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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Cholera Transmission in Ouest Department of Haiti: Dynamic Modeling and the Future of the Epidemic	journal.pntd.0004153	null	[ [ "After a massive earthquake struck the island nation of Haiti in 2010 , the introduction of an altered El Tor biotype of Vibrio cholerae O1 has led to one of the largest cholera outbreaks in recent history [1] [2] [3] .", "Almost four years after the identification of the first cholera cases , the transmi...	[ "In the current study , a comprehensive , data driven , mathematical model for cholera transmission in Haiti is presented .", "Along with the inclusion of short cycle human-to-human transmission and long cycle human-to-environment and environment-to-human transmission , this novel dynamic model incorporates both ...	[ "Based on the model-fitted trend and the observed incidence , there is evidence that after an initial period of intense transmission , the cholera epidemic in Haiti stabilized during the third year of the outbreak and became endemic .", "The model estimates indicate that the proportion of the population susceptib...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene function", "developmental biology", "x chromosome inactivation", "rna interference", "stem cells", "chromosome biology", "embryonic stem cells", "genomic imprinting", "gene expression", "genetics", "gene regulation", "epigenetics", "molecular genetics", "biology", "molecular cell b...	Female Bias in Rhox6 and 9 Regulation by the Histone Demethylase KDM6A	journal.pgen.1003489	null	[ [ "Homeobox ( HOX ) genes are known for their ability to regulate embryogenesis and guide tissue differentiation .", "These genes encode transcription factors that specify cell identity and regulate many embryonic programs including axis formation , limb development , and organogenesis [1] .", "Control ...	[ "The Rhox cluster on the mouse X chromosome contains reproduction-related homeobox genes expressed in a sexually dimorphic manner .", "We report that two members of the Rhox cluster , Rhox6 and 9 , are regulated by de-methylation of histone H3 at lysine 27 by KDM6A , a histone demethylase with female-biased expre...	[ "Homeobox ( HOX ) genes are known to be under epigenetic control during development .", "Here , we report that two mouse X-linked homeobox genes implicated in reproduction , Rhox6 and 9 , are activated by the histone demethylase KDM6A that removes methylation at lysine 27 of histone H3 .", "Kdm6a is one in a sm...	2013
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "cell biology/morphogenesis and cell biology", "immunology/immune response", "biochemistry/macromolecular assemblies and machines" ]	The Jacob2 Lectin of the Entamoeba histolytica Cyst Wall Binds Chitin and Is Polymorphic	journal.pntd.0000750	null	[ [ "The infectious and diagnostic stage of Entamoeba histolytica ( Eh ) , the cause of amebic dysentery and liver abscess , is a quadranucleate cyst [1] , [2] .", "Eh is morphologically indistinguishable from Entamoeba dispar ( Ed ) , a human commensal that does not cause disease [3] .", "Because Eh does...	[ "The infectious and diagnostic form of Entamoeba histolytica ( Eh ) , cause of amebic dysentery and liver abscess , is the quadranucleate cyst .", "The cyst wall of Entamoeba invadens ( Ei ) , a model for Eh , is composed of chitin fibrils and three sets of chitin-binding lectins that cross-link chitin fibrils ( ...	[ "For many years , we and others have used cysts of Entamoeba invadens ( Ei ) , a reptilian parasite , to model the infectious and diagnostic cysts of the human pathogen Entamoeba histolytica ( Eh ) .", "The Ei cyst wall is composed of chitin fibrils , as well as Jacob and Jessie lectins that have unique chitin-bi...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "education", "immunology", "geographical locations", "sociology", "social sciences", "ethnicities", "preventive medicine", "vaccination and immunization", "public and occupational health", "infectious diseases", "south ame...	Vaccination coverage in the context of the emerging Yellow Fever threat in French Guiana	journal.pntd.0007661	null	[ [ "Yellow fever ( YF ) is the most severe arbovirus to circulate in the Americas , with symptoms ranging from mild non-specific illness to hemorrhagic fever , a systemic illness characterized by high viremia , hepatic , renal and myocardial injury , hemorrhage , and high lethality [1] .", "A single-dose vac...	[ "French Guiana , a French overseas department located in South America between Brazil and Surinam , is the only European territory geographically located in the Amazonian forest complex and is considered endemic for yellow fever ( YF ) .", "In the context of the emergent threat of YF in Latin America , we conduct...	[ "Yellow fever ( YF ) is the most severe arbovirus to circulate in the Americas .", "French Guiana , a French overseas department located in South America between Brazil and Surinam , is the only European territory geographically located in the Amazonian forest complex and is considered endemic for YF .", "We co...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neutral theory", "population genetics", "markov model", "mathematics", "effective population size", "stochastic processes", "emergence", "forms of evolution", "theoretical biology", "evolutionary modeling", "biology", "evolutionary theory", "nonlinear dynamics", "genetic drift", "probab...	Structural Drift: The Population Dynamics of Sequential Learning	journal.pcbi.1002510	null	[ [ "Genetic drift refers to the change over time in genotype frequencies in a population due to random sampling .", "It is a central and well studied phenomenon in population dynamics , genetics , and evolution .", "A population of genotypes evolves randomly due to drift , but typically changes are neith...	[ "We introduce a theory of sequential causal inference in which learners in a chain estimate a structural model from their upstream “teacher” and then pass samples from the model to their downstream “student” .", "It extends the population dynamics of genetic drift , recasting Kimura's selectively neutral theory a...	[ "Human knowledge is often transmitted orally within a group via a sequence of communications between individuals .", "The children's game of Telephone is a familiar , simplified version .", "A phrase is uttered , understood , and then transmitted to another .", "Genetic information is communicated in an analo...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusion" ]	[]	Intravital Imaging of a Massive Lymphocyte Response in the Cortical Dura of Mice after Peripheral Infection by Trypanosomes	journal.pntd.0003714	null	[ [ "Human African trypanosomiasis , or sleeping sickness , results from infection by sub-species of the protozoan Trypanosoma brucei and is normally fatal if untreated .", "At early stages , trypanosomes multiply in the blood and peripheral organs where they are readily killed by available drugs .", "In ...	[ "Peripheral infection by Trypanosoma brucei , the protozoan responsible for sleeping sickness , activates lymphocytes , and , at later stages , causes meningoencephalitis .", "We have videoed the cortical meninges and superficial parenchyma of C56BL/6 reporter mice infected with T . b . brucei .", "By use of a ...	[ "African trypanosomes are motile parasites that cause sleeping sickness .", "They multiply first in the blood then cause death mainly by effects on the brain: immune system cells , including T cells and dendritic cells , play major roles in this .", "Thinking we might see the attack on the brain , we infected m...	2015
[ "Introduction", "Models", "Results", "Discussion" ]	[ "bacteriology", "organismal evolution", "species colonization", "ecology and environmental sciences", "invasive species", "applied mathematics", "population genetics", "microbiology", "mathematics", "microbial evolution", "population biology", "ecological metrics", "evolutionary theory", "...	Bet-hedging strategies in expanding populations	journal.pcbi.1006529	null	[ [ "The dynamics and evolutionary history of many biological species , from bacteria to humans , are characterized by invasions and expansions into new territory .", "The effectiveness of such expansions is crucial in determining the ecological range and therefore the success of a species .", "A large bo...	[ "In ecology , species can mitigate their extinction risks in uncertain environments by diversifying individual phenotypes .", "This observation is quantified by the theory of bet-hedging , which provides a reason for the degree of phenotypic diversity observed even in clonal populations .", "Bet-hedging in well...	[ "Ecological populations are often exposed to unpredictable and variable environmental conditions .", "A number of strategies have evolved to cope with such uncertainty .", "One of them is stochastic phenotypic switching , by which some individuals in the community are enabled to tackle adverse conditions , even...	2019
[ "Introduction", "Results", "Method" ]	[ "medicine and health sciences", "genetic networks", "breast tumors", "cardiovascular anatomy", "gene regulation", "cancers and neoplasms", "random variables", "covariance", "simulation and modeling", "oncology", "mathematics", "network analysis", "research and analysis methods", "computer ...	Condition-adaptive fused graphical lasso (CFGL): An adaptive procedure for inferring condition-specific gene co-expression network	journal.pcbi.1006436	null	[ [ "Gene co-expression network analysis is a useful tool for studying the complex regulatory machinery in organisms [1][2][3][4] .", "When the gene expression profiles under multiple conditions are available , comparing co-expression networks across conditions could reveal co-expression patterns that are com...	[ "Co-expression network analysis provides useful information for studying gene regulation in biological processes .", "Examining condition-specific patterns of co-expression can provide insights into the underlying cellular processes activated in a particular condition .", "One challenge in this type of analysis...	[ "Gene co-expression networks provide insights into the mechanism of cellular activity and gene regulation .", "Condition-specific mechanisms may be identified by constructing and comparing co-expression networks of multiple conditions .", "We propose a novel statistical method to jointly construct co-expression...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mus (mouse)", "none", "infectious diseases", "immunology" ]	Deletion of IL-4Rα on CD4 T Cells Renders BALB/c Mice Resistant to Leishmania major Infection	journal.ppat.0030068	null	[ [ "Experimental Leishmania major infection is widely used to explore the control of T helper 1 ( Th1 ) /Th2 differentiation and elucidate mechanisms underlying susceptibility/resistance to intracellular microbial infection [1 , 2] .", "Typically , susceptible BALB/c mice infected subcutaneously with L . maj...	[ "Effector responses induced by polarized CD4+ T helper 2 ( Th2 ) cells drive nonhealing responses in BALB/c mice infected with Leishmania major .", "Th2 cytokines IL-4 and IL-13 are known susceptibility factors for L . major infection in BALB/c mice and induce their biological functions through a common receptor ...	[ "Leishmaniasis is a disease induced by a protozoan parasite and transmitted by the sandfly .", "Several forms of infection are identified , and the different diseases have wide-ranging symptoms from localized cutaneous sores to visceral disease affecting many internal organs .", "Animal models of human cutaneou...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	G6PD Deficiency at Sumba in Eastern Indonesia Is Prevalent, Diverse and Severe: Implications for Primaquine Therapy against Relapsing Vivax Malaria	journal.pntd.0003602	null	[ [ "The majority of people suffering acute malaria caused by Plasmodium vivax cannot safely receive primaquine therapy to prevent multiple recurrent attacks called relapses .", "This extraordinary gap likely explains most of the heavy burdens of morbidity and mortality imposed by this long neglected species ...	[ "Safe treatment of Plasmodium vivax requires diagnosis of both the infection and status of erythrocytic glucose-6-phosphate dehydrogenase ( G6PD ) activity because hypnozoitocidal therapy against relapse requires primaquine , which causes a mild to severe acute hemolytic anemia in G6PD deficient patients .", "Man...	[ "G6PD deficiency affects over 400 million people worldwide .", "This enormously diverse disorder causes acute hemolytic anemia upon exposure to oxidizing chemicals , e . g . , naphthalene , some sulfa drugs , and certain antimalarials , including primaquine .", "The primary public health concern with G6PD defic...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "onchocerca volvulus", "helminths", "immunology", "biomarkers", "parasitic diseases", "animals", "onchocerca", "animal models", "urine", "developmental biology", "model organisms", "experimental organism systems", "researc...	Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum	journal.pntd.0006977	null	[ [ "Onchocerciasis , caused by the parasitic filarial nematode Onchocerca volvulus , remains a significant source of morbidity throughout sub-Saharan Africa [1] .", "O . volvulus infection is commonly diagnosed through the presence of microfilariae in skin snips , but skin samples can be further analyzed by ...	[ "The study of Onchocerca volvulus has been limited by its host range , with only humans and non-human primates shown to be susceptible to the full life cycle infection .", "Small animal models that support the development of adult parasites have not been identified .", "We hypothesized that highly immunodeficie...	[ "Onchocerciasis , caused by the filarial parasitic nematode Onchocerca volvulus , remains a significant source of morbidity throughout sub-Saharan Africa and is a primary cause of infectious blindness .", "Research on this disease has been hindered by an absence of suitable small animal hosts .", "Here we descr...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "chemical compounds", "gene regulation", "applied mathematics", "metabolic networks", "organic compounds", "simulation and modeling", "algorithms", "fungi", "model organisms", "mathematics", "simulated annealing", "network analysis", "experimental organism systems", "alcohols", "research...	OptRAM: In-silico strain design via integrative regulatory-metabolic network modeling	journal.pcbi.1006835	null	[ [ "Microbial-based cell factories can be used to advance environmentally friendly and economically viable industrial bioprocesses .", "Various strategies have been suggested to modify industrial strains to improve desired product yields .", "Traditional methods of strain screening mainly rely on mating ...	[ "The ultimate goal of metabolic engineering is to produce desired compounds on an industrial scale in a cost effective manner .", "To address challenges in metabolic engineering , computational strain optimization algorithms based on genome-scale metabolic models have increasingly been used to aid in overproducin...	[ "Computational strain design algorithms based on genome-scale metabolic models have increasingly been used to guide rational strain design for metabolic engineering .", "However , most strain optimization algorithms only utilize a metabolic network alone and cannot provide strategies that also involve transcripti...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics of the immune system", "genomic evolution", "immunity", "evolutionary immunology", "biology", "evolutionary biology", "comparative genomics", "immunology", "evolutionary processes", "immune response" ]	Distinct Effects on Diversifying Selection by Two Mechanisms of Immunity against Streptococcus pneumoniae	journal.ppat.1002989	null	[ [ "Diversifying selection on genes encoding pathogen antigens is a well known effect of host immunity [1] , [2] .", "Diversifying selection can maintain multiple alleles of a gene at appreciable frequencies in a population [3] .", "Acquired immune responses provide a fitness advantage for antigenic vari...	[ "Antigenic variation to evade host immunity has long been assumed to be a driving force of diversifying selection in pathogens .", "Colonization by Streptococcus pneumoniae , which is central to the organism's transmission and therefore evolution , is limited by two arms of the immune system: antibody- and T cell...	[ "Streptococcus pneumoniae , or pneumococcus , is a leading cause of morbidity and mortality in young children and elderly persons worldwide .", "Current pneumococcus vaccines target a limited number of clinically important serotypes , while strains with serotypes not targeted by current vaccines are increasing in...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "body fluids", "pathology and laboratory medicine", "highly-active antiretroviral therapy", "immune physiology", "cytokines", "antiviral therapy", "pathogens", "immunology", "microbiology", "lymphoid org...	Infection and depletion of CD4+ group-1 innate lymphoid cells by HIV-1 via type-I interferon pathway	journal.ppat.1006819	null	[ [ "Innate lymphoid cells ( ILCs ) represent a novel family of cellular subsets that produce large amounts of T cell-associated cytokines in response to innate stimulation in the absence of antigens [1 , 2] .", "Based on the expression of specific transcription factors , cell surface markers and signature cy...	[ "Innate lymphoid cells ( ILCs ) are severely depleted during chronic HIV-1 infection by unclear mechanisms .", "We report here that human ILC1s comprising of CD4+ and CD4- subpopulations were present in various human lymphoid organs but with different transcription programs and functions .", "Importantly , CD4+...	[ "Innate lymphoid cells ( ILCs ) , including ILC1 , ILC2 and ILC3 populations , represent a novel cellular family of the immune system and have potentials to produce large amounts of T cell-associated cytokines in response to innate stimulation in the absence of specific antigen stimulation .", "ILCs have emerged ...	2018
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "taxonomy", "organismal evolution", "medicine and health sciences", "body fluids", "genome evolution", "pathology and laboratory medicine", "chemical compounds", "pathogens", "microbiology", "organic compounds", "viruses", "urine", "phylogenetics", "data management", "rna viruses", "am...	An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides	journal.ppat.1007368	null	[ [ "Viral evolutionary rates can vary strongly depending on the method used to estimate them [1 , 2] .", "Among Baltimore groups , the fastest evolving entities are single-stranded ( ss ) RNA and reverse-transcribing ( RT ) viruses , with rates ranging between 10−2 and 10−5 substitutions per site per year ( ...	[ "Infection with human BK polyomavirus , a small double-stranded DNA virus , potentially results in severe complications in immunocompromised patients .", "Here , we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing .", "Our data reveal the highest genomic evolutionary rate...	[ "Little is known about the mechanisms of evolution and viral immune escape in double-stranded DNA ( dsDNA ) viruses .", "Here , we study the evolution of BK polyomavirus and observe the highest genomic evolutionary rate described so far for a dsDNA virus , in the range of RNA viruses , which usually evolve rapidl...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Systemic Expression of Kaposi Sarcoma Herpesvirus (KSHV) Vflip in Endothelial Cells Leads to a Profound Proinflammatory Phenotype and Myeloid Lineage Remodeling In Vivo	journal.ppat.1004581	null	[ [ "Kaposi sarcoma herpesvirus ( KSHV ) , also called human herpersvirus 8 ( HHV-8 ) , one of the most recently discovered human oncoviruses [1] , displays tropism for different cell types and a dual oncogenic role , both in lymphomagenesis and vascular oncogenesis .", "KSHV is specifically associated with K...	[ "KSHV is the causative agent of Kaposi sarcoma ( KS ) , a spindle-shaped endothelial cell neoplasm accompanied by an inflammatory infiltrate .", "To evaluate the role of KSHV vFLIP in the pathogenesis of KS , we constructed mice with inducible expression of vFLIP in endothelial cells .", "Abnormal cells with en...	[ "Kaposi’s sarcoma ( KS ) is the most common cancer in men infected with HIV , and also among the most frequent malignancies in Sub-Equatorial Africa .", "KS is a tumor of endothelial cell origin that is caused by infection with a gamma-herpesvirus , called KS herpesvirus ( KSHV ) or human herpesvirus 8 ( HHV-8 ) ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "cell cycle and cell division", "cell processes", "brassica", "gene function", "plant science", "model organisms", "molecular genetics", "plants", "arabidopsis thaliana", "research and analysis methods", "chromosome biology", "plant genetics", "plant and algal models", "cell b...	Crossover Localisation Is Regulated by the Neddylation Posttranslational Regulatory Pathway	journal.pbio.1001930	A genetic study finds the neddylation pathway (known to-date for post-translational protein modification) is involved in regulating crossover localization but not crossover number during meiosis in Arabidopsis.	[ [ "Meiosis is a modified cell cycle where two rounds of chromosome segregation follow a single S phase , resulting in the production of haploid gametes .", "Recombination is a key step in meiosis I , as it results in genetic crossover ( CO ) formation , which establishes physical links between the homologue...	[ "Crossovers ( COs ) are at the origin of genetic variability , occurring across successive generations , and they are also essential for the correct segregation of chromosomes during meiosis .", "Their number and position are precisely controlled , however the mechanisms underlying these controls are poorly under...	[ "During meiosis , two successive chromosomal divisions follow a single S phase , resulting in the formation of four haploid cells , each with half of the parental genetic material .", "This reduction in chromosome number occurs during the first meiotic division , when homologous chromosomes ( paternal and materna...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/cell differentiation", "developmental biology/molecular development", "developmental biology/developmental evolution", "developmental biology/developmental molecular mechanisms" ]	HOXA13 Is Essential for Placental Vascular Patterning and Labyrinth Endothelial Specification	journal.pgen.1000073	null	[ [ "For placental mammals , fetal development is contained in an intrauterine environment where the efficient exchange of oxygen , nutrients , and metabolic waste between the maternal and fetal blood supplies is facilitated by the placenta .", "Central to the placenta's function is its vascular labyrinth , a...	[ "In eutherian mammals , embryonic growth and survival is dependent on the formation of the placenta , an organ that facilitates the efficient exchange of oxygen , nutrients , and metabolic waste between the maternal and fetal blood supplies .", "Key to the placenta's function is the formation of its vascular laby...	[ "Defects in placental development are a common cause of mid-gestational lethality .", "Key to the placenta's function is its vascular labyrinth , a series of finely branched vessels that facilitate the efficient exchange of gases , nutrients , and metabolic waste between the maternal and fetal blood supplies .", ...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "protozoans", "signs and symptoms", "leishmania", "neglected tropical diseases", "infectious diseases", "whit...	Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis	journal.pntd.0005116	null	[ [ "Cutaneous Leishmaniasis ( CL ) caused by Leishmania braziliensis is characterized by a broad spectrum of clinical manifestations , ranging from localized CL to Mucosal Leishmaniasis ( rev . in [1] ) .", "A hallmark feature of the immunological response in localized CL is a strong Th1 type immune response...	[ "The initial response to Leishmania parasites is essential in determining disease development or resistance .", "In vitro , a divergent response to Leishmania , characterized by high or low IFN-γ production has been described as a potential tool to predict both vaccine response and disease susceptibility in vivo ...	[ "Control and development of Cutaneous Leishmaniasis ( CL ) are dependent on the host immunological response .", "One of the key molecules in determining elimination of Leishmania parasites from the infected host cell is the cytokine interferon gamma ( IFN-γ ) .", "The aim of this study was to investigate which ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "molecular cell biology", "virology", "genetics", "biology", "microbiology", "host-pathogen interaction", "genetics and genomics" ]	SUMO-Interacting Motifs of Human TRIM5α are Important for Antiviral Activity	journal.ppat.1002019	null	[ [ "Cells have developed many mechanisms to restrict viral infection .", "The adaptative", "immune response provides major protection against viral pathogens , but recently", "dominant-acting inhibitory gene products , called restriction factors , have been", "discovered that also play an importa...	[ "Human TRIM5α potently restricts particular strains of murine leukemia viruses", "( the so-called N-tropic strains ) but not others ( the B- or NB-tropic strains )", "during early stages of infection .", "We show that overexpression of SUMO-1 in human", "293T cells , but not in mouse MDTF cells , profoundly...	[ "TRIM5α is an intrinsic immunity protein that provides a post-entry block of", "retroviral infection , which depends on its specific ability to recognize", "retroviral capsid ( CA ) .", "Human TRIM5α is able to recognize and block", "infection by N-tropic murine leukemia virus ( N-MLV ) as well as other vir...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "cancer genetics", "pediatric oncology", "pediatrics", "molecular genetics", "pediatric orthopedics", "pediatrics and child health", "biology", "autosomal dominant", "clinical genetics", "gene identification and analysis", "genetics", "human genetics", "genetics and genomics" ]	Loss-of-Function Mutations in PTPN11 Cause Metachondromatosis, but Not Ollier Disease or Maffucci Syndrome	journal.pgen.1002050	null	[ [ "Cartilage tumor syndromes are characterized by multiple cartilaginous bone tumors that develop in childhood , often causing significant morbidity and predisposing to chondrosarcoma .", "Tumors can form as exostoses ( on the surface of bone ) , as in the autosomal dominant , multiple osteochondroma ( here...	[ "Metachondromatosis ( MC ) is a rare , autosomal dominant , incompletely penetrant combined exostosis and enchondromatosis tumor syndrome .", "MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2 , the genes responsible for autosomal domin...	[ "Children with cartilage tumor syndromes form multiple tumors of cartilage next to joints .", "These tumors can occur inside the bones , as with Ollier disease and Maffuci syndrome , or on the surface of bones , as in the Multiple Osteochondroma syndrome ( MO ) .", "In a hybrid syndrome , called metachondromato...	2011
[ "Introduction", "Model", "Results", "Discussion" ]	[ "computational biology/population genetics", "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "evolutionary biology/evolutionary ecology", "microbiology/microbial evolution and genomics", "computational biology/evolutionary modeling", "ev...	A Model for Damage Load and Its Implications for the Evolution of Bacterial Aging	journal.pgen.1001076	null	[ [ "Evolution by natural selection generally produces phenotypes that maximize fitness , but many factors can interfere .", "Genetic constraints can lead to a suboptimal phenotype , but an optimal phenotype may not be achieved even when an optimal genotype is possible .", "If the rate of deleterious muta...	[ "Deleterious mutations appearing in a population increase in frequency until stopped by natural selection .", "The ensuing equilibrium creates a stable frequency of deleterious mutations or the mutational load .", "Here I develop the comparable concept of a damage load , which is caused by harmful non-heritable...	[ "Almost all living organisms deteriorate with time through the process of aging or senescence .", "Because most studies on senescence examined organisms possessing a juvenile state , it was thought that bacteria , which reproduce by producing two apparently identical daughter cells , were immortal and not senesce...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "proteins", "genetics", "molecular genetics", "biology", "genetics and genomics" ]	Mediator Acts Upstream of the Transcriptional Activator Gal4	journal.pbio.1001290	We show that Mediator, a protein originally isolated on the basis of its ability to respond to transcriptional activators, and thought to be regulated by an activator, can also be the master that controls the activator.	[ [ "Cells regulate the expression of their genes according to requirement [1] .", "Activators recruit chromatin-remodeling or chromatin-modifying complexes that change the structure of chromatin to promote transcription [2] , [3] , while repressors recruit chromatin-modifying complexes that change the struct...	[ "The proteasome inhibitor MG132 had been shown to prevent galactose induction of the S . cerevisiae GAL1 gene , demonstrating that ubiquitin proteasome-dependent degradation of transcription factors plays an important role in the regulation of gene expression .", "The deletion of the gene encoding the F-box prote...	[ "The expression levels of proteins are tightly regulated , not only via their production but also via their degradation .", "Genes are transcribed only if their encoded proteins are required by the environmental or developmental conditions of a cell , and once a certain protein is no longer needed , it is rapidly...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "organism development", "heart development", "organogenesis", "biology and life sciences", "morphogenesis" ]	Foxf Genes Integrate Tbx5 and Hedgehog Pathways in the Second Heart Field for Cardiac Septation	journal.pgen.1004604	null	[ [ "Cardiac septation , the morphogenetic process that transitions the looped heart tube into the multi-chambered heart observed in mammals , is complex and often goes awry in Congenital Heart Disease ( CHD ) .", "Atrioventricular septation is the crucial process that separates the common atrioventricular ca...	[ "The Second Heart Field ( SHF ) has been implicated in several forms of congenital heart disease ( CHD ) , including atrioventricular septal defects ( AVSDs ) .", "Identifying the SHF gene regulatory networks required for atrioventricular septation is therefore an essential goal for understanding the molecular ba...	[ "Atrioventricular septal defects ( AVSDs ) are a common severe class of congenital heart defects .", "Recent work demonstrates that events in the second heart field ( SHF ) progenitors , rather than in the heart , drive atrioventricular ( AV ) septation .", "Our laboratory has shown that both Hedgehog signaling...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/tropical and travel-associated diseases", "infectious diseases" ]	Viral and Epidemiological Determinants of the Invasion Dynamics of Novel Dengue Genotypes	journal.pntd.0000894	null	[ [ "Dengue virus ( DENV ) is the most wide-spread arbovirus affecting human populations .", "During the last decades it has increasingly become a major public health problem with significant economic and social impact [1]–[3] .", "It is transmitted between humans in urban and peri-urban settings predomin...	[ "Dengue has become a major concern for international public health .", "Frequent epidemic outbreaks are believed to be driven by a complex interplay of immunological interactions between its four co-circulating serotypes and large fluctuations in mosquito densities .", "Viral lineage replacement events , caused...	[ "Dengue fever and the more severe dengue haemorrhagic fever and dengue shock syndrome are mosquito borne viral infections that have seen a major increase in terms of global distribution and total case numbers over the last few decades .", "There are currently four antigenically distinct and potentially co-circula...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "animal models of disease", "tropical diseases", "microbiology", "seasons", "rift valley fever", "age groups", "neglected tropical diseases", "veterinary science", "researc...	Drivers for Rift Valley fever emergence in Mayotte: A Bayesian modelling approach	journal.pntd.0005767	null	[ [ "Rift Valley fever ( RVF ) is a major vector-borne , zoonotic , and hemorrhagic fever ( Phlebovirus , Family Bunyaviridae ) that severely affects human health , animal health and livestock production mainly in Sub-Saharan Africa [1–3] .", "Its potential for spread and emergence in current disease-free are...	[ "Rift Valley fever ( RVF ) is a major zoonotic and arboviral hemorrhagic fever .", "The conditions leading to RVF epidemics are still unclear , and the relative role of climatic and anthropogenic factors may vary between ecosystems .", "Here , we estimate the most likely scenario that led to RVF emergence on th...	[ "Rift Valley fever ( RVF ) is an arboviral hemorrhagic fever affecting primarily livestock in Africa and in the Arabian Peninsula .", "The conditions leading to RVF emergence are not fully understood , mainly because of data scarcity .", "Applied to the island of Mayotte ( our ecosystem under study ) , for whic...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "biochemistry", "neurological disorders", "pharmacology", "biophysics" ]	Amyloid as a Depot for the Formulation of Long-Acting Drugs	journal.pbio.0060017	Amyloids have the properties required of a long-acting drug because they are stable depots that guarantee a controlled release of the active peptide drug from the amyloid termini.	[ [ "Amyloid fibrils , which are highly organized protein/peptide aggregates , are the hallmark of amyloid disease [1] .", "More than 20 human diseases are associated with disease-specific protein/peptide aggregation and amyloid fibril formation .", "For example , in Parkinson disease , the protein α-synu...	[ "Amyloids are highly organized protein aggregates that are associated with both neurodegenerative diseases such as Alzheimer disease and benign functions like skin pigmentation .", "Amyloids self-polymerize in a nucleation-dependent manner by recruiting their soluble protein/peptide counterpart and are stable aga...	[ "Amyloids are highly organized protein aggregates that are associated with both neurodegenerative diseases such as Alzheimer disease and benign functions such as skin pigmentation .", "Amyloids self-polymerize by recruiting their soluble protein counterpart and remain stable against harsh physical , chemical , an...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "biology" ]	Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases	journal.ppat.1002020	null	[ [ "For HIV to infect cells , the viral envelope ( Env ) protein must bind to the host protein CD4 and then to a coreceptor , most commonly CCR5 ( R5 HIV ) ( reviewed in [1] ) .", "The importance of CCR5 for HIV-1 pathogenesis is shown by the fact that individuals who are homozygous for an inactivating 32 ba...	[ "HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells .", "Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic ( R5 ) virus strains .", "As an approach to inactivating CCR5 , we introduc...	[ "For HIV to enter T cells , the virus first binds to a primary surface receptor CD4 and then to a coreceptor , either CCR5 or CXCR4 .", "Previously we engineered zinc-finger nucleases ( ZFNs ) to specifically disrupt the CCR5 gene in primary human T cells , the predominant cell type infected and killed by HIV .",...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Dual Regulation of Gene Expression Mediated by Extended MAPK Activation and Salicylic Acid Contributes to Robust Innate Immunity in Arabidopsis thaliana	journal.pgen.1004015	null	[ [ "How network properties , such as robustness against network perturbations , emerge from biological networks has been a central question in systems biology [1] , [2] .", "Possible modulation of network robustness in a biologically relevant context and mechanisms underlying the modulation are areas of stud...	[ "Network robustness is a crucial property of the plant immune signaling network because pathogens are under a strong selection pressure to perturb plant network components to dampen plant immune responses .", "Nevertheless , modulation of network robustness is an area of network biology that has rarely been explo...	[ "Robustness of a network is defined by how consistently it performs upon removal of some of its components .", "It is a common strategy for plant pathogens to attack components of the plant immune signaling network in an attempt to dampen plant immunity .", "Therefore , it is crucial for the plant immune signal...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "luciferase", "milk", "immune cells", "breast milk", "pathology and laboratory medicine", "body fluids", "enzymes", "pathogens", "gene regulation", "immunology", "carcinomas", "enzymology", "cancers and neoplasms", "microbiology", "diet"...	A cancer-associated Epstein-Barr virus BZLF1 promoter variant enhances lytic infection	journal.ppat.1007179	null	[ [ "Epstein-Barr virus ( EBV ) causes infectious mononucleosis and is associated with a variety of different types of human malignancies , including B-cell lymphomas and nasopharyngeal carcinoma .", "EBV infects approximately 90% of the world’s population , and like all herpesviruses , EBV persists in the ho...	[ "Latent Epstein-Barr virus ( EBV ) infection contributes to both B-cell and epithelial-cell malignancies .", "However , whether lytic EBV infection also contributes to tumors is unclear , although the association between malaria infection and Burkitt lymphomas ( BLs ) may involve excessive lytic EBV replication ....	[ "Whether excessive lytic EBV infection increases the risk of EBV-induced cancers is not clear .", "A particular variant ( Zp-V3 ) of the viral promoter driving expression of the EBV immediate-early BZLF1 ( Z ) protein that mediates lytic viral reactivation has been reported to be over-represented ( relative to th...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "in situ hybridization", "molecular probe techniques", "gene regulation", "animals", "animal models", "developmental biology", "model organisms", "experimental organism systems", "sequence motif analysis", "molecular biology techniques", "embryos", "sea squirts", "research and analysis metho...	Differential gene expression along the animal-vegetal axis in the ascidian embryo is maintained by a dual functional protein Foxd	journal.pgen.1006741	null	[ [ "In many animal embryos , localized maternal factors create differential gene expression patterns along the animal-vegetal axis [1–3] , and the subsequent developmental program proceeds on the basis of this initial patterning .", "In ascidian unfertilized eggs , several identified and unidentified materna...	[ "In many animal embryos , a specific gene expression pattern is established along the animal-vegetal axis soon after zygotic transcription begins .", "In the embryo of the ascidian Ciona intestinalis , soon after the division that separates animal and vegetal hemispheres into distinct blastomeres , maternal Gata ...	[ "In embryogenesis of most animals , a specific gene expression pattern is established along the animal-vegetal axis first .", "In the embryo of the ascidian Ciona intestinalis , the activity of the maternal factor Gata . a is suppressed by β-catenin , which is active only in the vegetal hemisphere , and thereby t...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "infectious diseases", "immunology", "evolutionary biology", "genetics and genomics" ]	Adaptation to Human Populations Is Revealed by Within-Host Polymorphisms in HIV-1 and Hepatitis C Virus	journal.ppat.0030045	null	[ [ "The cellular immune response mediated by CD8+ cytotoxic T-lymphocytes ( CTLs ) performs a critical role in the immune control of human viruses such as human immunodeficiency virus ( HIV-1 ) [1] and hepatitis C virus ( HCV ) [2] .", "Consequently , the major histocompatibility ( MHC ) loci that encode the...	[ "CD8+ cytotoxic T-lymphocytes ( CTLs ) perform a critical role in the immune control of viral infections , including those caused by human immunodeficiency virus type 1 ( HIV-1 ) and hepatitis C virus ( HCV ) .", "As a result , genetic variation at CTL epitopes is strongly influenced by host-specific selection fo...	[ "The rapid accumulation of genetic variation in human viruses , such as human immunodeficiency virus type 1 ( HIV-1 ) and hepatitis C virus ( HCV ) , enables these pathogens to elude the immune system and forestalls the development of effective vaccines .", "This variation may be shaped by selection due to host-s...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Presence of Virus Neutralizing Antibodies in Cerebral Spinal Fluid Correlates with Non-Lethal Rabies in Dogs	journal.pntd.0002375	null	[ [ "Rabies is a highly lethal disease caused by the neurotropic rabies virus ( RABV ) .", "It has been estimated that about 55 , 000 persons died from rabies each year mostly in Africa and Asia [1] .", "Successful vaccines have been developed for the prophylaxis of the disease .", "Timely post-exposu...	[ "Rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations .", "However , increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans .", "Non-lethal rabies infection ...	[ "Inexorable lethality is still commonly attributed to rabies infection , although there is increasing evidence for non-lethal infection and even recovery from clinical rabies in various animal species and humans .", "This paper reports non-lethal infection in dogs .", "The striking difference between dogs that ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "functional genomics", "metabolic processes", "parallel evolution", "evolutionary adaptation", "catabolism", "microbial genetics", "microbial genomics", "amino acid metabolism", "proteins", "metabolic pathways", "proteomics", "genetic drift", "biochemistry", "genetics", "biology and life...	Mutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environments	journal.pgen.1004872	null	[ [ "Adaptation to novel environments can proceed either through many mutations with small effects or through few mutations with large effects [1] .", "Adaptation to complex environments is the norm in biology , but a clear understanding of the adaptive processes employed by organisms in ecologically diverse ...	[ "Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection .", "Adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes if many...	[ "Changing environmental conditions are the norm in biology .", "However , understanding adaptation to complex environments presents many challenges .", "For example , adaptation to resource-rich environments can potentially have many successful evolutionary trajectories to increased fitness .", "Even in condi...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "nuclear staining", "immune physiology", "immunology", "parasitic protozoans", "protozoans", "antibodies", "immunologic techniques", "research and analysis methods", "monoclonal antibodies", "specimen preparation and treatment", "...	Species-Specific Immunodetection of an Entamoeba histolytica Cyst Wall Protein	journal.pntd.0004697	null	[ [ "Entamoeba histolytica is a protozoan parasite that causes an estimated 30–50 million cases of illness and kills 100 , 000 people annually [1 , 2] .", "It has a dual-stage life cycle , consisting of motile trophozoites that colonize and invade the colonic epithelium and of robust , chitinaceous cysts that...	[ "Entamoeba histolytica causes intestinal disease in endemic settings throughout the world .", "Diagnosis of E . histolytica infection would be improved by the identification of biomarkers that are expressed by cysts of E . histolytica , but not by cysts of closely related commensal species of Entamoeba .", "Her...	[ "Entamoeba histolytica is a prevalent human parasite requiring sensitive and specific detection .", "Assays available for Entamoeba detection utilize antibodies to detect parasite protein in stool , and they distinguish E . histolytica from nonpathogenic commensal amoeba .", "However , these tests have exhibite...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/gene function", "genetics and genomics", "genetics and genomics/functional genomics" ]	Off-Target Effects of Psychoactive Drugs Revealed by Genome-Wide Assays in Yeast	journal.pgen.1000151	null	[ [ "Neuropsychiatric disorders will effect 25% of all individuals at some point in their lives , with devastating social and economic consequences [1] .", "This constellation of diseases encompasses schizophrenia , depression , age-related memory and cognition decline , and the degeneration of neuromuscular ...	[ "To better understand off-target effects of widely prescribed psychoactive drugs , we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system .", "Because the known human targets of these drugs do not exist in yeast , we could employ the yeast ge...	[ "Neuropsychiatric disorders such as depression and psychosis affect one-quarter of all individuals during their lifetime , and despite efforts to improve the selectivity of psychoactive drugs , all are associated with side effects .", "Drug efficacy and tolerance are known to be linked to an individual's genetic ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Influenza Virus Induces Cholesterol-Enriched Endocytic Recycling Compartments for Budozone Formation via Cell Cycle-Independent Centrosome Maturation	journal.ppat.1005284	null	[ [ "Endocytic transport pathways are important to arrange the plasma membrane components for diversified cellular processes at the plasma membrane including virus budding .", "Endocytosed proteins are first delivered to the early/sorting endosomes , from where proteins are either recycled back to the plasma ...	[ "Influenza virus particles are assembled at the plasma membrane in concert with incorporation of the virus genome , but the details of its spatio-temporal regulation are not understood .", "Here we showed that influenza virus infection induces the assembly of pericentrosomal endocytic recycling compartment ( ERC ...	[ "Influenza virus particles are assembled at the plasma membrane in concert with incorporation of the virus genome , but the details of its spatiotemporal regulation are unknown .", "We found that the virus genome is transported to the plasma membrane using cholesterol-enriched recycling endosomes through cell cyc...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "bacterial biofilms", "gram negative", "microbial mutation", "ecology", "coastal ecology", "microbial pathogens", "marine and aquatic sciences", "biology", "microbiology", "marine biology", "bacterial pathogens", "microbial ecology" ]	A Communal Bacterial Adhesin Anchors Biofilm and Bystander Cells to Surfaces	journal.ppat.1002210	null	[ [ "Bacterial biofilm formation is the process by which bacteria attach to abiotic surfaces , the surfaces of other unicellular organisms , the epithelia of multicellular organisms , and interfaces such as that between air and water .", "Surface adhesion enables bacteria to arrange themselves favorably in th...	[ "While the exopolysaccharide component of the biofilm matrix has been intensively studied , much less is known about matrix-associated proteins .", "To better understand the role of these proteins , we undertook a proteomic analysis of the V . cholerae biofilm matrix .", "Here we show that the two matrix-associ...	[ "The bacterial multilayer biofilm consists of matrix-enclosed cells attached to each other to form large aggregates .", "The base of these aggregates may be attached to a living or non-living surface .", "The biofilm matrix most often contains at least one exopolysaccharide component and may also contain protei...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "collective animal behavior", "computer and information sciences", "animal behavior", "zoology", "cognition", "population modeling", "network analysis", "social networks", "information theory", "biology and life sciences", "computational biology", "cognitive science", "neuroscience", "anim...	Confidence Sharing: An Economic Strategy for Efficient Information Flows in Animal Groups	journal.pcbi.1003862	null	[ [ "Animals living in groups sense their surroundings both directly , by environmental cues , and indirectly , through countless social interactions .", "There is an abundance of experimental evidence for the usefulness of social information in increasing both the range ( the “many eyes” principle ) [1]–[5] ...	[ "Social animals may share information to obtain a more complete and accurate picture of their surroundings .", "However , physical constraints on communication limit the flow of information between interacting individuals in a way that can cause an accumulation of errors and deteriorated collective behaviors .", ...	[ "Cooperative groups are abundant on all scales of the biological world .", "Despite much empirical evidence on a wide variety of natural communication schemes , there is still a growing need for rigorous tools to quantify and understand the information flows involved .", "Here , we borrow techniques from inform...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "immunology", "biology", "computational biology" ]	Chemotactic Migration of T Cells towards Dendritic Cells Promotes the Detection of Rare Antigens	journal.pcbi.1002763	null	[ [ "Upon maturation , T lymphocytes continuously circulate in the blood and secondary lymphoid organs such as LNs and spleen .", "When they encounter dendritic cells ( DCs ) that present cognate antigen , the T cells become activated and subsequently start to proliferate .", "Before such an immune respon...	[ "In many immunological processes chemoattraction is thought to play a role in guiding cells to their sites of action .", "However , based on in vivo two-photon microscopy experiments in the absence of cognate antigen , T cell migration in lymph nodes ( LNs ) has been roughly described as a random walk .", "Alth...	[ "T lymphocytes are important actors of the immune system that find and kill infected cells .", "Before a T cell can mount such an immune response , it has to be activated through contact with a dendritic cell ( DC ) carrying antigen relevant to the specificity of the T cell receptor .", "This process typically ...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/pharmacogenomics", "computational biology/macromolecular structure analysis", "biochemistry/bioinformatics", "pharmacology/adverse reactions" ]	Harvesting Candidate Genes Responsible for Serious Adverse Drug Reactions from a Chemical-Protein Interactome	journal.pcbi.1000441	null	[ [ "Identifying genetic risk factors responsible for serious adverse drug reactions ( SADRs ) is one of the priorities in pharmacogenetics [1] .", "As it is not practical to perform genome-wide association study due to the lack of samples [2] , candidate gene selection has been an important strategy .", ...	[ "Identifying genetic factors responsible for serious adverse drug reaction ( SADR ) is of critical importance to personalized medicine .", "However , genome-wide association studies are hampered due to the lack of case-control samples , and the selection of candidate genes is limited by the lack of understanding ...	[ "Why do tragedies caused by Vioxx or Avandia only happen to certain individuals ?", "The unexpected bindings among drugs and human proteins might play important roles in such serious adverse drug reactions ( SADRs ) .", "To mine these unexpected chemical-protein interactions , 162 drug molecules known to cause ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/medical microbiology" ]	Mycobacteria Exploit Host Hyaluronan for Efficient Extracellular Replication	journal.ppat.1000643	null	[ [ "Infectious diseases caused by mycobacteria are serious threats to human health .", "Tuberculosis is caused by infection with mycobacteria , most frequently with Mycobacterium tuberculosis but also with Mycobacterium bovis , Mycobacterium africanum , Mycobacterium microti , and Mycobacterium canetii and k...	[ "In spite of the importance of hyaluronan in host protection against infectious organisms in the alveolar spaces , its role in mycobacterial infection is unknown .", "In a previous study , we found that mycobacteria interact with hyaluronan on lung epithelial cells .", "Here , we have analyzed the role of hyalu...	[ "Mycobacterium tuberculosis and Mycobacterium bovis are major bacterial pathogens that kill approximately 2 million people annually by causing tuberculosis .", "The M . tuberculosis complex has several strategies to parasitize the host .", "After infection is established , these pathogens are rarely eliminated ...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "carbohydrate metabolism", "medicine and health sciences", "body fluids", "diagnostic radiology", "functional magnetic resonance imaging", "chemical compounds", "oxygen", "carbohydrates", "neuroscience", "glucose metabolism", "organic compounds", "glucose", "magnetic resonance imaging", "o...	Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI	journal.pcbi.1004971	null	[ [ "Functional magnetic resonance imaging ( fMRI ) measures brain activity by detecting associated changes in blood oxygenation through the blood-oxygen-level dependent ( BOLD ) response .", "The BOLD response is caused by time-dependent changes in deoxyhemoglobin ( dHb ) concentration [1] .", "Although ...	[ "Functional magnetic resonance imaging ( fMRI ) measures brain activity by detecting the blood-oxygen-level dependent ( BOLD ) response to neural activity .", "The BOLD response depends on the neurovascular coupling , which connects cerebral blood flow , cerebral blood volume , and deoxyhemoglobin level to neuron...	[ "Functional magnetic resonance imaging ( fMRI ) is a widely used technique for measuring brain activity .", "However , the signal registered by fMRI is not a direct measurement of the neuronal activity in the brain , but it is influenced by the interplay between the metabolism , blood flow and blood volume in the...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "genetics and genomics/gene expression", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "genetics and genomics/gene function", "genetics and genomics/gene therapy", "genetics and genomics" ]	The Polyproline Site in Hinge 2 Influences the Functional Capacity of Truncated Dystrophins	journal.pgen.1000958	null	[ [ "Duchenne muscular dystrophy ( DMD ) is a lethal X-linked recessive disease caused by mutations in the 2 . 2 MB dystrophin gene [1]–[3] .", "In skeletal muscle , dystrophin provides a flexible connection between the cytoskeleton and the dystrophin-glycoprotein complex at the sarcolemma , myotendinous junc...	[ "Mutations in dystrophin can lead to Duchenne muscular dystrophy or the more mild form of the disease , Becker muscular dystrophy .", "The hinge 3 region in the rod domain of dystrophin is particularly prone to deletion mutations .", "In-frame deletions of hinge 3 are predicted to lead to BMD , however the seve...	[ "Dystrophin functions like a large molecular spring between the muscle cytoskeleton and the extracellular matrix in order to protect the membrane from contraction-induced injury .", "Mutations in dystrophin can lead to a severe muscle wasting disease called Duchenne muscular dystrophy ( DMD ) in young boys .", ...	2010
[ "Introduction", "Results", "Future directions", "Materials and methods" ]	[ "open science", "blastocysts", "methods and resources", "engineering and technology", "signal processing", "applied mathematics", "biologists", "simulation and modeling", "algorithms", "developmental biology", "scientists", "mathematics", "science and technology workforce", "research and a...	CellProfiler 3.0: Next-generation image processing for biology	journal.pbio.2005970	null	[ [ "Image analysis software is now used throughout biomedical research in order to reduce subjective bias and quantify subtle phenotypes when working with microscopy images .", "Automated microscopes are further transforming modern research .", "Experiments testing chemical compounds or genetic perturbat...	[ "CellProfiler has enabled the scientific research community to create flexible , modular image analysis pipelines since its release in 2005 .", "Here , we describe CellProfiler 3 . 0 , a new version of the software supporting both whole-volume and plane-wise analysis of three-dimensional ( 3D ) image stacks , inc...	[ "The “big-data revolution” has struck biology: it is now common for robots to prepare cell samples and take thousands of microscopy images .", "Looking at the resulting images by eye would be extremely tedious , not to mention subjective .", "Thus , many biologists find they need software to analyze images easi...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "cell biology", "yeast and fungi", "in vitro", "immunology", "microbiology", "mus (mouse)" ]	Environmental Dimensionality Controls the Interaction of Phagocytes with the Pathogenic Fungi Aspergillus fumigatus and Candida albicans	journal.ppat.0030013	null	[ [ "The frequency of invasive mycoses due to opportunistic fungal pathogens has increased significantly over the past decades .", "These infections are associated with high morbidity and mortality .", "They directly correlate with increasing patient populations that are at risk for developing invasive fu...	[ "The fungal pathogens Aspergillus fumigatus and Candida albicans are major health threats for immune-compromised patients .", "Normally , macrophages and neutrophil granulocytes phagocytose inhaled Aspergillus conidia in the two-dimensional ( 2-D ) environment of the alveolar lumen or Candida growing in tissue mi...	[ "Aspergillus fumigatus and Candida albicans are the most common of all human pathogenic fungal germs .", "Normally , inhaled Aspergillus spores are destroyed by alveolar macrophages and polymorphonuclear neutrophils ( PMNs ) , both of which are lung phagocytes , i . e . , cells that kill inhaled microbes by inges...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "fluorescence imaging", "medicine and health sciences", "immune cells", "gene regulation", "cell cycle and cell division", "metabolic processes", "cell processes", "immunology", "biological cultures", "in vivo imaging", "ht1080 cells", "dna damage", "proteolysis", "dna", ...	Activation-induced deaminase (AID) localizes to the nucleus in brief pulses	journal.pgen.1007968	null	[ [ "Activation-induced deaminase ( AID ) is essential for the three processes that diversify immunoglobulin ( Ig ) gene sequence and structure: somatic hypermutation , class switch recombination , and gene conversion [1–6] .", "In B cells of the germinal center and other lymphoid tissues , AID deaminates C t...	[ "Activation-induced deaminase ( AID ) converts C to U and 5-methyl-C to T . These mutagenic activities are critical to immunoglobulin ( Ig ) gene diversification and epigenetic reprogramming , but they must be tightly controlled to prevent compromising cell fitness .", "AID acts in the nucleus but localizes predo...	[ "Activation-induced deaminase ( AID ) is a mutagenic factor that plays a critical role in immunoglobulin gene diversification and also functions in early development to reprogram methylated regions of the genome .", "AID must be tightly regulated to prevent compromising cell fitness , but how this occurs is not t...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/gene expression", "biophysics/theory and simulation", "computational biology/systems biology", "cell biology/cell signaling" ]	Quantification of Circadian Rhythms in Single Cells	journal.pcbi.1000580	null	[ [ "The circadian rhythm of organisms ranging from cyanobacteria to humans beats at the cellular level; it is a remarkable manifestation of celestial mechanics mirrored in molecular biology .", "The standard view is that the mammalian circadian clock is a hierarchically organized system , governed by the sup...	[ "Bioluminescence techniques allow accurate monitoring of the circadian clock in single cells .", "We have analyzed bioluminescence data of Per gene expression in mouse SCN neurons and fibroblasts .", "From these data , we extracted parameters such as damping rate and noise intensity using two simple mathematica...	[ "Earth's 24-h-rotation around its axis is mirrored in the circadian clock that resides within each of our cells , controlling expression of ∼10% of all genes .", "The circadian clock is constructed as a negative feedback loop , in which clock proteins inhibit their own synthesis .", "During the last decade , a ...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "neglected tropical diseases", "fascioliasis" ]	Development and Evaluation of a New Lateral Flow Immunoassay for Serodiagnosis of Human Fasciolosis	journal.pntd.0001376	null	[ [ "Fascioliosis ( = fascioliasis ) is a plant-borne zoonosis caused by infection with trematode species of the genus Fasciola .", "Human fasciolosis is a re-emerging disease present worldwide , and can be produced by Fasciola hepatica and Fasciola gigantica .", "In Europe , the Americas and Oceania , on...	[ "Human fasciolosis is a re-emerging disease worldwide and is caused by species of the genus Fasciola ( F . hepatica and F . gigantica ) .", "Human fasciolosis can be diagnosed by classical coprological techniques , such as the Kato-Katz test , to reveal parasite eggs in faeces .", "However , although 100% speci...	[ "Fasciolosis is an important plant-borne trematode zoonosis .", "This disease is of both clinical and veterinary relevance and , according to the WHO , is considered a re-emerging disease that is spreading around the world .", "Fasciolosis has a serious impact on health because of the large size of the parasite...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "infectious diseases/infectious diseases of the nervous system", "microbiology/cellular microbiology and pathogenesis", "microbiology/innate immunity" ]	Fcγ Receptor I Alpha Chain (CD64) Expression in Macrophages Is Critical for the Onset of Meningitis by Escherichia coli K1	journal.ppat.1001203	null	[ [ "Professional phagocytes , including neutrophils and macrophages ( MØ ) express a specific set of phagocytic receptors that recognize , bind to and mediate internalization of microbial pathogens [1] , [2] , [3] .", "Although MØ receptor-mediated phagocytosis generally leads to the destruction of the patho...	[ "Neonatal meningitis due to Escherichia coli K1 is a serious illness with unchanged morbidity and mortality rates for the last few decades .", "The lack of a comprehensive understanding of the mechanisms involved in the development of meningitis contributes to this poor outcome .", "Here , we demonstrate that d...	[ "Escherichia coli K1 is the most common cause of meningitis in premature infants; the mortality rate of this disease ranges from 5% to 30% .", "A better understanding of the pathogenesis of E . coli K1 meningitis is needed to develop new preventative strategies .", "We have shown that outer membrane protein A (...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "biology", "computational biology", "metabolic networks", "metabolism" ]	Prediction of Microbial Growth Rate versus Biomass Yield by a Metabolic Network with Kinetic Parameters	journal.pcbi.1002575	null	[ [ "Traditional metabolic modeling techniques involve the reconstruction of kinetic models based on detailed knowledge on enzyme kinetic parameters for all enzymes in a certain system [1] .", "These models are limited to small-scale systems due to lack of sufficient data on kinetic constants and the highly c...	[ "Identifying the factors that determine microbial growth rate under various environmental and genetic conditions is a major challenge of systems biology .", "While current genome-scale metabolic modeling approaches enable us to successfully predict a variety of metabolic phenotypes , including maximal biomass yie...	[ "While current genome-scale metabolic modeling approaches enable us to successfully predict a variety of metabolic phenotypes , identifying the factors that determine microbial growth rate and the prediction of growth rates under various conditions is still an open challenge .", "Here we present a metabolic netwo...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Ubiquilin 1 Promotes IFN-γ-Induced Xenophagy of Mycobacterium tuberculosis	journal.ppat.1005076	null	[ [ "Mycobacterium tuberculosis ( Mtb ) infects one-third of the world’s population .", "It can remain dormant in its host for decades and ultimately kills more people than any other bacteria .", "Mtb survives within macrophages by preventing its own delivery to the degradative , phagolysosomal compartmen...	[ "The success of Mycobacterium tuberculosis ( Mtb ) as a pathogen rests upon its ability to grow intracellularly in macrophages .", "Interferon-gamma ( IFN-γ ) is critical in host defense against Mtb and stimulates macrophage clearance of Mtb through an autophagy pathway .", "Here we show that the host protein u...	[ "More people die from Mycobacterium tuberculosis ( Mtb ) , the causative agent of tuberculosis ( TB ) , than any other bacterial pathogen .", "It has long been appreciated that Mtb can survive and divide within macrophages , white blood cells that normally kill bacteria .", "Macrophages are able to partially co...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "typhus", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "respiratory infections", "immunology", "social sciences", "pulmonology", "social geography", "health care", "bacterial diseases", "signs and symptoms", "patien...	Hospitalisations and outpatient visits for undifferentiated fever attributable to scrub typhus in rural South India: Retrospective cohort and nested case-control study	journal.pntd.0007160	null	[ [ "Scrub typhus is a febrile illness caused by Orientia tsutsugamushi , a bacterial species belonging to the genus Orientia ( family Rickettsiaceae ) [1] .", "The infection is transmitted by the larvae ( chiggers ) of trombiculid mites which infect mammals as incidental hosts [2] .", "Scrub typhus occur...	[ "The burden of scrub typhus in endemic areas is poorly understood .", "This study aimed at estimating the proportion of hospitalisations and outpatient visits for undifferentiated fever in the community that may be attributable to scrub typhus .", "The study was a retrospective cohort with a nested case-control...	[ "Scrub typhus is an important cause of fever in many Asian countries , including China , India , Vietnam and Japan .", "It is caused by the intra-cellular bacteria Orientia tsutsugamushi and is transmitted to humans by mite larvae ( chiggers ) which attach to the skin of the host .", "Scrub typhus is potentiall...	2019
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "biotechnology", "xenopus laevis", "microbiology", "animal models", "developmental biology", "model organisms", "morphogenesis", "biology", "mouse", "evolutionary genetics", "drug discovery", "systems biology", "yeast and fungal models", "saccharomyces cerevisiae", "evolutionary biology"...	Evolutionarily Repurposed Networks Reveal the Well-Known Antifungal Drug Thiabendazole to Be a Novel Vascular Disrupting Agent	journal.pbio.1001379	Analysis of a genetic module repurposed between yeast and vertebrates reveals that a common antifungal medication is also a potent vascular disrupting agent.	[ [ "Systems biology has shown great promise in providing a better understanding of human disease and in identifying new disease targets .", "These methods typically leave off once the target is identified , and further research transitions to established paradigms for drug discovery .", "However , the va...	[ "Studies in diverse organisms have revealed a surprising depth to the evolutionary conservation of genetic modules .", "For example , a systematic analysis of such conserved modules has recently shown that genes in yeast that maintain cell walls have been repurposed in vertebrates to regulate vein and artery grow...	[ "Yeast cells and vertebrate blood vessels would not seem to have much in common .", "However , we have discovered that during the course of evolution , a group of proteins whose function in yeast is to maintain cell walls has found an alternative use in vertebrates regulating angiogenesis .", "This remarkable r...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "fungal genomics", "functional genomics", "fungal genetics", "genetics", "biology and life sciences", "genomics" ]	Pooled Segregant Sequencing Reveals Genetic Determinants of Yeast Pseudohyphal Growth	journal.pgen.1004570	null	[ [ "The budding yeast Saccharomyces cerevisiae undergoes a pronounced growth transition in response to nitrogen limitation or glucose limitation , forming multicellular pseudohyphal filaments that can spread outward from a colony and/or invade the surface of a solid growth substrate [1] , [2] .", "Yeast pseu...	[ "The pseudohyphal growth response is a dramatic morphological transition and presumed foraging mechanism wherein yeast cells form invasive and surface-spread multicellular filaments .", "Pseudohyphal growth has been studied extensively as a model of conserved signaling pathways controlling stress responses , cell...	[ "Cellular processes in eukaryotes are brought about through the contributions of large gene sets , and a continuing obstacle in studying these processes lies in the identification of critical constituent genes .", "The yeast pseudohyphal growth transition is an important example of a complex cellular growth trans...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	An Optimal Free Energy Dissipation Strategy of the MinCDE Oscillator in Regulating Symmetric Bacterial Cell Division	journal.pcbi.1004351	null	[ [ "Similar to man-made systems that commonly employ sustained oscillations to measure time and length , living organisms use molecular oscillators to process spatiotemporal information for regulation .", "For example , the periodic pole-to-pole oscillation of Min proteins in Escherichia coli designates the ...	[ "Sustained molecular oscillations are ubiquitous in biology .", "The obtained oscillatory patterns provide vital functions as timekeepers , pacemakers and spacemarkers .", "Models based on control theory have been introduced to explain how specific oscillatory behaviors stem from protein interaction feedbacks ,...	[ "This paper presents a unique dissipation mode of converting biochemical free energy in ATP to regulatory function through the MinCDE bio-oscillator that marks the mid-cell position for symmetric bacterial cell division .", "Through assessing the oscillator’s performance-to-cost relation , we demonstrate that som...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "none", "computational biology" ]	Query-Dependent Banding (QDB) for Faster RNA Similarity Searches	journal.pcbi.0030056	null	[ [ "Many functional RNAs conserve a base-paired secondary structure .", "Conserved RNA secondary structure induces long-distance pairwise correlations in homologous RNA sequences .", "When performing database searches to identify homologous structural RNAs , it is desirable for RNA similarity search prog...	[ "When searching sequence databases for RNAs , it is desirable to score both primary sequence and RNA secondary structure similarity .", "Covariance models ( CMs ) are probabilistic models well-suited for RNA similarity search applications .", "However , the computational complexity of CM dynamic programming ali...	[ "Database similarity searching is the sine qua non of computational molecular biology .", "Well-known and powerful methods exist for primary sequence searches , such as Blast and profile hidden Markov models .", "However , for RNA analysis , biologists rely not only on primary sequence but also on conserved RNA...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "gastroenterology and hepatology", "immunology", "microbiology", "drosophila", "eubacteria" ]	A Model of Bacterial Intestinal Infections in Drosophila melanogaster	journal.ppat.0030173	null	[ [ "A major arm of the Drosophila host defense against microbial infections is the systemic humoral response that consists primarily of the massive synthesis and release of potent antimicrobial peptides ( AMPs ) by cells of the fat body ( reviewed in [1 , 2] ) .", "The role of these AMPs in fighting infectio...	[ "Serratia marcescens is an entomopathogenic bacterium that opportunistically infects a wide range of hosts , including humans .", "In a model of septic injury , if directly introduced into the body cavity of Drosophila , this pathogen is insensitive to the host's systemic immune response and kills flies in a day ...	[ "The gut is a crucial interface of the host with its environment and represents an important portal of entry for pathogens .", "Here , we have developed a novel model of intestinal infections in the genetic model organism Drosophila melanogaster using the potent entomopathogen bacterium Serratia marcescens .", ...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "ecology and environmental sciences", "medicine and health sciences", "pathology and laboratory medicine", "microbiology", "viral structure", "signs and symptoms", "aquatic environments", "microscopy", "fresh water", "centrifugation", "research and analysis methods", "separation processes", ...	Structure of the Macrobrachium rosenbergii nodavirus: A new genus within the Nodaviridae?	journal.pbio.3000038	Macrobrachium rosenbergii nodavirus (MrNV) is an economically important pathogen of freshwater prawns. Determination of the structure of the MrNV virion by cryo-electron microscopy reveals a capsid protein that is highly divergent from other known nodaviruses but has a surprising resemblance to plant-infecting tombusvi...	[ [ "The giant freshwater prawn M . rosenbergii is widely cultivated in tropical and subtropical areas for food .", "The global production of this species has increased dramatically from about 3 , 000 tons in 1980 to more than 220 , 000 tons in 2014 [1] .", "However , productivity is threatened by white-t...	[ "Macrobrachium rosenbergii nodavirus ( MrNV ) is a pathogen of freshwater prawns that poses a threat to food security and causes significant economic losses in the aquaculture industries of many developing nations .", "A detailed understanding of the MrNV virion structure will inform the development of strategies...	[ "The freshwater prawn Macrobrachium rosenbergii is widely cultivated for food .", "Production is threatened by Macrobrachium rosenbergii nodavirus ( MrNV ) , the causative agent of white-tail disease .", "Outbreaks in hatcheries often result in mortality rates of up to 100% in larvae and post-larvae , leading t...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "evidence-based healthcare/clinical decision-making", "pathology/neuropathology", "infectious diseases/neglected tropical diseases", "neurological disorders/infectious diseases of the nervous system", "immunology/immune response", "dermatology/skin infections", "public health and epidemiology/infectious...	Preventing Nerve Function Impairment in Leprosy: Validation and Updating of a Prediction Rule	journal.pntd.0000283	null	[ [ "Preventing permanent disabilities due to nerve function impairment ( NFI ) [1] remains a major concern in leprosy control .", "Mycobacterium leprae , the causative agent of leprosy , infiltrates Schwann cells of peripheral nerve fibers [2] .", "Subsequently , the nerve fibers can be damaged by accumu...	[ "To validate and update a prediction rule for estimating the risk of leprosy-related nerve function impairment ( NFI ) .", "Prospective cohort using routinely collected data , in which we determined the discriminative ability of a previously published rule and an updated rule with a concordance statistic ( c ) ."...	[ "Leprosy is caused by a bacterium that attacks the peripheral nerves .", "This may cause nerve function impairment ( NFI ) , resulting in handicaps and disabilities .", "Therefore , prediction and prevention of NFI is extremely important in the management of leprosy .", "In 2000 , a prediction rule for NFI wa...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/animal genetics", "genetics and genomics/gene discovery", "molecular biology/transcription initiation and activation", "genetics and genomics/gene expression", "developmental biology/aging", "developmental biology/cell differentiation", "molecul...	ETS-4 Is a Transcriptional Regulator of Life Span in Caenorhabditis elegans	journal.pgen.1001125	null	[ [ "The emerging picture from studies with model organisms is that animal life span is regulated by coordination of gene regulatory networks in response to environmental inputs .", "In C . elegans a number of transcription factors function as genetic modifiers of aging , including Forkhead ( DAF-16 and PHA-4...	[ "Aging is a complex phenotype responsive to a plethora of environmental inputs; yet only a limited number of transcriptional regulators are known to influence life span .", "How the downstream expression programs mediated by these factors ( or others ) are coordinated into common or distinct set of aging effector...	[ "Animal life span is regulated in response to developmental and environmental inputs through coordinate changes in gene expression .", "Thus , longevity determinants include DNA-binding proteins that regulate gene expression by controlling transcription .", "Here , we explored the physiological role of the tran...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection	journal.ppat.1005201	null	[ [ "The infecting HIV genome integrates into host chromatin where , transcriptionally silent and unaffected by antiretroviral therapy ( ART ) , it represents a major challenge towards efforts to eradicate infection [1] .", "Virologic latency is defined as durable , quiescent infection from which replication-...	[ "Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection .", "Despite low or lack of CD4 receptor expression on Vδ2 T cells , infection of these cells has previously been reported .", "We found that upregulation of the CD4 receptor may render primary ...	[ "Antiretroviral therapy ( ART ) has led to a decreased HIV-related morbidity and mortality across the world .", "While successful ART restores health , it does not cure infection as latent HIV-1 remains integrated within different cell populations , unaffected by ART .", "To date resting memory CD4+ T cells are...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systemic lupus erythematosus", "medicine", "rheumatology", "genome analysis tools", "genomics", "x chromosome inactivation", "immune cells", "b cells", "chromosome biology", "genome scans", "monocytes", "genetics", "t cells", "epigenetics", "immunology", "biology", "dna modification...	Genome-Wide DNA Methylation Analysis of Systemic Lupus Erythematosus Reveals Persistent Hypomethylation of Interferon Genes and Compositional Changes to CD4+ T-cell Populations	journal.pgen.1003678	null	[ [ "Systemic lupus erythematosus ( SLE ) is a complex autoimmune disease characterized by an impaired clearance of apoptotic cells , the production of auto-antibodies against nuclear antigens , and the deposition of immune complexes that lead to tissue damage in multiple organs .", "SLE patients suffer from ...	[ "Systemic lupus erythematosus ( SLE ) is an autoimmune disease with known genetic , epigenetic , and environmental risk factors .", "To assess the role of DNA methylation in SLE , we collected CD4+ T-cells , CD19+ B-cells , and CD14+ monocytes from 49 SLE patients and 58 controls , and performed genome-wide DNA m...	[ "We have analyzed DNA methylation , an epigenetic modification that influences gene expression , in lupus patients and control subjects .", "Our analysis was run in three different immune cell types , T-cells , B-cells , and monocytes , to discern common epigenetic effects in lupus from cell type-specific effects...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Infection-Induced Retrotransposon-Derived Noncoding RNAs Enhance Herpesviral Gene Expression via the NF-κB Pathway	journal.ppat.1005260	null	[ [ "While only ~1 . 5% of mammalian genomes consist of protein coding sequence , upwards of 75% of the genome is transcribed [1 , 2] .", "A considerable amount of this transcription generates stable non-protein-coding RNAs ( ncRNAs ) of potential biological relevance .", "Similarly , transcription from t...	[ "Short interspersed nuclear elements ( SINEs ) are highly abundant , RNA polymerase III-transcribed noncoding retrotransposons that are silenced in somatic cells but activated during certain stresses including viral infection .", "How these induced SINE RNAs impact the host-pathogen interaction is unknown .", "...	[ "Short interspersed nuclear elements ( SINEs ) are noncoding mobile genetic elements that are present at ~106 copies per mammalian genome , roughly comprising 10% of mammalian genomic real estate .", "SINEs are typically transcriptionally silenced , though in some cases viral infection can promote their expressio...	2015
[ "Introduction", "Methods", "Results/Discussion" ]	[]	A Network Approach to Analyzing Highly Recombinant Malaria Parasite Genes	journal.pcbi.1003268	null	[ [ "The human malaria parasite Plasmodium falciparum causes approximately 1 million deaths each year , primarily in young children in sub-Saharan Africa [1] .", "In endemic regions , individuals develop clinical immunity to severe disease in childhood , but continue to suffer malaria infections and mild illn...	[ "The var genes of the human malaria parasite Plasmodium falciparum present a challenge to population geneticists due to their extreme diversity , which is generated by high rates of recombination .", "These genes encode a primary antigen protein called PfEMP1 , which is expressed on the surface of infected red bl...	[ "The human malaria parasite kills nearly 1 million people each year globally .", "Frequent genetic exchange between malaria parasites creates enormous genetic diversity that largely explains the lack of an effective vaccine for the disease .", "Traditional phylogenetic tools cannot accommodate this type of dive...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "medicine and health sciences", "neurochemistry", "sleep", "dopaminergics", "neuroscience", "animals", "biomechanics", "biological locomotion", "animal models", "physiological processes", "drosophila melanogaster", "model organisms", "experimental organism systems", "chr...	Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function	journal.pgen.1006507	null	[ [ "Circadian clocks are ubiquitous in the living world , driving rhythms at many levels , from the molecular to the behavioral [1] .", "The main defining characteristics of these clocks are that:", "( i ) they are self-sustained , ticking for many days in constant external conditions ,", "( ii ) the...	[ "Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity .", "In many organisms , oxidative stress and aging negatively impact the circadian system and sleep .", "Conversely , loss of the clock decreases resistance to oxidative stress , and may redu...	[ "Circadian clocks are highly conserved from flies to humans .", "They control rhythms in most physiological functions , with free-running periods close to 24 h .", "Clock disruption , as occurs in shift-work or jet lag , is increasingly suspected to reduce healthspan .", "Aging and neurodegenerative disorders...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	A Gene Family Derived from Transposable Elements during Early Angiosperm Evolution Has Reproductive Fitness Benefits in Arabidopsis thaliana	journal.pgen.1002931	null	[ [ "Recent technological advances have enabled the sequencing of hundreds of eukaryotic genomes , emphasizing that protein-coding genes constitute only a small fraction of the DNA [1] , [2] .", "Since then , attention has increasingly shifted to deciphering other parts of the genome , the so-called non-codin...	[ "The benefits of ever-growing numbers of sequenced eukaryotic genomes will not be fully realized until we learn to decipher vast stretches of noncoding DNA , largely composed of transposable elements .", "Transposable elements persist through self-replication , but some genes once encoded by transposable elements...	[ "The genomes of complex organisms are mostly made up not of ordinary genes but of transposable elements .", "Transposable elements have been called “selfish DNA” because they normally persist by copying themselves , not by helping the organism to survive or reproduce .", "Yet transposable elements can help orga...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "virology", "plant pathogens", "plant pathology", "viral replication complex", "biology", "microbiology", "viral replication" ]	The SNARE Protein Syp71 Is Essential for Turnip Mosaic Virus Infection by Mediating Fusion of Virus-Induced Vesicles with Chloroplasts	journal.ppat.1003378	null	[ [ "The host endomembrane system directly contributes to the formation of virus-induced membrane-bound virus factory for positive-strand RNA virus replication [1] , [2] .", "Depending on the virus , membranes from distinct cellular organelles such as the endoplasmic reticulum ( ER ) , chloroplast , mitochond...	[ "All positive-strand RNA viruses induce the biogenesis of cytoplasmic membrane-bound virus factories for viral genome multiplication .", "We have previously demonstrated that upon plant potyvirus infection , the potyviral 6K2 integral membrane protein induces the formation of ER-derived replication vesicles that ...	[ "Potyviruses constitute the largest group of known plant viruses which includes many agriculturally important viruses .", "Like all other positive-strand RNA viruses , potyviruses induce the cytoplasmic membranous-bound virus factory for viral genome multiplication .", "But the mechanism by which such a factory...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "reproductive system", "microbiology", "vertebrates", "animals", "mammals", "fibroblasts", "epithelial cells", "animal models", "developmental biology", "model organisms", "immunoprecipitation", "connective tissue cells", "molecular biology techniques", "r...	A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus	journal.ppat.1005755	null	[ [ "Human cytomegalovirus ( HCMV or Human herpesvirus 5 ) is a member of the Betaherpesvirinae genus and encodes over 165 genes [1] .", "Viral infection is largely asymptomatic in healthy individual but establishes a lifelong mainly latent state in the host .", "However , infection of an immune compromis...	[ "In human cytomegalovirus ( HCMV ) , tropism to epithelial and endothelial cells is dependent upon a pentameric complex ( PC ) .", "Given the structure of the placenta , the PC is potentially an important neutralizing antibody target antigen against congenital infection .", "The guinea pig is the only small ani...	[ "Congenital CMV is a leading cause of mental retardation and deafness in newborns .", "An effective vaccine against congenital CMV remains an elusive goal .", "HCMV encodes a pentameric glycoprotein complex ( PC ) necessary for tropism to epithelial , endothelial and myeloid cells .", "Given the structure of ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Accession Numbers" ]	[ "eubacteria", "eukaryotes", "computational biology" ]	Detecting Coevolution in and among Protein Domains	journal.pcbi.0030211	null	[ [ "Coevolution is prevalent at species , organismic , and molecular levels .", "At the molecular level , selective constraints operate on the entire system , which often require coordinated changes of its components .", "The most well-known example is the compensatory substitution of nucleic acid pairs ...	[ "Correlated changes of nucleic or amino acids have provided strong information about the structures and interactions of molecules .", "Despite the rich literature in coevolutionary sequence analysis , previous methods often have to trade off between generality , simplicity , phylogenetic information , and specifi...	[ "The sequences of different components within and across genes often undergo coordinated changes in order to maintain the structures or functions of the genes .", "Identifying the coordinated changes—the “coevolution”—of those components in the context of evolution is important in predicting the structures , inte...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "respiratory medicine/copd and allied disorders", "genetics and genomics/gene discovery", "respiratory medicine/lung cancer" ]	A Genome-Wide Association Study in Chronic Obstructive Pulmonary Disease (COPD): Identification of Two Major Susceptibility Loci	journal.pgen.1000421	null	[ [ "COPD is expected to be the third leading cause of worldwide mortality and the fifth leading cause of morbidity by the year 2020 [1] .", "Cigarette smoking is the major risk factor for COPD but smokers show considerable variation in their risk of developing airflow obstruction .", "Familial aggregatio...	[ "There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease ( COPD ) .", "The only known genetic risk factor is severe deficiency of α1-antitrypsin , which is present in 1–2% of individuals with COPD .", "We conducted a genome-wide association study ( GWA...	[ "There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease ( COPD ) , which is a heritable multi-factorial trait .", "Identifying the genetic determinants of COPD risk will have tremendous public health importance .", "This study describes the first geno...	2009
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "mus (mouse)", "immunology", "plasmodium" ]	Malaria Impairs T Cell Clustering and Immune Priming despite Normal Signal 1 from Dendritic Cells	journal.ppat.0030143	null	[ [ "The activation of a protective and highly specific immune response requires a system that can survey , decipher , and quickly respond to infection in an appropriate manner .", "Dendritic cells ( DCs ) participate in all of these important activities , and upon detection of a “danger signal” , rapidly mat...	[ "Interactions between antigen-presenting dendritic cells ( DCs ) and T cells are essential for the induction of an immune response .", "However , during malaria infection , DC function is compromised and immune responses against parasite and heterologous antigens are reduced .", "Here , we demonstrate that mala...	[ "Malaria is a major infectious disease , affecting 500 million people and causing 2 . 7 million deaths each year .", "The severity of malaria is , in part , due to the failure of the host immune system to effectively clear an infection and generate protective immunity .", "Dendritic cells ( DCs ) are central to...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chromosomal inheritance", "phenotypes", "heredity", "gene identification and analysis", "genetics", "molecular genetics", "biology", "genetics and genomics", "gene function" ]	HAL-2 Promotes Homologous Pairing during Caenorhabditis elegans Meiosis by Antagonizing Inhibitory Effects of Synaptonemal Complex Precursors	journal.pgen.1002880	null	[ [ "Generation of haploid gametes during sexual reproduction depends critically on the ability of homologous chromosomes to identify and form pairwise associations with their appropriate partners .", "Pairing is essential to enable homologs to orient and segregate away from each other at the meiosis I divisi...	[ "During meiosis , chromosomes align with their homologous pairing partners and stabilize this alignment through assembly of the synaptonemal complex ( SC ) .", "Since the SC assembles cooperatively yet is indifferent to homology , pairing and SC assembly must be tightly coordinated .", "We identify HAL-2 as a k...	[ "For successful segregation of homologous chromosomes during sexual reproduction , homologs must first identify and pair with their correct partners .", "Further , many organisms stabilize and maintain alignment between paired homologs through assembly of a highly ordered structure known as the synaptonemal compl...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "cell death", "medicine and health sciences", "immune cells", "immunology", "cell processes", "cell differentiation", "immune receptor signaling", "developmental biology", "membrane receptor signaling", "research and analysis methods", "white blood cells", ...	Ebola virus glycoprotein directly triggers T lymphocyte death despite of the lack of infection	journal.ppat.1006397	null	[ [ "Ebola virus ( EBOV ) is one of the deadliest pathogens known to exist as evidenced by the latest outbreak in West Africa that resulted in more than 28 , 000 confirmed and suspected infections including more than 11 , 000 fatalities [1] .", "Currently , experimental EBOV candidate vaccines and monoclonal ...	[ "Fatal outcomes of Ebola virus ( EBOV ) infections are typically preceded by a ‘sepsis-like’ syndrome and lymphopenia despite T cells being resistant to Ebola infection .", "The mechanisms that lead to T lymphocytes death remain largely unknown; however , the degree of lymphopenia is highly correlative with fatal...	[ "The latest outbreak of Ebola virus ( EBOV ) in West Africa resulted in more than 28 , 000 human infections including more than 11 , 000 deaths thus highlighting the necessity for the development of countermeasures .", "Monocytes and dendritic cells are among the primary targets of EBOV infection; infection of th...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Relative Risk of Visceral Leishmaniasis in Brazil: A Spatial Analysis in Urban Area	journal.pntd.0002540	null	[ [ "Visceral leishmaniasis ( VL ) is a vector-borne disease highly influenced by social and environmental factors .", "The majority ( >90% ) of cases is concentrated in six countries: Bangladesh , Brazil , Ethiopia , India , Nepal and Sudan [1] .", "In Brazil , the VL is caused by Leishmania infantum , b...	[ "Visceral leishmaniasis ( VL ) is a vector-borne disease whose factors involved in transmission are poorly understood , especially in more urban and densely populated counties .", "In Brazil , the VL urbanization is a challenge for the control program .", "The goals were to identify the greater risk areas for h...	[ "Visceral leishmaniasis ( VL ) is a vector-borne disease whose factors involved in transmission are poorly understood , especially in more urban and densely populated counties .", "In Brazil , the increasing occurrence of human VL cases in urban centers is a challenge for the control program .", "We aimed to id...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology", "mathematics", "computational biology", "evolutionary biology", "biophysics", "genetics and genomics" ]	Canalization of Gene Expression in the Drosophila Blastoderm by Gap Gene Cross Regulation	journal.pbio.1000049	DuringDrosophila development, the expression patterns of gap genes are much less variable than the Bicoid morphogen gradient. Modeling and experiments show that this specific instance of canalization or developmental robustness occurs by gap gene cross regulation.	[ [ "C . H . Waddington inferred developmental canalization of gene expression by noting that differentiation leads to the formation of discrete types of tissue , rather than a continuous blend , and that genotypic and environmental variation is suppressed at the phenotypic level in wild-type but not mutant organ...	[ "Developing embryos exhibit a robust capability to reduce phenotypic variations that occur naturally or as a result of experimental manipulation .", "This reduction in variation occurs by an epigenetic mechanism called canalization , a phenomenon which has resisted understanding because of a lack of necessary mol...	[ "Animals have an astonishing ability to develop reliably in spite of variable conditions during embryogenesis .", "More than 60 years ago , it was proposed that this property of development , called canalization , results from genetic interactions that adjust biochemical reactions so as to bring about reliable ou...	2009
[ "Introduction", "Methods", "Results/Discussion" ]	[ "none", "computational biology" ]	A Computational Approach to the Functional Screening of Genomes	journal.pcbi.0030174	null	[ [ "The search for LUCA , the Last Unknown Common Ancestor , is an open problem in evolutionary theory , which has been addressed using many different approaches .", "After the completion of several bacterial genomes , some authors tried to infer a possible minimal genome ruling out of non essential genes fr...	[ "Comparative genomics usually involves managing the functional aspects of genomes , by simply comparing gene-by-gene functions .", "Following this approach , Mushegian and Koonin proposed a hypothetical minimal genome , Minimal Gene Set ( MGS ) , aiming for a possible oldest ancestor genome .", "They obtained M...	[ "The origins of life represent a fascinating problem that has been addressed using different approaches and a wide variety of technologies .", "A theoretical approach consists of inferring a possible oldest ancestor genome from a well-defined comparison of current ones .", "A crucial problem concerns the valida...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/disease models", "developmental biology/aging", "neurological disorders/cognitive neurology and dementia" ]	Insulin Signaling and Dietary Restriction Differentially Influence the Decline of Learning and Memory with Age	journal.pbio.1000372	Novel C. elegans associative learning and memory assays reveal that insulin/IGF-1 signaling and dietary restriction pathways differentially maintain age-related memory decline by influencing expression levels of the transcription factor CREB.	[ [ "A guiding proposition of longevity research is that treatments that extend survival will also be generally beneficial to the health of the organism .", "However , many specifics of this concept remain to be tested .", "In humans , aging is often accompanied by declines in cognitive function .", "...	[ "Of all the age-related declines , memory loss is one of the most devastating .", "While conditions that increase longevity have been identified , the effects of these longevity-promoting factors on learning and memory are unknown .", "Here we show that the C . elegans Insulin/IGF-1 receptor mutant daf-2 improv...	[ "In humans , aging is often associated with a decline in cognitive function .", "Progress toward an understanding of the molecular mechanisms underlying the initiation and progression of age-related neuronal decline could be hastened by the development of experimental systems that quickly test early and true symp...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "t helper cells", "medicine and health sciences", "immune cells", "microbiome", "immunology", "cell-mediated immunity", "microbiology", "parasitic diseases", "microbial genomics", "digestive system", "white blood cells", "animal cells", "medical microbiology", "gene expres...	TPL-2 restricts Ccl24-dependent immunity to Heligmosomoides polygyrus	journal.ppat.1006536	null	[ [ "Heligmosomoides polygyrus is a natural murine intestinal helminth , used to model chronic human helminth infections .", "Resistance to H . polygyrus is mediated by genetic strain specific responses [1] , as well as protective immune mechanisms attributed to the strength of the type-2 immune response [2] ...	[ "TPL-2 ( COT , MAP3K8 ) kinase activates the MEK1/2-ERK1/2 MAPK signaling pathway in innate immune responses following TLR , TNFR1 and IL-1R stimulation .", "TPL-2 contributes to type-1/Th17-mediated autoimmunity and control of intracellular pathogens .", "We recently demonstrated TPL-2 reduces severe airway al...	[ "Helminth infections remain a huge global burden , causing significant morbidity in both animals and humans .", "Morbidity and recurring infections are associated with limited access to anthelmintic drugs .", "While vaccination remains the best available solution to treat helminthiasis , mechanisms of natural o...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "immunology", "tropical diseases", "microbiology", "parasitic diseases", "protozoan life cycles", "parasitic protozoans", "developmental biology", "protozoans", "pharm...	EAPB0503: An Imiquimod analog with potent in vitro activity against cutaneous leishmaniasis caused by Leishmania major and Leishmania tropica	journal.pntd.0006854	null	[ [ "Cutaneous leishmaniasis ( CL ) is caused by Leishmania parasite and is classified by the World Health Organization ( WHO ) as one of the most common neglected tropical diseases [1] .", "During the past decade , an alarming increase in the incidence of CL was documented , ranging from 2 . 1 million cases ...	[ "Cutaneous Leishmaniasis ( CL ) is a parasitic infection classified by the WHO as one of the most uncontrolled spreading neglected diseases .", "Syria is endemic for Leishmania tropica and Leishmania major , causing CL in the Eastern Mediterranean .", "The large-scale displacement of Syrian refugees exacerbated...	[ "Cutaneous Leishmaniasis ( CL ) is a parasitic infection caused by Leishmania ( L . ) parasites .", "In the Old World and the Near East , CL is mainly caused by L . major and L . tropica .", "The ongoing Syrian war and the resulting massive population displacement led to an alarming increase in the incidence of...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	LAB-1 Targets PP1 and Restricts Aurora B Kinase upon Entrance into Meiosis to Promote Sister Chromatid Cohesion	journal.pbio.1001378	At the onset of the first meiotic division, the protein LAB-1 recruits the PP1 phosphatase to cohesion complexes, preventing Aurora B kinase from targeting cohesins for degradation prematurely and thereby ensuring proper progression of meiotic events in C. elegans.	[ [ "Timely establishment and subsequent removal of Sister Chromatid Cohesion ( SCC ) between sister chromatids is necessary to facilitate faithful segregation of chromosomes in mitosis and meiosis .", "Failure to correctly segregate chromosomes in either mitosis or meiosis has been associated with tumorigene...	[ "Successful execution of the meiotic program depends on the timely establishment and removal of sister chromatid cohesion .", "LAB-1 has been proposed to act in the latter by preventing the premature removal of the meiosis-specific cohesin REC-8 at metaphase I in C . elegans , yet the mechanism and scope of LAB-1...	[ "A critical step for achieving successful cell division is the regulation of how the cohesin complexes that bind sister chromatids are initially deposited , then maintained , and finally removed to allow the chromatids to separate into daughter cells .", "This is particularly challenging during meiosis , when the...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "action potentials", "medicine and health sciences", "chemical compounds", "applied mathematics", "membrane potential", "fibrosis", "electrophysiology", "genetic algorithms", "neuroscience", "simulation and modeling", "algorithms", "developmental biology", "probability distribution", "math...	Modeling an Excitable Biosynthetic Tissue with Inherent Variability for Paired Computational-Experimental Studies	journal.pcbi.1005342	null	[ [ "One of the major challenges in the field of cardiac electrophysiology is quantifying the electrical dynamics of myocytes in the context of their environment .", "The electrical activity of cardiomyocytes in vivo is modulated by the other excitable and unexcitable cells to which they are coupled , as well...	[ "To understand how excitable tissues give rise to arrhythmias , it is crucially necessary to understand the electrical dynamics of cells in the context of their environment .", "Multicellular monolayer cultures have proven useful for investigating arrhythmias and other conduction anomalies , and because of their ...	[ "One of the major challenges in trying to understand how arrhythmias can form in cardiac tissue is studying how the electrical activity of cardiac cells is affected by their surroundings .", "Current approaches have focused on studying cardiac cells in vitro and using computational models to elucidate the mechani...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "body fluids", "pathology and laboratory medicine", "enzyme-linked immunoassays", "pathogens", "cell processes", "immunology", "microbiology", "pulmonology", "pneumonia", "sepsis", "signs and symptoms", "immunologic technique...	PSGL-1 on Leukocytes is a Critical Component of the Host Immune Response against Invasive Pneumococcal Disease	journal.ppat.1005500	null	[ [ "Streptococcus pneumoniae ( pneumococcus ) is one of the major causes of invasive disease accounting for more deaths than any other vaccine-preventable bacterial infection .", "This microorganism colonizes the human nasopharynx , being one of the leading causes of acute otitis media , community-acquired p...	[ "Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such as Streptococcus pneumoniae .", "A major role of the P-selectin glycoprotein ligand-1 ( PSGL-1 ) on leukocytes against invasive pneumococcal disease is described in this study .", "Phagocytosis experiments using d...	[ "S . pneumoniae is one of the most important and devastating human pathogens worldwide , mainly affecting young children , elderly people and immunocompromised patients .", "In terms of host immune defense against invasive pneumococcal isolates , professional phagocytes require receptor-mediated recognition of ce...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "danio (zebrafish)", "computational biology", "neuroscience" ]	Topological Reorganization of Odor Representations in the Olfactory Bulb	journal.pbio.0050178	Two-photon calcium imaging in the zebrafish olfactory bulb reveals that mitral cells show more selective responses to odors than interneurons, and odor-evoked firing patterns of populations of mitral cells evolve over hundreds of milliseconds to become more distinct for different odors, thus providing more information ...	[ [ "The brain continuously processes patterns of sensory input to extract relevant information about the environment .", "In most or even all sensory systems , afferent activity patterns exhibit a topological organization in which defined stimulus variables are mapped along spatial coordinates in the brain ....	[ "Odors are initially represented in the olfactory bulb ( OB ) by patterns of sensory input across the array of glomeruli .", "Although activated glomeruli are often widely distributed , glomeruli responding to stimuli sharing molecular features tend to be loosely clustered and thus establish a fractured chemotopi...	[ "Many sensory brain areas contain topographic maps where the physical location of neuronal activity contains information about a stimulus feature .", "In the first central processing center of the olfactory pathway , the olfactory bulb , chemically distinct odors often elicit spatially segregated input activity s...	2007
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "schistosoma", "invertebrates", "schistosoma mansoni", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "helminths", "immunology", "parasitic diseases", "animals", "developmental biology", "molecular development", ...	Species dependent impact of helminth-derived antigens on human macrophages infected with Mycobacterium tuberculosis: Direct effect on the innate anti-mycobacterial response	journal.pntd.0005390	null	[ [ "Infection with helminth parasites and microbial pathogens present very different challenges to the mammalian immune system , and distinct immune effector mechanisms have evolved to combat infection with these different classes of organisms .", "Typically , infection with microbial pathogens requires the ...	[ "In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome .", "While Mycobacterium tuberculosis ( Mtb ) gives rise to a pro-inflammatory Th1 response , a Th2 response is typical of helminth infections .", "A strong Th2 response has bee...	[ "The innate immune system is the first response against invading pathogens like the bacterium Mycobacterium tuberculosis ( Mtb ) or parasitic worms ( helminths ) .", "The adaptive immune response takes over after being primed by the innate immune response .", "Infection with Mycobacterium tuberculosis typically...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "chemical biology/protein chemistry and proteomics", "neuroscience", "genetics and genomics/functional genomics" ]	Genome-Wide Analyses Reveal a Role for Peptide Hormones in Planarian Germline Development	journal.pbio.1000509	Genomic/peptidomic analyses of the planarian Schmidtea mediterranea identifies >200 neuropeptides and uncovers a conserved neuropeptide required for proper maturation and maintenance of the reproductive system.	[ [ "Platyhelminthes ( flatworms ) inhabit a variety of aquatic and terrestrial environments and members of the phylum are thought to parasitize most vertebrate species [1] .", "The remarkable ability of flatworms to maintain plasticity in their reproductive cycles is a key to their success .", "As an exa...	[ "Bioactive peptides ( i . e . , neuropeptides or peptide hormones ) represent the largest class of cell-cell signaling molecules in metazoans and are potent regulators of neural and physiological function .", "In vertebrates , peptide hormones play an integral role in endocrine signaling between the brain and the...	[ "Flatworms cause diseases affecting hundreds of millions of people , so understanding what influences their reproductive activity is of fundamental importance .", "Neurally derived signals have been suggested to coordinate sexual reproduction in free-living flatworms , yet the neuroendocrine signaling repertoire ...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "clinical laboratory sciences", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "microbiology", "neuroscience", "artificial neural networks", "viruses", "diarrhea", "filoviruses", "mathematics", "forecasting", "statistic...	Transforming Clinical Data into Actionable Prognosis Models: Machine-Learning Framework and Field-Deployable App to Predict Outcome of Ebola Patients	journal.pntd.0004549	null	[ [ "The 2014–15 EVD outbreak in West Africa has eclipsed in magnitude all combined past EVD outbreaks since the disease was first identified in 1976 [1] .", "As of February 17 , 2016 ( http://www . cdc . gov/vhf/ebola/outbreaks/2014-west-africa/case-counts . html ) , a total of 28 , 639 cases have been repor...	[ "Assessment of the response to the 2014–15 Ebola outbreak indicates the need for innovations in data collection , sharing , and use to improve case detection and treatment .", "Here we introduce a Machine Learning pipeline for Ebola Virus Disease ( EVD ) prognosis prediction , which packages the best models into ...	[ "We introduce a machine-learning framework and field-deployable app to predict outcome of Ebola patients from their initial clinical symptoms .", "Recent work from other authors also points out to the clinical factors that can be used to better understand patient prognosis , but there is currently no predictive m...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "cell walls", "chemical compounds", "phosphates", "caulobacter", "cell cycle and cell division", "cell processes", "cell polarity", "materials science", "cellular structures and organelles", "bacteria", "macromolecules", "polymers", "polymer chemistry", "chemistry", ...	A specialized MreB-dependent cell wall biosynthetic complex mediates the formation of stalk-specific peptidoglycan in Caulobacter crescentus	journal.pgen.1007897	null	[ [ "The shape of most bacteria is determined by a cell wall made of peptidoglycan ( PG ) , a mesh-like heteropolymer that surrounds the cytoplasmic membrane and provides resistance against the internal osmotic pressure [1 , 2] .", "The backbone of PG is formed by strands of alternating N-acetylglucosamine ( ...	[ "Many bacteria have complex cell shapes , but the mechanisms producing their distinctive morphologies are still poorly understood .", "Caulobacter crescentus , for instance , exhibits a stalk-like extension that carries an adhesive holdfast mediating surface attachment .", "This structure forms through zonal pe...	[ "Bacteria show a variety of different cell shapes that are critical for survival in the environmental niche they inhabit .", "While the mechanisms generating the prototypic rod-shaped and coccoid morphologies have been studied intensively , only little is known about the processes that underlie the formation of m...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "antigen processing and recognition", "entomology", "dengue fever", "neglected tropical diseases", "immunology", "biology", "arboviral infections", "zoology", "infectious disease control", "immune response", "immunoglobulins" ]	First Attempt To Validate Human IgG Antibody Response to Nterm-34kDa Salivary Peptide as Biomarker for Evaluating Exposure to Aedes aegypti Bites	journal.pntd.0001905	null	[ [ "Numerous mosquito species of the genus Aedes ( Dipteria: Culicidae ) are vectors of major ( re ) -emerging human arboviruses , such as Dengue and Chikungunya .", "Aedes aegypti species is the primary vector of these diseases worldwide .", "No effective treatment and vaccine are currently available an...	[ "Much effort is being devoted for developing new indicators to evaluate the human exposure to Aedes mosquito bites and the risk of arbovirus transmission .", "Human antibody ( Ab ) responses to mosquito salivary components could represent a promising tool for evaluating the human-vector contact .", "To develop ...	[ "Aedes aegypti mosquito is the primary vector of major ( re ) -emerging human arboviruses , such as Dengue and Chikungunya .", "In absence of effective treatment and vaccine , the evaluation of human exposure to vector bites is crucial to estimate the risk of the viruses' transmission .", "Currently , exposure ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Survival of the Replication Checkpoint Deficient Cells Requires MUS81-RAD52 Function	journal.pgen.1003910	null	[ [ "Faithful completion of DNA replication and accurate transmission of the genetic information to daughter cells is of paramount importance .", "To ensure genome integrity , cells have evolved a sophisticated mechanism that supervises the replication process , the replication checkpoint [1] .", "Replica...	[ "In checkpoint-deficient cells , DNA double-strand breaks ( DSBs ) are produced during replication by the structure-specific endonuclease MUS81 .", "The mechanism underlying MUS81-dependent cleavage , and the effect on chromosome integrity and viability of checkpoint deficient cells is only partly understood , es...	[ "The replication checkpoint ensures a smooth duplication of the genome .", "It counteracts the replication stress , which can cause chromosome rearrangements as found in most tumours .", "Given the importance of dealing with perturbed replication , and since in tumours secondary mutations or epigenetic changes ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "circuit models", "computational neuroscience", "olfactory system", "biology", "sensory systems", "neuroscience", "coding mechanisms" ]	Sparse Distributed Representation of Odors in a Large-scale Olfactory Bulb Circuit	journal.pcbi.1003014	null	[ [ "Lateral inhibition is one of the critical mechanisms underlying responses to sensory neurons [1] , but the detailed mechanisms at the network level in the olfactory system are not clear [e . g . 2] .", "In the Limulus eye [1] and the cat retina [3] it mediates contrast enhancement between areas of differ...	[ "In the olfactory bulb , lateral inhibition mediated by granule cells has been suggested to modulate the timing of mitral cell firing , thereby shaping the representation of input odorants .", "Current experimental techniques , however , do not enable a clear study of how the mitral-granule cell network sculpts o...	[ "In the paper we address the role of lateral inhibition in a neuronal network .", "It is an essential and widespread mechanism of neural processing that has been demonstrated in many brain systems .", "A key finding that would reveal how and to what extent it can modulate input signals and give rise to some for...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell motility", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "molecular probe techniques", "pathogens", "immunology", "microbiology", "directed cell migration", "salmonellosis", "bacterial diseases", "developmental biology", "enteroba...	Salmonella Typhimurium effector SseI inhibits chemotaxis and increases host cell survival by deamidation of heterotrimeric Gi proteins	journal.ppat.1007248	null	[ [ "Salmonella enterica serovars are pathogenic bacteria that cause severe diseases ranging from enteric fever ( e . g . by Salmonella Typhi ) to gastroenteritis and bacteraemia caused by non-typhoidal Salmonella ( NTS ) .", "Salmonella Typhimurium , the model organism of NTS infection , has a broad host spe...	[ "Salmonella enterica serotype Typhimurium ( S . Typhimurium ) is one of the most frequent causes of food-borne illness in humans and usually associated with acute self-limiting gastroenteritis .", "However , in immunocompromised patients , the pathogen can disseminate and lead to severe systemic diseases .", "S...	[ "Salmonella Typhimurium is one of the most common causes of gastroenteritis in humans .", "In immunocompromised patients , the pathogen can cause systemic infections .", "Crucial virulence factors are encoded on two Salmonella pathogenicity islands SPI-1 and SPI-2 .", "While SPI-1 encodes virulence factors es...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "luciferase", "molecular probe techniques", "enzymes", "enzymology", "immunoblotting", "plasmid construction", "signal inhibition", "immunoprecipitation", "dna construction", "molecular biology techniques", "research and analysis methods", "proteins", "oxidoreductases", ...	Vaccinia Virus Protein C6 Inhibits Type I IFN Signalling in the Nucleus and Binds to the Transactivation Domain of STAT2	journal.ppat.1005955	null	[ [ "The innate immune response is the first line of defense against invading pathogens .", "Interferons ( IFNs ) are one of the key players in this early response to infection and are particularly important to protect against viruses , as can be seen by the increased susceptibility of IFNα/β receptor ( IFNAR...	[ "The type I interferon ( IFN ) response is a crucial innate immune signalling pathway required for defense against viral infection .", "Accordingly , the great majority of mammalian viruses possess means to inhibit this important host immune response .", "Here we show that vaccinia virus ( VACV ) strain Western...	[ "In response to a viral infection , infected host cells mount an early , innate immune response to limit viral replication and spread .", "Type I interferons ( IFNs ) are produced by a cell when a viral infection is detected and are a crucial aspect of this early immune response .", "IFNs are released from the ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "epidemiology", "biology", "microbiology", "parasitology" ]	Soil-Transmitted Helminth Infections and Nutritional Status in School-age Children from Rural Communities in Honduras	journal.pntd.0002378	null	[ [ "Honduras is among 30 countries in the Americas that are endemic for soil-transmitted helminth ( STH ) infections , which are caused by four species of intestinal nematodes: the common roundworm , Ascaris lumbricoides; the whipworm , Trichuris trichiura; and the hookworms , Necator americanus and Ancylostoma ...	[ "Soil-transmitted helminth ( STH ) infections are endemic in Honduras and efforts are underway to decrease their transmission .", "However , current evidence is lacking in regards to their prevalence , intensity and their impact on children's health .", "To evaluate the prevalence and intensity of STH infection...	[ "Soil-transmitted helminth ( STH ) infections are endemic in Honduras but their impact on children's health is not well studied .", "With the purpose of determining the prevalence and intensity of STH infections and their association with nutritional status in a sample of Honduran children , a cross-sectional stu...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cryptococcosis", "cryptococcus neoformans", "medicine and health sciences", "cryptococcus", "immune cells", "pathology and laboratory medicine", "respiratory infections", "pathogens", "immunology", "microbiology", "pulmonology", "animal models", "fungi", "model organisms"...	Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans	journal.ppat.1007627	null	[ [ "The ubiquitous encapsulated yeast Cryptococcus neoformans causes invasive fungal infections in immunocompromised patients , particularly those with AIDS , solid organ transplants , and cancer [1] .", "Even with optimal combination antifungal therapy , cryptococcosis has a high morbidity and mortality rat...	[ "Cryptococcus neoformans is a leading cause of invasive fungal infections among immunocompromised patients .", "However , the cellular constituents of the innate immune response that promote clearance versus progression of infection upon respiratory acquisition of C . neoformans remain poorly defined .", "In th...	[ "Cryptococcus neoformans is a fungus that is prevalent throughout the environment and can cause a fatal infection of the central nervous system when inhaled into the lungs by patients with impaired immune systems .", "Our understanding of the immune responses that either help clear C . neoformans from the lungs o...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "chemical properties", "physics", "biochemistry", "lipids", "computational chemistry", "transmembrane proteins", "protein interactions", "molecular dynamics", "biochemistry simulations", "proteins", "biophysic al simulations", "dimerization", "statistical mechanics", "chemistry", "transm...	The Free Energy Landscape of Dimerization of a Membrane Protein, NanC	journal.pcbi.1003417	null	[ [ "Cellular membranes not only separate the contents of a cell from its surroundings , they also play a key role in cell regulation and metabolism .", "Accounting for approximately a quarter of the coding regions of an organism's genome [1] , membrane proteins control the transport of solutes between a cell...	[ "Membrane proteins are frequently present in crowded environments , which favour lateral association and , on occasions , two-dimensional crystallization .", "To better understand the non-specific lateral association of a membrane protein we have characterized the free energy landscape for the dimerization of a b...	[ "Cells are surrounded by selectively-permeable bilayer membranes , enabling the cell to control its internal environment .", "Embedded within these membranes are a variety of membrane proteins , many of which facilitate this environmental control and are integral to numerous metabolic processes .", "Their locat...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "immune system proteins", "proteins", "immunity", "innate immunity", "protein structure", "vector biology", "immunology", "biology", "microbiology", "anopheles", "host-pathogen interaction" ]	Molecular Basis for Genetic Resistance of Anopheles gambiae to Plasmodium: Structural Analysis of TEP1 Susceptible and Resistant Alleles	journal.ppat.1002958	null	[ [ "Thioester-containing proteins ( TEPs ) are a major component of the innate immune response of insects to invasion by bacteria and protozoa [1] , [2] .", "Anopheles gambiae thioester-containing protein 1 ( TEP1 ) is a complement-like protein that plays a central role in the opsonization of gram-negative b...	[ "Thioester-containing protein 1 ( TEP1 ) is a central component in the innate immune response of Anopheles gambiae to Plasmodium infection .", "Two classes of TEP1 alleles , TEP1S and TEP1R , are found in both laboratory strains and wild isolates , related by a greater or lesser susceptibility , respectively to...	[ "Anopheles mosquitoes transmit malaria , the world's most devastating parasitic disease , of which Anopheles gambiae is the principal vector for malaria in Sub-Saharan Africa .", "Different populations of mosquitoes vary widely in how readily they become infected with malaria parasites , while some strains do not...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "medicine and health sciences", "kinesins", "microtubules", "muscle tissue", "geometry", "animals", "aspect ratio", "simulation and modeling", "animal models", "drosophila melanogaster", "model organisms", "systems science", "mathematics", "molecular motors", "experime...	Mechanical positioning of multiple nuclei in muscle cells	journal.pcbi.1006208	null	[ [ "One of the fundamental challenges of cell biology is to define principles of spatial organization of the cell [1] , and , in particular , to unravel the mechanisms that control the position , size , and shape of organelles .", "The nucleus is the principal organelle and organizational center of eukaryoti...	[ "Many types of large cells have multiple nuclei .", "In skeletal muscle fibers , the nuclei are distributed along the cell to maximize their internuclear distances .", "This myonuclear positioning is crucial for cell function .", "Although microtubules , microtubule associated proteins , and motors have been ...	[ "How the cell organizes its interior is one of the fundamental biological questions , but the principles of organelles’ positioning remains largely unclear .", "In this study we use computational modeling and image analysis to elucidate mechanisms of positioning of multiple nuclei in muscle cells .", "We start ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell growth and division", "cell biology", "developmental biology/morphogenesis and cell biology", "cell biology/cell signaling" ]	Ligand-Independent Traffic of Notch Buffers Activated Armadillo in Drosophila	journal.pbio.1000169	Full-length Notch receptor binds to the Wnt pathway effector β-catenin and mediates its endocytosis and degradation, demonstrating a novel mechanism by which Notch may modulate Wnt pathway activity.	[ [ "The Notch gene of Drosophila encodes a member of a family of conserved single transmembrane receptors with key tasks in the information processing activity of animal cells [1]–[4] .", "They are involved in a wide variety of processes during development but their best characterized function is in the proc...	[ "Notch receptors act as ligand-dependent membrane-tethered transcription factors with a prominent role in binary cell fate decisions during development , which is conserved across species .", "In addition there is increasing evidence for other functions of Notch , particularly in connection with Wnt signalling: N...	[ "Establishment of the correct shape and pattern of tissues within an organism requires the integration of molecular information present in signalling and transcriptional networks and demands delicate exchanges and balances of their activities .", "A large body of experimental work has revealed close correlations ...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "infectious diseases/tropical and travel-associated diseases", "infectious diseases/neglected tropical diseases" ]	A Coproantigen Diagnostic Test for Strongyloides Infection	journal.pntd.0000955	null	[ [ "The diagnosis of gastrointestinal infections typically relies on either empirical clinical diagnosis , or demonstration of the pathogen using standard microbiological techniques .", "However , a number of important gastrointestinal pathogens are difficult to detect using such techniques , and in some of ...	[ "Accurate diagnosis of infection with the parasite Strongyloides stercoralis is hampered by the low concentration of larvae in stool , rendering parasitological diagnosis insensitive .", "Even if the more sensitive agar plate culture method is used repeated stool sampling is necessary to achieve satisfactory sens...	[ "Strongyloides stercoralis is almost unique among human nematode infections in its ability to replicate within a patient's body , potentially leading to life-long infections if left untreated .", "Given the potential for severe life threatening Strongyloides infections and the unsatisfactory results of current pa...	2011

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