet transforms", "action potentials", "medicine and health sciences", "engineering and technology", "signal processing", "membrane potential", "electrophysiology", "neuroscience", "neurites", "calcium signaling", "neuronal dendrites", "neuroimaging", "research and analysis methods", "...	An open source tool for automatic spatiotemporal assessment of calcium transients and local ‘signal-close-to-noise’ activity in calcium imaging data	journal.pcbi.1006054	null	[ [ "Calcium ions mediate fast signaling to regulate neuronal development , synaptic transmission , and synaptic plasticity [1–5] .", "Calcium imaging has become a standard technique for mapping neuronal activity in neurons in vitro and in vivo [6 , 7] .", "Although calcium signaling of neurons is well in...	[ "Local and spontaneous calcium signals play important roles in neurons and neuronal networks .", "Spontaneous or cell-autonomous calcium signals may be difficult to assess because they appear in an unpredictable spatiotemporal pattern and in very small neuronal loci of axons or dendrites .", "We developed an op...	[ "Calcium imaging has become a standard tool to investigate local , spontaneous , or cell-autonomous calcium signals in neurons .", "Some of these calcium signals are fast and ‘small’ , thus making it difficult to identify real signaling events due to an unavoidable signal noise .", "Therefore , it is difficult ...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "immune cells", "antigen-presenting cells", "immunology", "biology", "scrub typhus" ]	Orientia tsutsugamushi Subverts Dendritic Cell Functions by Escaping from Autophagy and Impairing Their Migration	journal.pntd.0001981	null	[ [ "Dendritic cells ( DCs ) are the most potent antigen-presenting cells ( APCs ) that initiate and orchestrate immune responses [1] .", "Upon pathogen infection , DCs capture foreign antigen and undergo maturational changes including increased surface expression of major histocompatibility complex ( MHC ) a...	[ "Dendritic cells ( DCs ) are the most potent antigen-presenting cells that link innate and adaptive immune responses , playing a pivotal role in triggering antigen-specific immunity .", "Antigen uptake by DCs induces maturational changes that include increased surface expression of major histocompatibility comple...	[ "Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi infection and is one of the main causes of febrile illness in the Asia-Pacific region .", "If not properly treated with antibiotics , patients often develop severe vasculitis that affects multiple organs , and the mortality rate of untreat...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Multicopy Single-Stranded DNA Directs Intestinal Colonization of Enteric Pathogens	journal.pgen.1005472	null	[ [ "Retron reverse transcriptases ( RT ) in bacteria were first described in Myxococcus xanthus [1] and E . coli [2] in the 1980s and are now known to be widely distributed in the genomes of eubacteria and archaea ( reviewed in [3] ) .", "All retrons contain three regions essential for production of msDNA: m...	[ "Multicopy single-stranded DNAs ( msDNAs ) are hybrid RNA-DNA molecules encoded on retroelements called retrons and produced by the action of retron reverse transcriptases .", "Retrons are widespread in bacteria but the natural function of msDNA has remained elusive despite 30 years of study .", "The major road...	[ "Multicopy single-stranded DNA ( msDNA ) is a unique molecule consisting of both an RNA and DNA portion .", "This molecule is produced by a reverse transcriptase and has no known natural function despite more than 30 years of study .", "We report that msDNA is important for both Salmonella Typhimurium and an en...	2015
[ "Introduction", "Design and Implementation", "Results", "Availability and Future Directions" ]	[]	VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires	journal.pcbi.1004503	null	[ [ "The advent of high throughput sequencing ( HTS ) has opened a new venue for the studies of genomics of adaptive immunity that involve deep profiling of T-cell receptor ( TCR ) and B-cell receptor ( BCR ) gene repertoires encoding a myriad of antigen specificities .", "Huge volumes of complex data produce...	[ "Despite the growing number of immune repertoire sequencing studies , the field still lacks software for analysis and comprehension of this high-dimensional data .", "Here we report VDJtools , a complementary software suite that solves a wide range of T cell receptor ( TCR ) repertoires post-analysis tasks , prov...	[ "High-throughput profiling of T- and B-cell antigen receptor repertoires promises great advances in our understanding of the mechanisms underlying adaptive immune system function , treatment of autoimmune and infectious diseases , and development of novel approaches in cancer immunotherapy .", "A number of recent...	2015
[ "Introduction", "Model", "Results", "Discussion" ]	[ "mathematics", "computational biology/metabolic networks", "computational biology/systems biology" ]	Mathematical Model of a Cell Size Checkpoint	journal.pcbi.1001036	null	[ [ "Dividing cells maintain a stable size from one generation to the next .", "This suggests that they contain homeostatic mechanisms in which the division cycle is triggered when a particular size is attained .", "However , the biochemical mechanisms for this have remained unknown puzzles for decades ."...	[ "How cells regulate their size from one generation to the next has remained an enigma for decades .", "Recently , a molecular mechanism that links cell size and cell cycle was proposed in fission yeast .", "This mechanism involves changes in the spatial cellular distribution of two proteins , Pom1 and Cdr2 , as...	[ "Cells delay division into two daughter cells until they reach a particular size .", "However , the molecular-level mechanisms by which they do this have remained unknown until recently .", "A cell-size checkpoint mechanism in rod-shaped fission yeast cells has recently been shown to involve two proteins , Pom1...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "birds", "ecology" ]	Projected Impacts of Climate and Land-Use Change on the Global Diversity of Birds	journal.pbio.0050157	Evaluating changes in range size of land bird species using Millenium Ecosystem Assessment scenarios reveals that land conversion, as well as climate change, will lead to the decline of many species, particularly those in the tropics.	[ [ "Accelerated climate change and the destruction of natural habitats through direct human activities are two of the greatest threats to terrestrial biodiversity .", "In recent decades , they have led to substantial range contractions and species extinctions [1–5] .", "Even more dramatic environmental c...	[ "Over the past few decades , land-use and climate change have led to substantial range contractions and species extinctions .", "Even more dramatic changes to global land cover are projected for this century .", "We used the Millennium Ecosystem Assessment scenarios to evaluate the exposure of all 8 , 750 land ...	[ "Land conversion and climate change have already had significant impacts on biodiversity and associated ecosystem services .", "Using future land-cover projections from the recently completed Millennium Ecosystem Assessment , we found that 950–1 , 800 of the world's 8 , 750 species of land birds could be imperile...	2007

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