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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "dermatology", "invertebrates", "united states", "medicine and health sciences", "ixodes", "pathology and laboratory medicine", "pathogens", "california", "geographical locations", "microbiology", "rickettsia", "animals", "north america", "developmental biology", "nymphs", "signs and s...	The Eco-epidemiology of Pacific Coast Tick Fever in California	journal.pntd.0005020	null	[ [ "Rickettsia philipii ( type strain “Rickettsia 364D” ) is a spotted fever group ( SFG ) rickettsia closely related to Rickettsia rickettsii , the etiologic agent of Rocky Mountain spotted fever ( RMSF ) [1–3] .", "First isolated in 1966 from an adult Pacific Coast tick , Dermacentor occidentalis , collect...	[ "Rickettsia philipii ( type strain “Rickettsia 364D” ) , the etiologic agent of Pacific Coast tick fever ( PCTF ) , is transmitted to people by the Pacific Coast tick , Dermacentor occidentalis .", "Following the first confirmed human case of PCTF in 2008 , 13 additional human cases have been reported in Californ...	[ "Rickettsia philipii , a spotted fever group rickettsia , is the etiologic agent of Pacific Coast tick fever , an emerging tick-borne disease transmitted by the Pacific Coast tick ( Dermacentor occidentalis ) .", "The Pacific Coast tick’s range , and thus potential for exposure to R . philipii , includes most of ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/neuronal and glial cell biology", "genetics and genomics/animal genetics", "ophthalmology/retinal disorders", "genetics and genomics/gene expression", "ophthalmology", "neurological disorders/neuro-ophthalmology and neuro-otology", "developmental biology/neurodevelopment", "neuroscience/...	CLRN1 Is Nonessential in the Mouse Retina but Is Required for Cochlear Hair Cell Development	journal.pgen.1000607	null	[ [ "Usher syndrome ( USH ) is characterized by bilateral combined blindness and deafness , and is the most common cause of the dual sensory deficit [1] .", "To date , there are 11 chromosomal loci with 9 genes identified , and over 100 mutations directly associated with USH ( for reviews see [2]–[4] ) .", ...	[ "Mutations in the CLRN1 gene cause Usher syndrome type 3 ( USH3 ) , a human disease characterized by progressive blindness and deafness .", "Clarin 1 , the protein product of CLRN1 , is a four-transmembrane protein predicted to be associated with ribbon synapses of photoreceptors and cochlear hair cells , and rec...	[ "Usher syndrome ( USH ) is a progressive disease affecting two primary senses: vision and hearing .", "Often by the third decade of life , affected persons have lost the majority of their rod photoreceptors , which leads to night blindness and peripheral vision loss .", "Similarly , hearing loss often progresse...	2009
[ "Introduction", "Results/Discussion", "Material and Methods" ]	[ "morphogens", "biochemical simulations", "developmental biology", "organism development", "biophysic al simulations", "adhesion molecules", "molecular development", "signaling", "biology", "computational biology", "signaling networks", "pattern formation" ]	Cell-Sorting at the A/P Boundary in the Drosophila Wing Primordium: A Computational Model to Consolidate Observed Non-Local Effects of Hh Signaling	journal.pcbi.1002025	null	[ [ "During embryonic development of complex multicellular organisms , spatial reference", "points need to be established within tissues .", "These are often formed by specialized", "groups of cells that are capable of signaling to neighboring cells .", "Such signaling", "centers define coordi...	[ "Non-intermingling , adjacent populations of cells define compartment boundaries;", "such boundaries are often essential for the positioning and the maintenance of", "tissue-organizers during growth .", "In the developing wing primordium of", "Drosophila melanogaster , signaling by the secreted protein", ...	[ "In developing animal tissues , cells can often re-arrange locally and mix", "relatively freely .", "However , in some stereotypic and crucially important", "instances during body development , cells will strictly not intermingle , and", "instead form sharp boundaries along which they will sort out from eac...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biological data management", "population modeling", "biology", "genomics", "computational biology" ]	Environmental and State-Level Regulatory Factors Affect the Incidence of Autism and Intellectual Disability	journal.pcbi.1003518	null	[ [ "Autism spectrum disorders ( ASD ) are a collection of chronic , complex neuropsychiatric diseases with well-characterized comorbidities and increasing apparent prevalence [1] .", "With few and limited effective treatments and considerable financial burden , its etiology remains a scientific puzzle .", ...	[ "Many factors affect the risks for neurodevelopmental maladies such as autism spectrum disorders ( ASD ) and intellectual disability ( ID ) .", "To compare environmental , phenotypic , socioeconomic and state-policy factors in a unified geospatial framework , we analyzed the spatial incidence patterns of ASD and ...	[ "Disease clusters are defined as geographically compact areas where a particular disease , such as a cancer , shows a significantly increased rate .", "It is presently unclear how common such clusters are for neurodevelopmental maladies , such as autism spectrum disorders ( ASD ) and intellectual disability ( ID ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele	journal.pgen.1005527	null	[ [ "The classical model for selection , and the one that has received most attention , is the “hard sweep” model , in which a single mutation conveys higher fitness immediately upon occurrence , and rapidly rises in frequency , eventually reaching fixation [17 , 33] .", "Under this model , we can partition t...	[ "Methods for detecting the genomic signatures of natural selection have been heavily studied , and they have been successful in identifying many selective sweeps .", "For most of these sweeps , the favored allele remains unknown , making it difficult to distinguish carriers of the sweep from non-carriers .", "I...	[ "Methods for detecting the genomic signatures of natural selection have been heavily studied , and they have been successful in identifying genomic regions under positive selection .", "However , methods that detect positive selective sweeps do not typically identify the favored allele , or even the haplotypes ca...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "hair growth", "telogen phase", "neuroscience", "cell differentiation", "epithelial cells", "physiological processes", "developmental biology", "stem cells", "chromatophores", "anagen phase", "developmental neuroscience", "animal cells", "melanocytes", "ge...	CD34 defines melanocyte stem cell subpopulations with distinct regenerative properties	journal.pgen.1008034	null	[ [ "Neural crest-derived melanocyte stem cells ( McSCs ) are responsible for producing differentiated melanocytes during each hair follicle ( HF ) cycle .", "During embryogenesis , neural crest cells emerging from neural tube generate melanoblasts which migrate to specific destinations including eye , epider...	[ "Melanocyte stem cells ( McSCs ) are the undifferentiated melanocytic cells of the mammalian hair follicle ( HF ) responsible for recurrent generation of a large number of differentiated melanocytes during each HF cycle .", "HF McSCs reside in both the CD34+ bulge/lower permanent portion ( LPP ) and the CD34- sec...	[ "The hair follicle ( HF ) undergoes three different stages , anagen , catagen , and telogen during each hair cycle .", "In anagen , melanocyte stem cells ( McSCs ) give rise to differentiated melanocytes which are responsible for coloration of hair .", "In catagen , melanocytes undergo apoptosis while McSCs are...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Conformational Dynamics and Binding Free Energies of Inhibitors of BACE-1: From the Perspective of Protonation Equilibria	journal.pcbi.1004341	null	[ [ "Alzheimer’s disease is a neurodegenerative disorder characterized by loss of memory and failure in cognitive abilities , resulting from synaptic dysfunction and neuronal death in the brain [1–5] .", "Major damages found in the brains of Alzheimer’s patients include cerebral and vascular deposits of insol...	[ "BACE-1 is the β-secretase responsible for the initial amyloidogenesis in Alzheimer’s disease , catalyzing hydrolytic cleavage of substrate in a pH-sensitive manner .", "The catalytic mechanism of BACE-1 requires water-mediated proton transfer from aspartyl dyad to the substrate , as well as structural flexibilit...	[ "Formation of insoluble amyloid plaques in the vascular and hippocampal areas of the brain characterizes Alzheimer’s disease , a devastating neurodegenerative disorder causing dementia .", "Site-specific hydrolytic catalysis of β-secretase , or BACE-1 , is responsible for production of oligomerative amyloid β-pep...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "endocrine tumors", "carcinomas", "endometrial carcinoma", "cancers and neoplasms", "oncology", "mutation", "methylation", "adenocarcinomas", "head and neck tumors", "epigenetics", "dna", "dna methylation", "chromatin", "head and neck squamous cell carcino...	Significant associations between driver gene mutations and DNA methylation alterations across many cancer types	journal.pcbi.1005840	null	[ [ "DNA methylation ( DNAm ) is highly dysregulated in cancers from many organs [1 , 2] , displaying aberrant CpG island ( CGI ) hypermethylation and long-range blocks of hypomethylation .", "Moreover , dysregulated DNAm at specific locations within the genome can often be used to divide heterogeneous tumors...	[ "Recent evidence shows that mutations in several driver genes can cause aberrant methylation patterns , a hallmark of cancer .", "In light of these findings , we hypothesized that the landscapes of tumor genomes and epigenomes are tightly interconnected .", "We measured this relationship using principal compone...	[ "Mutations that alter the function of driver genes by changing DNA nucleotides have been recognized as key players in cancer progression .", "However , recent evidence has shown that DNA methylation , which can control gene expression , is also highly dysregulated in cancer and contributes to carcinogenesis .", ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemical simulations", "cellular neuroscience", "synapses", "computational neuroscience", "biology", "computational biology", "neuroscience", "neurophysiology" ]	Computational Investigation of the Changing Patterns of Subtype Specific NMDA Receptor Activation during Physiological Glutamatergic Neurotransmission	journal.pcbi.1002106	null	[ [ "Synaptic neurotransmission in excitatory neural circuits is governed primarily by the activation of AMPA receptors ( AMPARs ) and NMDA receptors ( NMDARs ) , two types of ionotropic glutamate receptors located on dendritic spines .", "Although AMPARs are critical in mediating action potential firing thro...	[ "NMDA receptors ( NMDARs ) are the major mediator of the postsynaptic response during synaptic neurotransmission .", "The diversity of roles for NMDARs in influencing synaptic plasticity and neuronal survival is often linked to selective activation of multiple NMDAR subtypes ( NR1/NR2A-NMDARs , NR1/NR2B-NMDARs , ...	[ "Release of glutamate from one neuron onto glutamate receptors on adjacent neurons serves as the primary basis for neuronal communication .", "Further , different types of glutamate signals produce unique responses within the neuronal network , providing the ability for glutamate receptors to discriminate between...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public and occupational health", "infectious diseases", "helminth infections", "medicine and health sciences", "schistosomiasis", "diagnostic medicine", "infectious disease epidemiology", "epidemiology", "global health", "neglected tropical diseases", "tropical diseases", "parasitic diseases"...	Diagnostic Performance of Schistosoma Real-Time PCR in Urine Samples from Kenyan Children Infected with Schistosoma haematobium: Day-to-day Variation and Follow-up after Praziquantel Treatment	journal.pntd.0002807	null	[ [ "An estimated 119 million people are infected with Schistosoma haematobium worldwide [1] with sub-Saharan Africa as the major geographical area at risk [2] .", "In up to 75% of infected individuals both urinary and genital tracts are affected , hence the recent renaming of “urinary” to “urogenital” schist...	[ "In an effort to enhance accuracy of diagnosis of Schistosoma haematobium , this study explores day-to-day variability and diagnostic performance of real-time PCR for detection and quantification of Schistosoma DNA compared to other diagnostic tools in an endemic area before and after treatment .", "Previously co...	[ "Schistosoma haematobium is a blood fluke that causes severe urogenital pathology and affects millions of people , mainly in sub-Sahara Africa .", "Current diagnosis is based on microscopic examination of urine samples , but this method is not only observer dependent , but also known for its low sensitivity and h...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "nuclear import", "medicine and health sciences", "protein interactions", "pathology and laboratory medicine", "hela cells", "molecular probe techniques", "gene regulation", "pathogens", "cell processes", "biological cultures", "microbiology", "immunoblotting", "retroviruses", "viruses", ...	Multiple components of the nuclear pore complex interact with the amino-terminus of MX2 to facilitate HIV-1 restriction	journal.ppat.1007408	null	[ [ "Human myxovirus resistance 2 ( MX2/MXB ) is an interferon-stimulated gene ( ISG ) , and a key contributor to the type-1 interferon-induced post-entry inhibition of human immunodeficiency virus type-1 ( HIV-1 ) infection [1–3] .", "The MX2-mediated block to HIV-1 infection occurs after reverse transcripti...	[ "Human myxovirus resistance 2 ( MX2/MXB ) is an interferon-induced post-entry inhibitor of human immunodeficiency virus type-1 ( HIV-1 ) infection .", "While the precise mechanism of viral inhibition remains unclear , MX2 is localized to the nuclear envelope , and blocks the nuclear import of viral cDNAs .", "T...	[ "The movement of large molecules into the cell nucleus is regulated at specific sites within the nuclear envelope termed nuclear pores .", "To infect cells productively , human immunodeficiency virus type-1 ( HIV-1 ) must traverse the nuclear envelope to enable integration of the viral DNA into the genomic DNA of...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "neutral lipids", "diet", "developmental biology", "fungi", "model organisms", "nutrition", "experimental organism systems", "hypoxia", "plants", "saccharomyces", "research and analysis methods", "lipids", "fats", "life cycles", "algae", "yeast", "bi...	Both living bacteria and eukaryotes in the mosquito gut promote growth of larvae	journal.pntd.0006638	null	[ [ "Mosquitoes are aquatic during their juvenile stages and grow by feeding on organic detritus , unicellular organisms and small invertebrates [1 , 2] .", "Larval and adult stage mosquitoes also host a community of living microbes in their digestive tract that form a gut microbiota [3 , 4] .", "Laborato...	[ "We recently reported that larval stage Aedes aegypti and several other species of mosquitoes grow when living bacteria are present in the gut but do not grow when living bacteria are absent .", "We further reported that living bacteria induce a hypoxia signal in the gut , which activates hypoxia-induced transcri...	[ "Studies conducted in our laboratory indicate that several species of mosquito larvae require living bacteria in their gut to grow .", "Previous results also show that living bacteria reduce gut oxygen levels below 5% and that bacteria-induced gut hypoxia functions as a signal that activates several processes in ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "virology", "in vitro", "homo (human)", "saccharomyces" ]	HIV-1 Vpr-Mediated G2 Arrest Involves the DDB1-CUL4AVPRBP E3 Ubiquitin Ligase	journal.ppat.0030085	null	[ [ "Human immunodeficiency virus type 1 ( HIV-1 ) viral protein R ( Vpr ) accessory protein is a small 96−amino acid protein that plays several roles during virus infection ( reviewed in [1 , 2] ) .", "In particular , the protein mediates cell cycle arrest at the G2/M transition in various mammalian cells [3...	[ "Human immunodeficiency virus type 1 ( HIV-1 ) viral protein R ( Vpr ) has been shown to cause G2 cell cycle arrest in human cells by inducing ATR-mediated inactivation of p34cdc2 , but factors directly engaged in this process remain unknown .", "We used tandem affinity purification to isolate native Vpr complexe...	[ "Human immunodeficiency virus type 1 ( HIV-1 ) , the causative agent of AIDS , encodes several proteins termed accessory , which play a critical role in viral pathogenesis .", "Collectively , HIV-1 accessory proteins Vif , Vpr , Vpu , and Nef have been shown to manipulate host cell biology to promote viral replic...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience", "developmental biology/aging" ]	Manipulation of Behavioral Decline in Caenorhabditis elegans with the Rag GTPase raga-1	journal.pgen.1000972	null	[ [ "The decline of motor function with age can lead to personal decreases in quality of life and medical morbidity , and also poses challenges for society as a whole .", "Life expectancy has increased substantially and may be expected to increase even further as a result of ongoing research into the molecula...	[ "Normal aging leads to an inexorable decline in motor performance , contributing to medical morbidity and decreased quality of life .", "While much has been discovered about genetic determinants of lifespan , less is known about modifiers of age-related behavioral decline and whether new gene targets may be found...	[ "As humans and animals age , there is an inevitable decrease in functional capacity .", "Elderly individuals can suffer from a decline in motor function , or the ability to move .", "Genetic studies in model organisms have led to the identification of genes that can prolong lifespan .", "Elongation of lifespa...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "immunology/autoimmunity", "cardiovascular disorders/heart failure" ]	Presence of Circulating Anti-Myosin Antibodies in Endomyocardial Fibrosis	journal.pntd.0000661	null	[ [ "Endomyocardial Fibrosis ( EMF ) is a tropical cardiomyopathy of unclear etiopathogenesis and poor prognosis , which is endemic in certain regions of sub-Saharan Africa [1] .", "It is probably the commonest form of restrictive cardiomyopathy , affecting primarily children and adolescents .", "The dist...	[ "Endomyocardial Fibrosis ( EMF ) is a tropical restrictive cardiomyopathy of unknown etiology with high prevalence in Sub-Saharan Africa , for which it is unclear whether the primary target of injury is the endocardial endothelium , the subendocardial fibroblast , the coronary microcirculation or the myocyte .", ...	[ "Endomyocardial Fibrosis is a tropical disease in which the heart cannot open properly to receive blood due to a scar that covers its inner layer .", "It affects mainly children and adolescents , and has a poor prognosis because the cause and mechanisms of scarring are unknown .", "The conventional treatment is...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "systems biology", "plant science", "plant biology", "genetics", "biology", "genomics", "molecular cell biology", "agricultural biotechnology", "genetics and genomics", "agriculture" ]	Genetic Regulation by NLA and MicroRNA827 for Maintaining Nitrate-Dependent Phosphate Homeostasis in Arabidopsis	journal.pgen.1002021	null	[ [ "High yielding crops require the application of large amounts of nitrogen ( N ) and", "phosphorus ( P ) fertilizers .", "However , most of the crop plants are able to take up", "less than 40% of the applied N and P fertilizers and the rest of it is lost", "to the environment .", "This lead...	[ "Plants need abundant nitrogen and phosphorus for higher yield .", "Improving plant", "genetics for higher nitrogen and phosphorus use efficiency would save", "potentially billions of dollars annually on fertilizers and reduce global", "environmental pollution .", "This will require knowledge of molecular...	[ "Higher crop yields require increased use of fertilizers , especially for the prime", "macronutrients nitrogen and phosphorus .", "Increasing nitrogen and phosphorus use", "efficiency in plants would decrease crop production cost and reduce", "environmental pollution .", "In an attempt to isolate the regu...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genome-wide association studies", "medicine and health sciences", "body fluids", "bipolar disorder", "mathematics", "statistics (mathematics)", "genome analysis", "mood disorders", "research and analysis methods", "genome complexity", "mathematical and statistical techniques", "gene expressio...	Identification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue	journal.pgen.1007607	null	[ [ "Schizophrenia and affective disorders , comprising bipolar disorder and major depressive disorder , constitute a significant global burden of disease .", "Worldwide it is estimated that more than 21 million individuals are living with schizophrenia , 60 million with bipolar disorder and over 400 million ...	[ "Schizophrenia and the affective disorders , here comprising bipolar disorder and major depressive disorder , are psychiatric illnesses that lead to significant morbidity and mortality worldwide .", "Whilst understanding of their pathobiology remains limited , large case-control studies have recently identified s...	[ "An estimated 21 million people live worldwide with schizophrenia , 60 million with bipolar disorder , and 400 million with major depressive disorder .", "Recent genome-wide association studies have shed light on the genetic variants linked to these disorders , and increasing evidence suggests that their genetic ...	2018
[ "Introduction", "Material and methods", "Results", "Discussion", "Conclusion" ]	[ "livestock", "medicine and health sciences", "body fluids", "ruminants", "tropical diseases", "diet", "vertebrates", "animals", "mammals", "animal products", "bacterial diseases", "nutrition", "meat", "veterinary science", "infectious diseases", "food", "veterinary diseases", "zoon...	Exploring local knowledge and perceptions on zoonoses among pastoralists in northern and eastern Tanzania	journal.pntd.0005345	null	[ [ "Zoonoses account for the most commonly reported emerging and re-emerging infectious diseases ( EIDs ) in Sub-Saharan Africa [1] .", "There is a large number of human diseases that originate from both domestic and wild animals ( 900 + ) , and a smaller number of zoonoses ( 250+ ) , which are diseases tran...	[ "Zoonoses account for the most commonly reported emerging and re-emerging infectious diseases in Sub-Saharan Africa .", "However , there is limited knowledge on how pastoral communities perceive zoonoses in relation to their livelihoods , culture and their wider ecology .", "This study was carried out to explor...	[ "Zoonoses are diseases transmissible between animals and humans .", "Risk factors include animal slaughter , the handling and preparing food of animal origin and particularly the consumption of such food when raw or undercooked .", "Pastoralists are daily in contact with their livestock and are likely to be mor...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "caenorhabditis", "gene regulation", "parasitic diseases", "animals", "nematode infections", "animal models", "developmental biology", "caenorhabditis elegans", "model organisms", "experimental organism systems", "epigene...	RNAi-mediated knockdown of daf-12 in the model parasitic nematode Strongyloides ratti	journal.ppat.1007705	null	[ [ "In order to survive , nematodes have to be able to adapt to their surrounding conditions .", "In the well-studied model organism Caenorhabditis elegans , worms are able to switch between rapid development through a third stage larvae and the development of long lived dauer third stage larvae , which enab...	[ "The gene daf-12 has long shown to be involved in the dauer pathway in Caenorhabditis elegans ( C . elegans ) .", "Due to the similarities of the dauer larvae of C . elegans and infective larvae of certain parasitic nematodes such as Strongyloides spp .", ", this gene has also been suspected to be involved in t...	[ "Strongyloides ratti is a model parasitic nematode of interest for its use in understanding basic biology and the development of novel helminth therapies .", "However a lack of genetic tools has stymied progress , although CRISPR/Cas9 has recently been reported .", "After determining whether RNAi might work in ...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "infographics", "medicine and health sciences", "body fluids", "tropical diseases", "parasitic diseases", "parasitic protozoans", "reticulocytes", "bone marrow cells", "protozoans", "red blood cells", "bioassays and physiological analysis", "research and analysis methods", "...	Tracking Resilience to Infections by Mapping Disease Space	journal.pbio.1002436	This study shows that infections cause sick hosts to loop through disease space on their return back to health; resilient individuals take tiny loops through this space, minimizing the impact of the infection.	[ [ "As a field , we study infectious diseases to learn how to reduce their impact .", "One common method is to use antibiotics to limit pathogen growth .", "An alternative approach , which potentially avoids the risk of pathogen evolution of antibiotic resistance , is to limit the damage caused by the in...	[ "Infected hosts differ in their responses to pathogens; some hosts are resilient and recover their original health , whereas others follow a divergent path and die .", "To quantitate these differences , we propose mapping the routes infected individuals take through “disease space . ”", "We find that when plott...	[ "When we get sick , we long for recovery; thus , a major goal of medicine is to promote resilience—the ability of a host to return to its original health following an infection .", "While in the laboratory we can study the response to infection with precise knowledge of inoculation time and dose , sick patients i...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/tropical and travel-associated diseases", "immunology/immunity to infections", "cell biology/cell signaling" ]	MAP Kinase Phosphatase-2 Plays a Critical Role in Response to Infection by Leishmania mexicana	journal.ppat.1001192	null	[ [ "The mitogen-activated protein ( MAP ) kinase phosphatases ( MKPs ) are a family of dual specific phosphatases which regulate the functional activity of the major MAP kinase subfamilies through tyrosine and threonine dephosphorylation [1] .", "At least eleven isoforms exist each with different structures ...	[ "In this study we generated a novel dual specific phosphatase 4 ( DUSP4 ) deletion mouse using a targeted deletion strategy in order to examine the role of MAP kinase phosphatase-2 ( MKP-2 ) in immune responses .", "Lipopolysaccharide ( LPS ) induced a rapid , time and concentration-dependent increase in MKP-2 pr...	[ "In cells of the immune system are switch-on enzymes called kinases which regulate responses to infectious agents such as Leishmania .", "However , in the same cells there are switch-off enzymes known as phosphatases which function to turn off the kinases once they have done their work .", "A lot of studies hav...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	RNAi-Dependent and Independent Control of LINE1 Accumulation and Mobility in Mouse Embryonic Stem Cells	journal.pgen.1003791	null	[ [ "Long-interspersed elements-1 ( LINE-1 or L1 ) belong to the most abundant class of autonomous transposable elements ( TEs ) in mammalian genomes .", "While most L1s are truncated and unable to transcribe or retrotranspose , a fraction of young , full-length L1s are capable of mobilization [1] .", "Ac...	[ "In most mouse tissues , long-interspersed elements-1 ( L1s ) are silenced via methylation of their 5′-untranslated regions ( 5′-UTR ) .", "A gradual loss-of-methylation in pre-implantation embryos coincides with L1 retrotransposition in blastocysts , generating potentially harmful mutations .", "Here , we show...	[ "A basal network of gene regulation orchestrates the processes ensuring maintenance of genome integrity .", "Eukaryotic small RNAs generated by the RNAse-III Dicer have emerged as central players in this network , by mediating gene silencing at the transcriptional or post-transcriptional level via RNA interferenc...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/viral infections", "gastroenterology and hepatology/hepatology", "infectious diseases", "computational biology" ]	Temporal Proteome and Lipidome Profiles Reveal Hepatitis C Virus-Associated Reprogramming of Hepatocellular Metabolism and Bioenergetics	journal.ppat.1000719	null	[ [ "Persistent infection with hepatitis C virus ( HCV ) , a single-stranded positive RNA virus of the Flaviviridae family , is a major cause of liver disease and a global public health problem .", "Chronically infected individuals develop variable degrees of hepatic inflammation and fibrosis , and are at inc...	[ "Proteomic and lipidomic profiling was performed over a time course of acute hepatitis C virus ( HCV ) infection in cultured Huh-7 . 5 cells to gain new insights into the intracellular processes influenced by this virus .", "Our proteomic data suggest that HCV induces early perturbations in glycolysis , the pento...	[ "As parasites , viruses rely on the cells they infect to provide the energy and building blocks required for their survival and propagation .", "However , relatively little is known about the extent to which viruses modulate host cell metabolism and the consequences of these disruptions .", "Here we integrate p...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	α2-Macroglobulin Can Crosslink Multiple Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) Molecules and May Facilitate Adhesion of Parasitized Erythrocytes	journal.ppat.1005022	null	[ [ "About 630 , 000 ( 0 . 3% ) of the approximately 200 million malaria cases each year are fatal [1] .", "The majority occur among African children below the age of five years , who die of severe Plasmodium falciparum malaria [2] .", "The particular virulence of P . falciparum parasites is related to th...	[ "Rosetting , the adhesion of Plasmodium falciparum-infected erythrocytes to uninfected erythrocytes , involves clonal variants of the parasite protein P . falciparum erythrocyte membrane protein 1 ( PfEMP1 ) and soluble serum factors .", "While rosetting is a well-known phenotypic marker of parasites associated w...	[ "Erythrocytes infected by parasites causing severe P . falciparum malaria often form rosettes by binding a number of uninfected erythrocytes .", "Several of the parasite proteins involved are known , whereas the identity of the corresponding host receptor ( s ) on the surrounding erythrocytes is not .", "Althou...	2015
[ "Introduction", "Results", "Discussion" ]	[ "classical mechanics", "neuronal differentiation", "neuroscience", "cell differentiation", "developmental biology", "damage mechanics", "epigenetics", "mammalian genomics", "chromatin", "heterochromatin", "contractile proteins", "actins", "chromosome biology", "animal cells", "proteins",...	Role of dynamic nuclear deformation on genomic architecture reorganization	journal.pcbi.1007289	null	[ [ "In a typical nucleus during interphase , the long strands of genomic DNA are organized in a cell-type specific spatial architecture that plays an important role in DNA transcription , repair , and replication [1] .", "This architecture is partly determined by chromatin loops that form a higher-order geno...	[ "Higher-order genomic architecture varies according to cell type and changes dramatically during differentiation .", "One of the remarkable examples of spatial genomic reorganization is the rod photoreceptor cell differentiation in nocturnal mammals .", "The inverted nuclear architecture found in adult mouse ro...	[ "The motion and spatial reorganization of sub-nuclear domains have been extensively studied using microscopy , but the underlying mechanisms that promote the reorganization are still poorly understood .", "We found that dynamic nuclear deformation provides a driving force for long-range migration and aggressive c...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Proximity-dependent proteomics of the Chlamydia trachomatis inclusion membrane reveals functional interactions with endoplasmic reticulum exit sites	journal.ppat.1007698	null	[ [ "Chlamydia trachomatis is an obligate intracellular bacterium that infects mucosal epithelial cells of the endocervix and conjunctiva .", "It infects millions of people every year and is the etiological agent of ocular trachoma [1 , 2] .", "Although C . trachomatis infections are effectively treated w...	[ "Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection , responsible for millions of infections each year .", "Despite this high prevalence , the elucidation of the molecular mechanisms of Chlamydia pathogenesis has been difficult due to limitations in genetic tools and its in...	[ "Chlamydia are obligate intracellular bacteria that require the establishment and maintenance of a host vacuole ( the inclusion ) for their developmental growth .", "Chlamydiae modify the inclusion membrane through the secretion of type III membrane proteins and recruited host factors .", "These membrane modifi...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biomacromolecule-ligand interactions", "medicine and health sciences", "medicinal chemistry", "african trypanosomiasis", "enzymes", "tropical diseases", "enzymology", "chemical biology", "neglected tropical diseases", "pharmacology", "enzyme chemistry", "veterinary science", "infectious dis...	Structures of Trypanosoma brucei Methionyl-tRNA Synthetase with Urea-Based Inhibitors Provide Guidance for Drug Design against Sleeping Sickness	journal.pntd.0002775	null	[ [ "Human African trypanosomiasis ( HAT ) , also called sleeping sickness , is a disease caused by the protozoan parasite Trypanosoma brucei .", "Up to 60 million people in sub-Saharan Africa are estimated to be at risk for the infection [1] .", "The disease usually occurs in two stages .", "In the f...	[ "Methionyl-tRNA synthetase of Trypanosoma brucei ( TbMetRS ) is an important target in the development of new antitrypanosomal drugs .", "The enzyme is essential , highly flexible and displaying a large degree of changes in protein domains and binding pockets in the presence of substrate , product and inhibitors ...	[ "Infection by the protozoan parasite Trypanosoma brucei causes sleeping sickness , also called human African trypanosomiasis .", "Without treatment , the disease is fatal yet current therapeutic options are inadequate and better medicines are needed .", "We have previously reported several potent inhibitors of ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Envelope Deglycosylation Enhances Antigenicity of HIV-1 gp41 Epitopes for Both Broad Neutralizing Antibodies and Their Unmutated Ancestor Antibodies	journal.ppat.1002200	null	[ [ "Two rare human monoclonal antibodes ( mAbs ) , 2F5 and 4E10 , bind to linear epitopes in the gp160 membrane proximal external region ( MPER ) [1] , [2] .", "The core sequence of 2F5 epitope is aa 662–668 ( ELDKWAS ) , and that of 4E10 is aa 671–676 NWFDIT [3] .", "The crystal structures of the 2F5 an...	[ "The HIV-1 gp41 envelope ( Env ) membrane proximal external region ( MPER ) is an important vaccine target that in rare subjects can elicit neutralizing antibodies .", "One mechanism proposed for rarity of MPER neutralizing antibody generation is lack of reverted unmutated ancestor ( putative naive B cell recepto...	[ "Critical to the design of an effective HIV-1 vaccine that will induce long-lasting broadly neutralizing antibodies is to understand why broad neutralizing antibodies are not induced .", "One hypothesis is that there are “holes” in the naïve B cell repertoires for unmutated B cell receptors that can bind to HIV-1...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "immune system proteins", "infectious diseases", "medicine and health sciences", "chagas disease", "proteins", "protozoan infections", "neglected tropical diseases", "biology and life sciences", "immunology", "tropical diseases", "antibodies", "immunologic techniques", "imm...	Development of Peptide-Based Lineage-Specific Serology for Chronic Chagas Disease: Geographical and Clinical Distribution of Epitope Recognition	journal.pntd.0002892	null	[ [ "Chagas disease ( South American trypanosomiasis ) is still considered to be the most important parasitic disease in Latin America , despite notable success with control of household infestation by the triatomine insect vectors .", "Up to 8 million people are estimated to be chronically infected with the ...	[ "Chagas disease , caused by infection with the protozoan Trypanosoma cruzi , remains a serious public health issue in Latin America .", "Genetically diverse , the species is sub-divided into six lineages , known as TcI–TcVI , which have disparate geographical and ecological distributions .", "TcII , TcV , and T...	[ "Chagas disease remains a significant public health issue in Latin America .", "Caused by the single-celled parasite Trypanosoma cruzi , the main route of infection is via contact with contaminated faeces from blood-sucking triatomine bugs , but following successful insecticide spraying campaigns , congenital , f...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "innate immune system", "medicine and health sciences", "model organisms", "pathology and laboratory medicine", "immunity", "host-pathogen interactions", "virology", "biology and life sciences", "immunology", "microbiology", "pathogenesis", "research and analysis methods", ...	Different Modes of Retrovirus Restriction by Human APOBEC3A and APOBEC3G In Vivo	journal.ppat.1004145	null	[ [ "Retroviruses are enveloped RNA viruses that infect many different species including humans .", "The constant “battle” between retroviruses and mammalian cells has resulted in the evolution of proteins that act as cellular restriction factors .", "These restriction factors provide defense against retr...	[ "The apolipoprotein B editing complex 3 ( A3 ) cytidine deaminases are among the most highly evolutionarily selected retroviral restriction factors , both in terms of gene copy number and sequence diversity .", "Primate genomes encode seven A3 genes , and while A3F and 3G are widely recognized as important in the...	[ "APOBEC3 genes are part of the host's arsenal against virus infections .", "Humans have 7 APOBEC3 genes and determining how each specifically functions to inhibit retroviruses like HIV is complicated , because all 7 can be produced in a given cell type or tissue .", "This is important , because some viruses mak...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/viral replication and gene regulation", "virology" ]	Nuclear Export and Import of Human Hepatitis B Virus Capsid Protein and Particles	journal.ppat.1001162	null	[ [ "Hepatitis B virus ( HBV ) is an important human pathogen [1] , [2] , [3] .", "Despite the success of HBV vaccination program in certain countries [4] , there is no nationwide vaccination program in most endemic areas in Asia and Africa .", "Vaccine failure and non-responsive cases are not uncommon [5...	[ "It remains unclear what determines the subcellular localization of hepatitis B virus ( HBV ) core protein ( HBc ) and particles .", "To address this fundamental issue , we have identified four distinct HBc localization signals in the arginine rich domain ( ARD ) of HBc , using immunofluorescence confocal microsc...	[ "Chronic infection with hepatitis B virus ( HBV ) could lead to cirrhosis and highly malignant liver cancer .", "At present , treatment of hepatitis B is not very effective , due to notorious side effects and drug resistance .", "The virus can synthesize a core protein for its own replication .", "Clinically ...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "urology", "public health and epidemiology", "science policy and economics", "bladder and ureteric disorders", "parasitic diseases", "preventive medicine", "cost-benefit analysis", "global health", "neglected tropical diseases", "infectious disease control", "urologic infections", ...	Utility of Repeated Praziquantel Dosing in the Treatment of Schistosomiasis in High-Risk Communities in Africa: A Systematic Review	journal.pntd.0001321	null	[ [ "Schistosomiasis remains a significant health burden for many parts of the world , particularly where health resources are most limited [1] .", "Of the 239 million people with active Schistosoma infection in 2009 [2] , 85% lived in sub-Saharan Africa , where an estimated 150 , 000 deaths/year were attribu...	[ "Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities .", "In a systematic review of published studies , we examined evidence for incremental benefits from repeated praziquantel dosing , given 2 to 8 weeks after an initial dose , in Schistosoma-endemic ...	[ "Infection by Schistosoma worms causes serious disease among people who live in areas of Africa , South America , and Asia where these parasites are regularly transmitted .", "Although yearly treatment with the drug praziquantel is fairly effective in reducing or eliminating active infection , it does not cure ev...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "biochemical simulations", "mathematics", "statistics", "regulatory networks", "synthetic biology", "biology", "computational biology", "signaling networks", "genetics and genomics" ]	Maximizing the Information Content of Experiments in Systems Biology	journal.pcbi.1002888	null	[ [ "Mathematical models of biomolecular systems are by design and necessity abstractions of a much more complicated reality [1] , [2] .", "In mathematics , and the theoretical sciences more generally , such abstraction is seen primarily as a virtue which allows us to capture the essential features or definin...	[ "Our understanding of most biological systems is in its infancy .", "Learning their structure and intricacies is fraught with challenges , and often side-stepped in favour of studying the function of different gene products in isolation from their physiological context .", "Constructing and inferring global mat...	[ "For most biological signalling and regulatory systems we still lack reliable mechanistic models .", "And where such models exist , e . g . in the form of differential equations , we typically have only rough estimates for the parameters that characterize the biochemical reactions .", "In order to improve our k...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Semi-automated Curation of Metabolic Models via Flux Balance Analysis: A Case Study with Mycoplasma gallisepticum	journal.pcbi.1003208	null	[ [ "The ability to determine a relationship between an organism's genome and its molecular physiology quantitatively , based upon current understanding of metabolism and molecular biology , continues to improve at a dramatic pace .", "Establishment of a quantitative model allows for the compact and integrate...	[ "Primarily used for metabolic engineering and synthetic biology , genome-scale metabolic modeling shows tremendous potential as a tool for fundamental research and curation of metabolism .", "Through a novel integration of flux balance analysis and genetic algorithms , a strategy to curate metabolic networks and ...	[ "Flux balance analysis ( FBA ) is a powerful approach for genome-scale metabolic modeling .", "It provides metabolic engineers with a tool for manipulating , predicting , and optimizing metabolism for biotechnological and biomedical purposes .", "However , we posit that it can also be used as tool for fundament...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "taxonomy", "biogeography", "ecology and environmental sciences", "population genetics", "geographical locations", "parasitic protozoans", "trypanosoma brucei", "phylogenetics", "data management", "protozoans", "population biology", "africa", "computer and information sciences", "geography...	Genomic analyses of African Trypanozoon strains to assess evolutionary relationships and identify markers for strain identification	journal.pntd.0005949	null	[ [ "Trypanosomes are single-celled , eukaryotic parasites of mammalian bloodstreams that are a major health and economic burden on communities with endemic circulating strains .", "This is especially true in sub-Saharan Africa , where trypanosomes belonging to the species Trypanosoma brucei are vectored betw...	[ "African trypanosomes of the sub-genus Trypanozoon ) are eukaryotic parasitesthat cause disease in either humans or livestock .", "The development of genomic resources can be of great use to those interested in studying and controlling the spread of these trypanosomes .", "Here we present a large comparative an...	[ "Trypanosomes are a major health threat to the people and livestock of Sub-Saharan Africa .", "Building genomic resources and understanding the genetic structure of these parasites will aid researchers trying to control their spread .", "To this end , we compared the genomes from 83 trypanosome strains , identi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational neuroscience", "biology and life sciences", "computational biology", "neuroscience", "coding mechanisms" ]	Hippocampal Remapping Is Constrained by Sparseness rather than Capacity	journal.pcbi.1003986	null	[ [ "The neuronal representation of space that is necessary for navigation and orientation has been traditionally assigned to the hippocampal place cell system [1] , where cells fire only at few distinct locations and are silent elsewhere .", "Since the discovery of grid cells in the medial entorhinal cortex ...	[ "Grid cells in the medial entorhinal cortex encode space with firing fields that are arranged on the nodes of spatial hexagonal lattices .", "Potential candidates to read out the space information of this grid code and to combine it with other sensory cues are hippocampal place cells .", "In this paper , we inv...	[ "The mammalian brain represents space in the population of hippocampal place cells as well as in the population of medial entorhinal cortex grid cells .", "Since both populations are active at the same time , space information has to be synchronized between the two .", "Both brain areas are reciprocally connect...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/bioinformatics", "computational biology/systems biology", "computational biology/genomics" ]	Cohesive versus Flexible Evolution of Functional Modules in Eukaryotes	journal.pcbi.1000276	null	[ [ "Phylogenetic profiling is a successful method to predict or confirm functional relations between proteins .", "If the phylogenetic patterns of two proteins are alike , they are likely to be functionally related [1] .", "However , this does not necessarily mean that all functionally related proteins h...	[ "Although functionally related proteins can be reliably predicted from phylogenetic profiles , many functional modules do not seem to evolve cohesively according to case studies and systematic analyses in prokaryotes .", "In this study we quantify the extent of evolutionary cohesiveness of functional modules in e...	[ "Components of a protein complex or a metabolic pathway strongly cooperate to perform a specific function .", "Because of this functional interdependence , proteins that form a complex or pathway are expected to be present and absent together in different species .", "Phylogenetic profiling methods , in which p...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/emerging viral diseases" ]	Rapid Identification of Known and New RNA Viruses from Animal Tissues	journal.ppat.1000163	null	[ [ "Clinical laboratories are rapidly adopting viral species-specific nucleic acid amplification for virus identification , thereby increasing the sensitivity of detection and reducing the time needed for diagnosis .", "Although widely successful , these methods are limited for detecting divergent viruses du...	[ "Viral surveillance programs or diagnostic labs occasionally obtain infectious samples that fail to be typed by available cell culture , serological , or nucleic acid tests .", "Five such samples , originating from insect pools , skunk brain , human feces and sewer effluent , collected between 1955 and 1980 , res...	[ "Viral surveillance programs aim to identify circulating viruses to safeguard the public and livestock from viral outbreaks .", "Occasionally , samples suspected of harboring a virus cause severe disease in laboratory animals , but the identity of the virus eludes researchers .", "Here , we applied a simple vir...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/morphogenesis and cell biology", "cell biology/cell growth and division", "genetics and genomics/cancer genetics", "cell biology/developmental molecular mechanisms", "genetics and genomics/genetics of disease", "genetics and genomics/gene function", "developmental biology/neurodev...	Drosophila Xpd Regulates Cdk7 Localization, Mitotic Kinase Activity, Spindle Dynamics, and Chromosome Segregation	journal.pgen.1000876	null	[ [ "Metazoan Cdk7 regulates cell cycle progression as the major Cdk-activating kinase ( CAK ) that is active in vivo [1]–[3] .", "As a subunit of TFIIH ( transcription factor IIH ) , the CAK complex consisting of Cdk7 ( Cyclin dependent kinase 7 ) , CycH and Mat1 also functions in transcription by phosphoryl...	[ "The trimeric CAK complex functions in cell cycle control by phosphorylating and activating Cdks while TFIIH-linked CAK functions in transcription .", "CAK also associates into a tetramer with Xpd , and our analysis of young Drosophila embryos that do not require transcription now suggests a cell cycle function f...	[ "Mutations in human xpd cause three different syndromes—XP ( xeroderma pigmentosum ) , TTD ( trichothiodystrophy ) , and CS ( Cockayne syndrome ) —and various different phenotypes , such as sun-induced hyperpigmentation of the skin , cutaneous abnormalities , neuronal degeneration , and developmental retardation ."...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "peritoneal lavage", "trauma surgery", "medicine and health sciences", "immune cells", "chemical compounds", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "diet", "organic compounds", "staphylococcus aureus", "surgical and invasive medical p...	Diminished neutrophil extracellular trap (NET) formation is a novel innate immune deficiency induced by acute ethanol exposure in polymicrobial sepsis, which can be rescued by CXCL1	journal.ppat.1006637	null	[ [ "Sepsis is a complex clinical manifestation of dysregulated host inflammatory responses to infection causing damage to vital organs that often results in death [1] .", "Treatment of sepsis requires prolonged intensive care and thus , results in an increased economic burden .", "It is well known that m...	[ "Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens .", "Animal models and human studies demonstrate that alcohol intoxication is a key risk factor for sepsis-induced mortality .", "Multiple chemokines , such as CXCL1 , CXCL2 and CXCL5 are critical for neutrophil re...	[ "Sepsis is still a leading cause of morbidity and mortality in critically ill patients .", "Multiple organ failure and mortality in sepsis is caused by uncontrolled activation of the immune system .", "This results in impaired ability to control bacterial colonization and dissemination along with excessive infl...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "developmental biology", "mammals", "mus (mouse)", "molecular biology", "genetics and genomics" ]	A Dominant, Recombination-Defective Allele of Dmc1 Causing Male-Specific Sterility	journal.pbio.0050105	Meiosis occurs in both the male and female germ lines; here the authors describe a mutation that affects only male meiosis, causing sterility.	[ [ "Genetic recombination occurs in all organisms and is critical for repair of DNA damage , proper chromosome segregation during meiosis , and genetic diversification .", "Recombination in yeast and mice is initiated by the formation and processing of double-strand breaks ( DSBs ) .", "Meiotic DSBs are ...	[ "DMC1 is a meiosis-specific homolog of bacterial RecA and eukaryotic RAD51 that can catalyze homologous DNA strand invasion and D-loop formation in vitro .", "DMC1-deficient mice and yeast are sterile due to defective meiotic recombination and chromosome synapsis .", "The authors identified a male dominant ster...	[ "About 10%–15% of couples are infertile due to defects in meiosis ( the process by which egg or sperm cells containing a single copy of each chromosome are produced ) .", "Because studying the genetics of meiosis in humans is difficult , we performed genetic screens in mice and identified a novel mutation in Dmc1...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "bartonella", "medicine and health sciences", "pathology and laboratory medicine", "medical microbiology", "microbial pathogens", "pathogens", "biology and life sciences", "microbiology", "bacterial pathogens" ]	Bartonella henselae Endocarditis in Laos – ‘The Unsought Will Go Undetected’	journal.pntd.0003385	null	[ [ "There has been emerging interest in the importance of Bartonella henselae endocarditis in the wealthier countries of Asia [1]–[3] but few data from poorer countries .", "We describe two patients admitted with this condition at Mahosot Hospital , Vientiane , Lao PDR ( Laos ) , and discuss the public healt...	[ "Both endocarditis and Bartonella infections are neglected public health problems , especially in rural Asia .", "Bartonella endocarditis has been described from wealthier countries in Asia , Japan , Korea , Thailand and India but there are no reports from poorer countries , such as the Lao PDR ( Laos ) , probabl...	[ "Infection of heart valves ( endocarditis ) with bacteria is an important condition , especially afflicting those with rheumatic heart disease , and has a high mortality if untreated .", "Most of the evidence for optimal antibiotic and surgical management comes from wealthy countries .", "There are no published...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "biliary system", "invertebrates", "taxonomy", "medicine and health sciences", "liver", "body fluids", "helminths", "bile", "animals", "trematodes", "solutions", "clonorchis sinensis", "phylogenetics", "data management", "materials science", "phylogenetic analysis", "sequence motif a...	Characterization of a novel organic solute transporter homologue from Clonorchis sinensis	journal.pntd.0006459	null	[ [ "Clonorchis sinensis is a liver fluke that parasitizes the bile ducts of mammals [1] .", "Clonorchiasis was prevalent in China [2] , Thailand [3] , Vietnam [4] , and Korea [5] .", "Globally , an estimated 15 million people are infected with C . sinensis , with most of these cases occurring in China [2...	[ "Clonorchis sinensis is a liver fluke that can dwell in the bile ducts of mammals .", "Bile acid transporters function to maintain the homeostasis of bile acids in C . sinensis , as they induce physiological changes or have harmful effects on C . sinensis survival .", "The organic solute transporter ( OST ) tra...	[ "Clonorchiasis is a neglected tropical disease caused by the liver fluke , Clonorchis sinensis .", "C . sinensis is a biological carcinogen , causing cholangiocarcinoma in humans .", "Juvenile flukes migrate to and grow to adults in the bile ducts .", "The bile is chemo-attractive to the flukes and stimulates...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/functional genomics", "cell biology/cell growth and division", "oncology/gastrointestinal cancers", "genetics and genomics", "genetics and genomics/medical genetics", "genetics and genomics/cancer genetics" ]	Allelic Variation at the 8q23.3 Colorectal Cancer Risk Locus Functions as a Cis-Acting Regulator of EIF3H	journal.pgen.1001126	null	[ [ "Although inherited susceptibility is responsible for ∼30% of all CRC [1] , high-penetrance germline mutations in APC , the mismatch repair ( MMR ) genes , MUTYH , SMAD4 , BMPR1A ( ALK3 ) and STK11 account for <6% of all CRC [2] .", "Recent genome-wide association ( GWA ) studies we have conducted have vi...	[ "Common genetic variation at human 8q23 . 3 is significantly associated with colorectal cancer ( CRC ) risk .", "To elucidate the basis of this association we compared the frequency of common variants at 8q23 . 3 in 1 , 964 CRC cases and 2 , 081 healthy controls .", "Reporter gene studies showed that the single...	[ "Common inherited variation on human chromosome 8q23 influences the risk of developing colorectal cancer ( CRC ) .", "To understand the basis of this association we have compared the frequency of common genetic variants at 8q23 in ∼2 , 000 CRC cases and ∼2 , 000 healthy controls .", "Functional analyses of vari...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacterial genomics", "molecular machines", "protein translation", "gene expression", "genetics", "biology and life sciences", "molecular genetics", "microbiology", "genomics", "molecular biology", "microbial genomics" ]	EF-P Dependent Pauses Integrate Proximal and Distal Signals during Translation	journal.pgen.1004553	null	[ [ "During protein synthesis each amino acid is detached from an aminoacyl-tRNA and incorporated into the nascent peptide .", "Although the basic peptidyl transfer reaction is the same for all amino acids , the speed of incorporation is not uniform .", "It is affected by several factors including the abu...	[ "Elongation factor P ( EF-P ) is required for the efficient synthesis of proteins with stretches of consecutive prolines and other motifs that would otherwise lead to ribosome pausing .", "However , previous reports also demonstrated that levels of most diprolyl-containing proteins are not altered by the deletion...	[ "Elongation factor P ( EF-P ) is a well-conserved bacterial protein .", "Although it can enhance protein synthesis in vitro , it is generally regarded as an ancillary factor required for robust translation of transcripts with stretches of consecutive prolines .", "In this work we performed ribosome profiling to...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Biological Significance of Photoreceptor Photocycle Length: VIVID Photocycle Governs the Dynamic VIVID-White Collar Complex Pool Mediating Photo-adaptation and Response to Changes in Light Intensity	journal.pgen.1005215	null	[ [ "Most organisms and nearly all eukaryotes respond to light in their environment , and do so through the use of proteins specially adapted to respond to light .", "Such photoreceptor proteins most often sense light through the use of prosthetic groups , chromophores , chosen by evolution for their ability ...	[ "Most organisms on earth sense light through the use of chromophore-bearing photoreceptive proteins with distinct and characteristic photocycle lengths , yet the biological significance of this adduct decay length is neither understood nor has been tested .", "In the filamentous fungus Neurospora crassa VIVID ( V...	[ "Sensing light from the environment using a variety of photoreceptors is of great adaptive significance for most eukaryotes .", "A key feature of photoreceptors is the photocycle length , the time taken to decay from the initial signaling light state back to the receptive dark state; however , the significance of...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences	journal.pcbi.1004300	null	[ [ "In contrast to SSD , multistate design ( MSD ) minimizes the free energy of multiple protein conformations ( “states” ) simultaneously .", "This enables negative design , which involves destabilizing a certain conformation to shift relative occupancy to alternate conformations , which is useful in design...	[ "Computational protein design has found great success in engineering proteins for thermodynamic stability , binding specificity , or enzymatic activity in a ‘single state’ design ( SSD ) paradigm .", "Multi-specificity design ( MSD ) , on the other hand , involves considering the stability of multiple protein sta...	[ "The ability to design a new protein with a desired activity has been a longstanding goal of computational biologists , to create proteins with new binding activity or increased stability .", "An even more ambitious goal is multi-specificity design , which extends general protein design by creating a sequence tha...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "urology", "medicine and health sciences", "reproductive system", "gonads", "obstetrics and gynecology", "gene regulation", "reproductive physiology", "epithelial cells", "germ cells", "oocytes", "micrornas", "female subfertility", "women's health", "subfertility", "animal cells", "gen...	MiR-202 controls female fecundity by regulating medaka oogenesis	journal.pgen.1007593	null	[ [ "In fish , female fecundity is tightly linked to the proper completion of oogenesis in the ovary , whereby undifferentiated germinal stem cells undergo meiosis , dramatically increase their size and ultimately form the eggs [1] .", "Such an important differentiation process requires interactions between t...	[ "Female gamete production relies on coordinated molecular and cellular processes that occur in the ovary throughout oogenesis .", "In fish , as in other vertebrates , these processes have been extensively studied both in terms of endocrine/paracrine regulation and protein expression and activity .", "The role o...	[ "The role of small non-coding RNAs in the regulation of animal reproduction remains poorly investigated , despite a growing interest for the importance of miRNAs in a wide variety of biological processes .", "Here , we analyzed the role of miR-202 , a miRNA predominantly expressed in gonads in vertebrate .", "W...	2018
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "immunology", "rna extraction", "animals", "animal models", "drosophila melanogaster", "model organisms", "genome analysis", "insect vectors", "extraction techniques", "drosophila", "research and analysis methods", "epidemio...	Mating-Induced Transcriptome Changes in the Reproductive Tract of Female Aedes aegypti	journal.pntd.0004451	null	[ [ "Aedes aegypti is a major vector of arboviruses that impact human health , including those causing dengue and chikungunya [1] .", "Collectively , these neglected infections cause significant human morbidity and mortality .", "Among these arboviral threats , dengue is considered the most important , as...	[ "The Aedes aegypti mosquito is a significant public health threat , as it is the main vector of dengue and chikungunya viruses .", "Disease control efforts could be enhanced through reproductive manipulation of these vectors .", "Previous work has revealed a relationship between male seminal fluid proteins tran...	[ "Female post-mating behavior has important consequences for mosquito populations and their ability to transmit diseases .", "Male Aedes aegypti seminal fluid substances transferred during mating cause many important changes to female behavior and physiology , including blood feeding behavior , egg development , a...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "t helper cells", "invertebrates", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "helminths", "immunology", "animals", "liver diseases", "trematodes", "clonorchis sinensis", "developmental biology", "gastroenter...	Clonorchis sinensis adult-derived proteins elicit Th2 immune responses by regulating dendritic cells via mannose receptor	journal.pntd.0006251	null	[ [ "Clonorchiasis , resulted from Clonorchis sinensis ( C . sinensis ) infection , is a major but surprisingly neglected public health problem in Asia , notably in China and Korea .", "About 15 million people are infected with C . sinensis worldwide .", "Among which , China has the biggest share with aro...	[ "Clonorchis sinensis ( C . sinensis ) is the most widespread human liver fluke in East Asia including China and Korea .", "Clonorchiasis as a neglected tropical zoonosis , leads to serious economic and public health burden in China .", "There are considerable evidences for an etiological relation between chroni...	[ "In China , the morbidity of clonorchiasis resulting from the infection of Clonorchis sinensis ( C . sinensis ) increased every year and 1 . 5 to 2 million patients develop to the late stage—liver fibrosis , cirrhosis or cholangiocarcinoma .", "Proinflammatory and profibrotic cytokines produced by cells of the in...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "deletion mutation", "animal genetics", "rna interference", "caenorhabditis", "signaling networks", "animals", "akt signaling cascade", "animal models", "mutation", "guanine nucleotide exchange factors", "caenorhabditis elegans", "model organisms", "signaling cascades", ...	Developmental fidelity is imposed by genetically separable RalGEF activities that mediate opposing signals	journal.pgen.1008056	null	[ [ "Developmental patterning of the C . elegans vulva precursor cell ( VPC ) fates is a textbook system for analysis of cell-cell signaling .", "The vulva develops from six roughly equipotent VPCs–P3 . p through P8 . p –that are induced to assume a 3°-3°-2°-1°-2°-3° pattern of cells fates .", "The anchor...	[ "The six C . elegans vulval precursor cells ( VPCs ) are induced to form the 3°-3°-2°-1°-2°-3° pattern of cell fates with high fidelity .", "In response to EGF signal , the LET-60/Ras-LIN-45/Raf-MEK-2/MEK-MPK-1/ERK canonical MAP kinase cascade is necessary to induce 1° fate and synthesis of DSL ligands for the la...	[ "Developmental signals are increasingly conceptualized in the context of networks rather than linear pathways .", "Patterning of C . elegans vulval fates is mostly governed by two major signaling cascades that operate antagonistically to induce two cell identities .", "An additional pair of minor cascades suppo...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "parasite groups", "vacuoles", "toxoplasma gondii", "enzymes", "enzymology", "parasitic protozoans", "parasitology", "apicomplexa", "protozoans", "toxoplasma", "mitochondria", "bioenergetics", "immunologic techniques", "cellular structures and organelles", "research and analysis methods"...	A unique dynamin-related protein is essential for mitochondrial fission in Toxoplasma gondii	journal.ppat.1007512	null	[ [ "Members of the Apicomplexa phylum are unicellular obligate parasites .", "Being eukaryotes , they share many features of common model organisms , such as a double-membrane nuclear envelope and a conserved endomembrane system .", "However , they are also set apart by various novel characteristics , su...	[ "The single mitochondrion of apicomplexan protozoa is thought to be critical for all stages of the life cycle , and is a validated drug target against these important human and veterinary parasites .", "In contrast to other eukaryotes , replication of the mitochondrion is tightly linked to the cell cycle .", "A...	[ "Mitochondria fission is mediated by an elaborate “fission complex” of dynamin and receptor proteins , best studied in organisms such as yeast and mammalian cells .", "Little is known about this process in apicomplexan parasites , unicellular eukaryotes characterised by a single , lasso-shaped mitochondrion .", ...	2019
[ "Introduction", "Material and Methods", "Results/Discussion", "Conclusions" ]	[]	Deep Sequencing Analysis of the Ixodes ricinus Haemocytome	journal.pntd.0003754	null	[ [ "Ticks are versatile blood-feeding arthropod vectors for a wide variety of pathogens including viruses , bacteria , protozoa , fungi , and nematodes [1] .", "Successfully transmitted pathogens must overcome physical , cellular , and humoral barriers in the tick en route from being acquired ( by feeding on...	[ "Ixodes ricinus is the main tick vector of the microbes that cause Lyme disease and tick-borne encephalitis in Europe .", "Pathogens transmitted by ticks have to overcome innate immunity barriers present in tick tissues , including midgut , salivary glands epithelia and the hemocoel .", "Molecularly , invertebr...	[ "Ixodes ricinus transmits Lyme disease and tick-borne encephalitis in Europe .", "Tick-borne pathogens ingested with a blood meal persist in the tick gut and , during the next feeding stage , disseminate through the haemolymph to pass into a vertebrate host via the salivary glands .", "Invertebrate immunity is ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "immunology/immunomodulation", "immunology/innate immunity", "immunology/leukocyte signaling and gene expression", "immunology/immunity to infections", "immunology/leukocyte activation" ]	CD14 Signaling Restrains Chronic Inflammation through Induction of p38-MAPK/SOCS-Dependent Tolerance	journal.ppat.1000687	null	[ [ "Toll-like receptor ( TLR ) signaling orchestrates the innate response to danger-associated molecular patterns ( DAMPs ) associated with pathogens and/or select endogenous molecules .", "The principal proinflammatory DAMPs of the spirochetal pathogen Borrelia burgdorferi , the causative agent of Lyme dise...	[ "Current thinking emphasizes the primacy of CD14 in facilitating recognition of microbes by certain TLRs to initiate pro-inflammatory signaling events and the importance of p38-MAPK in augmenting such responses .", "Herein , this paradigm is challenged by demonstrating that recognition of live Borrelia burgdorfer...	[ "Macrophages express CD14 which partners with Toll-like receptor 2/1 to recognize bacterial lipoproteins such as those of Borrelia burgdorferi , the causative agent of Lyme disease .", "In vitro evidence demonstrates that blocking CD14 recognition of bacterial components ablates innate host cell inflammatory resp...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "physics", "chemistry", "biology" ]	Viral Capsid Proteins Are Segregated in Structural Fold Space	journal.pcbi.1002905	null	[ [ "Viral capsid proteins protect the viral genome by forming a closed protein shell around it .", "Most of currently found viral shells with known structure are spherical in shape and observe icosahedral symmetry [1] .", "Comprised of a large number of proteins , such large , symmetrical complexes assum...	[ "Viral capsid proteins assemble into large , symmetrical architectures that are not found in complexes formed by their cellular counterparts .", "Given the prevalence of the signature jelly-roll topology in viral capsid proteins , we are interested in whether these functionally unique capsid proteins are also str...	[ "Viruses are increasingly viewed not as pathogens that parasitize all domains of life , but as useful nanoplatforms for synthetic maneuvers in a wide range of biomedical and materials science applications .", "One of the most well-known examples of virus-based nanotools developed so far features viral capsules as...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "microbiology", "genetics and genomics", "microbiology/medical microbiology" ]	Functional Genetic Diversity among Mycobacterium tuberculosis Complex Clinical Isolates: Delineation of Conserved Core and Lineage-Specific Transcriptomes during Intracellular Survival	journal.ppat.1000988	null	[ [ "Mycobacterium tuberculosis represents a unique opportunity to explore the impact of evolution and genetic diversity on bacterial host adaptation and pathogenesis .", "Tuberculosis is an ancient disease , with evidence that the causative agent M . tuberculosis has been co-evolving with its human host sinc...	[ "Tuberculosis exerts a tremendous burden on global health , with ∼9 million new infections and ∼2 million deaths annually .", "The Mycobacterium tuberculosis complex ( MTC ) was initially regarded as a highly homogeneous population; however , recent data suggest the causative agents of tuberculosis are more genet...	[ "Genetic polymorphisms among bacterial pathogens are exploited by epidemiologists to monitor disease outbreaks and transmission of specific strains .", "Genetic variations occur under selective pressures imposed by the human host , leading to variation amongst clinical isolates .", "Tuberculosis ( TB ) is an an...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "protons", "medicine and health sciences", "urea", "ecology and environmental sciences", "pathology and laboratory medicine", "chemical compounds", "phosphates", "pathogens", "microbiology", "carbohydrates", "organic compounds", "glucose", "plant science", "enterobacteriaceae", "plant ec...	Modifying and reacting to the environmental pH can drive bacterial interactions	journal.pbio.2004248	null	[ [ "Microbes thrive essentially everywhere on this planet , usually as part of complex multispecies communities [1] .", "The interactions between the microbes influence their growth and survival and thus the composition of those communities [2–8] .", "Although microbial interactions are of clear importan...	[ "Microbes usually exist in communities consisting of myriad different but interacting species .", "These interactions are typically mediated through environmental modifications; microbes change the environment by taking up resources and excreting metabolites , which affects the growth of both themselves and also ...	[ "Microbes typically live alongside many other species in complex communities .", "These microbial communities are very important for us because they also live in and on our bodies and can determine our health and well-being .", "The composition and function of these communities , such as who is part of such a c...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "protozoans", "leishmania", "pathology and laboratory medicine", "immunity", "host-pathogen interactions", "immune activation", "biology and life sciences", "immunology", "pathogenesis", "parasitic protozoans", "organisms" ]	Extracellular Vesicles from Leishmania-Infected Macrophages Confer an Anti-infection Cytokine-Production Profile to Naïve Macrophages	journal.pntd.0003161	null	[ [ "Leishmaniases are a disease complex caused by about 21 trypanosomatid protozoa of the genus Leishmania [1]–[3] .", "Parasites of that genus have been co-evolving with their mammals and insect hosts for thousands of years .", "It is not surprising , therefore , that they are well adapted to these host...	[ "Extracellular vesicles ( EVs ) are structures with phospholipid bilayer membranes and 100–1000 nm diameters .", "These vesicles are released from cells upon activation of surface receptors and/or apoptosis .", "The production of EVs by dendritic cells , mast cells , macrophages , and B and T lymphocytes has be...	[ "Leishmaniases are a group of diseases—each one individually called leishmaniasis—that are caused by the protozoan Leishmania .", "They affect millions of people and thousands of dogs in tropical and mediterranean countries .", "Macrophages are the main cellular hosts of Leishmania in the mammalian host , where...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Recovery of an Antiviral Antibody Response following Attrition Caused by Unrelated Infection	journal.ppat.1003843	null	[ [ "Infection or vaccination usually induces high levels of antigen-specific antibodies ( Abs ) in the systemic circulation and mucosal surfaces .", "These Abs can be maintained for long periods of time in the absence of re-infection , despite the relatively short half-life of serum immunoglobulins , which i...	[ "The homeostatic mechanisms that regulate the maintenance of immunological memory to the multiple pathogen encounters over time are unknown .", "We found that a single malaria episode caused significant dysregulation of pre-established Influenza A virus-specific long-lived plasma cells ( LLPCs ) resulting in the ...	[ "Antibody responses to infectious pathogens are critical in host survival , recovery and protection from reinfection; they also correlate with the success of vaccination .", "It is currently thought that antibody serum titers are maintained at protective levels over long periods of time by specialized long-lived ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry/molecular evolution", "biochemistry/biocatalysis", "genetics and genomics/functional genomics", "biochemistry/chemical biology of the cell", "biochemistry/macromolecular chemistry", "computational biology/evolutionary modeling", "biophysics/biomacromolecule-ligand interactions", "biochem...	Quantitative Comparison of Catalytic Mechanisms and Overall Reactions in Convergently Evolved Enzymes: Implications for Classification of Enzyme Function	journal.pcbi.1000700	null	[ [ "Using the Enzyme Commission ( EC ) classification to describe function [1] and the structure and sequence similarity between proteins as a measure of homology , numerous works have reported cases of divergence and convergence of function in enzymes [2]–[17] .", "During divergence of function , gene dupli...	[ "Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry , providing a window on the different structural strategies nature has used to evolve required catalysts .", "Identification and use of this information to improve reaction classificati...	[ "When species evolve , their genes duplicate and diverge to allow for adaptation of their functional repertoires to the changing environment .", "In this scenario , unrelated genes can convergently evolve to produce proteins with the same molecular function , termed “functionally analogous . ”", "A quantitative...	2010
[ "Introduction", "Results", "Discussion", "Models" ]	[ "physics", "systems biology", "theoretical biology", "biology and life sciences", "physical sciences", "computational biology", "biophysics" ]	Kinetic Memory Based on the Enzyme-Limited Competition	journal.pcbi.1003784	null	[ [ "The importance of cellular memory , in which information from experienced environmental exposures is preserved within cellular states , has received a great deal of attention in recent years .", "The capability of cells to translate environmental exposures into cellular memory has been reported in variou...	[ "Cellular memory , which allows cells to retain information from their environment , is important for a variety of cellular functions , such as adaptation to external stimuli , cell differentiation , and synaptic plasticity .", "Although posttranslational modifications have received much attention as a source of ...	[ "Cellular memory exists in a wide range of organisms from prokaryotes to eukaryotes and can persist , in some cases , for days at a time .", "Mounting evidence supports the notion that cells indeed can retain information associated with previous environmental exposures via posttranslational modifications .", "M...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "gene regulation", "long non-coding rnas", "dna transcription", "developmental biology", "mammalian genomics", "embryos", "embryology", "proteins", "gene expression", "genetic loci", "animal genomics", "homeobox", "biochemistry", "rna", "nucleic acids", "genetics", "protein domains",...	Psip1/p52 regulates posterior Hoxa genes through activation of lncRNA Hottip	journal.pgen.1006677	null	[ [ "The mammalian genome encodes ~10 , 000 long noncoding RNAs ( lncRNAs ) [1] .", "Although very few of these molecules have been functionally characterised , a small number have been shown to function by binding to various protein complexes to regulate gene expression[2–6] .", "Some lncRNAs have been r...	[ "Long noncoding RNAs ( lncRNAs ) have been implicated in various biological functions including the regulation of gene expression , however , the functionality of lncRNAs is not clearly understood and conflicting conclusions have often been reached when comparing different methods to investigate them .", "Moreove...	[ "Long noncoding RNAs ( lncRNAs ) have been implicated in various biological functions including regulation of gene expression .", "However , the mechanism through which they regulate gene expression is not clearly understood .", "Here we show that a transcriptional co activator—Psip1 specifically regulates the ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/gene function", "biochemistry", "developmental biology/developmental molecular mechanisms" ]	Molecular Evidence for a Functional Ecdysone Signaling System in Brugia malayi	journal.pntd.0000625	null	[ [ "Human filarial parasitic nematodes are responsible for two chronic severely debilitating tropical diseases: lymphatic filariasis and onchocerciasis .", "The global efforts in the treatment and control of the spread of infection for both parasites so far have resulted in limited success .", "Also , th...	[ "Filarial nematodes , including Brugia malayi , the causative agent of lymphatic filariasis , undergo molting in both arthropod and mammalian hosts to complete their life cycles .", "An understanding of how these parasites cross developmental checkpoints may reveal potential targets for intervention .", "Pharma...	[ "Filarial parasites such as Brugia malayi and Onchocerca volvulus are the causative agents of the tropical diseases lymphatic filariasis and onchocerciasis , which infect 150 million people , mainly in Africa and Southeast Asia .", "Filarial nematodes have a complex life cycle that involves transmission and devel...	2010
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "biochemistry", "biology", "molecular cell biology", "biophysics" ]	Transport of Fibroblast Growth Factor 2 in the Pericellular Matrix Is Controlled by the Spatial Distribution of Its Binding Sites in Heparan Sulfate	journal.pbio.1001361	A single-molecule imaging study reveals that heparan sulfate chains in the pericellular matrix present a structured network of binding sites that controls FGF2 transport.	[ [ "The notion of gradients of morphogens and of epithelial-mesenchymal signal relays is common currency in developmental biology [1]–[4] .", "Moreover , organism homeostasis often depends on similar transport of effector proteins , such as growth factors , cytokines , and chemokines from source to target ce...	[ "The heparan sulfate ( HS ) chains of proteoglycans are a key regulatory component of the extracellular matrices of animal cells , including the pericellular matrix around the plasma membrane .", "In these matrices they regulate transport , gradient formation , and effector functions of over 400 proteins central ...	[ "The development , homeostasis , and repair of animal tissues requires communication between cells mediated by effector proteins , which are released from source cells and must move through the surrounding extracellular matrix to reach their receptors on target cells .", "A major component of the extracellular ma...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "computational biology/macromolecular sequence analysis", "computational biology/genomics" ]	Decoding of Superimposed Traces Produced by Direct Sequencing of Heterozygous Indels	journal.pcbi.1000113	null	[ [ "Direct fluorescent sequencing of two dissimilar templates produces a mixed trace , which appears as if the traces obtained for each template separately were superimposed onto each other .", "Simultaneous sequencing of completely unrelated templates occurs during sequencing of RT-PCR products containing a...	[ "Direct Sanger sequencing of a diploid template containing a heterozygous insertion or deletion results in a difficult-to-interpret mixed trace formed by two allelic traces superimposed onto each other .", "Existing computational methods for deconvolution of such traces require knowledge of a reference sequence o...	[ "In DNA , information is encoded as a sequence of four types of building blocks–nucleotides .", "The most common technique for determining such sequences , the Sanger method , outputs a single consensus for a pool of DNA molecules in the analyzed sample .", "When these are identical , each site in the output co...	2008
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "schizosaccharomymes", "viruses", "biochemistry", "cell biology", "virology", "molecular biology", "genetics and genomics" ]	SREBP Controls Oxygen-Dependent Mobilization of Retrotransposons in Fission Yeast	journal.pgen.0030131	null	[ [ "Transposable elements are mobile DNA sequences that are present in most eukaryotic organisms and occupy a large fraction of sequenced genomes; for example , human ( ∼50% ) [1] , C . elegans ( 12% ) [2] , and plants ( 10%–80% ) [3] .", "Once viewed as simple mutagens , transposable elements are increasing...	[ "Retrotransposons are mobile genetic elements that proliferate through an RNA intermediate .", "Transposons do not encode transcription factors and thus rely on host factors for mRNA expression and survival .", "Despite information regarding conditions under which elements are upregulated , much remains to be l...	[ "Transposons are present at high copy number in diverse organisms ranging from single-celled bacteria to complex mammals and plants .", "Transposons are mobile genetic elements that can replicate and move to new locations within the genome .", "An ongoing debate exists regarding whether transposons are merely g...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "microbiology", "evolutionary biology", "genetics and genomics" ]	Understanding the Evolutionary Fate of Finite Populations: The Dynamics of Mutational Effects	journal.pbio.0050094	Experimental evolution of bacteriophage reveals that mutational effects are dynamic and dependent on genetic background, thus providing fundamental and testable insights into the nature of adaptation.	[ [ "The process of adaptation in finite populations is determined by the distribution of mutational effects on fitness and the size of the population .", "In large populations , beneficial mutations are frequently fixed , whereas deleterious mutations will only be fixed if they are of vanishingly small effec...	[ "The most consistent result in more than two decades of experimental evolution is that the fitness of populations adapting to a constant environment does not increase indefinitely , but reaches a plateau .", "Using experimental evolution with bacteriophage , we show here that the converse is also true .", "In p...	[ "In any population , two factors determine whether the average fitness of individuals will increase ( adaptation ) or decrease: the size of the population and the distribution of mutational effects ( i . e . , the relative rates and effect sizes of beneficial and deleterious mutations ) .", "Although it is relati...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "biochemistry", "microbial ecology", "virology", "microbial evolution", "genetics", "molecular genetics", "biology", "microbiology", "host-pathogen interaction", "genetics and genomics", "viral evolution" ]	Viral Evasion of a Bacterial Suicide System by RNA–Based Molecular Mimicry Enables Infectious Altruism	journal.pgen.1003023	null	[ [ "Toxin-antitoxin ( TA ) systems are ubiquitously distributed in plasmids and chromosomes of prokaryotes [1]–[3] .", "TA systems are divided into three Types , depending upon the nature of the interacting partners [4] .", "These small , bicistronic , genetic loci were originally identified as plasmid m...	[ "Abortive infection , during which an infected bacterial cell commits altruistic suicide to destroy the replicating bacteriophage and protect the clonal population , can be mediated by toxin-antitoxin systems such as the Type III protein–RNA toxin-antitoxin system , ToxIN .", "A flagellum-dependent bacteriophage ...	[ "Bacteria are under constant attack by their viral parasites , bacteriophages , which outnumber bacteria by an estimated ten-to-one .", "The constant selection pressure from this predation promotes the evolution and dissemination of bacterial bacteriophage-resistance mechanisms .", "One family of protective sys...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "infectious diseases/infectious diseases of the nervous system", "virology", "virology/emerging viral diseases", "infectious diseases/viral infections", "virology/host antiviral responses", "virology/mechanisms of resistance and susceptibility, including host genetics", "virology/effects of virus infect...	IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity	journal.ppat.1000757	null	[ [ "West Nile virus ( WNV ) is a neurotropic flavivirus and is an emerging public health threat .", "Infection with WNV now constitutes the leading cause of mosquito-borne and epidemic encephalitis in humans in the United States [1] .", "WNV is enveloped and contains a single strand positive sense RNA ge...	[ "The innate immune response is essential for controlling West Nile virus ( WNV ) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined .", "Herein , we show that IPS-1 , the central adaptor protein to RIG-I-like receptor ( RLR ) signaling , is essential for triggeri...	[ "West Nile virus ( WNV ) is a mosquito-transmitted RNA virus that has emerged in the Western hemisphere and is now the leading cause of arboviral encephalitis in the United States .", "However , the virus/host interface that controls WNV pathogenesis is not well understood .", "Previous studies have established...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "zoonoses", "hantavirus", "hantavirus pulmonary syndrome", "viral diseases", "infectious disease modeling" ]	Pathogenesis and Host Response in Syrian Hamsters following Intranasal Infection with Andes Virus	journal.ppat.1002426	null	[ [ "Hantaviruses ( family Bunyaviridae; genus hantavirus ) are enveloped viruses which contain a tri-segmented , single-stranded , negative sense RNA genome encoding four proteins; the nucleoprotein , two glycoproteins ( GN and GC ) and an RNA dependant RNA polymerase [1] .", "Currently , at least 22 hantavi...	[ "Hantavirus pulmonary syndrome ( HPS ) , also referred to as hantavirus cardiopulmonary syndrome ( HCPS ) , is a rare but frequently fatal disease caused by New World hantaviruses .", "In humans HPS is associated with severe pulmonary edema and cardiogenic shock; however , the pathogenesis of this disease remains...	[ "New World hantaviruses , including Andes virus ( ANDV ) , are rodent-borne pathogens which are associated with hantavirus pulmonary syndrome ( HPS ) and case fatality rates up to 50% .", "The pathogenesis of HPS remains unclear; however , it is believed to involve a delicate balance of virus infection and delete...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "rna-binding proteins", "nucleic acid synthesis", "rna interference", "enzymes", "plant cell biology", "rna extraction", "microbiology", "enzymology", "chloroplasts", "plant science", "epigenetics", "rna synthesis", "cellular structures and organelles", "extraction techn...	The Barley stripe mosaic virus γb protein promotes chloroplast-targeted replication by enhancing unwinding of RNA duplexes	journal.ppat.1006319	null	[ [ "Positive sense ssRNA viruses consist of one or more highly structured genomic ( g ) RNAs .", "Complex secondary motifs within viral gRNAs are required for efficient viral protein translation [1 , 2] , RNA synthesis [3 , 4] , cell-to-cell movement [5] and encapsidation [6 , 7] .", "Current virology st...	[ "RNA viruses encode various RNA binding proteins that function in many steps of viral infection cycles .", "These proteins function as RNA helicases , methyltransferases , RNA-dependent RNA polymerases , RNA silencing suppressors , RNA chaperones , movement proteins , and so on .", "Although many of the protein...	[ "In order to maximize reproduction , RNA viruses often encode multifunctional proteins to perform different activities during replication .", "We report that the Barley stripe mosaic virus γb VSR protein is recruited to viral replication sites through interactions with the αa replicase subunit protein where it en...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "chemical compounds", "disaccharides", "sialic acids", "carbohydrates", "organic compounds", "animal models", "physiological processes", "model organisms", "experimental organism systems", "cellular structures and organelles", "mapk signaling cascades", "resea...	GPI-anchor signal sequence influences PrPC sorting, shedding and signalling, and impacts on different pathomechanistic aspects of prion disease in mice	journal.ppat.1007520	null	[ [ "The cellular prion protein ( PrPC ) is a cell surface GPI-anchored protein ( GPI-AP ) with two putative N-glycosylation sites [1 , 2] targeted to detergent-resistant membranes ( DRMs; or lipid rafts ) [3] .", "All GPI-APs share a common GPI-anchor core structure which is highly conserved among species an...	[ "The cellular prion protein ( PrPC ) is a cell surface glycoprotein attached to the membrane by a glycosylphosphatidylinositol ( GPI ) -anchor and plays a critical role in transmissible , neurodegenerative and fatal prion diseases .", "Alterations in membrane attachment influence PrPC-associated signaling , and t...	[ "The prion protein ( PrPC ) is a glycoprotein attached to the neuronal surface via a GPI-anchor .", "When misfolded to PrPSc , it leads to fatal neurodegenerative diseases which propagates from host to host .", "PrPSc is the principal component of the infectious agent of prion diseases , the “prion” .", "Misf...	2019
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "vertebrates", "animals", "shigella", "animal models", "osteichthyes", "bacterial diseases", "developmental biology", "mod...	Septins restrict inflammation and protect zebrafish larvae from Shigella infection	journal.ppat.1006467	null	[ [ "Septins , a poorly understood component of the cytoskeleton , are highly-conserved guanosine triphosphate ( GTP ) binding proteins organized into 4 groups based on sequence homology ( the SEPT2 , SEPT3 , SEPT6 , and SEPT7 groups ) .", "Septins from different groups assemble into hetero-oligomeric complex...	[ "Shigella flexneri , a Gram-negative enteroinvasive pathogen , causes inflammatory destruction of the human intestinal epithelium .", "Infection by S . flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system .", "Recent work has revealed that components o...	[ "Shigella are human-adapted Escherichia coli and cause bacillary dysentery via inflammatory destruction of the gut epithelium .", "In this study , we use a zebrafish ( Danio rerio ) model of Shigella infection to discover new roles for the cytoskeleton in inflammation and infection control .", "Septins , a poor...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/synthetic biology", "physiology/pattern formation", "physiology", "physiology/integrative physiology", "neuroscience", "computational biology/systems biology" ]	A New Integrated Variable Based on Thermometry, Actimetry and Body Position (TAP) to Evaluate Circadian System Status in Humans	journal.pcbi.1000996	null	[ [ "Circadian system disruption in humans has been associated with the development of chronic illnesses and worsening of pre-existing conditions such as cancer , premature ageing , metabolic syndrome , cardiovascular diseases , cognitive impairment and mood disorders ( for a review , see [1] ) .", "Therefore...	[ "The disruption of the circadian system in humans has been associated with the development of chronic illnesses and the worsening of pre-existing pathologies .", "Therefore , the assessment of human circadian system function under free living conditions using non-invasive techniques needs further research .", "...	[ "Faced with environmental cycles and daily alternation between light and darkness , organisms have evolved a time measuring mechanism , the biological clocks .", "Besides following circadian rhythms , all physiological variables must be coordinated with one another , like an orchestra led by a conductor; if the a...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "deletion mutation", "microbial mutation", "microbiology", "dna-binding proteins", "plasmid construction", "viruses", "mutation", "rna viruses", "polymerases", "dna construction", "molecular biology techniques", "research and analysis methods", "proteins", "viral replicat...	Genetic economy in picornaviruses: Foot-and-mouth disease virus replication exploits alternative precursor cleavage pathways	journal.ppat.1006666	null	[ [ "The Picornaviridae family of single-stranded positive-sense RNA viruses has evolved mechanisms to increase genetic economy and compensate for their relative small genome size .", "All picornaviral proteins are initially produced as precursors that are progressively cleaved into the final products and som...	[ "The RNA genomes of picornaviruses are translated into single polyproteins which are subsequently cleaved into structural and non-structural protein products .", "For genetic economy , proteins and processing intermediates have evolved to perform distinct functions .", "The picornavirus precursor protein , P3 ,...	[ "Positive-strand RNA viruses are generally typified by a small genome size .", "To compensate for this limitation they have evolved ways of multiplying the functions achievable from a small genome , thus increasing ‘genetic economy’ .", "In the picornavirus family of RNA viruses the viral proteins are produced ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Multi-Scale Model of Hepcidin Promoter Regulation Reveals Factors Controlling Systemic Iron Homeostasis	journal.pcbi.1003421	null	[ [ "Hepcidin is a humoral polypeptide that plays a central role in systemic iron homeostasis ( reviewed in [1] ) .", "One main function of hepcidin is to maintain constant levels of iron circulating in the blood despite imbalances in external iron availability: Iron overload in the blood stimulates hepcidin ...	[ "Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels .", "Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades .", "Deregulation of either pathway causes iron-relat...	[ "The nutritional iron uptake is tightly regulated because the body has limited capacity of iron excretion .", "Mammals maintain iron homeostasis by a negative feedback loop , in which the peptide hepcidin senses the iron blood level and controls iron resorption .", "Molecular perturbations in the homeostasis lo...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell death", "urology", "medicine and health sciences", "rna interference", "maternal health", "obstetrics and gynecology", "reproductive endocrinology", "cell processes", "reproductive physiology", "endocrine physiology", "miscarriage and stillbirth", "tyrosine kinase signaling cascade", "...	The Epidermal Growth Factor Receptor Critically Regulates Endometrial Function during Early Pregnancy	journal.pgen.1004451	null	[ [ "Human reproduction is remarkably inefficient with a mere 30% of human chorionic gonadotropin ( hCG ) positive pregnancies resulting in live birth [1]–[3] .", "Furthermore , an estimated 9% of couples are considered infertile [4] .", "Pregnancy is a complex , sequential series of events including fert...	[ "Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns .", "The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy .", "The goal of this study is to define the role of the ERB...	[ "Approximately 10% of reproductive aged women are considered infertile .", "While great strides have been made in assisted reproductive technologies , overall success rates , especially considering the cost , remain low .", "Studies indicate that due to its sequential nature , nearly 75% of pregnancy failures a...	2014
[ "Introduction", "Results", "Discussion", "Models" ]	[ "developmental neuroscience", "computational neuroscience", "biology and life sciences", "computational biology", "neuroscience", "neural circuit formation" ]	A Reaction-Diffusion Model of Cholinergic Retinal Waves	journal.pcbi.1003953	null	[ [ "Throughout the nervous system , correlated spontaneous activity drives developmental programs [1] , [2] .", "Within the retina , these events manifest as slow , spreading waves of depolarizations and are thus termed retinal waves .", "Waves are observed in a variety of species and progress through th...	[ "Prior to receiving visual stimuli , spontaneous , correlated activity in the retina , called retinal waves , drives activity-dependent developmental programs .", "Early-stage waves mediated by acetylcholine ( ACh ) manifest as slow , spreading bursts of action potentials .", "They are believed to be initiated ...	[ "Both within the visual system and more generally , two general processes describe nervous system development: first , genetically determined cues provide a coarse layout of cells and connections and second , neuronal activity removes unwanted cells and refines connections .", "This activity occurs not just throu...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	A Novel Bacterial Pathogen of Biomphalaria glabrata: A Potential Weapon for Schistosomiasis Control?	journal.pntd.0003489	null	[ [ "Schistosomiasis , the second-most widespread human parasitic disease after malaria , is caused by flatworms of the genus Schistosoma ( Platyhelminthes , Digenea ) , currently known to consist of 22 species , three of which Schistosoma haematobium , Schistosoma japonicum , and Schistosoma mansoni are the prin...	[ "Schistosomiasis is the second-most widespread tropical parasitic disease after malaria .", "Various research strategies and treatment programs for achieving the objective of eradicating schistosomiasis within a decade have been recommended and supported by the World Health Organization .", "One of these approa...	[ "The present paper reports the isolation and the characterization of a new microbial pathogen of the freshwater snail , Biomphalaria glabrata .", "Genetic analyses revealed that the species has not been previously described and could be classified into the Paenibacillus genus .", "These bacteria invade most sna...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "clinical laboratory sciences", "diagnostic medicine", "travel-associated diseases", "neglected tropical diseases", "infectious disease control", "viral diseases" ]	Analytical and Clinical Performance of the CDC Real Time RT-PCR Assay for Detection and Typing of Dengue Virus	journal.pntd.0002311	null	[ [ "Dengue is a human disease caused by infection with any one of four genetically related dengue virus serotypes ( DENV-1 , -2 , -3 and - 4 ) , which are transmitted to humans by Aedes sp mosquitoes .", "Dengue is the most widespread mosquito-borne viral disease , with an estimated 390 million cases reporte...	[ "Dengue is an acute illness caused by the positive-strand RNA dengue virus ( DENV ) .", "There are four genetically distinct DENVs ( DENV-1–4 ) that cause disease in tropical and subtropical countries .", "Most patients are viremic when they present with symptoms; therefore , RT-PCR has been increasingly used i...	[ "Significant expansion of the four DENV serotypes ( DENV-1 , -2 , -3 and -4 ) has been reported throughout tropical and sub-tropical regions of the world , with estimates of 390 million cases annually .", "The need has arisen for expanded diagnostic testing for DENV infections in the United States , as dengue inf...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "plasmodium falciparum", "genome-wide association studies", "medicine", "infectious diseases", "genetic association studies", "genetics", "biology", "human genetics", "malaria", "parasitic diseases" ]	Imputation-Based Meta-Analysis of Severe Malaria in Three African Populations	journal.pgen.1003509	null	[ [ "Severe malaria , meaning life-threatening complications of Plasmodium falciparum infection , kills on the order of a million African children each year [1] .", "However this represents only a small proportion of the total number of infected individuals , the majority of whom recover without life-threaten...	[ "Combining data from genome-wide association studies ( GWAS ) conducted at different locations , using genotype imputation and fixed-effects meta-analysis , has been a powerful approach for dissecting complex disease genetics in populations of European ancestry .", "Here we investigate the feasibility of applying...	[ "Malaria kills nearly a million people every year , most of whom are young children in Africa .", "The risk of developing severe malaria is known to be affected by genetics , but so far only a handful of genetic risk factors for malaria have been identified .", "We studied over a million DNA variants in over 5 ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "enterobacter", "medicine and health sciences", "body fluids", "gut bacteria", "pathology and laboratory medicine", "pathogens", "tropical diseases", "microbiology", "parasitic diseases", "escherichia coli", "bacterial diseases", "prokaryotic models", "metagenomics", "model organisms", "...	Diagnosis of Bacterial Bloodstream Infections: A 16S Metagenomics Approach	journal.pntd.0004470	null	[ [ "Bacterial bloodstream infection ( bBSI ) is one of the biggest causes of mortality in critically ill patients [1 , 2] .", "Rapid and accurate diagnosis of bBSI is crucial for the survival of the patient .", "The reference diagnostic test for bBSI is in vitro culture of the blood followed by identific...	[ "Bacterial bloodstream infection ( bBSI ) is one of the leading causes of death in critically ill patients and accurate diagnosis is therefore crucial .", "We here report a 16S metagenomics approach for diagnosing and understanding bBSI .", "The proof-of-concept was delivered in 75 children ( median age 15 mont...	[ "Bacterial bloodstream infection ( bBSI ) is one of the biggest causes of mortality in critically ill patients and standard diagnosis is still done by blood culture methods .", "Parallel deep sequencing of the 16S ribosomal RNA genes ( 16S metagenomics ) is a new and rapidly evolving research field for profiling ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "genome analysis tools", "biology", "genomics", "computational biology", "transcriptomes" ]	DeepSAGE Reveals Genetic Variants Associated with Alternative Polyadenylation and Expression of Coding and Non-coding Transcripts	journal.pgen.1003594	null	[ [ "Genome-wide association studies ( GWAS ) have associated genetic variants , such as single nucleotide polymorphisms ( SNPs ) and copy number variants ( CNVs ) , with numerous diseases and complex traits .", "However , the mechanisms through which genetic variants affect disease phenotypes or physical tra...	[ "Many disease-associated variants affect gene expression levels ( expression quantitative trait loci , eQTLs ) and expression profiling using next generation sequencing ( NGS ) technology is a powerful way to detect these eQTLs .", "We analyzed 94 total blood samples from healthy volunteers with DeepSAGE to gain ...	[ "Many genetic variants that are associated with diseases also affect gene expression levels .", "We used a next generation sequencing approach targeting 3′ transcript ends ( DeepSAGE ) to gain specific insight into how genetic variants affect the expression of genes and the usage and length of 3′-untranslated reg...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "transfection", "carbohydrate metabolism", "medicine and health sciences", "cardiovascular physiology", "natural antisense transcripts", "metabolic processes", "gene regulation", "carcinomas", "cancers and neoplasms", "glucose metabolism", "glycolysis", "angiogenesis", "oncology", "animal ...	EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma	journal.ppat.1007484	null	[ [ "The development of malignant tumors is divided into several stages: malignant transformation of cells , clonal proliferation of transformed cells , local infiltration and distant metastasis .", "An abnormal supply of energy and sustained angiogenesis , two of the ten characteristics of tumor development ...	[ "Abnormal metabolism and uncontrolled angiogenesis are two important characteristics of malignant tumors .", "The occurrence of both events involves many key molecular changes including miRNA .", "However , EBV encoded miRNAs are rarely mentioned as capable of regulating tumor metabolism and tumor angiogenesis ...	[ "The Epstein-Barr virus ( EBV ) , the first reported human tumor virus found to encode miRNAs , which closely related to malignant progression of tumors .", "In our study , we have observed that EBV-miR-BART1-5P , an EBV-BARTs encoded miRNA , promotes glycolysis and induces angiogenesis in NPC .", "Interestingl...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "mathematics", "statistics", "genetics", "biology", "statistical methods" ]	PUMA: A Unified Framework for Penalized Multiple Regression Analysis of GWAS Data	journal.pcbi.1003101	null	[ [ "Genome-wide association studies ( GWAS ) have identified many susceptibility loci underlying the molecular etiology of complex diseases [1] .", "These studies have been responsible for the discovery of many individual genes that contribute to disease risk [2]–[10] , for discoveries on the front line of p...	[ "Penalized Multiple Regression ( PMR ) can be used to discover novel disease associations in GWAS datasets .", "In practice , proposed PMR methods have not been able to identify well-supported associations in GWAS that are undetectable by standard association tests and thus these methods are not widely applied ."...	[ "Genome-wide association studies ( GWAS ) have identified hundreds of regions of the human genome that are associated with susceptibility to common diseases .", "Yet many lines of evidence indicate that many susceptibility loci , which cannot be detected by standard statistical methods , remain to be discovered ....	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "transfer rna", "medicine and health sciences", "natural antisense transcripts", "gene regulation", "blastomas", "cancers and neoplasms", "oncology", "neurological tumors", "micrornas", "genetic elements", "molecular biology techniques", "mammalian genomics", "rna ...	LINE-2 transposable elements are a source of functional human microRNAs and target sites	journal.pgen.1008036	null	[ [ "The emergence and evolution of gene regulatory networks is thought to underlie biological adaptations and speciation .", "Transposable elements ( TEs ) have been implicated in these processes because they can amplify in numbers and move into new regions of the genome .", "Genomic analyses indicate th...	[ "Transposable elements ( TEs ) are dynamically expressed at high levels in multiple human tissues , but the function of TE-derived transcripts remains largely unknown .", "In this study , we identify numerous TE-derived microRNAs ( miRNAs ) by conducting Argonaute2 RNA immunoprecipitation followed by small RNA se...	[ "Transposable elements ( TEs ) are repetitive sequences , that have contributed to the landscaping of the genome by jumping into new positions and amplifying in number .", "TEs have been suggested to play a role in gene regulation , but it remains poorly understood how they contribute to this process .", "In th...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/plant genetics and gene expression", "developmental biology/plant growth and development", "developmental biology/pattern formation", "developmental biology/stem cells" ]	Characterization of Transcriptome Remodeling during Cambium Formation Identifies MOL1 and RUL1 As Opposing Regulators of Secondary Growth	journal.pgen.1001312	null	[ [ "The development of multicellular organisms requires extensive cell-to-cell communication to integrate the activity of single cells into the context of the whole organism .", "Plant development is especially demanding in this respect due to the high degree of plasticity caused by their interdependence wit...	[ "Cell-to-cell communication is crucial for the development of multicellular organisms , especially during the generation of new tissues and organs .", "Secondary growth—the lateral expansion of plant growth axes—is a highly dynamic process that depends on the activity of the cambium .", "The cambium is a stem c...	[ "In contrast to animals , plants have the capacity to grow and form new organs throughout their entire life cycle , thereby building up some of the largest organisms on earth .", "This remarkable capacity is based on the activity of stem cell–like tissues—the meristems—located at shoot and root apices and , in a ...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "medicine and health sciences", "animals", "invertebrate genomics", "animal models", "drosophila melanogaster", "model organisms", "x-linked traits", "experimental organism systems", "y-linked traits", "drosophila", "research and analysis methods", "genetic linkage", "sex ...	Recurrent gene co-amplification on Drosophila X and Y chromosomes	journal.pgen.1008251	null	[ [ "Selfish genetic elements whose evolutionary trajectories are in conflict with those of their host were first described almost 100 years ago [1] .", "However , only in recent decades has it become apparent that the antagonistic coevolution resulting from genetic conflict has shaped genome content and stru...	[ "Y chromosomes often contain amplified genes which can increase dosage of male fertility genes and counteract degeneration via gene conversion .", "Here we identify genes with increased copy number on both X and Y chromosomes in various species of Drosophila , a pattern that has previously been associated with se...	[ "Sex chromosomes are hot spots for genetic conflict , and selfish genetic elements that increase their transmission are prone to originate on sex chromosomes .", "Previous work has shown that genes that co-amplify on both the X and Y chromosome are involved in sex chromosome drive in mice .", "Here , we use bio...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "infectious diseases/epidemiology and control of infectious diseases" ]	Elimination of Neglected Diseases in Latin America and the Caribbean: A Mapping of Selected Diseases	journal.pntd.0000964	null	[ [ "Of the 580 million people who live in Latin America and the Caribbean , around 195 million live in poverty ( defined as earning less than two dollars a day ) , and 71 million live in extreme poverty ( defined as earning less than one dollar per day ) [1] .", "Most of them , including indigenous populatio...	[ "In Latin America and the Caribbean , around 195 million people live in poverty , a situation that increases the burden of some infectious diseases .", "Neglected diseases , in particular , are often restricted to poor , marginalized sections of the population .", "Tools exist to combat these diseases , making ...	[ "Neglected diseases are often restricted to poor , marginalized sections of the population .", "Tools exist to combat these diseases , making it imperative to work towards their elimination .", "In 2009 , the Pan American Health Organization received a mandate to support the countries in the Region in eliminati...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome expression analysis", "medicine and health sciences", "diabetic endocrinology", "cell differentiation", "dna transcription", "hormones", "gene function", "diabetes mellitus", "developmental biology", "organism development", "network analysis", "genome analysis", "bioassays and physio...	An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development	journal.pgen.1004645	null	[ [ "The pancreas is a vital internal organ with exocrine and endocrine functions .", "The exocrine pancreas is composed of acinar cells that secrete digestive enzymes into a branched network of bicarbonate-secreting duct cells .", "Endocrine cells form clusters called islets of Langerhans that secrete ho...	[ "The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered .", "Here , we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets , and th...	[ "Discovery of specific pancreas developmental regulators has accelerated in recent years .", "In contrast , the global regulatory programs controlling pancreas development are poorly understood compared to other organs or tissues like heart or blood .", "Decoding this regulatory logic may accelerate development...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology", "biology", "microbiology" ]	Influenza HA Subtypes Demonstrate Divergent Phenotypes for Cleavage Activation and pH of Fusion: Implications for Host Range and Adaptation	journal.ppat.1003151	null	[ [ "Influenza A virus ( IAV ) is a significant human pathogen that is maintained in nature via an enzootic replication cycle among aquatic birds [1] .", "The full complement of IAV surface glycoproteins , the hemagglutinin ( HA ) and neuraminidase ( NA ) , is represented in wild aquatic birds , of which ther...	[ "The influenza A virus ( IAV ) HA protein must be activated by host cells proteases in order to prime the molecule for fusion .", "Consequently , the availability of activating proteases and the susceptibility of HA to protease activity represents key factors in facilitating virus infection .", "As such , under...	[ "IAV is associated with significant morbidity and mortality , and represents a challenging public health threat that affects social and economic welfare each year , particularly during IAV pandemics .", "Although we know that all human strains derive , either directly or via intermediate hosts , from avian viral ...	2013
[ "Introduction" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/theoretical neuroscience", "neuroscience/sensory systems" ]	Adaptive Gain Modulation in V1 Explains Contextual Modifications during Bisection Learning	journal.pcbi.1000617	null	[ [ "Neurons in the primary visual cortex ( V1 ) are driven by different sources .", "While early work emphasize the feedforward sensory input stream [1] , later investigations highlight the strong recurrent connectivity within V1 [2] or the top-down modulation by higher cortical areas [3] .", "Recurrent ...	[ "The neuronal processing of visual stimuli in primary visual cortex ( V1 ) can be modified by perceptual training .", "Training in bisection discrimination , for instance , changes the contextual interactions in V1 elicited by parallel lines .", "Before training , two parallel lines inhibit their individual V1-...	[ "Neuronal models of perceptual learning often focus on the feedforward information stream extending from the primary sensory area up to the prefrontal cortex .", "In these models , the stimulus representation in the sensory area remains unchanged during learning while higher cortical areas adapt the read out of t...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "collective animal behavior", "invertebrates", "control theory", "ecology and environmental sciences", "engineering and technology", "atmospheric science", "social sciences", "animals", "simulation and modeling", "control engineering", "systems science", "animal behavior", "mathematics", "...	Regulation of harvester ant foraging as a closed-loop excitable system	journal.pcbi.1006200	null	[ [ "Social insect colonies operate without central control .", "Colonies maintain coherence and plasticity in the face of perturbation and change , even though individuals have limited and uncertain information on the state of the group and the state of the environment .", "Collective behavior emerges fr...	[ "Ant colonies regulate activity in response to changing conditions without using centralized control .", "Desert harvester ant colonies forage for seeds , and regulate foraging to manage a tradeoff between spending and obtaining water .", "Foragers lose water while outside in the dry air , but ants obtain water...	[ "We investigate the collective behavior that allows colonies of desert harvester ants to regulate foraging activity in response to environmental conditions .", "We develop an analytical model connecting three processes:", "1 ) the interactions between foragers returning to the nest and available foragers waitin...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "genetics and genomics/gene discovery", "microbiology/cellular microbiology and pathogenesis", "infectious diseases/antimicrobials and drug resistance" ]	A Toxin–Antitoxin System Promotes the Maintenance of an Integrative Conjugative Element	journal.pgen.1000439	null	[ [ "Integrating and conjugative elements ( ICEs ) are a class of self-transmissible mobile genetic elements that contribute to horizontal gene exchange among bacteria [1] .", "With our increasing knowledge of bacterial genomes , ICEs and putative ICEs have been identified in the chromosomes of many gram-posi...	[ "SXT is an integrative and conjugative element ( ICE ) that confers resistance to multiple antibiotics upon many clinical isolates of Vibrio cholerae .", "In most cells , this ∼100 Kb element is integrated into the host genome in a site-specific fashion; however , SXT can excise to form an extrachromosomal circle...	[ "Integrative and conjugative elements ( ICEs ) are a diverse group of mobile genetic elements found in many bacteria .", "These elements integrate into the host chromosome as well as excise and transfer to other bacteria .", "SXT , an ICE that encodes resistances to multiple antibiotics , is currently present i...	2009
[ "Introduction", "Material and Methods", "Results", "Discussion" ]	[]	Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie	journal.ppat.1005077	null	[ [ "Scrapie in small ruminants , bovine spongiform encephalopathy ( BSE ) in cattle , chronic wasting disease ( CWD ) in cervids , transmissible mink encephalopathy ( TME ) or Creutzfeldt-Jakob disease ( CJD ) in humans belong to a group of fatal neurodegenerative diseases referred to as transmissible spongiform...	[ "Transmissible spongiform encephalopathies ( TSEs ) are a group of neurodegenerative diseases affecting a wide range of mammalian species .", "They are caused by prions , a proteinaceous pathogen essentially composed of PrPSc , an abnormal isoform of the host encoded cellular prion protein PrPC .", "Constrained...	[ "Prions are infectious pathogens causing irremediably fatal neurodegenerative diseases in human and in farmed or wild animals .", "They are formed from abnormally folded assemblies ( PrPSc ) of the host-encoded prion protein ( PrPC ) .", "Different PrPSc conformational variants or ‘strains’ can propagate in the...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell biology/cell signaling", "biophysics/theory and simulation", "cell biology/cytoskeleton" ]	Cortical Factor Feedback Model for Cellular Locomotion and Cytofission	journal.pcbi.1000310	null	[ [ "Dynamical assembly and disassembly of intracellular actin filaments play important", "roles in the shape change of eukaryotic cells and in their locomotion [1] .", "For", "cell motility being stimulated by the external chemical signals , molecular", "mechanisms of regulatory dynamics of actin...	[ "Eukaryotic cells can move spontaneously without being guided by external cues .", "For such spontaneous movements , a variety of different modes have been observed ,", "including the amoeboid-like locomotion with protrusion of multiple pseudopods ,", "the keratocyte-like locomotion with a widely spread lamel...	[ "Actin is a globular protein , assembling ( polymerizing ) into filaments .", "This", "process is called actin polymerization .", "Cell biologists have revealed that actin", "polymerization plays a central role in eukaryotic cell locomotion .", "Stimulated by", "internal/external molecular signals , act...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "molecular neuroscience", "drugs and devices", "microbiology", "neuroscience", "toxicology", "toxic agents", "neurotoxicology", "motor systems", "drug information", "peripheral nervous system", "signaling pathways", "neurotransmitters", "pharmacology", "neuroimaging", "bact...	Botulinum Neurotoxins A and E Undergo Retrograde Axonal Transport in Primary Motor Neurons	journal.ppat.1003087	null	[ [ "Through the years , bacterial and animal toxins have been the target of intense medical investigation due to their importance for human health [1] .", "As such , their structure-function relationships and mechanism of action have been extensively analysed , leading to the development of powerful vaccines...	[ "The striking differences between the clinical symptoms of tetanus and botulism have been ascribed to the different fate of the parental neurotoxins once internalised in motor neurons .", "Tetanus toxin ( TeNT ) is known to undergo transcytosis into inhibitory interneurons and block the release of inhibitory neur...	[ "Botulinum neurotoxins are the most toxic molecules known to mankind , and as a result , are currently listed among the top bio-threats .", "However , their ability to bind specifically to neurons and their inhibitory effects on regulated secretion prompted their clinical use in pathologies characterised by incre...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "biology" ]	E6 and E7 from Beta Hpv38 Cooperate with Ultraviolet Light in the Development of Actinic Keratosis-Like Lesions and Squamous Cell Carcinoma in Mice	journal.ppat.1002125	null	[ [ "Non-melanoma skin cancer ( NMSC ) is the most common cancer in adult fair-skinned populations [1] .", "Ultraviolet light ( UV ) is a key risk factor for the NMSC [2]–[4] .", "In addition , it appears that infectious agent ( s ) may favor skin carcinogenesis .", "This is suggested by the fact that...	[ "Cutaneous beta human papillomavirus ( HPV ) types appear to be involved in the development of non-melanoma skin cancer ( NMSC ) ; however , it is not entirely clear whether they play a direct role .", "We have previously shown that E6 and E7 oncoproteins from the beta HPV type 38 display transforming activities ...	[ "Epidemiological and biological lines of evidence support a possible involvement of a sub-group of human papillomaviruses ( HPV ) , referred to as cutaneous beta HPV types , in the development of non-melanoma skin cancer ( NMSC ) .", "However , their role in carcinogenesis , in particular whether they synergize w...	2011
[ "Introduction", "Results/Discussion", "Methods" ]	[ "infectious diseases/tropical and travel-associated diseases", "molecular biology/recombination", "infectious diseases/protozoal infections", "cell biology/cell adhesion", "genetics and genomics" ]	Plasmodium falciparum Erythrocyte Membrane Protein 1 Diversity in Seven Genomes – Divide and Conquer	journal.pcbi.1000933	null	[ [ "Plasmodium falciparum erythrocyte membrane protein 1 ( PfEMP1 ) mediates adhesion of infected erythrocytes ( IE ) to various host cells on the vascular lining , during the blood stage of malaria infection [1]–[2] .", "Naturally acquired protective antibodies in malaria-exposed individuals target PfEMP1 ,...	[ "The var gene encoded hyper-variable Plasmodium falciparum erythrocyte membrane protein 1 ( PfEMP1 ) family mediates cytoadhesion of infected erythrocytes to human endothelium .", "Antibodies blocking cytoadhesion are important mediators of malaria immunity acquired by endemic populations .", "The development o...	[ "About one million African children die from malaria every year .", "The severity of malaria infections in part depends on which type of the parasitic protein PfEMP1 is expressed on the surface of the infected red blood cells .", "Natural immunity to malaria is mediated through antibodies to PfEMP1 .", "There...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "aging", "public health and epidemiology", "model organisms", "genetics", "population genetics", "biology", "population biology", "genetics and genomics" ]	Reduced Life- and Healthspan in Mice Carrying a Mono-Allelic BubR1 MVA Mutation	journal.pgen.1003138	null	[ [ "Separation of duplicated chromosomes during mitosis is an intricate biological process whose molecular basis is incompletely understood .", "Inaccurate segregation of whole chromosomes results in numerical chromosome aberrations , referred to as aneuploidy [1] .", "Human aneuploidy is intimately asso...	[ "Mosaic Variegated Aneuploidy ( MVA ) syndrome is a rare autosomal recessive disorder characterized by inaccurate chromosome segregation and high rates of near-diploid aneuploidy .", "Children with MVA syndrome die at an early age , are cancer prone , and have progeroid features like facial dysmorphisms , short s...	[ "Aging is the main risk factor for the majority of chronic diseases and the leading cause of death and disability in humans .", "Humans age at different rates , but the molecular genetic basis underlying this phenomenon remains largely unknown .", "Efforts to understand how we age have focused on genetic change...	2012

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