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[ "Introduction", "Results", "Discussion" ]
[ "vertebrates", "teleost fishes", "neuroscience", "computational biology" ]
Synaptic Plasticity Can Produce and Enhance Direction Selectivity
journal.pcbi.0040032
null
[ [ "Control of animal behavior often requires the discrimination of the direction of movement of sensory images .", "In some behaviors , including tracking [1–5] and postural balance [6–9] , animals must determine the direction of sensory slip to generate appropriate compensatory movements to stabilize the s...
[ "The discrimination of the direction of movement of sensory images is critical to the control of many animal behaviors .", "We propose a parsimonious model of motion processing that generates direction selective responses using short-term synaptic depression and can reproduce salient features of direction selecti...
[ "Short-term synaptic plasticity is ubiquitous in brain circuits , but its function in sensorimotor processing remains unclear .", "We propose a parsimonious model of motion processing using short-term depression to produce directionally selective responses .", "In the model circuit , information from two spatia...
2008
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "cancer genetics", "immune cells", "mechanisms of signal transduction", "gene regulation", "immunology", "epigenetics", "molecular genetics", "gene expression", "biology", "dna modification", "immune response", "signal transduction", "monocytes", "genetics", "molecular cell biology", "...
Inflammation-Mediated Genetic and Epigenetic Alterations Drive Cancer Development in the Neighboring Epithelium upon Stromal Abrogation of TGF-β Signaling
journal.pgen.1003251
null
[ [ "Mounting evidence supports a cross talk between epithelial and stromal cells in cancer progression mediated by paracrine signals and extracellular matrix components [1] , [2] .", "For example , in a prostate cancer model , epithelial tumor progression induces loss of p53 function in stromal fibroblasts [...
[ "Deletion of tumor suppressor genes in stromal fibroblasts induces epithelial cancer development , suggesting an important role of stroma in epithelial homoeostasis .", "However , the underlying mechanisms remain to be elucidated .", "Here we report that deletion of the gene encoding TGFβ receptor 2 ( Tgfbr2 ) ...
[ "Cancer is no longer regarded as a problem of solely cancer cells .", "The development and metastasis of cancers clearly involves many aspects of the host .", "We sought to identify the molecular mechanisms underlying epithelial cancer development due to alterations in stromal cells .", "Using an animal model...
2013
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "vaccines", "preventive medicine", "viruses", "clinical medicine", "signs and symptoms", "rna viruses", "neglected tropical diseases", "pha...
Dengue illness index—A tool to characterize the subjective dengue illness experience
journal.pntd.0006593
null
[ [ "Interventional efficacy trials need to prospectively define criteria for what constitutes a “case” of dengue .", "Defining what will and will not be considered a “case” is not a simple task .", "It encompasses a number of considerations and nuances .", "The definition must be objective and easily...
[ "Dengue virus infections are a major cause of febrile illness that significantly affects individual and societal productivity and drives up health care costs principally in the developing world .", "Two dengue vaccine candidates are in advanced clinical efficacy trials in Latin America and Asia , and another has ...
[ "The Dengue Illness Index ( DII ) is a tool that was developed to improve and standardize the measurement of vaccine and drug efficacy in reducing moderate dengue illness by capturing the overall subjective disease experience of an individual based on how the totality of their symptoms impacts their wellness and da...
2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[]
Cyclin G Functions as a Positive Regulator of Growth and Metabolism in Drosophila
journal.pgen.1005440
null
[ [ "The growth of an organism is a highly coordinated process regulated by a wide range of different inputs .", "Members of the Insulin receptor ( InR ) and Target of rapamycin ( TOR ) signaling pathways are well established key players in the control of cell growth in higher eumetazoa .", "Studies in di...
[ "In multicellular organisms , growth and proliferation is adjusted to nutritional conditions by a complex signaling network .", "The Insulin receptor/target of rapamycin ( InR/TOR ) signaling cascade plays a pivotal role in nutrient dependent growth regulation in Drosophila and mammals alike .", "Here we identi...
[ "Size and growth of an organism are adjusted to nutritional conditions by a complex regulatory network involving the Insulin receptor and TOR signaling cascades .", "Drosophila melanogaster has been used in the past as a genetically tractable model to unravel the complex circuitry by genetic means .", "We have ...
2015
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]
[ "biochemistry", "cell biology", "biophysics" ]
Insights into Mad2 Regulation in the Spindle Checkpoint Revealed by the Crystal Structure of the Symmetric Mad2 Dimer
journal.pbio.0060050
Analysis of the crystal structure and biochemical activity of the symmetric closed Mad2 dimer support a unified model for Mad1-assisted conformational activation of Mad2 in the spindle checkpoint.
[ [ "At the metaphase–anaphase transition , a multisubunit ubiquitin ligase called the anaphase-promoting complex or cyclosome ( APC/C ) in complex with its mitosis-specific activator Cdc20 mediates the ubiquitination of securin and cyclin B [1 , 2] .", "Degradation of securin and cyclin B activates separase ...
[ "In response to misaligned sister chromatids during mitosis , the spindle checkpoint protein Mad2 inhibits the anaphase-promoting complex or cyclosome ( APC/C ) through binding to its mitotic activator Cdc20 , thus delaying anaphase onset .", "Mad1 , an upstream regulator of Mad2 , forms a tight core complex with...
[ "Chromosome missegregation during mitosis results in the gain or loss of chromosomes in the next generation of cells and can contribute to birth defects or cancer .", "A cellular surveillance system called the spindle checkpoint ensures that accurate chromosome segregation occurs by inhibiting the activity of the...
2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[]
A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter
journal.pgen.1005581
null
[ [ "The use of capsule endoscopy and balloon endoscopy has provided a better understanding of the features of small bowel ulcers among various gastrointestinal disorders , such as Crohn’s disease ( CD ) , intestinal tuberculosis , and nonsteroidal anti-inflammatory drug ( NSAID ) –induced enteropathy [1 , 2] .",...
[ "Previously , we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine ( CNSU ) .", "By whole-exome sequencing in five Japanese patients with CNSU and one unaffected indivi...
[ "Advanced diagnostic innovations such as capsule endoscopy and balloon endoscopy have provided better understanding of endoscopic findings of small bowel diseases .", "However , it remains difficult to diagnose small intestinal diseases such as Crohn’s disease , intestinal tuberculosis , and nonsteroidal anti-inf...
2015
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "glycosylamines", "medicine and health sciences", "chemical compounds", "pathology and laboratory medicine", "split-decomposition method", "microbiology", "protozoan life cycles", "organic compounds", "parasitic protozoans", "purines", "multiple alignment calculation", "developmental biology",...
Characterization of a Novel Endoplasmic Reticulum Protein Involved in Tubercidin Resistance in Leishmania major
journal.pntd.0004972
null
[ [ "Leishmania spp .", "are the causative agents of leishmaniasis , a parasitic protozoan disease that affects 12 million people worldwide with an estimated annual incidence of approximately 1 million , including both visceral and cutaneous cases [1] .", "The leishmaniasis chemotherapy is complicated bec...
[ "Tubercidin ( TUB ) is a toxic adenosine analog with potential antiparasitic activity against Leishmania , with mechanism of action and resistance that are not completely understood .", "For understanding the mechanisms of action and identifying the potential metabolic pathways affected by this drug , we employed...
[ "The identification of genes associated with drug resistance has contributed for understanding of the mechanisms of action of compounds against Leishmania , as well as , in the identification of the resistance mechanisms mediated by the proteins encoded by these genes .", "Differently from the mammalian host , Le...
2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]
[ "medicine and health sciences", "body fluids", "african trypanosomiasis", "geographical locations", "tropical diseases", "uganda", "social sciences", "parasitic diseases", "parasitic protozoans", "social geography", "protozoans", "neglected tropical diseases", "infectious disease control", ...
Gambian human African trypanosomiasis in North West Uganda. Are we on course for the 2020 target?
journal.pntd.0007550
null
[ [ "Human African Trypanosomiasis ( HAT ) is caused by species of Trypanosoma brucei s . l . transmitted by tsetse flies , with case fatality rates believed to be close to 100% [1 , 2] .", "In East and Southern Africa Trypanosoma brucei rhodesiense causes Rhodesian HAT ( rHAT ) , an acute and zoonotic form o...
[ "In 1994 , combined active and passive screening reported 1469 cases from the historic Gambian Human African Trypanosomiasis ( gHAT ) foci of West Nile , Uganda .", "Since 2011 systematic active screening has stopped and there has been reliance on passive screening .", "During 2014 , passive screening alone det...
[ "The number of gHAT cases across West Nile , Uganda has declined in the last 20 years .", "This decline is due to the impact of programmes of active and passive case detection and treatment which have recently been combined with tsetse control operations ( post 2011 ) .", "We carried out an active survey of gHA...
2019
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "immunology/cellular microbiology and pathogenesis", "cell biology/cellular death and stress responses", "cell biology/morphogenesis and cell biology", "cell biology/cell growth and division", "cell biology", "infectious diseases/neglected tropical diseases", "cell biology/microbial growth and developme...
Antiangiogenic and Antitumor Effects of Trypanosoma cruzi Calreticulin
journal.pntd.0000730
null
[ [ "Chagas′ disease affects 16 million people in South America , with 14 . 000 deaths per year and 0 . 7 million disability-adjusted life-years [1] .", "T . cruzi has a variety of molecules that modulate several effector arms of the immune system [2] , calreticulin ( TcCRT ) being one of them [3] .", "Tc...
[ "In Latin America , 18 million people are infected with Trypanosoma cruzi , the agent of Chagas' disease , with the greatest economic burden .", "Vertebrate calreticulins ( CRT ) are multifunctional , intra- and extracellular proteins .", "In the endoplasmic reticulum ( ER ) they bind calcium and act as chapero...
[ "In Latin America , 18 million people are infected with Trypanosoma cruzi , a protozoan that causes Chagas' disease .", "Vertebrate calreticulins ( CRTs ) are multifunctional , intra- and extracellular calcium binding , chaperone proteins .", "Since human CRT ( HuCRT ) inhibits capillary growth ( angiogenesis )...
2010
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "physics", "systems biology", "developmental biology", "stem cells", "induced pluripotent stem cells", "embryonic stem cells", "biophysics theory", "regulatory networks", "biology", "computational biology", "biophysics simulations", "biophysics", "signaling networks" ]
Systematic Search for Recipes to Generate Induced Pluripotent Stem Cells
journal.pcbi.1002300
null
[ [ "Recent studies have shown that cellular reprogramming can be achieved by manipulating a small number of genes [1] , [2] .", "This includes the generation of induced pluripotent stem cells ( iPSCs ) from somatic cells [3]–[6] and the conversion of one differentiated cell type directly to another ( transdi...
[ "Generation of induced pluripotent stem cells ( iPSCs ) opens a new avenue in regenerative medicine .", "One of the major hurdles for therapeutic applications is to improve the efficiency of generating iPSCs and also to avoid the tumorigenicity , which requires searching for new reprogramming recipes .", "We pr...
[ "Converting somatic cells back to the stem cell state ( called induced pluripotent stem cells or iPSCs ) exemplifies the recent advancement of cellular reprogramming that holds great promise for developing regenerative medicine .", "Generation of iPSCs is often achieved by overexpressing three to four genes in so...
2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "microbiology/microbial evolution and genomics", "microbiology" ]
Ameobal Pathogen Mimivirus Infects Macrophages through Phagocytosis
journal.ppat.1000087
null
[ [ "Acanthamoeba polyphaga mimivirus ( APMV ) , isolated from amoebae cultures , was identified for the first time in 2003 in our laboratory [1] .", "This double-stranded DNA virus is classified in the Mimiviridae family [1] .", "AMPV is probably responsible for pneumonia as suggested in human pneumonia ...
[ "Mimivirus , or Acanthamoeba polyphaga mimivirus ( APMV ) , a giant double-stranded DNA virus that grows in amoeba , was identified for the first time in 2003 .", "Entry by phagocytosis within amoeba has been suggested but not demonstrated .", "We demonstrate here that APMV was internalized by macrophages but n...
[ "The giant ( 750 nm ) double-stranded DNA virus Acanthamoeba polyphaga mimivirus ( APMV ) is likely responsible for pneumonia .", "We demonstrate here that APMV was internalized by macrophages but not by non-phagocytic cells , leading to productive replication .", "We also show that APMV invaded macrophages thr...
2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "infectious diseases", "plant science", "medicine and health sciences", "population modeling", "infectious disease epidemiology", "epidemiology", "dengue fever", "travel-associated diseases", "plant pathology", "biology and life sciences", "spatial epidemiology", "infectious disease modeling",...
The Spatial Dynamics of Dengue Virus in Kamphaeng Phet, Thailand
journal.pntd.0003138
null
[ [ "Dengue remains a major public health concern throughout global tropical and subtropical regions .", "An estimated 390 million people are infected by the mosquito-borne virus each year , of which 96 million develop symptomatic disease [1] .", "Thailand , like most countries in Southeast Asia , has exp...
[ "Dengue is endemic to the rural province of Kamphaeng Phet , Northern Thailand .", "A decade of prospective cohort studies has provided important insights into the dengue viruses and their generated disease .", "However , as elsewhere , spatial dynamics of the pathogen remain poorly understood .", "In particu...
[ "Transmission of dengue virus has long been studied in Kamphaeng Phet , Northern Thailand , but how cases are related in time and space is still unclear , as is the role of human movement in generating these patterns .", "Because of these knowledge gaps , public health officials cannot make educated decisions on ...
2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "infectious diseases/bacterial infections", "infectious diseases/infectious diseases of the nervous system", "immunology/innate immunity" ]
Microglia Are Mediators of Borrelia burgdorferi–Induced Apoptosis in SH-SY5Y Neuronal Cells
journal.ppat.1000659
null
[ [ "Lyme borreliosis is the most prevalent vector-borne illness in the northern hemisphere [1] , [2] .", "Transmission from the animal reservoir to the human host occurs via an Ixodes tick bite into the skin , where B . burgdorferi , the spirochete that causes Lyme disease , can then disseminate hematogenous...
[ "Inflammation has long been implicated as a contributor to pathogenesis in many CNS illnesses , including Lyme neuroborreliosis .", "Borrelia burgdorferi is the spirochete that causes Lyme disease and it is known to potently induce the production of inflammatory mediators in a variety of cells .", "In experimen...
[ "Lyme disease , which is transmitted to humans through the bite of a tick , is currently the most frequently reported vector-borne illness in the northern hemisphere .", "Borrelia burgdorferi is the bacterium that causes Lyme disease and it is known to readily induce inflammation within a variety of infected tiss...
2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "diabetes mellitus", "medicine and health sciences", "diabetic endocrinology", "gene identification and analysis", "gene expression", "genetics", "endocrinology", "biology and life sciences", "metabolic disorders" ]
Genome Wide Meta-analysis Highlights the Role of Genetic Variation in RARRES2 in the Regulation of Circulating Serum Chemerin
journal.pgen.1004854
null
[ [ "Chemerin has been extensively studied as an adipokine associated with obesity and related phenotypes [1]–[4] .", "It is secreted from adipose tissue as an 18-kDa precursor protein which is activated by several extracellular cleavage steps [5]–[7] .", "The class of proteases responsible for the transf...
[ "Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue .", "Genetic factors determining chemerin release from adipose tissue are yet unknown .", "We conducted a meta-analysis of genome-wide association studies ( GWAS ) for serum chemerin in three independent cohorts from E...
[ "Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue .", "In the present study we show that circulating chemerin is a heritable trait .", "In a meta-analysis of genome-wide association studies ( GWAS ) of 2 , 791 individuals from Germany and Finland , we identified commo...
2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "model organisms", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]
Pch2 Acts through Xrs2 and Tel1/ATM to Modulate Interhomolog Bias and Checkpoint Function during Meiosis
journal.pgen.1002351
null
[ [ "Meiosis is a specialized cell division program to produce haploid gametes .", "To achieve faithful chromosome segregation during meiosis I ( MI ) , cells utilize meiotic recombination to establish physical connections through the formation of chiasmata or crossing-over at the DNA level between homologous...
[ "Proper segregation of chromosomes during meiosis requires the formation and repair of double-strand breaks ( DSBs ) to form crossovers .", "Repair is biased toward using the homolog as a substrate rather than the sister chromatid .", "Pch2 is a conserved member of the AAA+-ATPase family of proteins and is impl...
[ "Sexually reproductive organisms utilize meiosis to produce gametes ( e . g . egg and sperm ) .", "During meiosis , chromosome numbers reduce to half ( haploid ) and fertilization restores their numbers to a diploid state so that ploidy can be maintained throughout generations .", "Meiosis involves two successi...
2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[]
Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction
journal.pcbi.1004508
null
[ [ "Protein phosphorylation and dephosphorylation is an important means of protein regulation that occur in both prokaryotic and eukaryotic organisms [1–5] .", "Phosphorylation of a protein may result in a conformational change in its structure , recruitment of binding partners or change of localization , le...
[ "Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components .", "In this study , we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationsh...
[ "Despite their importance in the signaling transduction , there is no systematic effort in identifying and characterizing the scaffold proteins in humans .", "In this work , we predicted scaffold proteins by integrating the available protein-protein interactions and kinase-substrate relationships .", "The predi...
2015
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "disease mapping", "infectious diseases", "public health and epidemiology", "chagas disease", "epidemiology", "infectious disease epidemiology", "neglected tropical diseases", "infectious disease control", "transfusion medicine", "parasitic diseases", "hematology" ]
Seroprevalence of Chagas Infection in the Donor Population
journal.pntd.0001771
null
[ [ "Chagas Disease is a common and economically devastating disease of Latin America , with an estimated infected population of over 7 million and over 100 million at risk [1] .", "Despite the significant number of immigrants from Chagas-endemic regions , prevalence data outside of its countries of origin re...
[ "We retrospectively calculated the prevalence and epidemiologic characteristics of Chagas infection in the New York blood donor population over three years utilizing the New York Blood Center's database of the New York metropolitan area donor population .", "Seventy Trypanosoma cruzi positive donors were identifi...
[ "Chagas Disease is a common and economically devastating disease of Latin America , with millions infected and many more at risk of infection .", "The hallmark of Chagas Disease is a long asymptomatic latent period ( after an often tiny bug bite ) followed by potentially fatal cardiac or gastrointestinal sequelae...
2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "immune cells", "cytokines", "streptococci", "immunologic subspecialties", "immunity to infections", "immunology", "microbiology", "host-pathogen interaction", "adaptive immunity", "immune defense", "pulmonary immunology", "immunologic techniques", "bacterial pathogens", "t cells", "immu...
Experimental Human Pneumococcal Carriage Augments IL-17A-dependent T-cell Defence of the Lung
journal.ppat.1003274
null
[ [ "Nasopharyngeal colonisation with Streptococcus pneumoniae ( the pneumococcus ) peaks in prevalence at 2–3 years of age [1] and declines thereafter becoming 10% or less in adult-hood and undetectable in the elderly [2] .", "Perturbations in host defence and/or increased pneumococcal pathogenicity facilita...
[ "Pneumococcal carriage is both immunising and a pre-requisite for mucosal and systemic disease .", "Murine models of pneumococcal colonisation show that IL-17A-secreting CD4+ T-cells ( Th-17 cells ) are essential for clearance of pneumococci from the nasopharynx .", "Pneumococcal-responding IL-17A-secreting CD4...
[ "Pneumococcal carriage is an important step in the development of cellular and humoral pneumococcal immunity but paradoxically may lead to mucosal diseases such as pneumonia .", "The frequency of carriage and pneumonia in young healthy adults is very low despite frequent exposures suggesting the presence of appro...
2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[]
mTOR Directs Breast Morphogenesis through the PKC-alpha-Rac1 Signaling Axis
journal.pgen.1005291
null
[ [ "Post-natal mammary epithelial morphogenesis is a complex process during which an extensively branched ductal network develops from a rudimentary epithelial bud [1] .", "Branching morphogenesis is most active during puberty and is regulated by endocrine hormones and local paracrine interactions with mesen...
[ "Akt phosphorylation is a major driver of cell survival , motility , and proliferation in development and disease , causing increased interest in upstream regulators of Akt like mTOR complex 2 ( mTORC2 ) .", "We used genetic disruption of Rictor to impair mTORC2 activity in mouse mammary epithelia , which decreas...
[ "The protein kinase mTOR is frequently activated in breast cancers , where it enhances cancer cell growth , survival , and metastastic spread to distant organs .", "Thus , mTOR is an attractive , clinically relevant molecular target for drugs designed to treat metastatic breast cancers .", "However , mTOR exist...
2015
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "viral transmission and infection", "nervous system", "pathogens", "immunology", "microbiology", "viruses", "euthanasia", "rna viruses", "cytotoxic t cells", "viral load", "white blood cel...
STING is required for host defense against neuropathological West Nile virus infection
journal.ppat.1007899
null
[ [ "Encephalitic Flavivirus infections , including West Nile virus ( WNV ) , are ongoing or emerging threats to global health [1–4] .", "In particular , WNV continues to re-emerge in the Americas , causing neuropathology and death in the most severe cases [3 , 5–7] .", "Since its emergence in the USA in ...
[ "West Nile Virus ( WNV ) , an emerging and re-emerging RNA virus , is the leading source of arboviral encephalitic morbidity and mortality in the United States .", "WNV infections are acutely controlled by innate immunity in peripheral tissues outside of the central nervous system ( CNS ) but WNV can evade the ac...
[ "In recent years , outbreaks of emerging and re-emerging neuroinvasive West Nile virus ( WNV ) infection have brought about a critical need to understand host factors that restrict neuropathology and disease .", "WNV infection in humans typically is either asymptomatic or results in a mild febrile illness , but i...
2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "genome-wide association studies", "genetics", "biology", "human genetics", "genetics and genomics" ]
A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol
journal.pgen.1002333
null
[ [ "Serum lipids are important determinants of cardiovascular disease and related morbidity [1] .", "The heritability of circulating lipid levels is estimated to be 40%–60% and recent genome-wide association ( GWA ) studies implicated a total of 95 loci associated with serum high-density lipoprotein choleste...
[ "Recent genome-wide association ( GWA ) studies described 95 loci controlling serum lipid levels .", "These common variants explain ∼25% of the heritability of the phenotypes .", "To date , no unbiased screen for gene–environment interactions for circulating lipids has been reported .", "We screened for varia...
[ "Circulating serum lipids contribute greatly to the global health by affecting the risk for cardiovascular diseases .", "Serum lipid levels are partly inherited , and already 95 loci affecting high- and low-density lipoprotein cholesterol , total cholesterol , and triglycerides have been found .", "Serum lipids...
2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "ecology", "computational biology", "evolutionary biology" ]
Compilation and Network Analyses of Cambrian Food Webs
journal.pbio.0060102
Analyses of Chengjiang and Burgess Shale food-web data suggest that most, but not all, aspects of the trophic structure of modern ecosystems were in place over a half-billion years ago.
[ [ "Perhaps the most fundamental property of life is its ability to use energy and materials to maintain and reproduce itself , in turn providing energy and materials to support more life .", "This generation and consumption of biomass enabled the evolution of biological diversity and concomitant trophic str...
[ "A rich body of empirically grounded theory has developed about food webs—the networks of feeding relationships among species within habitats .", "However , detailed food-web data and analyses are lacking for ancient ecosystems , largely because of the low resolution of taxa coupled with uncertain and incomplete ...
[ "Food webs , which depict the networks of feeding interactions among co-occurring species , display many regularities in their structure .", "For example , the distributions of links to prey and links from predators , the percentages of omnivores and herbivores , and the mean trophic level of species change syste...
2008
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "gene regulation", "anatomy and physiology", "cadherins", "dna transcription", "animal models", "developmental biology", "model organisms", "molecular development", "skeletal development", "molecular genetics", "morphogenesis", "chromatin", "myocytes", "musculoskeletal system...
Deregulation of the Protocadherin Gene FAT1 Alters Muscle Shapes: Implications for the Pathogenesis of Facioscapulohumeral Dystrophy
journal.pgen.1003550
null
[ [ "Developmental genetics has provided considerable insight into the regulatory networks controlling overall skeletal muscle development .", "Perturbation of these common mechanisms is associated with congenital abnormalities of the muscle lineage as well as with later-onset muscle pathologies [1] .", "...
[ "Generation of skeletal muscles with forms adapted to their function is essential for normal movement .", "Muscle shape is patterned by the coordinated polarity of collectively migrating myoblasts .", "Constitutive inactivation of the protocadherin gene Fat1 uncoupled individual myoblast polarity within chains ...
[ "Facioscapulohumeral muscular dystrophy ( FSHD ) is a hereditary human myopathy affecting groups of skeletal muscles in the face and shoulders .", "Despite recent advances on the molecular cascade initiated by its main genetic cause , with identification of DUX4 as the main pathogenic agent , how this leads to th...
2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "medicine", "infectious diseases" ]
Comparative Analysis of Measures of Viral Reservoirs in HIV-1 Eradication Studies
journal.ppat.1003174
null
[ [ "Treatment of HIV-1 infection with highly active antiretroviral therapy ( HAART ) can reduce plasma HIV-1 RNA levels in treated patients to below the detection limit of clinical assays ( 50 copies of HIV-1 RNA/ml ) [1]–[3] .", "The effective suppression of viremia initially encouraged hopes that the virus...
[ "HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy ( HAART ) .", "The best characterized reservoir is a small , difficult-to-quantify pool of resting memory CD4+ T cells carrying latent but replication-competent viral genomes .", "Because strategies targeting...
[ "Efforts to cure HIV-1 infection have focused on a small pool of CD4+ T cells that carry viral genetic information in a latent form .", "These cells persist even in patients on optimal antiretroviral therapy .", "Novel therapeutic strategies targeting latently infected cells are being developed , and therefore ...
2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "medicine", "bacterial diseases", "infectious diseases", "biology", "microbiology", "viral diseases" ]
Regulation of Mycobacterium tuberculosis-Dependent HIV-1 Transcription Reveals a New Role for NFAT5 in the Toll-Like Receptor Pathway
journal.ppat.1002620
null
[ [ "Mycobacterium tuberculosis ( MTb ) , the causative agent of tuberculosis ( TB ) , is the most common co-infection and cause of death in patients infected with human immunodeficiency virus type 1 ( HIV-1 ) [1] , [2] .", "Direct engagement of pathogen recognition receptors ( PRRs ) by MTb on mononuclear ph...
[ "Tuberculosis ( TB ) disease in HIV co-infected patients contributes to increased mortality by activating innate and adaptive immune signaling cascades that stimulate HIV-1 replication , leading to an increase in viral load .", "Here , we demonstrate that silencing of the expression of the transcription factor nu...
[ "The major cause of AIDS deaths globally has been tuberculosis ( TB ) , which is caused by the bacterium Mycobacterium tuberculosis ( MTb ) .", "Co-infection with MTb exacerbates human immunodeficiency virus type1 ( HIV-1 ) replication and disease progression via both innate and adaptive host immune responses to ...
2012
[ "Introduction", "Results and Discussion", "Materials and Methods" ]
[ "invertebrates", "ultraviolet radiation", "population genetics", "light", "animals", "invertebrate genomics", "electromagnetic radiation", "animal models", "dna damage", "developmental biology", "drosophila melanogaster", "model organisms", "dna", "population biology", "embryos", "dros...
The Adaptive Significance of Natural Genetic Variation in the DNA Damage Response of Drosophila melanogaster
journal.pgen.1005869
null
[ [ "One of the promises of population genomic analyses is that , when combined with genome annotation , it can provide a rich source of hypotheses regarding the manifold ways in which selection may modify biological function .", "Because these hypotheses are relatively agnostic with regard to our preconceive...
[ "Despite decades of work , our understanding of the distribution of fitness effects of segregating genetic variants in natural populations remains largely incomplete .", "One form of selection that can maintain genetic variation is spatially varying selection , such as that leading to latitudinal clines .", "Wh...
[ "Understanding how genetic and phenotypic diversity are generated and maintained in natural populations is a central question in biology .", "Latitudinal clines in D . melanogaster represent a model system for investigating the biological and population genetic basis for local adaptation .", "Recent technologic...
2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]
[ "biogeography", "parasite groups", "medicine and health sciences", "ecology and environmental sciences", "plasmodium", "population genetics", "tropical diseases", "parasitic diseases", "parasitic protozoans", "parasitology", "genetic mapping", "apicomplexa", "protozoans", "population biolo...
Limited differentiation among Plasmodium vivax populations from the northwest and to the south Pacific Coast of Colombia: A malaria corridor?
journal.pntd.0007310
null
[ [ "Malaria elimination is a public health priority .", "Yet , regardless of a notable reduction in the global malaria burden , more than 40% of the world’s population remains at risk of infection [1] .", "Although endemic areas of South America historically have had low to moderate malaria transmission ...
[ "Malaria remains endemic in several countries of South America with low to moderate transmission intensity .", "Regional human migration through underserved endemic areas may be responsible for significant parasite dispersion making the disease resilient to interventions .", "Thus , the genetic characterization...
[ "The regional movements of infected individuals that connect suitable transmission areas make malaria resilient to control efforts .", "Those movements are expected to leave genetic signatures in the parasite populations that can be detected using analytical tools .", "In this study , the genetic makeups of Pla...
2019
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "infectious diseases", "giardiasis", "neglected tropical diseases", "biology", "microbiology", "parasitic diseases", "parasitology" ]
Detection of Giardia duodenalis Assemblages A and B in Human Feces by Simple, Assemblage-Specific PCR Assays
journal.pntd.0001776
null
[ [ "Giardia duodenalis is an important cause of diarrhea in humans worldwide and is responsible for an estimated 2 . 8×108 cases per year [1] .", "The infection is transmitted by the fecal-oral route through ingestion of infective cysts .", "The prevalence of the infection is higher in developing countri...
[ "The flagellated protozoan Giardia duodenalis is a common gastrointestinal parasite of mammals , including humans .", "Molecular characterizations have shown the existence of eight genetic groups ( or assemblages ) in the G . duodenalis species complex .", "Human infections are caused by assemblages A and B , w...
[ "Giardia duodenalis is an important cause of diarrhoea in humans worldwide , even if the burden of infection is higher in developing countries where the poor sanitary conditions favour the contamination of water and food with infective cysts .", "The parasite is considered as a species complex that comprises at l...
2012
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "algorithms", "computerized simulations", "computer science", "computer modeling", "computational neuroscience", "single neuron function", "biology", "computational biology", "sensory systems", "neuroscience" ]
Models of Neocortical Layer 5b Pyramidal Cells Capturing a Wide Range of Dendritic and Perisomatic Active Properties
journal.pcbi.1002107
null
[ [ "Neocortical pyramidal cells in layer 5 ( L5 PCs ) are important input-output units in the cortical column .", "Their dendrites span the entire column , thus receiving input from all six layers , and the cells provide the major output from the column to various parts of the brain .", "These cells are ...
[ "The thick-tufted layer 5b pyramidal cell extends its dendritic tree to all six layers of the mammalian neocortex and serves as a major building block for the cortical column .", "L5b pyramidal cells have been the subject of extensive experimental and modeling studies , yet conductance-based models of these cells...
[ "The pyramidal cell of layer 5b in the mammalian neocortex extends its dendritic tree to all six layers of cortex , thus receiving inputs from the entire cortical column and supplying the major output of the column to other brain areas .", "L5b pyramidal cells have been the subject of extensive experimental and m...
2011
[ "Introduction", "Results", "Discussion", "Conclusions", "Methods" ]
[ "biotechnology", "genomic library construction", "sequence assembly tools", "plant science", "phylogenetic analysis", "genome analysis", "crops", "plant genomics", "dna construction", "molecular biology techniques", "plants", "research and analysis methods", "sequence analysis", "crop scie...
The Jujube Genome Provides Insights into Genome Evolution and the Domestication of Sweetness/Acidity Taste in Fruit Trees
journal.pgen.1006433
null
[ [ "Chinese jujube ( Ziziphus jujuba Mill . ) ( 2n = 2x = 24 ) , native to China , is one of the oldest cultivated fruit trees , with more than 7 , 000 years of domestication history [1] .", "It belongs to the Rhamnaceae family in the Rosales order .", "Jujube is valued as a woody crop and traditional he...
[ "Jujube ( Ziziphus jujuba Mill . ) belongs to the Rhamnaceae family and is a popular fruit tree species with immense economic and nutritional value .", "Here , we report a draft genome of the dry jujube cultivar ‘Junzao’ and the genome resequencing of 31 geographically diverse accessions of cultivated and wild ju...
[ "A balanced sweetness and acidity taste is among the most important characteristics of fruits .", "It is generally believed that human selection of sweetness plays a crucial role in the process of domestication from wild to cultivated fruit trees .", "However , the molecular mechanisms underlying fruit taste do...
2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]
[ "blood cells", "phosphorylation", "innate immune system", "medicine and health sciences", "immune cells", "enzyme-linked immunoassays", "immune physiology", "cytokines", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "developmental biology", "protozoans", ...
Trypanosoma cruzi-specific IFN-γ-producing cells in chronic Chagas disease associate with a functional IL-7/IL-7R axis
journal.pntd.0006998
null
[ [ "Chagas disease is a major health problem in Latin America and an increasing threat in other countries that are non-endemic for Trypanosoma cruzi infection [1–4] .", "The relevance of T cell-mediated immunity in controlling T . cruzi infection has been demonstrated in human T . cruzi infections and in exp...
[ "The severity of cardiac disease in chronic Chagas disease patients is associated with different features of T-cell exhaustion .", "Here , we assessed whether the ability of T cells to secrete IFN-γ in response to T . cruzi was linked to disruption in immune homeostasis and inflammation in patients with chronic C...
[ "Mechanisms of acquired immune response against Trypanosoma cruzi antigens include both humoral and cellular components that might be critical in a chronic infection .", "Through a vast number of studies , several groups have postulated that , similar to other chronic infections , T-cell responses in chronic Tryp...
2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "viruses", "infectious diseases", "virology", "immunology", "homo (human)", "insects" ]
The Mannose Receptor Mediates Dengue Virus Infection of Macrophages
journal.ppat.0040017
null
[ [ "Dengue is the most prevalent mosquito-borne viral disease worldwide and in the past 40 years has undergone a global resurgence such that almost half the world's population are currently living at risk in dengue-endemic areas [1] .", "There is a spectrum of disease severity following dengue virus ( DV ) i...
[ "Macrophages ( MØ ) and mononuclear phagocytes are major targets of infection by dengue virus ( DV ) , a mosquito-borne flavivirus that can cause haemorrhagic fever in humans .", "To our knowledge , we show for the first time that the MØ mannose receptor ( MR ) binds to all four serotypes of DV and specifically t...
[ "Dengue disease and its severe manifestations are a growing public health concern , with a third to half the world's population living in dengue-endemic areas .", "In recent years there have been significant advances in understanding dengue virus ( DV ) interactions with target cells such as macrophages , dendrit...
2008
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "spleen", "immunology", "microbiology", "animal models", "developmental biology", "model organisms", "experimental organism systems", "molecular development", "cytotox...
Cytotoxic effector functions of T cells are not required for protective immunity against fatal Rickettsia typhi infection in a murine model of infection: Role of TH1 and TH17 cytokines in protection and pathology
journal.pntd.0005404
null
[ [ "Rickettsioses are emerging febrile diseases that can be fatal and are caused by obligate intracellular bacteria of the family of Rickettsiaceae .", "This family consists of two genera: Orientia with only one member ( Orientia tsutsugamushi ) and Rickettsia ( R . ) that is further subdivided into four gro...
[ "Endemic typhus caused by Rickettsia ( R . ) typhi is an emerging febrile disease that can be fatal due to multiple organ pathology .", "Here we analyzed the requirements for protection against R . typhi by T cells in the CB17 SCID model of infection .", "BALB/c wild-type mice generate CD4+ TH1 and cytotoxic CD...
[ "Rickettsia typhi causes endemic typhus , a relatively mild disease .", "However , complications such as encephalitis , hepatitis , pneumonia and others can occur in severe cases .", "In immunodeficient CB17 SCID mice R . typhi causes a 100% fatal infection and we show here that adoptively transferred CD8+ as w...
2017
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "infectious diseases/helminth infections" ]
Alcoholism and Strongyloides stercoralis: Daily Ethanol Ingestion Has a Positive Correlation with the Frequency of Strongyloides Larvae in the Stools
journal.pntd.0000717
null
[ [ "The presence of Strongyloides stercoralis larvae was reported to be higher in the stools of chronic alcoholics than in the stools of nonalcoholic patients at the same hospital in two different studies in Brazil ( in Uberlândia , MG [1] and in Vitória , ES [2] ) .", "The association of ethanol abuse and S...
[ "Significantly higher prevalence of Strongyloides stercoralis has been reported in chronic alcoholic patients .", "The aim of this investigation was to report the prevalence of Strongyloides larvae in stools of chronic alcoholic patients with known daily ethanol intake .", "From January 2001 through December 20...
[ "It has been reported that Strongyloides stercoralis infection is more prevalent in chronic alcoholic patients than in non alcoholics living in the same country .", "In a retrospective study on the prevalence of S . stercoralis infection in a large sample of alcoholic patients , we demonstrate that this prevalenc...
2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "parastic protozoans", "medicine", "infectious diseases", "test evaluation", "diagnostic medicine", "leishmania", "leishmaniasis", "neglected tropical diseases", "protozoology", "biology", "microbiology", "parasitic diseases" ]
A FRET-Based Real-Time PCR Assay to Identify the Main Causal Agents of New World Tegumentary Leishmaniasis
journal.pntd.0001956
null
[ [ "The leishmaniases are a globally widespread group of vector-borne diseases that are endemic to 88 countries and affect an estimated 12 million people , with approximately 350 million people at risk worldwide [1] .", "Depending on the parasite species and host genetic background , infection can range from...
[ "In South America , various species of Leishmania are endemic and cause New World tegumentary leishmaniasis ( NWTL ) .", "The correct identification of these species is critical for adequate clinical management and surveillance activities .", "We developed a real-time polymerase chain reaction ( PCR ) assay and...
[ "Leishmaniasis is a neglected disease with more than two million new human infections annually worldwide .", "Tegumentary leishmaniasis , cutaneous and mucocutaneous , is mainly caused by five Leishmania species of the Viannia complex in South America .", "Different species can cause disease with similar sympto...
2013
[ "Introduction", "Methods", "Results", "Discussion" ]
[]
Streptococcus suis Meningitis: A Systematic Review and Meta-analysis
journal.pntd.0004191
null
[ [ "Bacterial meningitis is a severe infectious disease with a high mortality and morbidity .", "The estimated incidence is 2 . 6–6 per 100 , 000 adults per year in developed countries and several times higher in low-income settings [1] .", "Most pathogens causing bacterial meningitis are transmitted bet...
[ "Streptococcus suis is the most common cause of meningitis in pork consuming and pig rearing countries in South-East Asia .", "We performed a systematic review of studies on S . suis meningitis to define the clinical characteristics , predisposing factors and outcome .", "Studies published between January 1 , 1...
[ "Meningitis is a common manifestation of Streptococcus suis infection .", "S . suis is endemic in pork consuming and pig rearing countries .", "We systematically reviewed the clinical characteristics , predisposing factors and outcome of S . suis meningitis .", "We identified 913 patients included in 24 studi...
2015
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "cell motility", "medicine and health sciences", "topographic maps", "ocular anatomy", "brain", "retinal ganglion cells", "neuroscience", "ganglion cells", "nerve fibers", "chemoattractant axon guidance", "geography", "developmental neuroscience", "animal cells", "proteins", "axons", "...
Revisiting chemoaffinity theory: Chemotactic implementation of topographic axonal projection
journal.pcbi.1005702
null
[ [ "During development , neurons extend axon and dendrites [1–3] and axonal growth cones chemotactically migrate in response to extracellular guidance cue gradients and connect to their target sites .", "Because this axon guidance is a fundamental process in wiring neural circuits , many guidance cues and re...
[ "Neural circuits are wired by chemotactic migration of growth cones guided by extracellular guidance cue gradients .", "How growth cone chemotaxis builds the macroscopic structure of the neural circuit is a fundamental question in neuroscience .", "I addressed this issue in the case of the ordered axonal projec...
[ "This study revisited the chemoaffinity theory for topographic mapping in terms of chemotaxis .", "According to this theory , the axonal growth cone projects to specific targets based on positional information encoded by chemical gradients in both source and target areas .", "However , the mechanism by which th...
2017
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "computational biology/population genetics", "genetics and genomics/genomics", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "evolutionary biology/human evolution", "computational biology/comparative sequence analysis", "molecular biology/mol...
Human and Non-Human Primate Genomes Share Hotspots of Positive Selection
journal.pgen.1000840
null
[ [ "The respective contribution of neutral and advantageous mutations to genetic", "differences between species has been a pivotal question in molecular evolution for", "more than half a century [1] .", "Until recently , results were based on typically", "small genetic samples leading to controve...
[ "Among primates , genome-wide analysis of recent positive selection is currently", "limited to the human species because it requires extensive sampling of genotypic", "data from many individuals .", "The extent to which genes positively selected in", "human also present adaptive changes in other primates th...
[ "An advantageous mutation spreads from generation to generation in a population", "until individuals that carry it , because of their higher reproductive success ,", "completely replace those that do not .", "This process , commonly known as positive", "Darwinian selection , requires the selected mutation t...
2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "plant biology/plant-biotic interactions", "infectious diseases/fungal infections", "evolutionary biology/microbial evolution and genomics" ]
Evolution of Linked Avirulence Effectors in Leptosphaeria maculans Is Affected by Genomic Environment and Exposure to Resistance Genes in Host Plants
journal.ppat.1001180
null
[ [ "The fungus Leptosphaeria maculans causes blackleg ( phoma stem canker ) and is the major disease of Brassica napus ( canola ) worldwide [1] .", "The major source of inoculum is wind-borne ascospores , which are released from sexual fruiting bodies on infected stubble ( crop residue ) of previous crops an...
[ "Brassica napus ( canola ) cultivars and isolates of the blackleg fungus , Leptosphaeria maculans interact in a ‘gene for gene’ manner whereby plant resistance ( R ) genes are complementary to pathogen avirulence ( Avr ) genes .", "Avirulence genes encode proteins that belong to a class of pathogen molecules know...
[ "The fungus Leptosphaeria maculans causes blackleg , the major disease of canola worldwide .", "Populations of this fungus rapidly adapt to selection pressures such as the extensive sowing of canola with particular disease resistance genes .", "This can lead to a breakdown of resistance and severe economic loss...
2010
[ "Introduction", "Material and methods", "Results", "Discussion" ]
[]
The invasive giant African snail Lissachatina fulica as natural intermediate host of Aelurostrongylus abstrusus, Angiostrongylus vasorum, Troglostrongylus brevior, and Crenosoma vulpis in Colombia
journal.pntd.0007277
null
[ [ "The giant African snail , Lissachatina ( = Achatina ) fulica , is originally native to east Africa [1] .", "It is now one of the most widely distributed and invasive snail species in tropical and subtropical terrestrial ecosystems , and consequently is included among 100 of the world’s worst invasive ali...
[ "Several metastrongyloid lungworms are unreported pathogens in Colombia .", "Angiostrongylus vasorum and Crenosoma vulpis target the cardiopulmonary system of domestic and wild canids .", "Aelurostrongylus abstrusus and Troglostrongylus brevior infect felids and considering that six wild felid species exist in ...
[ "Several lungworm species are neglected pathogens in Colombia .", "Angiostrongylus vasorum and Crenosoma vulpis target the cardiopulmonary system of domestic and wild canids .", "Aelurostrongylus abstrusus and Troglostrongylus brevior infect domestic cats as well as wild felids .", "Angiostrongylus costaricen...
2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[]
Contribution of Host Intracellular Transport Machineries to Intercellular Movement of Turnip Mosaic Virus
journal.ppat.1003683
null
[ [ "Plant viruses move from the initially infected cell to neighboring cells during local spread and then over long distances through vascular tissues to establish a systemic infection in the plant .", "Transport of viruses between cells first involves the intracellular movement of the viral RNA from the sit...
[ "The contribution of different host cell transport systems in the intercellular movement of turnip mosaic virus ( TuMV ) was investigated .", "To discriminate between primary infections and secondary infections associated with the virus intercellular movement , a gene cassette expressing GFP-HDEL was inserted adj...
[ "Plant viruses move from the initially infected cell to neighboring cells during local movement and then over long distances through vascular tissue to establish a systemic infection in the plant .", "Virus intercellular transport requires viral and host factors to move viral RNA-protein complexes through plasmod...
2013
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "plant anatomy", "simulation and modeling", "insect pests", "plant science", "weevils", "coevolution", "pests", "research and analysis methods", "seeds", "agriculture", "pericarp", "phenotypes", "natural selection", "genetics", "biology and life sciences", "species interactions", "ev...
Approximate Bayesian estimation of coevolutionary arms races
journal.pcbi.1006988
null
[ [ "Few metaphors have captured the interest of evolutionary biologists and ecologists more than the coevolutionary arms race [1] .", "Whether between species , sexes , individuals , or genes , the idea of perpetually and reciprocally escalating defenses and counter-defenses has inspired an enormous amount o...
[ "Exaggerated traits involved in species interactions have long captivated the imagination of evolutionary biologists and inspired the durable metaphor of the coevolutionary arms race .", "Despite decades of research , however , we have only a handful of examples where reciprocal coevolutionary change has been rig...
[ "Exaggerated traits involved in species interactions , such as extreme running speeds in predator and prey , have long captivated the imagination of evolutionary biologists and inspired the durable metaphor of the coevolutionary arms race .", "Despite decades of research , however , we have only a handful of exam...
2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "molecular cell biology", "biology", "microbiology" ]
Phosphorylation of Calcineurin at a Novel Serine-Proline Rich Region Orchestrates Hyphal Growth and Virulence in Aspergillus fumigatus
journal.ppat.1003564
null
[ [ "Invasive fungal infections are a leading cause of death in immunocompromised patients [1] .", "With a 40–60% mortality rate , invasive aspergillosis , caused by the filamentous fungus Aspergillus fumigatus , is the most frequent fungal cause of mortality [2] .", "Through both genetic and pharmacologi...
[ "The fungus Aspergillus fumigatus is a leading infectious killer in immunocompromised patients .", "Calcineurin , a calmodulin ( CaM ) -dependent protein phosphatase comprised of calcineurin A ( CnaA ) and calcineurin B ( CnaB ) subunits , localizes at the hyphal tips and septa to direct A . fumigatus invasion an...
[ "Invasive fungal infections are a leading cause of death in immunocompromised patients .", "Translating molecular understanding into tangible clinical benefit has been difficult due to the fact that fungal pathogens and their hosts have similar physiology .", "The calcineurin pathway is an important signaling c...
2013
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "dimers (chemical physics)", "chemical characterization", "electricity", "dna-binding proteins", "mutation", "electrostatics", "protein structure", "thermodynamics", "physical chemistry", "research and analysis methods", "chemical properties", "dimerization", "proteins", "chemistry", "bi...
Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation
journal.pcbi.1004981
null
[ [ "The Aryl hydrocarbon Receptor ( AhR ) is a basic Helix-Loop-Helix PER-ARNT-SIM ( bHLH-PAS ) -containing transcription factor that responds to a variety of structurally diverse exogenous and endogenous chemicals with the modulation of gene expression and production of diverse biological and toxic effects in a...
[ "The Aryl hydrocarbon Receptor ( AhR ) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants , including dioxins .", "Recently , endogenous regulatory roles for the AhR in normal physiology and development have also been rep...
[ "Computational modeling combined with experimental validation may give insight into structural and functional properties of protein systems .", "The basic Helix-Loop-Helix PER-ARNT-SIM ( bHLH-PAS ) proteins show conserved functional domains despite the broad range of functions exerted by the different systems .",...
2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "virology/mechanisms of resistance and susceptibility, including host genetics", "virology/viral replication and gene regulation" ]
Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis
journal.ppat.1001175
null
[ [ "Genome-wide screens for host factors affecting RNA virus infections have led to the identification of several hundreds host proteins in recent years [1] , [2] , [3] , [4] , [5] , [6] , [7] .", "These works demonstrated complex interactions between the host and plus-stranded ( + ) RNA viruses , the larges...
[ "Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes .", "Previous studies showed that eukaryotic translation elongation factor ( eEF1A ) is one of the resident host proteins in the highly purified tombusvirus replicase complex .", "Using a random lib...
[ "Plus-stranded RNA viruses are important pathogens of plants , animals and humans .", "They replicate in the infected cells by assembling viral replicase complexes consisting of viral- and host-coded proteins .", "In this paper , we show that the eukaryotic translation elongation factor ( eEF1A ) , which is one...
2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "neurobiology of disease and regeneration", "cellular neuroscience", "medicine and health sciences", "cell biology", "neurology", "biology and life sciences", "molecular cell biology", "neuroscience" ]
Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation
journal.pbio.1001874
When stimulated by inflammation, peripheral blood cells signal directly to neurons in the brain via the transfer of functional RNA enclosed in extracellular vesicles.
[ [ "The influence of the immune system on the brain in the context of inflammation is highly relevant for a number of diseases , yet mechanisms for this interaction are not fully understood .", "The stereotypical response is the secretion of pro-inflammatory cytokines by immune cells .", "These periphera...
[ "Mechanisms behind how the immune system signals to the brain in response to systemic inflammation are not fully understood .", "Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje neurons ."...
[ "Peripheral infections leading to an inflammatory response can initiate signaling from the hematopoietic system to various organs including the brain .", "The traditional view of this communication between blood and brain is that individual factors are released by immune cells that in turn bind to neuronal or non...
2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "medicine", "veterinary diseases", "veterinary epidemiology", "veterinary microbiology", "epidemiology", "public health", "veterinary science" ]
Prevalence and Diversity of Bartonella Species in Commensal Rodents and Ectoparasites from Nigeria, West Africa
journal.pntd.0002246
null
[ [ "Bartonellae are Gram-negative facultative intracellular alpha-proteobacteria belonging to the family Bartonellaceae .", "Many Bartonella species have been affecting human life for centuries [1] .", "Since the first Bartonella species discovery , namely Bartonella bacilliformis , in 1905 by Alberto Le...
[ "Bartonellae are fastidious bacteria causing persistent bacteremia in humans and a wide variety of animals .", "In recent years there is an increasing interest in mammalian bartonelloses in general and in rodent bartonelloses in particular .", "To date , no studies investigating the presence of Bartonella spp ....
[ "Bartonella species are zoonotic vector-borne bacteria that typically parasitize the erythrocytes of mammalian hosts , resulting in long lasting infections .", "They are responsible for a wide range of clinical manifestations in both immunocompetent and immunocompromised hosts .", "Rodents and a wide range of s...
2013
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "infectious disease epidemiology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "animals", "protozoans", "rural areas", "neglected tropical diseases", "strongyloides stercoralis", "str...
High prevalence of S. Stercoralis infection among patients with Chagas disease: A retrospective case-control study
journal.pntd.0006199
null
[ [ "In recent years , the significant increase in the number of Latin American migrants in Europe has meant the introduction of parasitic endemic infections , such as Trypanosoma cruzi infection and strongyloidiasis [1–3] .", "Both are neglected tropical diseases ( NTD ) , sharing a similar epidemiological p...
[ "We evaluate the association between Trypanosoma cruzi infection and strongyloidiasis in a cohort of Latin American ( LA ) migrants screened for both infections in a non-endemic setting .", "Case-control study including LA individuals who were systematically screened for T . cruzi infection and strongyloidiasis b...
[ "Trypanosoma cruzi infection and strongyloidiasis are neglected tropical diseases , sharing a similar epidemiological burden in Latin America and producing life-long infections , leading to high morbidity and mortality .", "We conducted a case-control study in a non-endemic setting to evaluate a possible relation...
2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "infectious diseases/neglected tropical diseases" ]
High-Resolution Sonography: A New Technique to Detect Nerve Damage in Leprosy
journal.pntd.0000498
null
[ [ "Leprosy is the most common treatable peripheral nerve disorder worldwide [1] .", "Leprosy is caused by a chronic granulomatous immune response to infection of the skin and nerves with Mycobacterium leprae , which resides in macrophages and Schwann cells and is the only bacterium known to affect myelinati...
[ "Leprosy is the most common treatable peripheral nerve disorder worldwide with periods of acute neuritis leading to functional impairment of limbs , ulcer formation and stigmatizing deformities .", "Since the hallmarks of leprosy are nerve enlargement and inflammation , we used high-resolution sonography ( US ) a...
[ "Mycobacterium leprae , which causes leprosy , infects peripheral nerves resulting in functional impairment , ulcer formation and stigmatizing deformities .", "Early diagnosis of nerve involvement is important to avoid nerve related complications .", "We used non-invasive , high-resolution sonography ( US ) and...
2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]
[ "cell death", "medicine and health sciences", "gene regulation", "regulatory proteins", "cell processes", "dna-binding proteins", "neuroscience", "animal models", "developmental biology", "model organisms", "organism development", "developmental signaling", "stem cells", "gland development...
Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis
journal.pgen.1007047
null
[ [ "The lacrimal gland plays an essential role in protecting the ocular surface by secreting the aqueous components of the tear film .", "Defects associated with the lacrimal gland are the main cause of dry eye disease , which is highly prevalent in the geriatric population [1] .", "Left untreated , dry ...
[ "The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates .", "Here , we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development .", "In addition to preventing p53-independent apopto...
[ "The dry eye disease caused by lacrimal gland dysgenesis is one of the most common ocular ailments .", "In this study , we show that Shp2 mediates the sequential use of FGF signaling in lacrimal gland development .", "Our study identifies Alx4 as a novel target of Shp2 signaling and a causal gene for lacrimal g...
2017
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "knee joints", "medicine and health sciences", "body fluids", "diagnostic radiology", "pathology and laboratory medicine", "pathogens", "tropical diseases", "microbiology", "brucellosis", "organisms", "bacterial diseases", "signs and symptoms", "neglected tropical diseases", "bacteria", ...
A systematic review and meta-analysis of the prevalence of osteoarticular brucellosis
journal.pntd.0007112
null
[ [ "Brucellosis is a neglected disease worldwide and a growing public health concern in high-risk countries .", "It is caused by facultative , intracellular Brucella species .", "Brucella abortus ( cattle ) , Brucella melitensis ( goats and sheep ) , and Brucella suis ( pigs ) are known to be the most pa...
[ "Infection of bones and joints remains one of the most commonly described complications of brucellosis in humans and is predominantly reported in all ages and sexes in high-risk regions , such as the Middle East , Asia , South and Central America , and Africa .", "We aimed to systematically review the literature ...
[ "Brucellosis continues to be a global public health concern .", "It is caused by facultative , intracellular Brucella species .", "The most commonly described complication of brucellosis in humans is the infection of bones and joints , which is predominantly reported in all ages and sexes in high-risk regions ,...
2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "immunopathology", "medicine and health sciences", "animal genetics", "immunochemistry", "chagas disease", "clinical immunology", "heredity", "genetics", "protozoan infections", "biology and life sciences", "immunology", "tropical diseases", "parasitic diseases", "neglected tropical diseas...
Inhibition of Autoimmune Chagas-Like Heart Disease by Bone Marrow Transplantation
journal.pntd.0003384
null
[ [ "Epidemiological methods have been used to evaluate the incidence and distribution of endemic Chagas disease , to associate epiphenomenal clinical manifestations with the recognized pathology of the disease .", "Acute T . cruzi infections often resolve spontaneously , but the individual remains chronicall...
[ "Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease .", "The treatment available for chagasic cardiomyopathy is unsatisfactory .", "To study the disease pathology and its inhibition , we employed a syngeneic chicken model refractory to T . cruzi in which chickens hatched...
[ "Chagas heart disease , stemming from infection by the protozoan parasite Trypanosoma cruzi , which is endemic in South America , is now present on five continents .", "The treatment now available for the clinically manifested heart disease is considered unsatisfactory .", "We postulate that manifestations of C...
2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "medicine", "infectious diseases", "african trypanosomiasis", "parasitic diseases" ]
How Do Tsetse Recognise Their Hosts? The Role of Shape in the Responses of Tsetse (Glossina fuscipes and G. palpalis) to Artificial Hosts
journal.pntd.0001226
null
[ [ "Between 1997 and 2006 , about 250 , 000 new cases of Human African Trypanosomiasis ( HAT , or sleeping sickness ) were reported [1] .", "For >95%% of these cases , the disease started with a bite from one of four subspecies of tsetse: Glossina palpalis gambiensis ( in Guinea and Côte d'Ivoire ) , G . p ....
[ "Palpalis-group tsetse , particularly the subspecies of Glossina palpalis and G . fuscipes , are the most important transmitters of human African trypanomiasis ( HAT ) , transmitting >95% of cases .", "Traps and insecticide-treated targets are used to control tsetse but more cost-effective baits might be develope...
[ "While the numbers of cases of human African trypanosomiasis ( HAT ) is now less than 10 , 000 reported cases per year , progress against the tsetse species that spread the disease is poor , with ∼10 million square kilometres of sub-Saharan Africa still being infested .", "This widespread persistence of vectors a...
2011
[ "Introduction", "Methods", "Results/Discussion" ]
[ "genome expression analysis", "invertebrates", "medicine and health sciences", "functional genomics", "parasitic diseases", "animals", "genome analysis", "infectious diseases", "epidemiology", "disease vectors", "insects", "arthropoda", "mosquitoes", "transcriptome analysis", "genetics",...
Transcriptome Sequencing and Developmental Regulation of Gene Expression in Anopheles aquasalis
journal.pntd.0003005
null
[ [ "Anopheles aquasalis is a neotropical malaria vector , found along the northern coast of South America .", "Its geographical distribution extends from Brazil to Panama on the Atlantic shore and from Panama to Ecuador along the Pacific coast [1]–[6] .", "Their larvae develop preferentially in brackish ...
[ "Anopheles aquasalis is a major malaria vector in coastal areas of South and Central America where it breeds preferentially in brackish water .", "This species is very susceptible to Plasmodium vivax and it has been already incriminated as responsible vector in malaria outbreaks .", "There has been no high-thro...
[ "The mosquito Anopheles aquasalis is responsible for transmitting malaria parasites to humans in South America coastal areas .", "An .", "aquasalis females transmit Plasmodium vivax and Plasmodium falciparum , the two major malaria etiological agents in these endemic sites .", "Although the vectorial importan...
2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "meiosis", "cell division", "cell biology", "chromosome biology", "centromeres", "biology", "molecular cell biology" ]
Gamma-Tubulin Is Required for Bipolar Spindle Assembly and for Proper Kinetochore Microtubule Attachments during Prometaphase I in Drosophila Oocytes
journal.pgen.1002209
null
[ [ "In mitosis and male meiosis in animals , the establishment of spindle bipolarity is mediated by centrosomes that act as microtubule organizing centers ( MTOCs ) .", "These structures serve to organize and focus the growing microtubules to form a bipolar spindle .", "γ-Tubulin is a primary component o...
[ "In many animal species the meiosis I spindle in oocytes is anastral and lacks centrosomes .", "Previous studies of Drosophila oocytes failed to detect the native form of the germline-specific γ-tubulin ( γTub37C ) in meiosis I spindles , and genetic studies have yielded conflicting data regarding the role of γTu...
[ "Proper chromosome segregation during cell division is essential .", "Missegregation of mitotic chromosomes leads to cell death or cancer , and chromosome missegregation during meiosis leads to miscarriage and birth defects .", "Cells utilize a bipolar microtubule-based structure known as the meiotic or mitotic...
2011
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "virology", "biology", "microbiology" ]
Secretion of Genome-Free Hepatitis B Virus – Single Strand Blocking Model for Virion Morphogenesis of Para-retrovirus
journal.ppat.1002255
null
[ [ "The hepatitis B virus ( HBV ) is a global human pathogen that chronically infects hundreds of millions and causes a million fatalities yearly .", "It belongs to the Hepadnaviridae family , which also includes several related animal viruses such as the duck hepatitis B virus ( DHBV ) [1] .", "Hepadnav...
[ "As a para-retrovirus , hepatitis B virus ( HBV ) is an enveloped virus with a double-stranded ( DS ) DNA genome that is replicated by reverse transcription of an RNA intermediate , the pregenomic RNA or pgRNA .", "HBV assembly begins with the formation of an “immature” nucleocapsid ( NC ) incorporating pgRNA , w...
[ "Hepatitis B virus ( HBV ) , an important global human pathogen and the main cause of liver cancer worldwide , is classified as a para-retrovirus , as it replicates by reverse transcription , i . e . , copying of RNA to DNA , like retroviruses .", "However , different from retroviruses that are RNA viruses replic...
2011
[ "Introduction", "Results/Discussion", "Materials and Methods" ]
[ "microbiology/innate immunity", "immunology/innate immunity", "genetics and genomics/disease models", "genetics and genomics/gene function", "public health and epidemiology/infectious diseases", "infectious diseases/protozoal infections", "infectious diseases/tropical and travel-associated diseases", ...
Transmission Blocking Immunity in the Malaria Non-Vector Mosquito Anopheles quadriannulatus Species A
journal.ppat.1000070
null
[ [ "The Anopheles gambiae Giles complex comprises seven mosquito species and several incipient species [1]–[3] .", "Sibling species are closely related to each other , are morphologically indistinguishable , and can crossbreed in captivity; however , they vary greatly in their capacity to transmit human mala...
[ "Despite being phylogenetically very close to Anopheles gambiae , the major mosquito vector of human malaria in Africa , Anopheles quadriannulatus is thought to be a non-vector .", "Understanding the difference between vector and non-vector mosquitoes can facilitate development of novel malaria control strategies...
[ "Malaria is a mosquito-borne infectious disease that threatens almost half of the human population and kills 1 to 3 million people every year .", "In sub-Saharan Africa , where the vast majority of deaths occur , the capacity of mosquitoes to transmit malaria varies greatly even between closely related species ."...
2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "bacterial diseases", "infectious diseases", "tuberculosis", "medicine and health sciences" ]
Allele-Specific Induction of IL-1β Expression by C/EBPβ and PU.1 Contributes to Increased Tuberculosis Susceptibility
journal.ppat.1004426
null
[ [ "Tuberculosis ( TB ) , a chronic bacterial disease caused by Mycobacterium tuberculosis ( Mtb ) , remains a major global health problem that claims 1 . 4 million lives annually .", "Natural infection with Mtb is initiated by the deposition of Mtb-containing aerosol droplets onto lung alveolar surfaces , a...
[ "Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes , from long-term latent infection to different manifestations of progressive disease .", "Pro-inflammatory pathways , such as those controlled by IL-1β , have the contrasting potential both to prevent disease by restricting b...
[ "IL-1β is important for the initial establishment of antimicrobial adaptive immunity , but prolonged IL-1β expression can also cause progressive immunopathology during M . tuberculosis infection .", "The paradoxical activities of IL-1β in promoting both antimycobacterial immunity and chronic tissue damage have le...
2014
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "sequencing techniques", "antimicrobials", "medicine and health sciences", "chemical compounds", "split-decomposition method", "drugs", "microbiology", "organic compounds", "multiple alignment calculation", "antibiotic resistance", "serine", "antibiotics", "amino acids", "sequence motif an...
Novel Computational Protocols for Functionally Classifying and Characterising Serine Beta-Lactamases
journal.pcbi.1004926
null
[ [ "In this article we demonstrate the value of different clustering and analysis platforms for classifying an important superfamily of bacterial proteins , the beta-lactamases .", "Our approaches are based largely on the sequence properties of the relatives although structural information is considered for ...
[ "Beta-lactamases represent the main bacterial mechanism of resistance to beta-lactam antibiotics and are a significant challenge to modern medicine .", "We have developed an automated classification and analysis protocol that exploits structure- and sequence-based approaches and which allows us to propose a group...
[ "Beta-lactamases are bacterial proteins largely responsible for resistance to beta-lactam antibiotics and so pose a significant challenge to modern medicine .", "Whilst there are many studies cataloguing beta-lactamases , antibiotic screening has not always been consistent or comprehensive , causing confusion in ...
2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]
[ "antimicrobials", "medicine and health sciences", "toxins", "pathology and laboratory medicine", "endotoxins", "enzymes", "pathogens", "drugs", "microbiology", "enzymology", "toxicology", "toxic agents", "animal models", "model organisms", "helicobacter", "antibiotics", "experimental...
The redefinition of Helicobacter pylori lipopolysaccharide O-antigen and core-oligosaccharide domains
journal.ppat.1006280
null
[ [ "Helicobacter pylori is well-adapted to survival in the human stomach mucosa and establishes persistent infection , which causes chronic gastritis and can lead to peptic ulcer disease and gastric adenocarcinoma [1 , 2] .", "Lipopolysaccharide ( LPS ) , a highly acylated glycolipid compactly anchored in th...
[ "Helicobacter pylori lipopolysaccharide promotes chronic gastric colonisation through O-antigen host mimicry and resistance to mucosal antimicrobial peptides mediated primarily by modifications of the lipid A . The structural organisation of the core and O-antigen domains of H . pylori lipopolysaccharide remains un...
[ "The bacterial pathogen Helicobacter pylori chronically infects the human stomach and causes ulcers and gastric cancer .", "The H . pylori lipopolysaccharide harbors unique properties that promote persistent infection through immune evasion .", "Despite the key role of H . pylori lipopolysaccharide in the bacte...
2017
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "rheumatology", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "biopsy", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "surgical and invasive medical procedures", "developmental biology", "rheumatoid arthritis", ...
Leishmaniasis and tumor necrosis factor alpha antagonists in the Mediterranean basin. A switch in clinical expression
journal.pntd.0007708
null
[ [ "Tumor Necrosis Factor-α ( TNF-α ) is a crucial cytokine in the inflammatory cascade by activating the type 1 T helper ( Th1 ) immune response , enhancing the activity of the macrophages and essential for the formation and maintenance of granulomas [1] .", "Since TNF-α has been implicated in numerous immu...
[ "Tumor necrosis factor alpha ( TNF-α ) blockers are recognized as a risk factor for reactivation of granulomatous infections .", "Leishmaniasis has been associated with the use of these drugs , although few cases have been reported .", "We performed a retrospective observational study including patients with co...
[ "Tumor necrosis factor alpha ( TNF-α ) blockers are widely used in numerous inflammatory diseases such rheumatoid arthritis , psoriasis or inflammatory bowel diseases .", "They have been recognized as a risk factor for reactivation of granulomatous infections .", "Although few cases have been reported , Leishma...
2019
[ "Introduction", "Methods", "Results/Discussion" ]
[ "systems biology", "genetics", "biology", "computational biology", "genetics and genomics" ]
Parameters in Dynamic Models of Complex Traits are Containers of Missing Heritability
journal.pcbi.1002459
null
[ [ "The phenotypic variance cumulatively explained by marker loci found to associate with complex traits in genome-wide association studies ( GWAS ) is usually much less than the narrow-sense heritability [1]–[6] , the ratio of additive genetic variance to total phenotypic variance .", "Several explanations ...
[ "Polymorphisms identified in genome-wide association studies of human traits rarely explain more than a small proportion of the heritable variation , and improving this situation within the current paradigm appears daunting .", "Given a well-validated dynamic model of a complex physiological trait , a substantial...
[ "Despite an ever-increasing number of genome locations reported to be associated with complex human diseases or quantitative traits , only a small proportion of phenotypic variations in a typical quantitative trait can be explained by the discovered variants .", "We argue that this problem can partly be resolved ...
2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "motor systems", "medicine", "computational neuroscience", "biology", "neuroscience", "learning and memory", "physiotherapy and rehabilitation" ]
The Binding of Learning to Action in Motor Adaptation
journal.pcbi.1002052
null
[ [ "When learning to swim , the proper stroke motion is usually taught on the pool deck .", "Although a student might seem to have mastered this motion on dry land , upon entering the water she will have difficulty in accurately reproducing it underwater .", "However , after many laps , the student event...
[ "In motor tasks , errors between planned and actual movements generally result in adaptive changes which reduce the occurrence of similar errors in the future .", "It has commonly been assumed that the motor adaptation arising from an error occurring on a particular movement is specifically associated with the mo...
[ "Einstein once said: “Insanity is doing the same thing over and over again and expecting different results” .", "However , task repetition is generally the default procedure for training a motor skill .", "This can work because motor learning ensures that repetition of the same motor task will lead to actions t...
2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "infectious diseases", "public health and epidemiology", "infectious diseases/neglected tropical diseases", "public health and epidemiology/epidemiology", "infectious diseases/viral infections", "public health and epidemiology/global health", "public health and epidemiology/infectious diseases", "infe...
Epidemiology of Dengue Virus in Iquitos, Peru 1999 to 2005: Interepidemic and Epidemic Patterns of Transmission
journal.pntd.0000670
null
[ [ "Dengue viruses ( DENV ) are major re-emerging pathogens that have increased geographically from only 9 countries 60 years ago to more than 100 today .", "An estimated 2 . 5–3 . 0 billion people worldwide are at risk , with 50–100 million cases of dengue fever ( DF ) and 250 , 000–500 , 000 of the more se...
[ "Comprehensive , longitudinal field studies that monitor both disease and vector populations for dengue viruses are urgently needed as a pre-requisite for developing locally adaptable prevention programs or to appropriately test and license new vaccines .", "We report the results from such a study spanning 5 year...
[ "To develop prevention ( including vaccines ) and control programs for dengue fever , a significant mosquito-borne disease in the tropics , there is an urgent need for comprehensive long term field epidemiological studies .", "We report results from a study that monitored ∼2 , 400 school children and some adult f...
2010
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]
[ "biochemistry", "neurological disorders", "biophysics" ]
Conformational Equilibria in Monomeric α-Synuclein at the Single-Molecule Level
journal.pbio.0060006
A single-molecule study detects structured and unstructured conformers in equilibrium in monomeric α-synuclein. The β-like conformers increase with pathological mutations and under other conditions known to promote aggregation.
[ [ "A significant fraction ( possibly as much as 30% ) of proteins and segments of proteins in eukaryotic proteomes has been found to lack , at least partially , a well-defined three-dimensional structure .", "Proteins belonging to this class are usually called natively unfolded proteins ( NUPs ) [1] .", ...
[ "Human α-Synuclein ( αSyn ) is a natively unfolded protein whose aggregation into amyloid fibrils is involved in the pathology of Parkinson disease .", "A full comprehension of the structure and dynamics of early intermediates leading to the aggregated states is an unsolved problem of essential importance to rese...
[ "Natively unstructured proteins defy the classical “one sequence–one structure” paradigm of protein science .", "In pathological conditions , monomers of these proteins can aggregate in the cell , a process that underlies neurodegenerative diseases such as Alzheimer and Parkinson .", "A key step in the aggregat...
2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "medicine", "genome expression analysis", "infectious diseases", "gene expression", "genetics", "microbial pathogens", "molecular genetics", "biology", "genomics", "microbiology", "host-pathogen interaction", "fungal diseases", "genetics and genomics", "pathogenesis" ]
Candida albicans White and Opaque Cells Undergo Distinct Programs of Filamentous Growth
journal.ppat.1003210
null
[ [ "Morphological plasticity is key to the lifestyle of fungal pathogens such as Candida albicans , the most frequently isolated human fungal pathogen .", "The best-studied morphological switch in C . albicans is the transition between yeast and true hyphae or pseudohyphae ( filamentous forms ) .", "Pseu...
[ "The ability to switch between yeast and filamentous forms is central to Candida albicans biology .", "The yeast-hyphal transition is implicated in adherence , tissue invasion , biofilm formation , phagocyte escape , and pathogenesis .", "A second form of morphological plasticity in C . albicans involves epigen...
[ "Candida albicans is the most common human fungal pathogen , capable of growing as a commensal organism or as an opportunistic pathogen .", "Perhaps the best-studied aspect of C . albicans biology is the transition between the single-celled yeast form and the multicellular filamentous form .", "This transition ...
2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "sequence analysis", "genome complexity", "genomics", "dna modification", "genetics", "epigenetics", "biology", "epigenomics", "computational biology", "chromatin" ]
DNA Sequence Explains Seemingly Disordered Methylation Levels in Partially Methylated Domains of Mammalian Genomes
journal.pgen.1004143
null
[ [ "DNA methylation in metazoan genomes occurs mainly in the context of CpG dinucleotides and for the most part genomes are highly methylated and harbor only small regions with low or absent methylation [1] .", "These include CpG islands [1] , CpG island shores [2] and distal regulatory regions [3] , [4] .",...
[ "For the most part metazoan genomes are highly methylated and harbor only small regions with low or absent methylation .", "In contrast , partially methylated domains ( PMDs ) , recently discovered in a variety of cell lines and tissues , do not fit this paradigm as they show partial methylation for large portion...
[ "Methylation is an essential DNA modification , which is attracting a lot of attention as a regulator of gene expression .", "Recent technological advances have allowed the genome-wide measurement of methylation at single-nucleotide resolution , leading to the discovery of several new types of methylation pattern...
2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "medicine and health sciences", "neurology", "genetics", "biology and life sciences", "neuroscience", "molecular biology", "veterinary science" ]
An ARHGEF10 Deletion Is Highly Associated with a Juvenile-Onset Inherited Polyneuropathy in Leonberger and Saint Bernard Dogs
journal.pgen.1004635
null
[ [ "Charcot-Marie-Tooth ( CMT ) disease is a heterogeneous mix of hereditary motor and sensory neuropathies in humans , for which mutations in more than thirty genes have already been described ( Inherited Peripheral Neuropathies Mutation Database ) .", "CMT disease is the most common inherited disorder of t...
[ "An inherited polyneuropathy ( PN ) observed in Leonberger dogs has clinical similarities to a genetically heterogeneous group of peripheral neuropathies termed Charcot-Marie-Tooth ( CMT ) disease in humans .", "The Leonberger disorder is a severe , juvenile-onset , chronic , progressive , and mixed PN , characte...
[ "Leonberger dogs are a breed originally produced by crossing large-bodied dogs , including Saint Bernards and Newfoundlands .", "A peripheral neuropathy has been described in Leonbergers that is similar to a group of inherited polyneuropathies known as Charcot-Marie-Tooth disease in humans .", "We collected a c...
2014
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "cancer detection and diagnosis", "medicine", "genome expression analysis", "cancer genetics", "breast tumors", "statistics", "applied mathematics", "computational biology", "cancers and neoplasms", "basic cancer research", "algorithms", "oncology", "mathematics", "biostatistics", "perso...
Improving Breast Cancer Survival Analysis through Competition-Based Multidimensional Modeling
journal.pcbi.1003047
null
[ [ "Breast cancer remains the most common malignancy in females , with more than 200 , 000 cases of invasive breast cancer diagnosed in the United States annually [1] .", "Molecular profiling research in the last decade has revealed breast cancer to be a heterogeneous disease [2]–[4] , motivating the develop...
[ "Breast cancer is the most common malignancy in women and is responsible for hundreds of thousands of deaths annually .", "As with most cancers , it is a heterogeneous disease and different breast cancer subtypes are treated differently .", "Understanding the difference in prognosis for breast cancer based on i...
[ "We developed an extensible software framework for sharing molecular prognostic models of breast cancer survival in a transparent collaborative environment and subjecting each model to automated evaluation using objective metrics .", "The computational framework presented in this study , our detailed post-hoc ana...
2013
[ "Introduction", "Model", "Results", "Discussion", "Methods" ]
[ "bacteriology", "blood cells", "organismal evolution", "medicine and health sciences", "toxins", "immune cells", "pathology and laboratory medicine", "gene regulation", "population dynamics", "immunology", "microbiology", "social sciences", "neuroscience", "toxicology", "toxic agents", ...
Toxin production spontaneously becomes regulated by local cell density in evolving bacterial populations
journal.pcbi.1007333
null
[ [ "Many bacteria produce antimicrobial toxins that impede the growth of competing bacteria or even kill them [1–3] .", "A wide variety of such toxins has been discovered , ranging from narrow-range bacteriocins to broad-range antimicrobials that may even affect eukaryotic cells [4 , 5] .", "Because prod...
[ "The production of anticompetitor toxins is widespread among bacteria .", "Because production of such toxins is costly , it is typically regulated .", "In particular , many toxins are produced only when the local cell density is high .", "It is unclear which selection pressures shaped the evolution of density...
[ "Bacteria live in microbial communities , in which they compete with many other microbes for nutrients and space .", "In this competitive environment , almost all known bacterial strains produce toxins that impair or kill other bacteria .", "This chemical warfare is thought to be one of the major factors shapin...
2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "animal models", "genome-wide association studies", "animal genetics", "model organisms", "genetics", "biology", "genetics of disease", "genetics and genomics" ]
A SEL1L Mutation Links a Canine Progressive Early-Onset Cerebellar Ataxia to the Endoplasmic Reticulum–Associated Protein Degradation (ERAD) Machinery
journal.pgen.1002759
null
[ [ "Ataxia is a neurological symptom of defective motor coordination that can affect gait , balance , speech and gaze [1] .", "Human hereditary ataxias are rare heterogeneous disorders characterized by progressive degeneration of the cerebellum and cerebellar connections , with a variable degree of involveme...
[ "Inherited ataxias are characterized by degeneration of the cerebellar structures , which results in progressive motor incoordination .", "Hereditary ataxias occur in many species , including humans and dogs .", "Several mutations have been found in humans , but the genetic background has remained elusive in do...
[ "Hereditary ataxias are a heterogeneous group of rare disorders characterized by progressive cerebellar neurodegeneration .", "Several causative mutations have been identified in various forms of human ataxias .", "In addition to humans , inherited ataxias have been described in several other species , includin...
2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]
[ "infectious diseases/neglected tropical diseases", "infectious diseases/protozoal infections", "infectious diseases/antimicrobials and drug resistance" ]
Identification of Small Molecule Lead Compounds for Visceral Leishmaniasis Using a Novel Ex Vivo Splenic Explant Model System
journal.pntd.0000962
null
[ [ "New drugs are desperately needed to treat visceral leishmaniasis ( VL ) , and this in turn requires new approaches to discover novel lead compounds that might populate a pipeline of new therapeutics for patients with VL .", "Current therapies for the leishmaniases are toxic , difficult to deliver , expen...
[ "New drugs are needed to treat visceral leishmaniasis ( VL ) because the current therapies are toxic , expensive , and parasite resistance may weaken drug efficacy .", "We established a novel ex vivo splenic explant culture system from hamsters infected with luciferase-transfected Leishmania donovani to screen ch...
[ "Visceral leishmaniasis is a life threatening parasitic disease present in several countries of the world .", "New drugs are needed to treat this disease because treatments are becoming increasingly ineffective .", "We established a novel system to screen for new anti-leishmanial compounds that utilizes spleen ...
2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]
[ "phosphorylation", "cell motility", "medicine and health sciences", "breast tumors", "chemical compounds", "enzymes", "protein interaction networks", "enzymology", "cancers and neoplasms", "signaling networks", "mathematical models", "organic compounds", "oncology", "tyrosine", "network ...
Reconstruction and signal propagation analysis of the Syk signaling network in breast cancer cells
journal.pcbi.1005432
null
[ [ "Tyrosine phosphorylation of proteins acts as an efficient switch allowing to control key signaling pathways involved in cell proliferation , apoptosis , migration , and invasion , and is thus involved in oncogenesis .", "Understanding the functioning of such complex pathways is crucial for both fundament...
[ "The ability to build in-depth cell signaling networks from vast experimental data is a key objective of computational biology .", "The spleen tyrosine kinase ( Syk ) protein , a well-characterized key player in immune cell signaling , was surprisingly first shown by our group to exhibit an onco-suppressive funct...
[ "The complex nature of cancer hampers traditional biological approaches to unravel its molecular mechanisms and develop targeted drug therapies .", "Cancer affects a number of “hallmark” cellular processes controlled by multiple signaling pathways .", "Our goal is to identify the pathways that negatively affect...
2017
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "carbohydrate metabolism", "medicine and health sciences", "metabolic processes", "integrative physiology", "metabolic networks", "signaling networks", "liver diseases", "metabolites", "network analysis", "gastroenterology and hepatology", "lipid metabolism", "amino acid metabolism", "lipids...
SteatoNet: The First Integrated Human Metabolic Model with Multi-layered Regulation to Investigate Liver-Associated Pathologies
journal.pcbi.1003993
null
[ [ "Mathematical modelling provides an intuitive tool to investigate complex diseases that display multiple causal mechanisms and a complex pathobiology .", "In particular , liver-associated pathologies that have a high prevalence in Europe and other Western populations face poor prognosis , and the lack of ...
[ "Current state-of-the-art mathematical models to investigate complex biological processes , in particular liver-associated pathologies , have limited expansiveness , flexibility , representation of integrated regulation and rely on the availability of detailed kinetic data .", "We generated the SteatoNet , a mult...
[ "In this article we present SteatoNet , the most comprehensive computational network of hepatic metabolism and the interaction of the liver with extra-hepatic tissues .", "Generation of the SteatoNet involved the application of engineering strategies to resolve prevalent drawbacks in biological modelling and thus...
2014
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "reproductive system", "immunology", "microbiology", "anatomy and physiology", "gynecologic infections", "parasitic diseases", "parasitology", "parasite physiology", "cardiovascular", "histology", "women's health", "neglected tropical diseases", "immunologic techniques", "imm...
Increased Vascularity in Cervicovaginal Mucosa with Schistosoma haematobium Infection
journal.pntd.0001170
null
[ [ "Schistosomiasis is the most important parasite infection in the world after malaria [1] .", "Of the estimated 780 million people exposed to this fresh water parasite , 85 per cent live in Africa .", "Schistosoma haematobium and human immunodeficiency virus ( HIV ) are co-endemic in large parts of thi...
[ "Close to 800 million people in the world are at risk of schistosomiasis , 85 per cent of whom live in Africa .", "Recent studies have indicated that female genital schistosomiasis might increase the risk of human immunodeficiency virus ( HIV ) infection .", "The aim of this study is to quantify and analyse the...
[ "Schistosomiasis is a fresh water parasite infection that affects millions of people , especially in Africa .", "Recent knowledge about the genital manifestations of schistosomiasis; especially its possible association with human immunodeficiency virus ( HIV ) infection , has led to increased focus on this neglec...
2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "phosphorylation", "dimers (chemical physics)", "medicine and health sciences", "chemical compounds", "pathology and laboratory medicine", "organic compounds", "toxicology", "toxicity", "fungi", "tyrosine", "amino acids", "mitochondria", "bioenergetics", "cellular structures and organelles...
C-Terminal Tyrosine Residue Modifications Modulate the Protective Phosphorylation of Serine 129 of α-Synuclein in a Yeast Model of Parkinson's Disease
journal.pgen.1006098
null
[ [ "Parkinson´s disease ( PD ) is one of the most common neurodegenerative diseases and affects about 1% of the population older than 60 years [1] .", "PD proceeds with selective loss of dopamine-producing neurons of the substantia nigra pars compacta in the ventral midbrain [2 , 3] .", "Degeneration als...
[ "Parkinson´s disease ( PD ) is characterized by the presence of proteinaceous inclusions called Lewy bodies that are mainly composed of α-synuclein ( αSyn ) .", "Elevated levels of oxidative or nitrative stresses have been implicated in αSyn related toxicity .", "Phosphorylation of αSyn on serine 129 ( S129 ) m...
[ "Parkinson’s disease is characterized by loss of dopaminergic neurons in midbrain and the presence of αSyn protein inclusions .", "Human αSyn mimics the disease pathology in yeast resulting in cytotoxicity and aggregate formation .", "αSyn is abundantly phosphorylated at serine S129 and possesses four tyrosines...
2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "animal models", "signal transduction", "model organisms", "cell division", "developmental signaling", "genetics", "biology", "molecular cell biology", "mouse", "signaling in selected disciplines", "gene function" ]
Selective Disruption of Aurora C Kinase Reveals Distinct Functions from Aurora B Kinase during Meiosis in Mouse Oocytes
journal.pgen.1004194
null
[ [ "Haploid gametes are generated by meiosis , a unique cell division process that consists of a single round of DNA replication followed by two successive cell divisions .", "In the first division , meiosis I ( MI ) , homologous chromosomes segregate .", "The second division , meiosis II ( MII ) , is mo...
[ "Aurora B kinase ( AURKB ) is the catalytic subunit of the chromosomal passenger complex ( CPC ) , an essential regulator of chromosome segregation .", "In mitosis , the CPC is required to regulate kinetochore microtubule ( K-MT ) attachments , the spindle assembly checkpoint , and cytokinesis .", "Germ cells e...
[ "Precise control of chromosome segregation is essential for generating cells with the proper number of chromosomes .", "In germ cells , sperm and egg , an abnormal chromosome number leads to infertility , miscarriage , or , in the case of a live birth , developmental disorders such as Down Syndrome .", "For rea...
2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "immunology/antigen processing and recognition", "genetics and genomics/genetics of the immune system", "evolutionary biology/human evolution", "molecular biology/rna splicing", "immunology/autoimmunity", "genetics and genomics/bioinformatics", "genetics and genomics/population genetics" ]
Balancing Selection Maintains a Form of ERAP2 that Undergoes Nonsense-Mediated Decay and Affects Antigen Presentation
journal.pgen.1001157
null
[ [ "Balancing selection maintains advantageous genetic diversity in populations .", "Unlike positive and purifying selection , which favor fixation of the fittest allele , balancing selection results in enhanced genetic and phenotypic variability in populations .", "Diversity can be maintained by overdom...
[ "A remarkable characteristic of the human major histocompatibility complex ( MHC ) is its extreme genetic diversity , which is maintained by balancing selection .", "In fact , the MHC complex remains one of the best-known examples of natural selection in humans , with well-established genetic signatures and biolo...
[ "It has long been known that the extremely high levels of genetic diversity present in the major histocompatibility locus ( MHC ) are due to balancing selection , a type of natural selection that maintains advantageous genetic diversity in populations .", "The MHC encodes for molecules required for a type of anti...
2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[]
Characterization of CD8+ T Cell Differentiation following SIVΔnef Vaccination by Transcription Factor Expression Profiling
journal.ppat.1004740
null
[ [ "Vaccination of rhesus macaques with SIVΔnef can induce robust immune responses and can protect the majority of vaccinated animals from challenge with wild-type SIV virus strains [1–3] .", "To date , SIVΔnef is the most efficacious of all vaccine strategies analyzed in the macaque model .", "Although ...
[ "The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks , a process that is related to qualitative changes in CD8+ T cell responses induced by SIVΔnef .", "As a novel approach to characterize cell differentiation following vaccination , we used ...
[ "The live attenuated vaccine SIVΔnef can induce robust CD8+ T cell- mediated protection against infection with pathogenic SIV in macaques .", "Thus , there is substantial interest in characterizing these immune responses to inform HIV vaccine design .", "Animals challenged at 15–20 weeks post vaccination exhibi...
2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "genetics and genomics/genomics", "computational biology/sequence motif analysis", "computational biology/transcriptional regulation", "genetics and genomics/gene expression", "computational biology/comparative sequence analysis", "developmental biology/developmental evolution", "developmental biology/c...
Robust Target Gene Discovery through Transcriptome Perturbations and Genome-Wide Enhancer Predictions in Drosophila Uncovers a Regulatory Basis for Sensory Specification
journal.pbio.1000435
CisTarget X is a novel computational method that accurately predicts Atonal governed regulatory networks in the retina of the fruit fly.
[ [ "The development of the structural and functional properties of cells is largely determined via differential extraction of information from the genome by transcription factors ( TFs ) .", "The first detailed analyses of TF-controlled genetic programs have recently been performed in yeast [1] , [2] and in ...
[ "A comprehensive systems-level understanding of developmental programs requires the mapping of the underlying gene regulatory networks .", "While significant progress has been made in mapping a few such networks , almost all gene regulatory networks underlying cell-fate specification remain unknown and their disc...
[ "Tens of thousands of regulatory elements determine the spatiotemporal expression pattern of protein-coding genes in the metazoan genome .", "Each regulatory element , when bound by the appropriate transcription factors , can affect the temporal transcription of a nearby target gene in a particular cell type .", ...
2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "medicine", "bacterial diseases", "infectious diseases", "biology", "microbiology" ]
Additive Function of Vibrio vulnificus MARTXVv and VvhA Cytolysins Promotes Rapid Growth and Epithelial Tissue Necrosis During Intestinal Infection
journal.ppat.1002581
null
[ [ "Vibrio vulnificus is a motile , Gram-negative , opportunistic human pathogen capable of causing severe to life-threatening infection in individuals with predisposing conditions , including liver damage , hereditary hemochromatosis and compromised immune systems [1]–[3] .", "Infection can result from cons...
[ "Vibrio vulnificus is a pathogen that causes both severe necrotizing wound infections and life-threatening food-borne infections .", "Food-borne infection is particularly lethal as the infection can progress rapidly to primary septicemia resulting in death from septic shock and multiorgan failure .", "In this s...
[ "Vibrio vulnificus causes disease both by infection of wounds from seawater and by consumption of contaminated foods , especially oysters .", "Wound infection results in necrotizing fasciitis and edema in extremities with mortality of ∼25% as the incidence of septicemia is low .", "Contaminated food consumption...
2012
[ "Introduction", "Methods", "Results", "Discussion" ]
[]
Health Economic Evaluations of Visceral Leishmaniasis Treatments: A Systematic Review
journal.pntd.0003527
null
[ [ "During past decades , health economic evaluations have become increasingly important to the evaluation of new health technologies .", "Many countries have addressed common issues related to the process of health technology assessment ( HTA ) while elaborating guidelines regarding the process to evaluate ...
[ "The main objective of this study was to identify , describe , classify and analyze the scientific health economic evidence of VL-related technologies .", "A web search of combinations of free text and Mesh terms related to the economic evaluation of visceral leishmaniasis was conducted on scientific publication ...
[ "Visceral leishmaniasis ( VL ) , also known as kala azar , is a neglected tropical disease caused by parasitic protozoa of the genus Leishmania .", "VL is related to poverty and its consequences , which leads to its status of neglected disease .", "For that reason , cost-effective forms of diagnoses and treatme...
2015
[ "Introduction", "Results", "Discussion", "Methods" ]
[]
The Effect of Incentives and Meta-incentives on the Evolution of Cooperation
journal.pcbi.1004232
null
[ [ "Even though society is based on cooperation , achieving cooperation in social dilemmas is still a big challenge .", "The free-rider problem , for example , hinders cooperation .", "Many studies have addressed this problem , and the methods proposed for solving it include giving players sufficient abi...
[ "Although positive incentives for cooperators and/or negative incentives for free-riders in social dilemmas play an important role in maintaining cooperation , there is still the outstanding issue of who should pay the cost of incentives .", "The second-order free-rider problem , in which players who do not provi...
[ "Although social dilemmas can be resolved if punishing non-cooperators or rewarding cooperators works , such rewards and punishments , i . e . , external incentives , entail certain expenses .", "As a result , a cooperative player who shirks his or her duty to provide an incentive to other players will emerge , a...
2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]
[ "biophysics", "biology", "computational biology" ]
Two Misfolding Routes for the Prion Protein around pH 4.5
journal.pcbi.1003057
null
[ [ "The misfolding of the prion protein ( PrP ) , which is a key aspect of transmissible spongiform encephalopathies ( TSE ) , has been the subject of intense research during the past decades .", "Nonetheless , little is known about the underlying molecular mechanism .", "One serious hurdle remains the d...
[ "Using molecular dynamics simulations , we show that the prion protein ( PrP ) exhibits a dual behavior , with two possible transition routes , upon protonation of H187 around pH 4 . 5 , which mimics specific conditions encountered in endosomes .", "Our results suggest a picture in which the protonated imidazole ...
[ "Transmissible spongiform encephalopathies , which include the “mad cow” disease and the Creutzfeldt-Jakob disease , are related to the abnormal folding of a host protein termed the prion protein ( PrP ) .", "Many aspects of the underlying molecular mechanism still remain elusive .", "Among the hypotheses that ...
2013
[ "Introduction", "Results/Discussions", "Methods" ]
[]
The Molecular Mechanism of Ion-Dependent Gating in Secondary Transporters
journal.pcbi.1003296
null
[ [ "Ion-coupled secondary-active transporters are integral membrane proteins involved in the cellular uptake and release of various substrates across cell membranes .", "These transporters transport the main substrate uphill against its concentration gradient by coupling with the favorable downhill transport...
[ "LeuT-like fold Na-dependent secondary active transporters form a large family of integral membrane proteins that transport various substrates against their concentration gradient across lipid membranes , using the free energy stored in the downhill concentration gradient of sodium ions .", "These transporters pl...
[ "This study provides direct insights of how ion-dependent secondary transporters couples ion gradients to transport of a substrate .", "We conclude that the apo-form of a protein samples multiple conformational states separated by only small barriers .", "Binding of a single ion is sufficient to shift this conf...
2013
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "plant anatomy", "medicine and health sciences", "applied mathematics", "brassica", "light", "electromagnetic radiation", "physiological processes", "plant science", "model organisms", "mathematics", "experimental organism systems", "population biology", "plants", "arabidopsis thaliana", ...
Variation in plastic responses to light results from selection in different competitive environments—A game theoretical approach using virtual plants
journal.pcbi.1007253
null
[ [ "In the course of evolution , plants have evolved traits often specific to a certain environment .", "When growth conditions change , the selection pressure on trait values change , which subsequently can change selection on genotypes .", "However , due to phenotypic plasticity one genotype can exhibi...
[ "Phenotypic plasticity is a vital strategy for plants to deal with changing conditions by inducing phenotypes favourable in different environments .", "Understanding how natural selection acts on variation in phenotypic plasticity in plants is therefore a central question in ecology , but is often ignored in mode...
[ "Plants are able to respond to changes in the environment .", "Particularly , plants can show different structural traits ( e . g . stem height and leaf size ) in different planting densities .", "These trait changes are the result of so-called plastic responses that can be induced by changes in the light spect...
2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "molecular neuroscience", "developmental neuroscience", "cellular neuroscience", "synaptic plasticity", "neuromuscular junction", "neurobiology of disease and regeneration", "neuronal morphology", "axon guidance", "signaling pathways", "biology", "neuroscience", "neurophysiology" ]
The Highwire Ubiquitin Ligase Promotes Axonal Degeneration by Tuning Levels of Nmnat Protein
journal.pbio.1001440
Highwire, a conserved axonal E3 ubiquitin ligase, regulates the initiation of axonal degeneration after injury in Drosophila by regulating the levels of the NAD+ biosynthetic enzyme, Nmnat, and the Wnd kinase.
[ [ "Axon degeneration can be induced by a variety of insults , including injury .", "When an axon is transected from the cell body , the distal axon “stump” degenerates through a regulated self-destruction process called Wallerian degeneration [1] .", "This process appears to be actively regulated in axo...
[ "Axonal degeneration is a hallmark of many neuropathies , neurodegenerative diseases , and injuries .", "Here , using a Drosophila injury model , we have identified a highly conserved E3 ubiquitin ligase , Highwire ( Hiw ) , as an important regulator of axonal and synaptic degeneration .", "Mutations in hiw str...
[ "Axons degenerate after injury and during neurodegenerative diseases , but we are still searching for the cellular mechanism responsible for this degeneration .", "Here , using a nerve crush injury assay in the fruit fly Drosophila , we have identified a role for a conserved molecule named Highwire ( Hiw ) in the...
2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]
[ "genome-wide association studies", "medicine and health sciences", "genetic networks", "protein interactions", "applied mathematics", "immunology", "simulation and modeling", "algorithms", "mathematics", "statistics (mathematics)", "network analysis", "genome analysis", "research and analysi...
Extracting replicable associations across multiple studies: Empirical Bayes algorithms for controlling the false discovery rate
journal.pcbi.1005700
null
[ [ "Confidence in reported findings is a prerequisite for advancing any scientific field .", "Such confidence is achieved by showing replication of discoveries in new studies [1] .", "In recent years studies have shown low reproducibility of results in several domains , including economics [2] , psycholo...
[ "In almost every field in genomics , large-scale biomedical datasets are used to report associations .", "Extracting associations that recur across multiple studies while controlling the false discovery rate is a fundamental challenge .", "Here , we propose a new method to allow joint analysis of multiple studi...
[ "When analyzing results from multiple studies , extracting replicated associations is the first step towards making new discoveries .", "The standard approach for this task is to use meta-analysis methods , which usually make an underlying null hypothesis that a gene has no effect in all studies .", "On the oth...
2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]
[ "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "rna extraction", "microbiology", "geographical locations", "viruses", "multivariate analysis", "mathematics", "rna viruses", "statistics (mathematics)", "tanzania", "molecular biology techniq...
Development and validation of four one-step real-time RT-LAMP assays for specific detection of each dengue virus serotype
journal.pntd.0006381
null
[ [ "Dengue is a worldwide public health concern annually affecting more than 100 million people in tropical and subtropical areas [1 , 2] .", "It is caused by dengue virus ( DENV ) , the most common vector-borne viral pathogen of humans , transmitted by mosquitoes of the Aedes genus ( primarily A . aegypti a...
[ "4 one-step , real-time , reverse transcription loop-mediated isothermal amplification ( RT-LAMP ) assays were developed for the detection of dengue virus ( DENV ) serotypes by considering 2 , 056 full genome DENV sequences .", "DENV1 and DENV2 RT-LAMP assays were validated with 31 blood and 11 serum samples from...
[ "The co-existence of several dengue virus ( DENV ) serotypes within the same location and/or individuals as well as a single mosquito being able to carry multiple DENV serotypes highlight the necessity of specific diagnostic tools capable of detect and serotype DENV strains circulating worldwide .", "In addition ...
2018
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine and health sciences", "microcephaly", "pathology and laboratory medicine", "chikungunya infection", "infectious disease epidemiology", "pathogens", "geographical locations", "microbiology", "spatial epidemiology", "tropical diseases", "viruses", "developmental biology", "rna viruse...
Zika virus infection and microcephaly: Evidence regarding geospatial associations
journal.pntd.0006392
null
[ [ "On February 1 , 2016 , the World Health Organization ( WHO ) declared that the Zika virus ( ZIKV ) epidemic was an international public health emergency [1] .", "The increasing evidence of a causal relationship between ZIKV in pregnant women and an unpredicted rise in the incidence of microcephaly , late...
[ "Although the Zika virus ( ZIKV ) epidemic ceased to be a public health emergency by the end of 2016 , studies to improve knowledge about this emerging disease are still needed , especially those investigating a causal relationship between ZIKV in pregnant women and microcephaly in neonates .", "However , there a...
[ "The increasing evidence of a relationship between ZIKV in pregnant women and fetal congenital ZIKV syndrome with microcephaly has been reported in the literature over the last two years .", "Our findings suggest a spatial dependency between the diseases .", "Therefore , using the spatial pattern of ZIKV incide...
2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "medicine", "biology" ]
Mining the LIPG Allelic Spectrum Reveals the Contribution of Rare and Common Regulatory Variants to HDL Cholesterol
journal.pgen.1002393
null
[ [ "Numerous studies have associated low levels of high density lipoprotein cholesterol ( HDL-C ) with an increased risk of developing coronary heart disease ( CHD ) [1] , [2] , [3] , [4] , [5] , [6] , [7] .", "HDL-C levels are approximately 50% heritable [8] .", "Genome-wide association studies ( GWAS )...
[ "Genome-wide association studies ( GWAS ) have successfully identified loci associated with quantitative traits , such as blood lipids .", "Deep resequencing studies are being utilized to catalogue the allelic spectrum at GWAS loci .", "The goal of these studies is to identify causative variants and missing her...
[ "Genetic association studies have identified genomic regions that affect quantifiable traits such as lipid levels .", "When a gene and a trait are found to be associated with one another , the gene is often further studied to determine its role in affecting the trait .", "One approach is to sequence the gene in...
2011
[ "Introduction", "Results/Discussion", "Materials and Methods" ]
[ "genetic polymorphism", "natural selection", "genetics", "plant genetics", "population genetics", "biology", "evolutionary biology", "molecular genetics", "evolutionary genetics", "genetics and genomics" ]
Allelic Heterogeneity and Trade-Off Shape Natural Variation for Response to Soil Micronutrient
journal.pgen.1002814
null
[ [ "Some of the most important constraints that plants have to adapt to are those related to soil properties [1] , [2] .", "These are also possibly some of the least well studied constraints , because they are spatially heterogeneous , thus not prone to typical geographic clines [3] , [4] , and require analy...
[ "As sessile organisms , plants have to cope with diverse environmental constraints that may vary through time and space , eventually leading to changes in the phenotype of populations through fixation of adaptive genetic variation .", "To fully comprehend the mechanisms of evolution and make sense of the extensiv...
[ "Plants are studied for their ability to adapt to their environment and especially to the physical constraints to which they are subjected .", "It is expected that they evolve in promoting genetic variants favorable under their native conditions , which could lead to negative consequences in other conditions .", ...
2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[]
Neutral Models of Microbiome Evolution
journal.pcbi.1004365
null
[ [ "Our framework applies to a population of hosts and an available pool of microbial colonists .", "As a first step , we assume that hosts do not exert any preferences on the microbial taxa they acquire .", "Similarly , we assume that microbes do not interfere with host reproductive capacity , or the su...
[ "There has been an explosion of research on host-associated microbial communities ( i . e . , microbiomes ) .", "Much of this research has focused on surveys of microbial diversities across a variety of host species , including humans , with a view to understanding how these microbiomes are distributed across spa...
[ "Microbial communities associated with animals and plants ( i . e . , microbiomes ) are implicated in the day-to-day functioning of their hosts .", "However , we do not yet know how these host-microbiome associations evolve .", "In this paper , we develop a computational framework for modelling the evolution of...
2015
[ "Introduction", "Results", "Discussion", "Methods" ]
[ "neuroscience/neurobiology of disease and regeneration", "neurological disorders/neurorehabilitation and trauma", "neuroscience/sensory systems" ]
Axonal Dynamics of Excitatory and Inhibitory Neurons in Somatosensory Cortex
journal.pbio.1000395
Electrophysiology-delivery of fluorescent viral vectors-and two-photon microscopy were used to demonstrate the rapidity of axonal restructuring of both excitatory and inhibitory neurons in rodent cortical layer II/III following alterations in sensory experience.
[ [ "The adult cortex adapts to alterations in sensory experience .", "This experience-dependent plasticity is evidenced by the functional reorganization of the primary sensory maps of the brain [1]–[12] , synaptogenesis in the adult brain [13]–[16] , and reorganization of dendrites [17] , [18] .", "Detai...
[ "Cortical topography can be remapped as a consequence of sensory deprivation , suggesting that cortical circuits are continually modified by experience .", "To see the effect of altered sensory experience on specific components of cortical circuits , we imaged neurons , labeled with a genetically modified adeno-a...
[ "The adult brain is capable of learning new tasks and being shaped by new experiences .", "Evidence for experience-dependent plasticity of the adult cerebral cortex is seen in the functional rearrangement of cortical maps of sensory input and in the formation of new connections following alteration of sensory exp...
2010
[ "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine and health sciences", "ecology", "entomology", "epidemiology", "vector biology", "arthropod vectors", "biology and life sciences", "insect vectors", "zoology", "disease vectors", "behavioral ecology" ]
Host-Seeking Behavior and Dispersal of Triatoma infestans, a Vector of Chagas Disease, under Semi-field Conditions
journal.pntd.0003433
null
[ [ "Chagas disease , a vector-borne disease caused by the parasite Trypanosoma cruzi , affects from 7 to 8 million people in the Americas [1] .", "The vast majority of people infected are not detected [2] , [3] , and when the disease manifests clinically it cannot be reversed and can be fatal [2]–[4] .", ...
[ "Chagas disease affects millions of people in Latin America .", "The control of this vector-borne disease focuses on halting transmission by reducing or eliminating insect vector populations .", "Most transmission of Trypanosoma cruzi , the causative agent of Chagas disease , involves insects living within or v...
[ "Chagas disease is transmitted by triatomine bugs that actively disperse by walking and flying .", "The control of this vector-borne disease focuses on reducing or eliminating the insect vector populations .", "Most transmission of Trypanosoma cruzi , the causative agent of Chagas disease , involves insects liv...
2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "mus (mouse)", "genetics and genomics" ]
Regional Variation in the Density of Essential Genes in Mice
journal.pgen.0030072
null
[ [ "In the era of complete genomes , the total number of genes in a sequenced organism can now be predicted , but the function and selective importance of a substantial fraction of genes remains unknown .", "Some gene functions may be of central importance to the organism , whereas other gene functions may b...
[ "In most species , and particularly in vertebrates , the percentage of genes absolutely required for survival , the essential genes , has not been estimated .", "To obtain this estimation , we used the mouse as an experimental model to carry out high-efficiency N-ethyl-N-nitrosourea ( ENU ) mutagenesis screens in...
[ "The genome sequences of many organisms are now complete .", "However , speculation remains regarding the function of many newly discovered genes .", "There is also debate about the percentage of genes that are required to build an organism .", "These genes , which are necessary for the development of the org...
2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "transposons", "retrotransposons", "biology", "molecular cell biology", "molecular biology" ]
Rescuing Alu: Recovery of New Inserts Shows LINE-1 Preserves Alu Activity through A-Tail Expansion
journal.pgen.1002842
null
[ [ "Long INterspersed Element-1 ( LINE-1 or L1 ) and the Short INterspersed Element ( SINE ) Alu are non-long-terminal-repeat ( non-LTR ) retroelements that are responsible for approximately one third of the human genome [1] .", "Due to their ability to randomly insert throughout the genome [2] , both L1 and...
[ "Alu elements are trans-mobilized by the autonomous non-LTR retroelement , LINE-1 ( L1 ) .", "Alu-induced insertion mutagenesis contributes to about 0 . 1% human genetic disease and is responsible for the majority of the documented instances of human retroelement insertion-induced disease .", "Here we introduce...
[ "SINEs are mobile elements that are found ubiquitously throughout a large diversity of genomes from plants to mammals .", "The human SINE , Alu , is among the most successful mobile elements , with more than one million copies in the genome .", "Due to its high activity and ability to insert throughout the geno...
2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]
[ "connectomics", "neuroanatomy", "computational neuroscience", "biology", "neuroscience" ]
Communication Efficiency and Congestion of Signal Traffic in Large-Scale Brain Networks
journal.pcbi.1003427
null
[ [ "Constrained by finite resources , such as metabolism and physical space , which place severe limits on the number and density of synaptic connections , brain networks are an example of how optimized topology may facilitate information flow .", "The structural topology of cortical networks can be represen...
[ "The complex connectivity of the cerebral cortex suggests that inter-regional communication is a primary function .", "Using computational modeling , we show that anatomical connectivity may be a major determinant for global information flow in brain networks .", "A macaque brain network was implemented as a co...
[ "A fundamental question in systems neuroscience is how the structural connectivity of the cerebral cortex shapes global communication .", "Here , using computational modeling in conjunction with an anatomically realistic structural network , we show that cortico-cortical communication is constrained by high-level...
2014
[ "Introduction", "Materials and Methods", "Results/Discussion" ]
[]
Lipid Receptor S1P1 Activation Scheme Concluded from Microsecond All-Atom Molecular Dynamics Simulations
journal.pcbi.1003261
null
[ [ "Sphingolipids together with glycerol-based phospholipids are major structural components of cell membranes .", "In response to various extracellular stimuli , including growth factors , inflammatory cytokines , antigens , and agonists of some GPCRs , the sphingolipids can be metabolized into potent media...
[ "Sphingosine 1-phosphate ( S1P ) is a lysophospholipid mediator which activates G protein–coupled sphingosine 1-phosphate receptors and thus evokes a variety of cell and tissue responses including lymphocyte trafficking , endothelial development , integrity , and maturation .", "We performed five all-atom 700 ns ...
[ "The activation of G-protein-coupled receptors ( GPCRs ) depends on small differences in agonist and antagonist structures resulting in specific forces they impose on the helical bundle of the receptor .", "Having the crystal structures of GPCRs in different stages of activation it is possible to investigate the ...
2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]
[ "computational chemistry", "molecular dynamics", "biophysic al simulations", "chemistry", "biology", "computational biology" ]
Quantitative Predictions of Binding Free Energy Changes in Drug-Resistant Influenza Neuraminidase
journal.pcbi.1002665
null
[ [ "Current plans for managing future influenza pandemics include the use of therapeutic and prophylactic drugs , such as zanamivir [1] and oseltamivir [2] , that target the virus surface glycoprotein neuraminidase ( NA ) [3] .", "Inhibition of NA reduces the spread of the virus in the respiratory tract by i...
[ "Quantitatively predicting changes in drug sensitivity associated with residue mutations is a major challenge in structural biology .", "By expanding the limits of free energy calculations , we successfully identified mutations in influenza neuraminidase ( NA ) that confer drug resistance to two antiviral drugs ,...
[ "The capacity of the influenza virus to rapidly mutate and render resistance to a handful of FDA approved neuraminidase ( NA ) inhibitors represents a significant human health concern .", "To gain an atomic-level understanding of the mechanisms behind drug resistance , we applied a novel computational approach to...
2012