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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", "Materials and Methods", "Results and Discussion" ]	[]	Molecular Design, Synthesis and Trypanocidal Activity of Dipeptidyl Nitriles as Cruzain Inhibitors	journal.pntd.0003916	null	[ [ "Chagas disease is caused by the protozoan parasite Trypanosoma cruzi , which is transmitted by blood-sucking reduviid bugs of the subfamily Triatominae [1–3] .", "Also known as American trypanosomiasis , Chagas disease remains a serious public health problem in Latin America [4 , 5] and its spread from n...	[ "A series of compounds based on the dipeptidyl nitrile scaffold were synthesized and assayed for their inhibitory activity against the T . cruzi cysteine protease cruzain .", "Structure activity relationships ( SARs ) were established using three , eleven and twelve variations respectively at the P1 , P2 and P3 p...	[ "Chagas disease is a parasitic infection with high morbidity and mortality that is endemic in much of Latin America where it remains a serious public health problem .", "With increased migration , Chagas disease represents an emerging worldwide challenge and there is an urgent , unmet need for safe and effective ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "horizontal gene transfer", "medicine and health sciences", "microbiology", "gene transfer", "bacterial diseases", "enterobacteriaceae", "bacteria", "bacterial pathogens", "foodborne diseases", "infectious diseases", "escherichia coli infections", "medical microbiology", "microbial pathogens...	Silencing by H-NS Potentiated the Evolution of Salmonella	journal.ppat.1004500	null	[ [ "Horizontal gene transfer ( HGT ) has profoundly shaped the course of bacterial speciation and diversification .", "The uptake of ‘pre-assembled’ genetic loci involved in antibiotic resistance , virulence , phage resistance or novel modes of metabolism can instantly confer beneficial phenotypes to the rec...	[ "The bacterial H-NS protein silences expression from sequences with higher AT-content than the host genome and is believed to buffer the fitness consequences associated with foreign gene acquisition .", "Loss of H-NS results in severe growth defects in Salmonella , but the underlying reasons were unclear .", "A...	[ "H-NS is an abundant DNA-binding protein found in enteric bacteria including the important pathogens Escherichia , Salmonella , Vibrio , and Yersinia , that plays a primary role in defending the bacterial genome by silencing AT-rich foreign genes .", "H-NS has been hypothesized to facilitate the evolution of bact...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "infographics", "simulation and modeling", "epistasis", "mutation", "population biology", "research and analysis methods", "computer and information sciences", "fitness epistasis", "evolutionary genetics", "population metrics", "birth rates", "population size", "data visualization", "hered...	Every which way? On predicting tumor evolution using cancer progression models	journal.pcbi.1007246	null	[ [ "Improving our ability to predict the paths of tumor progression is helpful for diagnostic , prognostic , and treatment purposes as , for example , it would allow us to identify genes that block the most common paths of disease progression [1–4] .", "This interest in predicting paths of progression is not...	[ "Successful prediction of the likely paths of tumor progression is valuable for diagnostic , prognostic , and treatment purposes .", "Cancer progression models ( CPMs ) use cross-sectional samples to identify restrictions in the order of accumulation of driver mutations and thus CPMs encode the paths of tumor pro...	[ "Knowing the likely paths of tumor progression is instrumental for cancer precision medicine as it would allow us to identify genetic targets that block disease progression and to improve therapeutic decisions .", "Direct information about paths of tumor progression is scarce , but cancer progression models ( CPM...	2019
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine", "microbial metabolism", "microbiology", "bacterial biochemistry", "animal models", "metagenomics", "model organisms", "microbial physiology", "medical microbiology", "biology", "proteomics", "mouse", "microbial ecology", "community ecology", "systems biology...	Effects of Diet on Resource Utilization by a Model Human Gut Microbiota Containing Bacteroides cellulosilyticus WH2, a Symbiont with an Extensive Glycobiome	journal.pbio.1001637	Artificial human gut microbial communities implanted into germ-free mice provide insights into how species-level responses to changes in diet give rise to community-level structural and functional reconfiguration and how types of bacteria prioritize use of available nutrients in vivo.	[ [ "A growing body of evidence indicates that the tens of trillions of microbial cells that inhabit our gastrointestinal tracts extend our biological capabilities in important ways .", "Microbial enzymes process many compounds that would otherwise pass through our intestines unaltered [1] , and cases of part...	[ "The human gut microbiota is an important metabolic organ , yet little is known about how its individual species interact , establish dominant positions , and respond to changes in environmental factors such as diet .", "In this study , gnotobiotic mice were colonized with an artificial microbiota comprising 12 s...	[ "Our intestines are populated by an almost unimaginably large number of microbial cells , most of which are bacteria .", "This species assemblage operates as a microbial metabolic organ , performing myriad tasks that contribute to our well-being , including processing components of our diet .", "The way this in...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "condensed matter physics", "microbiology", "organisms", "fungi", "molecular biology techniques", "fungal diseases", "dna", "fungal pathogens", "extraction techniques", "research and analysis methods", "seque...	Molecular detection of airborne Emergomyces africanus, a thermally dimorphic fungal pathogen, in Cape Town, South Africa	journal.pntd.0006174	null	[ [ "Emergomyces africanus is an emerging opportunistic dimorphic fungal pathogen that causes emergomycosis , a systemic and often-fatal HIV-associated mycosis in South Africa [1 , 2] .", "It is a member of a newly-described genus within the family Ajellomycetaceae called Emergomyces , so-named because of the...	[ "Emergomyces africanus is a thermally dimorphic fungus that causes a systemic mycosis in immunocompromised persons in South Africa .", "Infection is presumed to follow inhalation of airborne propagules .", "We developed a quantitative PCR protocol able to detect as few as 5 Es .", "africanus propagules per da...	[ "Emergomyces africanus is a recently described dimorphic fungus that causes a serious and often fatal disease in immunocompromised patients in South Africa .", "Infection is presumed to occur via inhalation of infectious propagules; however , no attempts have yet been made to detect this fungus in the air .", "...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "immune cells", "lymphocyte proliferation", "viral transmission and infection", "immunity to infections", "immunology", "microbiology", "lymphocyte activation", "herpesviruses", "viral load", "animal models of infection", "white blood cells", "epstein-barr virus", "viral cle...	Defining Immune Engagement Thresholds for In Vivo Control of Virus-Driven Lymphoproliferation	journal.ppat.1004220	null	[ [ "The gamma-herpesviruses ( γHVs ) infect >90% of humans and cause diseases including nasopharyngeal carcinoma , African Burkitt's lymphoma and Kaposi's Sarcoma .", "Their colonization of circulating memory B cells is crucial to persistence and hence to disease ontogeny .", "Viral latency gene expressi...	[ "Persistent infections are subject to constant surveillance by CD8+ cytotoxic T cells ( CTL ) .", "Their control should therefore depend on MHC class I-restricted epitope presentation .", "Many epitopes are described for γ-herpesviruses and form a basis for prospective immunotherapies and vaccines .", "Howeve...	[ "Chronic viral infections cause huge morbidity and mortality worldwide .", "γ-herpesviruses provide an example relevant to all human demographics , causing , inter alia , Hodgkin's disease , Burkitt's lymphoma , Kaposi's Sarcoma , and nasopharyngeal carcinoma .", "The proliferation of latently infected B cells ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Comparison of Vector Competence of Aedes mediovittatus and Aedes aegypti for Dengue Virus: Implications for Dengue Control in the Caribbean	journal.pntd.0003462	null	[ [ "Dengue virus ( DENV , Family Flaviridae , Genus Flavivirus ) is most commonly transmitted to humans by the bite of an infected Aedes aegypti mosquito .", "Worldwide , Ae .", "aegypti and Aedes albopictus are the main vectors for DENV transmission , however Ae . albopictus has not been found in Puerto...	[ "Aedes mediovittatus mosquitoes are found throughout the Greater Antilles in the Caribbean and often share the same larval habitats with Ae .", "Aegypti , the primary vector for dengue virus ( DENV ) .", "Implementation of vector control measures to control dengue that specifically target Ae .", "Aegypti may ...	[ "Dengue is a potentially life-threatening tropical disease caused by four serotypes of virus , dengue virus 1 , -2 , -3 , and -4 .", "Worldwide , as many as 390 million people become infected with dengue virus each year after being bitten by infectious Aedes mosquitoes .", "Unfortunately , there is no commercia...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "developmental biology", "plant science", "gene expression", "plant genomics", "genetics", "biology and life sciences", "molecular genetics", "plant genetics", "genomics", "plant biotechnology" ]	Apomictic and Sexual Germline Development Differ with Respect to Cell Cycle, Transcriptional, Hormonal and Epigenetic Regulation	journal.pgen.1004476	null	[ [ "In flowering plants , both sexual and asexual reproduction through seeds ( apomixis ) is common .", "Apomixis occurs in more than 400 plant species belonging to over 40 families , but it is poorly represented in crop species .", "Apomixis leads to clonal offspring by conservation of the maternal geno...	[ "Seeds of flowering plants can be formed sexually or asexually through apomixis .", "Apomixis occurs in about 400 species and is of great interest for agriculture as it produces clonal offspring .", "It differs from sexual reproduction in three major aspects: ( 1 ) While the sexual megaspore mother cell ( MMC )...	[ "In flowering plants , asexual reproduction through seeds ( apomixis ) likely evolved from sexual ancestors several times independently .", "Only three key developmental steps differ between sexual reproduction and apomixis .", "In contrast to sexual reproduction , in apomicts the first cell of the female repro...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "genomics", "genetic disorders", "phenotypes", "genetic association studies", "genome analysis", "heredity", "genetics", "biology and life sciences", "population genetics", "quantitative traits", "computational biology", "evolutionary biology", "gene disr...	Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population	journal.pgen.1004494	null	[ [ "After widespread success with genome-wide association studies ( GWAS ) of common variants , several studies have recently begun to identify rare ( with <0 . 5% allele frequency ) and low-frequency ( 0 . 5–5% ) variants in complex diseases and traits such as triglycerides [1] , insulin processing [2] , bone m...	[ "Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity , large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants , even in phenotypically relevant genes .", "Isolated populations with recent bottlenecks of...	[ "We explored the coding regions of 3 , 000 Finnish individuals with 3 , 000 non-Finnish Europeans ( NFEs ) using whole-exome sequence data , in order to understand how an individual from a bottlenecked population might differ from an individual from an out-bred population .", "We provide empirical evidence that t...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Prospective Antiretroviral Treatment of Asymptomatic, HIV-1 Infected Controllers	journal.ppat.1003691	null	[ [ "HIV-infected “controllers” are individuals who are HIV-seropositive but are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy ( ART ) [1] .", "These individuals are rare , comprising less than 1–7% of the HIV-infected population , depending upon the plasma HIV RNA cri...	[ "The study of HIV-infected “controllers” who are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy ( ART ) may provide insights for HIV cure and vaccine strategies .", "Despite maintaining very low levels of plasma viremia , controllers have elevated immune activation and acce...	[ "HIV-infected “controllers” are rare individuals who are HIV-seropositive but are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy ( ART ) .", "There has been intense interest in characterizing these unique individuals because they have been considered as a potential model fo...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "protein metabolism", "pathology and laboratory medicine", "intracellular pathogens", "viral transmission and infection", "pathogens", "immunology", "microbiology", "mutation", "centrifugation", "research and analysis methods", ...	Proteomics of intracellular Salmonella enterica reveals roles of Salmonella pathogenicity island 2 in metabolism and antioxidant defense	journal.ppat.1007741	null	[ [ "Salmonella enterica is an invasive , facultative intracellular pathogen causing frequent infection of humans and animal hosts that range from gastroenteritis to typhoid fever , a systemic infection caused by human-restricted S . enterica serovars such as Typhi .", "S . enterica serovar Typhimurium ( STM ...	[ "Intracellular Salmonella enterica serovar Typhimurium ( STM ) deploy the Salmonella Pathogenicity Island 2-encoded type III secretion system ( SPI2-T3SS ) for the massive remodeling of the endosomal system for host cells .", "This activity results in formation of an extensive interconnected tubular network of Sa...	[ "The facultative intracellular bacterium Salmonella enterica has evolved sophisticated mechanisms to adapt to life inside a pathogen-containing vacuole in mammalian host cells .", "Intracellular Salmonella manipulate the host cell endosomal system resulting in formation of a complex network of tubular vesicles , ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "invertebrates", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "silkworms", "experimental organism systems", "embryos", "morphogenesis", "drosophila", "genetic engineering", "research and analysis methods", "embryology...	Bombyx mori P-element Somatic Inhibitor (BmPSI) Is a Key Auxiliary Factor for Silkworm Male Sex Determination	journal.pgen.1006576	null	[ [ "Genetic systems for sex determination in insects show high diversity in different species .", "Sex determination in the fruit fly , Drosophila melanogaster , is controlled hierarchically by X:A > Sxl > tra/tra2 > dsx and fru [1 , 2] .", "The X:A ratio of 1 promotes transcription of Sex-lethal ( Sxl )...	[ "Manipulation of sex determination pathways in insects provides the basis for a wide spectrum of strategies to benefit agriculture and public health .", "Furthermore , insects display a remarkable diversity in the genetic pathways that lead to sex differentiation .", "The silkworm , Bombyx mori , has been culti...	[ "The sex determination system extremely diverse among organisms including insects in which even each order occupy a different manner of sex determination .", "The silkworm , Bombyx mori , is a lepidopteran model insect with economic importance .", "The mechanism of the silkworm sex determination has been in mys...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	An Evolutionary Approach for Identifying Driver Mutations in Colorectal Cancer	journal.pcbi.1004350	null	[ [ "Our computational approach is based upon the evolutionary dynamics of the accumulation of driver and passenger mutations in a population of cells ( Fig 1 .", "( a ) ) .", "There are two phases ( Fig 1 .", "( b ) ) : a pre-initiation phase and a clonal expansion phase .", "During the pre-initi...	[ "The traditional view of cancer as a genetic disease that can successfully be treated with drugs targeting mutant onco-proteins has motivated whole-genome sequencing efforts in many human cancer types .", "However , only a subset of mutations found within the genomic landscape of cancer is likely to provide a fit...	[ "Evolutionary dynamic models have been intensively studied to elucidate the process of tumorigenesis .", "One key aspect of studying tumorigenesis is to distinguish the “driver” mutations providing a fitness advantage to cancer cells against neutral “passenger” or “hitchhiking” mutations .", "Many statistical m...	2015
[ "Introduction", "Methods and Materials", "Results", "Discussion" ]	[]	SAAS-CNV: A Joint Segmentation Approach on Aggregated and Allele Specific Signals for the Identification of Somatic Copy Number Alterations with Next-Generation Sequencing Data	journal.pcbi.1004618	null	[ [ "Profound somatic copy number alternations ( SCNAs ) are present in many types of tumors [1–3] , where they affect a larger fraction of the genome than other types of somatic variations [3 , 4] .", "The roles of SCNAs in promoting oncogenesis and tumor progression are under intensive study .", "In con...	[ "Cancer genomes exhibit profound somatic copy number alterations ( SCNAs ) .", "Studying tumor SCNAs using massively parallel sequencing provides unprecedented resolution and meanwhile gives rise to new challenges in data analysis , complicated by tumor aneuploidy and heterogeneity as well as normal cell contamin...	[ "Somatic copy number alterations ( SCNAs ) are essential in oncogensis and progression of a variety of cancers .", "Accurate identification and quatification of SCNAs are fundamental in the effort of cataloging different variants in cancer genome .", "This task has its own challenges due to complex nature of tu...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "glycolipids", "immune cells", "protein interactions", "antigen-presenting cells", "immunology", "glycoproteins", "immunomodulation", "major histocompatibility complex", "t cells", "biology", "proteomics", "immune response", "immunopathology", "biochemistry", "antigen processing and reco...	TLR4 and NKT Cell Synergy in Immunotherapy against Visceral Leishmaniasis	journal.ppat.1002646	null	[ [ "Visceral leishmaniasis ( VL ) is a deadly disease caused by the parasitic protozoan Leishmania donovani ( LD ) in India , Bangladesh , China , Nepal and Sudan; by L . Infantum in N . Africa and Southern Europe , and by L . chagasi in Latin America .", "There is a regional variation in response to antilei...	[ "NKT cells play an important role in autoimmune diseases , tumor surveillance , and infectious diseases , providing in most cases protection against infection .", "NKT cells are reactive to CD1d presented glycolipid antigens .", "They can modulate immune responses by promoting the secretion of type 1 , type 2 ,...	[ "Kala azar ( visceral leishmaniasis ) is a deadly disease caused by the parasitic protozoa Leishmania donovani .", "In absence of a suitable vaccine , the incidence of leishmaniasis has increased .", "The World Health Organization observes that , if the disease is not treated , the fatality rate in developing c...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Evolutionary Constraint and Disease Associations of Post-Translational Modification Sites in Human Genomes	journal.pgen.1004919	null	[ [ "Decreasing sequencing costs have led to unprecedented opportunities to explore human genomes [1 , 2] .", "Linking genome information to molecular mechanism and resulting phenotype , including disease , is a key aim of human genetics that is hindered by complex patterns of inter-individual variation [3] ....	[ "Interpreting the impact of human genome variation on phenotype is challenging .", "The functional effect of protein-coding variants is often predicted using sequence conservation and population frequency data , however other factors are likely relevant .", "We hypothesized that variants in protein post-transla...	[ "Individual human genomes differ in numerous and infrequent small-scale changes such as single nucleotide variants .", "Understanding the biological role of variation and impact on phenotypes such as physical appearance or disease risk is an important challenge .", "We studied human variation of post-translatio...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "body fluids", "chemical compounds", "pneumococcus", "pathology and laboratory medicine", "sialic acids", "viral transmission and infection", "enzymes", "pathogens", "enzymology", "microbiology", "carbohydrates", "organic compounds", "serine", "neurovirule...	Deacetylation of sialic acid by esterases potentiates pneumococcal neuraminidase activity for mucin utilization, colonization and virulence	journal.ppat.1006263	null	[ [ "Glycosylation is the most common posttranslational modification for proteins and lipids [1 , 2] .", "Given the abundance of the glycans , microbes have evolved mechanisms to take advantage of the carbohydrate-rich environment in the human body during colonization and , invasive infections [2] .", "St...	[ "Pneumococcal neuraminidase is a key enzyme for sequential deglycosylation of host glycans , and plays an important role in host survival , colonization , and pathogenesis of infections caused by Streptococcus pneumoniae .", "One of the factors that can affect the activity of neuraminidase is the amount and posit...	[ "Neuraminidase activity is critical for pneumococcal colonization and virulence as it is required for efficient cleavage of host glycans for nutritional requirements , attachment , and translocation of the microbe through biological membranes .", "Modifications , such as O-acetylation , in terminal sialic acid ca...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "steatosis", "anatomical pathology", "carbohydrate metabolism", "medicine and health sciences", "pathology and laboratory medicine", "diabetic endocrinology", "glucose metabolism", "cytopathology", "liver diseases", "hormones", "gastroenterology and hepatology", "research and analysis methods"...	A Computational Model of Hepatic Energy Metabolism: Understanding Zonated Damage and Steatosis in NAFLD	journal.pcbi.1005105	null	[ [ "Previous computational models of glucose homeostasis and liver energy metabolism have varied from those studying liver metabolism within the body as a whole to those focussed in detail on the regulation of specific enzymes depending upon the particular purpose of the study .", "For example , Kim et al . ...	[ "In non-alcoholic fatty liver disease ( NAFLD ) , lipid build-up and the resulting damage is known to occur more severely in pericentral cells .", "Due to the complexity of studying individual regions of the sinusoid , the causes of this zone specificity and its implications on treatment are largely ignored .", ...	[ "Fat build up in liver is known to increase the likelihood of developing numerous health problems around the body including cardiovascular problems , desensitisation to the hormone insulin leading to type 2 diabetes , and the development of fibrous tissue in liver ( fibrosis ) resulting in loss of liver function ( ...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "messenger rna", "microbiology", "dna transcription", "bacterial diseases", "mutation", "regulator genes", "enterobacteriaceae", "gene types", "bacteria", "bacterial pathogens", "digestive system", "infecti...	Salmonella invasion is controlled through the secondary structure of the hilD transcript	journal.ppat.1007700	null	[ [ "The success of bacterial pathogens relies upon a fine balance: They must rapidly induce functions dedicated to virulence in response to signals of the host , but withstand the often immense associated fitness costs that the production of these virulence proteins entails .", "This need is particularly acu...	[ "Virulence functions of bacterial pathogens are often energetically costly and thus are subjected to intricate regulatory mechanisms .", "In Salmonella , invasion of the intestinal epithelium , an essential early step in virulence , requires the production of a multi-protein type III secretion apparatus .", "Th...	[ "Pathogenic bacteria tightly regulate the expression of their virulence functions to balance survival and proliferation within an animal host against the fitness costs that these functions engender .", "Salmonella has evolved an energetically favorable means to invade the intestinal epithelium , required for its ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "immunology/immunity to infections", "immunology/immune response", "pathology/immunology" ]	VCAM-1 and VLA-4 Modulate Dendritic Cell IL-12p40 Production in Experimental Visceral Leishmaniasis	journal.ppat.1000158	null	[ [ "Very late antigen-4 ( VLA-4; α4 integrin; CD49d ) is expressed on most leukocytes and plays an important role in leukocyte trafficking by interacting with vascular cell adhesion molecule-1 ( VCAM-1; CD106 ) on endothelial cells to mediate tethering , rolling , firm adhesion and transendothelial migration [1]...	[ "Vascular cell adhesion molecule-1 ( VCAM-1 ) interacts with its major ligand very late antigen-4 ( VLA-4 ) to mediate cell adhesion and transendothelial migration of leukocytes .", "We report an important role for VCAM-1/VLA-4 interactions in the generation of immune responses during experimental visceral leishm...	[ "VCAM-1 and its major ligand VLA-4 are adhesion molecules required for the recruitment and movement of leukocytes within tissue .", "In this study , we have investigated the role of these molecules during an experimental infection with Leishmania donovani , a protozoan parasite that causes a chronic disease calle...	2008
[ "Introduction", "Results/Discussion", "Methods" ]	[ "genome-wide association studies", "medicine", "rna interference", "chronic kidney disease", "diabetic endocrinology", "gene expression", "endocrinology", "diabetes and endocrinology", "biology", "genetics", "diabetes mellitus type 1", "genomics", "genetics of disease", "nephrology", "ge...	New Susceptibility Loci Associated with Kidney Disease in Type 1 Diabetes	journal.pgen.1002921	null	[ [ "Diabetic kidney disease , or diabetic nephropathy ( DN ) , is the leading cause of end-stage renal disease ( ESRD ) worldwide [1] .", "It affects approximately 30% of patients with long-standing type 1 and type 2 diabetes [2] , [3] , and confers added risks of cardiovascular disease and mortality .", ...	[ "Diabetic kidney disease , or diabetic nephropathy ( DN ) , is a major complication of diabetes and the leading cause of end-stage renal disease ( ESRD ) that requires dialysis treatment or kidney transplantation .", "In addition to the decrease in the quality of life , DN accounts for a large proportion of the e...	[ "The global prevalence of diabetes has reached epidemic proportions , constituting a major health care problem worldwide .", "Diabetic kidney disease , or diabetic nephropathy ( DN ) —the major long term microvascular complication of diabetes—is associated with excess mortality among patients with type 1 diabetes...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	FUS Interacts with HSP60 to Promote Mitochondrial Damage	journal.pgen.1005357	null	[ [ "Amyotrophic lateral sclerosis ( ALS ) is a fatal neurodegenerative disease primarily affecting motor neurons .", "The Cu/Zn superoxide dismutase 1 ( SOD1 ) gene was the first ALS-associated gene whose mutations were identified in familial ALS ( fALS ) patients [1 , 2] .", "Subsequently , genetic stud...	[ "FUS-proteinopathies , a group of heterogeneous disorders including ALS-FUS and FTLD-FUS , are characterized by the formation of inclusion bodies containing the nuclear protein FUS in the affected patients .", "However , the underlying molecular and cellular defects remain unclear .", "Here we provide evidence ...	[ "Amyotrophic lateral sclerosis ( ALS ) and frontotemporal lobar degeneration ( FTLD ) are two groups of common and devastating neurodegenerative diseases , characterized by losses of selected groups of neurons .", "Mutations in the FUS gene have been associated with ALS , whereas inclusion bodies containing the F...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Assessment of the Impact of Potential Tetracycline Exposure on the Phenotype of Aedes aegypti OX513A: Implications for Field Use	journal.pntd.0003999	null	[ [ "Dengue fever is a viral infection , primarily transmitted by the mosquito Aedes aegypti , with an estimated incidence of 390 million infections annually [1] .", "There are currently no licensed vaccines [2 , 3] so control of the disease is focused on suppression of the vector .", "Commonly employed v...	[ "Aedes aegypti is the primary vector of dengue fever , a viral disease which has an estimated incidence of 390 million infections annually .", "Conventional vector control methods have been unable to curb the transmission of the disease .", "We have previously reported a novel method of vector control using a t...	[ "Dengue fever is spread by the mosquito Aedes aegypti and the most effective method to limit the spread of dengue is to reduce the mosquito population .", "We have previously reported a transgenic strain of Ae .", "aegypti which results in >90% population suppression: males , which do not transmit disease , are...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "mycology", "microbial physiology", "microbial evolution", "fungal genetics", "genetics", "fungal reproduction", "biology and life sciences", "microbiology", "evolutionary biology", "fungal structure" ]	White Cells Facilitate Opposite- and Same-Sex Mating of Opaque Cells in Candida albicans	journal.pgen.1004737	null	[ [ "Sexual reproduction is pervasive in eukaryotic organisms due to its propensity to permit genetic exchange , eliminate harmful mutations , and produce adaptive progeny to changing environments [1] , [2] .", "It has been demonstrated to be critical for environmental adaptation , morphological transitioning...	[ "Modes of sexual reproduction in eukaryotic organisms are extremely diverse .", "The human fungal pathogen Candida albicans undergoes a phenotypic switch from the white to the opaque phase in order to become mating-competent .", "In this study , we report that functionally- and morphologically-differentiated wh...	[ "In eukaryotic organisms , cells often undergo differentiation into distinct cell types in order to fulfill specialized roles .", "To achieve a certain function , different cell types may behave coordinately to complete a task that they may otherwise be incapable of completing independently .", "The human funga...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant biology/plant growth and development", "genetics and genomics/plant genetics and gene expression", "computational biology/transcriptional regulation" ]	Evidence for Antisense Transcription Associated with MicroRNA Target mRNAs in Arabidopsis	journal.pgen.1000457	null	[ [ "Non-coding genes , such as those producing miRNAs and small interfering RNAs ( siRNAs ) , are key components of gene expression in eukaryotes , forming a regulatory network superimposed on the central dogma of molecular biology [1] , [2] , [3] .", "miRNAs are expressed through nucleolytic maturation of h...	[ "Antisense transcription is a pervasive phenomenon , but its source and functional significance is largely unknown .", "We took an expression-based approach to explore microRNA ( miRNA ) -related antisense transcription by computational analyses of published whole-genome tiling microarray transcriptome and deep s...	[ "Antisense transcription is a pervasive but poorly understood phenomenon in a wide variety of organisms .", "We have found evidence for a novel source of antisense transcription in Arabidopsis thaliana associated with miRNA targets via computational analyses of published whole-genome tiling microarray data , deep...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "education", "sociology", "geographical locations", "social sciences", "bivariate analysis", "animals", "health care", "multivariate analysis", "mathematics", "signs and symptoms", "statistics (mathematic...	Prevalence, intensity and risk factors of tungiasis in Kilifi County, Kenya: I. Results from a community-based study	journal.pntd.0005925	null	[ [ "Tungiasis ( sand flea disease ) is a parasitic skin disease caused by female sand fleas ( Tunga penetrans ) penetrated into the skin of human or animal hosts .", "Tungiasis belongs to the family of neglected tropical diseases ( NTDs ) [1 , 2] .", "It is prevalent in resource-poor rural communities in...	[ "Tungiasis is a neglected tropical disease caused by female sand fleas ( Tunga penetrans ) embedded in the skin .", "The disease is associated with important morbidity .", "Tungiasis is endemic along the Coast of Kenya with a prevalence ranging from 11% to 50% in school-age children .", "Hitherto , studies on...	[ "Tungiasis ( sand flea disease ) is an ectoparasitic skin disease and belongs to the group of NTDs ( Neglected Tropical Diseases ) .", "It is caused by sand fleas penetrating into the skin of the feet , causing an inflammatory reaction with pain and itching .", "Attempts to remove the flea with inappropriate sh...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "medicine and health sciences", "diagnostic medicine", "biology and life sciences", "immunology", "microbiology" ]	Identification of sVSG117 as an Immunodiagnostic Antigen and Evaluation of a Dual-Antigen Lateral Flow Test for the Diagnosis of Human African Trypanosomiasis	journal.pntd.0002976	null	[ [ "Human African Trypanosomiasis ( HAT ) , or African Sleeping Sickness , is caused by two sub-species of Trypanosoma brucei .", "T . b .", "gambiense accounts for approximately 95% of HAT infections and occurs across East and Central sub-Saharan Africa .", "The remaining infections are caused by T ...	[ "The diagnosis of human African trypanosomiasis ( HAT ) caused by Trypanosoma brucei gambiense relies mainly on the Card Agglutination Test for Trypanosomiasis ( CATT ) .", "There is no immunodiagnostic for HAT caused by T . b .", "rhodesiense .", "Our principle aim was to develop a prototype lateral flow tes...	[ "Human African Trypanosomiasis ( HAT ) is caused by infection with Trypanosoma brucei gambiense or T . b .", "rhodesiense .", "The diagnosis of T . b .", "gambiense infections currently relies primarily on a Card Agglutination Test for Trypanosomiasis ( CATT ) , which has acknowledged limitations , and there ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meningococcal infections", "medicine", "bacterial diseases", "infectious diseases", "meningococcal disease", "immunity", "innate immunity", "immunology", "biology", "microbiology", "host-pathogen interaction", "bacterial pathogens", "meningoccal septicemia" ]	Design and Evaluation of Meningococcal Vaccines through Structure-Based Modification of Host and Pathogen Molecules	journal.ppat.1002981	null	[ [ "Neisseria meningitidis is a human specific pathogen that is a leading cause of bacteraemia and sepsis in children and young adults [1] .", "The initial symptoms of meningococcal disease are non-specific , so the diagnosis is often missed in its early stages; infection can then progress rapidly over only ...	[ "Neisseria meningitis remains a leading cause of sepsis and meningitis , and vaccines are required to prevent infections by this important human pathogen .", "Factor H binding protein ( fHbp ) is a key antigen that elicits protective immunity against the meningococcus and recruits the host complement regulator , ...	[ "Vaccines are currently available against several serogroups of Neisseria meningitidis .", "However broadly effective serogroup B vaccines are still required as capsule-based approaches cannot be implemented with this serogroup because of the risks of auto-immunity .", "As a result , vaccines based on proteins ...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "phosphorylation", "shrimp", "invertebrates", "medicine and health sciences", "immune cells", "rna interference", "immunology", "animals", "crustaceans", "epigenetics", "stat proteins", "digestive system", "white blood cells", "animal cells", "proteins", "genetic inter...	Binding of a C-type lectin’s coiled-coil domain to the Domeless receptor directly activates the JAK/STAT pathway in the shrimp immune response to bacterial infection	journal.ppat.1006626	null	[ [ "Like other invertebrates , the shrimp’s defense against microbial pathogens relies on innate immune responses , which generally encompass their recognition , killing and disposal through humoral and cellular mechanisms .", "Humoral responses are rapid and effective , and include recognition factors such ...	[ "C-type lectins ( CTLs ) are characterized by the presence of a C-type carbohydrate recognition domain ( CTLD ) that by recognizing microbial glycans , is responsible for their roles as pattern recognition receptors in the immune response to bacterial infection .", "In addition to the CTLD , however , some CTLs d...	[ "The JAK/STAT pathway mediates the effects of a large number of cytokines and growth factors .", "It is activated following binding of a cytokine or growth factor to its respective receptor .", "To date , over 50 cytokines and growth factors have been shown to utilize the pathway to regulate cell growth , survi...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "infectious disease epidemiology", "applied mathematics", "parasitic diseases", "mathematics", "neglected tropical diseases", "onchocerciasis", "infectious disease control", "complex systems", "infectious diseases", "epidemiology", "infectious di...	African Programme for Onchocerciasis Control 1995–2015: Model-Estimated Health Impact and Cost	journal.pntd.0002032	null	[ [ "Onchocerciasis is caused by Onchocerca volvulus , a filarial nematode restricted to human hosts .", "The adult female worms reside in subcutaneous nodules where they produce millions of microfilariae during their on-average ten-year life span [1] .", "The microfilariae are found predominantly migrati...	[ "Onchocerciasis causes a considerable disease burden in Africa , mainly through skin and eye disease .", "Since 1995 , the African Programme for Onchocerciasis Control ( APOC ) has coordinated annual mass treatment with ivermectin in 16 countries .", "In this study , we estimate the health impact of APOC and th...	[ "In 1995 , the World Health Organization launched the African Programme for Onchocerciasis Control ( APOC ) with the aim to control morbidity due to the parasitic infectious disease onchocerciasis ( river blindness ) .", "APOC aims to set up sustainable national control programs against onchocerciasis in 16 count...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/sensory systems", "computational biology/computational neuroscience", "neuroscience/neurodevelopment", "developmental biology/neurodevelopment", "neuroscience/neuronal signaling mechanisms", "neuroscience/theoretical neuroscience" ]	A Multi-Component Model of the Developing Retinocollicular Pathway Incorporating Axonal and Synaptic Growth	journal.pcbi.1000600	null	[ [ "During neural system development , groups of neurons project to various areas of the brain and produce stereotypical patterns of innervation .", "These organization patterns are an emergent property of the physiological mechanisms regulating neural behavior .", "In the visual system these mechanisms ...	[ "During development , neurons extend axons to different brain areas and produce stereotypical patterns of connections .", "The mechanisms underlying this process have been intensively studied in the visual system , where retinal neurons form retinotopic maps in the thalamus and superior colliculus .", "The mech...	[ "Neural development is a process that involves a wide range of behaviors .", "As a result of these behaviors , neurons are able to extend axons to different brain areas and produce stereotypical patterns of innervation .", "One of the most commonly studied of these projections is in the visual system , where re...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "antimicrobials", "medicine and health sciences", "luciferase", "toxins", "pathology and laboratory medicine", "gene regulation", "enzymes", "drugs", "microbiology", "enzymology", "toxicology", "toxic agents", "plasmid construction", "antibiotics", "bacterial genetics",...	Expression of Streptococcus pneumoniae Bacteriocins Is Induced by Antibiotics via Regulatory Interplay with the Competence System	journal.ppat.1005422	null	[ [ "Streptococcus pneumoniae is a Gram-positive opportunistic pathogen that resides in the human nasopharynx .", "Pneumococci can cause invasive and non-invasive infections to which children , the elderly and the immunocompromised are particularly susceptible .", "The carriage rate of S . pneumoniae in t...	[ "Pneumococcal bacteriocins ( pneumocins ) are antibacterial toxins that mediate intra-species competition within the human host .", "However , the triggers of pneumocin expression are poorly understood .", "Using RNA-sequencing , we mapped the regulon of the pneumocin cluster ( blp ) of Streptococcus pneumoniae...	[ "Streptococcus pneumoniae is an opportunistic pathogen with high carriage rates in children .", "Pneumococci express pneumocins that kill competing bacteria .", "Pneumocin expression is controlled by a pheromone-induced two-component system ( BlpR/H ) but the triggers for the system are poorly understood .", ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "parasitic diseases", "food-borne trematodes", "helminth infection", "clinical epidemiology", "hookworm infection", "neglected tropical diseases", "infectious disease control", "ascariasis", "infectious diseases", "soil-transmitted helminths", "p...	Low Efficacy of Single-Dose Albendazole and Mebendazole against Hookworm and Effect on Concomitant Helminth Infection in Lao PDR	journal.pntd.0001417	null	[ [ "Infections with the three common soil-transmitted helminths ( STHs ) , Ascaris lumbricoides , Trichuris trichiura , and hookworm ( Ancylostoma duodenale and Necator americanus ) , are a global public-health concern , particularly in areas where poor sanitation prevails [1] , [2] .", "STH infections are a...	[ "Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth ( STH ) infections .", "We assessed the efficacy of single oral doses of albendazole ( 400 mg ) and mebendazole ( 500 mg ) for the treatment of hookworm infection in school-aged children in Lao P...	[ "Parasitic worms remain a public health problem in developing countries .", "Regular deworming with the drugs albendazole and mebendazole is the current global control strategy .", "We assessed the efficacies of a single tablet of albendazole ( 400 mg ) and mebendazole ( 500 mg ) against hookworm in children of...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	The Cytokine and Chemokine Profiles in Patients with Hand, Foot and Mouth Disease of Different Severities in Shanghai, China, 2010	journal.pntd.0002599	null	[ [ "Hand , foot and mouth disease ( HFMD ) is an infectious disease caused by enteroviruses including enterovirus 71 ( EV71 ) and Coxsackievirus A16 .", "HFMD affects mainly young children under 5 years old .", "The first large EV71 outbreak occurred in Japan in 1973 [1] .", "Another two large outbre...	[ "Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand , foot , and mouth disease ( HFMD ) with pulmonary edema .", "Thus , immunomodulatory medicines such as steroids , including methylprednisolone , have been proposed to treat patients with severe HFMD in China , because it i...	[ "Systemic inflammation is characteristic of severe hand , foot , and mouth disease ( HFMD ) .", "Steroids are considered immunomodulators and have been officially recommended to treat the severe HFMD patients with CNS complications in China .", "So far , it is uncertain whether steroid treatment has an immunomo...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "flow cytometry", "cell motility", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "cytokines", "enzyme-linked immunoassays", "pathogens", "immunology", "microbiology", "retroviruses", "virus...	HMGB1 Is Involved in IFN-α Production and TRAIL Expression by HIV-1-Exposed Plasmacytoid Dendritic Cells: Impact of the Crosstalk with NK Cells	journal.ppat.1005407	null	[ [ "The innate immune response to infection serves as the first line defense against incoming pathogens and is essential for shaping the quality of the ensuing adaptive immune response [1] [2] .", "A unique subset of myeloid cells , dendritic cells ( DCs ) , mediate the link between innate and adaptive immun...	[ "Plasmacytoid dendritic cells ( pDCs ) are innate sensors of viral infections and important mediators of antiviral innate immunity through their ability to produce large amounts of IFN-α .", "Moreover , Toll-like receptor 7 ( TLR7 ) and 9 ( TLR9 ) ligands , such as HIV and CpG respectively , turn pDCs into TRAIL-...	[ "Plasmacytoid dendritic cells ( pDC ) are the most potent IFN-α-producing cells and serve as an essential link between innate and adaptive immunity .", "Exposure of pDCs to HIV-1 triggers IFN-α production , which in turn upregulates TNF-related apoptosis-inducing ligand ( TRAIL ) , turning pDCs into killer pDCs ,...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemistry", "biology" ]	Coarse-Grained Molecular Simulation of Epidermal Growth Factor Receptor Protein Tyrosine Kinase Multi-Site Self-Phosphorylation	journal.pcbi.1003435	null	[ [ "Classical polypeptide growth factor receptors are intrinsic membrane proteins , each possessing a ligand binding domain in the N-terminal extracellular portion of the molecule , a protein tyrosine kinase ( PTK ) domain in the C-terminal intracellular portion , and a single transmembrane ( TM ) domain in the ...	[ "Upon the ligand-dependent dimerization of the epidermal growth factor receptor ( EGFR ) , the intrinsic protein tyrosine kinase ( PTK ) activity of one receptor monomer is activated , and the dimeric receptor undergoes self-phosphorylation at any of eight candidate phosphorylation sites ( P-sites ) in either of th...	[ "The epidermal growth factor receptor ( EGFR ) is one of a large group of cell surface receptors that allow cells to respond to growth-stimulating signals in their environment .", "Upon sensing of growth factor , the EGFR is activated , which triggers a signaling cascade leading to the cell nucleus and ultimately...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "molecular probe techniques", "natural antisense transcripts", "gene regulation", "enzymes", "pathogens", "microbiology", "immunoblotting", "enzymology", "neuroscience", "viruses", "micrornas", "rna viruses", "molecular...	The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function	journal.pntd.0007537	null	[ [ "Zika virus ( ZIKV ) is a small , enveloped RNA virus classified within the family Flaviviridae , genus flavivirus , which also includes medically important pathogens such as dengue virus ( DENV ) , West Nile virus ( WNV ) , Japanese encephalitis virus ( JEV ) , and yellow fever virus ( YFV ) [1] , among othe...	[ "Infection by Zika virus ( ZIKV ) is linked to microcephaly and other neurological disorders , posing a significant health threat .", "Innate immunity is the first line of defense against invading pathogens , but relatively little is understood regarding host intrinsic mechanisms that guard against ZIKV .", "He...	[ "The E3 ligase TRIM56 was previously shown to inhibit the replication of several viruses in the family Flaviviridae , including dengue virus serotype 2 , yellow fever virus and bovine viral diarrhea virus , but had not demonstrable antiviral effect against hepatitis C virus , a hepatotropic virus in the same family...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "dermatology", "infectious diseases", "skin infections", "pharmacodynamics", "drugs and devices", "leishmaniasis", "neglected tropical diseases", "pharmacology", "parasitic diseases", "pharmacokinetics" ]	Dynamics of Parasite Clearance in Cutaneous Leishmaniasis Patients Treated with Miltefosine	journal.pntd.0001436	null	[ [ "Miltefosine is an oral antileishmanial drug widely used in the management of visceral leishmaniasis ( VL ) in the Indian subcontinent [1] .", "There is increasing evidence on the efficacy of miltefosine in New-World cutaneous leishmaniasis ( CL ) [2] .", "In Old-World CL the applicability of miltefos...	[ "Parasite loads were quantified in repeated skin biopsies from lesions of 2 patients with Old-World cutaneous leishmaniasis ( CL ) caused by Leishmania major and L . infantum during and after treatment with miltefosine .", "Miltefosine induced a rapid therapeutic effect on both infections with an initial decline ...	[ "The clinical evaluation of the ulcerated lesions in cutaneous leishmaniasis ( CL ) is both difficult and subjective .", "As a result , the evaluation of therapeutic efficacy of drugs for CL remains complicated .", "The relationship between dose and effect of antileishmanial drugs in CL is unclear and a good qu...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "gene regulation", "physiological processes", "substitution mutation", "mutation", "nonsense mutation", "forms of dna", "dna", "small interfering rnas", "gene expression", "rna splicing", "complementary dna", "biochemistry", "rna", "rna processing", "nuc...	Molecular Basis and Therapeutic Strategies to Rescue Factor IX Variants That Affect Splicing and Protein Function	journal.pgen.1006082	null	[ [ "Exonic mutations represent by far the most frequent cause of human genetic disorders , [1] and their pathogenic effect is usually attributed to alterations of the amino acid code .", "However , the exons contain also an intricate series of splicing regulatory elements ( “splicing code” ) that are essenti...	[ "Mutations that result in amino acid changes can affect both pre-mRNA splicing and protein function .", "Understanding the combined effect is essential for correct diagnosis and for establishing the most appropriate therapeutic strategy at the molecular level .", "We have identified a series of disease-causing ...	[ "Clarification of if an exonic variant has an effect on splicing and/or on protein function is an important aspect in clinical genetics and in development of appropriate therapeutic strategies , and most of published evidence consider splicing and protein function separately .", "In exons , the presence of dense ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/signaling networks", "biophysics/cell signaling and trafficking structures", "cell biology/cell signaling" ]	A Bipolar Clamp Mechanism for Activation of Jak-Family Protein Tyrosine Kinases	journal.pcbi.1000364	null	[ [ "Non-receptor protein tyrosine kinases of the Janus kinase ( Jak ) family play an essential role in signal transduction mediated by a host of cell surface receptors that lack intrinsic enzymatic activity .", "As a prominent example , the receptor for growth hormone ( GH ) , a therapeutically important cyt...	[ "Most cell surface receptors for growth factors and cytokines dimerize in order to mediate signal transduction .", "For many such receptors , the Janus kinase ( Jak ) family of non-receptor protein tyrosine kinases are recruited in pairs and juxtaposed by dimerized receptor complexes in order to activate one anot...	[ "Janus kinases ( Jaks ) interact with and activate receptors on the cell surface that mediate changes in gene expression .", "How these interactions are promoted and regulated is of central interest in fields such as cellular endocrinology and immunology .", "Here , detailed computational models of Jak activati...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemical bonding", "crystal structure", "chemical compounds", "permeability", "condensed matter physics", "organic compounds", "membrane proteins", "materials science", "basic amino acids", "amino acids", "crystallography", "cellular structures and organelles", "hydrogen bonding", "physic...	Crystal Structure of an Ammonia-Permeable Aquaporin	journal.pbio.1002411	The structure of an ammonia channel from plants extends our understanding of substrate specificity in different types of aquaporins and reveals an intriguing side pore that raises new questions.	[ [ "Nitrogen is a macronutrient that is often limiting for plant growth .", "Hence , efficient channeling and storage of ammonia , a central molecule in nitrogen metabolism , is of fundamental importance .", "Tonoplast Intrinsic Proteins ( TIPs ) belonging to the Major Intrinsic Protein family , also kno...	[ "Aquaporins of the TIP subfamily ( Tonoplast Intrinsic Proteins ) have been suggested to facilitate permeation of water and ammonia across the vacuolar membrane of plants , allowing the vacuole to efficiently sequester ammonium ions and counteract cytosolic fluctuations of ammonia .", "Here , we report the struct...	[ "Ammonia is a central molecule in nitrogen metabolism .", "Aquaporins are integral membrane proteins that form channels that accelerate the passive permeation of small polar uncharged molecules , like water and ammonia , across lipid membranes of the cell .", "Structural information of ammonia-permeable aquapor...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "chemical compounds", "enrichment culture", "engineering and technology", "atmospheric science", "bioenergy", "biological cultures", "metabolic networks", "organic compounds", "biogas", "metabolites", "materials science", "network analysis", "alcohols"...	RedCom: A strategy for reduced metabolic modeling of complex microbial communities and its application for analyzing experimental datasets from anaerobic digestion	journal.pcbi.1006759	null	[ [ "Microbial communities are of major importance for human health [1 , 2] , geochemical cycles [3 , 4] and biotechnological processes [5–7] .", "Despite of their importance , most microbial communities are still poorly understood due to their complex nature .", "Mathematical modeling can help to uncover...	[ "Constraint-based modeling ( CBM ) is increasingly used to analyze the metabolism of complex microbial communities involved in ecology , biomedicine , and various biotechnological processes .", "While CBM is an established framework for studying the metabolism of single species with linear stoichiometric models ,...	[ "Microbial communities are involved in many fundamental processes in nature , health and biotechnology .", "The elucidation of interdependencies between the involved players of microbial communities and how the interactions shape the composition , behavior and characteristic features of the consortium has become ...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology", "biology", "computational biology" ]	The Minimal Complexity of Adapting Agents Increases with Fitness	journal.pcbi.1003111	null	[ [ "What is the relationship between complexity and the fitness of evolved organisms , whether natural or artificial ?", "It is often assumed [1]–[4] that while evolving organisms grow in fitness , they develop functionally useful forms , and hence necessarily exhibit increasing complexity [5] .", "Some ...	[ "What is the relationship between the complexity and the fitness of evolved organisms , whether natural or artificial ?", "It has been asserted , primarily based on empirical data , that the complexity of plants and animals increases as their fitness within a particular environment increases via evolution by natu...	[ "It has often been asserted that as organisms adapt to natural environments with many independent forces and actors acting over a variety of different time scales , they become more complex .", "We investigate this question from the point of view of information theory as applied to the nervous systems of simple c...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "growth plate", "dimers (chemical physics)", "medicine and health sciences", "chondrocytes", "gene regulation", "bone", "connective tissue cells", "sequence motif analysis", "cartilage", "research and analysis methods", "sequence analysis", "transcriptional control", "animal cells", "bioin...	Synergistic co-regulation and competition by a SOX9-GLI-FOXA phasic transcriptional network coordinate chondrocyte differentiation transitions	journal.pgen.1007346	null	[ [ "In the formation and longitudinal growth of endochondral bones , committed mesenchymal cells condense and differentiate into chondrocytes to form a growth plate , within which chondrocytes undergo coordinated and sequential differentiation phases of proliferation , cell cycle exit and hypertrophy , resulting...	[ "The growth plate mediates bone growth where SOX9 and GLI factors control chondrocyte proliferation , differentiation and entry into hypertrophy .", "FOXA factors regulate hypertrophic chondrocyte maturation .", "How these factors integrate into a Gene Regulatory Network ( GRN ) controlling these differentiatio...	[ "In the development of the mammalian growth plate , while several transcription factors are individually well known for their key roles in regulating phases of chondrocyte differentiation , there is little information on how they interact and cooperate with each other .", "We took an unbiased genome wide approach...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "ecology and environmental sciences", "insect metamorphosis", "pathology and laboratory medicine", "parasite evolution", "parasitic diseases", "parasitology", "reproductive physiology", "developmental biology", "pupae", "zoology", "conservation biology", "epid...	Superparasitism Drives Heritable Symbiont Epidemiology and Host Sex Ratio in a Wasp	journal.ppat.1005629	null	[ [ "Heritable symbionts are common in natural populations of arthropods [1] , where they affect the biology of their host individual in diverse ways .", "They can be obligatory , providing physiologically crucial functions to their host , such as amino acid or vitamin anabolism [2] , or alternatively provide...	[ "Heritable microbial symbionts have profound impacts upon the biology of their arthropod hosts .", "Whilst our current understanding of the dynamics of these symbionts is typically cast within a framework of vertical transmission only , horizontal transmission has been observed in a number of cases .", "For ins...	[ "Most insects house heritable symbionts and these represent an important component of their biology , both as partners conveying beneficial traits such as defence against natural enemies , or as antagonists manipulating their hosts’ reproduction .", "Work on these bacteria mostly assumes that such phenotypes have...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "visual system", "biology", "sensory systems", "neuroscience" ]	Directional Summation in Non-direction Selective Retinal Ganglion Cells	journal.pcbi.1002969	null	[ [ "Regardless of their classification , virtually all ganglion cells receive input from multiple bipolar cells .", "For example , in the cat and guinea pig retina , as many as 150 bipolar cells synapse onto a single On type ganglion cells [1]–[3] .", "With the exception of the soma and very proximal den...	[ "Retinal ganglion cells receive inputs from multiple bipolar cells which must be integrated before a decision to fire is made .", "Theoretical studies have provided clues about how this integration is accomplished but have not directly determined the rules regulating summation of closely timed inputs along single...	[ "Visual information is coded by the output of retinal ganglion cells .", "Through evolution retinal ganglion cells acquired unique properties that allowed them to transmit to the brain such signals as direction of movement .", "The quest for the cellular mechanism of the detection of movement by retinal ganglio...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience", "neuroscience/animal cognition", "neuroscience/theoretical neuroscience" ]	Accurate Path Integration in Continuous Attractor Network Models of Grid Cells	journal.pcbi.1000291	null	[ [ "Since the discovery of grid cells in the dorsolateral band of the medial entorhinal", "cortex ( dMEC ) [1] , several ideas have been put forth on how", "grid-cell activity might emerge [2]–[7] .", "The theoretical ideas", "suggested so far fall into two categories .", "In continuous attra...	[ "Grid cells in the rat entorhinal cortex display strikingly regular firing", "responses to the animal's position in 2-D space and have been", "hypothesized to form the neural substrate for dead-reckoning .", "However , errors", "accumulate rapidly when velocity inputs are integrated in existing models of", ...	[ "Even in the absence of external sensory cues , foraging rodents maintain an", "estimate of their position , allowing them to return home in a roughly straight", "line .", "This computation is known as dead reckoning or path integration .", "A", "discovery made three years ago in rats focused attention on...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "demography", "china", "immunology", "geographical locations", "animals", "vaccines", "preventive medicine", "age groups", "adults", "population biology", "vaccination and immunization", "insect vectors", "public and occup...	The Spatio-temporal Distribution of Japanese Encephalitis Cases in Different Age Groups in Mainland China, 2004 – 2014	journal.pntd.0004611	null	[ [ "Japanese encephalitis ( JE ) is a viral disease transmitted by mosquitoes which can lead to severe viral encephalitis .", "The fatality rate among JE patients is approximately 30% , while 35% of the survivors show various degrees of neurological sequelae .", "JE is an infectious disease of the neuron...	[ "Japanese encephalitis ( JE ) is very prevalent in China , but the incidence of JE among children has been greatly reduced by extensive promotion of vaccinations .", "The incidence of JE among adults , however , has increased in some parts of China .", "Data on JE in mainland China , in terms of incidence , gen...	[ "It is well known that children are the population most susceptible to Japanese encephalitis ( JE ) , and the incidence of JE among children in China has been greatly reduced by extensive promotion of vaccinations aiming at children .", "The incidence of JE among adults , however , has increased in some parts of ...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cell binding", "antimicrobials", "cell physiology", "medicine and health sciences", "viral transmission and infection", "dose prediction methods", "drugs", "microbiology", "mathematical models", "bacterial diseases", "antibiotic resistance", "pharmaceutics", "antibiotics", "pharmacology",...	Predictive modelling of a novel anti-adhesion therapy to combat bacterial colonisation of burn wounds	journal.pcbi.1006071	null	[ [ "As we begin to lose the arms race against microbial infections , it is important that we develop new treatment strategies as a complement or alternative to antibiotics .", "In this paper , we use mathematical modelling to explain and predict the effects of a novel anti-adhesion therapy in the treatment o...	[ "As the development of new classes of antibiotics slows , bacterial resistance to existing antibiotics is becoming an increasing problem .", "A potential solution is to develop treatment strategies with an alternative mode of action .", "We consider one such strategy: anti-adhesion therapy .", "Whereas antibi...	[ "Humankind is engaged in an arms race; one we are in danger of losing .", "Since the development and application of the first antibiotics , resistant strains of bacteria have steadily emerged .", "As the rate of discovery of new antibiotics slows , the threat increases .", "At present , 700 , 000 individuals ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "cell biology", "genetics", "biology and life sciences", "molecular cell biology" ]	Sgo1 Regulates Both Condensin and Ipl1/Aurora B to Promote Chromosome Biorientation	journal.pgen.1004411	null	[ [ "Accurate chromosome segregation into daughter cells requires the formation of correct chromosome attachments to the mitotic spindle .", "Each of the sister kinetochores has to attach to microtubules ( MTs ) emanating from opposite spindle poles in order to achieve biorientation of sister chromatids .", ...	[ "Correct chromosome segregation is essential in order to prevent aneuploidy .", "To segregate sister chromatids equally to daughter cells , the sisters must attach to microtubules emanating from opposite spindle poles .", "This so-called biorientation manifests itself by increased tension and conformational cha...	[ "Accurate chromosome segregation is required for the equal distribution of genetic information to progeny .", "Failure to equally segregate chromosomes leads to aneuploidy , cell death or cancer .", "Proteins of the conserved shugoshin family contribute to accurate chromosome segregation in both meiosis and mit...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Sensorimotor Model of Obstacle Avoidance in Echolocating Bats	journal.pcbi.1004484	null	[ [ "Rhinolophidae are echolocating bats specialized in hunting for airborne prey among vegetation using echolocation .", "To cope with clutter echoes returning from vegetation they employ a unique sensorial strategy for detecting prey .", "They emit long narrow-band pulses and listen for frequency and am...	[ "Bat echolocation is an ability consisting of many subtasks such as navigation , prey detection and object recognition .", "Understanding the echolocation capabilities of bats comes down to isolating the minimal set of acoustic cues needed to complete each task .", "For some tasks , the minimal cues have alread...	[ "Echolocating bats can fly through complex environments in complete darkness .", "Swift and apparently effortless obstacle avoidance is the most fundamental function supported by biosonar .", "Despite this , we still do not know which acoustic cues , from among the many possible cues , bats actually exploit whi...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology", "ecology" ]	Phenotypic Mismatches Reveal Escape from Arms-Race Coevolution	journal.pbio.0060060	Who wins in the arms race between predators and prey? In the interaction between snakes and toxic newts, predators sometimes escape the arms race through the evolution of extreme resistance, but prey never come out ahead.	[ [ "The phenotypic interface of the predator–prey interaction between garter snakes and newts of the genus Taricha revolves around tetrodotoxin ( TTX ) .", "TTX is one of the most potent neurotoxins known , binding to the outer pore of voltage-gated sodium channels in nerve and muscle tissue , thereby blocki...	[ "Because coevolution takes place across a broad scale of time and space , it is virtually impossible to understand its dynamics and trajectories by studying a single pair of interacting populations at one time .", "Comparing populations across a range of an interaction , especially for long-lived species , can pr...	[ "Arms races between natural enemies can lead to the rapid evolution of extreme traits , high degrees of specialization , and the formation of new species .", "They also serve as the ecological model for the evolution of drug resistance by diseases and for host–pathogen interactions in general .", "Revealing who...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "genetics and genomics/gene discovery", "genetics and genomics/gene expression", "ophthalmology/inherited eye disorders", "genetics and genomics/disease models", "ophthalmology", "genetics and genomics", "ophthalmology/glaucoma" ]	Mapping of the Disease Locus and Identification of ADAMTS10 As a Candidate Gene in a Canine Model of Primary Open Angle Glaucoma	journal.pgen.1001306	null	[ [ "Elevated intraocular pressure is a strong risk factor for glaucoma development and progression [1] .", "In POAG , increased resistance to outflow of aqueous humor through the trabecular meshwork is the cause of elevated intraocular pressure [2] .", "Currently , the only proven treatments for POAG pat...	[ "Primary open angle glaucoma ( POAG ) is a leading cause of blindness worldwide , with elevated intraocular pressure as an important risk factor .", "Increased resistance to outflow of aqueous humor through the trabecular meshwork causes elevated intraocular pressure , but the specific mechanisms are unknown .", ...	[ "Primary open angle glaucoma ( POAG ) is a leading cause of vision loss and blindness affecting tens of millions of people .", "Ocular hypertension is a strong risk factor for the disease and the only effective target of treatment .", "Ocular hypertension results from increased resistance to outflow of aqueous ...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia	journal.pgen.1005493	null	[ [ "Blastomyces is a genus of a thermally dimorphic fungal pathogen , which is the etiological agent of blastomycosis , a lung infection that can become a systemic mycosis .", "In North America , Blastomyces is endemic in the Ohio and Mississippi river valleys , the Great Lakes region , and the St . Lawrence...	[ "Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis , histoplasmosis and paracoccidioidomycosis .", "Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis , Blastomyces ,...	[ "Dimorphic fungal pathogens including Blastomyces are the cause of major fungal diseases in North and South America .", "The genus Emmonsia includes species infecting small mammals as well as a newly emerging pathogenic species recently reported in HIV-positive patients in South Africa .", "Here , we synthesize...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "social sciences", "anthropology", "animals", "mammals", "viruses", "primates", "neanderthals", "phylogenetics", "data management", "ar...	Niche adaptation and viral transmission of human papillomaviruses from archaic hominins to modern humans	journal.ppat.1007352	null	[ [ "Papillomaviruses ( PVs ) are ubiquitous , non-enveloped , small double-stranded circular DNA viruses that cause proliferation of epithelial cells in a wide range of vertebrate host species , from reptiles to mammals [1 , 2] .", "Currently , over 200 PVs infecting primate hosts ( human and non-human ) hav...	[ "Recent discoveries on the origins of modern humans from multiple archaic hominin populations and the diversity of human papillomaviruses ( HPVs ) suggest a complex scenario of virus-host evolution .", "To evaluate the origin of HPV pathogenesis , we estimated the phylogeny , timing , and dispersal of HPV16 varia...	[ "Epidemiologic studies have demonstrated that persistent infection of select oncogenic human papillomaviruses ( HPVs ) is the main cause of cervix precancer and cancer .", "Nevertheless , our knowledge of the underlying evolutionary mechanisms driving the divergence and emergence of viral oncogenicity in specific...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "molecular biology/mrna stability", "biochemistry/transcription and translation", "molecular biology" ]	Targeting the Midgut Secreted PpChit1 Reduces Leishmania major Development in Its Natural Vector, the Sand Fly Phlebotomus papatasi	journal.pntd.0000901	null	[ [ "Emerging and reemerging vector-borne diseases pose significant threats to human and animal health [1] .", "The emergence of insecticide resistance as well as the lack of other efficient insecticidal tools to control disease vectors imply that new methodologies need to be developed in order to reduce vect...	[ "During its developmental cycle within the sand fly vector , Leishmania must survive an early proteolytic attack , escape the peritrophic matrix , and then adhere to the midgut epithelia in order to prevent excretion with remnants of the blood meal .", "These three steps are critical for the establishment of an i...	[ "For a successful development within the midgut of the sand fly vector , Leishmania must overcome several barriers which are imposed by the vector .", "The ability to overcome these barriers has been associated with species specificity , and interference with the sand fly vector-parasite balance can change the ou...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cancer genomics", "medicine and health sciences", "genetic networks", "basic cancer research", "oncology", "mutation", "network analysis", "silent mutation", "mutation databases", "research and analysis methods", "computer and information sciences", "genomics", "biological databases", "so...	NetNorM: Capturing cancer-relevant information in somatic exome mutation data with gene networks for cancer stratification and prognosis	journal.pcbi.1005573	null	[ [ "Tumourigenesis and cancer growth involve somatic mutations which appear and accumulate during cancer progression .", "These mutations impair the normal behaviour of various cancer genes , and give cancer cells an often devastating advantage to proliferate over normal cells [1–3] .", "Systematically a...	[ "Genome-wide somatic mutation profiles of tumours can now be assessed efficiently and promise to move precision medicine forward .", "Statistical analysis of mutation profiles is however challenging due to the low frequency of most mutations , the varying mutation rates across tumours , and the presence of a majo...	[ "The transition from a normal cell to a cancer cell is driven by genetic alterations , such as mutations , that induce uncontrolled cell proliferation .", "With the advent of next-generation sequencing technologies ( NGS ) in the last decade , thousands of tumours have been sequenced and their mutation profiles d...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "gene regulation", "pathogens", "immunology", "microbiology", "epithelial cells", "colitis", "histology", "developmental biology", "non-coding rna", "signs and s...	The L-Arginine Transporter Solute Carrier Family 7 Member 2 Mediates the Immunopathogenesis of Attaching and Effacing Bacteria	journal.ppat.1005984	null	[ [ "L-arginine ( L-Arg ) is a semi-essential amino acid whose metabolism can be dysregulated under diseased conditions .", "Transport of L-Arg is primarily dependent on the y+ transport system , which includes the cationic amino acid transporter ( CAT; SLC7A ) family of proteins [1] .", "SLC7A1 is consti...	[ "Solute carrier family 7 member 2 ( SLC7A2 ) is an inducible transporter of the semi-essential amino acid L-arginine ( L-Arg ) , which has been implicated in immune responses to pathogens .", "We assessed the role of SLC7A2 in murine infection with Citrobacter rodentium , an attaching and effacing enteric pathoge...	[ "Intestinal infections by attaching and effacing ( A/E ) bacteria widely impact human health , with major social and economic repercussions .", "Mucosal immunity plays a critical role in determining the outcome of these infections .", "The amino acid L-arginine regulates inflammatory responses to bacterial path...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "taxonomy", "medicine", "infectious diseases", "african trypanosomiasis", "molecular systematics", "neglected tropical diseases", "biology", "evolutionary biology", "infectious disease control", "evolutionary systematics" ]	Cryptic Diversity within the Major Trypanosomiasis Vector Glossina fuscipes Revealed by Molecular Markers	journal.pntd.0001266	null	[ [ "Control of Human African Trypansomiasis ( HAT ) has largely been based upon the detection and treatment of human cases [1] .", "Anti-vector interventions , whilst hugely successful in reducing transmission of Animal African Trypanosomiasis ( AAT ) , have rarely been implemented on a programmatic scale [2...	[ "The tsetse fly Glossina fuscipes s . l . is responsible for the transmission of approximately 90% of cases of human African trypanosomiasis ( HAT ) or sleeping sickness .", "Three G . fuscipes subspecies have been described , primarily based upon subtle differences in the morphology of their genitalia .", "Her...	[ "Glossina fuscipes s . l . tsetse flies are responsible for transmission of approximately 90% of the cases of Human African Typanosomiasis in Sub Saharan Africa .", "It was previously proposed on the basis of morphology that G . fuscipes is composed of three sub-species .", "Using genetic evidence from G . fusc...	2011
[ "Introduction", "Results", "Materials and methods" ]	[ "carbohydrate metabolism", "medicine and health sciences", "aspergillus fumigatus", "pathology and laboratory medicine", "chemical compounds", "aspergillus", "fungal genetics", "pathogens", "microbiology", "carbohydrates", "glucose metabolism", "organic compounds", "glucose", "animal model...	Filamentous fungal carbon catabolite repression supports metabolic plasticity and stress responses essential for disease progression	journal.ppat.1006340	null	[ [ "Microbial pathogenesis is a complex , multifactorial process in which interactions between a microbe and host shape disease development and outcome [1 , 2] .", "While many studies have focused on defining the molecular determinants required for fungal pathogenesis , molecular pathogenesis studies often f...	[ "Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi .", "While many fungal factors critical for infection establishment are known , genes essential for disease persistence and progression are ill defined .", "We propose that fu...	[ "Medical treatment advances such as organ transplants and chemotherapies that suppress the immune system have increased the number of patients susceptible to invasive fungal diseases .", "The most common filamentous fungus isolated from these infections is the environmental mold , Aspergillus fumigatus , the caus...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "soil-transmitted helminths", "cutaneous larva migrans", "neglected tropical diseases", "hookworm", "parasitic diseases" ]	Life Quality Impairment Caused by Hookworm-Related Cutaneous Larva Migrans in Resource-Poor Communities in Manaus, Brazil	journal.pntd.0001355	null	[ [ "Hookworm-related cutaneous larva migrans ( CLM ) is a parasitic skin disease caused by the migration of animal hookworm larvae such as Ancylostoma braziliense , A . caninum or Uncinaria stenocephala in the epidermis .", "The infection occurs when third-stage larvae come into contact with human skin and p...	[ "Hookworm-related cutaneous larva migrans ( CLM ) is a common but neglected tropical skin disease caused by the migration of animal hookworm larvae in the epidermis .", "The disease causes intense pruritus and is associated with important morbidity .", "The extent to which CLM impairs skin disease-associated li...	[ "Hookworm-related cutaneous larva migrans ( CLM ) is a parasitic skin disease common in developing countries with hot climates .", "In resource-poor settings , CLM is associated with considerable morbidity .", "The disease is caused by animal hookworm larvae that penetrate the skin and migrate aimlessly in the ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "public health and epidemiology", "epidemiology", "genetic epidemiology" ]	Genes Contributing to Pain Sensitivity in the Normal Population: An Exome Sequencing Study	journal.pgen.1003095	null	[ [ "Chronic pain has a prevalence of nearly 20% in Europe [1] and similar estimates are reported for North America .", "The symptom is poorly controlled by existing therapies and the resulting personal and socio-economic burden is considerable .", "While many analgesic drugs are available , the vast majo...	[ "Sensitivity to pain varies considerably between individuals and is known to be heritable .", "Increased sensitivity to experimental pain is a risk factor for developing chronic pain , a common and debilitating but poorly understood symptom .", "To understand mechanisms underlying pain sensitivity and to search...	[ "Chronic widespread pain is a complex clinical problem .", "Identification of underlying genetic factors would shed light on the biology of pain and offer targets for novel therapies .", "We aimed to identify rare genetic variants in the normal population associated with pain sensation by performing exome seque...	2012
[ "Introduction", "Methods", "Results and Discussion" ]	[ "stiffness", "mechanical properties", "classical mechanics", "fluid mechanics", "mechanical stress", "materials science", "damage mechanics", "cellular structures and organelles", "cytoskeleton", "bending", "mechanical tension", "deformation", "fluid dynamics", "continuum mechanics", "fl...	Immersed Boundary Models for Quantifying Flow-Induced Mechanical Stimuli on Stem Cells Seeded on 3D Scaffolds in Perfusion Bioreactors	journal.pcbi.1005108	null	[ [ "The culture of stem cell populations in dynamic set-ups , for example in perfusion bioreactors , holds great potential for the production of tissue engineered constructs [1] .", "The use of bioreactors permits automated seeding and expansion of progenitor cells [2 , 3] , facilitating the production of cl...	[ "Perfusion bioreactors regulate flow conditions in order to provide cells with oxygen , nutrients and flow-associated mechanical stimuli .", "Locally , these flow conditions can vary depending on the scaffold geometry , cellular confluency and amount of extra cellular matrix deposition .", "In this study , a no...	[ "Tissue Engineering involves the combination of cells , growth factors and biomaterials into artificial constructs which , upon implantation , can improve the healing capacity of the human body .", "A remaining challenge involves providing physical stimuli to individual cells , thereby guiding them towards the pr...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immune cells", "retrovirology and hiv immunopathogenesis", "immunity to infections", "immunology", "immune defense", "infectious diseases", "hiv", "t cells", "immune response", "immunopathology", "clinical immunology", "immunity", "viral diseases" ]	Functional Cure of SIVagm Infection in Rhesus Macaques Results in Complete Recovery of CD4+ T Cells and Is Reverted by CD8+ Cell Depletion	journal.ppat.1002170	null	[ [ "A minority of HIV-1-infected patients , defined as elite controllers ( ECs ) , demonstrate that effective control of viral replication and disease progression is possible in the absence of treatment [1] .", "Deciphering the mechanisms of natural infection control in these patients is a critical step for ...	[ "Understanding the mechanism of infection control in elite controllers ( EC ) may shed light on the correlates of control of disease progression in HIV infection .", "However , limitations have prevented a clear understanding of the mechanisms of elite controlled infection , as these studies can only be performed...	[ "A small proportion of HIV-infected patients control viral replication and disease progression in the absence of any antiretroviral treatment .", "Understanding the mechanisms of viral control in these elite controllers may help to identify new therapeutic approaches in order to control HIV infection .", "Howev...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "body fluids", "pathology and laboratory medicine", "biopsy", "enzymes", "pathogens", "immunology", "rna extraction", "microbiology", "enzymology", "surgical and invasive medical procedures", "dna transcription", "retroviruse...	Gut and blood differ in constitutive blocks to HIV transcription, suggesting tissue-specific differences in the mechanisms that govern HIV latency	journal.ppat.1007357	null	[ [ "The major barrier to a cure for HIV is thought to be latently-infected cells that do not produce HIV constitutively but can be induced to produce infectious virus upon activation [1–3] .", "The latent HIV reservoir cannot be eliminated using currently available antiretroviral drugs , and due to their lon...	[ "Latently-infected CD4+ T cells are widely considered to be the major barrier to a cure for HIV .", "Much of our understanding of HIV latency comes from latency models and blood cells , but most HIV-infected cells reside in lymphoid tissues such as the gut .", "We hypothesized that tissue-specific environments ...	[ "Available antiretroviral drugs significantly prolong life expectancy and reduce morbidity in people living with HIV .", "However , HIV can escape host immune responses and drug treatment by establishing a reversibly silent ( \"latent\" ) infection in CD4+ T cells .", "This latent infection represents the major...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "parasite groups", "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "plasmodium", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "parasitology", "vaccines", "preventive medicine", "apicomplexa", "protozoans", "antibodies...	An Antibody Screen of a Plasmodium vivax Antigen Library Identifies Novel Merozoite Proteins Associated with Clinical Protection	journal.pntd.0004639	null	[ [ "Intensified research and funding have helped to significantly reduce the morbidity and mortality of malaria , and an increasing number of countries are now aiming to eliminate this disease [1–3] .", "In Asia-Pacific and the Americas , however , interrupting local Plasmodium vivax transmission will be par...	[ "Elimination of Plasmodium vivax malaria would be greatly facilitated by the development of an effective vaccine .", "A comprehensive and systematic characterization of antibodies to P . vivax antigens in exposed populations is useful in guiding rational vaccine design .", "In this study , we investigated antib...	[ "Plasmodium vivax is now the predominant malaria parasite outside Africa .", "Because P . vivax can remain dormant in the liver for months , identifying and treating P . vivax in asymptomatic individuals is difficult .", "Additionally , current widely-used vector control measures are less efficient against mosq...	2016
[ "Introduction", "Material and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "animal models of disease", "immunology", "microbiology", "animal models", "preventive medicine", "model organisms", "immunologic adjuvants", "antibodies", "immunologic techniques", "vaccination and immunizati...	Vaccination with the Surface Proteins MUL_2232 and MUL_3720 of Mycobacterium ulcerans Induces Antibodies but Fails to Provide Protection against Buruli Ulcer	journal.pntd.0004431	null	[ [ "Buruli ulcer ( BU ) is a neglected tropical disease of the skin and subcutaneous tissue reported from over 30 countries worldwide .", "BU is most prevalent in West African countries like Cote d’Ivoire , Cameroon , Benin and Ghana [1 , 2] .", "Mycobacterium ulcerans , the causative agent of BU , produ...	[ "Buruli ulcer , caused by infection with Mycobacterium ulcerans , is a chronic ulcerative neglected tropical disease of the skin and subcutaneous tissue that is most prevalent in West African countries .", "M . ulcerans produces a cytotoxic macrolide exotoxin called mycolactone , which causes extensive necrosis o...	[ "Buruli ulcer is a slow progressing ulcerative disease of the skin and subcutaneous tissue that is most prevalent in West African rural communities .", "Mycobacterium ulcerans , the causative agent of the disease , produces a toxin called mycolactone , which is held responsible for the extensive tissue damage see...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Broad-Spectrum Antiviral Protein ZAP Restricts Human Retrotransposition	journal.pgen.1005252	null	[ [ "Host restriction factor proteins are part of the intrinsic immune system of the cell , forming an early line of defense against viral infection .", "Intrinsic immunity is triggered when viral RNAs are recognized by pattern-recognition receptors , such as Toll-like and retinoic acid-inducible gene ( RIG-I...	[ "Intrinsic immunity describes the set of recently discovered but poorly understood cellular mechanisms that specifically target viral pathogens .", "Their discovery derives in large part from intensive studies of HIV and SIV that revealed restriction factors acting at various stages of the retroviral life cycle ....	[ "Retrotransposons are mobile DNA elements that duplicate themselves by a \"copy and paste\" mechanism using an RNA intermediate .", "They are insertional mutagens that have had profound effects on genome evolution , fostering DNA deletions , insertions and rearrangements , and altering gene expression .", "LINE...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "skin", "biosensors", "cell physiology", "invertebrates", "cell motility", "medicine and health sciences", "integumentary system", "engineering and technology", "caenorhabditis", "cell cycle and cell division", "cell processes", "animals", "cell polarity", "animal models", "developmental...	CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis	journal.pgen.1006415	null	[ [ "Understanding how the cellular behaviors that underlie embryonic morphogenesis are regulated is a longstanding and fundamental goal of developmental biology .", "One such cell behavior that can reshape tissues during embryogenesis is mediolateral intercalation , whereby cells within the same plane interd...	[ "Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis .", "As such , intercalation requires orchestration of cell polarity across the plane of the tissue .", "CDC-42 is a Rho family GTPase with key functions in cell polarity , yet its role during epithelial inter...	[ "As embryos develop , tissues must change shape to establish an animal’s form .", "One key form-shaping movement , cell intercalation , often occurs when a tissue elongates in a preferred direction .", "How cells in epithelial sheets can intercalate while maintaining tissue integrity is not well understood .", ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "biochemical simulations", "biology and life sciences", "computational biology", "biophysics", "biophysical simulations" ]	Different Inward and Outward Conduction Mechanisms in NaVMs Suggested by Molecular Dynamics Simulations	journal.pcbi.1003746	null	[ [ "Na+ flux through voltage gated sodium channels ( NaV ) is crucial for initiating action potentials in the membranes of electrically excitable cells .", "They mediate a variety of biological functions such as muscle contraction , propagation of nerve impulses , release of hormones and many more [1] .", ...	[ "Rapid and selective ion transport is essential for the generation and regulation of electrical signaling pathways in living organisms .", "Here , we use molecular dynamics ( MD ) simulations with an applied membrane potential to investigate the ion flux of bacterial sodium channel NaVMs .", "5 . 9 µs simulatio...	[ "Voltage gated sodium channels are essential components of living cell membranes .", "They regulate the cell potential by facilitating permeation of ions across the membrane .", "In the past decades , studies revealed that the bacterial selectivity filter ( SF ) exhibits a constricted architecture lined with el...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/viral infections", "cell biology/cell signaling" ]	Release of Intracellular Calcium Stores Facilitates Coxsackievirus Entry into Polarized Endothelial Cells	journal.ppat.1001135	null	[ [ "Coxsackievirus B ( CVB ) , a member of the enterovirus family , is associated with a number of diverse syndromes including aseptic meningitis , myocarditis , febrile illness , and diabetes [1] .", "CVBs are transmitted via the fecal-oral route and encounter the polarized epithelium lining the gastrointes...	[ "Group B coxsackieviruses ( CVB ) are associated with viral-induced heart disease and are among the leading causes of aseptic meningitis worldwide .", "Here we show that CVB entry into polarized brain microvasculature and aortic endothelial cells triggers a depletion of intracellular calcium stores initiated thro...	[ "Enteroviruses are associated with a number of diverse syndromes such as myocarditis , febrile illness , and are the main causative agents of aseptic meningitis .", "No effective therapeutics exist to combat non-poliovirus enterovirus infections .", "A better understanding of the mechanisms by which these virus...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immune cells", "cytokines", "viral classification", "immunity to infections", "population genetics", "microbiology", "retroviruses", "immunodeficiency viruses", "mechanisms of resistance and susceptibility", "sexually transmitted diseases", "immune defense", "population biology"...	HIV Protective KIR3DL1/S1-HLA-B Genotypes Influence NK Cell-Mediated Inhibition of HIV Replication in Autologous CD4 Targets	journal.ppat.1003867	null	[ [ "NK cells function in innate immune responses to transformed and virally infected cells .", "They can exert their anti-viral effects soon after encountering infected targets without prior sensitization [1] .", "NK cell function is determined by signals from activating and inhibitory cell surface recep...	[ "Carriage of the genetic combination encoding a high expression inhibitory Killer Immunoglobulin-like Receptor ( KIR ) 3DL1 with its ligand , HLA-B57 ( h/y+B57 ) is associated with slower time to AIDS and better HIV viral load control than being a Bw6 homozygote ( Bw6hmz ) .", "Natural Killer ( NK ) cells fro...	[ "Natural Killer ( NK ) cells function in anti-tumor and anti-viral defenses , including those directed against HIV .", "HIV infected cells can activate NK cells , which , once activated , inhibit HIV replication in infected targets .", "NK cell activation levels depend on the interaction of cell surface recepto...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "molecular biology/rna-protein interactions", "genetics and genomics/gene expression", "molecular biology/mrna stability", "cell biology/microbial growth and development", "genetics and genomics/gene function", "infectious diseases/pr...	Universal Features of Post-Transcriptional Gene Regulation Are Critical for Plasmodium Zygote Development	journal.ppat.1000767	null	[ [ "Early post-fertilization development in multi-cellular organisms relies on mRNAs supplied in the oocyte in translationally silent P body related storage particles known as P granules .", "Translation of these maternal mRNA pools depends on fertilization and occurs prior to maternal to zygote transition w...	[ "A universal feature of metazoan sexual development is the generation of oocyte P granules that withhold certain mRNA species from translation to provide coding potential for proteins during early post-fertilization development .", "Stabilisation of translationally quiescent mRNA pools in female Plasmodium gameto...	[ "Transmission of malaria relies on ingestion of male and female sexual precursor cells ( gametocytes ) from the human host by the mosquito vector .", "Fertilization results in the formation of a diploid zygote that transforms into the ookinete , the motile form of the parasite that is capable of escaping the host...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biology", "computational biology" ]	Stochastic Modeling of Expression Kinetics Identifies Messenger Half-Lives and Reveals Sequential Waves of Co-ordinated Transcription and Decay	journal.pcbi.1002772	null	[ [ "Experimental evidence suggest that the majority of mRNAs are degraded with a first-order decay rate [2] , [21] .", "This allows to characterize mRNA disappearance time profiles by a first-order rate equation ( 1 ) where is the decay rate ( or half-life , with ) , is the mRNA concentration and is the prom...	[ "The transcriptome in a cell is finely regulated by a large number of molecular mechanisms able to control the balance between mRNA production and degradation .", "Recent experimental findings have evidenced that fine and specific regulation of degradation is needed for proper orchestration of a global cell respo...	[ "The amount of a given transcript in a cell is determined by a fine tuned balance of production and degradation in a complex regulatory network .", "Regulation of transcription controls when transcription occurs and how much mRNA is created , whereas regulation of degradation controls the rate at which messengers...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology/theoretical ecology", "ecology/population ecology", "science policy", "infectious diseases/epidemiology and control of infectious diseases" ]	Comparing Models for Early Warning Systems of Neglected Tropical Diseases	journal.pntd.0000033	null	[ [ "One of the best documented patterns in the dynamics of vector-transmitted diseases is their periodicity at seasonal and interannual temporal scales [1–7] .", "These periodicities are the basis for the proposal that early warning systems ( EWS ) are feasible and useful tools for planning and decision maki...	[ "Early warning systems ( EWS ) are management tools to predict the occurrence of epidemics of infectious diseases .", "While climate-based EWS have been developed for malaria , no standard protocol to evaluate and compare EWS has been proposed .", "Additionally , there are several neglected tropical diseases wh...	[ "Early Warning Systems ( EWS ) are management tools to predict the occurrence of epidemics .", "They are based on the dependence of a given infectious disease on environmental variables .", "Although several neglected tropical diseases are sensitive to the effect of climate , our ability to predict their dynami...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics", "biology", "evolutionary biology", "genetics and genomics" ]	Evolution of Sex-Specific Traits through Changes in HOX-Dependent doublesex Expression	journal.pbio.1001131	Analysis in Drosophila suggests that evolutionary changes in the spatial regulation of the transcription factor doublesex play a key role in the origin, diversification, and loss of sex-specific structures.	[ [ "Sexual dimorphism is a common feature of animal morphology .", "Most lineages display unique sets of sex-specific traits , indicating that new sexual characters are gained and old ones are lost , frequently in evolution .", "At the genetic level , the origin of sex-specific structures from sexually m...	[ "Almost every animal lineage is characterized by unique sex-specific traits , implying that such traits are gained and lost frequently in evolution .", "However , the genetic mechanisms responsible for these changes are not understood .", "In Drosophila , the activity of the sex determination pathway is restric...	[ "Most animals are sexually dimorphic , yet each species has a different set of sex-specific traits .", "Much of evolutionary biology since Darwin has focused on explaining these differences .", "In contrast to the well-developed theories of sexual selection ( how and why males compete for females ) we are still...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "virology", "plant biology", "plant pathology", "biology", "genomics", "microbiology", "genetics and genomics" ]	Historical Contingencies Modulate the Adaptability of Rice Yellow Mottle Virus	journal.ppat.1002482	null	[ [ "Rice yellow mottle virus , of the genus Sobemovirus , causes a major disease in Africa [1] .", "The virus has a narrow host range restricted to the two cultivated rice species , Oryza sativa and O . glaberrima , and a few wild grasses [2] .", "The Asiatic rice O . sativa , which was introduced to Eas...	[ "The rymv1-2 and rymv1-3 alleles of the RYMV1 resistance to Rice yellow mottle virus ( RYMV ) , coded by an eIF ( iso ) 4G1 gene , occur in a few cultivars of the Asiatic ( Oryza sativa ) and African ( O . glaberrima ) rice species , respectively .", "The most salient feature of the resistance breaking ( RB ) pro...	[ "A fundamental question in virus evolution is whether emergence into a new host species/cultivar requires adaptation of the virus during the early stages of infection or whether it is largely via a chance transmission of a viral strain with the requisite characteristics .", "Our studies of the breakdown of RYMV1 ...	2012
[ "Introduction", "Methods", "Results and Discussion" ]	[ "population modeling", "infectious disease modeling", "biology", "computational biology" ]	Synthesising 30 Years of Mathematical Modelling of Echinococcus Transmission	journal.pntd.0002386	null	[ [ "Echinococcosis is a parasitic disease caused by the larvae of fox and dog cestode worms of the genus Echinococcus .", "It is a complex zoonosis that has domestic and sylvatic lifecycles , and a range of different intermediate and definitive host species .", "The two most clinically relevant species a...	[ "Echinococcosis is a complex zoonosis that has domestic and sylvatic lifecycles , and a range of different intermediate and definitive host species .", "The complexities of its transmission and the sparse evidence on the effectiveness of control strategies in diverse settings provide significant challenges for th...	[ "Echinococcosis is a complex zoonosis for which there is sparse evidence on the effectiveness of control strategies in diverse settings .", "This presents significant challenges for the design of effective public health policy against this disease .", "Mathematical modelling is a useful tool for simulating cont...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "medicine and health sciences", "cell biology", "protein translation", "gene expression", "genetics", "influenza", "biology and life sciences", "viral diseases", "molecular cell biology" ]	Influenza A Virus Host Shutoff Disables Antiviral Stress-Induced Translation Arrest	journal.ppat.1004217	null	[ [ "Transcription of Influenza A virus ( IAV ) genes is performed by a viral polymerase that generates 5′-capped and polyadenylated ( poly[A] ) messenger RNAs ( mRNAs ) structurally similar to host mRNAs [1] .", "Despite this similarity , IAV transcripts gain preferential access to cellular translation machi...	[ "Influenza A virus ( IAV ) polymerase complexes function in the nucleus of infected cells , generating mRNAs that bear 5′ caps and poly ( A ) tails , and which are exported to the cytoplasm and translated by host machinery .", "Host antiviral defences include mechanisms that detect the stress of virus infection a...	[ "Like all viruses , Influenza A virus ( IAV ) is absolutely dependent on host-cell protein synthesis machinery .", "This dependence makes the virus vulnerable to the innate ability of cells to inhibit protein synthesis in response to various types of stress .", "This inhibition , termed translation arrest , hel...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "medicine and health sciences", "mitochondrial dna", "forms of dna", "mitochondria", "biology and life sciences", "bioenergetics", "dna", "energy-producing organelles" ]	In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication	journal.pgen.1004832	null	[ [ "In their inner membrane , mitochondria harbor the oxidative phosphorylation ( OXPHOS ) system , which generates ATP needed to drive energetically unfavorable cellular reactions .", "Most OXPHOS components are encoded in the nuclear genome , but genes for 13 essential subunits are encoded by a separate mi...	[ "Mitochondrial DNA ( mtDNA ) encodes for proteins required for oxidative phosphorylation , and mutations affecting the genome have been linked to a number of diseases as well as the natural ageing process in mammals .", "Human mtDNA is replicated by a molecular machinery that is distinct from the nuclear replisom...	[ "Mitochondria are cytoplasmatic organelles that produce most of the adenosine triphosphate ( ATP ) used by the cell as a source of chemical energy .", "A subset of proteins required for ATP production is encoded by a distinct mitochondrial DNA genome ( mtDNA ) .", "Proper maintenance of mtDNA is essential , sin...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells	journal.pgen.1005304	null	[ [ "Upon stimulation of cells with extracellular ligands , class I phosphoinositide 3-kinases ( PI3Ks ) generate lipids that modulate the function of a range of signalling proteins , including protein kinases ( such as Akt/PKB ) , regulators of small GTPases and adaptor proteins .", "These PI3K effectors reg...	[ "The organismal roles of the ubiquitously expressed class I PI3K", "isoform p110β remain largely unknown .", "Using a new kinase-dead", "knockin mouse model that mimics constitutive pharmacological inactivation of p110β , we document that full inactivation of p110β leads to embryonic lethality in a substantia...	[ "Class I PI3Ks are important signalling enzymes and drug targets in cancer and inflammation .", "We report that p110α and p110β , the two ubiquitously expressed class I PI3K isoforms , control fertility , with no evidence for such a role for p110δ , a PI3K highly expressed in leukocytes .", "Infertility is ther...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "chemical compounds", "organic compounds", "metabolites", "genome analysis", "crops", "plants", "vitamin c", "crop science", "gene expression", "chemistry", "vitamins", "tomatoes", "genetic loci", "fruits", "agriculture", "biochemistry", "eukaryot...	Genome-wide association analysis identifies a natural variation in basic helix-loop-helix transcription factor regulating ascorbate biosynthesis via D-mannose/L-galactose pathway in tomato	journal.pgen.1008149	null	[ [ "Tomato represents an important source of nutrients and fiber for the human diet and is a model system for studying fruit biology [1] .", "Cultivated tomatoes carry only a small fraction of the available genetic variation in this crop , since breeders have primarily focused on fruit size and stress resist...	[ "Tomato ( Solanum lycopersicum ) is one of the highest-value vegetable crops worldwide .", "Understanding the genetic regulation of primary metabolite levels can inform efforts aimed toward improving the nutrition of commercial tomato cultivars , while maintaining key traits such as yield and stress tolerance .",...	[ "Deciphering the diverse , interconnected plant metabolome can facilitate crop improvement .", "In this study , the use of a combination of multiple technologies has allowed us to obtain novel functional and genetic insights into our GWAS investigating variation in ascorbate accumulation in tomato .", "The InDe...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biophysics/theory and simulation", "biochemistry/theory and simulation", "computational biology", "biophysics", "computational biology/molecular dynamics" ]	Chromophore Protonation State Controls Photoswitching of the Fluoroprotein asFP595	journal.pcbi.1000034	null	[ [ "Fluorescent proteins have been widely used as genetically encodable fusion tags to monitor protein localizations and dynamics in live cells [1]–[3] .", "Recently , a new class of green fluorescent protein ( GFP ) -like proteins has been discovered , which can be reversibly photoswitched between a fluores...	[ "Fluorescent proteins have been widely used as genetically encodable fusion tags for biological imaging .", "Recently , a new class of fluorescent proteins was discovered that can be reversibly light-switched between a fluorescent and a non-fluorescent state .", "Such proteins can not only provide nanoscale res...	[ "Proteins whose fluorescence can be reversibly switched on and off hold great promise for applications in high-resolution optical microscopy and nanotechnology .", "To systematically exploit the potential of such photoswitchable proteins and to enable rational improvements of their properties requires a detailed ...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "action potentials", "medicine and health sciences", "engineering and technology", "depolarization", "signal processing", "membrane potential", "electrophysiology", "neuroscience", "simulation and modeling", "research and analysis methods", "animal cells", "sensory neurons", "cellular neuros...	Resurgent Na+ Current Offers Noise Modulation in Bursting Neurons	journal.pcbi.1007154	null	[ [ "Real-time signal detection in uncertain settings is a fundamental problem for information and communication systems .", "Our nervous system performs the daunting task of extracting meaningful information from natural environments and guides precise behaviors .", "Sensory neurons for instance use effi...	[ "Neurons utilize bursts of action potentials as an efficient and reliable way to encode information .", "It is likely that the intrinsic membrane properties of neurons involved in burst generation may also participate in preserving its temporal features .", "Here we examined the contribution of the persistent a...	[ "The nervous system extracts meaningful information from natural environments to guide precise behaviors .", "Sensory neurons encode and relay such complex peripheral information as electrical events , known as action potentials or spikes .", "The timing intervals between the spikes carry stimulus-relevant info...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "neurological disorders", "neurology", "genetics", "biology", "molecular cell biology", "neuroscience", "genetics and genomics" ]	Genetic Interaction between MTMR2 and FIG4 Phospholipid Phosphatases Involved in Charcot-Marie-Tooth Neuropathies	journal.pgen.1002319	null	[ [ "Phosphoinositides ( PIs ) constitute potent signaling molecules with a specific and restricted distribution at intracellular membranes that is strictly controlled by the concerted action of kinases and phosphatases [1] , [2] .", "PIs are key regulators of membrane trafficking as they contribute to assemb...	[ "We previously reported that autosomal recessive demyelinating Charcot-Marie-Tooth ( CMT ) type 4B1 neuropathy with myelin outfoldings is caused by loss of MTMR2 ( Myotubularin-related 2 ) in humans , and we created a faithful mouse model of the disease .", "MTMR2 dephosphorylates both PtdIns3P and PtdIns ( 3 , 5...	[ "Charcot-Marie-Tooth type 4B1 ( CMT4B1 ) and Charcot-Marie-Tooth type 4J ( CMT4J ) are severe autosomal recessive demyelinating neuropathies with childhood onset .", "We previously demonstrated that loss of the phospholipid phosphatase MTMR2 causes CMT4B1 with myelin outfoldings in human and mouse and that loss o...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "geomorphology", "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "landforms", "chlamydia trachomatis", "pathogens", "topography", "tropical diseases", "geographical locations", "immunology", "microbiology", "bacterial ...	Prevalence of signs of trachoma, ocular Chlamydia trachomatis infection and antibodies to Pgp3 in residents of Kiritimati Island, Kiribati	journal.pntd.0005863	null	[ [ "Trachoma is the leading infectious cause of blindness and the subject of an international campaign for elimination as a public health problem [1 , 2] .", "The strategy for elimination uses the acronym “SAFE”: surgery for advanced disease; and antibiotics , facial cleanliness and environmental improvement...	[ "In some Pacific Island countries , such as Solomon Islands and Fiji , active trachoma is common , but ocular Chlamydia trachomatis ( Ct ) infection and trachomatous trichiasis ( TT ) are rare .", "On Tarawa , the most populous Kiribati island , both the active trachoma sign “trachomatous inflammation—follicular”...	[ "Ocular infection with Chlamydia trachomatis causes trachoma .", "It is the leading infectious cause of blindness , and the target of an international campaign for elimination as a public health problem .", "Trachoma is endemic to Tarawa , the most populated island of Kiribati , housing approximately half the n...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models of disease", "immunology", "cell-mediated immunity", "microbiology", "vaccines", "infectious disease immunology", "antibacterial therapy", "mathematics", "statistics (mathematics)", "population modeling", "population biology", "vaccination and immunization", "research and anal...	The Effects of Vaccination and Immunity on Bacterial Infection Dynamics In Vivo	journal.ppat.1004359	null	[ [ "Salmonella enterica causes systemic diseases ( typhoid and paratyphoid fever ) [1] , food-borne gastroenteritis and non-typhoidal septicaemia ( NTS ) [2]–[4] in humans and in many other animal species world-wide .", "Current measures to control S . enterica infections are sub-optimal .", "The emergen...	[ "Salmonella enterica infections are a significant global health issue , and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host .", "We have combined in vivo tracking of molecularly tagged bacterial subp...	[ "The bacterium Salmonella enterica causes gastroenteritis and the severe systemic diseases typhoid , paratyphoid fever and non-typhoidal septicaemia ( NTS ) .", "Treatment of systemic disease with antibiotics is becoming increasingly difficult due to the acquisition of resistance .", "Licensed vaccines are avai...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Syndromic Approach to Arboviral Diagnostics for Global Travelers as a Basis for Infectious Disease Surveillance	journal.pntd.0004073	null	[ [ "Globalization has resulted in a steep increase in travel and trade . [1 , 2]", "In recent decades it has contributed to the spread of diseases that traditionally emerged only regionally but now threaten populations across the globe , stressing the need for global health surveillance . [1 , 2]", "Amon...	[ "Arboviruses have overlapping geographical distributions and can cause symptoms that coincide with more common infections .", "Therefore , arbovirus infections are often neglected by travel diagnostics .", "Here , we assessed the potential of syndrome-based approaches for diagnosis and surveillance of neglected...	[ "Physicians attending travelers with particular symptoms often neglect those infections that are transmitted by arthropods like ticks and mosquitoes ( arboviruses ) or don’t test for the appropriate arboviruses .", "This is because arboviruses cause symptoms that are similar to more common infections and because ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models of infection", "infectious disease immunology", "clinical immunology", "population modeling", "medical microbiology", "microbial pathogens", "immunology", "biology and life sciences", "infectious disease modeling", "computational biology", "microbiology", "population biology" ]	Granulocytes Impose a Tight Bottleneck upon the Gut Luminal Pathogen Population during Salmonella Typhimurium Colitis	journal.ppat.1004557	null	[ [ "Acute infections constitute highly complex interactions between pathogens and their hosts .", "The complexity arises from dynamic changes in pathogen gene expression , pathogen growth , barriers limiting the initial colonization and host defenses which limit further pathogen growth and survival during th...	[ "Topological , chemical and immunological barriers are thought to limit infection by enteropathogenic bacteria .", "However , in many cases these barriers and their consequences for the infection process remain incompletely understood .", "Here , we employed a mouse model for Salmonella colitis and a mixed inoc...	[ "Salmonella Typhimurium can colonize the human intestine and cause severe diarrhea .", "In recent years , it has become clear that this pathogen profits from inflammatory changes in the intestinal lumen , as the inflamed gut helps Salmonella to out-compete the resident microbiota .", "Granulocytes transmigratin...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "evolutionary biology", "statistics", "population genetics", "geographical locations", "simulation and modeling", "mathematics", "test statistics", "population biology", "research and analysis methods", "sex chromosomes", "chromosome biology", "mathematical and statistical techniques", "x ch...	The inference of sex-biased human demography from whole-genome data	journal.pgen.1008293	null	[ [ "Human population-genetic studies generally assume that the proportions of reproducing females and males are equal .", "However , human history contains sex-biased demographic events ( “sex-bias” ) which are defined by having unequal female and male effective population sizes , NeF and NeM .", "Some e...	[ "Sex-biased demographic events ( “sex-bias” ) involve unequal numbers of females and males .", "These events are typically inferred from the relative amount of X-chromosomal to autosomal genetic variation and have led to conflicting conclusions about human demographic history .", "Though population size changes...	[ "Sex-biased demographic events involve unequal numbers of females and males , and is referred to as “sex-bias” .", "In humans , short-range migrations ( e . g . , due to marriage practices ) are known to be sex-biased , and some long-range migrations , such as the one out of Africa , are hypothesized to be sex-bi...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "model organisms", "plant and algal models", "plant microbiology", "plant biology", "plant pathology", "biology", "microbiology", "host-pathogen interaction", "arabidopsis thaliana" ]	Mutations in FLS2 Ser-938 Dissect Signaling Activation in FLS2-Mediated Arabidopsis Immunity	journal.ppat.1003313	null	[ [ "Pattern-Recognition Receptors ( PRRs ) can initiate innate immunity by perception of conserved Pathogen- ( or Microbe- ) Associated Molecular Patterns ( PAMPs or MAMPs ) [1] , [2] .", "This process , which has been termed PAMP-triggered immunity ( PTI ) , serves as an initial defense response against pat...	[ "FLAGELLIN-SENSING 2 ( FLS2 ) is a leucine-rich repeat/transmembrane domain/protein kinase ( LRR-RLK ) that is the plant receptor for bacterial flagellin or the flagellin-derived flg22 peptide .", "Previous work has shown that after flg22 binding , FLS2 releases BIK1 kinase and homologs and associates with BAK1 k...	[ "As a Pattern-Recognition Receptor ( PRR ) that detects conserved microbial molecules , FLS2 mediates the plant innate immunity responses triggered by bacterial flagellin or the flagellin epitope flg22 .", "Even though several protein kinases including BAK1 , BKK1 , BIK1 are known to play early roles in FLS2-medi...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "molecular biology/dna replication", "molecular biology/chromatin structure", "molecular biology/transcription initiation and activation", "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "genetics and genomics/genome projects", "g...	Transcription Initiation Activity Sets Replication Origin Efficiency in Mammalian Cells	journal.pgen.1000446	null	[ [ "DNA replication initiation is thought to be the most highly regulated process in genome duplication as cells must ensure that replication origins ( ORIs ) fire precisely once before cell division .", "A large number of studies during the last twenty years have provided a good understanding of the molecul...	[ "Genomic mapping of DNA replication origins ( ORIs ) in mammals provides a powerful means for understanding the regulatory complexity of our genome .", "Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0 . 4% of the mouse genome with detailed molecular analysi...	[ "The duplication of the genetic information of a cell starts from specific sites on the chromosomes called DNA replication origins .", "Their number varies from a few hundred in yeast cells to several thousands in human cells , distributed along the genome at comparable distances in both systems .", "An importa...	2009
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "livestock", "medicine and health sciences", "ecology and environmental sciences", "microbiome", "chemical compounds", "ruminants", "microbiology", "diet", "vertebrates", "animals", "mammals", "metagenomics", "nutrition", "microbial genetics", "methane", "microbial genomics", "ecosys...	Bovine Host Genetic Variation Influences Rumen Microbial Methane Production with Best Selection Criterion for Low Methane Emitting and Efficiently Feed Converting Hosts Based on Metagenomic Gene Abundance	journal.pgen.1005846	null	[ [ "By 2050 , the human population will grow to over 9 billion people , and in the same time frame , global meat consumption is projected to increase by 73% [1] .", "However , intensive food production puts a strain on the environment , and there is a need to produce more food ethically and in a way that doe...	[ "Methane produced by methanogenic archaea in ruminants contributes significantly to anthropogenic greenhouse gas emissions .", "The host genetic link controlling microbial methane production is unknown and appropriate genetic selection strategies are not developed .", "We used sire progeny group differences to ...	[ "Methane is a highly potent greenhouse gas and ruminants are the major source of methane emissions from anthropogenic activities .", "Here we show in an experiment with cattle that genetic selection of low-emitting animals is a viable option based on a newly developed selection criterion .", "The experimental d...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "cell biology", "in vitro", "eukaryotes", "eubacteria" ]	Edema Toxin Impairs Anthracidal Phospholipase A2 Expression by Alveolar Macrophages	journal.ppat.0030187	null	[ [ "Bacillus anthracis , the etiological agent of anthrax , is a spore-forming Gram-positive bacterium [1] .", "Even though anthrax is primarily a disease of herbivores , all mammals are susceptible to B . anthracis infection .", "Human infection can occur via cutaneous , gastrointestinal , or respirator...	[ "Bacillus anthracis , the etiological agent of anthrax , is a spore-forming Gram-positive bacterium .", "Infection with this pathogen results in multisystem dysfunction and death .", "The pathogenicity of B . anthracis is due to the production of virulence factors , including edema toxin ( ET ) .", "Recently ...	[ "All mammals are susceptible to infection by Bacillus anthracis , the etiological agent of anthrax .", "Infection can occur either accidentally or as a potential consequence of a terrorism threat .", "Pulmonary infection is the most life-threatening form of the disease , causing a near 100% mortality .", "Des...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/immunity to infections", "microbiology/microbial evolution and genomics", "microbiology/innate immunity", "ecology/environmental microbiology", "microbiology/cellular microbiology and pathogenesis", "infectious diseases/gastrointestinal infections" ]	Like Will to Like: Abundances of Closely Related Species Can Predict Susceptibility to Intestinal Colonization by Pathogenic and Commensal Bacteria	journal.ppat.1000711	null	[ [ "The mammalian intestine hosts a microbial community of astonishing density and complexity .", "This intricate association presumably required significant coevolution of the host and its microbiota .", "Apparently , this coevolution has been guided by positive selection for factors that result in a st...	[ "The intestinal ecosystem is formed by a complex , yet highly characteristic microbial community .", "The parameters defining whether this community permits invasion of a new bacterial species are unclear .", "In particular , inhibition of enteropathogen infection by the gut microbiota ( = colonization resistan...	[ "The commensal microbiota , populating the intestinal tract to high levels , is fundamental to human health .", "It exerts beneficial effects on the immune system and contributes to protection against gastrointestinal infections ( = colonization resistance ) by largely unknown mechanisms .", "Here , we reveal c...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	The COP9 Signalosome Converts Temporal Hormone Signaling to Spatial Restriction on Neural Competence	journal.pgen.1004760	null	[ [ "Neural specification generates diverse neural cells that are located at exact positions necessary for specialized functions .", "It is well established that positional cues , such as extrinsic signals and intrinsic tissue-specific transcriptional factors , play key roles in neural specification and neuro...	[ "During development , neural competence is conferred and maintained by integrating spatial and temporal regulations .", "The Drosophila sensory bristles that detect mechanical and chemical stimulations are arranged in stereotypical positions .", "The anterior wing margin ( AWM ) is arrayed with neuron-innervate...	[ "A critical step in building a functional nervous system is to generate neurons at the appropriate locations .", "Neural competence is acquired at the precursor stage with the expression of specific transcription factors .", "One such critical factor is Senseless ( Sens ) , as precursors lacking Sens fail to de...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "genomics", "biology", "computational biology", "genetics and genomics" ]	Construction and Analysis of an Integrated Regulatory Network Derived from High-Throughput Sequencing Data	journal.pcbi.1002190	null	[ [ "Eukaryotic gene regulation is performed at multiple levels , each distinguished by different spatial and temporal characteristics .", "The combination and orchestration between regulatory mechanisms in various levels are central to a precise gene expression pattern , which is essential to many critical b...	[ "We present a network framework for analyzing multi-level regulation in higher eukaryotes based on systematic integration of various high-throughput datasets .", "The network , namely the integrated regulatory network , consists of three major types of regulation: TF→gene , TF→miRNA and miRNA→gene .", "We ident...	[ "The precise control of gene expression lies at the heart of many biological processes .", "In eukaryotes , the regulation is performed at multiple levels , mediated by different regulators such as transcription factors and miRNAs , each distinguished by different spatial and temporal characteristics .", "These...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology/biocatalysis", "biotechnology/applied microbiology", "computational biology/metabolic networks", "biotechnology/bioengineering", "computational biology/systems biology" ]	Genome-Scale Reconstruction and Analysis of the Pseudomonas putida KT2440 Metabolic Network Facilitates Applications in Biotechnology	journal.pcbi.1000210	null	[ [ "Pseudomonas putida is one of the best studied species of the", "metabolically versatile and ubiquitous genus of the Pseudomonads [1]–[3] .", "As a species , it", "exhibits a wide biotechnological potential , with numerous strains ( some of which", "solvent-tolerant [4] , [5] ) able to efficie...	[ "A cornerstone of biotechnology is the use of microorganisms for the efficient", "production of chemicals and the elimination of harmful waste .", "Pseudomonas putida is an archetype of such microbes due to", "its metabolic versatility , stress resistance , amenability to genetic", "modifications , and vast...	[ "The pseudomonads include a diverse set of bacteria whose metabolic versatility", "and genetic plasticity have enabled their survival in a broad range of", "environments .", "Many members of this family are able to either degrade toxic", "compounds or to efficiently produce high value compounds and are ther...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "medicine", "biochemistry", "developmental biology", "biology", "proteomics", "molecular cell biology", "hematology" ]	PRMT4 Is a Novel Coactivator of c-Myb-Dependent Transcription in Haematopoietic Cell Lines	journal.pgen.1003343	null	[ [ "Protein arginine methyltransferases ( PRMTs ) constitute a family of nine members ( PRMT1-9 ) in mammals , which are characterised by a conserved catalytic domain [1] , [2] .", "They post-translationally mono- and dimethylate arginine residues in proteins using S-adenosylmethionine ( SAM ) as methyl grou...	[ "Protein arginine methyltransferase 4 ( PRMT4 ) –dependent methylation of arginine residues in histones and other chromatin-associated proteins plays an important role in the regulation of gene expression .", "However , the exact mechanism of how PRMT4 activates transcription remains elusive .", "Here , we iden...	[ "Our manuscript deals with the Protein arginine methyltransferase 4 ( PRMT4 ) , which modifies arginine residues in histones and other chromatin-associated proteins and plays an important role in the regulation of gene expression .", "We addressed the question of how the transcriptional function of PRMT4 might co...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "agriculture", "biology" ]	A Genome-Wide Survey of Imprinted Genes in Rice Seeds Reveals Imprinting Primarily Occurs in the Endosperm	journal.pgen.1002125	null	[ [ "Maternal and paternal alleles , inherited in plants and animals after fertilization , are usually equivalently expressed during the developmental cycle .", "In plants and in placental animals , a subset of genes is preferentially transcribed depending on the gender of the parent from which the gene origi...	[ "Genomic imprinting causes the expression of an allele depending on its parental origin .", "In plants , most imprinted genes have been identified in Arabidopsis endosperm , a transient structure consumed by the embryo during seed formation .", "We identified imprinted genes in rice seed where both the endosper...	[ "The expression of maternal or paternal alleles in either a preferentially or exclusively uniparental manner , termed imprinting , is prevalent in the transient endosperm of seeds in the model plant Arabidopsis .", "Cereals form seeds where both the embryo and endosperm are present at seed maturity .", "They ar...	2011

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