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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Dual miRNA Targeting Restricts Host Range and Attenuates Neurovirulence of Flaviviruses	journal.ppat.1004852	null	[ [ "Mosquito-borne flaviviruses such as dengue , yellow fever , Japanese encephalitis and West Nile viruses ( genus , Flavivirus; family , Flaviviridae ) are among the most significant arboviral pathogens of humans and domestic animals in many regions of the world .", "Depending on the particular virus , cli...	[ "Mosquito-borne flaviviruses are among the most significant arboviral pathogens worldwide .", "Vaccinations and mosquito population control programs remain the most reliable means for flavivirus disease prevention , and live attenuated viruses remain one of the most attractive flavivirus vaccine platforms .", "...	[ "Despite advances in developing flavivirus live attenuated vaccine ( LAV ) candidates , a concern exists that they might not be safe in the environment due to their intrinsic genetic instability leading to potential reversion back to wild-type that could be associated with possible dissemination of these mutated vi...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue	journal.ppat.1004641	null	[ [ "CD200R is an Immunoglobulin superfamily family member that is expressed by hematopoietic cells , with notably high expression on myeloid cells [1] .", "The ligand of CD200R , CD200 ( OX2 ) , is broadly expressed by cells of hematopoietic and non-hematopoietic origins [2] .", "The primary function of ...	[ "CD200 receptor ( CD200R ) negatively regulates peripheral and mucosal innate immune responses .", "Viruses , including herpesviruses , have acquired functional CD200 orthologs , implying that viral exploitation of this pathway is evolutionary advantageous .", "However , the role that CD200R signaling plays dur...	[ "Immune inhibitory receptors , including CD200 receptor ( CD200R ) , can limit immune responses in the mucosa to restrict reactivity to the plethora of harmless antigens that mucosal surfaces are continually exposed to .", "However , viruses may exploit these suppressive mechanisms to enable their persistence and...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "action potentials", "medicine and health sciences", "neural networks", "engineering and technology", "electronics", "membrane potential", "ocular anatomy", "electrophysiology", "light", "neuroscience", "electromagnetic radiation", "luminance", "ganglion cells", "visible light", "compute...	Nonlinear decoding of a complex movie from the mammalian retina	journal.pcbi.1006057	null	[ [ "Decoding plays a central role in our efforts to understand the neural code [1–4] .", "While statistical analyses of neural responses can be used to directly estimate [5 , 6] or bound [7] the information content of spike trains , such analyses remain agnostic about what the encoded bits might mean or how ...	[ "Retina is a paradigmatic system for studying sensory encoding: the transformation of light into spiking activity of ganglion cells .", "The inverse problem , where stimulus is reconstructed from spikes , has received less attention , especially for complex stimuli that should be reconstructed “pixel-by-pixel” ."...	[ "Neurons in the retina transform patterns of incoming light into sequences of neural spikes .", "We recorded from ∼100 neurons in the rat retina while it was stimulated with a complex movie .", "Using machine learning regression methods , we fit decoders to reconstruct the movie shown from the retinal output ."...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "medicine and health sciences", "variant genotypes", "random variables", "covariance", "alleles", "genetic mapping", "probability distribution", "mathematics", "coronary heart disease", "statistics (mathematics)", "genome analysis", "cardiology", "researc...	Fast and general tests of genetic interaction for genome-wide association studies	journal.pcbi.1005556	null	[ [ "Large data sets are vital to counter low statistical power due to low allele frequency , small effect sizes , and multiple testing .", "This has driven the GWAS field towards more collaborative efforts as well as meta-analyses .", "Fortunately , there exists a standardized statistical methodology tha...	[ "A complex disease has , by definition , multiple genetic causes .", "In theory , these causes could be identified individually , but their identification will likely benefit from informed use of anticipated interactions between causes .", "In addition , characterizing and understanding interactions must be con...	[ "Interaction between organic molecules forms the basis of all biological systems .", "The availability of high-throughput genotyping and sequencing platforms enables us to cost-effectively genotype a large number of individuals .", "For sufficiently large datasets it is possible to reconstruct the genetic depen...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "gene regulation", "pathogens", "nasopharyngeal carcinoma", "carcinomas", "immunology", "microbiology", "cancers and neoplasms", "epithelial cells", "viruses", "oncology", "membrane protei...	Epstein-Barr virus activates F-box protein FBXO2 to limit viral infectivity by targeting glycoprotein B for degradation	journal.ppat.1007208	null	[ [ "Epstein-Barr virus ( EBV ) belongs to the γ-herpesvirus family , and more than 90% of individuals worldwide are asymptomatically infected with EBV .", "As the first discovered tumor virus , EBV has been identified in Burkitt’s lymphoma , Hodgkin’s disease , a subset of gastric cancers and nearly all non-...	[ "Epstein-Barr virus ( EBV ) is a human cancer-related virus closely associated with lymphoid and epithelial malignancies , and EBV glycoprotein B ( gB ) plays an essential role in viral entry into both B cells and epithelial cells by promoting cell-cell fusion .", "EBV gB is exclusively modified with high-mannose...	[ "EBV envelope glycoprotein B ( gB ) is a core component of the fusion machinery and plays an essential role in viral entry .", "EBV gB has been characterized as a high-mannose-containing glycoprotein , but the significance of this sugar type is unknown .", "In this work , we report the identification of FBXO2 ,...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "retrotransposons", "engineering and technology", "gene regulation", "plant science", "genetic elements", "plant genomics", "sequence motif analysis", "epigenetics", "dna", "plants", "chromatin", "dna methylation", "research and analysis methods", "bioengineering", "se...	Environmental and epigenetic regulation of Rider retrotransposons in tomato	journal.pgen.1008370	null	[ [ "Transposable elements ( TEs ) replicate and move within host genomes .", "Based on their mechanisms of transposition , TEs are either DNA transposons that use a cut-and-paste mechanism or retrotransposons that transpose through an RNA intermediate via a copy-and-paste mechanism [1] .", "TEs make up a...	[ "Transposable elements in crop plants are the powerful drivers of phenotypic variation that has been selected during domestication and breeding programs .", "In tomato , transpositions of the LTR ( long terminal repeat ) retrotransposon family Rider have contributed to various phenotypes of agronomical interest ,...	[ "Transposons are major constituents of plant genomes and represent a powerful source of internal genetic and epigenetic variation .", "For example , domestication of maize has been facilitated by a dramatic change in plant architecture , the consequence of a transposition event .", "Insertion of transposons nea...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "parasite groups", "body fluids", "plasmodium", "gametocytes", "tropical diseases", "parasitic diseases", "parasitic protozoans", "animals", "parasitology", "germ cells", "apicomplexa", "protozoans", "infectious disease control", "insect...	Predominance of asymptomatic and sub-microscopic infections characterizes the Plasmodium gametocyte reservoir in the Peruvian Amazon	journal.pntd.0005674	null	[ [ "As countries in the Americas develop plans for malaria pre-elimination , a better understanding of Plasmodium transmission epidemiology is necessary to implement effective interventions , in particular for Plasmodium vivax [1 , 2] .", "In Peru , similar to other regions in Amazonia , P . vivax is respons...	[ "Malaria transmission requires that Anopheles mosquitoes ingest Plasmodium gametocyte stages circulating in the human bloodstream .", "In the context of malaria elimination , understanding the epidemiology of gametocytes relative to all Plasmodium infections and the contribution of asymptomatic and sub-microscopi...	[ "Malaria elimination , i . e . the complete interruption of parasite transmission in a region , is in the agenda of health authorities in countries that achieved substantial reduction of the disease burden in the past decade .", "However , our understanding of transmission epidemiology for low transmission areas ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation" ]	A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication	journal.ppat.1000216	null	[ [ "All known positive strand RNA viruses replicate their genomes in association with remodeled cellular membranes .", "Assembly of replication complexes on membranes is believed to have several advantages .", "Membranes provide a scaffold that increases the local concentration of proteins involved in re...	[ "Replication of many RNA viruses is accompanied by extensive remodeling of intracellular membranes .", "In poliovirus-infected cells , ER and Golgi stacks disappear , while new clusters of vesicle-like structures form sites for viral RNA synthesis .", "Virus replication is inhibited by brefeldin A ( BFA ) , imp...	[ "All positive strand RNA viruses replicate their genomes in association with membranous structures that are formed after infection by remodeling pre-existing cellular organelles .", "The role of membranes and the mechanisms exploited by viral proteins to orchestrate the formation and functioning of viral membrano...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics", "biology", "microbiology" ]	Sub-Inhibitory Concentrations of Human α-defensin Potentiate Neutralizing Antibodies against HIV-1 gp41 Pre-Hairpin Intermediates in the Presence of Serum	journal.ppat.1003431	null	[ [ "HIV envelope glycoprotein ( Env ) is a trimer each monomer of which consists of non-covalently associated transmembrane ( gp41 ) and surface ( gp120 ) subunits [1] .", "The gp120 binding to CD4 induces the formation of the gp120 coreceptor binding site and enables recruitment of HIV coreceptors ( CCR5 or...	[ "Human defensins are at the forefront of the host responses to HIV and other pathogens in mucosal tissues .", "However , their ability to inactivate HIV in the bloodstream has been questioned due to the antagonistic effect of serum .", "In this study , we have examined the effect of sub-inhibitory concentration...	[ "Human neutrophil peptide 1 ( HNP-1 ) is a small cationic peptide that can directly block HIV-1 entry in the absence of serum .", "However , since serum attenuates the anti-HIV activity of this peptide , HNP-1 is unlikely to inhibit infection in the bloodstream .", "Here , we demonstrate that sub-inhibitory dos...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Critical Role for PDGFRα Signaling in Medial Nasal Process Development	journal.pgen.1003851	null	[ [ "Neural crest cells ( NCCs ) are a transient and multipotent cell population unique to vertebrates .", "During development , NCCs give rise to a broad variety of cell types , which contribute to the formation of the peripheral nervous system , cardiac outflow tract , pigment cells , and the majority of cr...	[ "The primitive face is composed of neural crest cell ( NCC ) derived prominences .", "The medial nasal processes ( MNP ) give rise to the upper lip and vomeronasal organ , and are essential for normal craniofacial development , but the mechanism of MNP development remains largely unknown .", "PDGFRα signaling i...	[ "Craniofacial anomalies , including cleft lip and palate , are frequent birth defects .", "Although these are often associated with defects in neural crest development , the more severe phenotypic manifestations of midline defects is facial clefting , which is poorly understood .", "In this work , we show that ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "cell biology", "physiology", "immunology" ]	Creatine Kinase–Mediated ATP Supply Fuels Actin-Based Events in Phagocytosis	journal.pbio.0060051	A tight connection exists between local recruitment of creatine kinase-B (CK-B) and actin remodeling activity in phagocytic cups of macrophages. Complement-mediated phagocytosis is stimulated in the presence of enzymatic-active CK-B, indicating that local ATP supply stimulates actin-driven particle uptake events.	[ [ "Dynamic reorganization and stabilization of the actin cytoskeleton and membrane-shape alterations of cells are intimately and reciprocally coupled events that are essential for a variety of distinct cell functions such as adhesion , motility , cytokinesis , and endocytosis [1] .", "One of the processes t...	[ "Phagocytosis requires locally coordinated cytoskeletal rearrangements driven by actin polymerization and myosin motor activity .", "How this actomyosin dynamics is dependent upon systems that provide access to ATP at phagosome microdomains has not been determined .", "We analyzed the role of brain-type creatin...	[ "To do work , cells need energy in the form of ATP .", "High and sudden energy demand is seen during cell-shape change , a process in which ATP fuels the cytoskeletal machinery that drives cell-morphology alteration .", "How a cell organizes high-energy surges without disrupting global ATP homeostasis remains a...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	HITS-CLIP Analysis Uncovers a Link between the Kaposi’s Sarcoma-Associated Herpesvirus ORF57 Protein and Host Pre-mRNA Metabolism	journal.ppat.1004652	null	[ [ "Kaposi’s sarcoma-associated herpesvirus ( KSHV; HHV-8 ) is a human gammaherpesvirus and the etiological agent for Kaposi’s sarcoma ( KS ) , primary effusion lymphoma ( PEL ) , KSHV-inflammatory cytokine syndrome ( KICS ) , and some cases of multicentric Castleman’s disease ( MCD ) [1–4] .", "The KSHV lif...	[ "The Kaposi’s sarcoma associated herpesvirus ( KSHV ) is an oncogenic virus that causes Kaposi’s sarcoma , primary effusion lymphoma ( PEL ) , and some forms of multicentric Castleman’s disease .", "The KSHV ORF57 protein is a conserved posttranscriptional regulator of gene expression that is essential for virus ...	[ "During viral replication , the oncogenic Kaposi’s sarcoma-associated herpesvirus ( KSHV ) modulates both host and viral gene expression .", "KSHV ORF57 is a multifunctional posttranscriptional regulator that is essential for viral replication and stabilizes viral RNAs .", "Previous studies demonstrated that OR...	2015
[ "Introduction", "Methods", "Results and discussion", "Conclusions" ]	[ "computer applications", "parasite groups", "medicine and health sciences", "plasmodium", "population genetics", "tropical diseases", "geographical locations", "parasitic diseases", "parasitic protozoans", "parasitology", "apicomplexa", "protozoans", "molecular biology techniques", "popula...	VivaxGEN: An open access platform for comparative analysis of short tandem repeat genotyping data in Plasmodium vivax populations	journal.pntd.0005465	null	[ [ "In the Asia-Pacific region , Plasmodium vivax is responsible for between 20 and 280 million malaria cases per year , inflicting a significant burden of morbidity and mortality .", "Over the last decade , the prevalence of P . falciparum has declined in many endemic countries as a result of intensified ma...	[ "The control and elimination of Plasmodium vivax will require a better understanding of its transmission dynamics , through the application of genotyping and population genetics analyses .", "This paper describes VivaxGEN ( http://vivaxgen . menzies . edu . au ) , a web-based platform that has been developed to s...	[ "The Plasmodium vivax malaria parasite inflicts significant morbidity in endemic populations across the globe , but has been overshadowed by the more fatal P . falciparum parasite .", "In malaria-endemic regions outside of Africa , the declining prevalence of P . falciparum is coupled with a proportionate rise in...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "classical mechanics", "fluid mechanics", "mathematical models", "epithelial cells", "guanine nucleotide exchange factors", "molecular motors", "actin motors", "gtpase signaling", "reaction dynamics", "motor proteins", "research and analysis methods", "physica...	Bistable front dynamics in a contractile medium: Travelling wave fronts and cortical advection define stable zones of RhoA signaling at epithelial adherens junctions	journal.pcbi.1005411	null	[ [ "Spatial and temporal patterns of intracellular signaling are thought to play important roles in determining their functional outcomes .", "This is exemplified by the RhoA GTPase , a major regulator of actomyosin-based contractility in eukaryotic cells [1 , 2] .", "Characteristically , localized RhoA ...	[ "Mechanical coherence of cell layers is essential for epithelia to function as tissue barriers and to control active tissue dynamics during morphogenesis .", "RhoA signaling at adherens junctions plays a key role in this process by coupling cadherin-based cell-cell adhesion together with actomyosin contractility ...	[ "Mathematical models play a key role in uncovering mechanisms responsible for the formation of patterns in cells and tissues .", "The well known Turing mechanism based on nonlinear reaction kinetics and differential diffusion explains the formation of static patterns , while positive feedback interactions can gen...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Enhanced CD8 T Cell Responses through GITR-Mediated Costimulation Resolve Chronic Viral Infection	journal.ppat.1004675	null	[ [ "The adaptive immune system has evolved to detect and remove virally infected cells .", "However , multiple viruses , such as human immunodeficiency virus ( HIV ) , hepatitis C virus ( HCV ) or hepatitis B virus ( HBV ) have acquired successful counter-measures to escape from anti-viral immunity , thereby...	[ "Chronic infections are characterized by the inability to eliminate the persisting pathogen and often associated with functional impairment of virus-specific T-cell responses .", "Costimulation through Glucocorticoid-induced TNFR-related protein ( GITR ) can increase survival and function of effector T cells .", ...	[ "The ability of the immune system to rapidly respond to a viral infection is a prerequisite for the survival of an individual .", "The immediate reaction of innate immune cells and the subsequent response of antigen-specific lymphocytes is usually effective for rapid neutralization and removal of the invading vir...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "medicine and health sciences", "helminths", "tropical diseases", "parasitic diseases", "animals", "health care", "mathematics", "forecasting", "statistics (mathematics)", "neglected tropical diseases", "infectious disease control", "morbidity", "research ...	Mapping Soil Transmitted Helminths and Schistosomiasis under Uncertainty: A Systematic Review and Critical Appraisal of Evidence	journal.pntd.0005208	null	[ [ "Helminth infections from as soil-transmitted helminths ( STHs ) and schistosomes are among the most prevalent neglected tropical diseases ( NTDs ) affecting human populations living in countries where clean water , sanitation , and hygiene ( WASH ) are limited .", "STHs and schistosomes , affect more tha...	[ "Spatial modelling of STH and schistosomiasis epidemiology is now commonplace .", "Spatial epidemiological studies help inform decisions regarding the number of people at risk as well as the geographic areas that need to be targeted with mass drug administration; however , limited attention has been given to prop...	[ "In recent years spatial modelling studies of schistosome and soil-transmitted helminth infections have become commonplace; however there is no standard framework for uncertainty evaluation and reporting .", "In this study we aim to identify faults in existing studies and propose a framework for evaluation and re...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	MiR-24 Is Required for Hematopoietic Differentiation of Mouse Embryonic Stem Cells	journal.pgen.1004959	null	[ [ "MicroRNAs ( miRNAs ) are small ( ~22 nucleotide ) RNA molecules that regulate gene expression post-transcriptionally .", "They are implicated in important cellular processes such as apoptosis , proliferation , and differentiation [1] .", "Work from many laboratories , including our own , shows that m...	[ "Overexpression of miRNA , miR-24 , in mouse hematopoietic progenitors increases monocytic/ granulocytic differentiation and inhibits B cell development .", "To determine if endogenous miR-24 is required for hematopoiesis , we antagonized miR-24 in mouse embryonic stem cells ( ESCs ) and performed in vitro differ...	[ "Studies of mouse embryos and embryonic stem cells ( ESCs ) have defined the ontogeny of mammalian embryonic hematopoietic cells .", "The ESC differentiation system has been valuable for dissecting the molecular regulation of the development of mesoderm into HPCs .", "Extracellular signals regulate a complex ne...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mhc class i genes", "medicine and health sciences", "immune physiology", "immunology", "alleles", "mutation", "protein expression", "clinical medicine", "gene types", "molecular biology techniques", "research and analysis methods", "immune system proteins", "major histocompatibility complex...	Quantifying immune-based counterselection of somatic mutations	journal.pgen.1008227	null	[ [ "In every human cell , proteins are constantly being degraded into component peptides , and a subset of this pool of peptides are displayed on MHC class I receptor proteins ( encoded by human leukocyte antigen or HLA genes ) .", "As somatic mutations arise , some cause differences in MHC-displayed peptide...	[ "Somatic mutations in protein-coding regions can generate ‘neoantigens’ causing developing cancers to be eliminated by the immune system .", "Quantitative estimates of the strength of this counterselection phenomenon have been lacking .", "We quantified the extent to which somatic mutations are depleted in pept...	[ "Cancer immunotherapy and personalized cancer vaccines depend on clearance of cancer and pre-cancer cells by the immune system .", "However , little is known about the strength of this phenomenon as it acts on the cell populations which give rise to tumors .", "Here we provide an initial quantitative estimate o...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "chemical bonding", "condensed matter physics", "geometry", "mathematics", "protein structure prediction", "protein structure", "hydrogen bonding", "physical chemistry", "protein structure determination", "proteins", "chemistry", "beta helix", "molecular biology", "dihedral angles", "phy...	A new clustering and nomenclature for beta turns derived from high-resolution protein structures	journal.pcbi.1006844	null	[ [ "Ordered protein structures consist of elements of regular secondary structure , such as alpha helices and beta-sheet strands , and irregular elements of structure referred to as loops or coil regions .", "Loops comprise half of residues in protein structures .", "Due to the globular nature of folded ...	[ "Protein loops connect regular secondary structures and contain 4-residue beta turns which represent 63% of the residues in loops .", "The commonly used classification of beta turns ( Type I , I’ , II , II’ , VIa1 , VIa2 , VIb , and VIII ) was developed in the 1970s and 1980s from analysis of a small number of pr...	[ "Folded proteins consist of elements of regular secondary structure , such as alpha helices and beta sheets connected by irregular structures called loops .", "Loops have a varying length and typically contain U-shaped beta turns which abruptly change the direction of the chain .", "Beta turns are formed by fou...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "social and behavioral sciences", "population modeling", "social networks", "sociology", "biology", "computational biology", "infectious disease modeling" ]	Effects of Heterogeneous and Clustered Contact Patterns on Infectious Disease Dynamics	journal.pcbi.1002042	null	[ [ "Contacts sufficient for transmission of infectious disease occur repeatedly within stable relationships such as between sex partners or within households and workplaces .", "Epidemiologists increasingly use random network models that explicitly capture such interactions to study disease dynamics [1] .", ...	[ "The spread of infectious diseases fundamentally depends on the pattern of contacts between individuals .", "Although studies of contact networks have shown that heterogeneity in the number of contacts and the duration of contacts can have far-reaching epidemiological consequences , models often assume that conta...	[ "The transmission dynamics of infectious diseases are sensitive to the patterns of interactions among susceptible and infectious individuals .", "Human social contacts are known to be highly heterogeneous ( the number of social contacts ranges from few to very many ) and to be highly clustered ( the social contac...	2011
[ "Introduction", "Pathogenesis and Clinical Features", "Epidemiology", "Global Prevalence of Trachoma", "Global Burden of Trachoma", "Economic Cost of Trachoma", "Trachoma Control and Its Cost-effectiveness", "Conclusions and Future Directions" ]	[ "public health and epidemiology/epidemiology", "public health and epidemiology/infectious diseases", "review" ]	The Global Burden of Trachoma: A Review	journal.pntd.0000460	null	[ [ "Trachoma is the leading infectious cause of blindness worldwide .", "Overall it is the eighth commonest blinding disease [1] .", "Trachoma is caused by the obligate intracellular bacterium C . trachomatis .", "Recurrent episodes of conjunctival infection and the associated chronic inflammation it...	[ "Trachoma is the commonest infectious cause of blindness worldwide .", "Recurrent infection of the ocular surface by Chlamydia trachomatis , the causative agent , leads to inturning of the eyelashes ( trichiasis ) and blinding corneal opacification .", "Trachoma is endemic in more than 50 countries .", "It is...	[ "This review examines the various attempts to estimate the burden of disease from trachoma , the commonest infectious cause of blindness worldwide .", "Reports vary considerably because of differences in methodology and changing estimates of the number of people affected .", "Currently about 1 . 3 million are b...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "information entropy", "vocalization", "vertebrates", "social sciences", "neuroscience", "animals", "animal models", "probability distribution", "mathematics", "animal behavior", "experimental organism systems", "computational neuroscience", "zoology", "thermodynamics", "coding mechanism...	Invariant neural responses for sensory categories revealed by the time-varying information for communication calls	journal.pcbi.1006698	null	[ [ "Information theoretic analyses are well suited to the study of neural representation since this mathematical framework was developed to quantify and optimize the encoding of informative signals in communication channels [1] .", "In sensory systems , Information Theory ( IT ) has been applied extensively ...	[ "Although information theoretic approaches have been used extensively in the analysis of the neural code , they have yet to be used to describe how information is accumulated in time while sensory systems are categorizing dynamic sensory stimuli such as speech sounds or visual objects .", "Here , we present a nov...	[ "Just as the recognition of faces requires neural representations that are invariant to scale and rotation , the recognition of behaviorally relevant auditory objects , such as spoken words , requires neural representations that are invariant to the speaker uttering the word and to his or her location .", "Here ,...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "parasite groups", "medicine and health sciences", "pathology and laboratory medicine", "immunology", "parasitology", "global health", "immunoregulation", "public and occupational health", "infectious diseases", "white blood cells", "inflammation", "animal cells", "t cells",...	Real-Time Imaging Reveals the Dynamics of Leukocyte Behaviour during Experimental Cerebral Malaria Pathogenesis	journal.ppat.1004236	null	[ [ "CM is a severe complication of Plasmodium falciparum infection and is responsible for an estimated 627 , 000 deaths annually , particularly among children [1] .", "CM is strongly associated with parasitised red blood cell ( pRBC ) sequestration in the vasculature of the brain [2] , [3] .", "The resul...	[ "During experimental cerebral malaria ( ECM ) mice develop a lethal neuropathological syndrome associated with microcirculatory dysfunction and intravascular leukocyte sequestration .", "The precise spatio-temporal context in which the intravascular immune response unfolds is incompletely understood .", "We dev...	[ "Cerebral malaria ( CM ) is a severe complication of Plasmodium falciparum infection that takes a significant toll on human life .", "Blockage of the brain blood vessels contributes to the clinical signs of CM , however we know little about the precise pathological events that lead to this disease .", "To this ...	2014
[ "Introduction", "Methods", "Results and Discussion" ]	[ "medicine", "functional genomics", "immunology", "parasitic diseases", "neglected tropical diseases", "glycoproteins", "veterinary science", "infectious diseases", "veterinary diseases", "zoonoses", "veterinary parasitology", "comparative genomics", "biology", "proteomics", "vectors and ...	Salivary Gland Transcriptomes and Proteomes of Phlebotomus tobbi and Phlebotomus sergenti, Vectors of Leishmaniasis	journal.pntd.0001660	null	[ [ "Sand flies are bloodsucking nematoceran Diptera that transmit the protozoan parasites of the genus Leishmania .", "Similar to that of other bloodsucking arthropods , sand fly saliva comprises antihemostatic , immunomodulatory , and antigenic components .", "The saliva is deposited into the host skin ...	[ "Phlebotomus tobbi is a vector of Leishmania infantum , and P . sergenti is a vector of Leishmania tropica .", "Le .", "infantum and Le .", "tropica typically cause visceral or cutaneous leishmaniasis , respectively , but Le .", "infantum strains transmitted by P . tobbi can cause cutaneous disease .", "T...	[ "Phlebotomine female sand flies require a blood meal for egg development , and it is during the blood feeding that pathogens can be transmitted to a host .", "Leishmania parasites are among these pathogens and can cause disfiguring cutaneous or even possibly fatal visceral disease .", "The Leishmania parasites ...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cell motility", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "immunology", "tropical diseases", "microbiology", "alphaviruses", "fibroblasts", "viruses"...	Immunomodulatory drug methotrexate used to treat patients with chronic inflammatory rheumatisms post-chikungunya does not impair the synovial antiviral and bone repair responses	journal.pntd.0006634	null	[ [ "Alphaviruses , transmitted by bites of infected mosquitoes , are globally distributed and capable to cause significant inflammatory diseases including arthritis and encephalitis [1] .", "Old World alphaviruses , such as Chikungunya virus ( CHIKV ) , Ross River virus ( RRV ) and O’Nyong-Nyong virus ( ONNV...	[ "Chikungunya virus ( CHIKV ) is a mosquito-transmitted RNA alphavirus causing major outbreaks of infectious chronic inflammatory rheumatisms ( CIR ) .", "Recently , methotrexate ( MTX ) , a disease modifying anti-rheumatic drug has been used successfully to treat patients suffering from rheumatoid-like arthritis ...	[ "Chikungunya is a mosquito-borne virus ( CHIKV ) and has been incriminated in the development of arthralgia ( pain of the joint ) and arthritis particularly in elderly patients .", "Methotrexate ( MTX ) has been used widely to effectively treat these chronic rheumatic symptoms .", "Using a model of primary huma...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "gastroenterology and hepatology/gastrointestinal infections", "infectious diseases/helminth infections", "public health and epidemiology/infectious diseases", "microbiology/parasitology", "infectious diseases/epidemiology and control of infectious diseases" ]	Detection of Schistosoma mansoni Eggs in Feces through their Interaction with Paramagnetic Beads in a Magnetic Field	journal.pntd.0000073	null	[ [ "In areas with recent introduction of Schistosoma mansoni transmission or areas where control efforts have reduced parasitic burden , the classical parasitological methods for finding eggs in stools do not demonstrate sufficient sensitivity [1] , [2] , [3] .", "Travelers may have light S . mansoni infecti...	[ "Diagnosis of intestinal schistosomiasis in low endemic areas is a problem because often control measures have reduced egg burdens in feces to below the detection limits of classical coproparasitological methods .", "Evaluation of molecular methods is hindered by the absence of an established standard with maximu...	[ "Schistosomiasis mansoni is a parasitic infection that affects approximately 200 million people , mainly in the tropics .", "The worms live inside the veins of intestines and liver and produce eggs that are eliminated within feces .", "If the eggs reach water , a ciliated larva is released and enters snails to ...	2007
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "body fluids", "pathology and laboratory medicine", "cardiovascular anatomy", "endothelial cells", "immunology", "cloning", "epithelial cells", "integrins", "signs and symptoms", "platelets", "molecular biology techniques", "...	Platelets Guide Leukocytes to Their Sites of Extravasation	journal.pbio.1002459	This study identifies a previously unanticipated role for platelets as pathfinders, guiding leukocytes to the sites at which they can exit the microvasculature; this process appears to be critical for an effective immune response.	[ [ "Directed migration of leukocytes from the vasculature to the site of injury or infection is a prerequisite for effective immune responses .", "Neutrophils are the first immune cells infiltrating the inflamed tissue , followed by a second wave of inflammatory monocytes ( iMOs ) amplifying the inflammatory...	[ "Effective immune responses require the directed migration of leukocytes from the vasculature to the site of injury or infection .", "How immune cells “find” their site of extravasation remains largely obscure .", "Here , we identified a previously unrecognized role of platelets as pathfinders guiding leukocyte...	[ "White blood cells ( leukocytes ) are the effector cells of the immune system .", "The movement ( extravasation ) of leukocytes from the bloodstream to the surrounding tissue is a prerequisite for proper host defense .", "Platelets are anucleate cell particles that circulate in the blood and play a fundamental ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "genetics and genomics", "homo (human)", "virology" ]	Regulatory Polymorphisms in the Cyclophilin A Gene, PPIA, Accelerate Progression to AIDS	journal.ppat.0030088	null	[ [ "As an obligate intracellular parasite , HIV type 1 ( HIV-1 ) utilizes host cell factors for its replication .", "Human cyclophilin A ( CypA ) , also known as peptidyl prolyl isomerase A ( PPIA ) , is a ubiquitous cytoplasmic protein ( by convention , we refer to the protein as CypA and the gene as PPIA )...	[ "Human cyclophilin A , or CypA , encoded by the gene peptidyl prolyl isomerase A ( PPIA ) , is incorporated into the HIV type 1 ( HIV-1 ) virion and promotes HIV-1 infectivity by facilitating virus uncoating .", "We examined the effect of single nucleotide polymorphisms ( SNPs ) and haplotypes within the PPIA gen...	[ "Individual risk of acquiring HIV type 1 ( HIV-1 ) infection and developing AIDS is not equal; some people are more prone to HIV/AIDS than others .", "Susceptibility to HIV-1/AIDS is likely determined by a combination of environmental , viral , and host genetic factors .", "Genetic variations in host cellular f...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biology", "computational biology", "evolutionary biology" ]	Predictability of Evolutionary Trajectories in Fitness Landscapes	journal.pcbi.1002302	null	[ [ "One of the most intriguing questions in evolutionary biology is: to what extent evolution is deterministic and to what extent it is stochastic and hence unpredictable ?", "In other words , what happens if “the tape of evolution is replayed:” are we going to see completely different outcomes or the constr...	[ "Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution .", "However , these experiments deal with individual enzymes and explore a tiny part of the fitness landscape .", "We report an exhaustive analysis of fitness landscapes c...	[ "Is evolution deterministic , hence predictable , or stochastic , that is unpredictable ?", "What would happen if one could “replay the tape of evolution”: will the outcomes of evolution be completely different or is evolution so constrained that history will be repeated ?", "Arguably , these questions are amon...	2011
[ "Introduction", "Methods", "Discussion" ]	[ "medicine and health sciences", "education", "sociology", "vertebrates", "social sciences", "diet", "parasitic diseases", "animals", "mammals", "parasitology", "health care", "animal products", "developmental biology", "nutrition", "meat", "amniotes", "food", "swine", "behavior",...	Effects of ‘The Vicious Worm’ educational tool on Taenia solium knowledge retention in Zambian primary school students after one year	journal.pntd.0007336	null	[ [ "Taenia solium is a zoonotic parasite known as the pork tapeworm , which infects over 50 million people worldwide [1] .", "Invasion of the human brain by the larval stage of the parasite is known as neurocysticercosis ( NCC ) , which can cause neurological deficits including severe progressive headache , ...	[ "Taenia solium is a neglected zoonotic parasite endemic throughout many low-income countries worldwide , including Zambia , where it causes human and pig diseases with high health and socioeconomic burdens .", "Lack of knowledge is a recognized risk factor , and consequently targeted health educational programs c...	[ "The zoonotic parasite Taenia solium , commonly known as the pork tapeworm , causes substantial public health and economic losses worldwide .", "It is commonly found in low-income countries where pigs are raised in areas of poor sanitation , including Zambia .", "The links between the parasite and its different...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "animal types", "medicine and health sciences", "domestic animals", "tropical diseases", "vector-borne diseases", "vertebrates", "parasitic diseases", "parasitic protozoans", "animals", "mammals", "dogs", "pets and companion animals", "protozoans", "neglected tropical diseases", "infecti...	Are the London Declaration’s 2020 goals sufficient to control Chagas disease?: Modeling scenarios for the Yucatan Peninsula	journal.pntd.0006337	null	[ [ "While the World Health Organization’s ( WHO ) London Declaration on Neglected Tropical Diseases has proposed 2020 goals of “100% of countries certified with no intradomiciliary transmission” , “100% of countries with certification of transfusional transmission interrupted” , and “100% of countries with contr...	[ "The 2020 Sustainable Development goals call for 100% certified interruption or control of the three main forms of Chagas disease transmission in Latin America .", "However , how much will achieving these goals to varying degrees control Chagas disease; what is the potential impact of missing these goals and if t...	[ "While World Health Organization’s ( WHO ) London Declaration on Neglected Tropical Diseases has proposed 2020 goals of 100% certified interruption or control of the three main forms of Chagas disease transmission ( vectorial , congenital , and transfusional ) in Latin America , the impact of achieving and/or missi...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physiology/cell signaling", "computational biology/transcriptional regulation", "biophysics/theory and simulation", "computational biology/signaling networks" ]	Rescuing Loading Induced Bone Formation at Senescence	journal.pcbi.1000924	null	[ [ "Mechanical stimuli are anabolic for bone and hold promise to counteract skeletal fragility associated with bone loss pathologies [1] , [2] .", "Exercise based strategies are especially attractive given the critical need for inexpensive options to treat osteoporosis worldwide [3] .", "However , readil...	[ "The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe , effective , and , critically , inexpensive given the prevailing overburdened health care systems .", "While vigorous skeletal loading is anabolic and holds promise , deficits in mechanotransduction accrued with age ma...	[ "Post-menopausal and age-related osteoporosis afflicts large segments of the population and can markedly increase skeletal fragility .", "Bone fractures that occur as a consequence substantially increase health care expenditures and raise levels of morbidity .", "While strategies that prevent further loss of bo...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Spontaneous Cdc42 Polarization Independent of GDI-Mediated Extraction and Actin-Based Trafficking	journal.pbio.1002097	This study of fission yeast reveals that the active and inactive forms of the small GTPase Cdc42 have different rates of lateral diffusion in the membrane, providing insights into how it becomes spontaneously polarized, thereby determining the polarity of the cell.	[ [ "Cell polarization is an evolutionary , ancient cellular property that , in eukaryotes , centers around the Rho-family GTPase Cdc42 .", "Cdc42 , which cycles between active GTP-bound and inactive GDP-bound forms , is locally activated by Guanine nucleotide Exchange Factors ( GEFs ) and accumulates at pres...	[ "The small Rho-family GTPase Cdc42 is critical for cell polarization and polarizes spontaneously in absence of upstream spatial cues .", "Spontaneous polarization is thought to require dynamic Cdc42 recycling through Guanine nucleotide Dissociation Inhibitor ( GDI ) -mediated membrane extraction and vesicle traff...	[ "Cell polarization is a critical feature of most cells that underlies their functional organization .", "A central polarity factor called Cdc42 , a small GTPase targeted to the plasma membrane by prenylation , promotes cell polarization in its active GTP-bound form .", "Cdc42 is a key polarity factor because it...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology" ]	Characterisation of the Native Lipid Moiety of Echinococcus granulosus Antigen B	journal.pntd.0001642	null	[ [ "The larval stage of the cestode parasite Echinococcus granulosus is the causative agent of cystic echinococcosis ( hydatid disease ) in a range of mammalian species ( mainly domestic ungulates ) as well as in humans .", "It is a unilocular fluid-filled cyst , which steadily grows inside host visceras ( m...	[ "Antigen B ( EgAgB ) is the most abundant and immunogenic antigen produced by the larval stage ( metacestode ) of Echinococcus granulosus .", "It is a lipoprotein , the structure and function of which have not been completely elucidated .", "EgAgB apolipoprotein components have been well characterised; they sha...	[ "The larva of the cestode parasite Echinococcus granulosus affects a wide range of livestock mammals and humans , causing cystic echinococcosis ( hydatid disease ) , a zoonosis with significant economic and public health impact .", "The disease is characterised by the growth of a fluid-filled cyst in the host's v...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "social sciences", "neuroscience", "learning and memory", "cognitive neuroscience", "cognition", "memory", "vision", "research and analysis methods", "information retrieval", "sensory physiology", "memory recall", "research assessment", "working memory", "...	Independent working memory resources for egocentric and allocentric spatial information	journal.pcbi.1006563	null	[ [ "Imagine trying to locate your friends while watching a crowded street parade .", "If you catch only a glimpse of them in the crowd before they are obscured by others , remembering how far they were from a nearby building ( a stable landmark in the external world ) may provide a useful cue to help you loc...	[ "Visuospatial working memory enables us to maintain access to visual information for processing even when a stimulus is no longer present , due to occlusion , our own movements , or transience of the stimulus .", "Here we show that , when localizing remembered stimuli , the precision of spatial recall does not re...	[ "Human capacity to maintain spatial information over brief interruptions is strongly limited .", "However , while studies of visual working memory typically examine recall in sparse displays , consisting only of the stimuli to remember , natural scenes are commonly filled with other objects that—although not requ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "biochemistry", "model organisms", "biology" ]	Mitochondrial Oxidative Stress Alters a Pathway in Caenorhabditis elegans Strongly Resembling That of Bile Acid Biosynthesis and Secretion in Vertebrates	journal.pgen.1002553	null	[ [ "In mammals , cholesterol is necessary for the structure and function of membranes , and is the substrate for the biosynthesis of signalling molecules such as sexual steroids , bioactive compounds such as vitamin D , and bile acids ( BAs ) [1] .", "Cholesterol is converted into BAs through a series of oxi...	[ "Mammalian bile acids ( BAs ) are oxidized metabolites of cholesterol whose amphiphilic properties serve in lipid and cholesterol uptake .", "BAs also act as hormone-like substances that regulate metabolism .", "The Caenorhabditis elegans clk-1 mutants sustain elevated mitochondrial oxidative stress and display...	[ "Cholesterol metabolism , in particular the transport of cholesterol in the blood by lipoproteins , is an important determinant of human cardiovascular health .", "Bile acids are breakdown products of cholesterol that have detergent properties and are secreted into the gut by the liver .", "Bile acids carry out...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "brassica", "social sciences", "dna transcription", "model organisms", "genome analysis", "epigenetics", "dna", "plants", "dna methylation", "chromatin", "arabidopsis thaliana", "research and analysis methods", "economic models", "chromosome biology", ...	Limited Contribution of DNA Methylation Variation to Expression Regulation in Arabidopsis thaliana	journal.pgen.1006141	null	[ [ "It has been long speculated that epigenetic modifications , in particular DNA methylation , contribute to heritable phenotypic variation [1 , 2] .", "That the potential exists is not in doubt , especially in plants .", "Modern sequencing technology allows us to investigate DNA methylation on a genome...	[ "The extent to which epigenetic variation affects complex traits in natural populations is not known .", "We addressed this question using transcriptome and DNA methylation data from a sample of 135 sequenced A . thaliana accessions .", "Across individuals , expression was significantly associated with cis-meth...	[ "It has been demonstrated experimentally that epigenetic variation , in particular DNA methylation , can transmit information across generations .", "However , it is difficult to evaluate the importance of such effects in natural populations due to complex genetic background effects , making experimental the sepa...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "293t cells", "pathogens", "biological cultures", "microbiology", "vertebrates", "animals", "mammals", "retroviruses", "viruses", "immunodeficiency viruses", "primates", "rna viruses", "research and analysis methods", ...	Species-specific vulnerability of RanBP2 shaped the evolution of SIV as it transmitted in African apes	journal.ppat.1006906	null	[ [ "RanBP2 ( also known as Nup358 ) is the major constituent of the cytoplasmic filaments extruding from the mammalian nuclear pore complex , where it mediates cargo import and export [1 , 2] .", "Depletion of RanBP2 negatively affects HIV-1 and HIV-2 infection and nuclear import [3–9] .", "Although HIV-...	[ "HIV-1 arose as the result of spillover of simian immunodeficiency viruses ( SIVs ) from great apes in Africa , namely from chimpanzees and gorillas .", "Chimpanzees and gorillas were , themselves , infected with SIV after virus spillover from African monkeys .", "During spillover events , SIV is thought to req...	[ "Multiple times , HIV-1 has entered the human population after emerging from a viral reservoir that exists in African primates .", "First , simian immunodeficiency virus ( SIV ) made the jump from monkeys into African great apes , and then from apes ( namely , chimpanzees and gorillas ) into humans .", "It is w...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	Local Effect of Enhancer of Zeste-Like Reveals Cooperation of Epigenetic and cis-Acting Determinants for Zygotic Genome Rearrangements	journal.pgen.1004665	null	[ [ "Ciliates provide extraordinary model organisms with which to gain understanding into the organization of eukaryotic genomes .", "The differentiation of the somatic nucleus from the zygotic nucleus is characterized by massive and reproducible rearrangements at the DNA level [1] .", "In Paramecium tetr...	[ "In the ciliate Paramecium tetraurelia , differentiation of the somatic nucleus from the zygotic nucleus is characterized by massive and reproducible deletion of transposable elements and of 45 , 000 short , dispersed , single-copy sequences .", "A specific class of small RNAs produced by the germline during meio...	[ "The unicellular eukaryote Paramecium tetraurelia provides an extraordinary model for studying the mechanisms involved in zygotic genome rearrangements .", "At each sexual cycle , differentiation of the somatic nucleus from the zygotic nucleus is characterized by extensive remodeling of the entire somatic genome ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "specimen preparation and treatment", "mechanical treatment of specimens", "biochemistry", "cellular neuroscience", "neurochemistry", "behavioral neuroscience", "specimen disruption", "neuronal morphology", "biology and life sciences", "neurotransmitters", "electroporation", "neuroscience", ...	Mmp1 Processing of the PDF Neuropeptide Regulates Circadian Structural Plasticity of Pacemaker Neurons	journal.pgen.1004700	null	[ [ "The rotation of the earth around its own axis imposes cyclic changes on environmental conditions , primarily through variations on luminosity and temperature .", "The existence of an endogenous , self-sustained and entrainable circadian clock in almost every living organism allows them to anticipate thos...	[ "In the Drosophila brain , the neuropeptide PIGMENT DISPERSING FACTOR ( PDF ) is expressed in the small and large Lateral ventral neurons ( LNvs ) and regulates circadian locomotor behavior .", "Interestingly , PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result...	[ "Circadian clocks have evolved as mechanisms that allow organisms to adapt to the day/night cyclical changes , a direct consequence of the rotation of the Earth .", "In the last two decades , and due to its amazing repertoire of genetic tools , Drosophila has been at the leading front in the discovery of genes th...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "cell biology", "plant biology", "immunology" ]	Rice XB15, a Protein Phosphatase 2C, Negatively Regulates Cell Death and XA21-Mediated Innate Immunity	journal.pbio.0060231	The rice protein phosphatase 2C XB15 is a negative regulator of pathogen recognition receptor kinase-mediated cell death and innate immunity.	[ [ "Protein kinases regulate most cellular signal transduction pathways including cell growth and proliferation , cellular differentiation , morphogenesis , gene transcription , and immunity [1–3] .", "Adaptive immunity , restricted to vertebrates , is characterized by the creation of antigen-specific recept...	[ "Perception of extracellular signals by cell surface receptors is of central importance to eukaryotic development and immunity .", "Kinases that are associated with the receptors or are part of the receptors themselves modulate signaling through phosphorylation events .", "The rice ( Oryza sativa L . ) XA21 rec...	[ "Resistance to pathogens is critical to plant and animal survival .", "Plants , unlike animals , lack an adaptive immune system and instead rely on the innate immune response to protect against infection .", "To elucidate the molecular mechanism of plant innate immunity , we are studying the signaling cascade m...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations	journal.pcbi.1004421	null	[ [ "The ability to reliably measure and predict the effects of amino acid mutations in proteins is of fundamental importance to protein engineering and design and for understanding protein evolution and human genetic variation .", "Data regarding the effects of individual mutations originate from two major s...	[ "Systematic mappings of the effects of protein mutations are becoming increasingly popular .", "Unexpectedly , these experiments often find that proteins are tolerant to most amino acid substitutions , including substitutions in positions that are highly conserved in nature .", "To obtain a more realistic distr...	[ "Understanding and predicting the effects of single nucleotide polymorphisms ( SNPs ) is of fundamental importance in many fields .", "Systematic experimental mappings of the effects of such mutations within a given gene/protein comprise an essential experimental tool for determining protein function and for refi...	2015
[ "Introduction", "Materials and Methods", "Discussion" ]	[]	Biological Control of the Chagas Disease Vector Triatoma infestans with the Entomopathogenic Fungus Beauveria bassiana Combined with an Aggregation Cue: Field, Laboratory and Mathematical Modeling Assessment	journal.pntd.0003778	null	[ [ "Chagas disease , caused by infection with the parasite Trypanosoma cruzi , is the most important vector-borne disease in Latin America .", "It currently affects about 7–8 M people [1] .", "The blood-sucking insect Triatoma infestans ( Hemiptera , Reduviidae ) is the most widespread and relevant vecto...	[ "Current Chagas disease vector control strategies , based on chemical insecticide spraying , are growingly threatened by the emergence of pyrethroid-resistant Triatoma infestans populations in the Gran Chaco region of South America .", "We have already shown that the entomopathogenic fungus Beauveria bassiana has...	[ "Triatomine bugs are the causative agent of Chagas disease ( American trypanosomiasis ) , they transmit the parasite Trypanosoma cruzi by infectious blood-sucking .", "In the southern Cone of South America , Triatoma infestans is the major disease vector .", "The efficacy of chemical control strategies is mostl...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Machines vs. Ensembles: Effective MAPK Signaling through Heterogeneous Sets of Protein Complexes	journal.pcbi.1003278	null	[ [ "Much of our reasoning about the function of biological systems relies on the formation of multi-subunit protein complexes [1] .", "In some cases , such as the ribosome and the proteasome , these complexes take the form of intricate molecular machines with well-defined quaternary structures [2]–[4] .", ...	[ "Despite the importance of intracellular signaling networks , there is currently no consensus regarding the fundamental nature of the protein complexes such networks employ .", "One prominent view involves stable signaling machines with well-defined quaternary structures .", "The combinatorial complexity of sig...	[ "Intracellular signaling networks are central to a cell's ability to adapt to its environment .", "Developing the capacity to effectively manipulate such networks would have a wide range of applications , from cancer therapy to synthetic biology .", "This requires a thorough understanding of the mechanisms of s...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/functional genomics", "genetics and genomics/gene expression", "evolutionary biology/animal behavior" ]	The Drosophila foraging Gene Mediates Adult Plasticity and Gene–Environment Interactions in Behaviour, Metabolites, and Gene Expression in Response to Food Deprivation	journal.pgen.1000609	null	[ [ "The question of how phenotypic plasticity evolves has been the subject of vigorous debate ( reviewed in [1] , [2] , [3] ) , as has the related question of whether allelic variation in single genes can have large impacts on plasticity [3] .", "Phenotypic plasticity is defined as the degree to which the en...	[ "Nutrition is known to interact with genotype in human metabolic syndromes , obesity , and diabetes , and also in Drosophila metabolism .", "Plasticity in metabolic responses , such as changes in body fat or blood sugar in response to changes in dietary alterations , may also be affected by genotype .", "Here w...	[ "Normal individual differences in the foraging ( for ) gene of the fruit fly Drosophila melanogaster result in two behavioral types called rover and sitter .", "Larval rovers show a greater behavioral response to changes in their food environment than sitters .", "The for gene makes an enzyme called PKG , which...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "quantum chemistry", "crystal structure", "enzymes", "split-decomposition method", "dna clamps", "condensed matter physics", "enzymology", "multiple alignment calculation", "protein structure", "dna", "dna structure", "crystallography", "ground state", "research and analysis methods", "s...	Statistical investigations of protein residue direct couplings	journal.pcbi.1006237	null	[ [ "Contacts among residues largely determine a protein’s three-dimensional structure .", "For proteins sharing a common structure , such contacts generally produce correlated substitution patterns between residue pairs .", "Over evolutionary time substitutions at one residue position often result in com...	[ "Protein Direct Coupling Analysis ( DCA ) , which predicts residue-residue contacts based on covarying positions within a multiple sequence alignment , has been remarkably effective .", "This suggests that there is more to learn from sequence correlations than is generally assumed , and calls for deeper investiga...	[ "The success of Direct Coupling Analysis ( DCA ) for protein structure prediction suggests that multiple sequence alignments implicitly contain more structural information than had previously been realized , and prompts deeper investigations of the sequence correlations uncovered by either DCA or other approaches ....	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "hematology/lymphomas and chronic lymphoblastic leukemia", "virology/persistence and latency", "virology/viral replication and gene regulation", "cell biology", "virology/viruses and cancer" ]	Nucleophosmin Phosphorylation by v-Cyclin-CDK6 Controls KSHV Latency	journal.ppat.1000818	null	[ [ "Nucleophosmin ( NPM ) is a multifunctional nucleolar phosphoprotein that constantly shuttles between nucleus and cytoplasm [1] .", "It functions as a molecular chaperone and has been linked to a number of cellular processes from ribosome maturation and transcriptional control to apoptosis ( reviewed in [...	[ "Nucleophosmin ( NPM ) is a multifunctional nuclear phosphoprotein and a histone chaperone implicated in chromatin organization and transcription control .", "Oncogenic Kaposi's sarcoma herpesvirus ( KSHV ) is the etiological agent of Kaposi's sarcoma , primary effusion lymphoma ( PEL ) and multicentric Castleman...	[ "Latency is the predominant mode of viral persistence in KS and PEL tumors , and has a fundamental impact on KSHV tumorigenesis .", "Establishment and maintenance of latency involves a number of viral and cellular factors .", "This study provides a novel functional link between LANA and v-cyclin by showing that...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "immune physiology", "spleen", "immunology", "parasitic diseases", "parasitic protozoans", "bone marrow cells", "organisms", "protozoans", "leishmania", "research and analysis methods", "white blood cells", ...	Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis	journal.ppat.1006422	null	[ [ "Emergency hematopoiesis in response to severe bacterial infection is associated with an expansion of hematopoietic stem/progenitor cells ( HSPCs ) and their progeny , mediated by a combination of environmental cues , including inflammatory cytokines and microbial products [1–4] .", "Activated , prolifera...	[ "Cells of the immune system are derived from hematopoietic stem cells ( HSCs ) residing in the bone marrow .", "HSCs become activated in response to stress , such as acute infections , which adapt the bone marrow output to the needs of the immune response .", "However , the impact of infection-adapted HSC activ...	[ "Hematopoietic stem cells ( HSCs ) are responsible for the generation of all blood cells and thus play an important but often underappreciated role in the host response to infections .", "HSCs are normally dormant , but they can become activated in response to stress , such as infections .", "This stress respon...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/cellular microbiology and pathogenesis", "microbiology/parasitology" ]	Rhomboid 4 (ROM4) Affects the Processing of Surface Adhesins and Facilitates Host Cell Invasion by Toxoplasma gondii	journal.ppat.1000858	null	[ [ "Motility by apicomplexan parasites occurs by a unique form of locomotion called gliding , which relies on the apical secretion of adhesins followed by translocation of adhesin-receptor complexes along the cell surface to the back of the parasite [1] .", "Studies in T . gondii have elucidated the essentia...	[ "Host cell attachment by Toxoplasma gondii is dependent on polarized secretion of apical adhesins released from the micronemes .", "Subsequent translocation of these adhesive complexes by an actin-myosin motor powers motility and host cell invasion .", "Invasion and motility are also accompanied by shedding of ...	[ "Apicomplexan parasites invade host cells using a multi-step process that depends on regulated secretion of adhesins , attachment to the cell , and active penetration .", "Coordinating these activities requires control of proper timing and release of surface proteins that mediate adhesion .", "Parasites like To...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "enzyme-linked immunoassays", "immunology", "vaccines", "preventive medicine", "peptide libraries", "cytotoxic t cells", "vaccination and immunization", "immunologic techniques", "research and analysis methods",...	Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area	journal.pntd.0005263	null	[ [ "Japanese encephalitis ( JE ) virus ( JEV ) is the cause of around 68 000 cases of encephalitis per year in Asia , mostly in children [1] .", "JEV is a single stranded positive sense RNA virus of the family Flaviviridae , genus Flavivirus .", "The JEV genome is 11 kb comprising a single 10 . 3 kb open...	[ "Japanese encephalitis ( JE ) virus ( JEV ) causes severe epidemic encephalitis across Asia , for which the live attenuated vaccine SA14-14-2 is being used increasingly .", "JEV is a flavivirus , and is closely related to dengue virus ( DENV ) , which is co-endemic in many parts of Asia , with clinically relevant...	[ "The Flavivirus genus member Japanese encephalitis ( JE ) virus ( JEV ) , causes severe brain disease in tens of thousands of children across Asia every year .", "JE is vaccine preventable , and the immune response to JEV plays a major role in disease outcome .", "However , the response to JEV is hard to study ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "gene regulation", "cell cycle and cell division", "cell processes", "rna extraction", "microbiology", "protein expression", "molecular biology techniques", "synthesis phase", "extraction techniques", "research and analysis methods", "small interfering rnas", "proteins", "hyp...	Spring viraemia of carp virus modulates p53 expression using two distinct mechanisms	journal.ppat.1007695	null	[ [ "The tumor suppressor p53 is a crucial cellular stress sensor that triggers apoptosis , cell-cycle arrest , and a series life biology processes by responding to environmental stresses such as DNA damage , hyperproliferative signals , and hypoxia [1 , 2] .", "The corresponding cellular responses mediated b...	[ "p53 , which regulates cell-cycle arrest and apoptosis , is a crucial target for viruses to release cells from cell-cycle checkpoints or to protect cells from apoptosis for their own benefit .", "Viral evasion mechanisms of aquatic viruses remain mysterious .", "Here , we report the spring viremia of carp virus...	[ "Upon viral infiltration , host cells employ p53 to defend against infection .", "Thus , viruses need to inhibit these antiviral surveillance mechanisms in the host to efficiently spread to new hosts .", "To date , the evasion mechanisms against fish p53 remain unclear .", "In this study , we reveal that SVCV...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/immunity to infections", "immunology/immune response", "infectious diseases/viral infections", "microbiology", "immunology/immunity to infections" ]	A Therapeutic Antibody against West Nile Virus Neutralizes Infection by Blocking Fusion within Endosomes	journal.ppat.1000453	null	[ [ "Neutralizing antibodies can inhibit virus infection by impeding one of several critical steps of the virus lifecycle .", "These include blocking attachment to the cell surface , interaction with host factors required for internalization , and structural transitions on the virion that drive membrane fusio...	[ "Defining the precise cellular mechanisms of neutralization by potently inhibitory antibodies is important for understanding how the immune system successfully limits viral infections .", "We recently described a potently inhibitory monoclonal antibody ( MAb E16 ) against the envelope ( E ) protein of West Nile v...	[ "Antibodies are essential components of the immune response against many pathogens , including viruses .", "A greater understanding of the mechanisms by which the most strongly inhibitory antibodies act may influence the design and production of novel vaccines or antibody-based therapies .", "Our group recently...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "gene regulation", "293t cells", "enzymes", "biological cultures", "enzymology", "plasmid construction", "phosphatases", "isomerism", "dna construction", "dna", "molecular biology techniques", "isomerization", "research and analysis methods", "small interfering rnas", ...	Prolyl isomerization of FAAP20 catalyzed by PIN1 regulates the Fanconi anemia pathway	journal.pgen.1007983	null	[ [ "The Fanconi anemia ( FA ) DNA repair pathway resolves DNA interstrand cross-links ( ICLs ) and other obstacles encountered during DNA replication [1 , 2] .", "Germ-line mutation of at least 22 genes involved in this pathway not only causes a childhood blood disorder of bone marrow failure , FA , but also...	[ "The Fanconi Anemia ( FA ) pathway is a multi-step DNA repair process at stalled replication forks in response to DNA interstrand cross-links ( ICLs ) .", "Pathological mutation of key FA genes leads to the inherited disorder FA , characterized by progressive bone marrow failure and cancer predisposition .", "T...	[ "Fanconi anemia ( FA ) is a devastating disease of children that leads to birth defects , bone marrow failure , and a variety of cancers early in their lives .", "Germ-line mutations in FA genes disrupt the DNA repair process , namely the FA pathway , resulting in genome instability and clinical features of FA pa...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biotechnology", "signal processing", "biomimetics", "biomechanics", "biological systems engineering", "mathematics", "computational neuroscience", "coding mechanisms", "bioengineering", "biology", "nonlinear dynamics", "biophysics", "speech signal processing", "biophysic al simulations", ...	Prosthetic Avian Vocal Organ Controlled by a Freely Behaving Bird Based on a Low Dimensional Model of the Biomechanical Periphery	journal.pcbi.1002546	null	[ [ "The complex motor behavior originating the rich vocalizations of adult oscine birds results from the interaction between a central pattern generator ( the brain ) and a nonlinear biomechanical periphery ( the bird's vocal organ ) [1] , [2] .", "The fact that this complex behavior is learned , together wi...	[ "Because of the parallels found with human language production and acquisition , birdsong is an ideal animal model to study general mechanisms underlying complex , learned motor behavior .", "The rich and diverse vocalizations of songbirds emerge as a result of the interaction between a pattern generator in the b...	[ "Brain Machine Interfaces ( BMIs ) decode motor instructions from neuro-physiological recordings and feed them to bio-mimetic effectors .", "Many applications achieve high accuracy on a limited number of tasks by applying statistical methods to these data to extract features corresponding to certain motor instruc...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/macromolecular structure analysis", "computational biology/sequence motif analysis", "biochemistry/protein folding", "biophysics/biomacromolecule-ligand interactions", "computational biology/macromolecular sequence analysis", "biochemistry/bioinformatics", "biochemistry/biomacromo...	Accurate Prediction of DnaK-Peptide Binding via Homology Modelling and Experimental Data	journal.pcbi.1000475	null	[ [ "Hsp70 molecular chaperones are part of the quality control machinery that functions to assist protein folding .", "Members of the Hsp70 family have been implicated in refolding of misfolded proteins , folding of newly synthesized polypeptide chains , disassembly of larger aggregates and translocation of ...	[ "Molecular chaperones are essential elements of the protein quality control machinery that governs translocation and folding of nascent polypeptides , refolding and degradation of misfolded proteins , and activation of a wide range of client proteins .", "The prokaryotic heat-shock protein DnaK is the E . coli re...	[ "Molecular chaperones are essential elements of the protein quality control machinery that governs translocation and folding of nascent polypeptides , refolding and degradation of misfolded proteins , and activation of a wide range of client proteins .", "This variety of functions results from the existence of mu...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "dermatology", "pediatrics and child health", "homo (human)", "genetics and genomics" ]	Variants in a Novel Epidermal Collagen Gene (COL29A1) Are Associated with Atopic Dermatitis	journal.pbio.0050242	The gene underlying atopic dermatitis susceptibility has been identified by gene mapping as expressing a novel collagen, whose expression is lacking in the outer epidermis of atopic dermatitis patients.	[ [ "Atopic dermatitis ( AD ) is a chronic inflammatory skin disease that is characterized by intensely itchy skin lesions .", "AD is one of the most common chronic diseases in childhood affecting 10%–20% of children in industrialized societies [1] , with a steady increase over the past decades [2 , 3] .", ...	[ "Atopic dermatitis ( AD ) is a common chronic inflammatory skin disorder and a major manifestation of allergic disease .", "AD typically presents in early childhood often preceding the onset of an allergic airway disease , such as asthma or hay fever .", "We previously mapped a susceptibility locus for AD on Ch...	[ "Atopic dermatitis ( AD , eczema ) is a common chronic inflammatory skin disorder and a major manifestation of allergic disease .", "Typically , AD first occurs in early childhood , often preceding the onset of allergic airways disease , such as asthma and hay fever .", "A family history of allergic disorders i...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "immunology", "parasitic diseases", "helminth infection", "global health", "neglected tropical diseases", "immunomodulation", "infectious diseases", "soil-transmitted helminths", "disease ecology", "public health", "immune response", "clinical ...	Maternal Geohelminth Infections Are Associated with an Increased Susceptibility to Geohelminth Infection in Children: A Case-Control Study	journal.pntd.0001753	null	[ [ "Soil-transmitted helminths ( STHs , also known as geohelminths or intestinal helminths ) are estimated to infect 2 billion people worldwide [1] .", "These parasites , of which Ascaris lumbricoides and Trichuris trichiura are the most prevalent , are a major cause of morbidity related to malnutrition and ...	[ "Children of mothers infected with soil-transmitted helminths ( STH ) may have an increased susceptibility to STH infection .", "We did a case-control study nested in a birth cohort in Ecuador .", "Data from 1 , 004 children aged 7 months to 3 years were analyzed .", "Cases were defined as children with Ascar...	[ "Soil-transmitted helminths ( intestinal worms ) are among the most common childhood infections worldwide and are a significant cause of morbidity particularly among poor populations living in developing countries .", "The potent immune modulatory effects of these parasites have been suggested to be a determinant...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "skin", "blood cells", "dermatology", "invertebrates", "medicine and health sciences", "body fluids", "integumentary system", "pathology and laboratory medicine", "immune physiology", "immune cells", "ears", "immunology", "saliva", "animals", "organisms", "skin infections", "antibodi...	Mosquito Saliva Increases Endothelial Permeability in the Skin, Immune Cell Migration, and Dengue Pathogenesis during Antibody-Dependent Enhancement	journal.ppat.1005676	null	[ [ "During the transmission of arthropod-borne diseases , blood-feeding insects deposit pathogen-containing saliva into the skin [1] .", "How factors in arthropod saliva impact pathogen replication , host responses , and disease outcome is an area of active research .", "The four serotypes of dengue viru...	[ "Dengue remains the most prevalent arthropod-borne viral disease in humans .", "While probing for blood vessels , Aedes aegypti and Ae .", "albopictus mosquitoes transmit the four serotypes of dengue virus ( DENV1-4 ) by injecting virus-containing saliva into the skin .", "Even though arthropod saliva is know...	[ "Mosquitoes inject saliva into the skin while probing for blood vessels .", "Saliva facilitates blood feeding and can contain pathogens when the mosquito is infected .", "In tropical regions , Aedes mosquitoes transmit the four serotypes of dengue virus ( DENV1-4 ) and infect almost 400 million humans every yea...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemical simulations", "biology", "computational biology", "microbiology", "microbial growth and development" ]	Interplay between the Localization and Kinetics of Phosphorylation in Flagellar Pole Development of the Bacterium Caulobacter crescentus	journal.pcbi.1002602	null	[ [ "The localization of proteins is highly regulated throughout all kingdoms of life .", "In eukaryotic cells , asymmetric distributions of proteins contribute to a diverse set of processes including cell-shape determination and motility [1] , embryonic development [2] , stem-cell maintenance [3] , and the s...	[ "Bacterial cells maintain sophisticated levels of intracellular organization that allow for signal amplification , response to stimuli , cell division , and many other critical processes .", "The mechanisms underlying localization and their contribution to fitness have been difficult to uncover , due to the often...	[ "The development of multicellularity requires specialization and differentiation of individual cells .", "The process of differentiation requires the breaking of cellular symmetry , which can be achieved via asymmetric localization of proteins; cell division then gives rise to cells with different compositions an...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "genetic networks", "applied mathematics", "signaling networks", "genetic algorithms", "simulation and modeling", "algorithms", "mathematics", "network analysis", "genome analysis", "pharmacology", "research and analysis methods", "computer and information sci...	Executable pathway analysis using ensemble discrete-state modeling for large-scale data	journal.pcbi.1007317	null	[ [ "Gene set and pathway analysis have become one of the first choices for gaining mechanistic insights from high-throughput sequencing and gene/protein profiling techniques [1] .", "Typically , gene set analysis uses a set of pathway genes to estimate its modulation and discounts pathway topology .", "T...	[ "Pathway analysis is widely used to gain mechanistic insights from high-throughput omics data .", "However , most existing methods do not consider signal integration represented by pathway topology , resulting in enrichment of convergent pathways when downstream genes are modulated .", "Incorporation of signal ...	[ "21st-century biotechnology has enabled measurements of genes and proteins at large scale by RNA sequencing and proteomics technologies .", "In particular , RNA-sequencing has become a first step of unbiased interrogation .", "These studies frequently produce a long list of differentially abundant genes , which...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "infectious diseases", "cell biology", "virology", "immunology", "eukaryotes", "homo (human)" ]	The Ebola Virus VP35 Protein Is a Suppressor of RNA Silencing	journal.ppat.0030086	null	[ [ "An important criterion for productive virus infection is that the virus evades host antiviral immune responses .", "In plants , insects , and nematodes , the basis of these protective immune responses is formed by the RNA interference ( RNAi ) mechanism [1–4] .", "During virus infection , RNAi agains...	[ "RNA silencing or interference ( RNAi ) is a gene regulation mechanism in eukaryotes that controls cell differentiation and developmental processes via expression of microRNAs .", "RNAi also serves as an innate antiviral defence response in plants , nematodes , and insects .", "This antiviral response is trigge...	[ "Cells have evolved mechanisms to protect themselves from virus infection .", "A well-known antiviral mechanism in mammals is the interferon ( IFN ) response of the innate immune system .", "In plants , insects , and worms , RNA silencing or RNA interference ( RNAi ) is a strong antiviral defence mechanism .", ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "animal genetics", "quantitative traits", "epistasis", "speciation", "biology", "hybridization", "evolutionary genetics", "trait locus", "heredity", "animal evolution", "genetics", "haploinsufficiency", "evolutionary biology", "evolutionary processes", "genetics...	Interallelic and Intergenic Incompatibilities of the Prdm9 (Hst1) Gene in Mouse Hybrid Sterility	journal.pgen.1003044	null	[ [ "Hybrid sterility is a condition in which two fertile parental forms produce progeny with disturbed gametogenesis .", "In mammals and Drosophila , it affects spermatogenesis more often than oogenesis [1] .", "Hybrid sterility acts as a reproductive barrier between species [2] .", "Although its mol...	[ "The Dobzhansky-Muller model of incompatibilities explains reproductive isolation between species by incorrect epistatic interactions .", "Although the mechanisms of speciation are of great interest , no incompatibility has been characterized at the gene level in mammals .", "The Hybrid sterility 1 gene ( Hst1 ...	[ "Disturbed gametogenesis in the progeny of two fertile parental forms is called hybrid sterility; it is an important part of reproductive barriers between species .", "The Dobzhansky-Muller model of incompatibilities explains reproductive isolation between species by incorrect interactions between genes .", "Hy...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "emerging infectious diseases", "virology", "biology", "microbiology", "viral diseases" ]	Novel Polyomaviruses of Nonhuman Primates: Genetic and Serological Predictors for the Existence of Multiple Unknown Polyomaviruses within the Human Population	journal.ppat.1003429	null	[ [ "Over recent years the rate of identification of new viruses within human and animal populations has increased exponentially .", "Since 2007 , more than 20 novel animal polyomaviruses have been discovered , and 12 genetically distinct human polyomaviruses are currently known .", "Polyomaviruses are no...	[ "Polyomaviruses are a family of small non-enveloped DNA viruses that encode oncogenes and have been associated , to greater or lesser extent , with human disease and cancer .", "Currently , twelve polyomaviruses are known to circulate within the human population .", "To further examine the diversity of human po...	[ "Polyomaviruses are able to cause severe disease in immunocompromised individuals .", "The discovery of Merkel cell polyomavirus and its association with Merkel cell carcinoma has increased interest in these viruses , resulting in the identification of several novel human polyomaviruses in recent years .", "The...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Recent Selective Sweeps in North American Drosophila melanogaster Show Signatures of Soft Sweeps	journal.pgen.1005004	null	[ [ "The ability to identify genomic loci subject to recent positive selection is essential for our efforts to uncover the genetic basis of phenotypic evolution and to understand the overall role of adaptation in molecular evolution .", "The fruit fly Drosophila melanogaster is one of the classic model organi...	[ "Adaptation from standing genetic variation or recurrent de novo mutation in large populations should commonly generate soft rather than hard selective sweeps .", "In contrast to a hard selective sweep , in which a single adaptive haplotype rises to high population frequency , in a soft selective sweep multiple a...	[ "Evolutionary adaptation is a process in which beneficial mutations increase in frequency in response to selective pressures .", "If these mutations were previously rare or absent from the population , adaptation should generate a characteristic signature in the genetic diversity around the adaptive locus , known...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "simulation languages", "computer science", "programming languages", "biophysic al simulations", "computational neuroscience", "single neuron function", "biology", "computational biology" ]	The Layer-Oriented Approach to Declarative Languages for Biological Modeling	journal.pcbi.1002521	null	[ [ "Scientists who construct computational models of biological processes often find it necessary to use several different software tools in order to carry out various forms of data analysis and model simulation .", "However , each tool may employ its own model description format , consisting of diverse synt...	[ "We present a new approach to modeling languages for computational biology , which we call the layer-oriented approach .", "The approach stems from the observation that many diverse biological phenomena are described using a small set of mathematical formalisms ( e . g . differential equations ) , while at the sa...	[ "The pursuit for understanding of neural function by computational modeling has produced a variety of software tools , with each tool targeting specific audiences and often requiring input in its own distinct language .", "Consequently , comprehending and communicating neuroscience models is a difficult and time-...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "archaea", "microbiology", "molecular biology", "genetics and genomics" ]	Genetic and Physical Mapping of DNA Replication Origins in Haloferax volcanii	journal.pgen.0030077	null	[ [ "In all prokaryotic organisms , and in certain unicellular eukaryotes , DNA replication is thought to initiate at well-defined chromosomal sites .", "These origins of replication serve as assembly sites for the protein machinery that unwinds the DNA duplex and initiates bidirectional DNA synthesis [1 , 2]...	[ "The halophilic archaeon Haloferax volcanii has a multireplicon genome , consisting of a main chromosome , three secondary chromosomes , and a plasmid .", "Genes for the initiator protein Cdc6/Orc1 , which are commonly located adjacent to archaeal origins of DNA replication , are found on all replicons except pla...	[ "Haloferax volcanii is a member of the archaea , which are renowned for thriving in extreme environments .", "Archaea have circular chromosomes like bacteria but use enzymes similar to those found in eukaryotes to replicate their DNA .", "Few archaeal species have systems for genetics , and this has limited our...	2007
[ "Introduction", "Results", "Discussion", "Materials & methods" ]	[ "small nucleolar rnas", "oxidative stress", "gene regulation", "dna-binding proteins", "dna transcription", "fungi", "model organisms", "experimental organism systems", "epigenetics", "chromatin", "schizosaccharomyces", "research and analysis methods", "chromosome biology", "proteins", "...	Bases of antisense lncRNA-associated regulation of gene expression in fission yeast	journal.pgen.1007465	null	[ [ "Eukaryotic genomes are pervasively transcribed [1] , generating plenty of non-coding ( nc ) transcripts , distinct from the housekeeping rRNAs , tRNAs and sn ( o ) RNAs , and that are arbitrarily classified into small ( < 200 nt ) and long ( ≥ 200 nt ) ncRNAs [2 , 3] .", "Long ( l ) ncRNAs are produced b...	[ "Antisense ( as ) lncRNAs can regulate gene expression but the underlying mechanisms and the different cofactors involved remain unclear .", "Using Native Elongating Transcript sequencing , here we show that stabilization of antisense Exo2-sensitivite lncRNAs ( XUTs ) results in the attenuation , at the nascent t...	[ "Examples of regulatory antisense ( as ) lncRNAs acting on gene expression have been reported in multiple model organisms .", "However , despite their regulatory importance , aslncRNAs have been poorly studied , and the molecular bases for aslncRNAs-mediated regulation remain incomplete .", "One reason for the ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/evolutionary modeling", "cell biology/cell growth and division", "computational biology/genomics", "cell biology/nuclear structure and function" ]	Comparative Analysis of DNA Replication Timing Reveals Conserved Large-Scale Chromosomal Architecture	journal.pgen.1001011	null	[ [ "Mammalian genomes are complex and heterogeneous entities , consisting of many thousands of functional elements that are packed into chromosomes and organized in nuclear space .", "Our understanding of the global implications of genome organization , its effect on gene regulation and its evolutionary cons...	[ "Recent evidence suggests that the timing of DNA replication is coordinated across megabase-scale domains in metazoan genomes , yet the importance of this aspect of genome organization is unclear .", "Here we show that replication timing is remarkably conserved between human and mouse , uncovering large regions t...	[ "During S-phase of the cell cycle , chromosomal DNA is replicated in a complex process involving the coordinated activity of thousands of replication forks , each of which duplicates a long stretch of DNA .", "Recent experiments revealed that the genome is replicating as a mosaic of large-scale early and late chr...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	MicroRNA-Dependent Transcriptional Silencing of Transposable Elements in Drosophila Follicle Cells	journal.pgen.1005194	null	[ [ "In many , if not most , eukaryotes , RNA silencing is responsible for the regulation of gene expression via the association of small , 20–30 nucleotide ( nt ) -long , non-coding RNAs with Argonaute proteins ( reviews: [1–4] ) .", "Partial or perfect base pairing between the small RNAs and their RNA targe...	[ "RNA interference-related silencing mechanisms concern very diverse and distinct biological processes , from gene regulation ( via the microRNA pathway ) to defense against molecular parasites ( through the small interfering RNA and the Piwi-interacting RNA pathways ) .", "Small non-coding RNAs serve as specifici...	[ "The fine-tuning of gene expression required for the normal development of multicellular organisms involves small RNAs that are called microRNAs ( miRNAs ) .", "MiRNAs can reduce the stability or the activity of the many cellular messenger RNAs that contain miRNA complementary sequences .", "In animal gonads , ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "eye infections", "medicine", "bacterial diseases", "infectious diseases", "ophthalmology", "neglected tropical diseases", "trachoma" ]	The Easiest Children to Reach Are Most Likely to Be Infected with Ocular Chlamydia trachomatis in Trachoma Endemic Areas of Niger	journal.pntd.0001983	null	[ [ "Mass drug administration with oral azithromycin is known to be effective against trachoma , a blinding eye disease caused by ocular Chlamydia trachomatis .", "To achieve global elimination by 2020 , the WHO recommends district-level mass treatment with antibiotics at 80% coverage for a minimum of 3 years...	[ "Control programs for trachoma use mass antibiotic distributions to treat ocular Chlamydia trachomatis in an effort to eliminate this disease worldwide .", "To determine whether children infected with ocular Chlamydia are more likely to present later for examination than those who are uninfected , we compare the ...	[ "Trachoma is the most common cause of blindness from an infection in the world .", "The bacterium that causes trachoma is called Chlamydia trachomatis and it can be treated with the antibiotic azithromycin .", "Experts recommend trying to reach at least 80% of children for treatment in a community but it is unk...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "molecular probe techniques", "gene regulation", "neuronal differentiation", "immunoblotting", "cell differentiation", "developmental biology", "immunoprecipitation", "stem cells", "molecular biology techniques", "research and analysis methods", "animal cells", "gene expression", "molecular ...	Smek promotes corticogenesis through regulating Mbd3’s stability and Mbd3/NuRD complex recruitment to genes associated with neurogenesis	journal.pbio.2001220	null	[ [ "Neural stem cells ( NSCs ) are self-renewing , multipotent cells that generate major neural cell types , including neurons and glia , in the developing central nervous system ( CNS ) [1 , 2] .", "During neurogenesis , NSCs are derived from neuroepithelial cells ( NECs ) , which first divide symmetrically...	[ "The fate of neural progenitor cells ( NPCs ) during corticogenesis is determined by a complex interplay of genetic or epigenetic components , but the underlying mechanism is incompletely understood .", "Here , we demonstrate that Suppressor of Mek null ( Smek ) interact with methyl-CpG–binding domain 3 ( Mbd3 ) ...	[ "Neural progenitor cells are self-renewing , multipotent cells that generate major neural cell types , including neurons and glia .", "Their fate during development of the cerebral cortex is determined by a complex interplay of genetic and epigenetic components .", "It has been shown that Suppressor of Mek null...	2017
[ "Introduction", "Methods", "Results and discussion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "ultraviolet radiation", "helminths", "database searching", "light", "disinfection", "animals", "electromagnetic radiation", "health care", "preventive medicine", "developmental biology", "ascaris", ...	Ultraviolet sensitivity of WASH (water, sanitation, and hygiene) -related helminths: A systematic review	journal.pntd.0007777	null	[ [ "In 2016 , WASH-related helminth infections ( e . g . schistosomiasis , soil-transmitted helminthiases , taeniasis ) were responsible for over 9 . 5 million years lost due to ill-health , disability or early death [1] .", "They are transmitted through contact with ( or consumption of ) water , food , and ...	[ "Helminthiases are a group of disabling neglected tropical diseases that affect billions of people worldwide .", "Current control methods use preventative chemotherapy but reinfection is common and an inter-sectoral approach is required if elimination is to be achieved .", "Household and community scale water t...	[ "Helminth infections are currently controlled by mass administration of anthelmintic drugs which are effective at treating the diseases but cannot prevent reinfection .", "As we work to eliminate these diseases , complimentary control methods such as improving access to water , sanitation , and hygiene will be cr...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "in vitro", "homo (human)", "genetics and genomics", "mammals" ]	The ets-Related Transcription Factor GABP Directs Bidirectional Transcription	journal.pgen.0030208	null	[ [ "Since the discovery that more than 10% of the protein-coding genes in the human genome are located on opposite strands with transcription start sites less than 1 kb away from each other , there has been considerable interest in determining why such an arrangement exists [1–3] .", "Studies in mammals and ...	[ "Approximately 10% of genes in the human genome are distributed such that their transcription start sites are located less than 1 kb apart on opposite strands .", "These divergent gene pairs have a single intergenic segment of DNA , which in some cases appears to share regulatory elements , but it is unclear whet...	[ "Surveys of the locations of genes in the human genome have revealed that a surprising number of genes , greater than 10% , have transcription start sites within 1 kb of one another on opposite strands .", "These divergent gene pairs , sometimes referred to as bidirectional genes , are common in organisms such as...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "cellular stress responses", "gene regulation", "cell processes", "dna transcription", "molecular biology techniques", "research and analysis methods", "transcriptional control", "artificial gene amplification and extension", "proteins", "gene expression", "molecular biology...	Regulation of transcription elongation in response to osmostress	journal.pgen.1007090	null	[ [ "Cells sense and robustly respond to environmental fluctuations to maximize cell fitness .", "An increase in extracellular osmolarity provokes immediate cellular responses that are crucial for cell survival .", "These responses are mainly controlled by the High Osmolarity Glycerol ( HOG ) pathway [1 ,...	[ "Cells trigger massive changes in gene expression upon environmental fluctuations .", "The Hog1 stress-activated protein kinase ( SAPK ) is an important regulator of the transcriptional activation program that maximizes cell fitness when yeast cells are exposed to osmostress .", "Besides being associated with t...	[ "Cells coordinate various intracellular activities in response to sudden changes in the environment to maximize survival and cell fitness .", "Clear examples of this are the regulation of gene expression and cell cycle progression .", "Stress-Activated Protein Kinase ( SAPK ) signaling pathway acts as the centr...	2017
[ "Introduction", "Methods", "Results/Discussion" ]	[ "public and occupational health", "political science", "infectious diseases", "veterinary diseases", "medicine and health sciences", "global health", "biology and life sciences", "social sciences", "veterinary science" ]	One Health: Past Successes and Future Challenges in Three African Contexts	journal.pntd.0002884	null	[ [ "One Health acknowledges the close relationships between humans , animals and ecosystems , promoting the potential added benefits to each sector or species that emerge as a result of its operationalisation ( Figure 1 ) .", "Whilst attempts to categorically define One Health are many and varied , the gener...	[ "The recent emergence of zoonotic diseases such as Highly Pathogenic Avian Influenza ( HPAI ) and Severe Acute Respiratory Syndrome ( SARS ) have contributed to dominant Global Health narratives around health securitisation and pandemic preparedness , calling for greater co-operation between the health , veterinary...	[ "The One Health movement requires more robust evidence around its practical implementation if it is to truly become a way forwards for addressing health issues at the human , animal and ecosystem interface .", "The research in this paper discusses some of the recent successes and challenges with both Emerging and...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/infectious diseases of the nervous system", "cell biology/cell signaling", "infectious diseases/fungal infections", "cell biology/morphogenesis and cell biology", "neurological disorders/infectious diseases of the nervous system", "microbiology", "infectious diseases/respiratory inf...	Cryptococcal Cell Morphology Affects Host Cell Interactions and Pathogenicity	journal.ppat.1000953	null	[ [ "Unicellular organisms exhibit morphological changes under a wide variety of environmental conditions .", "In many pathogenic fungi , the ability to switch cell morphology is integral to the infection cycle .", "Dimorphic fungi , such as Blastomyces dermatitidis and Histoplasma capsulatum , grow in th...	[ "Cryptococcus neoformans is a common life-threatening human fungal pathogen .", "The size of cryptococcal cells is typically 5 to 10 µm .", "Cell enlargement was observed in vivo , producing cells up to 100 µm .", "These morphological changes in cell size affected pathogenicity via reducing phagocytosis by ho...	[ "Cryptococcus neoformans is a common life-threatening opportunistic human fungal pathogen .", "C . neoformans grows as a budding yeast in vitro with typical cell sizes ranging from 5 to 10 µm in diameter .", "Early reports suggested the presence of enlarged cells in human infections yet the identity of these ce...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "inflammatory diseases", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "microbiology", "salmonella typhi", "pulmonology", "vaccines", "pneumonia", "bacterial diseases", "signs and symptoms", "enterobacteriaceae", "infectious disease contro...	Integration of enteric fever surveillance into the WHO-coordinated Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) platform: A low cost approach to track an increasingly important disease	journal.pntd.0005999	null	[ [ "Enteric fever ( typhoid/paratyphoid ) is a major cause of mortality and morbidity in many low and middle-income countries .", "In 2015 , it was estimated to cause about 178 , 000 deaths and 17 million illnesses; 85% of all cases occur in three countries—Bangladesh , India and Pakistan [1–3] .", "The ...	[ "Lack of surveillance systems and accurate data impede evidence-based decisions on treatment and prevention of enteric fever , caused by Salmonella Typhi/Paratyphi .", "The WHO coordinates a global Invasive Bacterial–Vaccine Preventable Diseases ( IB-VPD ) surveillance network but does not monitor enteric fever ....	[ "Typhoid/paratyphoid fever imposes a major global burden , specifically in low-and-middle-income countries ( LMICs ) .", "However , it is challenging to implement evidence-based decisions for treatment and prevention because of lack of data from comprehensive surveillance systems , which are often expensive and d...	2017
[ "Introduction", "Methods", "Results and Discussion" ]	[ "infectious diseases/neglected tropical diseases", "biophysics/theory and simulation", "pharmacology/drug development", "infectious diseases/protozoal infections", "computational biology/molecular dynamics" ]	Novel Naphthalene-Based Inhibitors of Trypanosoma brucei RNA Editing Ligase 1	journal.pntd.0000803	null	[ [ "Subspecies of Trypanosoma brucei ( T . brucei ) are the causative agents of human African trypanosomiasis ( HAT , also known as African sleeping sickness ) in sub-Saharan Africa .", "Neglected tropical diseases , including parasitic trypanosomal illnesses like HAT , Chagas disease , and leishmaniasis , a...	[ "Neglected tropical diseases , including diseases caused by trypanosomatid parasites such as Trypanosoma brucei , cost tens of millions of disability-adjusted life-years annually .", "As the current treatments for African trypanosomiasis and other similar infections are limited , new therapeutics are urgently nee...	[ "African sleeping sickness is a devastating disease that plagues sub-Saharan Africa .", "Neglected tropical diseases like African sleeping sickness cause significant death and suffering in the world's poorest countries .", "Current treatments for African sleeping sickness either have high costs , terrible side ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "in vitro", "molecular biology", "eubacteria", "computational biology" ]	Positive and Negative Design in Stability and Thermal Adaptation of Natural Proteins	journal.pcbi.0030052	null	[ [ "Despite recent advances in computational protein design [1] , there is no complete understanding of basic principles that govern design and selection of naturally occurring proteins [2] .", "In particular , the physical basis for the ability of proteins to achieve an adaptation to a wide variety of exter...	[ "The aim of this work is to elucidate how physical principles of protein design are reflected in natural sequences that evolved in response to the thermal conditions of the environment .", "Using an exactly solvable lattice model , we design sequences with selected thermal properties .", "Compositional analysis...	[ "What mechanisms does Nature use in her quest for thermophilic proteins ?", "It is known that stability of a protein is mainly determined by the energy gap , or the difference in energy , between native state and a set of incorrectly folded ( misfolded ) conformations .", "Here we show that Nature makes thermop...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods", "Statistical analyses" ]	[ "invertebrates", "bacteriophages", "animals", "wolbachia", "animal models", "viruses", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism systems", "population biology", "embryos", "bacteria", "drosophila", "research and analysis methods", "em...	The phage gene wmk is a candidate for male killing by a bacterial endosymbiont	journal.ppat.1007936	null	[ [ "Wolbachia ( order Rickettsiales ) infect an estimated 40–52% of all arthropod species [1 , 2] and 47% of filarial nematode species [3] , making them the most widespread intracellular bacterial symbiont in animals .", "Concentrated in host testes and ovaries , Wolbachia primarily transmit cytoplasmically ...	[ "Wolbachia are the most widespread maternally-transmitted bacteria in the animal kingdom .", "Their global spread in arthropods and varied impacts on animal physiology , evolution , and vector control are in part due to parasitic drive systems that enhance the fitness of infected females , the transmitting sex of...	[ "Male killing is an adaptive trait for bacteria that are maternally transmitted through host populations .", "Such bacteria are common in arthropods and resultantly have significant impacts on host population size , mating strategy , and evolution .", "Moreover , male-killing bacteria are under recent scrutiny ...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immunology", "animal models", "model organisms", "clinical medicine", "experimental organism systems", "cytotoxic t cells", "bacteria", "research and analysis methods", "white blood cells", "major histocompatibility complex", ...	MHC Ib molecule Qa-1 presents Mycobacterium tuberculosis peptide antigens to CD8+ T cells and contributes to protection against infection	journal.ppat.1006384	null	[ [ "As the causative agent of tuberculosis ( TB ) , Mycobacterium tuberculosis ( Mtb ) is a continuing global public health concern that kills approximately 2 million people annually , with an estimated one-third of the world’s population infected with Mtb [1] .", "The emergence of multidrug-resistant Mtb , ...	[ "A number of nonclassical MHC Ib molecules recognizing distinct microbial antigens have been implicated in the immune response to Mycobacterium tuberculosis ( Mtb ) .", "HLA-E has been identified to present numerous Mtb peptides to CD8+ T cells , with multiple HLA-E-restricted cytotoxic T lymphocyte ( CTL ) and r...	[ "The disease tuberculosis ( TB ) is caused by the microbe Mycobacterium tuberculosis ( Mtb ) , and remains a major public health concern .", "More research is needed to understand the diverse immune responses against Mtb to develop better vaccines .", "Mouse Qa-1 and its human counterpart HLA-E are nonclassical...	2017
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "linguistics", "medicine and health sciences", "protein metabolism", "metabolic processes", "social sciences", "glycolysis", "diabetes mellitus", "endocrine disorders", "computer and information sciences", "endocrinology", "metabolic pathways", "gene expression", "chemistry", "metabolic di...	Using the Semantic Web for Rapid Integration of WikiPathways with Other Biological Online Data Resources	journal.pcbi.1004989	null	[ [ "Pathway analysis and visualisation of data on pathways provide insights into the underlying biology of effects found in genomics , proteomics , and metabolomics experiments [1–4] .", "WikiPathways is a pathway repository where content is provided by the community at large [5 , 6] .", "In a given path...	[ "The diversity of online resources storing biological data in different formats provides a challenge for bioinformaticians to integrate and analyse their biological data .", "The semantic web provides a standard to facilitate knowledge integration using statements built as triples describing a relation between tw...	[ "WikiPathways is a crowd-sourced online platform for biological pathways .", "It is based on the same underlying platform as Wikipedia .", "Pathways are saved as graphical images embedded in a set of meta data elements ( i . e . references , list of pathways elements , and context annotations ) .", "Pathways ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "cellular structures", "signal transduction", "cellular stress responses", "molecular cell biology", "cell biology", "viral immune evasion", "veterinary microbiology", "virology", "biology", "microbiology", "host-pathogen interaction", "molecular biology", "veterinary science" ]	African Swine Fever Virus Uses Macropinocytosis to Enter Host Cells	journal.ppat.1002754	null	[ [ "ASFV is a 200 nm large DNA virus that infects different species of swine , causing acute and often fatal disease [1]–[3] .", "Infection by ASFV is characterized by the absence of a neutralizing immune response , which has so far hampered the development of a conventional vaccine .", "A strong hazard ...	[ "African swine fever ( ASF ) is caused by a large and highly pathogenic DNA virus , African swine fever virus ( ASFV ) , which provokes severe economic losses and expansion threats .", "Presently , no specific protection or vaccine against ASF is available , despite the high hazard that the continued occurrence o...	[ "ASFV is a highly pathogenic zoonotic virus , which can cause severe economic losses and bioterrorism threats .", "No vaccine against ASFV is available so far .", "A strong hazard of ASFV dissemination through EU countries from Caucasian areas has recently emerged , thus making urgent to acquire knowledge and t...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients	journal.pntd.0004179	null	[ [ "In Spain , leishmaniasis is an endemic zoonosis caused by Leishmania infantum .", "The national mean annual incidence is 0 . 45 cases/100 , 000 inhabitants , similar to that traditionally reported for the capital , Madrid ( 0 . 5 cases/100 , 000 inhabitants ) [1] .", "A few years ago , an unusual , l...	[ "Spain has one of the world’s largest pools of organ donors and is a global leader in terms of the number of transplants it performs .", "The current outbreak of leishmaniasis in Fuenlabrada ( in the southwest of the region of Madrid , Spain ) has involved 600 clinical cases since late 2009 ( prevalence 0 . 2% ) ...	[ "We have used cytokine release assays to determine the prevalence of Leishmania infantum infection in solid organ transplant ( SOT ) recipients living in an area where the organism is endemic following an outbreak .", "Some 21 . 05% of SOT recipients with no previous history of leishmaniasis had been in contact w...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "flow cytometry", "cell death", "medicine and health sciences", "autophagic cell death", "body fluids", "pathology and laboratory medicine", "intracellular pathogens", "cardiovascular anatomy", "pathogens", "cell processes", "analysis of variance", "mutation", "mathematics", "statistics (m...	Heterogeneity in pneumolysin expression governs the fate of Streptococcus pneumoniae during blood-brain barrier trafficking	journal.ppat.1007168	null	[ [ "The complex battle between the microbial virulence strategies and the host’s counter-defensive mechanisms governs the ultimate outcome of infection .", "Traditional approaches involving the bulk population based model considers each interacting partner as a functionally homogenous entity , overlooking th...	[ "Outcome of host-pathogen encounter is determined by the complex interplay between protective bacterial and host defense strategies .", "This complexity further amplifies with the existence of cell-to-cell phenotypic heterogeneity in pathogens which remains largely unexplored .", "In this study , we illustrated...	[ "Streptococcus pneumoniae , the Gram-positive diplococci , is the primary etiological agent of bacterial meningitis .", "In order to cause central nervous system ( CNS ) infections , SPN has to breach the blood-brain barrier , however , the pneumococcal determinants involved in this process remain unidentified ."...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome expression analysis", "genetic networks", "functional genomics", "genome scans", "statistics", "population genetics", "microbiology", "histone modification", "genome analysis tools", "model organisms", "mathematics", "trait locus analysis", "epigenetics", "biostatistics", "geneti...	Genetic Modifiers of Chromatin Acetylation Antagonize the Reprogramming of Epi-Polymorphisms	journal.pgen.1002958	null	[ [ "Recent studies have shown that individuals largely differ in their epigenomic chromatin signatures .", "This finding makes tracking epigenetic marks in natural populations attractive , including investigating their possible contribution to the variation of common physiological traits .", "So far , ep...	[ "Natural populations are known to differ not only in DNA but also in their chromatin-associated epigenetic marks .", "When such inter-individual epigenomic differences ( or “epi-polymorphisms” ) are observed , their stability is usually not known: they may or may not be reprogrammed over time or upon environmenta...	[ "Chemical modifications of chromatin , such as DNA methylation , incorporation of histone variants , or post-translational modifications of histone proteins , constitute the “epigenome” and confer specific properties to genome functions .", "Epigenomes differ from one individual to another , opening the exciting ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral transmission and infection", "viral classification", "enzymes", "viral enzymes", "immunology", "host-pathogen interaction", "microbiology", "animal models", "model organisms", "rna viruses", "signaling pathways", "viral nucleic acid", "viral clearance", "enzyme classes", "viral im...	RIG-I and MDA-5 Detection of Viral RNA-dependent RNA Polymerase Activity Restricts Positive-Strand RNA Virus Replication	journal.ppat.1003610	null	[ [ "The innate immune system is an ancient set of host defense mechanisms that utilize germline-encoded receptors for the recognition of pathogens [1] .", "This set of receptors , termed pathogen recognition receptors ( PRRs ) , binds to the pathogen's own structural or pathogen-induced molecules and trigger...	[ "Type I interferons ( IFN ) are important for antiviral responses .", "Melanoma differentiation-associated gene 5 ( MDA-5 ) and retinoic acid-induced gene I ( RIG-I ) proteins detect cytosolic double-stranded RNA ( dsRNA ) or 5′-triphosphate ( 5′-ppp ) RNA and mediate IFN production .", "Cytosolic 5′-ppp RNA an...	[ "Type I interferons ( IFN ) are critical for mounting effective antiviral responses by the host cells .", "For RNA viruses , it is believed that IFN is triggered exclusively by viral double-stranded RNA ( dsRNA ) or RNA containing a 5′-triphosphate ( 5′-ppp ) that is produced during viral genome replication or tr...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "medicine and health sciences", "immune physiology", "body fluids", "pathology and laboratory medicine", "spleen", "pathogens", "microbiology", "vertebrates", "animals", "mammals", "animal models", "viruses", "model organisms", "rna viruses", "signs and symptoms", "global...	Severe Hemorrhagic Fever in Strain 13/N Guinea Pigs Infected with Lujo Virus	journal.pntd.0001801	null	[ [ "Beginning in the 1930s , novel pathogenic arenaviruses have been increasingly recognized as emerging threats to human health [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] .", "During the 1960s and 1970s , several previously unknown arenaviruses emerged as a significant public health threats ...	[ "Lujo virus ( LUJV ) is a novel member of the Arenaviridae family that was first identified in 2008 after an outbreak of severe hemorrhagic fever ( HF ) .", "In what was a small but rapidly progressing outbreak , this previously unknown virus was transmitted from the critically ill index patient to 4 attending he...	[ "The pathogenic arenaviruses are a diverse group of human pathogens capable of causing a wide range of human illness ranging from encephalitis to severe hemorrhagic fever throughout the New and Old World .", "In 2008 , a previously unknown virus ( now named Lujo virus ) caused a high case fatality outbreak ( 80% ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "helminth infections", "schistosomiasis", "medicine and health sciences", "drug research and development", "drug discovery for neglected diseases", "neglected tropical diseases", "biology and life sciences", "pharmacology", "drug discovery", "tropical diseases", "parasitic diseases", "parasito...	Inhibition or Knockdown of ABC Transporters Enhances Susceptibility of Adult and Juvenile Schistosomes to Praziquantel	journal.pntd.0003265	null	[ [ "Schistosomiasis is a highly prevalent tropical disease caused by parasitic flatworms of the genus Schistosoma .", "It is widespread , affecting hundreds of millions throughout the tropics and sub-tropics , with devastating effects on human health and economic development .", "Estimates suggest that s...	[ "Parasitic flatworms of the genus Schistosoma cause schistosomiasis , a neglected tropical disease that affects hundreds of millions .", "Treatment of schistosomiasis depends almost entirely on the drug praziquantel ( PZQ ) .", "Though essential to treating and controlling schistosomiasis , a major limitation o...	[ "Schistosomes are parasitic flatworms that cause schistosomiasis , a tropical disease affecting hundreds of millions worldwide .", "Praziquantel ( PZQ ) is the current drug of choice against schistosomiasis , and , indeed , is the only approved antischistosomal treatment available in most parts of the world .", ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunology/immunomodulation", "infectious diseases/neglected tropical diseases", "public health and epidemiology/infectious diseases", "infectious diseases/protozoal infections", "molecular biology", "immunology/immunity to infections", "pathology/molecular pathology" ]	Coinfection with Different Trypanosoma cruzi Strains Interferes with the Host Immune Response to Infection	journal.pntd.0000846	null	[ [ "Chagas disease ( CD ) , a life-long complex illness caused by the protozoan parasite Trypanosoma cruzi , was firstly described by Carlos Chagas in 1909 , but it is still acknowledged by the World Health Organization ( WHO ) as one of the most important neglected tropical diseases and as a significant public ...	[ "A century after the discovery of Trypanosoma cruzi in a child living in Lassance , Minas Gerais , Brazil in 1909 , many uncertainties remain with respect to factors determining the pathogenesis of Chagas disease ( CD ) .", "Herein , we simultaneously investigate the contribution of both host and parasite factors...	[ "Chagas disease , a life-long parasitic disease caused by the flagellate protozoan Trypanosoma cruzi , was discovered a century ago by the Brazilian physician Carlos Chagas , and remains one of the most neglected tropical diseases , affecting 13 million people in Latin America .", "Disease is characterized by dis...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology" ]	Transmission of West Nile Virus by Culex quinquefasciatus Say Infected with Culex Flavivirus Izabal	journal.pntd.0000671	null	[ [ "The majority of the >70 recognized flaviviruses ( family Flaviviridae , genus Flavivirus ) are arthropod-borne , and include some of the world's most historically- and medically-important viruses including Yellow fever ( YFV ) and the Dengue ( DENV ) viruses .", "Gaunt et al . [1] described four distinct...	[ "The natural history and potential impact of mosquito-specific flaviviruses on the transmission efficiency of West Nile virus ( WNV ) is unknown .", "The objective of this study was to determine whether or not prior infection with Culex flavivirus ( CxFV ) Izabal altered the vector competence of Cx .", "quinque...	[ "Unlike most known flaviviruses ( Family , Flaviviridae: Genus , Flavivirus ) , insect-only flaviviruses are a unique group of flaviviruses that only infect invertebrates .", "The study of insect-only flaviviruses has increased in recent years due to the discovery and characterization of numerous novel flavivirus...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna replication", "cell biology/cellular death and stress responses", "molecular biology/recombination", "cell biology/cell growth and division", "genetics and genomics/chromosome biology", "genetics and genomics/gene function", "molecular biology/dna repair" ]	Simultaneous Disruption of Two DNA Polymerases, Polη and Polζ, in Avian DT40 Cells Unmasks the Role of Polη in Cellular Response to Various DNA Lesions	journal.pgen.1001151	null	[ [ "DNA replication involves a rapid but fragile enzymatic mechanism that is frequently stalled by damage in the DNA template .", "To complete DNA replication , DNA lesions are bypassed by specialized DNA polymerases , a process called translesion synthesis ( TLS ) ( reviewed in [1] , [2] ) .", "A number...	[ "Replicative DNA polymerases are frequently stalled by DNA lesions .", "The resulting replication blockage is released by homologous recombination ( HR ) and translesion DNA synthesis ( TLS ) .", "TLS employs specialized TLS polymerases to bypass DNA lesions .", "We provide striking in vivo evidence of the co...	[ "DNA replication is a fragile biochemical reaction , as the replicative DNA polymerases are readily stalled by DNA lesions .", "The resulting replication blockage is released by translesion DNA synthesis ( TLS ) , which employs specialized TLS polymerases to bypass DNA lesions .", "There are at least seven TLS ...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods", "Model description" ]	[ "medicine and health sciences", "cardiovascular anatomy", "simulation and modeling", "diabetes mellitus", "endocrine disorders", "mitochondria", "bioenergetics", "cellular structures and organelles", "research and analysis methods", "oxidation-reduction reactions", "lipids", "endocrinology", ...	Mitochondrial respiration and ROS emission during β-oxidation in the heart: An experimental-computational study	journal.pcbi.1005588	null	[ [ "Fatty Acids ( FAs ) are main sources of cellular energy affecting mitochondrial energetics and redox balance .", "The lipid energy content becomes available from β-oxidation as reducing equivalents and acetyl CoA ( AcCoA ) of which the latter , after further processing in the tricarboxylic acid cycle , a...	[ "Lipids are main fuels for cellular energy and mitochondria their major oxidation site .", "Yet unknown is to what extent the fuel role of lipids is influenced by their uncoupling effects , and how this affects mitochondrial energetics , redox balance and the emission of reactive oxygen species ( ROS ) .", "Emp...	[ "Lipids are main sources of energy for liver and cardiac and skeletal muscle .", "Mitochondria are the main site of lipid oxidation which , in the heart , supplies most of the energy required for its blood pumping function .", "Paradoxically , however , lipids over supply impair mitochondrial function leading t...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "computational biology/transcriptional regulation", "molecular biology/transcription elongation", "biochemistry/transcription and translation" ]	Regulon-Specific Control of Transcription Elongation across the Yeast Genome	journal.pgen.1000614	null	[ [ "It is well known that RNA pol II accumulates under repressive conditions on some tightly regulated genes of higher eukaryotes , like human c-Myc [1] and Drosophila hsp70 [2] .", "RNA pol II pausing is in fact a frequent situation since a significant proportion of metazoan genes exhibits paused polymerase...	[ "Transcription elongation by RNA polymerase II was often considered an invariant non-regulated process .", "However , genome-wide studies have shown that transcriptional pausing during elongation is a frequent phenomenon in tightly-regulated metazoan genes .", "Using a combination of ChIP-on-chip and genomic ru...	[ "Transcription of DNA–encoded information into RNA is the first step in gene regulation .", "RNA polymerases initiate transcription at the promoter region and elongate the transcripts traveling throughout the gene until reaching the termination sequences .", "Classical models of transcriptional regulation were ...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "drug research and development", "drugs and devices", "protozoology", "biology", "microbiology", "drug discovery", "pharmacology", "parasitology" ]	Isothermal Microcalorimetry, a New Tool to Monitor Drug Action against Trypanosoma brucei and Plasmodium falciparum	journal.pntd.0001668	null	[ [ "Human African trypanosomiasis ( HAT ) , also known as African sleeping sickness , and malaria are important tropical diseases caused by protozoan parasites .", "HAT threatens millions of people living in sub-Saharan Africa [1] .", "In recent years , the number of cases dropped due to improved control...	[ "Isothermal microcalorimetry is an established tool to measure heat flow of physical , chemical or biological processes .", "The metabolism of viable cells produces heat , and if sufficient cells are present , their heat production can be assessed by this method .", "In this study , we investigated the heat flo...	[ "Microcalorimetry is a technology developed to record minute changes in temperature as a result of physical , chemical or biological reactions over time .", "The method has been applied to bacterial and eukaryotic cells and it was found that the metabolic activity of living cells in a culture medium produces enou...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "diagnostic radiology", "social sciences", "neuroscience", "learning and memory", "cognitive psychology", "mathematics", "statistics (mathematics)", "cognition", "brain mapping", "test statistics", "memory", "vision", "neuroimaging", "discrete mathematics"...	Saccades are phase-locked to alpha oscillations in the occipital and medial temporal lobe during successful memory encoding	journal.pbio.2003404	null	[ [ "Sampling of visual information has been shown to be rhythmic rather than continuous [1–3] .", "In particular , brain rhythms clocked by oscillations in the alpha ( 7–14 Hz ) range [4] constrain visual sampling: electroencephalography ( EEG ) /magnetoencephalography ( MEG ) studies in humans have shown th...	[ "Efficient sampling of visual information requires a coordination of eye movements and ongoing brain oscillations .", "Using intracranial and magnetoencephalography ( MEG ) recordings , we show that saccades are locked to the phase of visual alpha oscillations and that this coordination is related to successful m...	[ "In everyday life , we constantly move our eyes to sample visual information .", "In order to make the sampling efficient , these eye movements need to be coordinated with the intrinsic brain dynamics that constrain visual computations .", "The present study provides novel evidence for how this coordination is ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "crystal structure", "immunology", "condensed matter physics", "microbiology", "electron cryo-microscopy", "vaccines", "preventive medicine", "microscopy", "protein structure", "crystallography", "infectious disease control", "v...	Structural roles of PCV2 capsid protein N-terminus in PCV2 particle assembly and identification of PCV2 type-specific neutralizing epitope	journal.ppat.1007562	null	[ [ "In early 1990s , a postweaning multisystemic wasting syndrome ( PMWS ) outbreak in Western Canada [1] was reported due to the spreading of a small , non-enveloped virus containing a single-stranded , circular DNA genome , which was later diagnosed as the porcine circovirus ( PCV ) [2] .", "Subsequently ,...	[ "Postweaning multisystemic wasting disease ( PMWS ) in piglets caused by porcine circovirus type 2 ( PCV2 ) is one of the major threats to most pig farms worldwide .", "Among all the PCV types , PCV2 is the dominant genotype causing PMWS and associated diseases .", "Considerable efforts were made to study the v...	[ "Porcine circovirus type 2 ( PCV2 ) is considered as one of the most wide-spread pathogens threatening swine production by causing postweaning multisystemic wasting disease ( PMWS ) in piglets worldwide .", "Several VLP-based PCV2 vaccines are commercially available which significantly reduce the viral burden and...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "developmental biology" ]	Hox Paralog Group 2 Genes Control the Migration of Mouse Pontine Neurons through Slit-Robo Signaling	journal.pbio.0060142	Homeodomain-containing Hox factors are well-known for controlling body patterning, but a new study reveals a novel role for these genes in controlling the long-distance tangential migration of neurons in the mouse brain stem through transcriptional regulation of Robo receptor-Slit ligand family guidance molecules.	[ [ "In the developing central nervous system ( CNS ) , neurons migrate sometimes over long distances from their birthplace to their final location , where they condense in specific nuclei .", "As neuronal function depends upon precise connectivity with their targets , the final positioning of migrating neuro...	[ "The pontine neurons ( PN ) represent a major source of mossy fiber projections to the cerebellum .", "During mouse hindbrain development , PN migrate tangentially and sequentially along both the anteroposterior ( AP ) and dorsoventral ( DV ) axes .", "Unlike DV migration , which is controlled by the Netrin-1/D...	[ "In the developing central nervous system , neurons migrate sometimes over long distances from their birthplace to their final location , where they condense in specific nuclei .", "The precise positioning of migrating neurons is critical to the building of ordered connectivity with their target partners .", "L...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "ecology", "microbiology", "evolutionary biology", "genetics and genomics", "eubacteria" ]	From Parasite to Mutualist: Rapid Evolution of Wolbachia in Natural Populations of Drosophila	journal.pbio.0050114	A parasitic endosymbiont,Wolbachia, has rapidly evolved towards a more mutualistic lifestyle with itsDrosophila host in under 20 years, suggesting a dynamic interaction between parasitic and mutualistic lifestyles.	[ [ "When microbes that live within animal cells are transmitted only maternally , their reproductive success is directly tied to that of the matrilines they inhabit .", "Both intuition and mathematics suggest that such endosymbionts will be selected towards mutualism , if possible , increasing the fecundity ...	[ "Wolbachia are maternally inherited bacteria that commonly spread through host populations by causing cytoplasmic incompatibility , often expressed as reduced egg hatch when uninfected females mate with infected males .", "Infected females are frequently less fecund as a consequence of Wolbachia infection .", "...	[ "Wolbachia are endosymbiotic bacteria that live inside the cells of their invertebrate hosts .", "They are transmitted directly from mother to offspring , and spread through populations by manipulating the reproduction of their hosts .", "The most common reproductive manipulation responsible for the spread of t...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Persistent Chaos of Measles Epidemics in the Prevaccination United States Caused by a Small Change in Seasonal Transmission Patterns	journal.pcbi.1004655	null	[ [ "Acute immunizing infections remain a leading cause of death worldwide , and have accounted for a significant portion of all morbidity and mortality throughout human history , especially among children and in countries without adequate vaccination coverage [1–4] .", "Understanding the processes that deter...	[ "Epidemics of infectious diseases often occur in predictable limit cycles .", "Theory suggests these cycles can be disrupted by high amplitude seasonal fluctuations in transmission rates , resulting in deterministic chaos .", "However , persistent deterministic chaos has never been observed , in part because su...	[ "Measles epidemics continue to pose a significant public health risk wherever vaccination coverage is low .", "In such populations transmission rates tend to fluctuate seasonally , mirroring patterns of human aggregation , due to the timing of school terms , and/or the migration of workers and their families .", ...	2016

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