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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" ]	[ "reverse transcriptase-polymerase chain reaction", "fish", "gene knockout", "vertebrates", "animals", "alleles", "animal models", "osteichthyes", "developmental biology", "mutation", "model organisms", "experimental organism systems", "molecular biology techniques", "embryos", "frameshif...	Multiplexed CRISPR/Cas9-mediated knockout of 19 Fanconi anemia pathway genes in zebrafish revealed their roles in growth, sexual development and fertility	journal.pgen.1007821	null	[ [ "Fanconi anemia ( FA ) is a rare , mostly recessive , DNA repair deficiency disorder characterized by progressive bone marrow failure ( BMF ) , predisposition to cancer and developmental anomalies including hypogonadism and infertility [1 , 2] .", "About 2/3 of patients display congenital abnormalities af...	[ "Fanconi Anemia ( FA ) is a genomic instability syndrome resulting in aplastic anemia , developmental abnormalities , and predisposition to hematological and other solid organ malignancies .", "Mutations in genes that encode proteins of the FA pathway fail to orchestrate the repair of DNA damage caused by DNA int...	[ "Deficiencies in repair of DNA damage can cause diseases such as Fanconi anemia ( FA ) , which is characterized by birth defects , bone marrow failure , anemia , leukemia and other cancers .", "A set of proteins constitute the FA pathway and together orchestrate the DNA repair process .", "Inactivation of one o...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "allosteric regulation", "crystal structure", "chemical compounds", "aliphatic amino acids", "enzymes", "condensed matter physics", "enzymology", "organic compounds", "mutation", "network analysis", "amino acids", "crystallography", "enzyme chemistry", "aromatic amino acids", "alanine", ...	Dynamic Allostery Mediated by a Conserved Tryptophan in the Tec Family Kinases	journal.pcbi.1004826	null	[ [ "Kinase domains consist of a bi-lobal structure , the N- and C-lobes , which together create the catalytic site to transfer a phosphate from ATP to a substrate hydroxyl ( Fig 1A ) [1 , 2] .", "Transition between active and inactive kinase structures involves concerted motions of specific regions of second...	[ "Bruton’s tyrosine kinase ( Btk ) is a Tec family non-receptor tyrosine kinase that plays a critical role in immune signaling and is associated with the immunological disorder X-linked agammaglobulinemia ( XLA ) .", "Our previous findings showed that the Tec kinases are allosterically activated by the adjacent N-...	[ "Bruton’s tyrosine kinase ( Btk ) belongs to the Tec family of protein tyrosine kinases , and plays a crucial role in the signaling pathway in B-cells .", "Alteration of Btk activity results in the serious immunological disorder , X-linked agammaglobulinemia .", "Btk is a multi-domain protein and the activity o...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "cytokines", "molecular probe techniques", "gene regulation", "pathogens", "immunology", "microbiology", "immunoblotting", "developmental biology...	Fas-associated factor 1 mediates NADPH oxidase-induced reactive oxygen species production and proinflammatory responses in macrophages against Listeria infection	journal.ppat.1008004	null	[ [ "Innate immune cells are the first barrier encountered by invading microbial pathogens .", "Among these cells , phagocytes such as macrophages and neutrophils play key roles in host protection against bacterial infection .", "Upon recognition and phagocytosis of bacteria , phagocytes produce reactive ...	[ "Fas-associated factor 1 is a death-promoting protein that induces apoptosis by interacting with the Fas receptor .", "Until now , FAF1 was reported to interact potentially with diverse proteins and to function as a negative and/or positive regulator of several cellular possesses .", "However , the role of FAF1...	[ "Phagocytic NADPH oxidase plays a pivotal role in generating reactive oxygen species ( ROS ) and in defense against bacterial infections such as L . monocytogenes .", "ROS eliminate phagocytosed bacteria directly and are implicated in transduction of signals that mediate inflammatory responses .", "Here , we sh...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "phosphorylation", "medicine and health sciences", "immune cells", "gene regulation", "immunology", "cell processes", "fibroblasts", "fluorescence-activated cell sorting", "immunoprecipitation", "connective tissue cells", "rna isolation", "molecular biology techniques", "res...	TRIM2, a novel member of the antiviral family, limits New World arenavirus entry	journal.pbio.3000137	TRIM2, one of the proteins mutated in Charcot Marie Tooth Disease, blocks the entry of new world arenaviruses into cells, a novel mechanism for antiviral TRIM proteins, which generally restrict viruses at other stages of infection.	[ [ "Arenaviruses are enveloped single-stranded RNA viruses whose entry is mediated by the viral glycoprotein ( GP ) , generated by proteolytic processing of a precursor into the envelope proteins GP1 , GP2 , and stable signal peptide ( SSP ) , a third subunit required for virus–cell fusion [1] .", "The clade...	[ "Tripartite motif ( TRIM ) proteins belong to a large family with many roles in host biology , including restricting virus infection .", "Here , we found that TRIM2 , which has been implicated in cases of Charcot–Marie–Tooth disease ( CMTD ) in humans , acts by blocking hemorrhagic fever New World arenavirus ( NW...	[ "New World arenaviruses ( NWAs ) are rodent-transmitted viruses that cause high mortality when they evolve the ability to infect humans .", "Although these clade B pathogenic viruses are known to bind to transferrin receptor 1 and other receptors on the cell surface , the steps leading to their entry into the cel...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "enzymes", "pathogens", "293t cells", "biological cultures", "microbiology", "enzymology", "viruses", "mutation", "rna viruses", "viral load", "research and analysis m...	Virulence difference of five type I dengue viruses and the intrinsic molecular mechanism	journal.pntd.0007202	null	[ [ "Dengue virus ( DENV ) is currently the most popular mosquito-borne virus and widely spreads in tropical and subtropical regions[1] .", "A series of symptoms caused by DENV , such as dengue hemorrhagic fever/dengue shock syndrome ( DHF/DSS ) , seriously threaten human health[2 , 3] .", "Dengue virus b...	[ "Dengue virus ( DENV ) is the most important vector-borne virus globally .", "The safe and effective vaccines are still under development and there are no antiviral drugs for DENV induced diseases .", "In this study , we obtained five DENV1 isolates ( DENV1 A to E ) from the outbreak of dengue fever in 2014 of ...	[ "Dengue is the most important vector-borne viral infection that endangers an estimated 2 . 5 billion people globally .", "The recently licensed dengue vaccine has major weaknesses and there are no antiviral drugs for the treatment of dengue related diseases .", "Identifying the virulence determinants is importa...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "geographical locations", "tropical diseases", "parasitic diseases", "surgical and invasive medical procedures", "health care", "filariasis", "neglected tropical diseases", "infectious disease control", "lymphatic filariasis", "morbidity", "public and occupation...	Morbidity management and disability prevention for lymphatic filariasis in Sri Lanka: Current status and future prospects	journal.pntd.0006472	null	[ [ "A total of eight districts ( Colombo , Gampaha , Kalutara , Galle , Matara , Hambantota , Puttalam and Kurunegala ) belonging to three provinces ( Western , Southern and North Western ) in Sri Lanka were identified as endemic for LF during the elimination program ( see Fig 1 ) .", "Post-MDA surveillance ...	[ "Sri Lanka was acknowledged to have eliminated lymphatic filariasis ( LF ) as a public health problem in 2016 , largely due to its success in Mass Drug Administration ( MDA ) to interrupt disease transmission .", "Analysis of the Strengths , Weaknesses , Opportunities and Threats ( SWOT ) of the national Morbidit...	[ "Lymphatic filariasis ( LF ) is a tropical disease causing swelling of limbs ( lymphoedema , elephantiasis ) and male genitalia ( hydrocele ) .", "It is a disabling and deforming disease caused by parasitic worms transmitted by mosquitoes .", "The Sri Lankan Anti Filariasis Campaign was successful in reducing L...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computer and information sciences", "neural networks", "network analysis", "computational neuroscience", "evolutionary modeling", "biology and life sciences", "computational biology", "neuroscience", "artificial neural networks" ]	Evolution of Integrated Causal Structures in Animats Exposed to Environments of Increasing Complexity	journal.pcbi.1003966	null	[ [ "Many studies have sought to elucidate the role of information in evolution [1]–[4] , its relation to fitness [5]–[7] , and how information about the environment is acquired and inherited by an organism [8] , [9] .", "Common to most current approaches to characterize and quantify information in biology is...	[ "Natural selection favors the evolution of brains that can capture fitness-relevant features of the environment's causal structure .", "We investigated the evolution of small , adaptive logic-gate networks ( “animats” ) in task environments where falling blocks of different sizes have to be caught or avoided in a...	[ "The capacity to integrate information is a prominent feature of biological brains and has been related to cognitive flexibility as well as consciousness .", "To investigate how environment complexity affects the capacity for information integration , we simulated the evolution of artificial organisms ( “animats”...	2014
[ "Introduction", "Method", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "african trypanosomiasis", "nervous system", "sociology", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "parasitic protozoans", "animals", "glossina", "human families", "protozoans",...	Description of the first sleeping sickness case diagnosed in Burkina Faso since two decades	journal.pntd.0006677	null	[ [ "Human African trypanosomiasis ( HAT ) , or sleeping sickness , is a neglected tropical disease caused by the protozoan parasites Trypanosoma brucei ( T . b . ) gambiense and T . b . rhodesiense , which are transmitted through the bites of infected tsetse flies ( Glossina spp . ) .", "Control of T . b . g...	[ "Burkina Faso belongs to a group of countries in which human African trypanosomiasis ( HAT ) , caused by Trypanosoma brucei gambiense , is no longer considered to be a public health problem .", "Although no native cases have been detected since 1993 , there is still the risk of HAT re-emergence due to significant...	[ "In 2012 , the roadmap for the Control of Neglected Tropical Diseases ( NTD ) of the World Health Organization ( WHO ) included human African trypanosomiasis ( HAT ) to be eliminated as a public health problem by 2020 .", "To reach this ambitious objective in Burkina Faso , where the vector ( and consequently a r...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "multiple sclerosis", "hispanic people", "neurodegenerative diseases", "statistics", "immunology", "geographical locations", "genetic mapping", "ethnicities", "demyelinating disorders", "clinical medicine", "mathematics", "test statistics", "african american...	Admixture mapping reveals evidence of differential multiple sclerosis risk by genetic ancestry	journal.pgen.1007808	null	[ [ "Multiple sclerosis ( MS ) is an autoimmune disease of the central nervous system that results in demyelination and tissue loss .", "Association studies in White , non-Hispanic populations have discovered human leukocyte antigen ( HLA ) alleles conferring strong risk and protective effects and 200 non-HLA...	[ "Multiple sclerosis ( MS ) is an autoimmune disease with high prevalence among populations of northern European ancestry .", "Past studies have shown that exposure to ultraviolet radiation could explain the difference in MS prevalence across the globe .", "In this study , we investigate whether the difference i...	[ "Multiple sclerosis ( MS ) is an autoimmune disease that is mostly found in populations with northern European ancestry .", "Our study investigates whether there is evidence that the difference in MS prevalence around the globe could be explained by European MS genetic risk factors in African Americans , Hispanic...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Arming of MAIT Cell Cytolytic Antimicrobial Activity Is Induced by IL-7 and Defective in HIV-1 Infection	journal.ppat.1005072	null	[ [ "Mucosa-associated invariant T ( MAIT ) cells are a recently described subset of unconventional , innate-like T cells that are highly abundant in mucosal tissues , liver and circulation of healthy humans [1–4] .", "MAIT cells express a semi-invariant T cell receptor ( TCR ) , including Vα7 . 2 coupled wit...	[ "Mucosa-associated invariant T ( MAIT ) cells represent a large innate-like evolutionarily conserved antimicrobial T-cell subset in humans .", "MAIT cells recognize microbial riboflavin metabolites from a range of microbes presented by MR1 molecules .", "MAIT cells are impaired in several chronic diseases inclu...	[ "The mucosa-associated invariant T ( MAIT ) cells recognize antigens that are byproducts of the riboflavin biosynthesis pathway shared by many microbes .", "These antigens are presented by the MHC class I-like MR1 molecules and trigger rapid activation of MAIT cells in an innate-like fashion with deployment of ef...	2015
[ "Introduction", "Results/Discussion", "Materials and methods" ]	[ "biofilms", "medicine and health sciences", "vesicles", "extracellular matrix composition", "pathology and laboratory medicine", "pathogens", "biological cultures", "microbiology", "fungi", "experimental organism systems", "pharmacology", "cellular structures and organelles", "fungal pathoge...	Candida albicans biofilm–induced vesicles confer drug resistance through matrix biogenesis	journal.pbio.2006872	null	[ [ "Vesicles are released externally by cells of bacteria , archaea , and eukaryotes [1–3] .", "These extracellular vesicles ( EVs ) deliver cargo of RNA and protein that is protected by a surrounding lipid bilayer .", "Classes of EVs have been distinguished based upon their size , cargo , and mechanisms...	[ "Cells from all kingdoms of life produce extracellular vesicles ( EVs ) .", "Their cargo is protected from the environment by the surrounding lipid bilayer .", "EVs from many organisms have been shown to function in cell–cell communication , relaying signals that impact metazoan development , microbial quorum s...	[ "Candida albicans—the most common fungal pathogen in humans—often grows as a biofilm , resulting in an infection that is difficult to treat .", "These adherent communities tolerate extraordinarily high concentrations of antifungals due in large part to the protective extracellular matrix .", "The present study ...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biofilms", "medicine and health sciences", "crystal structure", "pathology and laboratory medicine", "chemical compounds", "monomers", "pathogens", "condensed matter physics", "microbiology", "organic compounds", "crystallography", "bacteria", "bacterial pathogens", "research and analysis...	Structural basis of DSF recognition by its receptor RpfR and its regulatory interaction with the DSF synthase RpfF	journal.pbio.3000123	Many Gram-negative bacteria communicate using quorum-sensing autoinducers called diffusible signal factors (DSFs). Structure-function studies in Burkholderia reveal the interaction of a DSF with its receptor as well as the interaction of the receptor with the DSF synthase.	[ [ "Quorum sensing is a form of bacterial cell–cell communication that enables populations of bacteria to synchronize their gene expression in order to coordinate group behaviors such as bioluminescence , sporulation , genetic competence , biofilm formation , motility , and virulence factor expression ( reviewed...	[ "The diffusible signal factors ( DSFs ) are a family of quorum-sensing autoinducers ( AIs ) produced and detected by numerous gram-negative bacteria .", "The DSF family AIs are fatty acids , differing in their acyl chain length , branching , and substitution but having in common a cis-2 double bond that is requir...	[ "Communication between many species of gram-negative bacteria is mediated by a family of cell–cell signaling autoinducers ( AIs ) known as the diffusible signal factors ( DSFs ) .", "DSFs are fatty acids , containing a signature cis-2 double bond critical for their activity .", "The DSFs differ from one another...	2019
[ "Introduction", "Results", "Discussion", "Models" ]	[ "classical mechanics", "gene regulation", "dna transcription", "molecular genetics", "thermodynamics", "chromatin", "chromosome biology", "gene expression", "biophysics theory", "biophysics", "physics", "systems biology", "biochemistry", "cell biology", "nucleic acids", "interdisciplin...	Torsion-Mediated Interaction between Adjacent Genes	journal.pcbi.1003785	null	[ [ "Transcription involves the separation of the two DNA strands by the RNA Polymerase complex during the initiation phase .", "The formation of this “transcription bubble” [1] can represent a significant energetic cost , determined by the universal thermodynamic properties of the DNA molecule , and may thus...	[ "DNA torsional stress is generated by virtually all biomolecular processes involving the double helix , in particular transcription where a significant level of stress propagates over several kilobases .", "If another promoter is located in this range , this stress may strongly modify its opening properties , and...	[ "During the transcription process , the genetic sequence encoded in the DNA molecule is expressed by an enzymatic complex .", "This process is often considered as independent for each gene , despite numerous reported cases of one transcribed gene perturbing a neighbor gene's expression , which is then regarded as...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary ecology", "ecology", "evolutionary biology", "global change ecology", "biology", "population ecology", "biodiversity", "behavioral ecology" ]	Quantitative Assessment of the Importance of Phenotypic Plasticity in Adaptation to Climate Change in Wild Bird Populations	journal.pbio.1001605	Parameterisation of a mechanistic population model with data from a 51-year study on great tits suggests that phenotypic plasticity is crucial for viability of bird populations under current climate change scenarios.	[ [ "Evidence that climate change influences many properties of wild populations of animals and plants is now ubiquitous [1]–[4] .", "As a consequence , there is widespread concern about the demographic and evolutionary effects of changing climate for the long-term viability of populations .", "A popular ...	[ "Predictions about the fate of species or populations under climate change scenarios typically neglect adaptive evolution and phenotypic plasticity , the two major mechanisms by which organisms can adapt to changing local conditions .", "As a consequence , we have little understanding of the scope for organisms t...	[ "Predictions about the effect of climate change on organisms often ignore the possibility that organisms can evolve , or that they have an inbuilt capacity to cope with changing conditions .", "In order to understand the potential for existing populations to adapt to climate change , and the relative risks of ext...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "sequencing techniques", "sequence analysis", "genome complexity", "genome evolution", "bioinformatics", "database and informatics methods", "biology and life sciences", "comparative genomics", "molecular biology techniques", "computational biology", "molecular biology", "research and analysis...	Synonymous Constraint Elements Show a Tendency to Encode Intrinsically Disordered Protein Segments	journal.pcbi.1003607	null	[ [ "The rapid development of comparative genomics approaches along with the fast increase in the number of sequenced genomes provides us with a clearer view on evolutionarily conserved and hence potentially functional genome regions [1] .", "All the underlying approaches are based on the notion that mutation...	[ "Synonymous constraint elements ( SCEs ) are protein-coding genomic regions with very low synonymous mutation rates believed to carry additional , overlapping functions .", "Thousands of such potentially multi-functional elements were recently discovered by analyzing the levels and patterns of evolutionary conser...	[ "Certain genomic regions code for multiple , overlapping functionalities that can be detected by analyzing the levels and patterns of their evolutionary conservation .", "The redundant nature of the genetic code facilitates the appearance of such multi-functional gene regions through evolution .", "At many of t...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "animal pathogens", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "bacterial diseases", "lymph nodes", "lymphatic system", "bacteria", "immune system proteins", "infectious diseases", "proteins", "tuberculosis", "acti...	Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis	journal.pntd.0004541	null	[ [ "Tuberculosis ( TB ) caused by mycobacteria of the Mycobacterium tuberculosis complex ( MTBC ) is one of the world's most common causes of death from infectious diseases [1] .", "Animal TB is caused by infection with Mycobacterium bovis and closely related members of the MTBC .", "Cattle are the main ...	[ "Mycobacteria of the Mycobacterium tuberculosis complex ( MTBC ) greatly impact human and animal health worldwide .", "The mycobacterial life cycle is complex , and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood .", "Eurasian wild boar ( Sus scrofa ) are natur...	[ "Mycobacteria of the Mycobacterium tuberculosis complex ( MTBC ) are zoonotic pathogens representing a serious health problem for humans and animals worldwide .", "The life cycle of mycobacteria is complex , and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood .",...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "biochemistry", "cell biology", "virology", "in vitro" ]	Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine γ-Herpesvirus 68	journal.ppat.0040025	null	[ [ "Gammaherpesviruses are DNA viruses comprising a subfamily of the Herpesviridae .", "These viruses , including Epstein-Barr virus , Kaposi's sarcoma-associated herpesvirus ( KSHV ) and murine γ-herpesvirus 68 ( γHV68 ) , are etiological agents of lymphoid and epithelial tumors in human or animals [1 , 2] ...	[ "All gammaherpesviruses express homologues of antiapoptotic B-cell lymphoma-2 ( BCL-2 ) to counter the clearance of infected cells by host antiviral defense machineries .", "To gain insights into the action mechanisms of these viral BCL-2 proteins , we carried out structural and biochemical analyses on the intera...	[ "In higher animals , defective or surplus cells are removed by a process known as apoptosis .", "On the other hand , defective or damaged cellular components are removed by a process known as autophagy .", "These two destructive processes are indispensable for the survival and development of an organism .", "...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/gene expression", "computational biology/transcriptional regulation", "developmental biology/pattern formation", "developmental biology/cell differentiation", "developmental biology/neurodevelopment", "computational biology/systems biology" ]	Robustness under Functional Constraint: The Genetic Network for Temporal Expression in Drosophila Neurogenesis	journal.pcbi.1000760	null	[ [ "Precise coordination of cell fate decisions is crucial in the development of multicellular organisms .", "In the developmental processes , where a series of events occurs at a specific place and time , gene regulatory networks are responsible for implementing reliable biological functions [1] , [2] .", ...	[ "Precise temporal coordination of gene expression is crucial for many developmental processes .", "One central question in developmental biology is how such coordinated expression patterns are robustly controlled .", "During embryonic development of the Drosophila central nervous system , neural stem cells call...	[ "Cell fate specification is of key importance in the development of multicellular organisms .", "To specify various cell fates correctly , genetic networks precisely coordinate spatial and temporal gene expression patterns during various developmental stages .", "One central question in developmental biology is...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology", "homo (human)", "genetics and genomics" ]	The Genetic Structure of Pacific Islanders	journal.pgen.0040019	null	[ [ "The populations in New Guinea and the islands immediately to the east ( the Bismarck and Solomons archipelagos ) are well-known for their great diversity in cultures , languages , and genetics , which by a number of measures is unsurpassed for a region of this size [1] .", "This area is referred to as Ne...	[ "Human genetic diversity in the Pacific has not been adequately sampled , particularly in Melanesia .", "As a result , population relationships there have been open to debate .", "A genome scan of autosomal markers ( 687 microsatellites and 203 insertions/deletions ) on 952 individuals from 41 Pacific populatio...	[ "The origins and current genetic relationships of Pacific Islanders have been the subjects of interest and controversy for many decades .", "By analyzing the variation of a large number ( 687 ) of genetic markers in almost 1 , 000 individuals from 41 Pacific populations , and comparing these with East Asians and ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	An Interaction between KSHV ORF57 and UIF Provides mRNA-Adaptor Redundancy in Herpesvirus Intronless mRNA Export	journal.ppat.1002138	null	[ [ "Post-transcriptional events which regulate mRNA biogenesis are fundamental to the control of gene expression [1] .", "A nascent mRNA is therefore steered through multimeric RNA-protein complexes that mediate its capping , splicing , polyadenylation , nuclear export and ultimately its translation [2] , [3...	[ "The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor , TAP , via a direct interaction with the export adaptor , Aly .", "Intriguingly however , depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export , suggesting the existence of additiona...	[ "Herpesviruses hijack cellular components to enhance viral gene expression .", "This is particularly important for the efficient nuclear export of herpesvirus intronless mRNAs to allow the production of viral proteins .", "We have previously demonstrated that Kaposi's sarcoma-associated herpesvirus encodes a co...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection	journal.ppat.1005053	null	[ [ "Dengue virus ( DV ) is a member of the Flavivirus genus of the Flaviviridae family .", "Dengue virus is a positive-sense , single-stranded RNA virus and it has four distinct serotypes ( DV1 to 4 ) .", "Infection by one serotype only confer resistance to the other serotypes for a few months and subseq...	[ "Dengue virus ( DV ) infection is the most prevalent mosquito-borne viral disease and its manifestation has been shown to be contributed in part by the host immune responses .", "In this study , pathogen recognition receptors , Toll-like receptor ( TLR ) 2 and TLR6 were found to be up-regulated in DV-infected hum...	[ "Despite the prevalence of dengue virus infection and the heavy economic burden it puts on the endemic countries , the immunopathogenesis of dengue virus infection remains unclear .", "Plasma leakage in dengue hemorrhagic fever ( DHF ) develops not when the viremia is at its peak in infected patients but when vir...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Novel Intergenic ETnII-β Insertion Mutation Causes Multiple Malformations in Polypodia Mice	journal.pgen.1003967	null	[ [ "The molecular causes of vertebrate malformations and the molecular basis of the variability in Mendelian syndromes are incompletely understood .", "While coding alterations have received a substantial amount of attention , the contribution of variation or mutation in intergenic regions , as well as the r...	[ "Mouse early transposon insertions are responsible for ∼10% of spontaneous mutant phenotypes .", "We previously reported the phenotypes and genetic mapping of Polypodia , ( Ppd ) , a spontaneous , X-linked dominant mutation with profound effects on body plan morphogenesis .", "Our new data shows that mutant mic...	[ "Mobile genetic elements , particularly early transposons ( ETn ) , cause malformations by inserting within genes leading to disruption of exons , splicing or polyadenylation .", "Few mutagenic early transposon insertions have been found outside genes and the effects of such insertions on surrounding gene regulat...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "gastrin", "microbiome", "pathology and laboratory medicine", "pathogens", "atrophy", "microbiology", "hormones", "histology", "helicobacter", "signs and symptoms", "gastroenterology and hepatology", "stomach", "bacteria", "bacterial pathogens", "microbi...	Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use	journal.ppat.1006653	null	[ [ "Gastric adenocarcinoma is the third most common cause of cancer related mortality worldwide[1] and most cases are associated with chronic Helicobacter pylori infection .", "Gastric cancer usually develops via the premalignant condition of gastric atrophy , which is associated with the loss of acid-secret...	[ "Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy .", "Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma , autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours , whereas p...	[ "Different conditions such as autoimmune atrophic gastritis and Helicobacter pylori associated atrophic gastritis are associated with different types of gastric cancer , specifically neuroendocrine tumours and adenocarcinoma .", "Both conditions result in reduced gastric acid secretion , potentially allowing non-...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "action potentials", "engineering and technology", "nervous system", "signal processing", "membrane potential", "brain", "electrophysiology", "neuroscience", "network analysis", "nerve fibers", "computer and information sciences", "animal cells", "axons", ...	Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on spatial response properties of relay cells	journal.pcbi.1005930	null	[ [ "Visual signals from the retina pass through the dorsal geniculate nucleus ( dLGN ) , the visual part of thalamus , on the way to the visual cortex .", "However , this is not simply a one-way flow of information: cortical cells feed back to both relay cells ( RCs ) and interneurons ( INs ) in the dLGN and...	[ "Despite half-a-century of research since the seminal work of Hubel and Wiesel , the role of the dorsal lateral geniculate nucleus ( dLGN ) in shaping the visual signals is not properly understood .", "Placed on route from retina to primary visual cortex in the early visual pathway , a striking feature of the dLG...	[ "The functional role of the dorsal lateral geniculate nucleus ( dLGN ) , placed on route from retina to primary visual cortex in the early visual pathway , is still poorly understood .", "A striking feature of the dLGN circuit is that dLGN cells not only receive feedforward input from the retina , but also a prom...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Abscission Is Regulated by the ESCRT-III Protein Shrub in Drosophila Germline Stem Cells	journal.pgen.1004653	null	[ [ "Abscission is the last step of cytokinesis when sister cells linked by a thin cytoplasmic bridge become physically separated .", "It takes place on the side of an electron dense structure called the midbody that resides within the bridge .", "Unexplored for many years , this late step of cell divisio...	[ "Abscission is the final event of cytokinesis that leads to the physical separation of the two daughter cells .", "Recent technical advances have allowed a better understanding of the cellular and molecular events leading to abscission in isolated yeast or mammalian cells .", "However , how abscission is regula...	[ "Abscission is the final step of cytokinesis which allows the physical separation of sister cells through the scission of a thin cytoplasmic bridge that links them at the end of mitosis .", "The duration of abscission varies depending on cell types , indicating that the event is developmentally regulated .", "R...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "microbial mutation", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "vertebrates", "rabbits", "animals", "mammals", "retroviruses", "primates", "animal models", "immunodeficiency viruses", "mutation"...	Epitopes for neutralizing antibodies induced by HIV-1 envelope glycoprotein BG505 SOSIP trimers in rabbits and macaques	journal.ppat.1006913	null	[ [ "The induction of neutralizing-antibody responses against human immunodeficiency virus type 1 ( HIV-1 ) is the objective of vaccine programs based on various soluble envelope glycoprotein ( Env ) trimers ( reviewed in [1–12] ) .", "The prototype native-like recombinant Env trimer is the BG505 SOSIP . 664 ...	[ "The native-like , soluble SOSIP . 664 trimer based on the BG505 clade A env gene of HIV-1 is immunogenic in various animal species , of which the most studied are rabbits and rhesus macaques .", "The trimer induces autologous neutralizing antibodies ( NAbs ) consistently but at a wide range of titers and with in...	[ "A protective vaccine would constitute a breakthrough in efforts to curb the global spread of HIV .", "Such a vaccine should induce antibodies inhibiting infection by most strains of the virus that circulate worldwide .", "Engineered SOSIP trimer mimics of the envelope glycoprotein on the surface of HIV particl...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "distance measurement", "ecology and environmental sciences", "crystal structure", "engineering and technology", "condensed matter physics", "aquatic environments", "materials science", "crystallography", "surfactants", "cellular structures and organelles", "thermodynamics", "detergents", "l...	The Environment Shapes the Inner Vestibule of LeuT	journal.pcbi.1005197	null	[ [ "Stringent regulation of neurotransmission is essential for brain function .", "Secondary active transporters from the solute carrier family 6 ( SLC6 ) terminate signal propagation by clearing released neurotransmitters from the synaptic cleft .", "This is achieved by coupling substrate transport to t...	[ "Human neurotransmitter transporters are found in the nervous system terminating synaptic signals by rapid removal of neurotransmitter molecules from the synaptic cleft .", "The homologous transporter LeuT , found in Aquifex aeolicus , was crystallized in different conformations .", "Here , we investigated the ...	[ "Crystal structures of the bacterial small amino acid transporter LeuT provided structural evidence for the alternating access model .", "Thereby , these structures shaped our understanding of the mechanisms underlying substrate translocation by neurotransmitter transporters .", "However , it has been questione...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/molecular evolution", "genetics and genomics/microbial evolution and genomics", "genetics and genomics/comparative genomics", "computational biology/transcriptional regulation", "computational biology/comparative sequence analysis", "microbiology/microbial evolution and genomics", "molecul...	Reconstruction of the Core and Extended Regulons of Global Transcription Factors	journal.pgen.1001027	null	[ [ "Organisms rely on regulatory networks to integrate and process signals from various sources and to orchestrate the transcription of genes controlling a range of cellular processes .", "Importantly , changes in the architecture of these regulatory networks play a significant role in survival or adaptation...	[ "The processes underlying the evolution of regulatory networks are unclear .", "To address this question , we used a comparative genomics approach that takes advantage of the large number of sequenced bacterial genomes to predict conserved and variable members of transcriptional regulatory networks across phyloge...	[ "An important property of living systems is the use of regulatory networks to appropriately program gene expression .", "Central to the function of regulatory networks are transcription factors that regulate gene expression by binding to specific DNA sequences .", "Despite the central role of these regulatory n...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "animal diseases", "medicine and health sciences", "antiviral immune response", "foot and mouth disease", "enzymes", "immunology", "enzymology", "vertebrates", "animals", "mammals", "sequence motif analysis", "molecular biology techniques", "zoology", "research and analys...	Innate immune sensor LGP2 is cleaved by the Leader protease of foot-and-mouth disease virus	journal.ppat.1007135	null	[ [ "Antiviral response against RNA viruses greatly relies on detection of infection by cytoplasmic sensors .", "Among the different pattern-recognition receptors ( PRRs ) involved in antiviral immunity , the retinoic acid-inducible gene-I ( RIG-I ) -like receptors ( RLRs ) , recognize non-self RNA species de...	[ "The RNA helicase LGP2 ( Laboratory of Genetics and Physiology 2 ) is a non-signaling member of the retinoic acid-inducible gene-I ( RIG-I ) -like receptors ( RLRs ) , whose pivotal role on innate immune responses against RNA viruses is being increasingly uncovered .", "LGP2 is known to work in synergy with melan...	[ "Foot-and-mouth disease virus ( FMDV ) is the causative agent of a devastating disease affecting livestock worldwide .", "FMDV is considered an extremely successful pathogen able to replicate and spread rapidly among its hosts .", "The induction of type-I interferon ( IFN ) response is a crucial event in mammal...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "viral diseases" ]	An “Escape Clock” for Estimating the Turnover of SIV DNA in Resting CD4+ T Cells	journal.ppat.1002615	null	[ [ "Treatment of HIV-1 infected individuals with highly active antiretroviral therapy ( HAART ) can suppress plasma viral RNA levels below the threshold of detection by standard diagnostic assays .", "However after cessation of even long-term HAART , virus replication is quickly re-established [1]–[4] .", ...	[ "Persistence of HIV DNA presents a major barrier to the complete control of HIV infection under current therapies .", "Most studies suggest that cells with latently integrated HIV decay very slowly under therapy .", "However , it is much more difficult to study the turnover and persistence of HIV DNA during act...	[ "New treatments for HIV have proved very successful at controlling viral replication and preventing the onset of AIDS .", "However , these treatments must be continued for life , because if they are stopped the virus rapidly ‘rebounds’ to its original levels .", "The reason for this rebound is the existence of ...	2012
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biochemistry", "biochemical simulations", "molecular dynamics", "proteins", "biology and life sciences", "chemistry", "physical sciences", "computational chemistry", "molecular mechanics", "biophysics", "biophysical simulations" ]	Molecular Simulation-Based Structural Prediction of Protein Complexes in Mass Spectrometry: The Human Insulin Dimer	journal.pcbi.1003838	null	[ [ "Proteomics , the large-scale characterization of proteins and their interactions , is key to understand cellular processes including signaling pathways , metabolism , and gene transcription [1]–[3] .", "Arguably , the most powerful tool for studying functional proteomics is protein electrospray ionizatio...	[ "Protein electrospray ionization ( ESI ) mass spectrometry ( MS ) -based techniques are widely used to provide insight into structural proteomics under the assumption that non-covalent protein complexes being transferred into the gas phase preserve basically the same intermolecular interactions as in solution .", ...	[ "Electrospray ionization ( ESI ) mass spectrometry ( MS ) plays a pivotal role in proteomics and structural biology .", "The applications of ESI-MS to protein complexes make use of the assumption that the vaporization of protein complexes into the gas phase ( as occurs during ESI-MS ) preserves the structural det...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "meiosis", "chromosome staining", "fish", "homologous chromosomes", "reproductive system", "medicine and health sciences", "chromosome structure and function", "cell cycle and cell division", "cell processes", "vertebrates", "animals", "animal models", "osteichthyes", "telomeres", "model...	The telomere bouquet is a hub where meiotic double-strand breaks, synapsis, and stable homolog juxtaposition are coordinated in the zebrafish, Danio rerio	journal.pgen.1007730	null	[ [ "Meiosis is a process that generates haploid gametes via one round of DNA replication and two rounds of chromosome segregation .", "Typically , homologous chromosomes ( homologs ) separate during meiosis I , and sister chromatids separate at meiosis II .", "Errors at either stage can lead to the produ...	[ "Meiosis is a cellular program that generates haploid gametes for sexual reproduction .", "While chromosome events that contribute to reducing ploidy ( homologous chromosome pairing , synapsis , and recombination ) are well conserved , their execution varies across species and even between sexes of the same speci...	[ "Inherent to reproduction is the transmission of genetic information from one generation to the next .", "In sexually reproducing organisms , each parent contributes an equal amount of genetic information , packaged in chromosomes , to the offspring .", "Diploid organisms , like humans , have two copies of ever...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "algorithms", "systems biology", "developmental biology", "computer science", "genomics", "mathematics", "physiology", "topology", "biology", "anatomy and physiology", "evolutionary biology", "computational biology", "genetics and genomics" ]	Colon Stem Cell and Crypt Dynamics Exposed by Cell Lineage Reconstruction	journal.pgen.1002192	null	[ [ "Mammalian stem cells and tissue dynamics in vivo are presently studied by lineage tracing methods [1] , [2] , which are dependent on the presence of specific stem cell markers [2] .", "These methods require generation of transgenic animals , development of sophisticated imaging modalities , and are conti...	[ "Stem cell dynamics in vivo are often being studied by lineage tracing methods .", "Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites .", "This method was applied here to explore different aspects of stem ce...	[ "The study of stem cell and tissue dynamics in vivo is often carried out by lineage tracing methods that depend on the presence of specific markers and on the availability of stem cells .", "In the current study , we applied a novel method for the reconstruction of cell lineage trees from microsatellite mutations...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology/developmental evolution", "developmental biology/pattern formation", "computational biology/systems biology", "computational biology/signaling networks" ]	Neutrality and Robustness in Evo-Devo: Emergence of Lateral Inhibition	journal.pcbi.1000226	null	[ [ "The evolution of life forms on our planet has led to the generation of an enormous variety of living structures .", "How such patterns of organization emerge [1]–[3] , how contingency [4] and constraints [5] , [6] shape them and how they acquire robustness [7] are unanswered questions that have been at t...	[ "Embryonic development is defined by the hierarchical dynamical process that translates genetic information ( genotype ) into a spatial gene expression pattern ( phenotype ) providing the positional information for the correct unfolding of the organism .", "The nature and evolutionary implications of genotype–phe...	[ "The diversity of life is a consequence of changes in the genotype ( genes and their interdependence ) , but it is upon the observable organism's morphology ( phenotype ) that natural selection acts .", "Thus , the study of genotype–phenotype mapping can reveal key mechanisms driving life's capacity of continuous...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "respiratory infections", "emerging viral diseases", "microbiology", "pulmonology", "genome sequencing", "metagenomics", "veterinary science", "infectious diseases", "veterinary diseases", "respiratory medicine", "biology", "microarrays", "virology", "veterinary virology", ...	Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony	journal.ppat.1002155	null	[ [ "Adenoviruses , first isolated in the 1950s from explanted adenoid tissue , are double-stranded nonenveloped DNA viruses that naturally infect many vertebrates , including humans and nonhuman primates .", "The human adenoviruses in the Mastadenovirus genus , comprised of all mammalian adenoviruses , are c...	[ "Adenoviruses are DNA viruses that naturally infect many vertebrates , including humans and monkeys , and cause a wide range of clinical illnesses in humans .", "Infection from individual strains has conventionally been thought to be species-specific .", "Here we applied the Virochip , a pan-viral microarray , ...	[ "Infection from adenoviruses , viruses that cause a variety of illnesses in humans , monkeys , and other animals , has conventionally been thought to be species-specific .", "We used the Virochip , a microarray designed to detect all viruses , to identify a new species of adenovirus ( TMAdV , or titi monkey adeno...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "diagnostic medicine", "epidemiology", "global health", "public health" ]	Accuracy of Urine Circulating Cathodic Antigen (CCA) Test for Schistosoma mansoni Diagnosis in Different Settings of Côte d'Ivoire	journal.pntd.0001384	null	[ [ "There is growing awareness , political commitment , and financial resources to control neglected tropical diseases ( NTDs ) [1]–[3] .", "Preventive chemotherapy , that is the repeated large-scale administration of drugs to at-risk populations , has become the key strategy for the control of several NTDs ...	[ "Promising results have been reported for a urine circulating cathodic antigen ( CCA ) test for the diagnosis of Schistosoma mansoni .", "We assessed the accuracy of a commercially available CCA cassette test ( designated CCA-A ) and an experimental formulation ( CCA-B ) for S . mansoni diagnosis .", "We conduc...	[ "We aimed to assess the accuracy of a commercially available rapid diagnostic test for the detection of an infection with the blood fluke Schistosoma mansoni in urine .", "In total , 446 school children from three different settings of south Côte d'Ivoire provided three stool and three urine samples .", "Stool ...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "rift valley fever virus", "immune cells", "immune physiology", "pathology and laboratory medicine", "cytokines", "pathogens", "immunology", "microbiology", "brain", "microglial cells", "encephalitis", "viruses", "d...	Neutrophil and macrophage influx into the central nervous system are inflammatory components of lethal Rift Valley fever encephalitis in rats	journal.ppat.1007833	null	[ [ "Africa suffers from periodic outbreaks of Rift Valley fever ( RVF ) , a disease of both livestock animals and humans .", "Abnormally heavy rainfall in 2018 led to cases of RVF in animals and people in the countries of South Sudan , Uganda , Gambia , Rwanda , Kenya , and the archipelago of Mayotte [1–3] ....	[ "Rift Valley fever virus ( RVFV ) causes severe disease in livestock concurrent with zoonotic transmission to humans .", "A subset of people infected with RVFV develop encephalitis , and significant gaps remain in our knowledge of how RVFV causes pathology in the brain .", "We previously found that , in Lewis r...	[ "Rift Valley fever is a disease of livestock and humans that occurs periodically in Africa and parts of the Middle East .", "People infected with Rift Valley fever virus can develop different clinical outcomes , including hemorrhagic fever or encephalitis .", "Understanding of the pathophysiological mechanisms ...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell death", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "293t cells", "pathogens", "immunology", "cell processes", "microbiology", "biological cultures", "plasmid construction", "viruses", "dna replication", "dna viruses", "dna ...	Interferon regulatory factor 8 regulates caspase-1 expression to facilitate Epstein-Barr virus reactivation in response to B cell receptor stimulation and chemical induction	journal.ppat.1006868	null	[ [ "Epstein-Barr virus ( EBV ) , a ubiquitous human gammaherpesvirus , is associated with malignant diseases , including Burkitt’s lymphoma , Hodgkin’s lymphoma , nasopharyngeal carcinoma , and NK/T cell lymphoma [1] .", "The genome of EBV is approximately 170 kb in length and encodes more than 80 genes .", ...	[ "Interferon regulatory factor 8 ( IRF8 ) , also known as interferon consensus sequence-binding protein ( ICSBP ) , is a transcription factor of the IRF family .", "IRF8 plays a key role in normal B cell differentiation , a cellular process that is intrinsically associated with Epstein-Barr virus ( EBV ) reactivat...	[ "Infection with Epstein-Barr virus ( EBV ) is closely associated with human cancers of both B cell and epithelial cell origin .", "The EBV life cycle is tightly regulated by both viral and cellular factors .", "Here , we demonstrate that interferon regulatory factor 8 ( IRF8 ) is required for EBV lytic replicat...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "diagnostic radiology", "ultrasound imaging", "education", "sociology", "geographical locations", "social sciences", "group a streptococcal infection", "uganda", "echocardiography", "cardiovascular medicine", "bacterial diseases", "human families", "genetic ...	Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case	journal.pntd.0004727	null	[ [ "Rheumatic heart disease ( RHD ) , the long-term consequence of acute rheumatic fever ( ARF ) , is the result of a complex interplay between host and environment .", "Endemic areas are consistently marked by poverty , poor sanitation , and limited access to primary healthcare [1] .", "These factors in...	[ "Echocardiographic screening for detection of latent RHD has shown potential as a strategy to decrease the burden of disease .", "However , further research is needed to determine optimal implementation strategies .", "RHD results from a complex interplay between environment and host susceptibility .", "Famil...	[ "Rheumatic heart disease ( RHD ) affects at least 33 million people , most of who live in low-resource environments .", "RHD is a cumulative process and there exists a latent period between early valve damage and presentation with symptoms .", "Echocardiographic screening ( ultrasound of the heart ) has proven ...	2016
[ "Introduction", "Results/Discussion", "Materials and methods" ]	[ "medicine and health sciences", "cluster analysis", "statistics", "applied mathematics", "brain", "marker genes", "simulation and modeling", "multivariate analysis", "algorithms", "mathematics", "genome analysis", "molecular biology techniques", "research and analysis methods", "mathematic...	PanoView: An iterative clustering method for single-cell RNA sequencing data	journal.pcbi.1007040	null	[ [ "Single-cell RNA-sequencing ( scRNA-seq ) has attracted great attention in recent years .", "Unlike traditional bulk RNA-seq analysis , scRNA-seq provides access to cell-to-cell variability at the single-cell level .", "This allows defining individual cell types , and subtypes , among a population con...	[ "Single-cell RNA-sequencing ( scRNA-seq ) provides new opportunities to gain a mechanistic understanding of many biological processes .", "Current approaches for single cell clustering are often sensitive to the input parameters and have difficulty dealing with cell types with different densities .", "Here , we...	[ "One of the important tasks in analyzing single-cell transcriptomics data is to classify cell subpopulations .", "Most computational methods require users to input parameters and sometimes the proper parameters are not intuitive to users .", "Hence , a robust but easy-to-use method is of great interest .", "W...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dengue virus", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "vertebrates", "animals", "mammals", "viruses", "primates", "rna viruses", "bioassays and physiological analysis", "antibodies", "cross r...	Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques	journal.pntd.0006903	null	[ [ "Serologic assays designed to detect Zika virus ( ZIKV ) infection suffer from cross-reactivity with antibodies to closely related dengue virus ( DENV ) , due to the high level of amino acid sequence identity ( average ~55% ) and structural similarity [1–4] between the two viruses .", "Humoral cross-react...	[ "The specificity of the antibody response against Zika virus ( ZIKV ) is not well-characterized .", "This is due , in part , to the antigenic similarity between ZIKV and closely related dengue virus ( DENV ) serotypes .", "Since these and other similar viruses co-circulate , are spread by the same mosquito spec...	[ "ZIKV has emerged as a vector-borne pathogen capable of causing serious illness in infected adults and congenital birth defects .", "The vulnerability of communities to future ZIKV outbreaks will depend , in part , on the prevalence and longevity of protective immunity , thought to be mediated principally by anti...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "rna", "molecular complexes", "nucleic acids", "genetic screens", "gene identification and analysis", "gene expression", "genetics", "biology and life sciences", "rna synthesis", "molecular biology", "rna stability", "dna transcription" ]	A Genetic Assay for Transcription Errors Reveals Multilayer Control of RNA Polymerase II Fidelity	journal.pgen.1004532	null	[ [ "Accurate transcription is an essential step in accessing the genetic information stored in genes .", "In eukaryotes , transcription of DNA into mRNA is carried out by RNA polymerase II ( Pol II ) , an enzyme comprised of 12 subunits .", "While there has been extensive research on core Pol II , includ...	[ "We developed a highly sensitive assay to detect transcription errors in vivo .", "The assay is based on suppression of a missense mutation in the active site tyrosine in the Cre recombinase .", "Because Cre acts as tetramer , background from translation errors are negligible .", "Functional Cre resulting fro...	[ "Mistakes made during the synthesis of messenger RNAs have been difficult to detect , both because mRNAs can be short lived , and because the translation of mRNAs into proteins has a much higher error rate that masks transcription errors .", "We present here a highly sensitive genetic screen that detects transcri...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/bioinformatics", "oncology/hematological malignancies", "hematology", "computational biology/genomics" ]	Identification of Networks of Co-Occurring, Tumor-Related DNA Copy Number Changes Using a Genome-Wide Scoring Approach	journal.pcbi.1000631	null	[ [ "Tumor development is generally thought to be a process in which healthy cells transform into malignant tumor cells through the step-wise acquisition of oncogenic alterations [1] , [2] .", "This implies that certain changes have to occur together for effective oncogenic transformation of a normal cell .",...	[ "Tumorigenesis is a multi-step process in which normal cells transform into malignant tumors following the accumulation of genetic mutations that enable them to evade the growth control checkpoints that would normally suppress their growth or result in apoptosis .", "It is therefore important to identify those co...	[ "It is generally accepted that a normal cell has to acquire multiple mutations in order to become a malignant tumor cell .", "Considerable effort has been invested in finding single genes involved in tumor initiation and progression , but relatively little is known about the constellations of cancer genes that ef...	2010
[ "Introduction", "Patients and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "pathology and laboratory medicine", "biopsy", "nervous system", "tropical diseases", "surgical and invasive medical procedures", "bacterial diseases", "signs and symptoms", "neglected tropical diseases", "immunologic techniques", "...	Revisiting primary neural leprosy: Clinical, serological, molecular, and neurophysiological aspects	journal.pntd.0006086	null	[ [ "Leprosy is a chronic infectious disease caused by the Mycobacterium leprae , an alcohol- and acid-resistant obligatory intracellular bacillus with predilection to infect peripheral nerves and skin .", "Its clinical forms are defined by the host immune response and bacillary load , resulting in a wide cli...	[ "Leprosy neuropathy is considered the most common peripheral neuropathy of infectious etiology worldwide , representing a public health problem .", "Clinical diagnosis of primary neural leprosy ( PNL ) is challenging , since no skin lesions are found and the slit skin smear bacilloscopy is negative .", "However...	[ "The long incubation period , insidious symptoms and signs of leprosy produce difficulties in its diagnosis and correct clinical classification , especially in its primary neural form characterized by negative bacilloscopy and lack of cutaneous lesions .", "Despite significant progress in leprosy control in recen...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "geographical locations", "sudan", "tropical diseases", "parasitic diseases", "headaches", "signs and symptoms", "neglected tropical diseases", "africa", "public and occupational health", "infectious diseases", "zoonoses", ...	Detection of Crimean-Congo Haemorrhagic Fever cases in a severe undifferentiated febrile illness outbreak in the Federal Republic of Sudan: A retrospective epidemiological and diagnostic cohort study	journal.pntd.0007571	null	[ [ "Undifferentiated febrile illness ( UFI ) is one of the most common reasons for people seeking healthcare in many low-income countries . [1]", "While illness and death due to some specific infections such as malaria are often well-quantified , others which can be caused by a wide range of pathogens , are ...	[ "Undifferentiated febrile illness ( UFI ) is one of the most common reasons for people seeking healthcare in low-income countries .", "While illness and death due to specific infections such as malaria are often well-quantified , others are frequently uncounted and their impact underappreciated .", "A number of...	[ "The Federal Republic of Sudan has had at least 12 outbreaks of febrile illness of unknown cause associated with symptoms of haemorrhage and high case fatality rates since 2012 .", "Outbreaks without clear diagnosis are concerning , particularly in countries such as Sudan where a range of high consequence disease...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "terpenes", "chemical compounds", "geographical locations", "tropical diseases", "sand flies", "parasitic diseases", "organic compounds", "animal anatomy", "neglected tropical diseases", "insect vectors", "zoology", "research and analysis methods", "infectio...	A temporal comparison of sex-aggregation pheromone gland content and dynamics of release in three members of the Lutzomyia longipalpis (Diptera: Psychodidae) species complex	journal.pntd.0006071	null	[ [ "There are over 800 known phlebotomine sand fly species , but only approximately 56 Lutzomyia and Phlebotomus species are proven or suspected vectors of human leishmaniasis [1] .", "Among them , L . longipalpis is the primary vector of Leishmania infantum , the etiological agent of visceral leishmaniasis ...	[ "Lutzomyia longipalpis is the South American vector of Leishmania infantum , the etiologic agent of visceral leishmaniasis ( VL ) .", "Male L . longipalpis produce a sex-aggregation pheromone that is critical in mating , yet very little is known about its accumulation over time or factors involved in release .", ...	[ "The Dipteran subfamily Phlebotominae includes the genera Lutzomyia and Phlebotomus among which several species are important vectors of parasitic and bacterial pathogens .", "The sand fly Lutzomyia longipalpis is considered the main vector of visceral leishmaniasis ( VL ) in the New World .", "Based on the mai...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/gene therapy", "virology/viruses and cancer", "computational biology", "genetics and genomics/epigenetics", "virology/host invasion and cell entry" ]	Deciphering the Code for Retroviral Integration Target Site Selection	journal.pcbi.1001008	null	[ [ "Retroviruses and retrotransposons are of profound importance to eukaryotic biology , evolution , and medicine .", "These retroelements constitute at least 40% of the mass of mammalian genomes [1] and 75% of the maize genome [2] .", "When retroelements are transcribed they remodel eukaryotic genomes b...	[ "Upon cell invasion , retroviruses generate a DNA copy of their RNA genome and integrate retroviral cDNA within host chromosomal DNA .", "Integration occurs throughout the host cell genome , but target site selection is not random .", "Each subgroup of retrovirus is distinguished from the others by attraction t...	[ "When HIV-1 , murine leukemia virus ( MLV ) , or other retroviruses infect a cell , the virus generates a DNA copy of the viral RNA genome and ligates the cDNA within host chromosomal DNA .", "This integration reaction occurs at sites throughout the host cell genome , but little is known about how integration sit...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Inactivation of PNKP by Mutant ATXN3 Triggers Apoptosis by Activating the DNA Damage-Response Pathway in SCA3	journal.pgen.1004834	null	[ [ "Spinocerebellar ataxia type 3 ( SCA3 ) , also known as Machado-Joseph disease ( MJD ) , is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the C-terminal coding region of the ATXN3 gene [1–3] .", "SCA3 is the most common dominantly inherited ataxia world-wide , and a lat...	[ "Spinocerebellar ataxia type 3 ( SCA3 ) , also known as Machado-Joseph disease ( MJD ) , is an untreatable autosomal dominant neurodegenerative disease , and the most common such inherited ataxia worldwide .", "The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-term...	[ "Spinocerebellar ataxia type 3 ( SCA3 ) is an untreatable neurodegenerative disease , and the most common dominantly inherited ataxia worldwide .", "SCA3 is caused by expansion of a CAG tri-nucleotide repeat sequence in the ATXN3 gene’s coding region .", "The expanded CAG sequences encode a run of the amino aci...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "microbiology/medical microbiology", "biochemistry/chemical biology of the cell", "microbiology/innate immunity", "microbiology", "infectious diseases/bacterial infections", "microbiology/microbial physiology and metabolism", "microbiology/cellular microbiology and pathogenesis", "bi...	The Bacterial Defensin Resistance Protein MprF Consists of Separable Domains for Lipid Lysinylation and Antimicrobial Peptide Repulsion	journal.ppat.1000660	null	[ [ "In order to combat increasingly antibiotic-resistant bacteria such as Staphylococcus aureus , Mycobacterium tuberculosis , Pseudomonas aeruginosa , and enterococci new antimicrobial strategies based on compounds with anti-virulence or anti-fitness properties are increasingly in the focus of research efforts ...	[ "Many bacterial pathogens achieve resistance to defensin-like cationic antimicrobial peptides ( CAMPs ) by the multiple peptide resistance factor ( MprF ) protein .", "MprF plays a crucial role in Staphylococcus aureus virulence and it is involved in resistance to the CAMP-like antibiotic daptomycin .", "MprF i...	[ "Certain bacterial immune-evasion factors such as the MprF protein are highly conserved in many bacterial pathogens and represent attractive targets for new ‘anti-virulence’ drugs .", "MprF , initially discovered in the major human pathogen Staphylococcus aureus , protects bacteria against ‘innate human antibioti...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/urological infections", "microbiology/immunity to infections", "immunology/immunity to infections", "infectious diseases/bacterial infections", "microbiology/cellular microbiology and pathogenesis" ]	Mucosal Immunization with Iron Receptor Antigens Protects against Urinary Tract Infection	journal.ppat.1000586	null	[ [ "The urinary tract is among the most common sites of bacterial infection .", "Over half ( 53% ) of all women and 14% of men experience at least one urinary tract infection ( UTI ) in their lifetime [1] , [2] , leading to an average of 6 . 8 million physician office visits , 1 . 3 million emergency room vi...	[ "Uncomplicated infections of the urinary tract , caused by uropathogenic Escherichia coli , are among the most common diseases requiring medical intervention .", "A preventive vaccine to reduce the morbidity and fiscal burden these infections have upon the healthcare system would be beneficial .", "Here , we de...	[ "Because urinary tract infections ( UTIs ) are a significant healthcare burden , it would be beneficial to develop a vaccine to prevent uncomplicated UTI caused by Escherichia coli .", "Using a large-scale screening process we uniformly identified proteins involved in iron uptake as potential vaccine candidates a...	2009
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "ixodes", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "rickettsia", "animals", "developmental biology", "systems science", "mathematics", "nymphs", "crops", "ticks", "population biology", ...	Hosts mobility and spatial spread of Rickettsia rickettsii	journal.pcbi.1006636	null	[ [ "Stochastic epidemic models have been used to guide control policies for tick-borne infectious diseases [1–3] .", "These models typically assume that vector and host populations are homogeneous , disregarding the movement of infected individuals and the consequent spatial spread of infectious diseases [4]...	[ "There are a huge number of pathogens with multi-component transmission cycles , involving amplifier hosts , vectors or complex pathogen life cycles .", "These complex systems present challenges in terms of modeling and policy development .", "A lethal tick-borne infectious disease , the Brazilian Spotted Fever...	[ "Complex systems as the Brazilian Spotted Fever ( BSF ) , present challenges in terms of modeling and policy development .", "BSF human cases have been associated with the presence and expansion of the capybara Hydrochoerus hydrochaeris , amplifier host for the agent Rickettsia rickettsii and primary host for the...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genetics and genomics/gene expression", "infectious diseases/neglected tropical diseases", "pharmacology", "biotechnology/bioengineering", "radiology and medical imaging" ]	Bioluminescent Imaging of Trypanosoma brucei Shows Preferential Testis Dissemination Which May Hamper Drug Efficacy in Sleeping Sickness	journal.pntd.0000486	null	[ [ "Human and animal African trypanosomoses are important protozoan infections endemic in Africa , Latin America and Asia , caused by several species such as Trypanosoma brucei , T . evansi , T . equiperdum , T . congolense and T . vivax .", "Different species , strains within the species and clones within v...	[ "Monitoring Trypanosoma spread using real-time imaging in vivo provides a fast method to evaluate parasite distribution especially in immunoprivileged locations .", "Here , we generated monomorphic and pleomorphic recombinant Trypanosoma brucei expressing the Renilla luciferase .", "In vitro luciferase activity...	[ "Human African trypanosomiasis or sleeping sickness , caused by two subspecies of Trypanosoma brucei , is endemic in Subsaharan Africa .", "There is no vaccine and the currently used drugs are toxic and can cause severe side effects and even death .", "At present , we do not know how and when parasites can leav...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "spleen", "immunology", "vaccines", "preventive medicine", "animal models", "developmental biology", "model organisms", "molecular development", "cytotoxic t cells", ...	The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells	journal.ppat.1005786	null	[ [ "Live-attenuated vaccines ( LAV ) generally provide the highest level of protection against infectious diseases .", "The most effective LAVs duplicate the pathogen-specific conditions of natural infection but have their replication curtailed by the innate and adaptive immune responses prior to the onset o...	[ "A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus ( YFV ) vaccines .", "Among more than 500 million vaccinees , only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection .", "This efficacy is pr...	[ "The 17D line yellow fever virus ( YFV ) vaccines are some of the safest and most effective live-attenuated virus vaccines ever produced , protecting recipients for life against deadly yellow fever ( YF ) .", "As a testament to this safety and efficacy , the 17D line of live-attenuated vaccines has become an impo...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Dependence of Intracellular and Exosomal microRNAs on Viral E6/E7 Oncogene Expression in HPV-positive Tumor Cells	journal.ppat.1004712	null	[ [ "Oncogenic human papillomaviruses ( HPVs ) , such as HPV16 and HPV18 , cause cervical cancer .", "Infections with oncogenic HPV types are moreover closely linked to the development of additional human malignancies in the oropharynx and anogenital region [1] .", "The viral E6 and E7 oncoproteins are cr...	[ "Specific types of human papillomaviruses ( HPVs ) cause cervical cancer .", "Cervical cancers exhibit aberrant cellular microRNA ( miRNA ) expression patterns .", "By genome-wide analyses , we investigate whether the intracellular and exosomal miRNA compositions of HPV-positive cancer cells are dependent on en...	[ "Oncogenic human papillomaviruses ( HPVs ) are major human carcinogens of broad biomedical importance .", "The growth of HPV-positive cervical cancer cells is critically dependent on sustained E6/E7 oncogene expression from endogenous viral DNA sequences .", "We here addressed the question of whether this proce...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "developmental biology/developmental molecular mechanisms", "computational biology" ]	Identification of Synaptic Targets of Drosophila Pumilio	journal.pcbi.1000026	null	[ [ "Drosophila melanogaster Pumilio ( Pum ) protein is one of the founding members of the PUF RNA-binding protein family .", "Its function in the posterior body patterning of Drosophila embryos is relatively well studied .", "Wharton and Struhl [1] first identified two copies of sequence elements located...	[ "Drosophila Pumilio ( Pum ) protein is a translational regulator involved in embryonic patterning and germline development .", "Recent findings demonstrate that Pum also plays an important role in the nervous system , both at the neuromuscular junction ( NMJ ) and in long-term memory formation .", "In neurons ,...	[ "The Drosophila Pumilio ( Pum ) protein was originally identified as a translational control factor for embryo patterning .", "Subsequent studies have identified Pum's role in multiple biological processes , including the maintenance of germline stem cell , the proliferation and migration of primordial germ cells...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "nutrition", "neglected tropical diseases", "parasitic diseases" ]	Association between Anaemia, Iron Deficiency Anaemia, Neglected Parasitic Infections and Socioeconomic Factors in Rural Children of West Malaysia	journal.pntd.0001550	null	[ [ "Anaemia is a specific condition where red blood cells are not providing adequate oxygen to the body tissues .", "It is usually caused by iron deficiency , which is the commonest micronutrient deficiency in both developing and developed countries [1] , [2] .", "Generally , it takes at least several we...	[ "Given that micronutrient deficiency , neglected intestinal parasitic infections ( IPIs ) and poor socioeconomic status are closely linked , we conducted a cross-sectional study to assess the relationship between IPIs and nutritional status of children living in remote and rural areas in West Malaysia .", "A tota...	[ "Micronutrient deficiency and intestinal parasitic infections ( IPIs ) share a similar geographical distribution .", "A conservative estimate indicated that almost 2 billion individuals suffer from anaemia due to iron deficiency ( ID ) , corresponding to 24 . 8% of the world's population .", "Crucially , most o...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell growth and division", "developmental biology/cell differentiation", "public health and epidemiology/infectious diseases", "microbiology/microbial growth and development", "microbiology/cellular microbiology and pathogenesis", "microbiology/medical microbiology", "cell biology/cytoskel...	A Novel System of Cytoskeletal Elements in the Human Pathogen Helicobacter pylori	journal.ppat.1000669	null	[ [ "Helicobacter pylori is a Gram negative , highly motile , microaerophilic , spiral-shaped organism , which colonizes the stomachs of at least half of the world's population [1] .", "Infection of humans results in persistent gastritis , which can develop into peptic ulcer disease and adenocarcinoma [2] , [...	[ "Pathogenicity of the human pathogen Helicobacter pylori relies upon its capacity to adapt to a hostile environment and to escape from the host response .", "Therefore , cell shape , motility , and pH homeostasis of these bacteria are specifically adapted to the gastric mucus .", "We have found that the helical...	[ "The human pathogen Helicobacter pylori lives in the hostile environment of the human stomach .", "H . pylori possesses a spiral shape and high motility that enable the bacterium to swim through the stomach lumen and to come into close contact with epithelial cells .", "High urease activity in the bacterium cou...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "clinical immunology", "synthetic biology", "immunology", "biology", "computational biology", "evolutionary biology", "microbiology", "molecular biology" ]	Immunogenetic Mechanisms Driving Norovirus GII.4 Antigenic Variation	journal.ppat.1002705	null	[ [ "Noroviruses ( NoVs ) are the leading cause of severe viral gastroenteritis and are responsible for 50% of all acute gastroenteritis outbreaks in the United States and Europe [1] .", "Although the severity of disease is usually moderate , lasting 1–3 days , infection can be especially virulent in young ch...	[ "Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII . 4 strains accounting for 80% of infections .", "The major capsid protein of GII . 4 strains is evolving rapidly , resulting in new epidemic strains with altered antigenic potentials .", "To test if antigenic drift may contribu...	[ "Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII . 4 strains accounting for 80% of infections .", "The major capsid protein of GII . 4 strains is evolving rapidly , resulting in new epidemic strains with altered antigenic sites .", "To define these sites we prepared the first ...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "biology and life sciences", "molecular biology", "cell biology" ]	Heterologous Aggregates Promote De Novo Prion Appearance via More than One Mechanism	journal.pgen.1004814	null	[ [ "Prions were first described as self-perpetuating infectious agents devoid of nucleic acids that cause several fatal neurodegenerative diseases .", "Prion diseases , also known as transmissible spongiform encephalopathies ( TSEs ) , were shown to infect a variety of mammals [1] .", "All known mammalia...	[ "Prions are self-perpetuating conformational variants of particular proteins .", "In yeast , prions cause heritable phenotypic traits .", "Most known yeast prions contain a glutamine ( Q ) /asparagine ( N ) -rich region in their prion domains .", "[PSI+] , the prion form of Sup35 , appears de novo at dramatic...	[ "Certain proteins can misfold into β-sheet-rich , self-seeding aggregates .", "Such proteins appear to be associated with neurodegenerative diseases such as prion , Alzheimer's and Parkinson's .", "Yeast prions also misfold into self-seeding aggregates and provide a good model to study how these rogue polymers ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Characterization of Spirometra erinaceieuropaei Plerocercoid Cysteine Protease and Potential Application for Serodiagnosis of Sparganosis	journal.pntd.0003807	null	[ [ "Spirometra erinaceieuropaei ( syn . S . erinacei or S . mansoni ) is an intestinal tapeworm of wild and domesticated carnivores [1] and is most commonly seen in Asia , whereas Spirometra mansonoides is mainly found in North America [2] .", "Sparganosis is a zoonotic parasitic disease caused by the pleroc...	[ "Sparganosis is a neglected but important food-borne parasitic zoonosis .", "Clinical diagnosis of sparganosis is difficult because there are no specific manifestations .", "ELISA using plerocercoid crude or excretory–secretory ( ES ) antigens has high sensitivity but has cross-reactions with other helminthiase...	[ "Sparganosis is a neglected tropical disease; its diagnosis is difficult and it is often misdiagnosed .", "ELISA using the crude or ES antigens of plerocercoids cross reacts with other helminthiases .", "Cysteine protease is a type of hydrolase and plays important roles in the development and survival of parasi...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "dermatology", "medicine and health sciences", "skeletal muscles", "liver diseases", "mutation", "gastroenterology and hepatology", "germline mutation", "pharmacology", "skin diseases", "tissue distribution", "musculoskeletal system", "gene expression", "thyroid", "muscles", "brain disea...	Role of duplicate genes in determining the tissue-selectivity of hereditary diseases	journal.pgen.1007327	null	[ [ "Hereditary diseases are caused by germline aberrations that are common to cells throughout the human body .", "For hundreds of these diseases , these germline aberrations have been identified and mapped to causal genes [1] , and many more causal genes are likely to be identified in coming years owing to ...	[ "A longstanding puzzle in human genetics is what limits the clinical manifestation of hundreds of hereditary diseases to certain tissues , while their causal genes are expressed throughout the human body .", "A general conception is that tissue-selective disease phenotypes emerge when masking factors operate in u...	[ "A longstanding enigma in human genetics is what limits the clinical manifestation of hundreds of hereditary diseases to certain tissues or cell types , while their causal genes are present and expressed throughout the human body .", "A general conception was that the tissue-wide robustness to the causal aberrati...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology", "biology", "microbiology" ]	Clostridium difficile 027/BI/NAP1 Encodes a Hypertoxic and Antigenically Variable Form of TcdB	journal.ppat.1003523	null	[ [ "Clostridium difficile is the leading cause of hospital-acquired diarrhea in developed countries [1] , [2] , [3] , [4] .", "This spore-forming anaerobic bacterium contaminates hospital environments and infects patients undergoing antibiotic therapy within health care facilities [2] , [5] , [6] .", "De...	[ "The Clostridium difficile exotoxin , TcdB , which is a major virulence factor , varies between strains of this pathogen .", "Herein , we show that TcdB from the epidemic BI/NAP1/027 strain of C . difficile is more lethal , causes more extensive brain hemorrhage , and is antigenically variable from TcdB produced ...	[ "During the past decade , the C . difficile BI/NAP1/027 strain has emerged and in some settings predominated as the cause of C . difficile infection .", "Moreover , in some reports C . difficile BI/NAP1/027 has been associated with more severe disease .", "The reasons for association of this strain with more se...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "saccharomyces", "computational biology" ]	Evolutionary Models for Formation of Network Motifs and Modularity in the Saccharomyces Transcription Factor Network	journal.pcbi.0030198	null	[ [ "One of the most fundamental questions in biology is how incremental evolutionary changes lead to the observed complexity in biological systems .", "The advent of genome sequencing and associated functional genomic technologies have provided the first evidence for the origins of complexity on an organism-...	[ "Many natural and artificial networks contain overrepresented subgraphs , which have been termed network motifs .", "In this article , we investigate the processes that led to the formation of the two most common network motifs in eukaryote transcription factor networks: the bi-fan motif and the feed-forward loop...	[ "Networks are a simple and general way of representing natural phenomena that range in scale from the social interactions between people to the organization of circuits on a microchip .", "Many networks have been found to contain repeated patterns of connections between small groups of nodes .", "These patterns...	2007
[ "Introduction", "Results", "Discussion", "Methods and materials" ]	[ "keratinocytes", "medicine and health sciences", "luciferase", "pathology and laboratory medicine", "enzymes", "pathogens", "cervical cancer", "immunology", "rna extraction", "microbiology", "enzymology", "cancers and neoplasms", "gene regulation", "epithelial cells", "viruses", "oncol...	Human papillomavirus type 16 antagonizes IRF6 regulation of IL-1β	journal.ppat.1007158	null	[ [ "The innate immune system is the first line of defense in response to danger signals from microbial invasion or tissue injury .", "Viruses are sensed by several immune receptors that activate signaling pathways leading to cytokine production .", "Many oncogenic viruses can deregulate several immune-re...	[ "Human papillomavirus type 16 ( HPV16 ) and other oncoviruses have been shown to block innate immune responses and to persist in the host .", "However , to avoid viral persistence , the immune response attempts to clear the infection .", "IL-1β is a powerful cytokine produced when viral motifs are sensed by inn...	[ "Oncoviruses block innate immune responses to persist in the host .", "However , to avoid viral persistence , the immune response attempts to clear the infection .", "IL-1β is a pro-inflammatory cytokine produced by the inflammasome pathway .", "Whether oncoviruses such as human papillomavirus ( HPV ) can act...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "medicine and health sciences" ]	Non-random Escape Pathways from a Broadly Neutralizing Human Monoclonal Antibody Map to a Highly Conserved Region on the Hepatitis C Virus E2 Glycoprotein Encompassing Amino Acids 412–423	journal.ppat.1004297	null	[ [ "Infection with hepatitis C virus ( HCV ) is a leading cause of chronic hepatitis , cirrhosis and hepatocellular carcinoma .", "The World Health Organization estimates an annual increase in the global burden by 3–4 million new infections [1] .", "Encouragingly for patients , advances in in vitro and i...	[ "A challenge for hepatitis C virus ( HCV ) vaccine development is to define epitopes that are able to elicit protective antibodies against this highly diverse virus .", "The E2 glycoprotein region located at residues 412–423 is conserved and antibodies to 412–423 have broadly neutralizing activities .", "Howeve...	[ "An effective hepatitis C virus ( HCV ) vaccine will require information on epitopes that are responsible for protective antibodies against this highly diverse virus .", "A region known to be highly conserved and responsible for broadly neutralizing antibodies is located on the E2 glycoprotein at 412–423 .", "T...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections" ]	Metabolic Changes Reveal the Development of Schistosomiasis in Mice	journal.pntd.0000807	null	[ [ "Schistosomiasis is a chronic parasitic disease caused by infection with schistosomes .", "As one of the most infectious species , Schistosoma japonicum is mainly endemic in Asia with over 1 million infected individuals and about 46 million people at risk in China , the Philippines and Indonesia [1]–[3] ....	[ "Schistosomiasis is a parasitic zoonosis caused by small trematode worms called schistosomes , amongst which Schistosoma japonicum ( S . japonicum ) is endemic in Asia .", "In order to understand the schistosome-induced changes in the host metabolism so as to facilitate early diagnosis of schistosomiasis , we sys...	[ "Schistosomiasis is an infectious disease resulting from the infection of parasitic trematode worms called schistosomes .", "About 600 million people are currently exposed to schistosomiasis and 200 million people are infected in about 76 countries .", "Current diagnostic methods are unable to detect schistosom...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "cardiovascular anatomy", "aneurysms", "alleles", "heart", "karyotypes", "turner syndrome", "sex chromosomes", "chromosomal disorders", "chromosome biology", "blood vessels", "aortic valve", "x chromosomes", "genetic loci", "clinical genetics", "cell bio...	TIMP3 and TIMP1 are risk genes for bicuspid aortic valve and aortopathy in Turner syndrome	journal.pgen.1007692	null	[ [ "Turner syndrome is the most common sex chromosome aneuploidy , where ~50% have a complete monosomy X and ~48% have either a partial loss , rearrangement , or mosaicism of a second X chromosome . [1]", "The remaining ~2% have a partial or mosaic Y chromosome .", "Although Turner syndrome can be compat...	[ "Turner syndrome is caused by complete or partial loss of the second sex chromosome , occurring in ~1 in 2 , 000 female births .", "There is a greatly increased incidence of aortopathy of unknown etiology , including bicuspid aortic valve ( BAV ) , thoracic aortic aneurysms , aortic dissection and rupture .", "...	[ "BAV is the most frequent congenital heart defect , occurring in about 1–2% of the population with 70% of cases occurring in males .", "BAV increases risk for thoracic aortic aneurysm ( TAA ) and early death .", "Approximately 30% of individuals with Turner syndrome have BAV/TAA , making this an important popul...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "genome-wide association studies", "engineering and technology", "lasers", "variant genotypes", "geographical locations", "genetic mapping", "ethnicities", "singapore", "genome analysis", "molecular biology techniques", "optical equipment", "molecular genetics", "genotyping", "research and...	Estimation of kinship coefficient in structured and admixed populations using sparse sequencing data	journal.pgen.1007021	null	[ [ "Understanding biological relatedness plays a central role in quantitative genetic studies of heritable traits and diseases .", "For example , complete pedigree information is required for linkage analysis and family-based association studies .", "In population-based association studies , inference of...	[ "Knowledge of biological relatedness between samples is important for many genetic studies .", "In large-scale human genetic association studies , the estimated kinship is used to remove cryptic relatedness , control for family structure , and estimate trait heritability .", "However , estimation of kinship is ...	[ "Inference of genetic relatedness from molecular markers has broad applications in many areas , including quantitative genetics , forensics , evolution and ecology .", "Classic estimators , however , are not suitable for low-coverage sequencing data , which have high levels of genotype uncertainty and missing dat...	2017
[ "Introduction", "Discussion", "Materials and Methods" ]	[ "ecology and environmental sciences", "medicine and health sciences", "microbiome", "pathology and laboratory medicine", "evolutionary biology", "microbiology", "species delimitation", "systems science", "mathematics", "speciation", "directed graphs", "microbial genomics", "computer and info...	On the Origins and Control of Community Types in the Human Microbiome	journal.pcbi.1004688	null	[ [ "The human microbiome is a complex and dynamic ecosystem [26] .", "When modeling a dynamic system we should first decide how complex the model needs to be so as to capture the phenomenon of interest .", "A detailed model of the intestinal microbiome would include mechanistic interactions among cells ,...	[ "Microbiome-based stratification of healthy individuals into compositional categories , referred to as “enterotypes” or “community types” , holds promise for drastically improving personalized medicine .", "Despite this potential , the existence of community types and the degree of their distinctness have been hi...	[ "We coexist with a vast number of microbes that live in and on our bodies , and play important roles in physiology and disease .", "Two interesting phenomena have been observed in the human microbiome .", "The first is the stratification of healthy individuals based on the relative abundances of their microbes ...	2016
[ "Introduction", "Results", "Materials and Methods", "Discussion" ]	[ "cell biology/nuclear structure and function" ]	Evidence of Activity-Specific, Radial Organization of Mitotic Chromosomes in Drosophila	journal.pbio.1000574	A fluorescently labeled protein specifically binding to genes was reproducibly found at the periphery of condensed mitotic fruit fly chromosomes, illustrating preservation of a radial structure between consecutive divisions.	[ [ "Over the past decades mitotic chromosomes have been shown to have a high degree of organization .", "However , the exact configuration of the DNA molecule and its reproducibility within a chromosome are unknown .", "Consolidation of the results from diverse experimental approaches has not yet led to ...	[ "The organization and the mechanisms of condensation of mitotic chromosomes remain unsolved despite many decades of efforts .", "The lack of resolution , tight compaction , and the absence of function-specific chromatin labels have been the key technical obstacles .", "The correlation between DNA sequence compo...	[ "Mitotic chromosomes of eukaryotes are relatively large rod-like cellular organelles , about 1 µm in diameter and 10 µm long , of well-studied composition but unknown structure .", "The question of whether all DNA sequences equally contribute to the interactions leading to the formation of mitotic chromosomes has...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "children", "cardiomyopathies", "medicine and health sciences", "tropical diseases", "randomized controlled trials", "parasitic diseases", "parasitic protozoans", "age groups", "electrocardiography", "clinical medicine", "protozoans", "bioassays and physiological analysis", "neglected tropic...	Electrocardiographic Abnormalities and Treatment with Benznidazole among Children with Chronic Infection by Trypanosoma cruzi: A Retrospective Cohort Study	journal.pntd.0004651	null	[ [ "Chagas’ disease is a chronic condition characterized by cardiovascular , digestive and neurologic manifestations , which is caused by a vector borne parasitic infection ( Trypanosoma cruzi ) endemic in Latin America [1] .", "Chagas’ disease is an important cause of premature death , disability , reduced ...	[ "Chronic infection by Trypanosoma cruzi could cause heart conduction disturbances .", "We sought to analyze electrocardiographic abnormalities among children with chronic T . cruzi infection with and without trypanocidal treatment with benznidazole .", "We studied 111 children 6–16 years of age with asymptomati...	[ "There are few data available on the natural history of electrocardiographic abnormalities among children with chronic Trypanosoma cruzi infection .", "Also , few studies analyzed the effect of benznidazole to prevent electrocardiographic abnormalities in this population .", "In the current study , electrocardi...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "immunology", "cytotoxic t cells", "research and analysis methods", "immune system proteins", "white blood cells", "animal cells", "proteins", "t cells", "spectrophotometry", "cytophotometry", "antibody-prod...	Varicella zoster virus productively infects human peripheral blood mononuclear cells to modulate expression of immunoinhibitory proteins and blocking PD-L1 enhances virus-specific CD8+ T cell effector function	journal.ppat.1007650	null	[ [ "Varicella zoster virus ( VZV ) is a lymphotropic , human alpha-herpesvirinae subfamily member that produces varicella ( chickenpox ) upon primary infection , after which virus establishes latency in ganglionic neurons along the entire neuraxis [1] .", "With aging or immunosuppression , such as seen in pa...	[ "Varicella zoster virus ( VZV ) is a lymphotropic alpha-herpesvirinae subfamily member that produces varicella on primary infection and causes zoster , vascular disease and vision loss upon reactivation from latency .", "VZV-infected peripheral blood mononuclear cells ( PBMCs ) disseminate virus to distal organs ...	[ "The burden of disease produced by VZV is significant , since 90% of the world population harbors latent virus .", "At least 50% of infected individuals will reactivate by 85 years of age to develop zoster , which is an established risk factor for stroke and myocardial infarction , as well as multisystem diseases...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "endocytosis", "viral entry", "cell biology", "viral transmission and infection", "virology", "biology and life sciences", "cell processes", "microbiology" ]	Crimean-Congo Hemorrhagic Fever Virus Entry into Host Cells Occurs through the Multivesicular Body and Requires ESCRT Regulators	journal.ppat.1004390	null	[ [ "Crimean-Congo hemorrhagic fever virus ( CCHFV ) is a tick-borne virus causing outbreaks of severe hemorrhagic disease in humans , with a fatality rate approaching 30% .", "The virus is endemic to much of Eastern Europe , the Middle East , Asia , and Africa , although recent studies have detected CCHFV in...	[ "Crimean-Congo hemorrhagic fever virus ( CCHFV ) is a tick-borne bunyavirus causing outbreaks of severe disease in humans , with a fatality rate approaching 30% .", "There are no widely accepted therapeutics available to prevent or treat the disease .", "CCHFV enters host cells through clathrin-mediated endocyt...	[ "Crimean-Congo hemorrhagic fever virus ( CCHFV ) is the cause of a severe , often fatal disease in humans .", "While it has been demonstrated that CCHFV cell entry depends on clathrin-mediated endocytosis , low pH , and early endosomes , the identity of the endosomes where virus penetrates into cell cytoplasm to ...	2014
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	In Vitro Whole Genome DNA Binding Analysis of the Bacterial Replication Initiator and Transcription Factor DnaA	journal.pgen.1005258	null	[ [ "DnaA is the highly conserved replication initiation protein found in virtually all bacteria [reviewed in 1 , 2–6] .", "DnaA binds to multiple 9 bp \"DnaA boxes\" ( DnaA binding sites; consensus sequence 5'-TTATNCACA ) in the origin of chromosomal replication ( oriC ) .", "Once properly bound to sites...	[ "DnaA , the replication initiation protein in bacteria , is an AAA+ ATPase that binds and hydrolyzes ATP and exists in a heterogeneous population of ATP-DnaA and ADP-DnaA .", "DnaA binds cooperatively to the origin of replication and several other chromosomal regions , and functions as a transcription factor at s...	[ "DNA binding proteins are involved in many cellular processes .", "The ability of these proteins to bind DNA is often modulated , either directly or indirectly .", "We determined the binding properties of Bacillus subtilis DnaA to genomic DNA at single nucleotide resolution using in vitro DNA affinity purificat...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular structures", "virology", "membranes and sorting", "biology", "microbiology", "molecular cell biology" ]	Membrane Assembly during the Infection Cycle of the Giant Mimivirus	journal.ppat.1003367	null	[ [ "Nucleocytoplasmic large DNA viruses ( NCLDVs ) , which include Poxviridae , Phycodnaviridae , Iridoviridae , Asfarviridae and Mimiviridae [1] , replicate and assemble in cytoplasmic inclusions called viral factories .", "Formation of these elaborate structures that enable spatial and temporal coordinatio...	[ "Although extensively studied , the structure , cellular origin and assembly mechanism of internal membranes during viral infection remain unclear .", "By combining diverse imaging techniques , including the novel Scanning-Transmission Electron Microscopy tomography , we elucidate the structural stages of membran...	[ "With a particle size comparable to that of small bacteria and a 1 . 2 Mbp double-strand DNA genome that carries more than 1000 open reading frames , the amoeba-infecting Mimivirus , along with other recently identified members of the Mimiviridae family , are the largest and most complex viruses yet identified .", ...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/immunity to infections", "immunology/immune response", "microbiology/innate immunity", "immunology/innate immunity", "immunology", "microbiology", "immunology/immunity to infections" ]	The Macrophage Scavenger Receptor A Is Host-Protective in Experimental Meningococcal Septicaemia	journal.ppat.1000297	null	[ [ "The innate immune system is a first line of defence against invading pathogens and macrophages play an integral role in the innate immune defence against bacterial infection .", "This is based on the recognition of conserved microbial structures , termed pathogen-associated molecular patterns ( PAMPs ) ,...	[ "Macrophage Scavenger Receptor A ( SR-A ) is a major non-opsonic receptor for Neisseria meningitidis on mononuclear phagocytes in vitro , and the surface proteins NMB0278 , NMB0667 , and NMB1220 have been identified as ligands for SR-A .", "In this study we ascertain the in vivo role of SR-A in the recognition of...	[ "Macrophages are innate immune cells that provide a first defence against infection .", "Several receptors on the surface of macrophages mediate recognition of invading pathogens , and one of these is the Macrophage Scavenger Receptor A ( SR-A ) .", "SR-A recognises Neisseria meningitidis , a bacterium that cau...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "genetics and genomics/animal genetics", "developmental biology/embryology", "genetics and genomics/gene discovery", "cell biology/cell growth and division", "genetics and genomics/gene function", "cell biology/cytoskeleton" ]	The Maternal-Effect Gene cellular island Encodes Aurora B Kinase and Is Essential for Furrow Formation in the Early Zebrafish Embryo	journal.pgen.1000518	null	[ [ "Following fertilization , an increase in cell number through cell division characterizes the initiation of early embryonic development .", "Cell division itself , and specifically cytokinesis , the physical process that divides a cell into two daughter cells , remains incompletely understood .", "Ear...	[ "Females homozygous for a mutation in cellular island ( cei ) produce embryos with defects in cytokinesis during early development .", "Analysis of the cytoskeletal events associated with furrow formation reveal that these defects include a general delay in furrow initiation as well as a complete failure to form ...	[ "The molecular details driving the splitting of cells in two during cell division , known as cytokinesis , remain incompletely understood , as is the coordination of this process with events that pattern the early animal embryo .", "The dearth of our knowledge in this subject is particularly evident in the case o...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Population Dynamics of Owned, Free-Roaming Dogs: Implications for Rabies Control	journal.pntd.0004177	null	[ [ "Rabies is a serious yet neglected public health threat in resource-limited communities in sub-Saharan Africa [1] .", "In these settings , the virus that causes this deadly disease is largely maintained in populations of free-roaming domestic dogs , and is transmitted to people through bites or other cont...	[ "Rabies is a serious yet neglected public health threat in resource-limited communities in Africa , where the virus is maintained in populations of owned , free-roaming domestic dogs .", "Rabies elimination can be achieved through the mass vaccination of dogs , but maintaining the critical threshold of vaccinatio...	[ "Rabies is a deadly disease caused by a virus that in Africa is maintained in populations of owned , free-roaming domestic dogs .", "Rabies can be controlled by mass vaccination , by ensuring that a certain proportion of the dog population is immune to the disease .", "Maintaining this proportion of immune anim...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "stem anatomy", "medicine and health sciences", "internodes", "fusarium", "pathology and laboratory medicine", "fungal genetics", "pathogens", "microbiology", "fusarium graminearum", "plant science", "plant pathology", "fungal diseases", "plants", "fungal pathogens", "...	Non-canonical fungal G-protein coupled receptors promote Fusarium head blight on wheat	journal.ppat.1007666	null	[ [ "Wheat is prone to FHB disease when warm moist weather coincides with Fusarium graminearum spores arriving during crop anthesis .", "Germinating fungal spores produce hyphae that invade the inner surface of the floral tissues , with or without the production of complex infection structures [1] .", "Th...	[ "Fusarium Head Blight ( FHB ) is the number one floral disease of cereals and poses a serious health hazard by contaminating grain with the harmful mycotoxin deoxynivalenol ( DON ) .", "Fungi adapt to fluctuations in their environment , coordinating development and metabolism accordingly .", "G-protein coupled ...	[ "Fusarium Head Blight ( FHB ) is the number one floral disease of cereals and poses a serious health hazard by contaminating grain with harmful mycotoxins .", "Fusarium graminearum adapts to the host plant environment , coordinating fungal development , metabolism and virulence .", "Here we show that non-classi...	2019
[ "Introduction", "Design and implementation", "Results", "Availability and future directions" ]	[ "taxonomy", "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "evolutionary biology", "split-decomposition method", "pathogens", "microbiology", "animals", "retroviruses", "viruses", "immunodeficiency viruses", "multiple alignment calculation", "phylogen...	Full-Length Envelope Analyzer (FLEA): A tool for longitudinal analysis of viral amplicons	journal.pcbi.1006498	null	[ [ "Next generation sequencing ( NGS ) has become an invaluable tool for studying HIV and other rapidly evolving viruses by providing direct high resolution measurements of viral genetic diversity within the host .", "NGS has been used to study immune escape [1–7] , drug resistance [3 , 7–12] , transmission ...	[ "Next generation sequencing of viral populations has advanced our understanding of viral population dynamics , the development of drug resistance , and escape from host immune responses .", "Many applications require complete gene sequences , which can be impossible to reconstruct from short reads .", "HIV env ...	[ "Viral populations constantly evolve and diversify .", "In this article we introduce a method , FLEA , for reconstructing and visualizing the details of evolutionary changes .", "FLEA specifically processes data from sequencing platforms that generate reads that are long , but error-prone .", "To study the ev...	2018
[ "Introduction", "Methods and materials", "Results", "Discussion", "Conclusion" ]	[ "medicine and health sciences", "immunology", "tropical diseases", "geographical locations", "vertebrates", "animals", "health care", "cobras", "clinical medicine", "reptiles", "neglected tropical diseases", "snakebite", "sri lanka", "treatment guidelines", "vipers", "hospitals", "sn...	A prospective cohort study of the effectiveness of the primary hospital management of all snakebites in Kurunegala district of Sri Lanka	journal.pntd.0005847	null	[ [ "Snakebite is a neglected health issue , mostly affecting rural agricultural communities of the developing countries [1] .", "Over 40 , 000 hospital admissions due to snakebites are officially recorded in Sri Lanka [2] .", "Hump-nosed pit vipers ( Hypnale spp . ) , Russell's viper ( Daboia russelii ) ...	[ "Sri Lanka records substantial numbers of snakebite annually .", "Primary rural hospitals are important contributors to health care .", "Health care planning requires a more detailed understanding of snakebite within this part of the health system .", "This study reports the management and epidemiology of all...	[ "Snakebite is a neglected tropical disease which mainly affects the rural population in tropical countries .", "In Sri Lanka the disease burden is an important cause of hospital admission ( > 40 , 000 recorded annually ) .", "Most of the previous epidemiological studies in the Island have been done in tertiary ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology and environmental sciences", "medicine and health sciences", "seed germination", "gene regulation", "plant physiology", "physiological processes", "micrornas", "plant science", "homeostasis", "plant pathology", "seedlings", "plant ecology", "plants", "plant reproduction", "gene ...	The miR165/166 Mediated Regulatory Module Plays Critical Roles in ABA Homeostasis and Response in Arabidopsis thaliana	journal.pgen.1006416	null	[ [ "The phytohormone abscisic acid ( ABA ) plays critical roles in plant growth and development , such as seed maturation , seed germination , seedling growth , stomatal movement , as well as plant responses to abiotic and biotic stress , including drought , salinity , cold and pathogen infection [1–4] .", "...	[ "The function of miR165/166 in plant growth and development has been extensively studied , however , its roles in abiotic stress responses remain largely unknown .", "Here , we report that reduction in the expression of miR165/166 conferred a drought and cold resistance phenotype and hypersensitivity to ABA durin...	[ "Functions of miRNAs in plant development and stress responses have been extensively studied .", "However , little is known about how a miRNA may perform critical functions in both plant development and abiotic stress responses .", "One well-known miRNA , miR165/166 , has critical roles in plant development .",...	2016
[ "Introduction", "Material and methods", "Result", "Discussion" ]	[ "mycobacterium leprae", "medicine and health sciences", "body fluids", "hela cells", "biological cultures", "tropical diseases", "epithelial cells", "bacterial diseases", "protein expression", "respiratory system", "cell cultures", "neglected tropical diseases", "molecular biology techniques...	The unique tropism of Mycobacterium leprae to the nasal epithelial cells can be explained by the mammalian cell entry protein 1A	journal.pntd.0006704	null	[ [ "Hansen's disease is a chronic infection with acid fast bacillus where skin and peripheral nerves are damaged by the infection with Mycobacterium leprae ( M . leprae ) .", "Although the number of Hansen’s disease cases has drastically decreased in developed countries , worldwide , the number of new cases ...	[ "Leprosy is a chronic infection where the skin and peripheral nervous system is invaded by Mycobacterium leprae .", "The infection mechanism remains unknown in part because culture methods have not been established yet for M . leprae .", "Mce1A protein ( 442 aa ) is coded by mce1A ( 1326 bp ) of M . leprae .", ...	[ "Mce1A protein is a cell surface protein encoded by the mce1A region of mce1 locus of M . tuberculosis and M . leprae , and is involved in the bacteria’s invasion into epithelial cells .", "Using cloned sub domains of mce1A and peptides synthesized for these sub domains , cell entry studies and binding studies we...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "influenza", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "viruses", "rna viruses", "materials science", "antibodies", "immunologic techniques", "olig...	IgA tetramerization improves target breadth but not peak potency of functionality of anti-influenza virus broadly neutralizing antibody	journal.ppat.1007427	null	[ [ "Secretory IgA antibodies ( SIgAs ) play an important role as a first line of defense by inactivating pathogens on mucosal surfaces; this is especially true in the case of viruses such as influenza [1 , 2] .", "Recently , extensive efforts were made to develop novel vaccines that induce immunity via the m...	[ "Mucosal immunoglobulins comprise mainly secretory IgA antibodies ( SIgAs ) , which are the major contributor to pathogen-specific immune responses in mucosal tissues .", "These SIgAs are highly heterogeneous in terms of their quaternary structure .", "A recent report shows that the polymerization status of SIg...	[ "SIgAs exist as mainly dimers and tetramers and play critical roles in mucosal immune responses against influenza .", "Detailed characterization of these anti-viral SIgA is important for better understanding of the mechanisms underlying anti-viral immunity .", "Here , we describe a means of generating a recombi...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "complement system", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "salmonellosis", "bacterial diseases", "enterobacteriaceae", "bacteria", "bacterial pathogens", "digestive system", "salmonella typhimur...	Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo	journal.ppat.1006925	null	[ [ "Non-typhoidal Salmonella like Salmonella enterica subsp .", "enterica sv .", "Typhimurium ( S . Typhimurium ) represent a major causative agent of gastroenteritis in humans worldwide [1 , 2] .", "Infection usually occurs through the ingestion of contaminated food or drinking water .", "Salmon...	[ "Effector molecules translocated by the Salmonella pathogenicity island ( SPI ) 1-encoded type 3 secretion system ( T3SS ) critically contribute to the pathogenesis of human Salmonella infection .", "They facilitate internalization by non-phagocytic enterocytes rendering the intestinal epithelium an entry site fo...	[ "Non-typhoidal Salmonella represent a major causative agent of gastroenteritis worldwide .", "Hallmark of the pathogenesis is their ability to actively invade the intestinal epithelium by virtue of their type 3 secretion system that delivers bacterial virulence factors directly into the host cell cytosol .", "T...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology", "virology" ]	Impaired Antibody Response Causes Persistence of Prototypic T Cell–Contained Virus	journal.pbio.1000080	Andreas Bergthaler and colleagues reveal that T cell control of systemic persistent viral infections requires support by antibodies produced by B cells, which may have important implications for future vaccination strategies against HIV and hepatitis C.	[ [ "Infections associated with persistent viremia include human immunodeficiency virus ( HIV ) and the hepatitis B and C viruses ( HBV , HCV ) , which affect more than 500 million people worldwide .", "However , available options to prevent and treat particularly HIV and HCV are unsatisfactory .", "To re...	[ "CD8 T cells are recognized key players in control of persistent virus infections , but increasing evidence suggests that assistance from other immune mediators is also needed .", "Here , we investigated whether specific antibody responses contribute to control of lymphocytic choriomeningitis virus ( LCMV ) , a p...	[ "Persistent viruses such as hepatitis C virus ( HCV ) or HIV can defeat the body's defense system and cause devastating epidemics worldwide .", "Recent attempts at vaccinating against HIV have relied on the induction of specific antiviral killer T lymphocytes but have failed to confer protection on the host .", ...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "physics", "physiological processes", "computer and information sciences", "medicine and health sciences", "computer modeling", "interdisciplinary physics", "physiology", "sleep", "biology and life sciences", "physical sciences", "biophysics", "neuroscience", "biophysical simulations" ]	Characterization of K-Complexes and Slow Wave Activity in a Neural Mass Model	journal.pcbi.1003923	null	[ [ "Several studies indicate a major role of slow wave sleep ( SWS ) in the consolidation of memories [1] , [2] .", "Especially its hallmarks , cortical slow oscillations ( SO ) , are hypothesized to be a key mechanism for the transfer of memory into the neocortical long-term storage [3] , [4] .", "Furth...	[ "NREM sleep is characterized by two hallmarks , namely K-complexes ( KCs ) during sleep stage N2 and cortical slow oscillations ( SOs ) during sleep stage N3 .", "While the underlying dynamics on the neuronal level is well known and can be easily measured , the resulting behavior on the macroscopic population lev...	[ "In recent years , sleep has drawn increasing attention due to its multifunctional role , e . g . the involvement in the consolidation of memory .", "While neural mass models have been successfully employed to describe the dynamics of the awake brain , the drastic changes that arise during sleep have been challen...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "urology", "medicine and health sciences", "quantitative trait loci", "caenorhabditis", "animals", "animal models", "caenorhabditis elegans", "regulator genes", "model organisms", "chromosome mapping", "gene types", "molecular biology techniques", "population biology", "...	Selection on a Subunit of the NURF Chromatin Remodeler Modifies Life History Traits in a Domesticated Strain of Caenorhabditis elegans	journal.pgen.1006219	null	[ [ "Organisms are faced with limited resources to invest in their growth , survival , and offspring .", "Because they cannot dedicate unlimited energy to all traits , they must prioritize energy distribution depending on their environment and sexual partners [1] .", "Trade-offs represent the combined cha...	[ "Evolutionary life history theory seeks to explain how reproductive and survival traits are shaped by selection through allocations of an individual’s resources to competing life functions .", "Although life-history traits evolve rapidly , little is known about the genetic and cellular mechanisms that control and...	[ "Sex and death are two fundamental concerns of each organism .", "These traits evolve rapidly in natural populations as animals seek to maximize their fitness in a given environment .", "For example , in mammals , lifespan , size , and fecundity vary over two order of magnitude .", "A key observation of evolu...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/membranes and sorting", "cell biology/plant genetics and gene expression", "plant biology/plant cell biology", "cell biology/plant cell biology" ]	HAP2(GCS1)-Dependent Gamete Fusion Requires a Positively Charged Carboxy-Terminal Domain	journal.pgen.1000882	null	[ [ "The fusion of gamete plasma membranes is a critical event in fertilization , but despite the ubiquity of the process among sexually reproducing eukaryotes , no conserved mechanism for gamete fusion has been described .", "At least two factors contribute to our lack of mechanistic insight .", "First ,...	[ "HAP2 ( GCS1 ) is a deeply conserved sperm protein that is essential for gamete fusion .", "Here we use complementation assays to define major functional regions of the Arabidopsis thaliana ortholog using HAP2 ( GCS1 ) variants with modifications to regions amino ( N ) and carboxy ( C ) to its single transmembran...	[ "Recent studies suggest that HAP2 ( GCS1 ) is a deeply conserved protein required for gamete membrane fusion , a critical yet poorly understood step in sexual reproduction .", "HAP2 ( GCS1 ) is present in many plant , protist , and animal genomes , and has been shown to be essential for fertilization in Arabidops...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "animal types", "medicine and health sciences", "pathology and laboratory medicine", "china", "pathogens", "post-exposure prophylaxis", "domestic animals", "tropical diseases", "microbiology", "geographical locations", "animals", "health care", "viruses", "vaccines", "preventive medicine...	Improper wound treatment and delay of rabies post-exposure prophylaxis of animal bite victims in China: Prevalence and determinants	journal.pntd.0005663	null	[ [ "Rabies is a fatal infectious disease , which causes severe neurological symptoms that unavoidably result in death .", "Although human rabies is currently untreatable [1] , appropriate post-exposure prophylaxis ( PEP ) can entirely prevent rabies [2 , 3] .", "Such PEP , which consists of local treatme...	[ "Rabies is invariably a fatal disease .", "Appropriate wound treatment and prompt rabies post-exposure prophylaxis ( PEP ) are of great importance to rabies prevention .", "The objective of this study was to investigate the prevalence and influencing factors of improper wound treatment and delay of rabies PEP a...	[ "Although the incidence of animal bites is increasing in China , residents’ knowledge about appropriate wound treatment and prompt PEP is insufficient .", "A face-to-face interview was conducted to investigate whether the wound was treated properly and to determine the time disparity between injury and consultati...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "public health", "medicine", "infectious diseases", "test evaluation", "public health and epidemiology", "diagnostic medicine", "fasciolosis", "neglected tropical diseases", "parasitic diseases" ]	Field Evaluation of a Coproantigen Detection Test for Fascioliasis Diagnosis and Surveillance in Human Hyperendemic Areas of Andean Countries	journal.pntd.0001812	null	[ [ "Fascioliasis is an important human and animal disease caused by the trematode species Fasciola hepatica and F . gigantica .", "At present , fascioliasis is emerging or re-emerging in numerous regions of Latin-America , Africa , Europe and Asia , both in humans and animals , a phenomenon which has partly ...	[ "Emergence of human fascioliasis prompted a worldwide control initiative including a pilot study in a few countries .", "Two hyperendemic areas were chosen: Huacullani , Northern Altiplano , Bolivia , representing the Altiplanic transmission pattern with high prevalences and intensities; Cajamarca valley , Peru ,...	[ "A coproantigen-detection technique ( MM3-COPRO ELISA ) was evaluated in 436 and 362 schoolchildren of Huacullani , Bolivia , and Cajamarca valley , Peru , respectively .", "Classical techniques for egg detection were used for comparison .", "In Huacullani , using Kato-Katz as gold standard , sensitivity and sp...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity	journal.pcbi.1004454	null	[ [ "Basic principles in reaction kinetics of biomolecules were described by the work of Guldberg & Waage [1–3] more than 150 years ago and recently resumed by Voit et al . , 2015 [4] in their perspective article \"150 years of mass action\" .", "The underlying concept is the law of mass action , describing t...	[ "The objectives of this work were the classification of dynamic metabolic biomarker candidates and the modeling and characterization of kinetic regulatory mechanisms in human metabolism with response to external perturbations by physical activity .", "Longitudinal metabolic concentration data of 47 individuals fr...	[ "Human metabolism is controlled through basic kinetic regulatory mechanisms , where the overall system aims to maintain a state of homeostasis .", "In response to external perturbations , such as environmental influences , nutrition or physical exercise , circulating metabolites show specific kinetic response pat...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "veterinary science" ]	An Unexpected Recurrent Transmission of Rift Valley Fever Virus in Cattle in a Temperate and Mountainous Area of Madagascar	journal.pntd.0001423	null	[ [ "Rift Valley fever ( RVF ) is an acute , zoonotic viral disease , caused by a phlebovirus belonging to the Bunyaviridae family [1] .", "It mainly affects domestic ruminants such as sheep , goats and cattle [2] .", "The main clinical signs of the disease are high mortality rates , especially in new-bor...	[ "Rift Valley fever is an acute , zoonotic viral disease of domestic ruminants , caused by a phlebovirus ( Bunyaviridae family ) .", "A large outbreak occurred in Madagascar in 2008–2009 .", "The goal of the present study was to evaluate the point prevalence of antibodies against Rift Valley Fever Virus ( RVFV )...	[ "Rift Valley fever ( RVF ) is a viral disease of domestic ruminants , which may affect humans .", "The RVF virus ( RVFV ) may be transmitted either by mosquitoes or through direct contact with vireamic body fluids or products .", "Until now , this disease had been described in arid , hot and irrigated or tropic...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "population genetics", "effective population size", "population modeling", "speciation", "population biology", "biology", "hybridization", "evolutionary genetics", "natural selection", "evolutionary processes", "gene flow", "genomics", "evolutionary biology", "computational biology", "ge...	Genomic Evidence for Island Population Conversion Resolves Conflicting Theories of Polar Bear Evolution	journal.pgen.1003345	null	[ [ "Despite polar bears' clear morphological and behavioral adaptations to their arctic environment [1] , [2] , their genetic relationship to brown bears remains unclear [3] , [4] , [5] , [6] .", "Analysis of maternally inherited mitochondrial DNA ( mtDNA ) shows that polar bears fall within the range of var...	[ "Despite extensive genetic analysis , the evolutionary relationship between polar bears ( Ursus maritimus ) and brown bears ( U . arctos ) remains unclear .", "The two most recent comprehensive reports indicate a recent divergence with little subsequent admixture or a much more ancient divergence followed by exte...	[ "The evolutionary genetic relationship between polar bears ( Ursus maritimus ) and brown bears ( U . arctos ) is a subject of continuing controversy .", "To address this we generated genome-wide sequence data for seven polar bears , two brown bears ( including one from the enigmatic ABC Islands population ) , and...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "nucleases", "molecular probe techniques", "deoxyribonucleases", "enzymes", "microbiology", "nucleocapsids", "viral structure", "dna-binding proteins", "enzymology", "polymerases", "forms of dna", "circular dna", "molecular biology techniques", "dna", "research and analysis methods", "...	HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways	journal.ppat.1006658	null	[ [ "Hepatitis B virus ( HBV ) is a small DNA virus that chronically infects 240 million people worldwide and causes approximately 686 , 000 deaths annually due to various severe liver diseases , including cirrhosis , hepatocellular carcinoma ( HCC ) and liver failure [1] .", "Currently approved direct-acting...	[ "Hepatitis B virus ( HBV ) core protein assembles viral pre-genomic ( pg ) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place .", "Several chemotypes of small molecules , including heteroaryldihydropyrimidines ( HAPs ) and sulfamoylbenzamides ( SBAs ) , have been d...	[ "Persistent HBV infection relies on stable maintenance of a nuclear episomal viral genome called covalently closed circular ( ccc ) DNA , the sole transcriptional template supporting viral replication .", "The currently available antiviral therapeutics fail to cure chronic HBV infection due to their failure to er...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	An Evolution-Based Approach to De Novo Protein Design and Case Study on Mycobacterium tuberculosis	journal.pcbi.1003298	null	[ [ "Computational protein design aims to identify new amino acid sequences that have desirable 3-dimensional ( 3D ) structure and biological function .", "This can be considered as a reversed procedure of protein folding and protein structure prediction , in that protein folding and protein structure predict...	[ "Computational protein design is a reverse procedure of protein folding and structure prediction , where constructing structures from evolutionarily related proteins has been demonstrated to be the most reliable method for protein 3-dimensional structure prediction .", "Following this spirit , we developed a nove...	[ "The goal of computational protein design is to create new protein sequences of desirable structure and biological function .", "Most protein design methods are developed to search for sequences with the lowest free-energy based on physics-based force fields following Anfinsen's thermodynamic hypothesis .", "A ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "hematologic cancers and related disorders", "acute myeloid leukemia", "leukemias", "medicine and health sciences", "myeloid leukemia", "genome evolution", "genetics", "biology and life sciences", "myelodysplastic syndromes", "genomics", "computational biology", "hematology" ]	Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing	journal.pgen.1004462	null	[ [ "Intratumoral heterogeneity is an emerging hallmark of cancer that can be interrogated genome-wide with next-generation sequencing .", "Critically , sub-populations of tumor cells are organized into hierarchies through clonal evolution .", "A powerful strategy for studying this population structure is...	[ "Next-generation sequencing has been used to infer the clonality of heterogeneous tumor samples .", "These analyses yield specific predictions—the population frequency of individual clones , their genetic composition , and their evolutionary relationships—which we set out to test by sequencing individual cells fr...	[ "Human cancers are genetically diverse populations of cells that evolve over the course of their natural history or in response to the selective pressure of therapy .", "In theory , it is possible to infer how this variation is structured into related populations of cells based on the frequency of individual muta...	2014
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[]	Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep	journal.pgen.1007739	null	[ [ "Arterial oxyhemoglobin saturation is a fundamental physiological trait that is tightly regulated at cellular and systemic levels to optimize tissue oxygen delivery .", "Reduced values , or hypoxemia , occurs secondary to acute and chronic respiratory or cardiovascular diseases , and rarely due to hemoglo...	[ "Sleep disordered breathing ( SDB ) -related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities .", "Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality .", "We conducted genome...	[ "Variation in oxyhemoglobin saturation , the proportion of oxygen-saturated to total hemoglobin in the blood , is associated with numerous disorders and is a predictor of health outcomes including mortality , incident heart failure , and dementia .", "Despite the fundamental role of oxygen saturation in normal an...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "learning", "machine learning algorithms", "decision making", "applied mathematics", "social sciences", "neuroscience", "learning and memory", "simulation and modeling", "algorithms", "cognitive psychology", "mathematics", "animal behavior", "artificial intelligence", "cognition", "zoolo...	Modeling sensory-motor decisions in natural behavior	journal.pcbi.1006518	null	[ [ "The primary focus of reinforcement learning has been on forward models that , given reward signals , can learn to produce policies , which specify action choices when immersed in an environment state .", "A state refers to information about the environment that is needed for decision making .", "An i...	[ "Although a standard reinforcement learning model can capture many aspects of reward-seeking behaviors , it may not be practical for modeling human natural behaviors because of the richness of dynamic environments and limitations in cognitive resources .", "We propose a modular reinforcement learning model that a...	[ "It is generally agreed that human actions can be formalized within the framework of statistical decision theory , which specifies a cost function for actions choices , and that the intrinsic value of actions is controlled by the brain’s dopaminergic reward machinery .", "Given behavioral data , the underlying su...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schoolchildren", "mycobacterium leprae", "medicine and health sciences", "pathology and laboratory medicine", "education", "disabilities", "sociology", "tropical diseases", "geographical locations", "social sciences", "bacterial diseases", "human families", "signs and symptoms", "neglecte...	Leprosy among schoolchildren in the Amazon region: A cross-sectional study of active search and possible source of infection by contact tracing	journal.pntd.0006261	null	[ [ "Mycobacterium leprae , the causative agent of leprosy , is primarily transmitted person-to-person and through the air .", "People living in leprosy-endemic regions are at greater risk of being exposed to the infection .", "The risk of developing the disease among paucibacillary ( PB ) contacts is 2–3...	[ "The high rate of leprosy cases among children under 15 years of age in Brazil indicates ongoing transmission within the community .", "The identification of the new leprosy cases among contacts can help identify the source of infection and interrupt the transmission chain .", "This study aims to determine the ...	[ "Leprosy is a disease that has long since been eradicated in the developed world , but it still affects poor people in developing countries , such as India , Brazil , and Indonesia .", "Because the causative agent of the disease may involve the skin and peripheral nerves , the disease can cause physical disabilit...	2018

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