Split (3)

train · 24.8k rows

headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "microcephaly", "pathology and laboratory medicine", "cost-effectiveness analysis", "chikungunya infection", "demography", "economic analysis", "pathogens", "geographical locations", "microbiology", "social sciences", "tropical diseases", "health care", "vir...	A Cost-Effectiveness Tool for Informing Policies on Zika Virus Control	journal.pntd.0004743	null	[ [ "In April 2015 , the first confirmed case of mosquito-borne Zika virus in the Americas was reported in Brazil [1] .", "Since then , the virus has spread to 41 countries and territories across the Americas , Oceania , the Pacific Islands , and Africa [2] , with over 1 . 5 million suspected and confirmed ca...	[ "As Zika virus continues to spread , decisions regarding resource allocations to control the outbreak underscore the need for a tool to weigh policies according to their cost and the health burden they could avert .", "For example , to combat the current Zika outbreak the US President requested the allocation of ...	[ "Using data on Zika virus , microcephaly , and Guillain-Barré syndrome cases from Brazil and Colombia , we compute ranges for the probability of a microcephaly outcome in infants born to Zika-infected women ( 0 . 49% to 2 . 10% , based on data from Northeast Brazil ) and the probability of Guillain-Barré syndrome i...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "circuit models", "computational neuroscience", "biology", "computational biology", "coding mechanisms" ]	Decorrelation of Neural-Network Activity by Inhibitory Feedback	journal.pcbi.1002596	null	[ [ "Neurons generate signals by weighting and combining input spike trains from presynaptic neuron populations .", "The number of possible signals which can be read out this way from a given spike-train ensemble is maximal if these spike trains span an orthogonal basis , i . e . if they are uncorrelated [1] ...	[ "Correlations in spike-train ensembles can seriously impair the encoding of information by their spatio-temporal structure .", "An inevitable source of correlation in finite neural networks is common presynaptic input to pairs of neurons .", "Recent studies demonstrate that spike correlations in recurrent neura...	[ "The spatio-temporal activity pattern generated by a recurrent neuronal network can provide a rich dynamical basis which allows readout neurons to generate a variety of responses by tuning the synaptic weights of their inputs .", "The repertoire of possible responses and the response reliability become maximal if...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "atmospheric science", "geographical locations", "tropical diseases", "vertebrates", "sand flies", "parasitic diseases", "parasitic protozoans", "animals", "mammals", "dogs", "protozoans", "leishmania", "neglected tropical diseases", "humidity", "insect ...	Hidden danger: Unexpected scenario in the vector-parasite dynamics of leishmaniases in the Brazil side of triple border (Argentina, Brazil and Paraguay)	journal.pntd.0006336	null	[ [ "Brazil is ranked among the countries with the highest number of Visceral Leishmaniasis ( VL ) cases in the world , with 92% of the South American cases ( i . e . , 3 , 289 cases in 2015 ) , and 43% of the people at risk of VL [1 , 2] .", "Increasing numbers of cases in the country are resulting from the ...	[ "Every year about 3 million tourists from around the world visit Brazil , Argentina and Paraguay´s triple border region where the Iguaçu Falls are located .", "Unfortunately , in recent years an increasing number of autochthonous canine and human visceral leishmaniasis ( VL ) cases have been reported .", "The p...	[ "Every year about 3 million tourists from around the world visit Brazil , Argentina and Paraguay´s triple border region where the Iguaçu Falls are located .", "Unfortunately , in recent years an increasing number of autochthonous canine and human visceral leishmaniasis ( VL ) cases have been reported in this area...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "agriculture", "biology" ]	Computational Prediction and Molecular Characterization of an Oomycete Effector and the Cognate Arabidopsis Resistance Gene	journal.pgen.1002502	null	[ [ "Oomycetes comprise a number of agriculturally important plant pathogens , including Phytophthora infestans ( potato and tomato late blight ) , P . ramorum ( sudden oak death ) and P . sojae ( soybean root rot ) .", "Hyaloperonospora arabidopsidis ( Hpa , downy mildew , formerly known as Peronospora paras...	[ "Hyaloperonospora arabidopsidis ( Hpa ) is an obligate biotroph oomycete pathogen of the model plant Arabidopsis thaliana and contains a large set of effector proteins that are translocated to the host to exert virulence functions or trigger immune responses .", "These effectors are characterized by conserved ami...	[ "Oomycete plant pathogens are among the most devastating agricultural pests and employ arsenals of effector proteins to manipulate their plant hosts .", "Some of these effectors , however , are recognized in the plant and trigger an immune response .", "Hyaloperonospora arabidopsidis ( Hpa ) causes downy mildew...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "primates", "biochemistry", "cell biology", "homo (human)", "animals", "neuroscience", "molecular biology", "genetics and genomics" ]	Enhancement of SMN2 Exon 7 Inclusion by Antisense Oligonucleotides Targeting the Exon	journal.pbio.0050073	Mutations inSMN1 cause spinal muscular atrophy; a nearly identical gene is not functional, but becomes functional in vitro and in vivo after addition of antisense oligos.	[ [ "Spinal muscular atrophy ( SMA ) , the most common genetic cause of infant mortality , is an autosomal recessive neuromuscular disease characterized by progressive loss of α-motor neurons in the anterior horns of the spinal cord , leading to limb and trunk paralysis and atrophy of voluntary muscles .", "B...	[ "Several strategies have been pursued to increase the extent of exon 7 inclusion during splicing of SMN2 ( survival of motor neuron 2 ) transcripts , for eventual therapeutic use in spinal muscular atrophy ( SMA ) , a genetic neuromuscular disease .", "Antisense oligonucleotides ( ASOs ) that target an exon or it...	[ "Spinal muscular atrophy ( SMA ) is a severe genetic disease that causes motor-neuron degeneration .", "SMA patients lack a functional SMN1 ( survival of motor neuron 1 ) gene , but they possess an intact SMN2 gene , which though nearly identical to SMN1 , is only partially functional .", "The defect in SMN2 ge...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "cost-effectiveness analysis", "chemical compounds", "economic analysis", "sodium chloride", "sociology", "geographical locations", "salts", "social sciences", "tropical diseases", "parasitic diseases", "north america", "filariasis", "pharmaceutics", "negl...	Economic performance and cost-effectiveness of using a DEC-salt social enterprise for eliminating the major neglected tropical disease, lymphatic filariasis	journal.pntd.0007094	null	[ [ "Lymphatic filariasis ( LF ) , a mosquito-borne neglected tropical disease ( NTD ) , commonly known as elephantiasis , is one of only parasitic six diseases currently targeted for potential global eradication by 2020 using preventive mass chemotherapy [1–3] .", "Despite the impressive expansion of a WHO-l...	[ "Salt fortified with the drug , diethylcarbamazine ( DEC ) , and introduced into a competitive market has the potential to overcome the obstacles associated with tablet-based Lymphatic Filariasis ( LF ) elimination programs .", "Questions remain , however , regarding the economic viability , production capacity ,...	[ "With less than three years remaining for meeting the initial 2020 target set by WHO for accomplishing the global elimination of Lymphatic Filariasis ( LF ) , concerns are emerging regarding the feasibility of meeting this goal using the current tablet-based Mass Drug Administration strategy .", "Salt fortified w...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "ecology/behavioral ecology", "biophysics/theory and simulation", "marine and aquatic sciences", "ecology/environmental microbiology", "ecology/theoretical ecology" ]	Inherent High Correlation of Individual Motility Enhances Population Dispersal in a Heterotrophic, Planktonic Protist	journal.pcbi.1000942	null	[ [ "Movement is fundamental to many ecological processes and often dictates relevant biotic and abiotic encounter rates , particularly for planktonic organisms inhabiting a highly dynamic and heterogeneous habitat .", "On the individual level , movement impacts encounter rates with favorable ( e . g . mates ...	[ "Quantitative linkages between individual organism movements and the resulting population distributions are fundamental to understanding a wide range of ecological processes , including rates of reproduction , consumption , and mortality , as well as the spread of diseases and invasions .", "Typically , quantitat...	[ "Organism movement is fundamental to how organisms interact with each other and the environment .", "Such movements are also important on the population level and determine the spread of disease and invasion , reproduction , consumption , and mortality .", "Theoretical ecologists have sought to predict populati...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "microbiology/microbial growth and development", "microbiology/cellular microbiology and pathogenesis", "microbiology/microbial physiology and metabolism" ]	A Mycobacterial Enzyme Essential for Cell Division Synergizes with Resuscitation-Promoting Factor	journal.ppat.1000001	null	[ [ "Though not formally considered virulence factors , genes required for bacterial cell division clearly are necessary for the growth , and thus , pathogenesis , of bacteria .", "The distinction between homeostatic and virulence genes is blurred when nonessential genes involved in vegetative cell division b...	[ "The final stage of bacterial cell division requires the activity of one or more enzymes capable of degrading the layers of peptidoglycan connecting two recently developed daughter cells .", "Although this is a key step in cell division and is required by all peptidoglycan-containing bacteria , little is known ab...	[ "Mycobacteria , like all peptidoglycan-containing bacteria , must extend and cleave the surrounding structurally rigid layer of peptidoglycan to grow and divide .", "The peptidoglycan hydrolases responsible for this cleavage often have redundant functions , both revealing their importance and making them difficul...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Mapping of Bancroftian Filariasis in Cameroon: Prospects for Elimination	journal.pntd.0004001	null	[ [ "Lymphatic filariasis ( LF ) is a parasitic disease caused by three species of thread-like nematode worms—Wuchereria bancrofti , Brugia malayi and Brugia timori—known as filariae .", "Of these three parasite species , W . bancrofti accounts for nearly 90 percent of LF infections worldwide .", "Brugia ...	[ "Lymphatic filariasis ( LF ) is one of the most debilitating neglected tropical diseases ( NTDs ) .", "It still presents as an important public health problem in many countries in the tropics .", "In Cameroon , where many NTDs are endemic , only scant data describing the situation regarding LF epidemiology was ...	[ "Lymphatic filariasis , commonly known as elephantiasis , is a parasitic disease caused by the filarial nematodes Wuchereria bancrofti , Brugia malayi and Brugia timori .", "It is widely distributed in the tropics where it results in a chronic and debilitating disease .", "Nearly 1 . 4 billion people in 73 coun...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "clinical laboratory sciences", "body fluids", "pathology and laboratory medicine", "tropical diseases", "biomarkers", "regression analysis", "bacterial diseases", "mathematics", "signs and symptoms", "statistics (mathematics)", "neglected tropical diseases", ...	Serum Procalcitonin and Peripheral Venous Lactate for Predicting Dengue Shock and/or Organ Failure: A Prospective Observational Study	journal.pntd.0004961	null	[ [ "Dengue is the most important arthropod-borne viral disease , and it exerts a high burden on populations and public health systems in most tropical countries [1 , 2] .", "The incidence has dramatically increased during the last 50 years ( by 30-fold ) for all four dengue virus serotypes ( DENV 1–4 ) in mo...	[ "Currently , there are no biomarkers that can predict the incidence of dengue shock and/or organ failure , although the early identification of risk factors is important in determining appropriate management to reduce mortality .", "Therefore , we sought to determine the factors associated with dengue shock and/o...	[ "Dengue is a major global health concern , particularly in tropical countries , and affects all age groups .", "Mortality rates among patients who have been hospitalized with severe dengue are 1 . 6–10 . 9% , and death in adults is mainly due to the development of dengue shock and organ dysfunction .", "In stat...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience" ]	Sparse Representation of Sounds in the Unanesthetized Auditory Cortex	journal.pbio.0060016	Patch clamp recordings in the auditory cortex of unanesthetized rats reveal that the population response to sounds is sparse and that most neurons are silent most of the time.	[ [ "How does a population of cortical neurons encode a sensory stimulus such as a sound ?", "At one extreme , the neural representation could be dense , engaging a large fraction of neurons , each with a broad receptive field .", "At the other extreme , the neural representation could be sparse , at any ...	[ "How do neuronal populations in the auditory cortex represent acoustic stimuli ?", "Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient , recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties .", "To quantif...	[ "How do neuronal populations in the auditory cortex represent sounds ?", "Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient , recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties .", "We quantified the re...	2008
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "medicine", "growth control", "cell differentiation", "endocrine physiology", "developmental biology", "organism development", "gastroenterology and hepatology", "endocrine cells", "morphogenesis", "endocrinology", "organogenesis", "diabetes and endocrinology", "biology", "pancreas" ]	Pancreatic Mesenchyme Regulates Epithelial Organogenesis throughout Development	journal.pbio.1001143	Genetic disruption of the pancreatic mesenchyme reveals that it is critical for the expansion of epithelial progenitors and for the proliferation of insulin-producing beta cells.	[ [ "Organogenesis is a complex and dynamic process that requires tight spatial and temporal regulation of differentiation , proliferation , and morphogenesis .", "The pancreas serves as an interesting model for the study of these processes as its epithelium gives rise to functionally distinct cells: endocrin...	[ "The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ .", "During organogenesis , the epithelial cells receive essential signals from the overlying mesenchyme .", "Previous studies , focusing on ex vivo tissue explants or complete knockout mice , have identifie...	[ "Embryonic development is a highly complex process that requires tight orchestration of cellular proliferation , differentiation , and migration as cells grow within loosely aggregated mesenchyme and more organized epithelial sheets to form organs and tissues .", "In addition to intrinsic cell-autonomous signals ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Variable Processing and Cross-presentation of HIV by Dendritic Cells and Macrophages Shapes CTL Immunodominance and Immune Escape	journal.ppat.1004725	null	[ [ "Cytotoxic CD8+ T cell ( CTL ) responses play an important role in the outcome of viral infections .", "CTL responses elicited during HIV or HCV infection follow a predictable immunodominance hierarchy , whereby immunodominant T cell responses are defined by a higher frequency in a population sharing a HL...	[ "Dendritic cells ( DCs ) and macrophages ( Møs ) internalize and process exogenous HIV-derived antigens for cross-presentation by MHC-I to cytotoxic CD8+ T cells ( CTL ) .", "However , how degradation patterns of HIV antigens in the cross-presentation pathways affect immunodominance and immune escape is poorly de...	[ "Pathogens such as HIV can enter cells by fusion at the plasma membrane for delivery in the cytosol , or by internalization in endolysosomal vesicles .", "Pathogens can be degraded in these various compartments into peptides ( epitopes ) displayed at the cell surface by MHC-I .", "The presentation of pathogen-d...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders/prion diseases" ]	Intraspecies Transmission of BASE Induces Clinical Dullness and Amyotrophic Changes	journal.ppat.1000075	null	[ [ "Prion diseases , or transmissible spongiform encephalopathies ( TSEs ) , are mammalian neurodegenerative disorders of sporadic , genetic , or infectious origin characterized by accumulation and deposition of an abnormal isoform ( PrPTSE ) of the cellular prion protein ( PrPC ) in the brain [1] .", "TSEs ...	[ "The disease phenotype of bovine spongiform encephalopathy ( BSE ) and the molecular/ biological properties of its prion strain , including the host range and the characteristics of BSE-related disorders , have been extensively studied since its discovery in 1986 .", "In recent years , systematic testing of the b...	[ "For approximately two decades , bovine spongiform encephalopathy ( BSE ) , now termed classical BSE ( BSE-C ) , has been regarded as the only and exclusive prion disorder affecting cattle .", "However , over the last 4 years , two additional bovine prion strains , bovine amyloidotic spongiform encephalopathy ( B...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "taxonomy", "organismal evolution", "acoustics", "ecology and environmental sciences", "social sciences", "vertebrates", "animals", "animal phylogenetics", "phylogenetics", "data management", "animal behavior", "zoology", "ecological metrics", "computer and information sciences", "animal...	Evolution of correlated complexity in the radically different courtship signals of birds-of-paradise	journal.pbio.2006962	null	[ [ "Adaptive radiations are driven by ecological differences that promote processes of diversification and speciation [1] .", "In contrast , phenotypic radiations , which occur in the absence of clear ecological differentiation , are less well understood .", "One commonly investigated mechanism for pheno...	[ "Ornaments used in courtship often vary wildly among species , reflecting the evolutionary interplay between mate preference functions and the constraints imposed by natural selection .", "Consequently , understanding the evolutionary dynamics responsible for ornament diversification has been a longstanding chall...	[ "Animals frequently vary widely in ornamentation , even among closely related species .", "Understanding the patterns that underlie this variation is a significant challenge , requiring comparisons among drastically different traits—like comparing apples to oranges .", "Here , we use novel analytical approaches...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "analytical chemistry", "synthetic biology", "chemistry", "biology", "computational biology", "chemical biology", "biophysics", "molecular biology", "genetics and genomics" ]	High-Precision, In Vitro Validation of the Sequestration Mechanism for Generating Ultrasensitive Dose-Response Curves in Regulatory Networks	journal.pcbi.1002171	null	[ [ "In order to test the extent to which we understand complex biochemical systems -and to improve our ability to exploit them in man-made technologies ( e . g . , synthetic biology; biosensors ) - it is important to reconstruct these processes in the laboratory .", "Illustrative examples of this include rec...	[ "Our ability to recreate complex biochemical mechanisms in designed , artificial systems provides a stringent test of our understanding of these mechanisms and opens the door to their exploitation in artificial biotechnologies .", "Motivated by this philosophy , here we have recapitulated in vitro the “target seq...	[ "Here we recreate in vitro the sequestration mechanism thought to underlie the extraordinary sensitivity ( the steepness of the input/output function ) of a number of genetic networks .", "We do so first using fluorescent molecular beacons , a well-established , DNA-based biosensor architecture , as our model sys...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "body weight", "medicine and health sciences", "fibroblasts", "animal models", "fluorescence-activated cell sorting", "physiological processes", "model organisms", "adipocytes", "physiological parameters", "homeostasis", "connective tissue cells", "experimental organism systems", "obesity", ...	FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis	journal.pbio.2001493	null	[ [ "Adult adipose tissue contains adipocyte progenitors that are critical to adipose homeostatic turnover as well as adaptive hyperplastic expansion and regeneration [1–4] .", "Peroxisome proliferator-activated receptor-γ ( PPARγ ) + adipocyte progenitors and preadipocytes—characteristic of cell surface mark...	[ "Adipocyte progenitors reside in the stromal vascular fraction ( SVF ) of adipose tissues that are composed of fibroblasts , immune cells , and endothelial cells .", "It remains to be elucidated how the SVF regulates adipocyte progenitor fate determination and adipose homeostasis .", "Here , we report that fibr...	[ "White adipose tissue ( WAT ) , which consists mostly of adipocytes , is not only a passive energy storage but also an active metabolic and endocrine organ in the body .", "The importance of maintaining proper adipose mass is emphasized by the fact that both adipose tissue excess—in obese individuals—and deficien...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Host immune responses induced by specific Mycobacterium leprae antigens in an overnight whole-blood assay correlate with the diagnosis of paucibacillary leprosy patients in China	journal.pntd.0007318	null	[ [ "Leprosy is a treatable infection that is caused by Mycobacterium leprae ( M . leprae ) and can result in skin lesions , nerve degeneration , and deformities .", "The current World Health Organization ( WHO ) directives for leprosy control programs encourage widespread administration of multidrug therapy ...	[ "Leprosy , caused by Mycobacterium leprae , affects over 200 , 000 people annually worldwide and remains endemic in the ethnically diverse , mountainous and underdeveloped southwestern provinces of China .", "Delayed diagnosis of leprosy persists in China , thus , additional knowledge to support early diagnosis ,...	[ "Leprosy , caused by Mycobacterium leprae , affects over 200 , 000 people annually worldwide and remains endemic in the ethnically diverse , mountainous and underdeveloped southwestern regions of China .", "Although it is curable , delayed diagnosis of leprosy persists in China , with a disability rate as high as...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/cell signaling and trafficking structures", "microbiology/cellular microbiology and pathogenesis", "biochemistry/membrane proteins and energy transduction", "microbiology/innate immunity" ]	Bordetella Adenylate Cyclase Toxin Mobilizes Its β2 Integrin Receptor into Lipid Rafts to Accomplish Translocation across Target Cell Membrane in Two Steps	journal.ppat.1000901	null	[ [ "The secreted adenylate cyclase toxin-hemolysin ( CyaA , ACT , or AC-Hly ) plays a key role in virulence of Bordetellae .", "This multifuctional protein binds the αMβ2 integrin ( CD11b/CD18 , CR3 or Mac-1 ) of myeloid phagocytic cells and delivers into their cytosol a calmodulin-activated adenylate cyclas...	[ "Bordetella adenylate cyclase toxin ( CyaA ) binds the αMβ2 integrin ( CD11b/CD18 , Mac-1 , or CR3 ) of myeloid phagocytes and delivers into their cytosol an adenylate cyclase ( AC ) enzyme that converts ATP into the key signaling molecule cAMP .", "We show that penetration of the AC domain across cell membrane p...	[ "The adenylate cyclase toxin ( CyaA ) of pathogenic Bordetellae eliminates the first line of host innate immune defense .", "It penetrates myeloid phagocytes , such as neutrophils , macrophage or dendritic cells , and subverts their signaling by catalyzing an extremely rapid conversion of intracellular ATP to the...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "flow cytometry", "gene regulation", "microbiology", "dna transcription", "model organisms", "molecular genetics", "cytometry", "chromatin", "gene expression", "biology", "molecular biology", "systems biology", "biochemical simulations", "cell biology", "protein translation", "genetics...	Promoter Sequence Determines the Relationship between Expression Level and Noise	journal.pbio.1001528	A single transcription factor can activate or repress expression by three different mechanisms: one that increases cell-to-cell variability in target gene expression (noise) and two that decrease noise.	[ [ "The cellular response to environmental changes is mediated through activation of TFs and subsequent coordinated activation and repression of dozens of target genes .", "However , gene expression is noisy [1] , and this limits the precision with which cells can regulate protein levels .", "Genome-wide...	[ "The ability of cells to accurately control gene expression levels in response to extracellular cues is limited by the inherently stochastic nature of transcriptional regulation .", "A change in transcription factor ( TF ) activity results in changes in the expression of its targets , but the way in which cell-to...	[ "In response to environmental changes , cells regulate the activity of transcription factors ( TFs ) , which in turn change the expression of dozens of downstream target genes by binding to their promoters .", "The response of each target gene is determined by the interplay between TF concentration and the contex...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "microbial metabolism", "microbiology", "rna synthesis", "bacterial pathogens", "microbial physiology", "microbial pathogens", "biology", "gram positive", "biochemistry", "rna", "bacterial physiology", "nucleic acids" ]	Sequence-Based Analysis Uncovers an Abundance of Non-Coding RNA in the Total Transcriptome of Mycobacterium tuberculosis	journal.ppat.1002342	null	[ [ "Mycobacterium tuberculosis presents a major threat to global health , causing around 10 million new cases of tuberculosis and 2 million deaths every year [1] .", "The bacteria typically establish a prolonged asymptomatic infection that progresses to active disease in only a minority of individuals .", ...	[ "RNA sequencing provides a new perspective on the genome of Mycobacterium tuberculosis by revealing an extensive presence of non-coding RNA , including long 5’ and 3’ untranslated regions , antisense transcripts , and intergenic small RNA ( sRNA ) molecules .", "More than a quarter of all sequence reads mapping o...	[ "Tuberculosis bacteria are able to hide quietly inside the body for years or decades before reawakening to cause disease .", "If we knew more about how the bacteria change from a harmless persistent form to an aggressive disease-causing form , we could develop drugs that would be more effective in treating active...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "virology/virus evolution and symbiosis", "virology/immunodeficiency viruses", "virology", "infectious diseases/hiv infection and aids", "virology/host antiviral responses" ]	Likely Role of APOBEC3G-Mediated G-to-A Mutations in HIV-1 Evolution and Drug Resistance	journal.ppat.1000367	null	[ [ "The human and mouse APOBEC3 ( A3 ) protein family members , hA3F and G and mA3 , respectively , are well-studied host factors that restrict retrovirus replication .", "[1]–[3] .", "These components of the innate cellular defense system inhibit retroviral propagation by inducing deamination of C-to-U ...	[ "The role of APOBEC3 ( A3 ) protein family members in inhibiting retrovirus infection and mobile element retrotransposition is well established .", "However , the evolutionary effects these restriction factors may have had on active retroviruses such as HIV-1 are less well understood .", "An HIV-1 variant that ...	[ "The search for new drugs to battle HIV-1 infections is a continuing struggle .", "APOBEC3G proteins have been shown to deaminate C-residues in HIV-1 minus strand DNA during its synthesis , resulting in G-to-A mutations in the RNA genome .", "The HIV-1 Vif protein has evolved to counteract APOBEC3G and thereby ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biophysics/macromolecular assemblies and machines", "physics/interdisciplinary physics", "cell biology/nuclear structure and function", "physics/condensed matter", "biophysics/theory and simulation", "computational biology/molecular dynamics", "computer science/numerical analysis and theoretical comput...	Spatial and Topological Organization of DNA Chains Induced by Gene Co-localization	journal.pcbi.1000678	null	[ [ "Statistical properties of long DNA chains in good solvents are accurately described by worm-like chain ( WLC ) models [28] .", "These types of models provide a coarse-grained description of protein-coated DNA ( e . g . the eukaryotic chromatin ) .", "They are simple enough to allow some analytical tr...	[ "Transcriptional activity has been shown to relate to the organization of chromosomes in the eukaryotic nucleus and in the bacterial nucleoid .", "In particular , highly transcribed genes , RNA polymerases and transcription factors gather into discrete spatial foci called transcription factories .", "However , ...	[ "The good operation of cells relies on a coordination between chromosome structure and genetic regulation which is yet to be understood .", "This can be seen in particular from the transcription machinery: in some eukaryotes and bacteria , transcription of highly active genes occurs within discrete foci called tr...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	A Network Inference Method for Large-Scale Unsupervised Identification of Novel Drug-Drug Interactions	journal.pcbi.1003374	null	[ [ "Understanding interactions between drugs is becoming increasingly important .", "A recent large-scale study of older adults ( ages 57–85 ) in the U . S . found that 29% of them use five or more prescription medications concurrently , and that as many as 4% may be at risk of having a major adverse drug-dr...	[ "Characterizing interactions between drugs is important to avoid potentially harmful combinations , to reduce off-target effects of treatments and to fight antibiotic resistant pathogens , among others .", "Here we present a network inference algorithm to predict uncharacterized drug-drug interactions .", "Our ...	[ "Over one in four adults older than 57 in the US take five or more prescriptions at the same time; as many as 4% are at risk of a major adverse drug-drug interaction .", "Potentially beneficial effects of drug combinations , on the other hand , are also important .", "For example , combinations of drugs with sy...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "chronic kidney disease", "genetics", "pediatric nephrology", "biology and life sciences", "nephrology", "gene function" ]	Nephronophthisis-Associated CEP164 Regulates Cell Cycle Progression, Apoptosis and Epithelial-to-Mesenchymal Transition	journal.pgen.1004594	null	[ [ "Nephronophthisis ( NPHP ) is an autosomal recessive polycystic kidney disease ( PKD ) attributed to dysfunction of the primary cilia [1] , antennae-like structures projecting from the cell surface which have sensory or mechanical functions [2] .", "To date , mutations in seventeen genes have been identif...	[ "We recently reported that centrosomal protein 164 ( CEP164 ) regulates both cilia and the DNA damage response in the autosomal recessive polycystic kidney disease nephronophthisis .", "Here we examine the functional role of CEP164 in nephronophthisis-related ciliopathies and concomitant fibrosis .", "Live cell...	[ "Nephronophthisis is a leading inherited cause of renal failure in children and young adults .", "This work contributes to understanding of the disease mechanism of nephronophthisis , which is characterized by multi-cystic and fibrotic kidneys .", "The genes mutated in patients with nephronophthisis all seem to...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "clinical immunology", "immunology", "biology" ]	Rational Design of a Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques	journal.ppat.1003521	null	[ [ "Dengue virus ( DENV ) is a member of the Flaviviridae family .", "DENV infection causes dengue fever ( DF ) and the more severe forms of the disease , dengue hemorrhagic fever ( DHF ) and dengue shock syndrome ( DSS ) .", "DENV has four serotypes ( DENV-1 to -4 ) , each of which is capable of causing...	[ "Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year .", "Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue , resulting in a continuously increasing number o...	[ "The four serotypes of dengue virus cause severe outbreaks globally in tropical countries with thousands of patients requiring hospitalization .", "The health care and indirect economic cost of dengue in endemic countries is huge .", "Despite this , no clinically approved vaccine or antiviral treatment is curre...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "flow cytometry", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "cytokines", "influenza", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "epithelial cells", "viruses", "an...	Influenza Virus Targets Class I MHC-Educated NK Cells for Immunoevasion	journal.ppat.1005446	null	[ [ "Influenza viruses are classified as members of the Orthomyxoviridae family , which are enveloped viruses with a segmented , negative , single-stranded RNA ( ssRNA ) genome that contains 7–8 gene segments .", "Structurally , influenza A virus expresses two surface glycoproteins , hemagglutinin and neurami...	[ "The immune response to influenza virus infection comprises both innate and adaptive defenses .", "NK cells play an early role in the destruction of tumors and virally-infected cells .", "NK cells express a variety of inhibitory receptors , including those of the Ly49 family , which are functional homologs of h...	[ "Influenza virus has developed a number of immune-evasion mechanisms to prolong its survival within the host .", "Development of functional NK cells is dependent on multiple factors such as the interaction between MHC-I and Ly49 receptors .", "NK cells that develop in the absence of these interactions are refer...	2016
[ "Introduction", "Methods", "Results and Discussion" ]	[ "genome expression analysis", "immune cells", "antigen-presenting cells", "immunology", "microbiology", "host-pathogen interaction", "parasitology", "immune defense", "t cells", "biology", "pathogenesis", "immune response", "immunity", "genomics", "genetics and genomics" ]	Distinct Transcriptional Signatures of Bone Marrow-Derived C57BL/6 and DBA/2 Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes	journal.pntd.0001980	null	[ [ "Leishmania ( L . ) amazonensis perpetuates in South and Central America , its main location being the wet forests of the Amazon basin .", "The perpetuation of this Leishmania species relies successively on two hosts which cohabit more or less transiently within this ecosystem: blood-feeding sand flies an...	[ "The inoculation of a low number ( 104 ) of L . amazonensis metacyclic promastigotes into the dermis of C57BL/6 and DBA/2 mouse ear pinna results in distinct outcome as assessed by the parasite load values and ear pinna macroscopic features monitored from days 4 to 22-phase 1 and from days 22 to 80/100-phase 2 .", ...	[ "The rapid and long term establishment of parasites such as L . amazonensis , otherwise known to strictly rely on subversion of macrophage and dendritic leucocyte ( DL ) lineages , is expected to reflect stepwise processes taking place in both the skin dermis where the infective form of the parasite and the skin-dr...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "biology", "molecular cell biology" ]	Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest	journal.pgen.1003405	null	[ [ "Neural Crest Cells ( NCCs ) are multi-potent progenitor cells , which after delaminating from the dorsal lip of the neural tube and migrating throughout the developing embryo , can differentiate along either ectodermal or mesodermal lineages [1]–[4] .", "For example , a subset of NCCs , the cardiac NCCs ...	[ "Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types , such as neurons , and mesodermal cell types , such as smooth muscle .", "The mechanisms controlling this cell fate choice are not known .", "The basic Helix-loop-Helix ( bHLH ) transcription factor Twist1 is expr...	[ "During vertebrate development , a unique population of cells , termed neural crest cells , migrates throughout the developing embryo , generating various cell types , for example , the smooth muscle that divides the aorta and pulmonary artery where they connect to the heart , and the autonomic neurons , which coor...	2013
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "cell motility", "medicine and health sciences", "nuclear staining", "cell cycle and cell division", "cell processes", "brain", "precursor cells", "neuroscience", "mutation", "developmental biology", "hindbrain", "cerebellum", "frameshift mutation", "research and analysis methods", "spec...	Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation	journal.pgen.1006746	null	[ [ "Brain development depends on spatiotemporally controlled gene expression .", "[1–3] Alterations in the expression pattern of such genes can result in neurodevelopmental disorders by impinging on key processes such as neural progenitor specification , cell division , and differentiation and the migration ...	[ "Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures .", "Rho guanine nucleotide exchange factor ( ARHGEF ) family members are key for controlling the spatiotemporal activation of Rho GTPase , t...	[ "During brain development , localized gene expression is crucial for the formation and function of specific brain regions .", "Various groups of proteins are known to regulate segmentation through controlled gene expression , among them , the Rho GTPase regulator family .", "In this study , we identified a fram...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "medicine", "movement disorders", "neurological disorders", "neurology", "sleep disorders" ]	Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1	journal.pgen.1002171	null	[ [ "Restless legs syndrome ( RLS ) is a common neurological disorder with a prevalence of up to 10 % , which increases with age [1] .", "Affected individuals suffer from an urge to move due to uncomfortable sensations in the lower limbs present in the evening or at night .", "The symptoms occur during re...	[ "Restless legs syndrome ( RLS ) is a sensorimotor disorder with an age-dependent prevalence of up to 10% in the general population above 65 years of age .", "Affected individuals suffer from uncomfortable sensations and an urge to move in the lower limbs that occurs mainly in resting situations during the evening...	[ "Restless legs syndrome ( RLS ) is one of the most common neurological disorders .", "Patients with RLS suffer from an urge to move the legs and unpleasant sensations located mostly deep in the calf .", "Symptoms mainly occur in resting situations in the evening or at night .", "As a consequence , initiation ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell physiology", "cellular stress responses", "molecular cell biology", "phycology", "cell biology", "electrophysiology", "physiology", "marine and aquatic sciences", "biology", "anatomy and physiology", "marine biology" ]	A Voltage-Gated H+ Channel Underlying pH Homeostasis in Calcifying Coccolithophores	journal.pbio.1001085	null	[ [ "Coccolithophores represent a pan-global group of oceanic phytoplankton , often forming massive monospecific blooms in oceanic waters .", "These unicellular eukaryote algae produce highly intricate calcium carbonate scales , known as coccoliths , and are the most numerous calcifying organisms in our ocean...	[ "Marine coccolithophorid phytoplankton are major producers of biogenic calcite , playing a significant role in the global carbon cycle .", "Predicting the impacts of ocean acidification on coccolithophore calcification has received much recent attention and requires improved knowledge of cellular calcification me...	[ "The production of calcium carbonate structures by marine organisms has a major influence on the Earth's carbon cycle and is responsible for the eventual formation of sedimentary rocks such as chalk and limestone .", "The major contributors to marine calcification are the coccolithophores , a family of unicellula...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "mathematics", "gastroenterology and hepatology", "computational biology", "homo (human)" ]	The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns	journal.pcbi.0030028	null	[ [ "Most tissues are renewed during the life of the organism through a continuous replacement of their differentiated cells by new mature cells that originate from tissue-specific stem cell lineages .", "Genetic and epigenetic somatic variations having long-term consequences are believed to preferentially af...	[ "The analysis of methylation patterns is a promising approach to investigate the genealogy of cell populations in an organism .", "In a stem cell–niche scenario , sampled methylation patterns are the stochastic outcome of a complex interplay between niche structural features such as the number of stem cells withi...	[ "The dynamics of the stem cell populations in human colon crypts are of interest to cancer researchers and stem cell biologists alike .", "One approach to studying stem cell divisions would be to adopt methods from population genetics: cells are sampled from crypts , DNA markers such as single nucleotide polymorp...	2007
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/genome projects", "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "evolutionary biology/evolutionary and comparative genetics" ]	Evolutionary Convergence and Nitrogen Metabolism in Blattabacterium strain Bge, Primary Endosymbiont of the Cockroach Blattella germanica	journal.pgen.1000721	null	[ [ "In 1887 , Blochmann first described symbiotic bacteria in the fatty tissue of blattids [1] .", "Later , Buchner [2] suggested that symbionts are involved in the decomposition of metabolic end-products from the insect host .", "A classic example is the cockroach .", "Several pioneering studies cor...	[ "Bacterial endosymbionts of insects play a central role in upgrading the diet of their hosts .", "In certain cases , such as aphids and tsetse flies , endosymbionts complement the metabolic capacity of hosts living on nutrient-deficient diets , while the bacteria harbored by omnivorous carpenter ants are involved...	[ "Bacterial endosymbionts from insects are subjected to a process of genome reduction from the moment they interact with their host , especially when the symbiosis is strict ( the partners live together permanently ) and the endosymbiont is maternally inherited .", "The type of genes that are retained correlates w...	2009
[ "Introduction", "Results", "Discussion", "Conclusions", "Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "gene regulation", "regulatory proteins", "immunology", "dna-binding proteins", "dna transcription", "gastroenterology and hepatology", "transcription factors", "inflammatory bowel disease", "white blood cells", "animal cells", ...	Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease	journal.pgen.1006641	null	[ [ "Inflammatory bowel disease ( IBD ) comprises a group of complex syndromes that arise from a dysfunctional interaction between the microbiota of the intestinal lumen and the immune system [1] .", "Loci associated with the heritability of susceptibility to IBD are shared in some measure with other chronic ...	[ "The FANTOM5 consortium utilised cap analysis of gene expression ( CAGE ) to provide an unprecedented insight into transcriptional regulation in human cells and tissues .", "In the current study , we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-...	[ "Macrophages are immune cells that form the first line of defense against pathogens , but also mediate tissue damage in inflammatory disease .", "Macrophages initiate inflammation by recognising and responding to components of bacterial cells .", "Macrophages of the wall of the gut are constantly replenished fr...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "neural networks", "visual object recognition", "vertebrates", "social sciences", "neuroscience", "animals", "mammals", "learning and memory", "magnetic resonance imaging", "primates", "percept...	Representations of regular and irregular shapes by deep Convolutional Neural Networks, monkey inferotemporal neurons and human judgments	journal.pcbi.1006557	null	[ [ "Recently , several studies compared the representations of visual images in deep Convolutional Neural Networks ( CNN ) with those of biological systems , such as the primate ventral visual stream [1–4] .", "These studies showed that the representation of visual objects in macaque inferior temporal ( IT )...	[ "Recent studies suggest that deep Convolutional Neural Network ( CNN ) models show higher representational similarity , compared to any other existing object recognition models , with macaque inferior temporal ( IT ) cortical responses , human ventral stream fMRI activations and human object recognition .", "Thes...	[ "The primate inferior temporal ( IT ) cortex is considered to be the final stage of visual processing that allows for object recognition , identification and categorization of objects .", "Electrophysiology studies suggest that an object’s shape is a strong determinant of the neuronal response patterns in IT .", ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/neglected tropical diseases", "immunology/immune response", "virology/emerging viral diseases", "infectious diseases/viral infections", "infectious diseases/respiratory infections", "immunology/immunity to infections", "virology/host antiviral responses" ]	Highly Differentiated, Resting Gn-Specific Memory CD8+ T Cells Persist Years after Infection by Andes Hantavirus	journal.ppat.1000779	null	[ [ "The family Bunyaviridae is comprised of five genera of tri-segmented negative-stranded RNA viruses , which are responsible for a considerable burden of zoonotic disease in man .", "While most are tick- or mosquito-borne , members of the genus Hantavirus are transmitted from chronically- and asymptomatica...	[ "In man , infection with South American Andes virus ( ANDV ) causes hantavirus cardiopulmonary syndrome ( HCPS ) .", "HCPS due to ANDV is endemic in Southern Chile and much of Argentina and increasing numbers of cases are reported all over South America .", "A case-fatality rate of about 36% together with the a...	[ "In man , hantavirus cardiopulmonary syndrome ( HCPS ) caused by Andes Virus ( ANDV ) is endemic in the Southern cone of Chile and Argentina but cases of HCPS are being increasingly reported all over South America since 1995 .", "HCPS is characterized by fulminant pulmonary edema which progresses to shock and dea...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "computer science", "computer modeling", "veterinary epidemiology", "ecology", "evolutionary modeling", "theoretical ecology", "biology", "computational biology", "veterinary science" ]	A Bayesian Inference Framework to Reconstruct Transmission Trees Using Epidemiological and Genetic Data	journal.pcbi.1002768	null	[ [ "Predicting the most likely transmission routes of a pathogen through a population during an epidemic outbreak provides valuable information , which can be used to inform intervention strategies and design control policies [1] , [2] .", "In principle , studying transmission routes during past epidemics is...	[ "The accurate identification of the route of transmission taken by an infectious agent through a host population is critical to understanding its epidemiology and informing measures for its control .", "However , reconstruction of transmission routes during an epidemic is often an underdetermined problem: data ab...	[ "In order to most effectively control the spread of an infectious disease , we need to better understand how pathogens spread within a host population , yet this is something we know remarkably little about .", "Cases close together in their locations and timing are often thought to be linked , but timings and lo...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "neuroscience/sensory systems", "cell biology/cellular death and stress responses", "genetics and genomics/disease models", "otolaryngology/ear pathologies" ]	Identification of Genetic and Chemical Modulators of Zebrafish Mechanosensory Hair Cell Death	journal.pgen.1000020	null	[ [ "Hearing loss and vestibular dysfunction are among the most common disorders requiring medical attention .", "Globally , over a third of older adults suffer from these conditions .", "Studies of both laboratory animals and humans reveal tremendous variation in hearing loss due to ageing as well as exo...	[ "Inner ear sensory hair cell death is observed in the majority of hearing and balance disorders , affecting the health of more than 600 million people worldwide .", "While normal aging is the single greatest contributor , exposure to environmental toxins and therapeutic drugs such as aminoglycoside antibiotics an...	[ "Loss of sensory hair cells in the inner ear is observed in the majority of hearing and balance disorders , affecting the health of more than 600 million people worldwide .", "Exposure to environmental toxins and certain pharmaceutical drugs such as aminoglycoside antibiotics and some cancer chemotherapy agents a...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational neuroscience", "biology and life sciences", "computational biology", "neuroscience", "coding mechanisms" ]	Poisson-Like Spiking in Circuits with Probabilistic Synapses	journal.pcbi.1003522	null	[ [ "Cortical neurons respond to repeated presentations of the same stimulus in a remarkably idiosyncratic way , and no identical responses are observed twice [1] , [2] , [3] , [4] .", "Although the spike count responses are on average reproducible ( ibid . ) , they display high variability .", "It is wel...	[ "Neuronal activity in cortex is variable both spontaneously and during stimulation , and it has the remarkable property that it is Poisson-like over broad ranges of firing rates covering from virtually zero to hundreds of spikes per second .", "The mechanisms underlying cortical-like spiking variability over such...	[ "Neurons in cortex fire irregularly and in an irreproducible way under repeated presentations of an identical stimulus .", "Where is this spiking variability coming from ?", "One unexplored possibility is that cortical variability originates from the amplification of a particular type of noise that is present t...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Mathematical Modeling of Interacting Glucose-Sensing Mechanisms and Electrical Activity Underlying Glucagon-Like Peptide 1 Secretion	journal.pcbi.1004600	null	[ [ "Glucose sensing by a variety of specialized cells located , for example , in the pancreas [1] , the brain [2] and the ingestive tract [3] , plays a crucial role in the control of body weight and blood glucose levels , and dysfunctional glucose sensing is involved in the development of obesity and diabetes [2...	[ "Intestinal L-cells sense glucose and other nutrients , and in response release glucagon-like peptide 1 ( GLP-1 ) , peptide YY and other hormones with anti-diabetic and weight-reducing effects .", "The stimulus-secretion pathway in L-cells is still poorly understood , although it is known that GLP-1 secreting cel...	[ "Metabolic diseases are to a great extent because of disturbances in hormone secretion .", "Endocrine cells releasing hormones with a role in metabolism typically possess a refined molecular system for nutrient sensing , which allows them to respond in an appropriate manner to changes in e . g . glucose levels ."...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/recombination", "genetics and genomics/nuclear structure and function", "molecular biology/chromosome structure", "genetics and genomics/chromosome biology", "genetics and genomics", "molecular biology/dna repair" ]	Genetic Analysis of Baker's Yeast Msh4-Msh5 Reveals a Threshold Crossover Level for Meiotic Viability	journal.pgen.1001083	null	[ [ "Meiosis produces haploid gametes from diploid progenitor cells .", "This reduction in ploidy results from the segregation of homologous chromosomes at the first meiotic division ( Meiosis I ) .", "In most organisms , the accurate segregation of chromosomes during Meiosis I requires crossing over betw...	[ "During meiosis , the Msh4-Msh5 complex is thought to stabilize single-end invasion intermediates that form during early stages of recombination and subsequently bind to Holliday junctions to facilitate crossover formation .", "To analyze Msh4-Msh5 function , we mutagenized 57 residues in Saccharomyces cerevisiae...	[ "In meiosis , sex cells that become eggs or sperm undergo a single round of DNA replication followed by two consecutive chromosomal divisions .", "In most organisms , the segregation of chromosomes at the first meiotic division is dependent upon at least one genetic exchange , or crossover event , between homolog...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	The Burden of Cholera in Uganda	journal.pntd.0002545	null	[ [ "Cholera was first reported in Uganda in 1971 , when 757 cases were reported to the World Health Organization ( WHO ) .", "During the subsequent years up to 1993 , Uganda reported cholera cases every 2–4 years to the WHO .", "From 1994 to 1998 , cholera was reported annually in Uganda [1] .", "In ...	[ "In 2010 , the World Health Organization released a new cholera vaccine position paper , which recommended the use of cholera vaccines in high-risk endemic areas .", "However , there is a paucity of data on the burden of cholera in endemic countries .", "This article reviewed available cholera surveillance data...	[ "Uganda has reported cholera cases to the World Health Organization every year since 1997 .", "Thus , the country may consider the introduction of a WHO-prequalified oral cholera vaccine .", "This article reviews cholera surveillance data from 1997–2010 with a focus on the 2005–2010 time period to identify high...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "theoretical biology", "ecology", "biology", "computational biology", "evolutionary biology" ]	Local Orientation and the Evolution of Foraging: Changes in Decision Making Can Eliminate Evolutionary Trade-offs	journal.pcbi.1002186	null	[ [ "The evolution of behavior is to a large extent the evolution of information processing [1]–[4] .", "On short timescales individuals respond to local information in the environment .", "For instance in foraging , a basic local information processing is that animals detect food , turn and move to food ...	[ "Information processing is a major aspect of the evolution of animal behavior .", "In foraging , responsiveness to local feeding opportunities can generate patterns of behavior which reflect or “recognize patterns” in the environment beyond the perception of individuals .", "Theory on the evolution of behavior ...	[ "Animals differ in how they sense and process information obtained from the environment .", "An important part of this information processing is used to find food .", "In terms of foraging , local decision making determines how successful individuals are at finding food on longer timescales .", "Using an arti...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/alternative splicing", "molecular biology/mrna stability", "molecular biology/rna splicing", "molecular biology/bioinformatics", "microbiology/parasitology", "infectious diseases/protozoal infections" ]	Spliced Leader Trapping Reveals Widespread Alternative Splicing Patterns in the Highly Dynamic Transcriptome of Trypanosoma brucei	journal.ppat.1001037	null	[ [ "Trypanosoma brucei is a unicellular eukaryotic parasite with a digenetic life cycle alternating between the tsetse fly and a variety of mammalian hosts .", "Besides its importance as a human and veterinary pathogen it has been key to the discovery and understanding of general biological principles such a...	[ "Trans-splicing of leader sequences onto the 5′ends of mRNAs is a widespread phenomenon in protozoa , nematodes and some chordates .", "Using parallel sequencing we have developed a method to simultaneously map 5′splice sites and analyze the corresponding gene expression profile , that we term spliced leader trap...	[ "Some organisms like the human and animal parasite Trypanosoma brucei add a leader sequence to their mRNAs through a reaction called trans-splicing .", "Until now the splice sites for most mRNAs were unknown in T . brucei .", "Using high throughput sequencing we have developed a method to identify the splice si...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics", "biochemistry", "biology", "microbiology" ]	H-NS Can Facilitate Specific DNA-binding by RNA Polymerase in AT-rich Gene Regulatory Regions	journal.pgen.1003589	null	[ [ "Transcription is initiated by binding of RNA polymerase to specific DNA sequences known as promoters [1] .", "Following promoter recognition the resulting complex undergoes a process of isomerisation .", "Hence , ∼14 base pairs ( bp ) of DNA , close to the transcription start site , are unwound [2] ....	[ "Extremely AT-rich DNA sequences present a challenging template for specific recognition by RNA polymerase .", "In bacteria , this is because the promoter −10 hexamer , the major DNA element recognised by RNA polymerase , is itself AT-rich .", "We show that Histone-like Nucleoid Structuring ( H-NS ) protein can...	[ "The information required to build and maintain a cell is written into an organism's DNA in the form of genes .", "When individual genes are “read , ” the DNA code is transcribed into an mRNA molecule by RNA polymerase .", "Hence , the DNA sequence adjacent to the start of a gene must contain a signal to recrui...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "bioengineering", "genetics", "biology", "evolutionary biology", "engineering" ]	Suicidal Autointegration of Sleeping Beauty and piggyBac Transposons in Eukaryotic Cells	journal.pgen.1004103	null	[ [ "Mobilization of transposable elements ( TEs ) is a DNA recombination reaction that can occur either via RNA ( retroelement/retrovirus ) or DNA intermediates ( DNA transposon ) .", "In non-replicative , ‘cut and paste’ DNA transposition , the excised transposon relocates from one genomic location to anoth...	[ "Transposons are discrete segments of DNA that have the distinctive ability to move and replicate within genomes across the tree of life .", "‘Cut and paste’ DNA transposition involves excision from a donor locus and reintegration into a new locus in the genome .", "We studied molecular events following the exc...	[ "Transposons ( “jumping genes” ) are ubiquitous , mobile genetic elements that make up significant fraction of genomes , and are best described as molecular parasites .", "During ‘cut and paste’ transposition , the excised transposon relocates from one genomic location to another .", "Here we focus on the molec...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "socioeconomic aspects of health", "non-clinical medicine", "nutrition", "neglected tropical diseases", "leprosy", "infectious disease control" ]	Recent Food Shortage Is Associated with Leprosy Disease in Bangladesh: A Case-Control Study	journal.pntd.0001029	null	[ [ "Leprosy is known as a disease of poverty .", "Only in the poorest areas of the world the infectious disease caused by Mycobacterium leprae is still endemic .", "A causal relationship between poverty and leprosy is difficult to demonstrate , and uncertainty exists about how leprosy and poverty are ass...	[ "Leprosy is remaining prevalent in the poorest areas of the world .", "Intensive control programmes with multidrug therapy ( MDT ) reduced the number of registered cases in these areas , but transmission of Mycobacterium leprae continues in most endemic countries .", "Socio-economic circumstances are considered...	[ "Although intensive control programs reduced the prevalence of leprosy worldwide , new cases of this infectious disease are still detected in several of the poorest areas of the world .", "Therefore the disease is known as a disease of poverty .", "To be able to control the disease it is important to know which...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cardiovascular disorders/vascular biology", "developmental biology/morphogenesis and cell biology", "cell biology/morphogenesis and cell biology", "cell biology/cell growth and division", "mathematics", "cell biology/cell adhesion", "computational biology/systems biology" ]	Topography of Extracellular Matrix Mediates Vascular Morphogenesis and Migration Speeds in Angiogenesis	journal.pcbi.1000445	null	[ [ "The physical properties of the ECM , such as density , heterogeneity , and stiffness , that affect cell behavior is also an area of current investigation .", "Matrigel , a popular gelatinous protein substrate for in vitro experiments of angiogenesis , is largely composed of collagen and laminin and conta...	[ "The extracellular matrix plays a critical role in orchestrating the events necessary for wound healing , muscle repair , morphogenesis , new blood vessel growth , and cancer invasion .", "In this study , we investigate the influence of extracellular matrix topography on the coordination of multi-cellular interac...	[ "A cell migrating in the extracellular matrix environment has to pull on the matrix fibers to move .", "When the matrix is too dense , the cell secretes enzymes to degrade the matrix proteins in order to get through .", "And when the matrix is too sparse , the cell produces matrix proteins to locally increase t...	2009
[ "Introduction", "Results and discussion", "Methods" ]	[ "sequencing techniques", "medicine and health sciences", "body fluids", "messenger rna", "parasitic diseases", "parasitic protozoans", "trypanosoma brucei", "protozoans", "genome analysis", "molecular biology techniques", "rna sequencing", "research and analysis methods", "genomics", "prot...	Transcriptomes of Trypanosoma brucei rhodesiense from sleeping sickness patients, rodents and culture: Effects of strain, growth conditions and RNA preparation methods	journal.pntd.0006280	null	[ [ "Trypanosoma brucei subspecies and related parasites infect humans , cattle , camels , and horses , causing substantial economic losses throughout the tropics [1 , 2] .", "Human sleeping sickness in East Africa is caused by Trypanosoma brucei rhodesiense , a zoonotic parasite which differs from Trypanosom...	[ "All of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in culture or in rodents .", "Drugs against sleeping sickness must however treat trypanosomes in humans .", "We here compare the transcriptomes of Trypanosoma brucei rhodesiense from the blood and cerebro...	[ "African trypanosomes cause sleeping sickness in humans and various diseases of domestic and wild animals .", "Until now , all of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in in vitro culture or in rodents .", "Drugs against sleeping sickness must howeve...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Wolbachia Reduces the Transmission Potential of Dengue-Infected Aedes aegypti	journal.pntd.0003894	null	[ [ "Dengue fever is caused by an RNA virus belonging to the genus Flavivirus and is primarily vectored by the mosquito Aedes aegypti .", "Dengue viruses ( DENVs ) causes a spectrum of symptoms ranging from a mild fever to the life-threatening dengue shock syndrome [1–4] and collectively has become the most p...	[ "Dengue viruses ( DENV ) are the causative agents of dengue , the world’s most prevalent arthropod-borne disease with around 40% of the world’s population at risk of infection annually .", "Wolbachia pipientis , an obligate intracellular bacterium , is being developed as a biocontrol strategy against dengue becau...	[ "Dengue is endemic in more than 100 countries and is transmitted by the mosquito Aedes aegypti .", "The use of the symbiotic bacterium Wolbachia has become a potential biocontrol approach against dengue virus for two reasons .", "First , Wolbachia spreads rapidly through populations by manipulating host reprodu...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[]	The Genome and Development-Dependent Transcriptomes of Pyronema confluens: A Window into Fungal Evolution	journal.pgen.1003820	null	[ [ "Fungi ( Eumycota ) are a group of eukaryotes that are present in almost all habitats; therefore they do not only play a great role in nature , but also influence human life in many ways [1] .", "About 100 , 000 fungal species have been described , but it is estimated that the actual number might exceed 1...	[ "Fungi are a large group of eukaryotes found in nearly all ecosystems .", "More than 250 fungal genomes have already been sequenced , greatly improving our understanding of fungal evolution , physiology , and development .", "However , for the Pezizomycetes , an early-diverging lineage of filamentous ascomycete...	[ "Fungi are a morphologically and physiologically diverse group of organisms with huge impacts on nearly all ecosystems .", "In recent years , genomes of many fungal species have been sequenced and have greatly improved our understanding of fungal biology .", "Ascomycetes are the largest fungal group with the hi...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "cancer genetics", "model organisms", "genetics", "biology", "mouse", "genetics and genomics", "gene function" ]	Intact p53-Dependent Responses in miR-34–Deficient Mice	journal.pgen.1002797	null	[ [ "The tumor-suppressor protein p53 is a master regulator of the stress response and provides a key barrier to cellular transformation and tumorigenesis [1] .", "Upon oncogene activation , DNA damage , and other forms of cellular stress , p53 accumulates in the nucleus where it induces or represses the tran...	[ "MicroRNAs belonging to the miR-34 family have been proposed as critical modulators of the p53 pathway and potential tumor suppressors in human cancers .", "To formally test these hypotheses , we have generated mice carrying targeted deletion of all three members of this microRNA family .", "We show that comple...	[ "MicroRNAs ( miRNAs ) are small , non-coding RNAs that broadly regulate gene expression .", "MicroRNA deregulation is a common feature of human cancers , and numerous miRNAs have oncogenic or tumor suppressive properties .", "Members of the miR-34 family ( miR-34a , miR-34b , and miR-34c ) have been widely spec...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "molecular probe techniques", "cell cycle and cell division", "cell processes", "fungi", "model organisms", "dna replication", "experimental organism systems", "dna", "molecular biology techniques", "synthesis phase", "cellular structures and organelles", "gel electrophoresis", "research and...	Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast	journal.pgen.1007041	null	[ [ "The faithful and timely duplication of a cell’s genome is required every round of division .", "During eukaryotic S phase , DNA replication initiates at multiple sites along each chromosome called origins of replication .", "Eukaryotic replication initiation has been best characterized in the budding...	[ "A form of dwarfism known as Meier-Gorlin syndrome ( MGS ) is caused by recessive mutations in one of six different genes ( ORC1 , ORC4 , ORC6 , CDC6 , CDT1 , and MCM5 ) .", "These genes encode components of the pre-replication complex , which assembles at origins of replication prior to S phase .", "Also , var...	[ "The origin recognition complex ( ORC ) is essential for licensing replication origins during M/G1 for their firing in the subsequent S phase .", "Individuals with a rare form of dwarfism called Meier-Gorlin syndrome ( MGS ) have mutations in proteins required for origin activation , including various subunits of...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "cell biology", "biology and life sciences" ]	The Analysis of Mutant Alleles of Different Strength Reveals Multiple Functions of Topoisomerase 2 in Regulation of Drosophila Chromosome Structure	journal.pgen.1004739	null	[ [ "Type II topoisomerases are large ATP-dependent homodimeric enzymes that transiently cleave double stranded DNA , pass a second DNA double helix through the break , and then reseal the break [1] , [2] .", "In this way , Topo II enzymes solve a variety of topological problems that normally arise in double ...	[ "Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial , as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism .", "In contrast to vertebrates t...	[ "Type II topoisomerases ( Topo II ) are enzymes that disentangle DNA molecules during essential cellular processes such as DNA replication , chromosome condensation and mitotic cell division .", "Topo II is a major component of mitotic chromosomes and it is a well known target for cancer chemotherapy .", "Topo ...	2014
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "physics", "genomics", "nucleic acids", "genetics", "epigenetics", "biology", "computational biology", "dna", "biophysics", "genetics and genomics" ]	Replication Fork Polarity Gradients Revealed by Megabase-Sized U-Shaped Replication Timing Domains in Human Cell Lines	journal.pcbi.1002443	null	[ [ "Comprehensive knowledge of genetic inheritance at different development stages relies on elucidating the mechanisms that regulate the DNA spatio-temporal replication program and its possible conservation during evolution [1] .", "In multi-cellular organisms , there is no clear consensus sequence where in...	[ "In higher eukaryotes , replication program specification in different cell types remains to be fully understood .", "We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and ...	[ "DNA replication in human cells requires the parallel progression along the genome of thousands of replication machineries .", "Comprehensive knowledge of genetic inheritance at different development stages relies on elucidating the mechanisms that regulate the location and progression of these machineries throug...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "computational biology", "evolutionary biology", "population biology", "genetics and genomics" ]	Positive Selection for New Disease Mutations in the Human Germline: Evidence from the Heritable Cancer Syndrome Multiple Endocrine Neoplasia Type 2B	journal.pgen.1002420	null	[ [ "Multiple endocrine neoplasia ( MEN ) type 2 is characterized by thyroid cancer , variable penetrance of tumors or hyperplasia in other endocrine organs and mutations in RET , the receptor tyrosine kinase proto-oncogene “rearranged during transfection” [1] , [2] .", "The disease is transmitted in an autos...	[ "Multiple endocrine neoplasia type 2B ( MEN2B ) is a highly aggressive thyroid cancer syndrome .", "Since almost all sporadic cases are caused by the same nucleotide substitution in the RET proto-oncogene , the calculated disease incidence is 100–200 times greater than would be expected based on the genome averag...	[ "Multiple endocrine neoplasia type 2B ( MEN2B ) is a highly aggressive thyroid cancer syndrome .", "MEN2B offspring with unaffected parents almost always received a new mutation from the father .", "Moreover , this mutation is almost always at the same nucleotide in the RET proto-oncogene .", "Thus MEN2B's in...	2012
[ "Model", "Results/Discussion" ]	[ "genetics and genomics/complex traits", "evolutionary biology", "genetics and genomics", "genetics and genomics/medical genetics", "genetics and genomics/population genetics" ]	Data and Theory Point to Mainly Additive Genetic Variance for Complex Traits	journal.pgen.1000008	null	[ [ "In view of the apparent conflict between the observations of high proportions of additive genetic variance ( often half or more of the phenotypic variance , and even more of the total genetic variance ) and the recent reports of epistasis at quantitative trait loci ( QTL ) [8] , we consider explanations beyo...	[ "The relative proportion of additive and non-additive variation for complex traits is important in evolutionary biology , medicine , and agriculture .", "We address a long-standing controversy and paradox about the contribution of non-additive genetic variation , namely that knowledge about biological pathways an...	[ "Genetic variation in quantitative or complex traits can be partitioned into many components due to additive , dominance , and interaction effects of genes .", "The most important is the additive genetic variance because it determines most of the correlation of relatives and the opportunities for genetic change b...	2008
[ "Introduction", "Results", "Methods" ]	[ "evolutionary modeling", "biology", "computational biology" ]	Evolutionary Capacitance and Control of Protein Stability in Protein-Protein Interaction Networks	journal.pcbi.1003023	null	[ [ "The toxicity due to protein misfolding and aggregation has a considerable effect on the viability of living organisms [1]– .", "Consequently , cells are under strong selection pressure to evolve thermodynamically stable [6] and aggregation-free protein sequences [7] .", "The internal region of stable...	[ "In addition to their biological function , protein complexes reduce the exposure of the constituent proteins to the risk of undesired oligomerization by reducing the concentration of the free monomeric state .", "We interpret this reduced risk as a stabilization of the functional state of the protein .", "We e...	[ "The folded form of proteins is only marginally stable in vivo and constantly faces the risk of aggregation , unfolding/misfolding , and other aberrant interactions .", "For most proteins , the folded form is also the functionally relevant one and forces of natural selection strongly modulate its stability .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Bacterial Effector Activates Jasmonate Signaling by Directly Targeting JAZ Transcriptional Repressors	journal.ppat.1003715	null	[ [ "A prevailing concept for plant-pathogen interactions highlights the continuing battles between the activation of plant immune responses upon pathogen perception and the subversion of host immunity by virulence factors produced by successful pathogens .", "One branch of the plant immunity system is based ...	[ "Gram-negative bacterial pathogens deliver a variety of virulence proteins through the type III secretion system ( T3SS ) directly into the host cytoplasm .", "These type III secreted effectors ( T3SEs ) play an essential role in bacterial infection , mainly by targeting host immunity .", "However , the molecul...	[ "Many Gram-negative bacterial pathogens rely on the type III secretion system , which is a specialized protein secretion apparatus , to inject virulence proteins , called effectors , into the host cells .", "The type III secreted effectors ( T3SEs ) directly target host substrates in order to promote bacterial co...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "antimicrobials", "animal models of infection", "organismal evolution", "infectious diseases", "microbial mutation", "medicine and health sciences", "emerging infectious diseases", "viral persistence and latency", "microbial evolution", "virology", "emerging viral diseases", "microbial control...	Estimating the Fitness Advantage Conferred by Permissive Neuraminidase Mutations in Recent Oseltamivir-Resistant A(H1N1)pdm09 Influenza Viruses	journal.ppat.1004065	null	[ [ "The influenza NA inhibitor antiviral drug oseltamivir is a key element of public health defences against influenza , and was used during the early stages of the A ( H1N1 ) pdm09 influenza pandemic to lessen the burden of disease in infected patients [1] , [2] .", "Resistance to oseltamivir most commonly ...	[ "Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection .", "Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses .", "Since the emergence of the pandemic 2009 A ( H1N1 ) influe...	[ "Antimicrobial resistance is an increasing problem for the treatment of infectious diseases .", "In 2007–2008 human seasonal A ( H1N1 ) influenza viruses rapidly acquired resistance to the most commonly used anti-influenza drug oseltamivir , via a H275Y amino acid mutation within the neuraminidase ( NA ) protein ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biophysics/protein folding", "cell biology/cell signaling", "biotechnology/protein chemistry and proteomics", "biochemistry/protein folding", "neurological disorders", "cell biology/membranes and sorting", "physiology/cell signaling", "neuroscience/neuronal signaling mechanisms", "biochemistry/cell...	Botulinum Neurotoxin Devoid of Receptor Binding Domain Translocates Active Protease	journal.ppat.1000245	null	[ [ "Botulinum neurotoxin ( BoNT ) inhibits synaptic exocytosis in peripheral cholinergic synapses causing botulism , a severe disease characterized by descending flaccid paralysis .", "Clostridium botulinum strains express seven BoNT isoforms known as serotypes A to G [1] .", "Each BoNT isoform is synthe...	[ "Clostridium botulinum neurotoxin ( BoNT ) causes flaccid paralysis by disabling synaptic exocytosis .", "Intoxication requires the tri-modular protein to undergo conformational changes in response to pH and redox gradients across endosomes , leading to the formation of a protein-conducting channel .", "The ∼50...	[ "Botulinum neurotoxin , widely acknowledged to be the most potent toxin known , is a modular nanomachine and a marvel of protein design .", "This neurotoxin exploits a modular design to achieve its potent toxicity , which relies on one of its modules—the heavy chain channel—to operate as a specific protein transl...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "body weight", "medicine and health sciences", "african americans", "surgical and invasive medical procedures", "ethnicities", "physiological parameters", "mathematics", "statistics (mathematics)", "chromosome mapping", "obesity", "molecular biology techniques", "research and analysis methods"...	African genetic ancestry interacts with body mass index to modify risk for uterine fibroids	journal.pgen.1006871	null	[ [ "Uterine leiomyomata , also referred to as fibroids , are benign growths arising from myometrial smooth muscle cells .", "As the most common pelvic tumor in women , prevalence of fibroids ranges from 20 to 77% [1–5] , and accounts for $9 . 4-$34 billion dollars annually in healthcare costs [5–7] .", "...	[ "Race , specifically African ancestry , and obesity are important risk factors for uterine fibroids , and likely interact to provide the right conditions for fibroid growth .", "However , existing studies largely focus on the main-effects rather than their interaction .", "Here , we firstly provide evidence for...	[ "Although it is postulated that obesity and non-modifiable risk factors such as race or genetic ancestry may interact to jointly influence uterine fibroid growth , most existing studies have not evaluated their interaction .", "In this study we exhibit evidence for interaction across several tiers of investigatio...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "physiology", "genetics", "biology", "anatomy and physiology", "genetics and genomics" ]	The Chicken Frizzle Feather Is Due to an α-Keratin (KRT75) Mutation That Causes a Defective Rachis	journal.pgen.1002748	null	[ [ "Birds have evolved many unique and interesting features , allowing them to adapt and radiate into various ecological niches .", "They display a great degree of diversity in feathers and other body parts .", "Domesticated birds exhibit an even greater diversity in phenotypes than their wild ancestors ...	[ "Feathers have complex forms and are an excellent model to study the development and evolution of morphologies .", "Existing chicken feather mutants are especially useful for identifying genetic determinants of feather formation .", "This study focused on the gene F , underlying the frizzle feather trait that h...	[ "With the availability of a sequenced chicken genome , the reservoir of variant plumage genes found in domestic chickens can provide insight into the molecular mechanisms underlying the diversity of feather forms .", "In this paper , we identify the molecular basis of the distinctive frizzle ( F ) feather phenoty...	2012
[ "Introduction", "Design and implementation", "Results and discussions", "Availability and future directions" ]	[ "rna-binding proteins", "chemical bonding", "3' utr", "messenger rna", "dna transcription", "untranslated regions", "genome analysis", "physical chemistry", "proteins", "gene expression", "chemistry", "cross-linking", "gene ontologies", "biochemistry", "rna", "polyadenylation", "nucl...	PRAS: Predicting functional targets of RNA binding proteins based on CLIP-seq peaks	journal.pcbi.1007227	null	[ [ "RNA-binding proteins ( RBPs ) are essential in many post-transcriptional regulatory processes , such as alternative splicing , stability , localization and editing [1] .", "For example , RBP Quaking plays important roles in pre-mRNA splicing and mRNA export [2]; RBP HuR is an mRNA stability and splicing ...	[ "RNA-protein interaction plays important roles in post-transcriptional regulation .", "Recent advancements in cross-linking and immunoprecipitation followed by sequencing ( CLIP-seq ) technologies make it possible to detect the binding peaks of a given RNA binding protein ( RBP ) at transcriptome scale .", "How...	[ "It is important to identify the functional targets of RBPs , which are essential regulators in post-transcriptional processes .", "PRAS aims to predict RBP targets based on the intensities and positions of the binding peaks obtained from CLIP-seq studies .", "We demonstrate that PRAS score outperforms other ex...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Tsetse Fly (G.f. fuscipes) Distribution in the Lake Victoria Basin of Uganda	journal.pntd.0003705	null	[ [ "Tsetse flies are responsible for the transmission of human African trypanosomiasis ( HAT ) , also known as sleeping sickness and its animal form ( nagana ) .", "Trypanosomiasis occurs in 38 sub-Saharan African countries with an average of 15 , 000 human cases reported annually ( period 2000–2012 [1] ) , ...	[ "Tsetse flies transmit trypanosomes , the causative agent of human and animal African trypanosomiasis .", "The tsetse vector is extensively distributed across sub-Saharan Africa .", "Trypanosomiasis maintenance is determined by the interrelationship of three elements: vertebrate host , parasite and the vector r...	[ "Trypanosomiasis is a vector-borne disease transmitted to both humans and animals by the tsetse fly .", "The tsetse vector is distributed across sub-Saharan Africa .", "Trypanosomiasis maintenance is determined by the interrelationship of three elements: vertebrate host , parasite and the vector responsible for...	2015
[ "Introduction", "Results", "Discussions", "Methods" ]	[ "dermatology", "innate immune system", "keratinocytes", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "gene regulation", "skin tumors", "immunology", "cancer treatment", "cancers and neoplasms", "epithelial cells", "oncology", "ski...	The ARE-binding protein Tristetraprolin (TTP) is a novel target and mediator of calcineurin tumor suppressing function in the skin	journal.pgen.1007366	null	[ [ "Calcineurin is the only known serine/threonine phosphatase under calcium/calmodulin control [1] .", "The active enzyme is a heterotrimeric complex formed by a larger catalytic subunit ( calcineurin A , CnA ) , a Ca2+-binding regulatory subunit ( calcineurin B , CnB ) and calmodulin [2] .", "CnB is ex...	[ "An increased incidence of skin inflammatory diseases is frequently observed in organtransplanted patients being treated with calcineurin inhibitor-based immunosuppressive agents .", "The mechanism of increased skin inflammation in this context has however not yet been clarified .", "Here we report an increased...	[ "It is known that a higher incidence of skin squamous cell carcinoma ( SCC ) development , as well as increased chronic skin inflammation , occurs in organ transplant patients with long-term use of calcineurin inhibitors as immunosuppressive drugs .", "Whether the increased skin inflammation contributes to the de...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "clinical research design", "epidemiology" ]	Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis	journal.pntd.0001562	null	[ [ "Dengue virus ( DENV ) causes the most prevalent mosquito-borne viral disease affecting humans , with 2 . 5–3 billion people at risk for infection and approximately 50 million cases of dengue each year [1] , [2] .", "The four DENV serotypes are transmitted to humans by Aedes aegypti and Ae .", "albopi...	[ "Tens of millions of dengue cases and approximately 500 , 000 life-threatening complications occur annually .", "New tools are needed to distinguish dengue from other febrile illnesses .", "In addition , the natural history of pediatric dengue early in illness in a community-based setting has not been well-defi...	[ "Dengue virus causes an estimated 50 million dengue cases and approximately 500 , 000 life-threatening complications annually .", "New tools are needed to distinguish dengue from other febrile illnesses .", "In addition , the natural history of pediatric dengue early in illness in a community-based setting has ...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "infectious diseases/antimicrobials and drug resistance", "microbiology" ]	The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module	journal.ppat.1001299	null	[ [ "Tuberculosis ( TB ) affects large parts of the world's population , particularly in developing countries [1] .", "The antibiotics isoniazid ( INH ) and ethambutol ( EMB ) [2] have been used for decades as frontline drugs to treat Mycobacterium tuberculosis infections , the causative agent of TB , but the...	[ "The d-arabinan-containing polymers arabinogalactan ( AG ) and lipoarabinomannan ( LAM ) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis .", "Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl ( Araf ) transferases whose structures ar...	[ "Tuberculosis ( TB ) , an infectious disease caused by the bacillus Mycobacterium tuberculosis , burdens large swaths of the world population .", "Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol .", "This front line compoun...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "infectious diseases/bacterial infections", "cell biology/cell signaling" ]	Identification of Host-Dependent Survival Factors for Intracellular Mycobacterium tuberculosis through an siRNA Screen	journal.ppat.1000839	null	[ [ "Successful parasitization of macrophages by Mycobacterium tuberculosis ( Mtb ) reflects the equilibrium between host and pathogen , which is established and maintained through the modulation of macrophage-signaling mechanisms .", "This leads to the attenuation of several cellular processes that include f...	[ "The stable infection of host macrophages by Mycobacterium tuberculosis ( Mtb ) involves , and depends on , the attenuation of the diverse microbicidal responses mounted by the host cell .", "This is primarily achieved through targeted perturbations of the host cellular signaling machinery .", "Therefore , in v...	[ "The adaptation of Mycobacterium tuberculosis ( Mtb ) involves dynamic interactions with the molecular components of the host cellular machinery .", "Therefore , targeting relevant host factors may provide an alternate approach for the chemotherapy of tuberculosis ( TB ) .", "To test this , we first performed a...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "geographical locations", "microbiology", "argentina", "saliva", "animals", "viral vectors", "viruses", "rna viruses", "insect vectors", ...	Vector competence of Aedes aegypti for different strains of Zika virus in Argentina	journal.pntd.0007433	null	[ [ "Zika virus ( ZIKV ) is a single-stranded positive sense RNA virus that was first isolated in 1947 in the Ziika Forest in Uganda from a sentinel Rhesus monkey [1 , 2] .", "One year later , this arthropod-borne virus ( arbovirus ) member of the genus Flavivirus was isolated from Aedes africanus mosquitoes ...	[ "The importance of Zika virus ( ZIKV ) has increased noticeably since the outbreak in the Americas in 2015 , when the illness was associated with congenital disorders .", "Although there is evidence of sexual transmission of the virus , the mosquito Aedes aegypti is believed to be the main vector for transmission...	[ "Zika virus is a flavivirus transmitted by mosquitoes , isolated for the first time in the Ziika Forest in Uganda in 1947 from a rhesus macaque monkey .", "The disease is usually asymptomatic , but sometimes it causes a mild illness that comes with fever , rash , joint pain , and conjunctivitis .", "The World H...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "chemical compounds", "aspergillus", "organic compounds", "membrane proteins", "aspergillus nidulans", "physiological processes", "fungi", "model organisms", "homeostasis", "amino acids", "calcium signaling", "cellular structures and organelles", "research a...	Palmitoylation of the Cysteine Residue in the DHHC Motif of a Palmitoyl Transferase Mediates Ca2+ Homeostasis in Aspergillus	journal.pgen.1005977	null	[ [ "In all eukaryotic cells , the cytosolic free calcium ( [Ca2+]c ) concentration is strictly and precisely controlled by complex interactions between various calcium-channels , calcium-pumps and calcium-antiporters and by calcium buffering in the cytoplasm .", "Finely tuned changes in [Ca2+]c mediate a var...	[ "Finely tuned changes in cytosolic free calcium ( [Ca2+]c ) mediate numerous intracellular functions resulting in the activation or inactivation of a series of target proteins .", "Palmitoylation is a reversible post-translational modification involved in membrane protein trafficking between membranes and in thei...	[ "Palmitoylation is a reversible post-translational modification catalyzed by palmitoyl acyltransferases ( PATs ) and proteins that undergo this modification are involved in numerous intracellular functions .", "Yeast Akr1p was the first characterized PAT whilst HIP14 , an Akr1p homolog in human , is one of the mo...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cell physiology", "medicine and health sciences", "enzymes", "cancer risk factors", "enzymology", "cell metabolism", "oncology", "stem cells", "enzyme metabolism", "epigenetics", "enzyme chemistry", "chromatin", "cell potency", "chromosome biology", "proteins", "animal cells", "gene...	Epigenetic regulation of cell fate reprogramming in aging and disease: A predictive computational model	journal.pcbi.1006052	null	[ [ "Aging is associated with profound changes in the epigenome involving large disturbances of the epigenetic landscape and genome architecture [1 , 2] .", "Studies in model organisms have not only revealed the complex changes occurring in chromatin structure and functioning during aging , but also the remar...	[ "Understanding the control of epigenetic regulation is key to explain and modify the aging process .", "Because histone-modifying enzymes are sensitive to shifts in availability of cofactors ( e . g . metabolites ) , cellular epigenetic states may be tied to changing conditions associated with cofactor variabilit...	[ "Cell reprogramming , a process that allows differentiated cells to re-acquire stem-like properties , is increasingly considered a critical phenomenon in tissue regeneration , aging and cancer .", "In light of the importance of metabolism in controlling cell fate , we designed a computational model capable of pre...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Enumeration of Smallest Intervention Strategies in Genome-Scale Metabolic Networks	journal.pcbi.1003378	null	[ [ "Stoichiometric and constraint-based modeling techniques such as flux balance analysis or elementary modes analysis have become standard tools for the mathematical and computational investigation of metabolic networks [1]–[4] .", "Although these methods rely solely on the structure ( stoichiometry ) of me...	[ "One ultimate goal of metabolic network modeling is the rational redesign of biochemical networks to optimize the production of certain compounds by cellular systems .", "Although several constraint-based optimization techniques have been developed for this purpose , methods for systematic enumeration of interven...	[ "Mathematical modeling has become an essential tool for investigating metabolic networks .", "One ultimate goal of metabolic network modeling is the rational redesign of biochemical networks to optimize the production of certain compounds by cellular systems .", "Accordingly , several optimization techniques ha...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "molecular probe techniques", "gene regulation", "hepacivirus", "pathogens", "messenger rna", "microbiology", "immunoblotting", "viral structure", "viruses", "rna viruses", "immunoprecipitation", "molecular biology techni...	Epidermal Growth Factor Receptor-Dependent Mutual Amplification between Netrin-1 and the Hepatitis C Virus	journal.pbio.1002421	The dependence receptor ligand Netrin-1 and the hepatitis C virus induce each other's expression, generating a mutual amplification loop with potential implications for the development of hepatocellular carcinoma.	[ [ "Cancers triggered by microbial oncogenes account for approximately 16% of cancer occurrences [1] .", "Hepatitis C virus ( HCV ) is a major etiologic agent of hepatocellular carcinoma ( HCC ) , the fifth most common cancer worldwide [2] .", "The epidermal growth factor receptor ( EGFR ) is a host fact...	[ "Hepatitis C virus ( HCV ) is an oncogenic virus associated with the onset of hepatocellular carcinoma ( HCC ) .", "The present study investigated the possible link between HCV infection and Netrin-1 , a ligand for dependence receptors that sustains tumorigenesis , in particular in inflammation-associated tumors ...	[ "Viruses and bacteria are implicated in 15%–20% of total cancer occurrences .", "Hepatitis C virus ( HCV ) infection is one of the main causative agents of liver cancer .", "“Dependence receptors” are a class of receptors that auto-activate and trigger apoptosis in the absence of their ligands , and “dependence...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "neuroscience" ]	Facilitation of AMPA Receptor Synaptic Delivery as a Molecular Mechanism for Cognitive Enhancement	journal.pbio.1001262	A small peptide from a neuronal cell adhesion molecule enhances synaptic plasticity in the hippocampus and results in improved cognitive performance in rats.	[ [ "Activity-dependent synaptic changes , generally termed synaptic plasticity , underlie multiple forms of cognitive function , such as learning and memory [1] .", "Strong interest has accrued in understanding the molecular and cellular mechanisms underlying these changes .", "Additionally , it is belie...	[ "Cell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity , and they have been linked to cognitive function in adult animals .", "We have previously developed a mimetic peptide ( FGL ) from the neural cell adhesion molecule ( NCAM ) that e...	[ "The human brain contains trillions of neuronal connections , called synapses , whose pattern of activity controls all our cognitive functions .", "These synaptic connections are dynamic and constantly changing in their strength and properties , and this process of synaptic plasticity is essential for learning an...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "hepatitis c", "medicine", "systems biology", "infectious diseases", "hepatitis", "theoretical biology", "biology", "computational biology", "viral diseases" ]	Replication Vesicles are Load- and Choke-Points in the Hepatitis C Virus Lifecycle	journal.ppat.1003561	null	[ [ "Hepatitis C virus ( HCV ) infection is a major global health problem , with approximately 170 million chronically infected individuals worldwide and 3 to 4 million new infections occurring each year [1] .", "Acute infection is mostly asymptomatic , however , it develops into a chronic infection in about ...	[ "Hepatitis C virus ( HCV ) infection develops into chronicity in 80% of all patients , characterized by persistent low-level replication .", "To understand how the virus establishes its tightly controlled intracellular RNA replication cycle , we developed the first detailed mathematical model of the initial dynam...	[ "Hepatitis C is a severe disease and a prime cause for liver transplantation .", "Up to 3% of the world's population are chronically infected with its causative agent , the Hepatitis C virus ( HCV ) .", "This capacity to establish long ( decades ) lasting persistent infection sets HCV apart from other plus-stra...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "medicine and health sciences", "cell cycle inhibitors", "senescence", "helminths", "gene regulation", "cell cycle and cell division", "cell processes", "animals", "liver diseases", "plasmid construction", "physiological processes", "developmental biology", ...	Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway	journal.pntd.0005268	null	[ [ "Liver fibrosis , a major health problem worldwide [1] , results from different etiologies of chronic liver injury , and eventually progresses into cirrhosis or hepatocellular carcinoma .", "Recently , liver fibrosis was viewed as a reversible process [2] .", "After years of prevention and treatment o...	[ "Liver fibrosis was viewed as a reversible process .", "The activation of hepatic stellate cells ( HSCs ) is a key event in the process of liver fibrosis .", "The induction of senescence of HSCs would accelerate the clearance of the activated HSCs .", "Previously , we demonstrated that soluble egg antigens ( ...	[ "Activation of hepatic stellate cells ( HSCs ) is a key event of liver fibrosis .", "Induction of activated HSCs apoptosis and inhibition of activated HSCs proliferation are the common anti-fibrotic strategies to block liver fibrosis .", "The induction of senescence of HSCs is responsible for the clearance of t...	2016
[ "Introduction", "Model", "Results", "Discussion" ]	[ "psychology", "ecology and environmental sciences", "animal behavior", "zoology", "ecology", "cognition", "behavior", "biology and life sciences", "sensory perception", "social sciences", "evolutionary biology", "cognitive science", "neuroscience", "learning and memory", "animal cognitio...	Collective Learning and Optimal Consensus Decisions in Social Animal Groups	journal.pcbi.1003762	null	[ [ "Associative learning tunes an organism's behavior to exploit statistical patterns in the environment and can improve decision-making accuracy across a wide range of scenarios [1]–[2] .", "In the vast majority of experiments on learning , the subject of study has been a single individual in isolation ( se...	[ "Learning has been studied extensively in the context of isolated individuals .", "However , many organisms are social and consequently make decisions both individually and as part of a collective .", "Reaching consensus necessarily means that a single option is chosen by the group , even when there are dissent...	[ "Learning is ubiquitous among animal species , allowing individuals to adjust their behavior in response to their environment to improve their chances of survival and reproduction .", "However , while many animals live and make decisions within social groups , it is not well understood how associative learning fu...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "functional genomics", "model organisms", "gene expression", "genetics", "molecular genetics", "biology", "computational biology", "yeast and fungal models", "microbiology", "genetics and genomics" ]	Deciphering the Transcriptional-Regulatory Network of Flocculation in Schizosaccharomyces pombe	journal.pgen.1003104	null	[ [ "Flocculation is an inherent characteristic of yeasts involving asexual aggregation of cells into flocs that separate rapidly from the medium ( reviewed recently in [1] , [2] ) .", "Individual yeast cells transition into this morphological state as an adaptation to various environmental stresses by shield...	[ "In the fission yeast Schizosaccharomyces pombe , the transcriptional-regulatory network that governs flocculation remains poorly understood .", "Here , we systematically screened an array of transcription factor deletion and overexpression strains for flocculation and performed microarray expression profiling an...	[ "Flocculation is a process that involves yeast cells adhering to one another to form clumps called flocs .", "This trait is important for industrial yeast applications as it provides a cost-effective and efficient method to remove yeast cells .", "The adherence between cells occurs by the binding of glycoprotei...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "computational biology" ]	Structure and Dynamics of the Membrane-Bound Cytochrome P450 2C9	journal.pcbi.1002152	null	[ [ "The liver-specific , mammalian cytochromes P450 ( CYPs ) are monooxygenases essential for drug metabolism [1] .", "CYPs accept two electrons from the CYP reductase ( CPR ) to oxidize a wide range of water-soluble and liposoluble xenobiotics .", "CYPs and the CPR are anchored in the membrane of the en...	[ "The microsomal , membrane-bound , human cytochrome P450 ( CYP ) 2C9 is a liver-specific monooxygenase essential for drug metabolism .", "CYPs require electron transfer from the membrane-bound CYP reductase ( CPR ) for catalysis .", "The structural details and functional relevance of the CYP-membrane interactio...	[ "We describe the first atomic-detail models and simulations of a full-length , membrane-bound mammalian cytochrome P450 .", "To date , all the structural studies of microsomal , drug-metabolizing cytochrome P450s have been performed using engineered , solubilized forms of the enzymes and it is not yet understood ...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "t helper cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "immunology", "tropical diseases", "vaccines", "bacterial diseases", "developmental biology", "molecular development", "cytotoxic t cells", "infectio...	A comparison of antigen-specific T cell responses induced by six novel tuberculosis vaccine candidates	journal.ppat.1007643	null	[ [ "Tuberculosis ( TB ) is an infectious disease of major global importance .", "An estimated ten million people were diagnosed with TB disease in 2017 and 1 . 6 million died [1] .", "Current efforts to curb the TB epidemic are insufficient to achieve the 2035 targets set by the World Health Organization...	[ "Eradication of tuberculosis ( TB ) , the world's leading cause of death due to infectious disease , requires a highly efficacious TB vaccine .", "Many TB vaccine candidates are in pre-clinical and clinical development but only a few can be advanced to large-scale efficacy trials due to limited global resources ....	[ "Tuberculosis ( TB ) causes more deaths than any other single infectious disease , and a new , improved vaccine is needed to control the epidemic .", "Many new TB vaccine candidates are in clinical development , but only one or two can be advanced to expensive efficacy trials .", "In this study , we compared ma...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "paleoclimatology", "ecology and environmental sciences", "ecological niches", "paleobiology", "ecology", "ecophysiology", "earth sciences", "paleontology", "biology and life sciences", "plant ecology", "paleoecology", "biodiversity", "macroecology", "paleobotany" ]	Plant Ecological Strategies Shift Across the Cretaceous–Paleogene Boundary	journal.pbio.1001949	The End-Cretaceous Impact Winter Killed Off Slow-Growing Plants The end-Cretaceous mass extinction caused the selective extinction of plant species with slow-growth strategies, consistent with an impact winter hypothesis.	[ [ "The Cretaceous–Paleogene boundary ( KPB ) is marked by the Chicxulub bolide impact and mass extinction [1]–[3] .", "In temperate North America , while the impact resulted in the extinction of more than 50% of plant species [4] , a major unresolved issue is whether this killing event was also a large-scal...	[ "The Chicxulub bolide impact caused the end-Cretaceous mass extinction of plants , but the associated selectivity and ecological effects are poorly known .", "Using a unique set of North Dakota leaf fossil assemblages spanning 2 . 2 Myr across the event , we show among angiosperms a reduction of ecological strate...	[ "Sixty-six million years ago the Chicxulub bolide impacted the Earth , marking the Cretaceous–Paleogene boundary ( KPB ) .", "This event caused the planet's most recent mass extinction , but the selectivity and functional consequences of the extinction on terrestrial plants has been largely unknown .", "A key u...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "genome expression analysis", "functional genomics", "animal genetics", "genome evolution", "gene function", "genome sequencing", "mutation", "genome analysis", "molecular genetics", "molecular biology techniques", "gene expression", "molecular biology", "transcrip...	Systematic Dissection of Coding Exons at Single Nucleotide Resolution Supports an Additional Role in Cell-Specific Transcriptional Regulation	journal.pgen.1004592	null	[ [ "Protein coding sequences have been shown to contain additional functional information such as splicing [1] , [2] , mRNA stability [3] , microRNA target sites [4] , and transcriptional enhancer activity [5]–[10] .", "Furthermore , by analyzing various genomic datasets , numerous exons were shown to intera...	[ "In addition to their protein coding function , exons can also serve as transcriptional enhancers .", "Mutations in these exonic-enhancers ( eExons ) could alter both protein function and transcription .", "However , the functional consequence of eExon mutations is not well known .", "Here , using massively p...	[ "Exons that code for protein can also have additional functions , such as regulating gene transcription through enhancer activity .", "Here , we changed every nucleotide in three different exons that also function as enhancers , and examined their enhancer activity to test whether nucleotide changes in these exon...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/genetics of disease", "genetics and genomics/population genetics", "evolutionary biology/genomics" ]	Characterising and Predicting Haploinsufficiency in the Human Genome	journal.pgen.1001154	null	[ [ "With array-based copy number detection and the current generation of sequencing technologies , our ability to discover genetic variation is running far ahead of our ability to interpret the functional impact of that variation .", "Several software tools exist for predicting the phenotypic impact of mutat...	[ "Haploinsufficiency , wherein a single functional copy of a gene is insufficient to maintain normal function , is a major cause of dominant disease .", "Human disease studies have identified several hundred haploinsufficient ( HI ) genes .", "We have compiled a map of 1 , 079 haplosufficient ( HS ) genes by sys...	[ "Humans , like most complex organisms , have two copies of most genes in their genome , one from the mother and one from the father .", "This redundancy provides a back-up copy for most genes , should one copy be lost through mutation .", "For a minority of genes , one functional copy is not enough to sustain n...	2010
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer	journal.ppat.1004767	null	[ [ "The HIV-1 envelope glycoprotein ( Env ) , a trimer comprising three gp120 and gp41 subunits , is the target of broadly neutralizing antibodies ( bNAbs ) that are known to prevent virus infection in animal models .", "The induction of bNAbs by vaccines is a highly desirable , but not yet achieved , goal ....	[ "The trimeric envelope ( Env ) spike is the focus of vaccine design efforts aimed at generating broadly neutralizing antibodies ( bNAbs ) to protect against HIV-1 infection .", "Three recent developments have facilitated a thorough investigation of the antigenic structure of the Env trimer:", "1 ) the isolation...	[ "The discovery of new broadly neutralizing antibodies against various epitopes on the HIV-1 envelope glycoprotein trimer and increased knowledge of its structure are guiding vaccine design .", "To increase our understanding of the interrelationships among the different epitopes , we generated a detailed antigenic...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Early Secreted Antigen ESAT-6 of Mycobacterium tuberculosis Promotes Protective T Helper 17 Cell Responses in a Toll-Like Receptor-2-dependent Manner	journal.ppat.1002378	null	[ [ "Tuberculosis ( TB ) remains a major health problem , with an estimated one third of the world's population infected with Mycobacterium tuberculosis , the causative agent of TB , resulting in ∼3 million deaths annually .", "Bacillus Calmette-Guérin ( BCG ) , the only TB vaccine presently used in humans , ...	[ "Despite its relatively poor efficacy , Bacillus Calmette-Guérin ( BCG ) has been used as a tuberculosis ( TB ) vaccine since its development in 1921 .", "BCG induces robust T helper 1 ( Th1 ) immune responses but , for many individuals , this is not sufficient for host resistance against Mycobacterium tuberculos...	[ "Tuberculosis is a global health problem , with one-third of the global population infected with tubercle bacteria .", "Numerous studies have shown that Th1 cell responses are indispensable for protective immunity against TB .", "However , while the vaccine strain BCG induces sufficient Th1 cell response , this...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "dementia", "genomics", "neurological disorders", "neurology", "genetics", "biology", "computational biology", "genetics and genomics" ]	Critical Evaluation of Imprinted Gene Expression by RNA–Seq: A New Perspective	journal.pgen.1002600	null	[ [ "Why diploid organisms would forgo the safety-net of a redundant genome and preferentially express one allele in a parent-of-origin dependent manner has been a matter of debate since the discovery of imprinted transcription .", "Our understanding of this issue as well as the range of processes affected by...	[ "In contrast to existing estimates of approximately 200 murine imprinted genes , recent work based on transcriptome sequencing uncovered parent-of-origin allelic effects at more than 1 , 300 loci in the developing brain and two adult brain regions , including hundreds present in only males or females .", "Our ind...	[ "Typically both copies of mammalian genes are expressed , but in some cases , “imprinting” restricts expression to the maternal or paternal copy .", "Having two copies of each gene is considered advantageous since in enables compensation when one does not function properly .", "Why imprinting evolved and its ut...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "helminth infections", "infectious diseases", "medicine and health sciences", "toxocariasis", "larva migrans", "neglected tropical diseases", "tropical diseases", "parasitic diseases" ]	Clinical Features and Course of Ocular Toxocariasis in Adults	journal.pntd.0002938	null	[ [ "Toxocariasis is a globally prevalent illness caused by infestation of the parasite Toxocara canis or Toxocara cati larvae , which is the most ubiquitous gastrointestinal helminth in dogs and cats [1] , [2] .", "Human beings generally become infected through ingestion of embryonated eggs from contaminated...	[ "To investigate the clinical features , clinical course of granuloma , serologic findings , treatment outcome , and probable infection sources in adult patients with ocular toxocariasis ( OT ) .", "In this retrospective cohort study , we examined 101 adult patients diagnosed clinically and serologically with OT ....	[ "Toxocariasis is one of America's most common neglected infections of poverty and a helminthiasis of global importance .", "Little is known about the epidemiologic , demographic , and clinical features of ocular toxocariasis ( OT ) in adult patients , and the treatment regimen for OT has not been standardized .",...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Synergistic and Independent Actions of Multiple Terminal Nucleotidyl Transferases in the 3’ Tailing of Small RNAs in Arabidopsis	journal.pgen.1005091	null	[ [ "MicroRNAs ( miRNAs ) , a class of small non-coding RNAs with 20–24 nt in size , are master regulators of gene expression at post-transcriptional levels in both plants and animals [1 , 2] .", "They impact various biological processes such as development , metabolism and response to different biotic and ab...	[ "All types of small RNAs in plants , piwi-interacting RNAs ( piRNAs ) in animals and a subset of siRNAs in Drosophila and C . elegans are subject to HEN1 mediated 3’ terminal 2’-O-methylation .", "This modification plays a pivotal role in protecting small RNAs from 3’ uridylation , trimming and degradation .", ...	[ "Small silencing RNAs are key regulators of gene expression in both plants and animals .", "HEN1-mediated 3’ terminal 2’-O-methylation plays a crucial role in small RNA stability control .", "In the absence of HEN1 , several types of small RNAs become frequently uridylated ( non-templated uridine addition ) and...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Structural Analysis of the Synthetic Duffy Binding Protein (DBP) Antigen DEKnull Relevant for Plasmodium vivax Malaria Vaccine Design	journal.pntd.0003644	null	[ [ "Plasmodium vivax is a causative agent of malaria , inflicting significant morbidity and impeding economic growth in highly endemic areas [1 , 2] .", "Increasing evidence indicates the severity of disease , economic impact , and burden of P . vivax has been severely underestimated [1 , 2] .", "Among t...	[ "The Plasmodium vivax vaccine candidate Duffy Binding Protein ( DBP ) is a protein necessary for P . vivax invasion of reticulocytes .", "The polymorphic nature of DBP induces strain-specific immune responses that pose unique challenges for vaccine development .", "DEKnull is a synthetic DBP based antigen that ...	[ "Plasmodium vivax is an oft neglected causative agent of human malaria .", "It inflicts tremendous burdens on public health infrastructures and causes significant detrimental effects on socio-economic growth throughout the world .", "P . vivax Duffy Binding Protein ( DBP ) is a surface protein that the parasite...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genetics of disease", "genetics and genomics/complex traits" ]	Genome-Wide Association Study Identifies ALDH7A1 as a Novel Susceptibility Gene for Osteoporosis	journal.pgen.1000806	null	[ [ "Osteoporosis , characterized primarily by low bone mineral density ( BMD ) , is a major public health problem because it increases susceptibility to low-trauma osteoporotic fractures ( OF ) .", "Hip fractures , which are the most common and severe form of OF , are associated with high morbidity and morta...	[ "Osteoporosis is a major public health problem .", "It is mainly characterized by low bone mineral density ( BMD ) and/or low-trauma osteoporotic fractures ( OF ) , both of which have strong genetic determination .", "The specific genes influencing these phenotypic traits , however , are largely unknown .", "...	[ "Osteoporosis is a major health concern worldwide .", "It is a highly heritable disease characterized mainly by low bone mineral density ( BMD ) and/or osteoporotic fractures .", "However , the specific genetic variants determining risk for low BMD or OF are largely unknown .", "Here , taking advantage of rec...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "dominican republic", "united states", "invertebrates", "medicine and health sciences", "body fluids", "legs", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "tropical diseases", "microbiology", "geographical locations", "limbs (anatomy)", "anim...	Transmission risk of two chikungunya lineages by invasive mosquito vectors from Florida and the Dominican Republic	journal.pntd.0005724	null	[ [ "Native to Africa , chikungunya virus ( CHIKV ) emerged to produce intermittent outbreaks from the 1950s in Southeast Asia ( Asian CHIKV lineage ) and regional outbreaks in India in the 1960s and 1970s [1 , 2] .", "Chikungunya also emerged in Kenya in 2004 ( Eastern/Central/Southern African , ECSA , CHIKV...	[ "Between 2014 and 2016 more than 3 , 800 imported human cases of chikungunya fever in Florida highlight the high risk for local transmission .", "To examine the potential for sustained local transmission of chikungunya virus ( CHIKV ) in Florida we tested whether local populations of Aedes aegypti and Aedes albop...	[ "The emergence of mosquito-borne chikungunya virus in the Americas starting in 2013 has been associated with geographically widespread outbreaks of human illness .", "Transmission of chikungunya virus in the U . S . is a major public health risk , especially in Florida where the environmental conditions are favor...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "diabetes and endocrinology/obesity", "genetics and genomics/complex traits", "genetics and genomics/gene discovery", "genetics and genomics/gene expression" ]	Use of Genome-Wide Expression Data to Mine the “Gray Zone” of GWA Studies Leads to Novel Candidate Obesity Genes	journal.pgen.1000976	null	[ [ "In the current age of genome-wide association ( GWA ) studies using hundreds of thousands of single nucleotide polymorphisms ( SNPs ) , obesity has been a popular phenotype to investigate .", "Obesity , often measured as the body mass index ( BMI ) and defined as BMI≥30 kg/m2 , is important not only beca...	[ "To get beyond the “low-hanging fruits” so far identified by genome-wide association ( GWA ) studies , new methods must be developed in order to discover the numerous remaining genes that estimates of heritability indicate should be contributing to complex human phenotypes , such as obesity .", "Here we describe ...	[ "Obesity has a strong genetic component and an estimated 45%–85% of the variation in adult relative weight is genetically determined .", "Many genes have recently been identified in genome-wide association studies .", "The individual effects of the identified genes , however , have been very modest , and their ...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "protein interactions", "dna-binding proteins", "protein structure", "epigenetics", "dna", "dna structure", "chromatin", "chromosome biology", "proteins", "gene expression", "histones", "molecular biology", "nucleosomes", "biochemistry", "biochemical simulations", "cell biology", "nu...	Binding of DNA-bending non-histone proteins destabilizes regular 30-nm chromatin structure	journal.pcbi.1005365	null	[ [ "In cells , DNA , with the help of a large number of proteins , is packaged into a higher order structure known as chromatin .", "In eukaryotes , in its simplest level of packaging , DNA is wrapped around histone proteins to form a “beads on a string” form of chromatin having a width ≈ 10 nm .", "The ...	[ "Why most of the in vivo experiments do not find the 30-nm chromatin fiber , well studied in vitro , is a puzzle .", "Two basic physical inputs that are crucial for understanding the structure of the 30-nm fiber are the stiffness of the linker DNA and the relative orientations of the DNA entering/exiting nucleoso...	[ "The fate of a cell is not just decided by the genetic code but also by the nature of the 3D organization of the protein-bound DNA , known as chromatin .", "Chromatin packaging is believed to be in a hierarchical manner , and one of the crucial stages in the packaging is argued to be having a zig-zag structure wi...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "protein interactions", "enzymes", "regulatory proteins", "enzymology", "microbiology", "emerging infectious diseases", "protein structure", "enzyme chemistry", "bacterial pathogens", "infectious diseases", "proteins", "medical microbiology", "enzyme regulat...	Identification of Ser/Thr kinase and Forkhead Associated Domains in Mycobacterium ulcerans: Characterization of Novel Association between Protein Kinase Q and MupFHA	journal.pntd.0003315	null	[ [ "Buruli ulcer is a disease of skin and soft tissues caused by the bacteria Mycobacterium ulcerans [1] .", "It is the third most important mycobacterial disease after tuberculosis and leprosy [2] , and the prevalence continues to increase in tropical and sub-tropical countries [3] .", "M . ulcerans evo...	[ "Mycobacterium ulcerans , the causative agent of Buruli ulcer in humans , is unique among the members of Mycobacterium genus due to the presence of the virulence determinant megaplasmid pMUM001 .", "This plasmid encodes multiple virulence-associated genes , including mup011 , which is an uncharacterized Ser/Thr p...	[ "Mycobacterium ulcerans is a slow growing pathogen , which is prevalent in many tropical and sub-tropical countries .", "M . ulcerans possesses unique signaling pathways with only 13 STPK containing genes .", "This is strikingly different from its closest homolog Mycobacterium marinum and surprisingly closer to...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Nucleoporin NUP153 Phenylalanine-Glycine Motifs Engage a Common Binding Pocket within the HIV-1 Capsid Protein to Mediate Lentiviral Infectivity	journal.ppat.1003693	null	[ [ "Retroviruses integrate their reverse transcribed genomes into host cell chromosomes to provide a permanent vantage from which to amplify themselves for subsequent transmission .", "As the nuclear envelope physically separates the host chromosomes from the cytoplasm during interphase , retroviruses have e...	[ "Lentiviruses can infect non-dividing cells , and various cellular transport proteins provide crucial functions for lentiviral nuclear entry and integration .", "We previously showed that the viral capsid ( CA ) protein mediated the dependency on cellular nucleoporin ( NUP ) 153 during HIV-1 infection , and now d...	[ "Lentiviruses such as HIV-1 possess mechanisms to bypass the nuclear envelope and reach the nuclear interior for viral DNA integration .", "Numerous nuclear transport proteins are important for HIV-1 infection , suggesting the viral nucleoprotein complex enters the nucleus by passing through nuclear pore complexe...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "microbial pathogens", "biology", "microbiology", "bacterial pathogens" ]	A Type IV Pilus Mediates DNA Binding during Natural Transformation in Streptococcus pneumoniae	journal.ppat.1003473	null	[ [ "Natural transformation , first discovered in Streptococcus pneumoniae [1] , is observed in many Gram-negative and Gram-positive bacteria [2] .", "It increases bacterial adaptability by promoting genome plasticity through intra- and inter-species genetic exchange [3] .", "In S . pneumoniae , a major h...	[ "Natural genetic transformation is widely distributed in bacteria and generally occurs during a genetically programmed differentiated state called competence .", "This process promotes genome plasticity and adaptability in Gram-negative and Gram-positive bacteria .", "Transformation requires the binding and int...	[ "Natural genetic transformation , first discovered in Streptococcus pneumoniae by Griffith in 1928 , is observed in many Gram-negative and Gram-positive bacteria .", "This process promotes genome plasticity and adaptability .", "In particular , it enables many human pathogens such as Streptococcus pneumoniae , ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "medicine", "clinical immunology", "autoimmune diseases", "diabetes mellitus type 1", "biology", "computational biology", "metabolic networks", "immunology" ]	Metabolic Regulation in Progression to Autoimmune Diabetes	journal.pcbi.1002257	null	[ [ "Type 1 diabetes ( T1D ) is an autoimmune disease that results from the selective destruction of insulin-producing β-cells in pancreatic islets .", "The diagnosis of T1D is commonly preceded by a long prodromal period which includes seroconversion to islet autoantibody positivity [1] and subtle metabolic ...	[ "Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes .", "The mechanisms behind these disturbances are unknown .", "Here we show the specificity of the...	[ "We have recently found that distinct metabolic disturbances precede β-cell autoimmunity in children who later progress to type 1 diabetes ( T1D ) .", "Here we performed a murine study using non-obese diabetic ( NOD ) mice that recapitulated the protocol used in human , followed up by independent studies where NO...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "schistosoma", "invertebrates", "schistosoma mansoni", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "helminths", "immunology", "light microscopy", "animals", "developmental biology", "microsco...	Schistosome egg antigens, including the glycoprotein IPSE/alpha-1, trigger the development of regulatory B cells	journal.ppat.1006539	null	[ [ "Helminths can persist for up to decades in the human host .", "This is hypothesized to be , at least in part , because of their evolutionarily adapted relationship with the host [1] .", "Helminths are well-known for their strong capacity to promote the regulatory arm of the hosts immune system , ther...	[ "Infection with the helminth Schistosoma ( S . ) mansoni drives the development of interleukin ( IL ) -10-producing regulatory B ( Breg ) cells in mice and man , which have the capacity to reduce experimental allergic airway inflammation and are thus of high therapeutic interest .", "However , both the involved a...	[ "Infection with helminth parasites is known to be inversely associated with hyper-inflammatory disorders .", "While Schistosoma ( S . ) mansoni has been described to exert its down-modulatory effects on inflammation by inducing a network of regulatory immune cells such as regulatory B ( Breg ) , the mechanisms of...	2017

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.