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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" ]	[]	Impact of the Use of a Rapid Diagnostic Test for Visceral Leishmaniasis on Clinical Practice in Ethiopia: A Retrospective Study	journal.pntd.0003738	null	[ [ "Visceral leishmaniasis ( VL ) is a vector borne , fatal disease caused by the protozoan parasite Leishmania .", "While Leishmania donovani is the etiologic agent in the East-African and Indian regions where transmission is anthroponotic , L infantum is the agent in the Mediterranean and Latin-American en...	[ "Diagnostic guidelines for Visceral Leishmaniasis ( VL ) in the East African region are complex .", "Patients meeting the VL clinical case definition should be tested by rK39 rapid diagnostic test ( RDT ) followed by the Direct Agglutination Test ( DAT ) or tissue aspiration if RDT-negative .", "Otherwise , RDT...	[ "The introduction of RDTs is one of the major advancements in leishmaniasis control programs .", "While the variability in performance from one endemic region to the other is well recognized , the utilization of these RDTs in the routine clinical setting has not been evaluated to date .", "In this study , we sh...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Development and Validation of a Novel Leishmania donovani Screening Cascade for High-Throughput Screening Using a Novel Axenic Assay with High Predictivity of Leishmanicidal Intracellular Activity	journal.pntd.0004094	null	[ [ "The protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis , a group of diseases that is prevalent in 98 countries and 3 territories with approximately 1 . 3 million new cases occurring annually .", "There are estimated to be 20 , 000 to 40 , 000 deaths per year [1] .", ...	[ "Visceral leishmaniasis is an important parasitic disease of the developing world with a limited arsenal of drugs available for treatment .", "The existing drugs have significant deficiencies so there is an urgent need for new and improved drugs .", "In the human host , Leishmania are obligate intracellular par...	[ "New drugs for visceral leishmaniasis , are urgently required as existing drugs have serious shortcomings including toxicity and drug resistance .", "This disease is caused by parasites from the Leishmania family which live inside human cells .", "Screening large collections of chemicals ( >100 , 000 ) to ident...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome-Wide Screen Reveals Replication Pathway for Quasi-Palindrome Fragility Dependent on Homologous Recombination	journal.pgen.1003979	null	[ [ "Long palindromic sequences ( inverted repeats ∼100 bp or more each without a spacer or with a short spacer ) present a threat to both prokaryotic and eukaryotic genome stability .", "In E . coli , long palindromes placed on plasmids are frequently excised and cause cell inviability when introduced to chr...	[ "Inverted repeats capable of forming hairpin and cruciform structures present a threat to chromosomal integrity .", "They induce double strand breaks , which lead to gross chromosomal rearrangements , the hallmarks of cancers and hereditary diseases .", "Secondary structure formation at this motif has been prop...	[ "Inverted repeats are found in many eukaryotic genomes including humans .", "They have a potential to cause chromosomal breakage and rearrangements that contribute to genome polymorphism and the development of diseases .", "Instability of inverted repeats is accounted for by their propensity to adopt DNA second...	2013
[ "Introduction", "Results", "Discussion", "Materials & methods" ]	[ "organismal evolution", "brassica", "dna-binding proteins", "hormones", "plant science", "model organisms", "plant hormones", "experimental organism systems", "sequence motif analysis", "plants", "research and analysis methods", "arabidopsis thaliana", "sequence analysis", "sequence alignm...	Evolution of the Auxin Response Factors from charophyte ancestors	journal.pgen.1008400	null	[ [ "Charophytes diverged from chlorophyte algae more than a billion years ago ( y . a . ) and led to land plants emergence around 450 million y . a . [2–6] .", "“Early divergent” clades display a range of body complexity going from unicellular algae in Mesostigmatophyceae and Chlorokybophyceae , to multicell...	[ "Auxin is a major developmental regulator in plants and the acquisition of a transcriptional response to auxin likely contributed to developmental innovations at the time of water-to-land transition .", "Auxin Response Factors ( ARFs ) Transcription Factors ( TFs ) that mediate auxin-dependent transcriptional cha...	[ "Plants transition from water to land was determining for the history of our planet , since it led to atmospheric and soil condition changes that promoted the appearance of other life forms .", "This transition initiated around 1 billion years ago from a Charophyte algae lineage that acquired features allowing it...	2019
[ "Introduction", "Results", "Methods" ]	[ "auditory system", "visual system", "mathematics", "computational neuroscience", "single neuron function", "statistics", "sensory systems", "biology", "neuroscience", "statistical methods" ]	Inferring Nonlinear Neuronal Computation Based on Physiologically Plausible Inputs	journal.pcbi.1003143	null	[ [ "Sensory perception in the visual and auditory systems involves the detection of elemental features such as luminance and sound intensity , and their subsequent processing into more abstract representations such as “objects” that comprise our perception .", "The neuronal computations performed during such...	[ "The computation represented by a sensory neuron's response to stimuli is constructed from an array of physiological processes both belonging to that neuron and inherited from its inputs .", "Although many of these physiological processes are known to be nonlinear , linear approximations are commonly used to desc...	[ "Sensory neurons are capable of representing a wide array of computations on sensory stimuli .", "Such complex computations are thought to arise in large part from the accumulation of relatively simple nonlinear operations across the sensory processing hierarchies .", "However , models of sensory processing typ...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "molecular biology/dna repair" ]	Altered Hematopoiesis in Mice Lacking DNA Polymerase μ Is Due to Inefficient Double-Strand Break Repair	journal.pgen.1000389	null	[ [ "In higher eukaryotes , DNA double strand breaks ( DSB ) are repaired through two main pathways: homologous recombination [1] and non-homologous end-joining ( NHEJ ) ( reviewed [2]–[4] ) .", "Although NHEJ predominates during the G0/G1 and early S phases of the cell cycle [5] , [6] , both mechanisms can a...	[ "Polymerase mu ( Polμ ) is an error-prone , DNA-directed DNA polymerase that participates in non-homologous end-joining ( NHEJ ) repair .", "In vivo , Polμ deficiency results in impaired Vκ-Jκ recombination and altered somatic hypermutation and centroblast development .", "In Polμ−/− mice , hematopoietic develo...	[ "Double-strand breaks ( DSB ) in DNA are a highly deleterious type of genetic damage , potentially causing genomic rearrangements or cell death if unrepaired .", "DSB can be triggered by environmental factors ( such as electromagnetic radiation or clastogenic chemicals ) or normal cell metabolism .", "The main ...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "immune cells", "spleen", "granulomas", "immunology", "vertebrates", "parasitic diseases", "dogs", "animals", "collagens", "mammals", "parasitic protozoans", "protozoans", "leishmania", "cellular structures and organelles", "animal...	Morphophysiological changes in the splenic extracellular matrix of Leishmania infantum-naturally infected dogs is associated with alterations in lymphoid niches and the CD4+ T cell frequency in spleens	journal.pntd.0006445	null	[ [ "In Brazil , visceral leishmaniasis is caused by Leishmania infantum , and the domestic dog is the main urban reservoir[1] .", "Additionally , dogs have been used as models for the study of human disease[2] because disease progression in dogs is similar to that in humans[3] .", "Concerning the immune ...	[ "The spleen is one of the main affected organs in canine visceral leishmaniasis ( CVL ) .", "Disorganization of the splenic white pulp ( SWP ) has been associated with immunosuppression and disease progression .", "This study aims to assess structural and cellular changes in the splenic extracellular matrix of ...	[ "Infected dogs play important roles in the transmission of visceral leishmaniasis .", "These dogs are considered reservoirs of parasites in urban areas and fail to mount an efficient anti-Leishmania immune response .", "However , the specific immunosuppression profile is not completely understood .", "In our ...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "pathology and laboratory medicine", "emerging viral diseases", "crimean-congo hemorrhagic fever", "tropical diseases", "microbiology", "animal models", "model organisms", "emerging infectious diseases", "population modeling", "neglected tropic...	Evaluation of Antiviral Efficacy of Ribavirin, Arbidol, and T-705 (Favipiravir) in a Mouse Model for Crimean-Congo Hemorrhagic Fever	journal.pntd.0002804	null	[ [ "Crimean-Congo hemorrhagic fever virus ( CCHFV ) is a negative-strand RNA virus belonging to the genus Nairovirus of the family Bunyaviridae .", "The virus is endemic in Africa , Asia , southeast Europe , and the Middle East .", "Hyalomma ticks transmit the virus to humans , wildlife , and livestock ....	[ "Mice lacking the type I interferon receptor ( IFNAR−/− mice ) reproduce relevant aspects of Crimean-Congo hemorrhagic fever ( CCHF ) in humans , including liver damage .", "We aimed at characterizing the liver pathology in CCHF virus-infected IFNAR−/− mice by immunohistochemistry and employed the model to evalua...	[ "Crimean-Congo hemorrhagic fever ( CCHF ) is endemic in Africa , Asia , southeast Europe , and the Middle East .", "The case fatality rate is 30–50% .", "Studies on pathophysiology and treatment of CCHF have been hampered by the lack of an appropriate animal model .", "We have employed CCHF virus-infected tra...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/cognitive neuroscience", "neuroscience/sensory systems" ]	Interaction between Attention and Bottom-Up Saliency Mediates the Representation of Foreground and Background in an Auditory Scene	journal.pbio.1000129	Bottom-up (stimulus-driven) and top-down (attentional) processes interact when a complex acoustic scene is parsed. Both modulate the neural representation of the target in a manner strongly correlated with behavioral performance.	[ [ "Attention is the cognitive process underlying our ability to focus on specific components of the environment while ignoring others .", "By its very definition , attention plays a key role in defining what foreground is , i . e . , an object of attention , and differentiating it from task-irrelevant clutt...	[ "The mechanism by which a complex auditory scene is parsed into coherent objects depends on poorly understood interactions between task-driven and stimulus-driven attentional processes .", "We illuminate these interactions in a simultaneous behavioral–neurophysiological study in which we manipulate participants' ...	[ "Attention is the cognitive process underlying our ability to focus on specific aspects of our environment while ignoring others .", "By its very definition , attention plays a key role in differentiating foreground ( the object of attention ) from unattended clutter , or background .", "We investigate the neur...	2009
[ "Introduction", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "medicine and health sciences", "simulation and modeling", "diabetes mellitus", "research design", "dyslipidemia", "endocrine disorders", "genome analysis", "type 2 diabetes", "research and analysis methods", "case-control studies", "endocrinology", "periph...	An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations	journal.pgen.1007139	null	[ [ "Given the summary statistics for a SNP across multiple traits , CPBayes estimates two different measures evaluating overall pleiotropic association and an optimal subset of associated traits underlying a pleiotropic signal .", "The evidence for aggregate-level pleiotropic association is given by the loca...	[ "Simultaneous analysis of genetic associations with multiple phenotypes may reveal shared genetic susceptibility across traits ( pleiotropy ) .", "For a locus exhibiting overall pleiotropy , it is important to identify which specific traits underlie this association .", "We propose a Bayesian meta-analysis appr...	[ "Genome-wide association studies ( GWAS ) have detected shared genetic susceptibility to various human diseases ( pleiotropy ) .", "We propose a Bayesian meta-analysis method CPBayes that simultaneously evaluates the evidence of overall pleiotropy while determining which traits are pleiotropic .", "This approac...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular structures", "cellular stress responses", "viral classification", "microbiology", "host-pathogen interaction", "animal models", "model organisms", "dna viruses", "cell nucleus", "animal models of infection", "biology", "mouse", "cell biology", "viral persistence and latency", "...	HSV-1 Genome Subnuclear Positioning and Associations with Host-Cell PML-NBs and Centromeres Regulate LAT Locus Transcription during Latency in Neurons	journal.ppat.1002852	null	[ [ "Herpes simplex virus type 1 ( HSV-1 ) , a major human pathogen , is a persistent human neurotropic virus and a model of long-term interaction between a host cell and a parasite .", "HSV-1 establishes a long-term latent infection in neurons of the trigeminal ( or Gasserian ) ganglia ( TG ) of the peripher...	[ "Major human pathologies are caused by nuclear replicative viruses establishing life-long latent infection in their host .", "During latency the genomes of these viruses are intimately interacting with the cell nucleus environment .", "A hallmark of herpes simplex virus type 1 ( HSV-1 ) latency establishment is...	[ "After an initial lytic infection , many viruses establish a lifelong latent infection that hides them from the host immune system activity until reactivation .", "To understand the resurgence of the associated diseases , it is indispensable to acquire a better knowledge of the different mechanisms involved in th...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "cellular neuroscience", "computational neuroscience", "biology", "neuroscience" ]	Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy	journal.pcbi.1002545	null	[ [ "CA1 pyramidal neurons receive numerous synaptic inputs across their extensive dendritic tree , with synapses located up to hundreds of micrometres from the soma [1] .", "Due to electrotonic filtering , a distal synapse evokes a smaller EPSP at the soma than a proximal synapse of equal synaptic strength a...	[ "CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma .", "Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally , a phenomenon called “synaptic democracy” .", "How this is established is unclear .", "The ba...	[ "Neurons receive information from other neurons via hundreds of contacts ( synapses ) spread across their dendritic branches .", "Input signals from synapses propagate along a dendrite to the cell body ( soma ) , where the neuron decides whether or not to produce an action potential .", "Signals that travel fur...	2012
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "eukaryotic cells", "molecular cell biology", "immune cells", "antigen processing and recognition", "immunity", "gene expression", "parasitology", "immunology", "host-pathogen interaction", "biology", "genomics", "microbiology", "cellular types", "immune response" ]	Reprogramming Neutral Lipid Metabolism in Mouse Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes	journal.pntd.0002276	null	[ [ "Leishmania spp are protozoan parasites that are transmitted in the dermis of the mammalian host by blood-feeding sand flies .", "Once in the dermis of the mouse , the metacyclic promastigotes enter , both macrophages and dendritic leucocytes ( DLs ) where they differentiate into amastigotes within the pa...	[ "After loading with live Leishmania ( L ) amazonensis amastigotes , mouse myeloid dendritic leucocytes/DLs are known to undergo reprogramming of their immune functions .", "In the study reported here , we investigated whether the presence of live L . amazonensis amastigotes in mouse bone marrow-derived DLs is abl...	[ "Once they have gained entry to mammals , live Leishmania ( L ) amazonensis amastigotes are known to subvert both macrophages and dendritic leucocytes ( DLs ) as host cells .", "These L . amazonensis amastigotes then may or may not proliferate in these two phagocytic leucocyte lineages , but in both cases the oth...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "ecology", "chemical biology", "insects" ]	The Scent of the Waggle Dance	journal.pbio.0050228	Waggle-dancing honey bees, in addition to attracting nest mates to a food source, also release a scent that recruits more workers to the advertised site.	[ [ "More than fifty years ago , Karl von Frisch demonstrated through a series of elegant experiments that the waggle dance of honey bees uses symbolic communication to convey information about a subject that is both spatially and temporally removed from the receiver of the signal [1] .", "The waggle dance is...	[ "The waggle dance of honey bee ( Apis mellifera L . ) foragers communicates to nest mates the location of a profitable food source .", "We used solid-phase microextraction and gas chromatography coupled with mass spectrometry to show that waggle-dancing bees produce and release two alkanes , tricosane and pentaco...	[ "A honey bee colony consists of many thousands of individuals , all of which help to perform the work that allows their colony to thrive .", "To coordinate their efforts , honey bees have evolved a complex communication system , no part of which is more sophisticated than the waggle dance .", "The waggle dance ...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "gene regulation", "regulatory proteins", "dna-binding proteins", "animals", "organisms", "physiological processes", "transcription factors", "epigenetics", "zoology", "molting", "genetic interference", "proteins", "g...	TGFβ signaling related genes are involved in hormonal mediation during termite soldier differentiation	journal.pgen.1007338	null	[ [ "The complex society of eusocial insects includes sterile castes with phenotypes specialized for individual social tasks .", "To clarify the mechanisms associated with acquiring sterile castes is a fundamental goal in the evolutionary biology of eusocial insects .", "In hymenopteran species ( bees , a...	[ "A working knowledge of the proximate factors intrinsic to sterile caste differentiation is necessary to understand the evolution of eusocial insects .", "Genomic and transcriptomic analyses in social hymenopteran insects have resulted in the hypothesis that sterile castes are generated by the novel function of c...	[ "The acquisition of a sterile caste is a key step in animal eusocial evolution .", "The soldier is the first acquired permanently sterile caste in termites , which are distantly related to hymenopteran eusocial insects ( bees , ants and wasps ) .", "However , the evolutionary background to acquiring the soldier...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "biofilms", "exopolysaccharides", "vesicles", "chemical compounds", "xanthomonas campestris", "microbiology", "organic compounds", "mutation", "plant science", "amino acid substitution", "amino acids", "plant pathology", "cellular structures and organelles", "bacteria", ...	Fatty acid DSF binds and allosterically activates histidine kinase RpfC of phytopathogenic bacterium Xanthomonas campestris pv. campestris to regulate quorum-sensing and virulence	journal.ppat.1006304	null	[ [ "Quorum-sensing is a process that bacterial cells communicate with each other to elicit specific physiological responses , including virulence against hosts [1 , 2] .", "How single-celled bacteria detect and respond to population density is a fundamental question in studying quorum sensing .", "Previo...	[ "As well as their importance to nutrition , fatty acids ( FA ) represent a unique group of quorum sensing chemicals that modulate the behavior of bacterial population in virulence .", "However , the way in which full-length , membrane-bound receptors biochemically detect FA remains unclear .", "Here , we provid...	[ "Besides roles in nutrition , lipids also function as important signals in the regulation of prokaryotic and eukaryotic cells .", "In bacteria , fatty acids are part of the language of cell-cell communication known as quorum sensing for a decade .", "However , how bacteria detect these signals and regulate viru...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "gene regulation", "dna-binding proteins", "invertebrate genomics", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "methylation", "experimental organism systems", "epigenetics", "morphogenesis", "chromatin", "drosophila...	Separate Polycomb Response Elements control chromatin state and activation of the vestigial gene	journal.pgen.1007877	null	[ [ "The patterns of chromatin histone modifications differ between cell types , reflecting the activity of genes for developmental programs .", "Tri-methylation of the lysine-27 residue of histone H3 ( H3K27me3 ) typically marks extended chromatin domains , leading to chromatin compaction and epigenetic gene...	[ "Patterned expression of many developmental genes is specified by transcription factor gene expression , but is thought to be refined by chromatin-mediated repression .", "Regulatory DNA sequences called Polycomb Response Elements ( PREs ) are required to repress some developmental target genes , and are widespre...	[ "Eukaryotic genes are packaged in chromatin , and their transcription relies on activators that recruit RNA polymerases and on repressive factors .", "In multicellular organisms , cell types have distinct patterns of gene expression , and these patterns are controlled by by the expression of cell-type-specific tr...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "electrophoretic mobility shift assay", "gene regulation", "pathogens", "microbiology", "hepatitis b virus", "plasmid construction", "viruses", "dna replication", "dna construction", "molecular biology techniques", "dna", ...	Interferon-inducible ribonuclease ISG20 inhibits hepatitis B virus replication through directly binding to the epsilon stem-loop structure of viral RNA	journal.ppat.1006296	null	[ [ "Hepatitis B virus ( HBV ) infection remains a significant health threat to humans , leading to the elevated rate of severe liver diseases , such as fulminant hepatitis , fibrosis , cirrhosis , primary hepatocellular carcinoma , and other clinical complications [1] .", "HBV is the prototype member of hepa...	[ "Hepatitis B virus ( HBV ) replicates its DNA genome through reverse transcription of a viral RNA pregenome .", "We report herein that the interferon ( IFN ) stimulated exoribonuclease gene of 20 KD ( ISG20 ) inhibits HBV replication through degradation of HBV RNA .", "ISG20 expression was observed at basal lev...	[ "HBV is a DNA virus but replicates its DNA via retrotranscription of a viral RNA pregenome .", "ISG20 , an antiviral RNase induced by interferons , inhibits the replication of many RNA viruses but the underlying molecular antiviral mechanism remains elusive .", "Since all the known viruses , except for prions ,...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "biochemistry/rna structure", "virology/viral replication and gene regulation", "biophysics/structural genomics", "biophysics/protein folding", "virology/virulence factors and mechanisms", "virology/emerging viral diseases", "biophysics/rna structure", "biochemistry/structural genomi...	The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes	journal.ppat.1000428	null	[ [ "The SARS coronavirus ( SARS-CoV ) is much more pathogenic for humans than any other coronavirus .", "Therefore , protein domains encoded by the SARS-CoV genome that are absent in other coronaviruses are of particular interest , because they may be responsible for the extraordinary virulence .", "The ...	[ "Since the outbreak of severe acute respiratory syndrome ( SARS ) in 2003 , the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus ( SARS-CoV ) , the non-structural proteins ( Nsps ) , have been determined .", "However , within the large Nsp3 ( 1922 amino-acid re...	[ "The genome of the SARS coronavirus codes for 16 non-structural proteins that are involved in replicating this huge RNA ( approximately 29 kilobases ) .", "The roles of many of these in replication ( and/or transcription ) are unknown .", "We attempt to derive conclusions concerning the possible functions of th...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "embryology", "molecular development", "biology" ]	Delineating a Conserved Genetic Cassette Promoting Outgrowth of Body Appendages	journal.pgen.1003231	null	[ [ "Development of the external genitalia is a crucial aspect of mammalian evolution that enables internal fertilization , a pivotal step towards land invasion .", "All therian mammals including metatherians develop external genitalia around their urogenital outlets .", "In mice , development of the embr...	[ "The acquisition of the external genitalia allowed mammals to cope with terrestrial-specific reproductive needs for internal fertilization , and thus it represents one of the most fundamental steps in evolution towards a life on land .", "How genitalia evolved remains obscure , and the key to understanding this p...	[ "Mammalian limbs and external genitalia are body appendages specialized for locomotion and internal fertilization , respectively .", "Despite their marked anatomical and functional differences , development of the limb and external genitalia appears to involve similar genetic controls , and some have suggested th...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "immunology/antigen processing and recognition", "microbiology/immunity to infections", "immunology/immune response", "infectious diseases/bacterial infections", "immunology/immunity to infections" ]	Hypoxia Induces an Immunodominant Target of Tuberculosis Specific T Cells Absent from Common BCG Vaccines	journal.ppat.1001237	null	[ [ "Mycobacterium tuberculosis remains a formidable health problem as it is estimated to infect one-third of the world's population and causes around 1 . 5 million deaths per year [1] .", "Control is largely based around the partially effective vaccine Mycobacterium bovis Bacille Calmette Guérin ( BCG ) and ...	[ "M . tuberculosis ( MTB ) species-specific antigenic determinants of the human T cell response are important for immunodiagnosis and vaccination .", "As hypoxia is a stimulus in chronic tuberculosis infection , we analyzed transcriptional profiles of MTB subject to 168 hours of hypoxia to test the hypothesis that...	[ "Mycobacterium tuberculosis ( the cause of tuberculosis ) can persist for many years in humans without causing disease but has the potential to reactivate .", "One of the conditions the bacterium must survive in these circumstances is hypoxia .", "In order to do so , the bacterium uses a characteristic set of g...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "molecular probe techniques", "enzymes", "enzymology", "plasmid construction", "dna replication", "dna construction", "dna", "molecular biology techniques", "gel electrophoresis", "ligases", "extraction techniques", "research and analysis methods", "electrophoretic techniques", "electropho...	The role of host DNA ligases in hepadnavirus covalently closed circular DNA formation	journal.ppat.1006784	null	[ [ "Hepadnavirus specifies a group of hepatotropic viruses that carry a single copy of the partially double stranded relaxed circular ( rc ) viral DNA genome in the enveloped virion particle [1] .", "Hepadnavirus infects mammalian and avian hosts with strict species-specific tropism , including human hepatit...	[ "Hepadnavirus covalently closed circular ( ccc ) DNA is the bona fide viral transcription template , which plays a pivotal role in viral infection and persistence .", "Upon infection , the non-replicative cccDNA is converted from the incoming and de novo synthesized viral genomic relaxed circular ( rc ) DNA , pre...	[ "Hepadnavirus cccDNA is the persistent form of viral genome , and in terms of human hepatitis B virus ( HBV ) , cccDNA is the basis for viral rebound after the cessation of therapy , as well as the elusiveness of a cure with current medications .", "Therefore , the elucidation of molecular mechanism of cccDNA for...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "cardiovascular anatomy", "tropical diseases", "fibrosis", "parasitic diseases", "parasitic protozoans", "animal models", "organisms", "developmental biology", "electrocardiography", "model organisms", "protozoans", "experimental organism systems", "bioassay...	TGF-β inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a pre-clinical study of chronic Chagas’ heart disease	journal.pntd.0007602	null	[ [ "Chronic chagasic cardiomyopathy ( CCC ) is the most common form of non- ischemic cardiomyopathy and one of the main causes of complications and death in Latin America , where the disease is endemic .", "It is estimated that ~7 million people are infected by Trypanosoma cruzi worldwide [1] , but this is a...	[ "TGF-β involvement in Chagas disease cardiomyopathy has been clearly demonstrated .", "The TGF-β signaling pathway is activated in the cardiac tissue of chronic phase patients and is associated with an increase in extracellular matrix protein expression .", "The aim of this study was to investigate the effect o...	[ "TGF-β is a key molecule in many physiological processes as well as pathologies .", "We have previously described the role of TGF-β in Chagas disease , caused by the eukaryotic protozoan parasite Trypanosoma cruzi .", "Besides the high disease burden in many countries , one of the severe aspects of Chagas disea...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cell motility", "neurochemistry", "chemical compounds", "dopaminergics", "neuroscience", "organic compounds", "hormones", "serotonin", "muscarinic acetylcholine receptors", "amines", "neurotransmitters", "neuropeptides", "catecholamines", "dopamine", "nicotinic acetylcholine receptors",...	Chemotactic migration of newly excysted juvenile Clonorchis sinensis is suppressed by neuro-antagonists	journal.pntd.0007573	null	[ [ "Clonorchis sinensis is the most common human liver fluke in East Asia , with more than 200 million people at risk of infection [1] .", "It primarily inhabits the bile duct , where it can induce serious pathological inflammatory changes , and chronic infection is associated with the development of cholang...	[ "The metacercariae of the Clonorchis sinensis liver fluke excyst in the duodenum of mammalian hosts , and the newly excysted juveniles ( CsNEJs ) migrate along the bile duct via bile chemotaxis .", "Cholic acid is a major component of bile that induces this migration .", "We investigated the neuronal control of...	[ "The liver fluke Clonorchis sinensis is a flatworm parasite dwelling in the bile duct , which can induce serious pathological inflammatory changes , and chronic infection is associated with bile duct cancer .", "In order to gain access to its habitat , C . sinensis larva follows chemical cues from the liver , a p...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary ecology", "computational biology/comparative sequence analysis", "microbio...	An Insect Herbivore Microbiome with High Plant Biomass-Degrading Capacity	journal.pgen.1001129	null	[ [ "Plant cell walls contain the largest reservoirs of organic carbon on Earth [1] .", "This carbon is largely inaccessible to most organisms , occurring in the form of cellulose , hemicelluloses , and lignin .", "Certain bacteria and fungi are capable of deconstructing these recalcitrant plant polymers ...	[ "Herbivores can gain indirect access to recalcitrant carbon present in plant cell walls through symbiotic associations with lignocellulolytic microbes .", "A paradigmatic example is the leaf-cutter ant ( Tribe: Attini ) , which uses fresh leaves to cultivate a fungus for food in specialized gardens .", "Using a...	[ "Leaf-cutter ants form massive subterranean colonies containing millions of workers that harvest hundreds of kilograms of leaves each year .", "They use these leaves to grow a mutualistic fungus that serves as the colony's primary food source .", "By farming fungus in specialized garden chambers , these dominan...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mitosis", "biochemistry", "dna replication", "cell biology", "chromosome biology", "chromosome structure and function", "centromeres", "cell cycle and cell division", "genetics", "biology and life sciences", "dna", "cell processes", "chromatids", "chromosomes" ]	The Chromosomal Association of the Smc5/6 Complex Depends on Cohesion and Predicts the Level of Sister Chromatid Entanglement	journal.pgen.1004680	null	[ [ "In order to maintain chromosome stability , cells need to overcome topological problems caused by the structure of the DNA molecule .", "One example of such topological problem is DNA supercoiling induced by replication or transcription .", "Another is sister chromatid intertwinings ( SCIs ) , which ...	[ "The cohesin complex , which is essential for sister chromatid cohesion and chromosome segregation , also inhibits resolution of sister chromatid intertwinings ( SCIs ) by the topoisomerase Top2 .", "The cohesin-related Smc5/6 complex ( Smc5/6 ) instead accumulates on chromosomes after Top2 inactivation , known t...	[ "When cells divide , sister chromatids have to be segregated away from each other for the daughter cells to obtain a correct set of chromosomes .", "Using yeast as model organism , we have analyzed the function of the cohesin and the Smc5/6 complexes , which are essential for chromosome segregation .", "Cohesin...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna replication", "microbiology/parasitology" ]	TbPIF5 Is a Trypanosoma brucei Mitochondrial DNA Helicase Involved in Processing of Minicircle Okazaki Fragments	journal.ppat.1000589	null	[ [ "Trypanosomes and related parasites cause tropical diseases such as sleeping sickness and Chagas disease .", "As one of the earliest diverging eukaryotes that contain a mitochondrion [1] , this group of parasites is well known for unusual biological properties .", "For example , their mitochondrial ge...	[ "Trypanosoma brucei's mitochondrial genome , kinetoplast DNA ( kDNA ) , is a giant network of catenated DNA rings .", "The network consists of a few thousand 1 kb minicircles and several dozen 23 kb maxicircles .", "Here we report that TbPIF5 , one of T . brucei's six mitochondrial proteins related to Saccharom...	[ "Trypanosoma brucei is a protozoan parasite that causes human sleeping sickness in sub-Saharan Africa .", "Trypanosomes are primitive eukaryotes and they have many unusual biological features .", "One prominent example is their mitochondrial genome , known as kinetoplast DNA or kDNA .", "kDNA , with a structu...	2009
[ "Introduction", "Results/Discussion", "Methods" ]	[ "microbial mutation", "virology", "population genetics", "biology", "evolutionary biology", "microbiology", "evolutionary genetics" ]	From Molecular Genetics to Phylodynamics: Evolutionary Relevance of Mutation Rates Across Viruses	journal.ppat.1002685	null	[ [ "Mutations result from biochemical processes such as replication errors , editing , or nucleic acid damage , but their spread and fixation is a population-genetics process that takes place over much broader scales .", "Remarkably , the neutral theory of molecular evolution posits that the mutation rate sh...	[ "Although evolution is a multifactorial process , theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear .", "To what extent these two biochemical and population-scale processes are related in nature , however , is largely unknown .", ...	[ "Viruses are an excellent system for addressing the evolutionary implications of mutation because their mutation rates vary by orders of magnitude , and their evolution takes place within the time frame of human observation .", "Theory posits a direct relationship between these two processes , but this has rarely...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetic networks", "protein metabolism", "engineering and technology", "enzymes", "metabolic networks", "enzymology", "network analysis", "genome analysis", "molecular biology techniques", "research and analysis methods", "computer and information sciences", "genomics", "gene mapping", "p...	Assessing key decisions for transcriptomic data integration in biochemical networks	journal.pcbi.1007185	null	[ [ "Most biological systems can be structured as networks , from cell signaling pathways to cell metabolism .", "These networks are invaluable for describing and understanding complex biological processes .", "For example , metabolic network reconstructions can illuminate the molecular basis of phenotype...	[ "To gain insights into complex biological processes , genome-scale data ( e . g . , RNA-Seq ) are often overlaid on biochemical networks .", "However , many networks do not have a one-to-one relationship between genes and network edges , due to the existence of isozymes and protein complexes .", "Therefore , de...	[ "Over the past two decades , systems biology approaches have permeated all fields of biology .", "Indeed , biological networks are commonly used for the analysis of omics datasets and to test hypotheses through computational simulations .", "Many of these types of studies require one to overlay omics data to a ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "zoology", "biology", "microbiology", "evolutionary biology", "population biology" ]	Ultrafast Evolution and Loss of CRISPRs Following a Host Shift in a Novel Wildlife Pathogen, Mycoplasma gallisepticum	journal.pgen.1002511	null	[ [ "Populations of animals are under constant threat from bacterial pathogens , which can be particularly destructive following a switch to a new host or the evolution of novel virulence mechanisms .", "Understanding the rate and process of evolutionary change in pathogens is thus important to assessing the ...	[ "Measureable rates of genome evolution are well documented in human pathogens but are less well understood in bacterial pathogens in the wild , particularly during and after host switches .", "Mycoplasma gallisepticum ( MG ) is a pathogenic bacterium that has evolved predominantly in poultry and recently jumped t...	[ "Documenting the evolutionary changes occurring in pathogens when they switch hosts is important for understanding mechanisms of adaptation and rates of evolution .", "We took advantage of a novel host–pathogen system involving a bacterial pathogen ( Mycoplasma gallisepticum , or MG ) and a songbird host , the Ho...	2012
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "medicine", "infectious diseases", "schistosomiasis", "parasitic diseases", "helminth infection" ]	Profiles of Small Non-Coding RNAs in Schistosoma japonicum during Development	journal.pntd.0001256	null	[ [ "Schistosomiasis is a chronic debilitating disease that afflicts more than 200 million individuals in the tropics and sub-tropics regions [1] .", "The agents of this disease , parasitic flatworms of the genus Schistosoma , have a complex developmental life cycle characterized by a distinct parasitic phase...	[ "The gene regulation mechanism along the life cycle of the genus Schistosoma is complex .", "Small non-coding RNAs ( sncRNAs ) are essential post transcriptional gene regulation elements that affect gene expression and mRNA stability .", "Preliminary studies indicated that sncRNAs in schistosomal parasites are ...	[ "Schistosomiasis , a debilitating disease , caused by agents of the genus Schistosoma afflicts more than 200 million people worldwide .", "Schistosomes could serve as an interesting model to explore gene regulation due to its evolutional position , complex life cycle and sexual dimorphism .", "We previously ind...	2011
[ "Results", "Discussion", "Methods" ]	[ "learning", "cell physiology", "action potentials", "medicine and health sciences", "neural networks", "membrane potential", "social sciences", "electrophysiology", "neuroscience", "learning and memory", "cognitive psychology", "mathematics", "algebra", "computer and information sciences",...	Robust spatial memory maps encoded by networks with transient connections	journal.pcbi.1006433	null	[ [ "How does the decay of the connections affect the net structure of the flickering complex F τ ?", "As shown on Fig 5A , the numbers of links N2 ( t ) and of the triple connections N3 ( t ) rapidly grow at the onset of the navigation and begin to saturate in about ts ≈ 4 minutes ( i . e . , by the time whe...	[ "The spiking activity of principal cells in mammalian hippocampus encodes an internalized neuronal representation of the ambient space—a cognitive map .", "Once learned , such a map enables the animal to navigate a given environment for a long period .", "However , the neuronal substrate that produces this map ...	[ "The reliability of our memories is nothing short of remarkable .", "Synaptic connections between neurons appear and disappear at a rapid rate , and the resulting networks constantly change their architecture due to various forms of neural plasticity .", "How can the brain develop a reliable representation of t...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "nervous system", "prefrontal cortex", "pervasive developmental disorders", "brain", "vertebrates", "social sciences", "neuroscience", "animals", "mammals", "developmental psychology", "animal models", "primates", "experimental organism systems", "nerve fi...	Parallel trends in cortical gray and white matter architecture and connections in primates allow fine study of pathways in humans and reveal network disruptions in autism	journal.pbio.2004559	null	[ [ "The functional specialization of the human cerebral cortex is critically dependent on the structural organization and connectivity of its cortical areas [1–5] .", "In recent years , evidence to support this structure-function relationship has focused on noninvasive methods through functional imaging and ...	[ "Noninvasive imaging and tractography methods have yielded information on broad communication networks but lack resolution to delineate intralaminar cortical and subcortical pathways in humans .", "An important unanswered question is whether we can use the wealth of precise information on pathways from monkeys to...	[ "Can the wealth of information from animal studies on the structure and connections of the cerebral cortex—the brain’s outer rim—be translated to understand neural communication in humans and disruption in brain diseases ?", "To address this question , we examined the prefrontal cortex , which is associated with ...	2018
[ "Introduction", "Results", "Discussion", "Concluding remarks", "Materials and methods" ]	[ "medicine and health sciences", "in situ hybridization", "molecular probe techniques", "nervous system", "brain", "vertebrates", "animals", "developmental biology", "molecular biology techniques", "amphioxus", "research and analysis methods", "embryology", "probe hybridization", "gene expr...	Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain	journal.pbio.2001573	null	[ [ "The vertebrate brain is arguably the most complex structure in nature .", "All vertebrates show a highly conserved construction plan , or Bauplan , of their central nervous system ( CNS ) , which involves several major anatomical and genetic partitions and their subsequent subdivisions [1] .", "Under...	[ "All vertebrate brains develop following a common Bauplan defined by anteroposterior ( AP ) and dorsoventral ( DV ) subdivisions , characterized by largely conserved differential expression of gene markers .", "However , it is still unclear how this Bauplan originated during evolution .", "We studied the relati...	[ "According to textbooks , vertebrate brains develop from a neural tube that rapidly becomes regionalized into the forebrain ( which includes the secondary prosencephalon and diencephalon ) , midbrain , and hindbrain .", "These regions are then further subdivided; in particular , the diencephalon gives rise to the...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "action potentials", "neural networks", "nervous system", "membrane potential", "electrophysiology", "neuroscience", "synaptic plasticity", "network analysis", "neuronal plasticity", "computer and information sciences", "developmental neuroscience", "network m...	Shaping Neural Circuits by High Order Synaptic Interactions	journal.pcbi.1005056	null	[ [ "Synfire chains , consisting of distinct groups of neurons that project to each other in a sequential order ( Fig 1A ) , were originally proposed as a model for sequence generation in the mammalian cortex [20] .", "Subsequently , compelling evidence has pointed to the possibility that this architecture un...	[ "Spike timing dependent plasticity ( STDP ) is believed to play an important role in shaping the structure of neural circuits .", "Here we show that STDP generates effective interactions between synapses of different neurons , which were neglected in previous theoretical treatments , and can be described as a sum...	[ "Plasticity between neural connections plays a key role in our ability to process and store information .", "One of the fundamental questions on plasticity , is the extent to which local processes , affecting individual synapses , are responsible for large scale structures of neural connectivity .", "Here we fo...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "physiology/muscle and connective tissue", "developmental biology/developmental molecular mechanisms", "computational biology/systems biology" ]	A Differential Wiring Analysis of Expression Data Correctly Identifies the Gene Containing the Causal Mutation	journal.pcbi.1000382	null	[ [ "Evolution , normal development , immune responses and aberrant processes such as", "diseases and cancer all involve at least some rewiring of regulatory circuits [1]–[3] .", "Indeed it is the", "subtle ( and sometimes not so subtle ) differences in circuit wiring that makes each", "individual...	[ "Transcription factor ( TF ) regulation is often post-translational .", "TF", "modifications such as reversible phosphorylation and missense mutations , which", "can act independent of TF expression level , are overlooked by differential", "expression analysis .", "Using bovine Piedmontese myostatin mutan...	[ "Evolution , development , and cancer are governed by regulatory circuits where the", "central nodes are transcription factors .", "Consequently , there is great interest", "in methods that can identify the causal mutation/perturbation responsible for", "any circuit rewiring .", "The most widely available...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Impact of Dendritic Size and Dendritic Topology on Burst Firing in Pyramidal Cells	journal.pcbi.1000781	null	[ [ "Neurons exhibit a wide range of intrinsic firing patterns with respect to both spike frequency and spike pattern [1]–[3] .", "A distinct type of firing pattern that is critically involved in neuronal signaling and synaptic plasticity is burst firing , the generation of clusters of spikes with short inter...	[ "Neurons display a wide range of intrinsic firing patterns .", "A particularly relevant pattern for neuronal signaling and synaptic plasticity is burst firing , the generation of clusters of action potentials with short interspike intervals .", "Besides ion-channel composition , dendritic morphology appears to ...	[ "Neurons possess highly branched extensions , called dendrites , which form characteristic tree-like structures .", "The morphology of these dendritic arborizations can undergo significant changes in many pathological conditions .", "It is still poorly known , however , how alterations in dendritic morphology a...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Reassessing Google Flu Trends Data for Detection of Seasonal and Pandemic Influenza: A Comparative Epidemiological Study at Three Geographic Scales	journal.pcbi.1003256	null	[ [ "Influenza remains a paradox for public health: While influenza epidemics are expected seasonally in temperate climates , their exact timing and severity remain largely unpredictable , making them a challenge to ongoing preparedness , surveillance and response efforts [1] .", "Surveillance efforts for inf...	[ "The goal of influenza-like illness ( ILI ) surveillance is to determine the timing , location and magnitude of outbreaks by monitoring the frequency and progression of clinical case incidence .", "Advances in computational and information technology have allowed for automated collection of higher volumes of elec...	[ "In November 2008 , Google Flu Trends was launched as an open tool for influenza surveillance in the United States .", "Engineered as a system for early detection and daily monitoring of the intensity of seasonal influenza epidemics , Google Flu Trends uses internet search data and a proprietary algorithm to prov...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immune cells", "viral transmission and infection", "immunology", "microbiology", "immunodeficiency viruses", "adaptive immunity", "immunotherapy", "animal models of infection", "viral clearance", "t cells", "biology", "immunity", "virology", "antivirals" ]	In Vivo Suppression of HIV by Antigen Specific T Cells Derived from Engineered Hematopoietic Stem Cells	journal.ppat.1002649	null	[ [ "Human hematopoietic stem cells ( HSCs ) , through development in the thymus , are capable of producing progeny T cells that generally display one of a vast repertoire of T cell receptors ( TCRs ) .", "In the case of many non-persistent viral infections , T cells bearing TCRs specific to viral antigens me...	[ "The HIV-specific cytotoxic T lymphocyte ( CTL ) response is a critical component in controlling viral replication in vivo , but ultimately fails in its ability to eradicate the virus .", "Our intent in these studies is to develop ways to enhance and restore the HIV-specific CTL response to allow long-term viral ...	[ "There is a desperate need for the development of new therapeutic strategies to eradicate HIV infection .", "HIV actively subverts the potent natural immune responses against it , particularly cellular cytotoxic T lymphocyte ( CTL ) responses .", "The development of a therapy that allows long-lived immune self-...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cardiovascular disorders" ]	Chagas Cardiomyopathy in the Context of the Chronic Disease Transition	journal.pntd.0000688	null	[ [ "Chagas disease , caused by the parasite Trypanosoma cruzi , affects an estimated 8 million people in the Americas [1] .", "Transmission occurs via inoculation of T . cruzi-infected feces of the triatomine vector through the bite wound or mucosal surfaces .", "Infection may also be acquired congenital...	[ "Patients with Chagas disease have migrated to cities , where obesity , hypertension and other cardiac risk factors are common .", "The study included adult patients evaluated by the cardiology service in a public hospital in Santa Cruz , Bolivia .", "Data included risk factors for T . cruzi infection , medical...	[ "Latin America is undergoing a transition from disease patterns characteristic of developing countries with high rates of infectious disease and premature deaths to a pattern more like industrialized countries , in which chronic conditions such as obesity , hypertension and diabetes are more common .", "Many rura...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "gram negative", "biology", "microbiology", "host-pathogen interaction", "bacterial biochemistry", "bacterial pathogens" ]	Deciphering the Acylation Pattern of Yersinia enterocolitica Lipid A	journal.ppat.1002978	null	[ [ "Lipopolysaccharide ( LPS ) is one of the major surface components of Gram-negative bacteria .", "The molecular structure of LPS is rather unique: an amphiphile with a hydrophobic region , the so-called lipid A , adjacent to a densely negatively charged polysaccharide .", "In Escherichia coli K-12 , t...	[ "Pathogenic bacteria may modify their surface to evade the host innate immune response .", "Yersinia enterocolitica modulates its lipopolysaccharide ( LPS ) lipid A structure , and the key regulatory signal is temperature .", "At 21°C , lipid A is hexa-acylated and may be modified with aminoarabinose or palmita...	[ "Lipopolysaccharide ( LPS ) is one of the major surface components of Gram-negative bacteria .", "The LPS contains a molecular pattern recognized by the innate immune system .", "Not surprisingly , the modification of the LPS pattern is a virulence strategy of several pathogens to evade the innate immune system...	2012
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genome evolution", "biology", "genomics", "evolutionary biology", "genetics and genomics" ]	An Endogenous Foamy-like Viral Element in the Coelacanth Genome	journal.ppat.1002790	null	[ [ "Foamy viruses are complex retroviruses thought exclusively to infect mammalian species , including cats , cows , horses , and non-human primates [1] .", "Although human-specific foamy viruses have not been found , humans can be naturally infected by foamy viruses of non-human primate origin [2]–[4] .", ...	[ "Little is known about the origin and long-term evolutionary mode of retroviruses .", "Retroviruses can integrate into their hosts' genomes , providing a molecular fossil record for studying their deep history .", "Here we report the discovery of an endogenous foamy virus-like element , which we designate ‘coel...	[ "The deep history of retroviruses is still obscure .", "Retroviruses can leave integrated copies within their hosts' genomes , providing a fossil record for studying their long-term evolution .", "Endogenous forms of foamy viruses , complex retroviruses known to infect only mammalian species , appear to be extr...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "mutagenesis", "biochemistry", "genetic mutation", "molecular cell biology", "mutation types", "nucleic acids", "proteins", "genetics", "biology", "genetics and genomics", "genetic engineering", "gene function" ]	Retrovolution: HIV–Driven Evolution of Cellular Genes and Improvement of Anticancer Drug Activation	journal.pgen.1002904	null	[ [ "Broadening the repertoire of natural molecules and generating variants that confer new phenotypes to human cells are appealing perspectives for the development of biomedical applications , and for understanding fundamental cellular processes .", "To this end , in classical procedures , libraries of mutan...	[ "In evolution strategies aimed at isolating molecules with new functions , screening for the desired phenotype is generally performed in vitro or in bacteria .", "When the final goal of the strategy is the modification of the human cell , the mutants selected with these preliminary screenings may fail to confer t...	[ "We exploited the error-prone replication machinery of HIV-1 and its ability to stably introduce transgenes in human cells to develop a novel system , Retrovolution , to generate libraries of mutants of cellular genes .", "When libraries are screened to isolate variants that modify the phenotype of the human cell...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "action potentials", "nervous system", "drugs", "membrane potential", "electrophysiology", "neuroscience", "ganglion cells", "interneurons", "pharmacology", "animal management", "animal performance", "cannabinoids", "animal cells", "neural pathways", "ag...	Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3	journal.pcbi.1005624	null	[ [ "Recent years have seen a resurgence of interest in the therapeutic role of cannabinoids ( CBs ) for several diseases and neurophyschiatric disorders such as psychosis , anxiety disorders , PTSD , and multiple sclerosis [1 , 2] .", "In particular , CB agonists have shown promising but mixed results in the...	[ "Much of the research on cannabinoids ( CBs ) has focused on their effects at the molecular and synaptic level .", "However , the effects of CBs on the dynamics of neural circuits remains poorly understood .", "This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaf...	[ "Research into cannabinoids ( CBs ) over the last several decades has found that they induce a large variety of oftentimes opposing effects on various neuronal receptors and processes .", "Due to this plethora of effects , disentangling how CBs influence neuronal circuits has proven challenging .", "This paper ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mycology", "plant microbiology", "biology", "microbiology" ]	The Cyclase-Associated Protein Cap1 Is Important for Proper Regulation of Infection-Related Morphogenesis in Magnaporthe oryzae	journal.ppat.1002911	null	[ [ "Magnaporthe oryzae , a heterothallic ascomycete , is the causal agent of rice blast , which is one of the most destructive diseases of rice in the world .", "It infects the rice plant in a manner typical of many foliar pathogens .", "Germ tubes differentiate into specialized infection structures call...	[ "Surface recognition and penetration are critical steps in the infection cycle of many plant pathogenic fungi .", "In Magnaporthe oryzae , cAMP signaling is involved in surface recognition and pathogenesis .", "Deletion of the MAC1 adenylate cyclase gene affected appressorium formation and plant infection .", ...	[ "In Magnaporthe oryzae , cAMP signaling is known to play an important role in surface recognition and plant penetration .", "The Mac1 adenylate cyclase is essential for plant infection .", "To better understand Mac1 activation mechanisms , in this study we used the affinity purification approach to identify pro...	2012
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "evolutionary biology", "genetics and genomics" ]	Evidence for Pervasive Adaptive Protein Evolution in Wild Mice	journal.pgen.1000825	null	[ [ "Several approaches have revealed evidence for adaptation at the molecular level .", "Local reductions in diversity , indicating selective sweeps , have been identified in populations of a number of species [1] , [2] .", "In Drosophila , reductions in neutral diversity have also been associated with i...	[ "The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years .", "The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adapt...	[ "The prevalence of natural selection at the DNA level remains a controversial issue in evolutionary biology .", "In particular , estimates of the proportion of adaptive amino acid changes ( α ) vary greatly between taxa , being 50% or more in bacteria and fruit flies , but at most 13% in hominids .", "Here , we...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virus evolution and symbiosis", "virology/vaccines", "virology/immunodeficiency viruses", "virology", "infectious diseases/viral infections", "infectious diseases/sexually transmitted diseases", "virology/host invasion and cell entry" ]	The Genotype of Early-Transmitting HIV gp120s Promotes α4β7 –Reactivity, Revealing α4β7+/CD4+ T cells As Key Targets in Mucosal Transmission	journal.ppat.1001301	null	[ [ "Despite widely available prevention modalities against HIV transmission , 2 . 6 million individuals are newly infected with HIV every year .", "Thus , there exists an urgent need for an effective HIV vaccine .", "A number of studies that have focused on the earliest events in HIV transmission raise t...	[ "Mucosal transmission of HIV is inefficient .", "The virus must breach physical barriers before it infects mucosal CD4+ T cells .", "Low-level viral replication occurs initially in mucosal CD4+ T cells , but within days high-level replication occurs in Peyer's patches , the gut lamina propria and mesenteric lym...	[ "In the first days following sexual transmission , HIV replication occurs initially at relatively low levels in mucosal tissues because of a paucity of CD4+ T cell targets for the virus to infect .", "After a period of days , virus accesses specific gut tissues that are enriched in activated CD4+ T cells , where ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutagenesis", "cellular stress responses", "cancer genetics", "genetic mutation", "dna replication", "nucleic acids", "genetics", "dna", "dna repair", "biology", "dna recombination", "molecular cell biology" ]	Stepwise Activation of the ATR Signaling Pathway upon Increasing Replication Stress Impacts Fragile Site Integrity	journal.pgen.1003643	null	[ [ "Accurate genome duplication is required at each cell generation to maintain genetic information .", "However , mammalian genomes contain regions that challenge the replication process , such as common fragile sites ( CFS ) .", "CFSs are loci that recurrently exhibit breaks on mitotic chromosomes foll...	[ "Breaks at common fragile sites ( CFS ) are a recognized source of genome instability in pre-neoplastic lesions , but how such checkpoint-proficient cells escape surveillance and continue cycling is unknown .", "Here we show , in lymphocytes and fibroblasts , that moderate replication stresses like those inducing...	[ "Accurate genome duplication is crucial at each cell generation to maintain genetic information .", "However , replication forks routinely face lesions on the DNA template and/or travel through sequences intrinsically difficult to replicate , such as common fragile sites ( CFS ) .", "To help the fork to proceed...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "protein interactions", "viral transmission and infection", "293t cells", "cell cycle and cell division", "biological cultures", "cell processes", "microbiology", "viral structure", "research and analysis methods", "proteins", "cell lines", "viral replication", "virions"...	Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration	journal.ppat.1005860	null	[ [ "As obligatory intracellular parasites , retroviruses depend on host cell machineries for successful replication .", "Over the years , many cellular proteins counteracting or aiding retroviral replication have been identified [reviewed in 1 , 2] .", "Expectedly , a large number of these factors are ca...	[ "Unlike for other retroviruses , only a few host cell factors that aid the replication of foamy viruses ( FVs ) via interaction with viral structural components are known .", "Using a yeast-two-hybrid ( Y2H ) screen with prototype FV ( PFV ) Gag protein as bait we identified human polo-like kinase 2 ( hPLK2 ) , a...	[ "Viruses are masters at exploiting host cell machineries for their replication .", "For human immunodeficiency virus type 1 ( HIV-1 ) , the best-studied representative of the Orthoretrovirinae subfamily from the genus lentiviruses , numerous important virus-host interactions have been described .", "In contrast...	2016
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "developmental biology", "computational biology/sequence motif analysis", "computational biology/transcriptional regulation", "cell biology/cell signaling", "genetics and genomics/plant genetics and gene expression", "molecular biology/transcription initiation and activation", "plant biology", "molecu...	De-Novo Discovery of Differentially Abundant Transcription Factor Binding Sites Including Their Positional Preference	journal.pcbi.1001070	null	[ [ "Gene regulation is a complex process controlled by many influential components such as the binding of proteins to DNA or the binding of miRNAs to mRNA , RNA editing , splicing of pre-mRNA , mRNA degradation , or post-translational modification .", "One of the fundamental regulatory steps is the binding o...	[ "Transcription factors are a main component of gene regulation as they activate or repress gene expression by binding to specific binding sites in promoters .", "The de-novo discovery of transcription factor binding sites in target regions obtained by wet-lab experiments is a challenging problem in computational ...	[ "Binding of transcription factors to promoters of genes , and subsequent enhancement or repression of transcription , is one of the main steps of transcriptional gene regulation .", "Direct or indirect wet-lab experiments allow the identification of approximate regions potentially bound or regulated by a transcri...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "biochemistry", "developmental biology", "pattern formation", "cell fate determination", "animal genetics", "model organisms", "organism development", "drosophila melanogaster", "signaling", "molecular development", "gene identification and analysis", "genetics", "molecula...	Negative Regulation of Notch Signaling by Xylose	journal.pgen.1003547	null	[ [ "Notch signaling is a juxtacrine cell-cell communication pathway with broad roles in animal development and adult tissue homeostasis [1] , [2] .", "Both gain- and loss-of-function mutations in Notch pathway components cause human disease [3]–[5] , and therapeutic approaches to alter the activity of Notch ...	[ "The Notch signaling pathway controls a large number of processes during animal development and adult homeostasis .", "One of the conserved post-translational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like ( EGF ) repeats with a C-X-S-X- ( P/A ) -C moti...	[ "In multi-cellular organisms , neighboring cells need to communicate with each other to ensure proper cell fate decisions and differentiation .", "Signaling through the Notch receptors is the primary means by which local cell-cell communication is accomplished in animals .", "Given the broad usage of Notch sign...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "geographical locations", "tropical diseases", "database searching", "microbiology", "parasitic diseases", "health care", "retroviruses", "viruses", "immunodeficiency viruses", "bacterial disea...	A Systematic Review of the Incidence, Risk Factors and Case Fatality Rates of Invasive Nontyphoidal Salmonella (iNTS) Disease in Africa (1966 to 2014)	journal.pntd.0005118	null	[ [ "Nontyphoidal Salmonellae ( NTS ) are a major cause of food borne infections throughout the developed and developing world [1] .", "Although infection most often results in self-limited acute gastroenteritis , NTS have been identified as a major cause of invasive bacterial infections in infants and young ...	[ "This study systematically reviews the literature on the occurrence , incidence and case fatality rate ( CFR ) of invasive nontyphoidal Salmonella ( iNTS ) disease in Africa from 1966 to 2014 .", "Data on the burden of iNTS disease in Africa are sparse and generally have not been aggregated , making it difficult ...	[ "Although Salmonella are a common global cause of mild gastro-intestinal illness that usually presents with self-limiting diarrhoea , the invasive nontyphoidal form of Salmonella disease manifests as bacteraemia which often presents only with fever .", "If left untreated , iNTS disease often results in death .", ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "engineering and technology", "motion detectors", "signal processing", "membrane potential", "electrophysiology", "light", "neuroscience", "signal filtering", "electromagnetic radiation", "luminance", "visible light", "neuronal dendrites", "animal cells", ...	A biophysical mechanism for preferred direction enhancement in fly motion vision	journal.pcbi.1006240	null	[ [ "Motion represents an essential visual cue , used for predator avoidance , prey capture and visual navigation throughout the animal kingdom .", "Accordingly , motion-sensitive neurons are found in various brain areas of vertebrates and invertebrates alike .", "Prominent and well-studied examples are r...	[ "Seeing the direction of motion is essential for survival of all sighted animals .", "Consequently , nerve cells that respond to visual stimuli moving in one but not in the opposite direction , so-called ‘direction-selective’ neurons , are found abundantly .", "In general , direction selectivity can arise by ei...	[ "Seeing the direction of motion is essential for survival of all sighted animals .", "Consequently , nerve cells that respond preferentially to visual stimuli moving in a certain direction are found abundantly .", "However , directional information is not represented at the level of single photoreceptors but ra...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "organism development", "genetic screens", "genetics", "organogenesis", "biology", "morphogenesis", "genetics and genomics" ]	A Systematic Screen for Tube Morphogenesis and Branching Genes in the Drosophila Tracheal System	journal.pgen.1002087	null	[ [ "Elucidating the genetic programs of organ formation and maintenance is a central goal of developmental biology and medicine .", "Many organogenesis genes have been isolated in systematic genetic screens in model organisms , and many others have been identified by their organ-selective expression patterns...	[ "Many signaling proteins and transcription factors that induce and pattern organs have been identified , but relatively few of the downstream effectors that execute morphogenesis programs .", "Because such morphogenesis genes may function in many organs and developmental processes , mutations in them are expected...	[ "Elucidating the genetic programs that control formation and maintenance of body organs is a central goal of developmental biology , and understanding how these programs go awry in disease has important implications for medicine .", "Many such organogenesis genes have been identified , but most are early-acting “...	2011
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "antimicrobials", "deletion mutation", "medicine and health sciences", "evolutionary biology", "cell cycle and cell division", "drugs", "cell processes", "population genetics", "microbiology", "precursor cells", "gene pool", "physiological processes", "mutation", "antibiotics", "material...	Essential gene deletions producing gigantic bacteria	journal.pgen.1008195	null	[ [ "In spite of controlling the most fundamental biological processes , essential genes are usually missing from loss-of-function mutant screens because strains carrying null mutations are not represented .", "Although essential functions can be studied using conditional alleles , such as temperature-sensiti...	[ "To characterize the consequences of eliminating essential functions needed for peptidoglycan synthesis , we generated deletion mutations of Acinetobacter baylyi by natural transformation and visualized the resulting microcolonies of dead cells .", "We found that loss of genes required for peptidoglycan precursor...	[ "Although essential genes control the most basic functions of bacterial life , they are difficult to study genetically because mutants lacking the functions die .", "We have developed a simple procedure for creating bacteria in which different essential genes have been completely deleted , making it possible to a...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular stress responses", "microbiology", "mitosis", "model organisms", "dna replication", "dna", "dna synthesis", "mycology", "chromosome biology", "schizosaccharomyces pombe", "biology", "molecular biology", "yeast", "cell biology", "nucleic acids", "genetics", "yeast and fungal...	Recovery of Arrested Replication Forks by Homologous Recombination Is Error-Prone	journal.pgen.1002976	null	[ [ "Maintenance of genome stability requires the faithful and accurate replication of the genetic material .", "Genome instability is a hallmark for most types of cancer and it is strongly associated with predisposition to cancer in many human syndromes ( for a review , see [1] , [2] ) .", "Genome instab...	[ "Homologous recombination is a universal mechanism that allows repair of DNA and provides support for DNA replication .", "Homologous recombination is therefore a major pathway that suppresses non-homology-mediated genome instability .", "Here , we report that recovery of impeded replication forks by homologous...	[ "The appropriate transmission of genetic material during successive cell divisions requires the accurate duplication and segregation of parental DNA .", "The semi-conservative replication of chromosomes during S-phase is highly accurate and prevents accumulation of deleterious mutations .", "However , during ea...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "kala-azar", "medicine and health sciences", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "vertebrates", "parasitic diseases", "dogs", "animals", "mammals", "parasitic protozoans", "protozoans", "leishmania", "neglected tropical diseases", "public a...	Failure of the dog culling strategy in controlling human visceral leishmaniasis in Brazil: A screening coverage issue?	journal.pntd.0007553	null	[ [ "Human visceral leishmaniasis ( VL ) is a neglected vector-borne disease of great public health significance .", "The disease is endemic in more than 60 countries , with estimated 200 , 000 to 400 , 000 human cases and 20 , 000 to 40 , 000 deaths occurring annually worldwide [1] .", "In the Americas ,...	[ "In the present study , we assessed the annual screening coverage ( i . e . , the percentage of dogs that are screened for anti-Leishmania antibodies annually ) in the municipality of Sobral , Ceará state , Brazil .", "Data on the number of dogs screened during 2008−2017 ( except 2010 ) were obtained from the Cen...	[ "The euthanasia of Leishmania-seropositive dogs has been recommended for controlling human visceral leishmaniasis ( VL ) in some countries where this zoonosis is endemic .", "We assessed the annual screening coverage ( i . e . , the percentage of dogs living in a given area that are screened for anti-Leishmania a...	2019
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[]	IL-22 Mediates Goblet Cell Hyperplasia and Worm Expulsion in Intestinal Helminth Infection	journal.ppat.1003698	null	[ [ "Type 2 immune responses are essential in protection against intestinal helminth infections , including the rodent hookworm Nippostrongylus brasiliensis ( Nb ) [1] .", "Type 2 immunity involves the recruitment of effector cells such as eosinophils , mast cells and production of IgE antibodies [2] and it i...	[ "Type 2 immune responses are essential in protection against intestinal helminth infections .", "In this study we show that IL-22 , a cytokine important in defence against bacterial infections in the intestinal tract , is also a critical mediator of anti-helminth immunity .", "After infection with Nippostrongyl...	[ "Intestinal helminth ( worm ) infections are some of the most common parasite infections in the world .", "Immunity to worm infection is dependent on the production of Type 2 cytokines , such as IL-4 and IL-13 , and the induction of mucosal defence mechanisms including production of mucus by intestinal goblet cel...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "yeast and fungi", "microbiology", "evolutionary biology", "molecular biology" ]	Many Globally Isolated AD Hybrid Strains of Cryptococcus neoformans Originated in Africa	journal.ppat.0030114	null	[ [ "The impact of hybridization between fungal species and varieties on their evolution", "is unresolved .", "Hybridization may be considered an evolutionary disadvantage because", "some interspecies hybrids have reduced fitness [1 , 2] .", "Alternatively , natural hybridization may be beneficial...	[ "Interspecific and intervarietal hybridization may contribute to the biological", "diversity of fungal populations .", "Cryptococcus neoformans is a pathogenic yeast and the most", "common fungal cause of meningitis in patients with AIDS .", "Most patients are", "infected with either of the two varieties ...	[ "Hybridization between individuals of different species or varieties is common", "among fungi .", "However , the impact of hybridization on the evolution of", "pathogenic fungi is unresolved .", "Several hybrids of phytopathogenic fungi", "exhibit expanded host ranges .", "To our knowledge , this report...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Glypican Is a Modulator of Netrin-Mediated Axon Guidance	journal.pbio.1002183	Work in nematodes shows that the proteoglycan glypican acts as an extracellular modulator of netrin signals during nervous system development, interacting with cells that express the netrin receptor.	[ [ "Directed migrations of developing axons are essential for the proper wiring of the nervous system .", "A host of guidance cues and their receptors instruct axon guidance decisions .", "However , how these cues and the growth cone’s responses to them are spatially and temporally regulated in vivo rema...	[ "Netrin is a key axon guidance cue that orients axon growth during neural circuit formation .", "However , the mechanisms regulating netrin and its receptors in the extracellular milieu are largely unknown .", "Here we demonstrate that in Caenorhabditis elegans , LON-2/glypican , a heparan sulfate proteoglycan ...	[ "During the development of the nervous system , migrating axons are guided as they navigate through complex environments to reach their target destinations .", "These directed migrations are essential to ensure the proper wiring and function of the nervous system and are instructed by guidance cues and receptors ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "invertebrates", "rna interference", "caenorhabditis", "animals", "dna transcription", "animal models", "developmental biology", "caenorhabditis elegans", "model organisms", "epigenetics", "embryos", "research and analysis methods", "embryology", "genome complexity", ...	A Conserved Nuclear Cyclophilin Is Required for Both RNA Polymerase II Elongation and Co-transcriptional Splicing in Caenorhabditis elegans	journal.pgen.1006227	null	[ [ "Transcription by RNA Polymerase II ( Pol II ) is a highly regulated process involving coordination of multiple processes that together modulate the level of gene expression and its temporal and spatial control [1–4] .", "Epigenetic mechanisms play important roles in both transcription initiation and elon...	[ "The elongation phase of transcription by RNA Polymerase II ( Pol II ) involves numerous events that are tightly coordinated , including RNA processing , histone modification , and chromatin remodeling .", "RNA splicing factors are associated with elongating Pol II , and the interdependent coupling of splicing an...	[ "mRNA splicing can occur co-transcriptionally; i . e . , splicing occurs as the RNA emerges from the RNA Polymerase II holoenzyme during transcription elongation .", "Recent studies suggest that defective splicing can cause defective transcription elongation , suggesting an interdependency of the two mechanisms ....	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "enzyme-linked immunoassays", "immunology", "tropical diseases", "variant genotypes", "genetic mapping", "biochemical analysis", "bacterial diseases", "developmental...	Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy	journal.pntd.0005754	null	[ [ "Leprosy reactions affect up to 50% of patients [1] .", "They are episodes that disrupt the natural course of disease , characterized by a strong and abrupt reactivation of immune responses [2–4] .", "Generally , nerve injury is present , which may lead to permanent incapacities .", "At the onset ...	[ "The pathways that trigger exacerbated immune reactions in leprosy could be determined by genetic variations .", "Here , in a prospective approach , both genetic and non-genetic variables influencing the amount of time before the development of reactional episodes were studied using Kaplan–Meier survival curves ,...	[ "Leprosy reactions are abrupt inflammatory episodes that can occur before , during or after treatment .", "Although reactional episodes are the main cause of physical disabilities in patients , there are few genetic studies evaluating this outcome .", "We studied the influence of both risk factors and genetic m...	2017
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "livestock", "medicine and health sciences", "tropical diseases", "geographical locations", "sudan", "rift valley fever", "neglected tropical diseases", "infectious disease control", "veterinarians", "africa", "veterinary science", "veterinary medicine", "infectious diseases", "veterinary ...	The One Health approach to identify knowledge, attitudes and practices that affect community involvement in the control of Rift Valley fever outbreaks	journal.pntd.0005383	null	[ [ "Global outbreak of zoonotic infections , not only affect human and animal health but also affect food security , and socio-economic stability .", "To control such outbreaks require local as well regional cooperation .", "Most zoonotic outbreaks begin and occur in settings where resources are poor and...	[ "Rift Valley fever ( RVF ) is a viral mosquito-borne disease with the potential for global expansion , causes hemorrhagic fever , and has a high case fatality rate in young animals and in humans .", "Using a cross-sectional community-based study design , we investigated the knowledge , attitudes and practices of ...	[ "Rift Valley fever ( RVF ) , is a neglected , emerging , mosquito-borne disease that has caused outbreaks in Africa and the Arabian Peninsula .", "RVF outbreaks have a severe negative impact on livestock , human health and economy , placing further demands on communities already experiencing high levels of povert...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "cell biology/gene expression", "molecular biology/transcription initiation and activation", "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "molecular biology/transcription elongation", "genetics and genomics/epigenetics", ...	The Euchromatic and Heterochromatic Landscapes Are Shaped by Antagonizing Effects of Transcription on H2A.Z Deposition	journal.pgen.1000687	null	[ [ "Chromatin dynamics is now well recognized as key in the regulation of nuclear processes such as gene expression , DNA replication and DNA repair , therefore impinging on biological phenomena such as cellular differentiation as well as normal and cancer development .", "Cells have developed strategies to ...	[ "A role for variant histone H2A . Z in gene expression is now well established but little is known about the mechanisms by which it operates .", "Using a combination of ChIP–chip , knockdown and expression profiling experiments , we show that upon gene induction , human H2A . Z associates with gene promoters and ...	[ "DNA in living cells is packaged into chromatin by histones and non-histone proteins .", "This packaging is very dynamic , allowing the controlled access of regulatory proteins such as transcription factors to DNA .", "Most chromatin is packaged with so-called canonical histones; namely H2A , H2B , H3 , and H4 ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Synthetic Lethality between Gene Defects Affecting a Single Non-essential Molecular Pathway with Reversible Steps	journal.pcbi.1003016	null	[ [ "Synthetic interactions between two mutations in different genes were first revealed in Drosophila by Dobzhansky in the 1940s [1] .", "Synthetic lethality ( SL ) describes that two viable single gene mutations lead to lethality ( synthetic-lethal ) or severely impair growth ( synthetic-sick ) when combine...	[ "Systematic analysis of synthetic lethality ( SL ) constitutes a critical tool for systems biology to decipher molecular pathways .", "The most accepted mechanistic explanation of SL is that the two genes function in parallel , mutually compensatory pathways , known as between-pathway SL .", "However , recent g...	[ "Organizing gene functions into molecular pathways is a major challenge in biology .", "The observation that two viable gene mutations become lethal when combined as a double mutant has been developed into a major genetic tool called synthetic lethality .", "The classic interpretation of synthetic lethality sti...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "zoonoses", "skin infections", "smallpox", "global health", "neglected tropical diseases", "viral diseases", "public health" ]	Assessing the Effectiveness of a Community Intervention for Monkeypox Prevention in the Congo Basin	journal.pntd.0001356	null	[ [ "Human monkeypox ( MPX ) is caused by infection with Monkeypox virus ( MPXV ) , a member of the Orthopoxvirus genus in the family Poxviridae .", "The clinical manifestations of severe MPX bear pronounced similarity to those of smallpox , though fatality rates are consistently lower for monkeypox [1]–[4] ....	[ "In areas where health resources are limited , community participation in the recognition and reporting of disease hazards is critical for the identification of outbreaks .", "This is particularly true for zoonotic diseases such as monkeypox that principally affect people living in remote areas with few health se...	[ "Human monkeypox is a potentially severe illness that begins with a high fever soon followed by the development of a smallpox-like rash .", "Both monkeypox and smallpox are caused by infection with viruses in the genus Orthopoxvirus .", "But smallpox , which only affected humans , has been eradicated , whereas ...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "pharmacology/drug resistance", "genetics and genomics/population genetics" ]	Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin Treatment	journal.pntd.0000072	null	[ [ "Onchocerca volvulus is the filarial nematode , transmitted by", "Simulium flies , that causes human onchocerciasis , or", "“river blindness” .", "It is estimated that 37 million people ,", "mostly in Africa , are infected with this worm [1] .", "At present , ivermectin", "( IVM , Mect...	[ "Onchocerca volvulus is the causative agent of", "onchocerciasis , or “river blindness” .", "Ivermectin has", "been used for mass treatment of onchocerciasis for up to 18 years , and", "recently there have been reports of poor parasitological responses to the", "drug .", "Should ivermectin resistance be...	[ "Onchocerca volvulus is the causative agent of onchocerciasis , or", "“river blindness” .", "Ivermectin has been used for mass", "treatment of onchocerciasis for up to 18 years , and recently there have been", "reports of poor parasitological responses to the drug and evidence of drug", "resistance .", ...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "computer science", "evolutionary ecology", "computer modeling", "theoretical biology", "ecology", "population modeling", "epidemiology", "infectious disease epidemiology", "theoretical ecology", "population biology", "infectious disease modeling", "biology", "evolutionary biology", "compu...	Host Resistance, Population Structure and the Long-Term Persistence of Bubonic Plague: Contributions of a Modelling Approach in the Malagasy Focus	journal.pcbi.1003039	null	[ [ "Although bubonic plague has marked human history by three pandemics ( Justinian plague in the – centuries , Medieval plague in the – centuries and Asiatic plague since 1894 [1] ) , this zoonosis caused by the coccobacillus Yersinia pestis is primarily a rodent disease .", "Its persistent circulation in w...	[ "Although bubonic plague is an endemic zoonosis in many countries around the world , the factors responsible for the persistence of this highly virulent disease remain poorly known .", "Classically , the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague suscept...	[ "Bubonic plague , known to have marked human history by three deadly pandemics , is an infectious disease which mainly circulates in wild rodent populations and is transmitted by fleas .", "Although this disease can be quickly lethal to its host , it has persisted on long-term in many rodent populations around th...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biophysic al simulations", "biology", "computational biology" ]	Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation	journal.pcbi.1002169	null	[ [ "Defining the rules of protein folding , a process by which a sequence of amino acids self-assembles into a specific functional conformation , is one of the great challenges in molecular biology [1]–[3] .", "In addition , deciphering the causes of misfolding , which can often result in the formation of -s...	[ "Identifying the forces that drive proteins to misfold and aggregate , rather than to fold into their functional states , is fundamental to our understanding of living systems and to our ability to combat protein deposition disorders such as Alzheimer's disease and the spongiform encephalopathies .", "We report h...	[ "In order to carry out their biological functions , most proteins fold into well-defined conformations known as native states .", "Failure to fold , or to remain folded correctly , may result in misfolding and aggregation , which are processes associated with a wide range of highly debilitating , and so far incur...	2011
[ "Introduction", "Results and Discussion", "Conclusions", "Materials and Methods" ]	[ "allosteric regulation", "crystal structure", "protein interaction networks", "condensed matter physics", "enzymology", "network analysis", "chaperone proteins", "protein structure", "dna", "dna structure", "crystallography", "enzyme chemistry", "computer and information sciences", "solid ...	Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication	journal.pcbi.1005299	null	[ [ "The evolutionary conserved and versatile 70-kilodalton ( kDa ) heat shock proteins Hsp70s play a central role in supervision of various protein folding processes and coordination of a broad range of cellular events–from maintenance of cellular homeostasis to regulation of the heat shock response [1–8] .", ...	[ "Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions .", "Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy o...	[ "The diversity of allosteric mechanisms in the Hsp70 proteins could range from modulation of the inter-domain interactions and conformational dynamics to fine-tuning of the Hsp70 interactions with co-chaperones .", "The goal of this study is to present a systematic computational analysis of the dynamic and evolut...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/antigen processing and recognition", "infectious diseases/hiv infection and aids", "virology/immune evasion", "immunology/immunity to infections", "virology/host antiviral responses" ]	The Antiviral Efficacy of HIV-Specific CD8+ T-Cells to a Conserved Epitope Is Heavily Dependent on the Infecting HIV-1 Isolate	journal.ppat.1001341	null	[ [ "One of the greatest challenges in developing an effective T-cell based vaccine against HIV-1 is its high genetic variability [1] .", "Group M HIV-1 has expanded globally into 15 major clades , sub-clades and several interclade circulating recombinant forms .", "These continually evolving HIV-1 clades...	[ "A major challenge to developing a successful HIV vaccine is the vast diversity of viral sequences , yet it is generally assumed that an epitope conserved between different strains will be recognised by responding T-cells .", "We examined whether an invariant HLA-B8 restricted Nef90–97 epitope FL8 shared between ...	[ "One of the greatest challenges to developing an effective HIV vaccine is the ability of HIV to rapidly alter its viral sequence .", "Such variation in viral sequence enables the virus to frequently evade recognition by the host immune system .", "To counteract this problem , there has been increasing interest ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Evolution and Design Governing Signal Precision and Amplification in a Bacterial Chemosensory Pathway	journal.pgen.1005460	null	[ [ "In living cells , adaptation to rapid changes in environmental conditions requires coordinated rearrangements of basic cellular processes to adjust the cellular homeostasis to the new conditions .", "In general , receptor molecules sense environmental changes and translate them into a cellular response b...	[ "Understanding the principles underlying the plasticity of signal transduction networks is fundamental to decipher the functioning of living cells .", "In Myxococcus xanthus , a particular chemosensory system ( Frz ) coordinates the activity of two separate motility systems ( the A- and S-motility systems ) , pro...	[ "Deciphering the circuit design of signal transduction networks is a fundamental question in cell biology .", "This task is challenging because many pathways are branched and control multiple cellular processes in response to one or several environmental signals .", "Studying pathway diversification in bacteria...	2015
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "microbiology", "parasitic protozoans", "animals", "parasitology", "glossina", "protozoans", "tsetse fly", "epidemiology", "pathogenesis", "disease vectors", "insects", "arthropoda", "trypanosoma", ...	An Investigation into the Protein Composition of the Teneral Glossina morsitans morsitans Peritrophic Matrix	journal.pntd.0002691	null	[ [ "The concept of blocking trypanosome development within its tsetse host has been underexplored , primarily due to a lack of understanding the molecular events involved in the vector-parasite interactions and also difficulties in accessing an established colony of tsetse flies needed to implement such studies ...	[ "Tsetse flies serve as biological vectors for several species of African trypanosomes .", "In order to survive , proliferate and establish a midgut infection , trypanosomes must cross the tsetse fly peritrophic matrix ( PM ) , which is an acellular gut lining surrounding the blood meal .", "Crossing of this mul...	[ "African trypanosomes are transmitted by the haematophagous tsetse vector .", "For transmission to occur , bloodmeal ingested trypanosomes must overcome numerous barriers imposed by the fly .", "The first obstacle is the crossing of peritrophic matrix ( PM ) , a cell-free structure that protects the midgut epit...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "innate immune system", "immunity", "virology", "emerging viral diseases", "biology and life sciences", "immunology", "microbiology", "immune system" ]	Sensing of Immature Particles Produced by Dengue Virus Infected Cells Induces an Antiviral Response by Plasmacytoid Dendritic Cells	journal.ppat.1004434	null	[ [ "The innate immune system acts as the first line of defense for the sensing of viral infection .", "This involves rapid recognition of pathogen-associated molecular patterns ( PAMPs ) , including viral nucleic acids , by pattern recognition receptors ( PRRs ) .", "This recognition results in an antivi...	[ "Dengue virus ( DENV ) is the leading cause of mosquito-borne viral illness and death in humans .", "Like many viruses , DENV has evolved potent mechanisms that abolish the antiviral response within infected cells .", "Nevertheless , several in vivo studies have demonstrated a key role of the innate immune resp...	[ "Viral recognition by the host often triggers an antiviral state , which suppresses viral spread and imparts adaptive immunity .", "Like many viruses , dengue virus ( DENV ) defeats the host-sensing pathway within infected cells .", "However , in vivo studies have demonstrated a key role of innate immunity in c...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "complement system", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "zymogens", "enzymes", "pathogens", "immunology", "microbiology", "enzymology", "enzyme inhibitors", "bacteria", "bacterial pathogens", "immune system proteins", "complement inh...	Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex	journal.ppat.1005404	null	[ [ "Complement is an interconnected system of serum and cell surface proteins that comprises a primary arm of innate immunity .", "Complement acts in the recognition and clearance of microbial invaders and terminal activation of the complement cascade can result in direct lysis of pathogens .", "In addit...	[ "Pathogens that traffic in blood , lymphatics , or interstitial fluids must adopt strategies to evade innate immune defenses , notably the complement system .", "Through recruitment of host regulators of complement to their surface , many pathogens are able to escape complement-mediated attack .", "The Lyme dis...	[ "The human complement system is a connected network of blood proteins capable of recognizing and eliminating microbial intruders .", "To avoid the destructive force of complement activation , many microorganisms that enter the bloodstream express molecules that disrupt key steps of the complement cascade by inter...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli	journal.pcbi.1004430	null	[ [ "Efficient processing of incoming sensory information is essential to an organism’s survival .", "Thus , understanding the strategies used by the brain to process such information ( the neural code ) remains an important problem in neuroscience .", "There is growing experimental evidence that the repr...	[ "Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems .", "Such responses emerge in higher brain areas , thereby suggesting that they occur by integrating afferent input .", "However , the mechanisms by which such integra...	[ "We provide the first experimental evidence showing that midbrain electrosensory neurons in the weakly electric fish species Apteronotus leptorhynchus can respond in an invariant manner to the heterogeneous stimulus waveforms associated with natural electrocommunication stimuli .", "Interestingly , hindbrain neur...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover	journal.pbio.1002291	Tolerance to errors during protein synthesis evolves rapidly through acceleration of protein turnover—a process determined by the combined rates of protein synthesis and degradation. However, this adaptation has deleterious side effects due to its energy costs.	[ [ "Fidelity of protein synthesis has a substantial impact on cellular survival [1 , 2] .", "There might be incorporation of one amino acid for another ( missense errors ) , premature termination of protein synthesis , frameshift errors and read-through of stop codons ( nonsense errors ) .", "Even if the...	[ "Translational errors occur at high rates , and they influence organism viability and the onset of genetic diseases .", "To investigate how organisms mitigate the deleterious effects of protein synthesis errors during evolution , a mutant yeast strain was engineered to translate a codon ambiguously ( mistranslati...	[ "Although fidelity of information transfer has a substantial impact on cellular survival , many steps in protein production are strikingly error-prone .", "Such errors during protein synthesis can have a substantial influence on viability and the onset of genetic diseases .", "These considerations raise the que...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "cell physiology", "medicine and health sciences", "pathology and laboratory medicine", "chemical compounds", "gene regulation", "endothelial cells", "pathogens", "cell processes", "salts", "microbiology", "epithelial cells", "viruses", "rna viruses", "glycosylation", "...	Endocytosis of flavivirus NS1 is required for NS1-mediated endothelial hyperpermeability and is abolished by a single N-glycosylation site mutation	journal.ppat.1007938	null	[ [ "Dengue virus ( DENV ) is a mosquito-borne flavivirus , and infection with any of its four serotypes ( DENV1-4 ) can result in inapparent infection , classic dengue fever , or dengue hemorrhagic fever/dengue shock syndrome–severe manifestations characterized by vascular leak that can lead to shock and death [...	[ "Arthropod-borne flaviviruses cause life-threatening diseases associated with endothelial hyperpermeability and vascular leak .", "We recently found that vascular leak can be triggered by dengue virus ( DENV ) non-structural protein 1 ( NS1 ) via the disruption of the endothelial glycocalyx-like layer ( EGL ) .",...	[ "Vascular leak is a hallmark of severe dengue disease .", "Recently , our group revealed a critical role for NS1 in induction of endothelial hyperpermeability and vascular leakage in an endothelial cell-intrinsic manner .", "However , the upstream pathway triggered by NS1 , as well as the molecular determinants...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "infectious diseases", "infectious diseases/neglected tropical diseases", "computational biology/comparative sequence analysis", "biochemistry/protein chemistry", "infectious diseases/helminth infections", "biochemistry/bioinformatics", "computational biology", "infectious diseases/t...	SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni	journal.pntd.0000449	null	[ [ "Proteases ( proteolytic enzymes , peptidases ) provide essential functions in all life forms [1] .", "Proteases function as key elements of parasitism including hatching , excystment , tissue/cell invasion , nutrient acquisition and immune evasion [2] , [3] .", "For trematode parasites causing diseas...	[ "Blood flukes of the genus Schistosoma are platyhelminth parasites that infect 200 million people worldwide .", "Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction .", "A network of proteolytic enzymes ( proteases ) facilitates hydrolysis of host hemoglobin a...	[ "Parasitic infection caused by blood flukes of the genus Schistosoma is a major global health problem .", "More than 200 million people are infected .", "Identifying and characterizing the constituent enzymes of the parasite's biochemical pathways should reveal opportunities for developing new therapies ( i . e...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "topographic maps", "ocular anatomy", "social sciences", "neuroscience", "simulation and modeling", "ganglion cells", "nerve fibers", "vision", "neuronal dendrites", "research and analysis methods", "geography", "animal cells", "axons", "cartography", "c...	Novel Models of Visual Topographic Map Alignment in the Superior Colliculus	journal.pcbi.1005315	null	[ [ "Processing sensory information is a critical task of the central nervous system , requiring the establishment of precisely ordered synaptic connectivity during development .", "In the visual system , image-forming regions are organized into topographics maps , such that neighboring neurons monitor adjace...	[ "The establishment of precise neuronal connectivity during development is critical for sensing the external environment and informing appropriate behavioral responses .", "In the visual system , many connections are organized topographically , which preserves the spatial order of the visual scene .", "The super...	[ "In order to process sensory stimuli , precise connections must be established between sensory neurons during development .", "In the visual system , many connections are organized topographically , such that neighboring neurons monitor adjacent regions of space .", "In the superior colliculus ( SC ) , convergi...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "plant science", "model organisms", "plant biology", "genetics", "biology", "genomics", "molecular cell biology", "genetics and genomics" ]	Transcriptome Analysis of the Arabidopsis Megaspore Mother Cell Uncovers the Importance of RNA Helicases for Plant Germline Development	journal.pbio.1001155	null	[ [ "The life cycle of flowering plants alternates between a diploid sporophytic and a haploid gametophytic phase .", "In contrast to animals , which form gametes directly by meitotic division from a diploid germline , plants form female and male spores by meiotic division during megasporogenesis and microspo...	[ "Germ line specification is a crucial step in the life cycle of all organisms .", "For sexual plant reproduction , the megaspore mother cell ( MMC ) is of crucial importance: it marks the first cell of the plant “germline” lineage that gets committed to undergo meiosis .", "One of the meiotic products , the fun...	[ "Germline specification is a key step in sexual reproduction .", "In plants , the reproductive lineage or “germline” doesn't arise early in development , as it does in animals; rather , the germline is specified during flower development .", "In the female reproductive organs of the flower , a single sporophyti...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/disease models", "developmental biology/neurodevelopment", "neurological disorders/movement disorders" ]	Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect	journal.pgen.1000914	null	[ [ "Parkinson's disease ( PD ) is a common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta ( SNpc ) and movement symptoms , including resting tremor , rigidity and postural instability [1] .", "The vast majority of PD patients are i...	[ "LRRK2 plays an important role in Parkinson's disease ( PD ) , but its biological functions are largely unknown .", "Here , we cloned the homolog of human LRRK2 , characterized its expression , and investigated its biological functions in zebrafish .", "The blockage of zebrafish LRRK2 ( zLRRK2 ) protein by morp...	[ "Parkinson's disease ( PD ) is a degenerative disease of the brain ( central nervous system ) that often impairs motor skills , speech , and other functions .", "PD was long thought to be caused by environmental factors , but the discovery of several gene mutations in the patients ( mostly with familial form of P...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "genome engineering", "cancer detection and diagnosis", "medicine and health sciences", "engineering and technology", "synthetic biology", "genomic library screening", "health care", "crispr", "synthetic bioengineering", "oncology", "decision analysis", "management engineeri...	Correction of copy number induced false positives in CRISPR screens	journal.pcbi.1006279	null	[ [ "CRISPR based loss-of-function screens have emerged as a powerful tool to interrogate multiple species and models [1] .", "The technology has been quickly adopted to identify essential genes in cancer , including several cancer cell line screens [2–4] .", "However , as reported in two studies [5 , 6] ...	[ "Cell autonomous cancer dependencies are now routinely identified using CRISPR loss-of-function viability screens .", "However , a bias exists that makes it difficult to assess the true essentiality of genes located in amplicons , since the entire amplified region can exhibit lethal scores .", "These false-posi...	[ "Cancer vulnerabilities have been identified by systematically disrupting individual genes in cancer cells and observing the resulting effect on cell proliferation .", "In recent years , a new gene editing technique called CRISPR has made it easier and cheaper to disrupt genes by precisely and completely suppress...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genetic Regulation of Bone Metabolism in the Chicken: Similarities and Differences to Mammalian Systems	journal.pgen.1005250	null	[ [ "The genetic basis of bone mineral density in the chicken is of both theoretical and practical importance .", "On the theoretical side , domestication is an example of intense directional selection causing wide-ranging differences in the phenotype of domestic animals compared to their wild progenitors .",...	[ "Birds have a unique bone physiology , due to the demands placed on them through egg production .", "In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling .", "We take advantage of the fact that bone traits have diverge...	[ "In this work we seek to further the understanding of bone genetics by mapping bone traits and gene expression in the chicken .", "Bone in female birds is special due to egg production .", "In this study , we combine the genetic mapping of bone traits with bone gene expression to find candidate quantitative tra...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "genome-wide association studies", "cell physiology", "medicine and health sciences", "breast tumors", "chemical characterization", "cancers and neoplasms", "oncology", "genome analysis", "sequence motif analysis", "epigenetics", "chromatin", "research and analysis methods", ...	Identification of breast cancer associated variants that modulate transcription factor binding	journal.pgen.1006761	null	[ [ "Genome-wide association studies ( GWAS ) have identified more than 90 genomic loci and common genetic variants associated with breast cancer [1–5] .", "The single nucleotide polymorphisms ( SNPs ) associated with breast cancer have been shown to be enriched in DNA regulatory regions [6 , 7] , with few re...	[ "Genome-wide association studies ( GWAS ) have discovered thousands loci associated with disease risk and quantitative traits , yet most of the variants responsible for risk remain uncharacterized .", "The majority of GWAS-identified loci are enriched for non-coding single-nucleotide polymorphisms ( SNPs ) and de...	[ "The promise of effective personalized medicine is dependent upon the ability to identify genetic variants in the population that influence disease risk and then use this information to accurately predict the likelihood of disease incidence for individual patients .", "High-risk individuals may be entered into cl...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Fusion of Large-Scale Genomic Knowledge and Frequency Data Computationally Prioritizes Variants in Epilepsy	journal.pgen.1003797	null	[ [ "Interpretation of high-resolution array comparative genomic hybridization ( aCGH ) data is made challenging by the large number of copy number variation ( CNV ) events identified in each individual .", "Analogous problems arise in interpretation of deep sequencing data where the number of variants rapidl...	[ "Curation and interpretation of copy number variants identified by genome-wide testing is challenged by the large number of events harbored in each personal genome .", "Conventional determination of phenotypic relevance relies on patterns of higher frequency in affected individuals versus controls; however , an i...	[ "Improvements in sequencing and microarray technologies have increased the resolution and scope of genetic testing .", "As a result , millions of variations are identified in each personal genome of unrelated individuals .", "In the context of testing for genetic diseases , identifying the variant or variants c...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/neuronal signaling mechanisms", "neuroscience/theoretical neuroscience", "biophysics/theory and simulation", "biochemistry/theory and simulation" ]	Dynamic Conformational Changes in MUNC18 Prevent Syntaxin Binding	journal.pcbi.1001097	null	[ [ "Intracellular membrane fusion in eukaryotes is mediated by a well-conserved fusion machinery composed of SNARE ( soluble N-ethylmaleimide-sensitive factor attachment protein receptor ) and SM ( Sec1/munc18-like ) proteins [1] .", "In the early studies , munc18a was shown to bind syntaxin , one of the cen...	[ "The Sec1/munc18 protein family is essential for vesicle fusion in eukaryotic cells via binding to SNARE proteins .", "Protein kinase C modulates these interactions by phosphorylating munc18a thereby reducing its affinity to one of the central SNARE members , syntaxin-1a .", "The established hypothesis is that ...	[ "Protein phosphorylation plays a significant regulatory role in multi-component systems engaged in signal transduction or coordination of cellular processes , by activating or deactivating proteins .", "The potential of phosphorylation to induce substantial conformational changes in proteins , thereby changing th...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Serine Protease EspC from Enteropathogenic Escherichia coli Regulates Pore Formation and Cytotoxicity Mediated by the Type III Secretion System	journal.ppat.1005013	null	[ [ "EPEC and EHEC are related pathogens causing severe diarrhoeal diseases .", "EPEC and EHEC form Attaching and Effacing ( A/E ) lesions on the mucosal intestinal surface , corresponding to the destruction of enterocyte microvilli and the intimate bacterial adherence to the host cell plasma membrane onto an...	[ "Type III secretion systems ( T3SSs ) are specialized macromolecular machines critical for bacterial virulence , and allowing the injection of bacterial effectors into host cells .", "The T3SS-dependent injection process requires the prior insertion of a protein complex , the translocon , into host cell membranes...	[ "Enteropathogenic Escherichia coli ( EPEC ) is an important diarrheal pathogen responsible for infant diarrhoea associated with significant morbidity and mortality rates in developing countries .", "Upon ingestion EPEC colonizes the intestinal mucosa , causing characteristic lesions on enterocytes .", "Using a ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "taxonomy", "medicine and health sciences", "ecology and environmental sciences", "immune physiology", "immunology", "population genetics", "antigenic variation", "vaccines", "phylogenetics", "data management", "population biology", "infectious disease control", "immune system proteins", "...	The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome	journal.ppat.1006966	null	[ [ "Pneumococcal conjugate vaccines ( PCV ) target capsular serotype-specific polysaccharides of the respiratory pathogen Streptococcus pneumoniae , which causes substantial morbidity and mortality [1 , 2] .", "Since the heptavalent PCV and 13-valent PCV were introduced in the United States ( US ) in 2000 an...	[ "In the United States , the introduction of the heptavalent pneumococcal conjugate vaccine ( PCV ) largely eliminated vaccine serotypes ( VT ) ; non-vaccine serotypes ( NVT ) subsequently increased in carriage and disease .", "Vaccination also disrupts the composition of the pneumococcal pangenome , which include...	[ "Pneumococcal disease caused by the bacteria Streptococcus pneumoniae remains a significant cause of morbidity and mortality despite the existence of an effective vaccine .", "This is because the vaccines only target a small proportion of the total pneumococcal population .", "Introduction of vaccine in the Uni...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Neural Modularity Helps Organisms Evolve to Learn New Skills without Forgetting Old Skills	journal.pcbi.1004128	null	[ [ "To test our hypotheses , we set up an environment in which there is a potential for catastrophic forgetting and where individuals able to avoid this forgetting receive a higher evolutionary fitness , meaning they are more likely to reproduce .", "The environment is an abstraction of a world in which an o...	[ "A long-standing goal in artificial intelligence is creating agents that can learn a variety of different skills for different problems .", "In the artificial intelligence subfield of neural networks , a barrier to that goal is that when agents learn a new skill they typically do so by losing previously acquired ...	[ "A long-standing goal in artificial intelligence ( AI ) is creating computational brain models ( neural networks ) that learn what to do in new situations .", "An obstacle is that agents typically learn new skills only by losing previously acquired skills .", "Here we test whether such forgetting is reduced by ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "immune cells", "pathology and laboratory medicine", "immunology", "colitis", "developmental biology", "fungi", "signs and symptoms", "gastroenterology and hepatology", "molecular devel...	Dectin-3 Deficiency Promotes Colitis Development due to Impaired Antifungal Innate Immune Responses in the Gut	journal.ppat.1005662	null	[ [ "Inflammatory bowel disease ( IBD ) , mainly Crohn disease and ulcerative colitis , is a chronic inflammatory disorder of the gut .", "Extensive studies have suggested that the etiology of IBD involves environmental and genetic factors that lead to dysfunction of the epithelial barrier , with consequent d...	[ "Interactions between commensal fungi and gut immune system are critical for establishing colonic homeostasis .", "Here we found that mice deficient in Dectin-3 ( Clec4d-/- ) , a C-type lectin receptor that senses fungal infection , were more susceptible to dextran sodium sulfate ( DSS ) -induced colitis compared...	[ "C-type lectin receptors ( CLRs ) comprise a diverse family of soluble and trans-membrane proteins that function as pattern recognition receptors ( PRRs ) .", "Dectin-3 ( also known as MCL/CLECSF8/Clec4d ) , a myeloid cell-specific CLR family member , could recognize bacterial and fungal components and induce int...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "population modeling", "epidemiology", "infectious disease epidemiology", "disease dynamics", "population dynamics", "population biology", "infectious disease modeling", "biology", "computational biology" ]	Culling Dogs in Scenarios of Imperfect Control: Realistic Impact on the Prevalence of Canine Visceral Leishmaniasis	journal.pntd.0002355	null	[ [ "Visceral leishmaniasis or kala-azar is the most severe clinical form of leishmaniasis , a serious public health problem worldwide [1] , [2] .", "In Latin America , the agent of the so-called American visceral leishmaniasis ( AVL ) is Leishmania ( Leishmania ) chagasi transmitted , in Brazil , mainly by s...	[ "Visceral leishmaniasis belongs to the list of neglected tropical diseases and is considered a public health problem worldwide .", "Spatial correlation between the occurrence of the disease in humans and high rates of canine infection suggests that in the presence of the vector , canine visceral leishmaniasis is ...	[ "Visceral leishmaniasis is listed as a neglected tropical disease and is considered a public health problem worldwide .", "The disease has been documented since 1885 , the first case being reported in India .", "After over 120 years , the incidence of the disease remains high despite control strategies implemen...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity	journal.pgen.1005780	null	[ [ "Making sense of a complex environment requires a high level of functional diversity in neuronal classes that comprise both the peripheral and central nervous system .", "Little is known about how limited genetic resources are utilized to reproducibly spawn a large number of neuronal classes .", "Sens...	[ "Sensory neuron diversity is required for organisms to decipher complex environmental cues .", "In Drosophila , the olfactory environment is detected by 50 different olfactory receptor neuron ( ORN ) classes that are clustered in combinations within distinct sensilla subtypes .", "Each sensilla subtype houses s...	[ "Drosophila uses 50 different olfactory receptor neuron ( ORN ) classes that are clustered in combinations within distinct sensilla subtypes to decipher a complex chemical environment .", "Each sensilla subtype houses 1–4 ORN identities that arise through asymmetric divisions from a single multipotent sensory org...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "missense mutation", "developmental biology", "mutation", "point mutation", "integrins", "animal genetics", "organism development", "invertebrate genetics", "cell biology", "cell adhesion", "embryogenesis", "genetics", "muscle development", "biology and life sciences", "organogenesis", ...	The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering	journal.pgen.1004756	null	[ [ "The formation and maintenance of three-dimensional tissue architecture requires fine-tuning of adhesion between cells and the extracellular matrix ( ECM ) .", "Integrins are the principal family of cell-ECM adhesion receptors in metazoans and are comprised of an alpha and beta subunit [1] .", "The ex...	[ "Talin serves an essential function during integrin-mediated adhesion in linking integrins to actin via the intracellular adhesion complex .", "In addition , the N-terminal head domain of talin regulates the affinity of integrins for their ECM-ligands , a process known as inside-out activation .", "We previousl...	[ "Cells are the building blocks of our bodies .", "How do cells rearrange to form three-dimensional body plans and maintain specific tissue structures ?", "Specialized adhesion molecules on the cell surface mediate attachment between cells and their surrounding environment to hold tissues together .", "Our wor...	2014
[ "Introduction", "Results", "Discussion", "Methods and models" ]	[ "action potentials", "medicine and health sciences", "vesicles", "nervous system", "membrane potential", "electrophysiology", "neuroscience", "synaptic plasticity", "cellular structures and organelles", "neuronal plasticity", "mood disorders", "developmental neuroscience", "animal cells", ...	Estimating short-term synaptic plasticity from pre- and postsynaptic spiking	journal.pcbi.1005738	null	[ [ "Short-term synaptic plasticity ( STP ) refers to fast and reversible changes of synaptic strength caused by the recent history of presynaptic spiking activity [1] .", "STP occurs on timescales from milliseconds to few seconds , and includes mechanisms for both facilitation of transmitter release , where ...	[ "Short-term synaptic plasticity ( STP ) critically affects the processing of information in neuronal circuits by reversibly changing the effective strength of connections between neurons on time scales from milliseconds to a few seconds .", "STP is traditionally studied using intracellular recordings of postsynap...	[ "Information processing in the nervous system critically depends on dynamic changes in the strength of connections between neurons .", "Short-term synaptic plasticity ( STP ) , changes that occur on timescales from milliseconds to a few seconds , is thought to play a role in tasks such as speech recognition , mot...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "immunology", "cell differentiation", "developmental biology", "molecular development", "bioassays and physiological analysis", "cytotoxic t cells", "research and analysis...	Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium	journal.ppat.1005832	null	[ [ "The effective control of infectious agents requires a range of different arms of the immune system .", "CD4+ T cells play a pivotal role in orchestrating these events , including support for both antibody production and the expansion and effector function of CD8+ T cells .", "However it is now well e...	[ "Cytomegalovirus ( CMV ) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people .", "Virus-specific CD8+ T cell responses have been investigated extensively through the use of...	[ "Cytomegalovirus ( CMV ) is a member of the herpesvirus family and most humans carry chronic CMV infection .", "This drives the development of large expansions of CD8+ CMV-specific T cells , which increase further during ageing .", "CMV infection is associated with vascular disease and increased risk of mortali...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetic networks", "quantitative traits", "genetic maps", "gene function", "genome sequencing", "genome analysis tools", "model organisms", "linkage maps", "trait locus analysis", "molecular genetics", "linkage (genetics)", "genome complexity", "biology", "trait locus", "phenotypes", ...	QTL Analysis of High Thermotolerance with Superior and Downgraded Parental Yeast Strains Reveals New Minor QTLs and Converges on Novel Causative Alleles Involved in RNA Processing	journal.pgen.1003693	null	[ [ "Many genetic traits are quantitative and show complex inheritance .", "Because these traits are so prevalent in nature , understanding the underlying factors is important for various biological fields and for applications like industrial biotechnology and agricultural practice [1] .", "Recently , bak...	[ "Revealing QTLs with a minor effect in complex traits remains difficult .", "Initial strategies had limited success because of interference by major QTLs and epistasis .", "New strategies focused on eliminating major QTLs in subsequent mapping experiments .", "Since genetic analysis of superior segregants fro...	[ "Most traits of organisms are determined by an interplay of different genes interacting in a complex way .", "For instance , nearly all industrially-important traits of the yeast Saccharomyces cerevisiae are complex traits .", "We have analyzed high thermotolerance , which is important for industrial fermentati...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Advances in the Diagnosis of Human Opisthorchiasis: Development of Opisthorchis viverrini Antigen Detection in Urine	journal.pntd.0004157	null	[ [ "Opisthorchis viverrini ( OV ) infection is a major public health problem in the Mekong River Basin region of Southeast Asia , especially in Thailand , the Lao People’s Democratic Republic ( Lao PDR ) , Cambodia , and Vietnam [1 , 2] .", "The clinical sequelae of chronic opisthorchiasis are several advanc...	[ "Many strategies to control opisthorchiasis have been employed in Thailand , but not in the other neighbouring countries .", "Specific control methods include mass drug administration ( MDA ) and health education to reduce raw fish consumption .", "These control efforts have greatly shifted the epidemiology of ...	[ "Improved diagnostic methods for the detection of Opisthorchis viverrini ( OV ) infection in humans is required for effective surveillance and control of this food borne parasite and the prevention of OV-induced bile duct cancer ( cholangiocarcinoma or CCA ) .", "In this study , a novel urinary antigen detection ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "virology/vaccines", "neurological disorders/infectious diseases of the nervous system", "immunology/immune response", "virology", "immunology", "virology/immune evasion", "immunology/immunity to infections", "virology/host antiviral responses" ]	The Production of Antibody by Invading B Cells Is Required for the Clearance of Rabies Virus from the Central Nervous System	journal.pntd.0000535	null	[ [ "Rabies viruses spread from peripheral sites of entry to the central nervous system ( CNS ) tissues via axonal transport thereby bypassing the specialized features of the neurovasculature known as the blood-brain barrier ( BBB ) .", "Once the virus reaches CNS tissues three alternative outcomes are likely...	[ "The pathogenesis of rabies is associated with the inability to deliver immune effectors across the blood-brain barrier and to clear virulent rabies virus from CNS tissues .", "However , the mechanisms that facilitate immune effector entry into CNS tissues are induced by infection with attenuated rabies virus .",...	[ "Every year over 50 , 000 people die from rabies worldwide , primarily due to the poor availability of rabies vaccine in developing countries .", "However , even when vaccines are available , human deaths from rabies occur if exposure to the causative virus is not recognized and vaccination is not sought in time ...	2009
[ "Introduction", "Results", "Discussion" ]	[ "mathematics/statistics", "genetics and genomics" ]	Practical Issues in Imputation-Based Association Mapping	journal.pgen.1000279	null	[ [ "We now describe more formally the imputation-based approaches to association mapping that we take here , and introduce notation for use in later sections .", "Readers whose primary interest is in our practical findings may wish to skip the Results section , and refer back to this section for reference ."...	[ "Imputation-based association methods provide a powerful framework for testing untyped variants for association with phenotypes and for combining results from multiple studies that use different genotyping platforms .", "Here , we consider several issues that arise when applying these methods in practice , includ...	[ "Genotype imputation is becoming a popular approach to comparing and combining results of multiple association studies that used different SNP genotyping platforms .", "The basic idea is to exploit the fact that , due to correlation among untyped and typed SNPs , genotypes of untyped SNPs in each study can be inf...	2008

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