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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "theoretical biology", "biology", "computational biology", "evolutionary biology", "genetics and genomics" ]	The Underlying Molecular and Network Level Mechanisms in the Evolution of Robustness in Gene Regulatory Networks	journal.pcbi.1002865	null	[ [ "Robustness to genetic and environmental perturbations is ubiquitous in biological systems [1] .", "An abundance of theoretical and experimental evidence has shown robustness operating at many levels ranging from microRNA precursors [2] to metabolic pathways [3] and gene regulatory networks [4] .", "B...	[ "Gene regulatory networks show robustness to perturbations .", "Previous works identified robustness as an emergent property of gene network evolution but the underlying molecular mechanisms are poorly understood .", "We used a multi-tier modeling approach that integrates molecular sequence and structure inform...	[ "Development from egg to embryo depends to a large extent on regulatory networks of genes called transcription factors .", "Previous research has shown these gene regulatory networks to be robust to perturbations at the level of the connections between transcription factors .", "Here , we investigate the mechan...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "parasite groups", "chemical compounds", "plasmodium", "drugs", "tropical diseases", "microbiology", "parasitic diseases", "parasitic protozoans", "antimalarials", "parasitology", "fungi", "apicomplexa", "protozoans", "pharmacology", "antimicrobial resis...	Substrate-analogous inhibitors exert antimalarial action by targeting the Plasmodium lactate transporter PfFNT at nanomolar scale	journal.ppat.1006172	null	[ [ "All currently used antimalarial drugs have caused resistance in the parasite [1] .", "Hence , novel druggable targets are urgently needed to reload and diversify the therapeutic arsenal .", "Hitting the glycolytic energy generation pathway is a tempting approach as it is crucial for parasite survival...	[ "Resistance against all available antimalarial drugs calls for novel compounds that hit unexploited targets in the parasite .", "Here , we show that the recently discovered Plasmodium falciparum lactate/proton symporter , PfFNT , is a valid druggable target , and describe a new class of fluoroalkyl vinylogous aci...	[ "The fight against malaria , i . e . one of the three major infectious diseases and transmitted by mosquitos , is conducted at three levels: i .", "transmission control ( by attacking the mosquito vector or biological processes of vector infection ) , ii .", "vaccination ( by stimulating the immune system to pr...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "reproductive system", "spermatocytes", "hormones", "germ cells", "animal models", "model organisms", "experimental organism systems", "dna", "epigenetics", "estrogens", "estradiol", "sperm", "homologous recombination", "research and analysis methods", "...	Germline and reproductive tract effects intensify in male mice with successive generations of estrogenic exposure	journal.pgen.1006885	null	[ [ "Data from human populations around the world provide evidence of a marked decline in male fertility during the past several decades .", "For example , a comprehensive analysis in 2000 of data from more than 100 studies in Western countries provided evidence of a decline in human spermatogenesis during th...	[ "The hypothesis that developmental estrogenic exposure induces a constellation of male reproductive tract abnormalities is supported by experimental and human evidence .", "Experimental data also suggest that some induced effects persist in descendants of exposed males .", "These multi- and transgenerational ef...	[ "Developmental exposure to manmade chemicals that interfere with endogenous hormones ( endocrine disrupting chemicals ) has been reported to adversely affect male reproductive health , increasing the incidence of reproductive tract abnormalities and reducing sperm production .", "Experimental evidence suggests th...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular structures", "subcellular organelles", "cellular stress responses", "streptococci", "enzymes", "regulatory proteins", "microbiology", "host-pathogen interaction", "animal models", "caenorhabditis elegans", "model organisms", "ligases", "bacterial pathogens", "enzyme classes", "...	Regulation of ATG4B Stability by RNF5 Limits Basal Levels of Autophagy and Influences Susceptibility to Bacterial Infection	journal.pgen.1003007	null	[ [ "Autophagy is an intracellular catabolic process by which cellular components are degraded through the lysosomal machinery .", "Conserved from yeast to humans , autophagy is fundamental to eukaryotic cell homeostasis [1] , [2] .", "Autophagy functions in diverse cellular processes such as growth and d...	[ "Autophagy is the mechanism by which cytoplasmic components and organelles are degraded by the lysosomal machinery in response to diverse stimuli including nutrient deprivation , intracellular pathogens , and multiple forms of cellular stress .", "Here , we show that the membrane-associated E3 ligase RNF5 regulat...	[ "Autophagy is an intracellular catabolic process by which a cell's own components are degraded through the lysosomal machinery .", "Autophagy is implicated in various cellular processes such as growth and development , cancer , and inflammation .", "Using biochemistry , cell biology , and genetic models , we id...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "medicine and health sciences", "ecuador", "forest ecology", "geographical locations", "tropical diseases", "parasitic diseases", "parasitic protozoans", "protozoans", "neglected tropical diseases", "infectious disease control", "agrochemicals", "infecti...	Distribution of triatomine species in domestic and peridomestic environments in central coastal Ecuador	journal.pntd.0005970	null	[ [ "Chagas disease has been recognized as one of the world’s 13 most neglected tropical diseases and continues to be an important social and economic problem in many Latin American countries[1] .", "About 8–9 million people are estimated to be infected with Trypanosoma cruzi in Latin America , including 2–5 ...	[ "Although the central coast of the Ecuador is considered endemic for Chagas disease , few studies have focused on determining the risk of transmission in this region .", "In this study we describe the triatomine household infestation in Manabí province ( Central Coast region ) , determine the rate of Trypanosoma ...	[ "Chagas disease is an important public health problem in most of Latin America , including Ecuador .", "It is caused by the parasite Trypanosoma cruzi , which in endemic areas is transmitted mainly by the feces of insects called triatomines .", "Control efforts in the region have reduced the number of new cases...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "gene regulation", "regulatory proteins", "condensed matter physics", "dna-binding proteins", "anisotropy", "dna transcription", "dna damage", "chemical equilibrium", "materials science", "transcription factors", "dna", "chemical dissociation", "thermodynamics", "physical chemistry", "tr...	Non-equilibrium repressor binding kinetics link DNA damage dose to transcriptional timing within the SOS gene network	journal.pgen.1007405	null	[ [ "Transcription regulation networks enable a cell to exert exquisite control over its biochemical pathways and are prevalent across the tree of life [1] .", "The gene promoters in simple network motifs share a single common transcription factor , thus enabling expression of an entire set of pathway genes i...	[ "Biochemical pathways are often genetically encoded as simple transcription regulation networks , where one transcription factor regulates the expression of multiple genes in a pathway .", "The relative timing of each promoter’s activation and shut-off within the network can impact physiology .", "In the DNA da...	[ "As the precise timing of gene expression is critical for cells to respond and adapt to new environments , it is important to understand the underlying mechanisms which control this timing .", "In this report , we studied the timing of transcription for genes in the bacterial DNA damage repair pathway ( known as ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "dengue virus", "innate immune system", "medicine and health sciences", "body fluids", "immune cells", "immune physiology", "cytokines", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "pediatrics", "viruses", "developmental biology", "sig...	Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India—Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity	journal.pntd.0004497	null	[ [ "Dengue virus ( DENV ) infects close to 390 million people every year of which about 96 million have clinical manifestations that range from undifferentiated febrile illness to fatal shock syndrome [1] .", "There are four serotypes of DENV ( DENV 1–4 ) and an initial infection with a single serotype ( pri...	[ "Dengue virus , a mosquito-borne flavivirus , is a causative agent for dengue infection , which manifests with symptoms ranging from mild fever to fatal dengue shock syndrome .", "The presence of four serotypes , against which immune cross-protection is short-lived and serotype cross-reactive antibodies that migh...	[ "Dengue virus is a human pathogen that causes dengue fever , which can either resolve after mild fever or lead to severe dengue hemorrhagic fever/dengue shock syndrome .", "The role of dengue virus levels in the blood and the kinetics of infection and immune response that results in severe dengue disease in human...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physics", "theoretical biology", "biology", "computational biology", "biophysics" ]	Binding Leverage as a Molecular Basis for Allosteric Regulation	journal.pcbi.1002148	null	[ [ "Protein function depends on the balance between different conformational states .", "This balance can be shifted by many external factors that regulate protein activity , including localized perturbations such as ligand binding or phosphorylation .", "When the perturbation site is not directly adjace...	[ "Allosteric regulation involves conformational transitions or fluctuations between a few closely related states , caused by the binding of effector molecules .", "We introduce a quantity called binding leverage that measures the ability of a binding site to couple to the intrinsic motions of a protein .", "We u...	[ "Allosteric protein regulation is the mechanism by which binding of a molecule to one site in a protein affects the activity at another site .", "Although the two classical phenomenological models , Monod-Wyman-Changeux ( MWC ) and Koshland-Némethy-Filmer ( KNF ) , span from the case of hemoglobin to membrane rec...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "enzymes", "enzymology", "alleles", "sequence motif analysis", "epigenetics", "dna", "molecular biology techniques", "dna methylation", "chromatin", "research and analysis methods", "sequence analysis", "artificial gene amplification and extension", "chromosome bio...	Epigenetic Switch Driven by DNA Inversions Dictates Phase Variation in Streptococcus pneumoniae	journal.ppat.1005762	null	[ [ "DNA methylation has been demonstrated as an epigenetic means of regulating many important biological processes in both prokaryotic and eukaryotic organisms .", "Cytosine methylation in the CpG dinucleotide context is essential for shaping embryonic cells into different cell types of the mammals; mutation...	[ "DNA methylation is an important epigenetic mechanism for phenotypic diversification in all forms of life .", "We previously described remarkable cell-to-cell heterogeneity in epigenetic pattern within a clonal population of Streptococcus pneumoniae , a leading human pathogen .", "We here report that the epigen...	[ "DNA methylation is a well-known epigenetic mechanism for phenotypic diversification in all forms of life .", "This study reports our discovery that the Spn556II type-I RM locus in human pathogen Streptococcus pneumoniae undergoes extensive DNA inversions among three homologous DNA methyltransferase genes .", "...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "medicine and health sciences", "pathology and laboratory medicine", "drugs", "immunology", "alternative splicing", "signs and symptoms", "analgesics", "molecular biology techniques", "pharmacology", "calcium signaling", "research and analysis methods", "specimen preparation ...	Profound analgesia is associated with a truncated peptide resulting from tissue specific alternative splicing of DRG CA8-204 regulated by an exon-level cis-eQTL	journal.pgen.1008226	null	[ [ "Car8 and its human ortholog ( CA8 ) are enzymatically inactive isoforms of carbonic anhydrase that inhibit activation of neuronal inositol 1 , 4 , 5-trisphosphate receptor type-1 ( ITPR1 ) by phosphorylation ( pITPR1 ) , and intracellular calcium release in mice .", "ITPR1 converts inositol trisphosphate...	[ "Carbonic anhydrase-8 ( CA8 ) is an intracellular protein that functions as an allosteric inhibitor of inositol trisphosphate receptor-1 ( ITPR1 ) critical to intracellular Ca++ release , synaptic functions and neuronal excitability .", "We showed previously that murine nociception and analgesic responses are reg...	[ "Carbonic anhydrase-8 ( CA8 ) inhibits IP3 binding to the inositol trisphosphate receptor-1 ( ITPR1 ) , which regulates intracellular calcium signaling critical to neuronal functions .", "Recessive CA8-null mutants are associated with spinocerebellar ataxia and neurodegenerative disorders .", "We have previousl...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "caffeine", "medicine and health sciences", "genetic networks", "alkaloids", "chemical compounds", "protein interaction networks", "network analysis", "genome analysis", "pharmacology", "genetic interactions", "research and analysis methods", "computer and information sciences", "genomics", ...	Network-assisted target identification for haploinsufficiency and homozygous profiling screens	journal.pcbi.1005553	null	[ [ "Chemical genomic screens have been extensively used to discover functional interactions between genes and small molecular compounds in vivo [1–8] .", "Due to its short generation time , inexpensive cultivation , and facile genetics , the budding yeast S . cerevisiae has been widely used as a platform for...	[ "Chemical genomic screens have recently emerged as a systematic approach to drug discovery on a genome-wide scale .", "Drug target identification and elucidation of the mechanism of action ( MoA ) of hits from these noisy high-throughput screens remain difficult .", "Here , we present GIT ( Genetic Interaction ...	[ "Chemical genomic screens have been developed to systematically explore compound-gene interactions with the goal of identifying new drugs and drug targets .", "Haploinsufficiency profiling and homozygous profiling screens measure the drug-induced growth sensitivities of deletion strains that are grown in the pres...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunopathology", "animal models of infection", "infectious disease immunology", "mycology", "clinical immunology", "medical microbiology", "microbial pathogens", "paracoccidioides brasiliensis", "biology and life sciences", "immunology", "pulmonary immunology", "immune suppression", "micro...	Indoleamine 2,3-Dioxygenase Controls Fungal Loads and Immunity in Paracoccidioidomicosis but is More Important to Susceptible than Resistant Hosts	journal.pntd.0003330	null	[ [ "Indoleamine-2 , 3-dioxygenase ( IDO ) is the major and rate limiting cytosolic enzyme of tryptophan catabolism along the kynurenines pathway [1] and is expressed primarily in macrophages , epithelial and dendritic cells ( DCs ) .", "The enzyme is induced by proinflammatory cytokines ( e . g . , IFN-γ ) ,...	[ "Paracoccidioidomycosis , a primary fungal infection restricted to Latin America , is acquired by inhalation of fungal particles .", "The immunoregulatory mechanisms that control the severe and mild forms of paracoccidioidomycosis are still unclear .", "Indoleamine 2 , 3-dioxygenase ( IDO ) , an IFN-γ induced e...	[ "Immunoprotection to paracoccidiodomycosis , a systemic mycosis endemic in Latin America , is mediated by T cell immunity whereas immunosuppression characterizes the severe forms of the disease .", "Indoleamine 2 , 3-dioxygenase ( IDO ) , an enzyme mainly induced by IFN-γ , catabolizes tryptophan along the kynure...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "endothelial cells", "enzymes", "ocular anatomy", "enzymology", "epithelial cells", "bone marrow cells", "developmental biology", "integrins", "signs and symptoms", "embryos", "cellular structures and o...	Rasa3 controls turnover of endothelial cell adhesion and vascular lumen integrity by a Rap1-dependent mechanism	journal.pgen.1007195	null	[ [ "Blood vessels consist of a layer of interconnected endothelial cells ( ECs ) delineating a luminal space through which blood flows .", "Our current knowledge of how lumens are established and maintained is still modest and has come essentially from in vitro systems .", "Only recently , studies have i...	[ "Rasa3 is a GTPase activating protein of the GAP1 family which targets R-Ras and Rap1 .", "Although catalytic inactivation or deletion of Rasa3 in mice leads to severe hemorrhages and embryonic lethality , the biological function and cellular location of Rasa3 underlying these defects remains unknown .", "Here ...	[ "Because it delivers oxygen and nutriments to every tissue in the body , the vascular system is essential to vertebrate life .", "Blood vessels consist of a layer of interconnected endothelial cells delineating a luminal space through which blood flows .", "Formation of vascular lumens is a critical step in vas...	2018
[ "Introduction", "Results", "Discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "parasite groups", "body fluids", "plasmodium", "demography", "tropical diseases", "parasitic diseases", "animals", "parasitic protozoans", "parasitology", "hormones", "apicomplexa", "protozoans", "population biology", "...	Disrupting Mosquito Reproduction and Parasite Development for Malaria Control	journal.ppat.1006060	null	[ [ "Despite recent progress in combating the malaria parasite , nearly 200 million infections and around 500 , 000 deaths are caused by malaria annually , mostly in young children in sub-Saharan Africa [1 , 2] .", "Even with new drugs and vaccines in the research pipeline [3] , control of the Anopheles speci...	[ "The control of mosquito populations with insecticide treated bed nets and indoor residual sprays remains the cornerstone of malaria reduction and elimination programs .", "In light of widespread insecticide resistance in mosquitoes , however , alternative strategies for reducing transmission by the mosquito vect...	[ "Mosquito control is the only intervention that can reduce malaria transmission from very high levels to close to zero .", "However , current mosquito control methods are severely threatened by the rapid spread of insecticide resistance in anopheline mosquito populations that transmit the malaria-causing Plasmodi...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "messenger rna", "dna transcription", "phylogenetics", "data management", "model organisms", "fungi", "phylogenetic analysis", "experimental organism systems", "sequence motif analysis", "research and analysis methods", "saccharomyces", "sequence analysis", "computer and inform...	Transcription apparatus of the yeast virus-like elements: Architecture, function, and evolutionary origin	journal.ppat.1007377	null	[ [ "Linear double-stranded DNA virus-like elements ( VLEs ) were found in the cytoplasm of several yeast species .", "Structural organization of these elements is quite uniform and they are often present as two or three differently sized DNA plasmids in yeast host cells [1] .", "Characteristic features o...	[ "Extrachromosomal hereditary elements such as organelles , viruses , and plasmids are important for the cell fitness and survival .", "Their transcription is dependent on host cellular RNA polymerase ( RNAP ) or intrinsic RNAP encoded by these elements .", "The yeast Kluyveromyces lactis contains linear cytopla...	[ "Yeast cytoplasmic double-stranded DNA virus-like elements ( VLEs , also known as linear plasmids ) were widely investigated in the past but the topic was almost entirely abandoned , partly due to an inability to express VLE-encoded proteins using conventional expression systems .", "In this study , we re-opened ...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "chemical compounds", "insertion mutation", "carbohydrates", "galactose", "organic compounds", "microhomology-mediated end joining", "surgical and invasive medical procedures", "mutation", "dna", "translocations", "chromosome biology", "chromosomal aberrations...	Microhomology-mediated end joining induces hypermutagenesis at breakpoint junctions	journal.pgen.1006714	null	[ [ "The presence of short stretches of overlapping sequence ( microhomology , MH ) is a frequent feature of pathogenic chromosomal translocation breakpoints in human cells and has been implicated in juxtaposing two DNA ends for the error-prone repair of DNA breaks in both yeast and vertebrates [1–3] .", "Thi...	[ "Microhomology ( MH ) flanking a DNA double-strand break ( DSB ) drives chromosomal rearrangements but its role in mutagenesis has not yet been analyzed .", "Here we determined the mutation frequency of a URA3 reporter gene placed at multiple locations distal to a DSB , which is flanked by different sizes ( 15- ,...	[ "Recurrent chromosome translocations juxtapose chromosomal fragments and alter expression of tumor suppressors or oncogenes at or near breakpoint junctions to develop distinct types of leukemias and childhood sarcomas .", "The prevalence of 2–20 bp of imperfect overlapping sequences ( a . k . a . microhomology [M...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Reversible Histone H3 Acetylation Cooperates with Mismatch Repair and Replicative Polymerases in Maintaining Genome Stability	journal.pgen.1003899	null	[ [ "Mutations are the prerequisites for evolution and the humoral immune response .", "However , mutations are often detrimental due to their ability to trigger both inherited and sporadic diseases .", "Base substitutions , 1-bp deletions , and 1-bp insertions are the most common mutations [1] , [2] .", ...	[ "Mutations are a major driving force of evolution and genetic disease .", "In eukaryotes , mutations are produced in the chromatin environment , but the impact of chromatin on mutagenesis is poorly understood .", "Previous studies have determined that in yeast Saccharomyces cerevisiae , Rtt109-dependent acetyla...	[ "Mutations strongly predispose humans to cancer and many other diseases .", "Despite significant progress , we still do not fully understand the molecular mechanisms that protect us from mutations .", "Human DNA is part of a highly organized complex called chromatin .", "Chromatin regulates our development , ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mycology", "biology", "microbiology", "evolutionary biology" ]	Discovery of a Modified Tetrapolar Sexual Cycle in Cryptococcus amylolentus and the Evolution of MAT in the Cryptococcus Species Complex	journal.pgen.1002528	null	[ [ "Sexual reproduction is ubiquitous throughout nature , generates population diversity , and has been described extensively in plants , animals , and microorganisms [1] .", "Sex is both costly and advantageous , and the ubiquity of sexual reproduction suggests that in general its benefits outweigh its cost...	[ "Sexual reproduction in fungi is governed by a specialized genomic region called the mating-type locus ( MAT ) .", "The human fungal pathogenic and basidiomycetous yeast Cryptococcus neoformans has evolved a bipolar mating system ( a , α ) in which the MAT locus is unusually large ( >100 kb ) and encodes >20 gene...	[ "Fungal gene clusters mediate sex determination , natural product synthesis , and metabolic functions .", "Eukaryotic organisms share features of gene cluster formation including translocations , inversions , gene conversion , and suppressed recombination .", "The C . neoformans/C .", "gattii mating-type ( MA...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "oncology", "biochemistry/experimental biophysical methods", "biochemistry/biomacromolecule-ligand interactions", "biochemistry/macromolecular assemblies and machines", "biochemistry/theory and simulation", "computational biology/molecular dynamics", "biochemistry/drug discovery" ]	Computational Analysis of Phosphopeptide Binding to the Polo-Box Domain of the Mitotic Kinase PLK1 Using Molecular Dynamics Simulation	journal.pcbi.1000880	null	[ [ "Mitotic cell division involves a tightly orchestrated series of events that precisely segregate an equal complement of chromosomes to two daughter cells .", "Abnormalities in mitosis generate aneuploid cells containing an unequal distribution of chromosomes , which may represent a starting point for the ...	[ "The Polo-Like Kinase 1 ( PLK1 ) acts as a central regulator of mitosis and is over-expressed in a wide range of human tumours where high levels of expression correlate with a poor prognosis .", "PLK1 comprises two structural elements , a kinase domain and a polo-box domain ( PBD ) .", "The PBD binds phosphoryl...	[ "Cell division is a key biological process and imperfections in the process can lead to diseases like cancer .", "Polo-Like Kinase 1 ( PLK1 ) is a protein kinase enzyme that controls cell division by interacting with many other proteins .", "Malfunction of PLK1 has been implicated in cancer .", "To understand...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/motor systems", "neuroscience/psychology", "computer science/systems and control theory", "neuroscience/theoretical neuroscience" ]	Risk-Sensitive Optimal Feedback Control Accounts for Sensorimotor Behavior under Uncertainty	journal.pcbi.1000857	null	[ [ "Risk-attitudes are an important determinant of human decision-making that expresses itself , for example , with individuals who are risk-seeking investing in highly volatile stocks and those who are risk-averse choosing governments bonds .", "Economic theory suggests that when making a decision that can ...	[ "Many aspects of human motor behavior can be understood using optimality principles such as optimal feedback control .", "However , these proposed optimal control models are risk-neutral; that is , they are indifferent to the variability of the movement cost .", "Here , we propose the use of a risk-sensitive op...	[ "In economic decision-making it is well-known that when decision-makers have several options , each associated with uncertain outcomes , their decision is not purely determined by the average payoff , but also takes into account the risk ( that is , variability of the payoff ) associated with each option .", "Som...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "statistical noise", "crystal structure", "pathology and laboratory medicine", "pathogens", "protein interaction networks", "split-decomposition method", "condensed matter physics", "microbiology", "viral structure", "retroviruses", "viruses", "immunodeficienc...	Co-evolution networks of HIV/HCV are modular with direct association to structure and function	journal.pcbi.1006409	null	[ [ "HIV and HCV are the cause of devastating infectious diseases that continue to wreak havoc worldwide .", "Both viruses are highly variable , possessing an extraordinary ability to tolerate mutations while remaining functionally fit .", "While individual residue mutations may be deleterious , these are...	[ "Mutational correlation patterns found in population-level sequence data for the Human Immunodeficiency Virus ( HIV ) and the Hepatitis C Virus ( HCV ) have been demonstrated to be informative of viral fitness .", "Such patterns can be seen as footprints of the intrinsic functional constraints placed on viral evo...	[ "HIV and HCV cause devastating infectious diseases for which no functional vaccine exists .", "A key problem is that while individual mutations in viral epitopes under immune pressure may substantially compromise viral fitness , immune escape is typically facilitated by other “compensatory” mutations that restore...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "helminths", "immunology", "geographical locations", "hookworms", "animals", "liver diseases", "vaccines", "preventive medicine", "infectious hepatitis", "hepatitis", "gastroenterology and...	Safety and immunogenicity of the Na-GST-1 hookworm vaccine in Brazilian and American adults	journal.pntd.0005574	null	[ [ "Over 400 million people are infected with hookworm , predominantly in resource-limited tropical regions of the world [1] .", "Hookworm is a soil-transmitted nematode helminth that is primarily acquired after skin contact with infective larvae found in soil contaminated with human feces .", "Following...	[ "ClinicalTrials . gov ( NCT01261130 for the Brazil trial and NCT01385189 for the US trial )" ]	[ "Hookworm infection caused by Necator americanus is a major neglected tropical disease with significant associated morbidity .", "New tools , such as vaccines , are needed due to the inadequacy of current control strategies .", "Glutathione-S-Transferase-1 of N . americanus ( Na-GST-1 ) is one of the lead hookw...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	HrpA, an RNA Helicase Involved in RNA Processing, Is Required for Mouse Infectivity and Tick Transmission of the Lyme Disease Spirochete	journal.ppat.1003841	null	[ [ "Lyme borreliosis is the most prevalent vector-transmitted disease in the northern hemisphere and has a significant impact on human health ( see [1] , [2] ) .", "The disease is caused by the spirochete Borrelia burgdorferi and related species .", "B . burgdorferi is maintained in nature by a complex e...	[ "The Lyme disease spirochete Borrelia burgdorferi must differentially express genes and proteins in order to survive in and transit between its tick vector and vertebrate reservoir .", "The putative DEAH-box RNA helicase , HrpA , has been recently identified as an addition to the spirochete's global regulatory ma...	[ "The bacterium causing Lyme disease , Borrelia burgdorferi , must differentially express genes and proteins in order to survive in and transit between its tick vector and animals that it infects .", "RNA helicases , enzymes that unwind double-stranded RNA , have recently emerged as major players in all types of p...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neurological disorders/neuromuscular diseases", "infectious diseases/infectious diseases of the nervous system", "infectious diseases/neglected tropical diseases", "neurological disorders/peripheral neuropathies", "public health and epidemiology/infectious diseases", "public health and epidemiology/scree...	Early Diagnosis of Neuropathy in Leprosy—Comparing Diagnostic Tests in a Large Prospective Study (the INFIR Cohort Study)	journal.pntd.0000212	null	[ [ "‘Early detection improves prognosis’ is a general axiom in medicine , and in leprosy delay in detection is strongly associated with an increased risk of neural impairment at diagnosis [1]–[4] .", "In addition , nerve function impairment ( NFI ) already present at diagnosis has been found to be a strong p...	[ "Leprosy is the most frequent treatable neuromuscular disease .", "Yet , every year , thousands of patients develop permanent peripheral nerve damage as a result of leprosy .", "Since early detection and treatment of neuropathy in leprosy has strong preventive potential , we conducted a cohort study to determin...	[ "Leprosy is the most frequent treatable disease of the peripheral nerves .", "Yet , every year , thousands of patients develop nerve damage as a result of leprosy .", "If this is detected and treated early , the prognosis is good .", "We conducted the largest prospective study on this topic to date to determi...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection	journal.ppat.1004954	null	[ [ "HIV-infected children typically progress more rapidly to AIDS than adults [1] .", "Without treatment , approximately 50% of HIV-1 infected children develop AIDS within a year and 50% will die before their second birthday in sub-Saharan Africa [1] .", "However , a minority of perinatally infected chil...	[ "HLA class I polymorphism has a major influence on adult HIV disease progression .", "An important mechanism mediating this effect is the impact on viral replicative capacity ( VRC ) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses .", "Factors that contribute to slow progres...	[ "HLA plays a central role in determining disease outcome in adult HIV infection .", "A principal mechanism by which this HLA effect is mediated is via viral replicative capacity ( VRC ) , protective HLA alleles such as HLA-B*57 driving the selection of viral escape mutants that reduce VRC .", "The factors contr...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Transcription of the Major Neurospora crassa microRNA–Like Small RNAs Relies on RNA Polymerase III	journal.pgen.1003227	null	[ [ "MicroRNAs ( miRNAs ) are small non-coding RNAs that regulate protein expression levels post-transcriptionally in a wide variety of cellular processes .", "miRNAs arise from discrete genomic loci and are processed by Dicer-like enzymes from stem-loop RNA precursors [1] , [2] .", "Since their initial d...	[ "Most plant and animal microRNAs ( miRNAs ) are transcribed by RNA polymerase II .", "We previously discovered miRNA–like small RNAs ( milRNAs ) in the filamentous fungus Neurospora crassa and uncovered at least four different pathways for milRNA production .", "To understand the evolutionary origin of milRNAs ...	[ "microRNAs ( miRNAs ) are small RNAs that are used by many organisms to regulate a wide variety of molecular , developmental , and physiological activities .", "In higher eukaryotes , such as animals and plants , the majority of the independent transcribed miRNAs are produced by RNA polymerase II ( Pol II ) , an ...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "gene regulation", "immunology", "fibroblasts", "dna transcription", "developmental biology", "clinical medicine", "connective tissue cells", "molecular development", "sequence motif analysis", "mamma...	Zbtb7a is a transducer for the control of promoter accessibility by NF-kappa B and multiple other transcription factors	journal.pbio.2004526	null	[ [ "The expression of protein-coding genes is governed by the combined activities of activating and repressing transcription factors ( TFs ) , which bind in a specific fashion to regulatory sequences in proximal promoter regions and at distal enhancers .", "The abilities of TFs to bind to their genomic targe...	[ "Gene expression in eukaryotes is controlled by DNA sequences at promoter and enhancer regions , whose accessibility for binding by regulatory proteins dictates their specific patterns of activity .", "Here , we identify the protein Zbtb7a as a factor required for inducible changes in accessibility driven by tran...	[ "Gene activation is driven by the binding of regulatory proteins to the specific DNA sequences that control each gene .", "However , these sequences are not always accessible for binding in every type of cell , and so differences in their accessibility can underlie the range of cell types in which particular gene...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "signal transduction", "signaling in cellular processes", "molecular cell biology", "heredity", "genetics", "biology", "molecular biology", "genetics and genomics" ]	The Nucleoside Diphosphate Kinase Gene Nme3 Acts as Quantitative Trait Locus Promoting Non-Mendelian Inheritance	journal.pgen.1002567	null	[ [ "In general , diploid organisms transmit homologous chromosomes at the Mendelian ( equal ) ratio to their offspring .", "However , several types of non-Mendelian inheritance have been described , and in mammals a prominent example is transmission ratio distortion ( TRD ) in the mouse , which is caused by ...	[ "The t-haplotype , a variant form of the t-complex region on mouse chromosome 17 , acts as selfish genetic element and is transmitted at high frequencies ( >95% ) from heterozygous ( t/+ ) males to their offspring .", "This phenotype is termed transmission ratio distortion ( TRD ) and is caused by the interaction...	[ "Selfish genetic elements , which promote their own propagation and thereby violate Mendel's laws , have attracted much attention within the scientific community and by the public .", "The molecular principles underlying their exceptional behaviour are , in general , not well understood .", "A notable exception...	2012
[ "Introduction", "Results/Discussion", "Methods" ]	[ "computational biology/synthetic biology", "biotechnology/bioengineering", "biochemistry/theory and simulation", "biochemistry/transcription and translation", "chemical biology/directed molecular evolution" ]	Design Principles for Ligand-Sensing, Conformation-Switching Ribozymes	journal.pcbi.1000620	null	[ [ "Nucleic acid binding species ( aptamers ) have emerged as a powerful tool for molecular recognition , and have begun to be widely adapted as biosensors , in drug-delivery systems , and as regulatory elements that control gene expression [1]–[4] .", "Naturally occurring nucleic acid regulatory elements , ...	[ "Nucleic acid sensor elements are proving increasingly useful in biotechnology and biomedical applications .", "A number of ligand-sensing , conformational-switching ribozymes ( also known as allosteric ribozymes or aptazymes ) have been generated by some combination of directed evolution or rational design .", ...	[ "Aptamers are nucleic acids that bind their cognate ligands ( ranging from metal ions to small molecules to proteins ) specifically and tightly .", "Through rational design and/or directed evolution , aptamers can be engineered into allosteric nucleic acids whose conformations can be regulated by their ligands ."...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis	journal.pbio.1002309	How does the antidiabetic drug metformin inhibit cancer? This metabolomic study shows that metformin blocks tumor cell proliferation independently of the classic metabolic checkpoints by suppressing mitochondrial-dependent biosynthesis.	[ [ "Metformin is a member of the biguanide class of drugs used for the treatment of type II diabetes .", "Metformin directly inhibits complex I of the mitochondrial electron transport chain ( ETC ) [1 , 2] , resulting in decreased complex I activity and oxidative phosphorylation ( OXPHOS ) in cells [3 , 4] ....	[ "Metformin is a biguanide widely prescribed to treat Type II diabetes that has gained interest as an antineoplastic agent .", "Recent work suggests that metformin directly antagonizes cancer cell growth through its actions on complex I of the mitochondrial electron transport chain ( ETC ) .", "However , the mec...	[ "Cancer is a disease characterized by unregulated proliferation of transformed cells .", "To meet the increased biosynthetic demands of proliferation , biosynthetic building blocks required for cellular growth must be generated in large quantities .", "As cancer cells increase their anabolic metabolism to promo...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Structural Basis for Feed-Forward Transcriptional Regulation of Membrane Lipid Homeostasis in Staphylococcus aureus	journal.ppat.1003108	null	[ [ "The cell membrane is an essential structure to bacteria .", "It primarily consists of a fluid phospholipid bilayer in which a variety of proteins are embedded .", "Most steps involved in phospholipid biosynthesis are therefore explored as targets for designing new antibacterial drugs [1] .", "The...	[ "The biosynthesis of membrane lipids is an essential pathway for virtually all bacteria .", "Despite its potential importance for the development of novel antibiotics , little is known about the underlying signaling mechanisms that allow bacteria to control their membrane lipid composition within narrow limits ."...	[ "An opportunistic Gram-positive pathogen , Staphylococcus aureus is a major threat to humans and animals , being responsible for a variety of infections ranging from mild superficial to severe infections such as infective endocarditis , septic arthritis , osteomyelitis and sepsis .", "The increasing resistance of...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cellular structures", "subcellular organelles", "protein interactions", "genetics", "molecular genetics", "biology", "proteomics", "molecular cell biology", "genetics of disease", "gene function" ]	The Centriolar Satellite Protein AZI1 Interacts with BBS4 and Regulates Ciliary Trafficking of the BBSome	journal.pgen.1004083	null	[ [ "Primary cilia are organized from centrioles that move to the cell periphery and form basal bodies .", "From the centrioles , microtubules extend and protrude from the cell surface to produce a cilium .", "Primary cilia house several signaling pathway receptors such as Hedgehog , Wnt and PDGFR , and a...	[ "Bardet-Biedl syndrome ( BBS ) is a well-known ciliopathy with mutations reported in 18 different genes .", "Most of the protein products of the BBS genes localize at or near the primary cilium and the centrosome .", "Near the centrosome , BBS proteins interact with centriolar satellite proteins , and the BBSom...	[ "Bardet-Biedl syndrome ( BBS ) is a genetically heterogeneous autosomal recessive ciliopathy with 18 causative genes reported to date .", "The syndrome is characterized by obesity , polydactyly , renal defects , hypogenitalism and retinal degeneration .", "Previous work has illustrated a role for BBS proteins i...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "public health and epidemiology/global health", "public health and epidemiology/infectious diseases", "public health and epidemiology/environmental health" ]	Quantitative Detection of Schistosoma japonicum Cercariae in Water by Real-Time PCR	journal.pntd.0000337	null	[ [ "Recent evidence of schistosomiasis re-emergence has been reported in the hilly and mountainous regions of Sichuan Province , reinforcing the need for active disease surveillance in these areas [1] .", "Meanwhile , endemic areas with active transmission persist in China , with the most recent data indicat...	[ "In China alone , an estimated 30 million people are at risk of schistosomiasis , caused by the Schistosoma japonicum parasite .", "Disease has re-emerged in several regions that had previously attained transmission control , reinforcing the need for active surveillance .", "The environmental stage of the paras...	[ "Schistosomiasis ranks second only to malaria among parasitic diseases with regard to the number of people infected and those at risk .", "Schistosoma japonicum is the species that causes human and animal disease in China , the Philippines , and to a lesser extent , Indonesia .", "Recent evidence of schistosomi...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "yeast and fungi", "computational biology", "genetics and genomics", "saccharomyces" ]	Superfamily Assignments for the Yeast Proteome through Integration of Structure Prediction with the Gene Ontology	journal.pbio.0050076	Protein three-dimensional structures were predicted for allSaccharomyces cerevisiae domains that were found to have no sequence similarity to any proteins of known structure.	[ [ "The yeast Saccharomyces cerevisiae is one of the most widely studied organisms , yet a large fraction of its proteins are of unknown structure and/or unknown function .", "Knowledge of the structure of a protein is critical to understand how it functions , and hence , a complete set of protein structures...	[ "Saccharomyces cerevisiae is one of the best-studied model organisms , yet the three-dimensional structure and molecular function of many yeast proteins remain unknown .", "Yeast proteins were parsed into 14 , 934 domains , and those lacking sequence similarity to proteins of known structure were folded using the...	[ "The three-dimensional structure of a protein can reveal much about that protein's evolutionary relationships and functions .", "Such information about all the proteins in an organism—the proteome—would offer a more global view of these relationships , but solving each structure individually would be a formidable...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "chemical characterization", "pathology and laboratory medicine", "gene regulation", "pathogens", "dna-binding proteins", "microbiology", "fungi", "regulator genes", "experimental organism systems", "gene types", "sequence motif analysis", "fungal pathogens", ...	Diversification of DNA binding specificities enabled SREBP transcription regulators to expand the repertoire of cellular functions that they govern in fungi	journal.pgen.1007884	null	[ [ "Evolutionary changes in gene expression patterns constitute a major source of phenotypic diversity [1–4] .", "The primary step through which all cells regulate expression of their genes is the binding of transcription regulators to cis-regulatory sequences .", "Not surprisingly , gains and losses of ...	[ "The Sterol Regulatory Element Binding Proteins ( SREBPs ) are basic-helix-loop-helix transcription regulators that control the expression of sterol biosynthesis genes in higher eukaryotes and some fungi .", "Surprisingly , SREBPs do not regulate sterol biosynthesis in the ascomycete yeasts ( Saccharomycotina ) a...	[ "Transcription regulation is the primary step by which most cells control the expression of their genes .", "At its core , this process is mediated by proteins ( transcription regulators ) that bind to short DNA regulatory elements in a sequence-specific manner .", "Recent research in multiple model organisms r...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/vaccines", "virology/animal models of infection", "virology" ]	Protection of Mice against Lethal Challenge with 2009 H1N1 Influenza A Virus by 1918-Like and Classical Swine H1N1 Based Vaccines	journal.ppat.1000745	null	[ [ "Influenza A viruses ( IAV ) , members of the Orthomyxoviridae family , cause severe respiratory diseases in humans with an average mortality rate of 36 , 000/year in the United States alone [1] .", "Apart from yearly seasonal outbreaks , IAV can cause frequent epidemics and occasional pandemics in humans...	[ "The recent 2009 pandemic H1N1 virus infection in humans has resulted in nearly 5 , 000 deaths worldwide .", "Early epidemiological findings indicated a low level of infection in the older population ( >65 years ) with the pandemic virus , and a greater susceptibility in people younger than 35 years of age , a ph...	[ "Influenza A viruses generally infect individuals of all ages and cause severe respiratory disease in very young children and elderly people ( >65 years ) .", "However , the 2009 pandemic H1N1 virus infection is predominantly seen in children and adults ( <35 years of age ) , but rarely in people older than 65 ye...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/protein chemistry", "genetics and genomics/genetics of disease", "gastroenterology and hepatology/stomach and duodenum" ]	Calpain 8/nCL-2 and Calpain 9/nCL-4 Constitute an Active Protease Complex, G-Calpain, Involved in Gastric Mucosal Defense	journal.pgen.1001040	null	[ [ "Calpain ( Clan CA-C2 , EC 3 . 4 . 22 . 17 ) is a family of intracellular Ca2+-regulated cysteine proteases found in almost all eukaryotic and some bacterial , and all the members of this family share homology in the protease domain [1] , [2] .", "Calpains play indispensable roles in biological processes ...	[ "Calpains constitute a superfamily of Ca2+-dependent cysteine proteases , indispensable for various cellular processes .", "Among the 15 mammalian calpains , calpain 8/nCL-2 and calpain 9/nCL-4 are predominantly expressed in the gastrointestinal tract and are restricted to the gastric surface mucus ( pit ) cells ...	[ "The continuous or improper ingestion of irritants , including alcohol , nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and Helicobacter pylori , often leads to serious gastropathies , affecting a wide range of people .", "A complex gastric defense system helps protect against these threats , for example by se...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "public health and epidemiology", "physiology/genomics", "physiology/renal, fluid, and electrolyte physiology", "cardiovascular disorders" ]	Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels	journal.pgen.1001045	null	[ [ "Magnesium is the second most abundant intra-cellular cation and is a co-factor in several important reactions , including nucleic acid synthesis and many enzymatic reactions [1] .", "Nearly 60% of magnesium in the human body resides in bone , 20% in skeletal muscle , and 20% in soft tissue .", "Altho...	[ "Magnesium , potassium , and sodium , cations commonly measured in serum , are involved in many physiological processes including energy metabolism , nerve and muscle function , signal transduction , and fluid and blood pressure regulation .", "To evaluate the contribution of common genetic variation to normal ph...	[ "Magnesium , potassium , and sodium are involved in important physiological processes .", "To better understand how common genetic variation may contribute to inter-individual differences in serum concentrations of these electrolytes , we evaluated single nucleotide polymorphisms ( SNPs ) across the genome in ass...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Protective Coupling of Mitochondrial Function and Protein Synthesis via the eIF2α Kinase GCN-2	journal.pgen.1002760	null	[ [ "Mitochondrial dysfunction and altered protein homeostasis are associated with numerous developmental and age-related diseases as well as the general process of aging [1] .", "The mitochondrial protein-folding environment is maintained by nuclear-encoded mitochondrial chaperones , which promote efficient ...	[ "Cells respond to defects in mitochondrial function by activating signaling pathways that restore homeostasis .", "The mitochondrial peptide exporter HAF-1 and the bZip transcription factor ATFS-1 represent one stress response pathway that regulates the transcription of mitochondrial chaperone genes during mitoch...	[ "Defects in mitochondrial function are associated with numerous age-related diseases including cancer and Parkinson's .", "Mitochondrial function relies upon maintenance of the mitochondrial proteome , which is comprised of nuclear and mitochondrial-encoded proteins .", "Nuclear-encoded polypeptides are transla...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/vaccines", "virology/virion structure, assembly, and egress", "virology/emerging viral diseases", "virology", "virology/immune evasion", "virology/host antiviral responses" ]	Natural Strain Variation and Antibody Neutralization of Dengue Serotype 3 Viruses	journal.ppat.1000821	null	[ [ "Dengue viruses ( DENVs ) are mosquito-borne flaviviruses and the agents of dengue fever and dengue hemorrhagic fever ( DHF ) .", "According to the World Health Organization , over 2 . 5 billion people are at risk of contracting dengue , 100 million people develop symptomatic infections and up to 50 , 000...	[ "Dengue viruses ( DENVs ) are emerging , mosquito-borne flaviviruses which cause dengue fever and dengue hemorrhagic fever .", "The DENV complex consists of 4 serotypes designated DENV1-DENV4 .", "Following natural infection with DENV , individuals develop serotype specific , neutralizing antibody responses .",...	[ "Dengue viruses are mosquito-borne flaviviruses and the agents of dengue fever and dengue hemorrhagic fever .", "It has been widely assumed that antibodies that neutralize dengue bind to regions on the viral envelope ( E ) protein that are conserved within each serotype .", "However , few studies have explored ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/virion structure, assembly, and egress", "computational biology/protein structure prediction", "computational biology/macromolecular structure analysis" ]	Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides	journal.pntd.0000721	null	[ [ "Fusogenic viral envelope glycoproteins are multimeric proteins that facilitate the fusion of viral and target cell lipid membranes during the initiation of infection .", "The membrane fusion process is energetically favorable and essentially irreversible , but has a considerable kinetic energy barrier [1...	[ "Viral fusogenic envelope proteins are important targets for the development of inhibitors of viral entry .", "We report an approach for the computational design of peptide inhibitors of the dengue 2 virus ( DENV-2 ) envelope ( E ) protein using high-resolution structural data from a pre-entry dimeric form of the...	[ "Virus surface proteins mediate interactions with target cells during the initial events in the process of infection .", "Inhibiting these proteins is therefore a major target for the development of antiviral drugs .", "However , there are a very large number of different viruses , each with their own distinct ...	2010
[ "Introduction", "Results", "Application", "Discussion", "Methods" ]	[ "chemical compounds", "markov models", "split-decomposition method", "organic compounds", "multiple alignment calculation", "mathematics", "basic amino acids", "protein structure", "amino acids", "research and analysis methods", "sequence analysis", "sequence alignment", "bioinformatics", ...	Inference of Functionally-Relevant N-acetyltransferase Residues Based on Statistical Correlations	journal.pcbi.1005294	null	[ [ "Just as one may infer genetic information from phenotypic patterns among parents and offspring , so one may infer biochemical and structural information from patterns of amino acid conservation and divergence among related proteins .", "In either case , careful statistical analyses are of course essentia...	[ "Over evolutionary time , members of a superfamily of homologous proteins sharing a common structural core diverge into subgroups filling various functional niches .", "At the sequence level , such divergence appears as correlations that arise from residue patterns distinct to each subgroup .", "Such a superfam...	[ "Protein sequence data , when gathered in great quantity , contain important but implicit biological information manifest as statistical correlations .", "Here we describe an approach to access this information by comprehensively modeling and characterizing the distribution of sequences belonging to a major prote...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "aging", "genome-wide association studies", "developmental biology", "organism development", "heredity", "genetic association studies", "genetics", "biology", "quantitative traits", "genetics and genomics", "complex traits", "human genetics" ]	An Assessment of the Individual and Collective Effects of Variants on Height Using Twins and a Developmentally Informative Study Design	journal.pgen.1002413	null	[ [ "Adult height is a model multigenic phenotype for genetic association studies .", "Twin and adoption studies suggest that height is highly heritable ( ∼80% ) [1] , [2] , [3] , but the identification of individual genetic variants that contribute large effects to normal-range adult height ( as with most co...	[ "In a sample of 3 , 187 twins and 3 , 294 of their parents , we sought to investigate association of both individual variants and a genotype-based height score involving 176 of the 180 common genetic variants with adult height identified recently by the GIANT consortium .", "First , longitudinal observations on h...	[ "We evaluated the developmental specificity of 176 SNPs known to affect adult height based on meta-analysis from the GIANT consortium .", "First , longitudinal observations on height spanning pre-adolescence through adulthood in a twin sample allowed us to investigate the individual effects of the previously iden...	2011
[ "Introduction", "Discussion", "Materials and Methods" ]	[ "host cells", "viral transmission and infection", "virology", "biology", "microbiology", "molecular cell biology", "viral replication" ]	Parvovirus-Induced Depletion of Cyclin B1 Prevents Mitotic Entry of Infected Cells	journal.ppat.1003891	null	[ [ "Parvoviruses are the only known viruses of vertebrates that contain single-stranded linear DNA genomes , and they present novel replicative DNA structures to cells during infection [1] , [2] .", "Unlike the DNA tumor viruses , parvoviruses do not drive quiescent cells into S-phase [3] .", "However , ...	[ "Parvoviruses halt cell cycle progression following initiation of their replication during S-phase and continue to replicate their genomes for extended periods of time in arrested cells .", "The parvovirus minute virus of mice ( MVM ) induces a DNA damage response that is required for viral replication and induct...	[ "DNA viruses induce cellular DNA damage responses that can present a block to infection that must be overcome , or alternatively , can be utilized to viral advantage .", "Parvoviruses , the only known viruses of vertebrates that contain single-stranded linear DNA genomes , induce a robust DNA damage response ( DD...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "biogeography", "dengue virus", "ecology and environmental sciences", "medicine and health sciences", "pathology and laboratory medicine", "engineering and technology", "transportation", "china", "pathogens", "population genetics", "geographical locations", "microbiology", "tropical diseases...	Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia	journal.pntd.0005694	null	[ [ "Dengue virus ( DENV ) is a growing threat to public health , with nearly 390 million infections every year worldwide , of which ~96 million are symptomatic [1 , 2] .", "An estimated 2 . 5 billion people are at risk of dengue infection [3] .", "Dengue is regarded as the world’s most important mosquito...	[ "The incidence of dengue has grown dramatically in recent decades worldwide , especially in Southeast Asia and the Americas with substantial transmission in 2014–2015 .", "Yet the mechanisms underlying the spatio-temporal circulation of dengue virus ( DENV ) serotypes at large geographical scales remain elusive ....	[ "In the past half century the incidence of dengue fever worldwide has increased 30-fold , with an estimated ~390 million infections per year .", "The years 2014 and 2015 were characterized by large dengue outbreaks worldwide , which are a threat to public health , especially in Asian countries .", "Here we use ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "autophagic cell death", "fish", "medicine and health sciences", "cell processes", "tropical diseases", "vertebrates", "animals", "animal models", "osteichthyes", "bacterial diseases", "developmental biology", "model organisms", "experimental organism systems", "molecular b...	The selective autophagy receptors Optineurin and p62 are both required for zebrafish host resistance to mycobacterial infection	journal.ppat.1007329	null	[ [ "Autophagy is a fundamental cellular pathway in eukaryotes that functions to maintain homeostasis by degradation of cytoplasmic contents in lysosomes [1] .", "During autophagy , protein aggregates or defective organelles are sequestered by double-membrane structures , called isolation membranes or phagoph...	[ "Mycobacterial pathogens are the causative agents of chronic infectious diseases like tuberculosis and leprosy .", "Autophagy has recently emerged as an innate mechanism for defense against these intracellular pathogens .", "In vitro studies have shown that mycobacteria escaping from phagosomes into the cytosol...	[ "Tuberculosis is a serious infectious disease that claims over a million lives annually .", "Vaccination provides insufficient protection and the causative bacterial pathogen , Mycobacterium tuberculosis , is becoming increasingly resistant to antibiotic therapy .", "Therefore , there is an urgent need for nove...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/comparative genomics", "microbiology/medical microbiology", "genetics and genomics/functional genomics", "computational biology/metabolic networks", "computational biology/genomics", "infectious diseases/bacterial infections", "genetics and geno...	Global Genotype-Phenotype Correlations in Pseudomonas aeruginosa	journal.ppat.1001074	null	[ [ "A principal goal of genomics is to acquire a global overview of the genetic information of a cell , its bioinformatic decoding into cellular metabolism in the context of the prevailing environment , and the expression of this metabolism as cellular-organismal phenotypes .", "Though much progress has been...	[ "Once the genome sequence of an organism is obtained , attention turns from identifying genes to understanding their function , their organization and control of metabolic pathways and networks that determine its physiology .", "Recent technical advances in acquiring genome-wide data have led to substantial progr...	[ "Phenotypic description has long been used to discriminate between bacteria and , with the publication of Bergey's Manual of Determinative Bacteriology in 1923 , microbiologists began to systematically describe and define bacterial species based on lists of phenotypes .", "Because growth phenotypes are directly a...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "systems biology", "medicine", "chronic obstructive pulmonary diseases", "genetics and genomics", "biology", "genomics", "respiratory medicine", "pulmonology" ]	A Systems Biology Approach Identifies Molecular Networks Defining Skeletal Muscle Abnormalities in Chronic Obstructive Pulmonary Disease	journal.pcbi.1002129	null	[ [ "Chronic Obstructive Pulmonary Disease ( COPD ) is an inflammatory process of the lung that generates progressive and largely poorly reversible airflow limitation [1] , [2] .", "COPD represents a high burden on healthcare systems worldwide , since it is the fourth cause of death and its prevalence is expe...	[ "Chronic Obstructive Pulmonary Disease ( COPD ) is an inflammatory process of the lung inducing persistent airflow limitation .", "Extensive systemic effects , such as skeletal muscle dysfunction , often characterize these patients and severely limit life expectancy .", "Despite considerable research efforts , ...	[ "Chronic Obstructive Pulmonary Disease ( COPD ) is a major life threatening disease of the lungs , characterized by airflow limitation and chronic inflammation .", "Progressive reduction of the body muscle mass is a condition linked to COPD that significantly decreases quality of life and survival .", "Physical...	2011
[ "Introduction", "Models", "Results/Discussion" ]	[ "phosphorylation", "enzymes", "applied mathematics", "enzymology", "phosphatases", "simulation and modeling", "algorithms", "probability distribution", "mathematics", "systems science", "algebra", "polynomials", "research and analysis methods", "computer and information sciences", "prote...	Enzyme sequestration by the substrate: An analysis in the deterministic and stochastic domains	journal.pcbi.1006107	null	[ [ "Probably the most studied form of protein modification is protein phosphorylation , the binding of a phosphoryl ( P O 3 - ) group using a kinase enzyme [1] .", "This , together with dephosphorylation by a phosphatase enzyme , contributes to the regulation of transcription factors , thus regulating the re...	[ "This paper is concerned with the potential multistability of protein concentrations in the cell .", "That is , situations where one , or a family of , proteins may sit at one of two or more different steady state concentrations in otherwise identical cells , and in spite of them being in the same environment .",...	[ "Models of multisite protein phosphorylation have been of great interest to the systems biology community , largely due to their ability to exhibit multistable behaviour .", "In the presence of excess substrate it has been shown that the number of stable steady states achieved can increase linearly with the numbe...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical compounds", "population genetics", "galactose", "carbohydrates", "organic compounds", "glucose", "alleles", "genetic mapping", "fungi", "model organisms", "experimental organism systems", "population biology", "saccharomyces", "research and analysis methods", "genetic polymorph...	Polymorphisms in the yeast galactose sensor underlie a natural continuum of nutrient-decision phenotypes	journal.pgen.1006766	null	[ [ "The nutrient composition of natural environments can fluctuate and organisms must induce metabolic pathways that allow them to utilize the available nutrients [1–3] .", "Recent studies have found that closely related microbes vary in both the types of nutrients they can utilize and the efficiency at whic...	[ "In nature , microbes often need to \"decide\" which of several available nutrients to utilize , a choice that depends on a cell’s inherent preference and external nutrient levels .", "While natural environments can have mixtures of different nutrients , phenotypic variation in microbes’ decisions of which nutrie...	[ "In nature , microbes often need to decide which of many potential nutrients to consume .", "This decision making process is complex , involving both intracellular constraints and the organism’s perception of the environment .", "To begin to mimic the complexity of natural environments , we grew cells in mixtur...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical bonding", "ion channel gating", "medicine and health sciences", "single channel recording", "molecular dynamics", "chemical compounds", "computational biology", "electrophysiology", "neuroscience", "organic compounds", "electron cryo-microscopy", "ion channels", "microscopy", "me...	Transmembrane helical interactions in the CFTR channel pore	journal.pcbi.1005594	null	[ [ "Cystic Fibrosis ( CF ) is a fatal genetic disease caused by inheritance of mutations in the gene coding for CFTR .", "Medical advances in recent years have significantly extended the life span of CF patients , but the disease has no cure and is inevitably fatal .", "Delineation of the molecular mecha...	[ "Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator ( CFTR ) gene affect CFTR protein biogenesis or its function as a chloride channel , resulting in dysregulation of epithelial fluid transport in the lung , pancreas and other organs in cystic fibrosis ( CF ) .", "Development of pharmaceutical s...	[ "Cystic Fibrosis is a severe genetic disorder caused by mutations in the gene coding for CFTR .", "This defect induces protein misfolding and channel dysfunction , resulting in the disruption of hydration of epithelial surfaces in different organs .", "Restoring channel activity in the mutant protein requires a...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "alkaloids", "medicine and health sciences", "chemical compounds", "disaccharides", "gustatory system", "oleic acid", "social sciences", "carbohydrates", "neuroscience", "organic compounds", "animals", "animal models", "drosophila melanogaster", "model organisms", "exp...	A subset of sweet-sensing neurons identified by IR56d are necessary and sufficient for fatty acid taste	journal.pgen.1007059	null	[ [ "Fat represents a calorically potent food source that yields approximately twice the amount of energy as carbohydrates or proteins per unit of mass .", "In mammals , dietary lipids are detected by taste cells , mechanosensory and olfactory neurons , as well as by post-ingestive feedback [1–4] .", "Die...	[ "Fat represents a calorically potent food source that yields approximately twice the amount of energy as carbohydrates or proteins per unit of mass .", "The highly palatable taste of free fatty acids ( FAs ) , one of the building blocks of fat , promotes food consumption , activates reward circuitry , and is thou...	[ "Fat represents a calorically potent food source that yields approximately twice the amount of energy as carbohydrates or proteins per unit of mass .", "Dietary lipids are comprised of both triacylglycerides and FAs , and growing evidence suggests that it is the free FAs that are detected by the gustatory system ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Mouse BAZ1A (ACF1) Is Dispensable for Double-Strand Break Repair but Is Essential for Averting Improper Gene Expression during Spermatogenesis	journal.pgen.1003945	null	[ [ "The nucleosome , a complex of eight histone proteins wrapped by 146 bp of DNA , is a fundamental packaging unit for nuclear DNA , controlling access by proteins involved in transcription , replication , recombination and repair .", "Granting or blocking DNA access can be effected through changes in histo...	[ "ATP-dependent chromatin remodelers control DNA access for transcription , recombination , and other processes .", "Acf1 ( also known as BAZ1A in mammals ) is a defining subunit of the conserved ISWI-family chromatin remodelers ACF and CHRAC , first purified over 15 years ago from Drosophila melanogaster embryos ...	[ "The eukaryotic genome is packaged into a periodic nucleoprotein complex known as chromatin .", "Wrapping of DNA around nucleosomes , the basic repeat unit of chromatin , enables packing of long stretches of DNA into a compact nucleus but also impedes access by protein factors involved in essential cellular proce...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Mechanism of Iron-Dependent Repressor (IdeR) Activation and DNA Binding: A Molecular Dynamics and Protein Structure Network Study	journal.pcbi.1004500	null	[ [ "Tuberculosis ( TB ) remains the largest killer amongst infectious diseases globally and is caused by the pathogen Mycobacterium tuberculosis ( M . tb ) .", "Based on the latest WHO report [1] , in the year 2013 , an estimated 9 million people acquired the disease and nearly 1 . 5 million succumbed to the...	[ "Metalloproteins form a major class of enzymes in the living system that are involved in crucial biological functions such as catalysis , redox reactions and as ‘switches’ in signal transductions .", "Iron dependent repressor ( IdeR ) is a metal-sensing transcription factor that regulates free iron concentration ...	[ "The importance of iron for tuberculosis infection and criticality of IdeR as an iron regulator in Mycobacterium tuberculosis have now been well-established .", "Although crystal structures of the protein in different forms are available , its dynamical properties have not been explored before .", "Macromolecul...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics", "biology", "computational biology" ]	A Combination of Transcriptional and MicroRNA Regulation Improves the Stability of the Relative Concentrations of Target Genes	journal.pcbi.1003490	null	[ [ "The interplay between transcriptional and post-transcriptional regulation attracted much interest in the past few years [1] .", "As in the purely transcriptional regulatory network [2] , motifs belonging to such mixed layer of interaction have been identified [3]–[6] and mathematically characterized [4] ...	[ "It is well known that , under suitable conditions , microRNAs are able to fine tune the relative concentration of their targets to any desired value .", "We show that this function is particularly effective when one of the targets is a Transcription Factor ( TF ) which regulates the other targets .", "This com...	[ "Gene expression is controlled by a complex network of regulatory interactions which may be organized in two complementary subnetworks: the transcriptional one , mediated by Transcription Factors ( TF ) , and the post-transcriptional one , in which a central role is played by microRNAs .", "In this paper we add a...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "infectious diseases", "infectious diseases/prion diseases", "biochemistry/protein chemistry", "neurological disorders/prion diseases" ]	Rapid End-Point Quantitation of Prion Seeding Activity with Sensitivity Comparable to Bioassays	journal.ppat.1001217	null	[ [ "The transmissible spongiform encephalopathies ( TSEs ) or prion diseases are fatal neurodegenerative disorders that include human Creutzfeldt-Jakob disease ( CJD ) , bovine spongiform encephalopathy ( BSE ) , sheep scrapie , cervid chronic wasting disease ( CWD ) , and transmissible mink encephalopathy ( TME...	[ "A major problem for the effective diagnosis and management of prion diseases is the lack of rapid high-throughput assays to measure low levels of prions .", "Such measurements have typically required prolonged bioassays in animals .", "Highly sensitive , but generally non-quantitative , prion detection methods...	[ "Prion diseases are deadly infectious neurodegenerative disorders of mammals which involve the misfolding of host prion protein .", "To better manage these diseases , we need to be able to detect and quantify the infectious particles , or prions , in biological samples .", "However , current tests lack the sens...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "segmentation", "signaling networks", "cell differentiation", "developmental biology", "body plan organization", "morphogenesis", "biophysics simulations", "pattern formation", "embryology", "regulatory networks", "biology", "biophysics", "biophysic al simulations", "computational biology"...	A Multi-cell, Multi-scale Model of Vertebrate Segmentation and Somite Formation	journal.pcbi.1002155	null	[ [ "The clock-and-wavefront model , initially proposed by Cooke and Zeeman in 1976 , describes a smoothly varying intracellular oscillator ( the segmentation clock ) that interacts with a posterior-propagating front of cell maturation in the PSM ( the wavefront ) to divide the PSM into periodic segments at regul...	[ "Somitogenesis , the formation of the body's primary segmental structure common to all vertebrate development , requires coordination between biological mechanisms at several scales .", "Explaining how these mechanisms interact across scales and how events are coordinated in space and time is necessary for a comp...	[ "Recent decades have seen a revolution in experimental techniques that has shifted the focus of experimental biology from behaviors at the micron ( cell ) scale to those at the nanometer ( molecular ) scale .", "An ever-increasing number of studies detail subcellular behaviors , genetic pathways and protein inter...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/complex traits", "genetics and genomics" ]	Genome-Wide Association Analyses Identify SPOCK as a Key Novel Gene Underlying Age at Menarche	journal.pgen.1000420	null	[ [ "Menarche is a most significant milestone in a female's physiological development .", "It happens when thickened endometrial tissue undergoes a sudden death due to fluctuations of hormone levels .", "Age at menarche ( AAM ) has a significant impact on a woman's health later in life .", "For exampl...	[ "For females , menarche is a most significant physiological event .", "Age at menarche ( AAM ) is a trait with high genetic determination and is associated with major complex diseases in women .", "However , specific genes for AAM variation are largely unknown .", "To identify genetic factors underlying AAM v...	[ "Menarche is a physical milestone in a woman's life .", "Age at menarche ( AAM ) is related to many common female health problems .", "AAM is mainly determined by genetic factors .", "However , the specific genes and the associated mechanisms underlying AAM are largely unknown .", "Here , taking advantage o...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Re-replication of a Centromere Induces Chromosomal Instability and Aneuploidy	journal.pgen.1005039	null	[ [ "During their life cycle , cells must duplicate their genome exactly once , then precisely segregate the two copies into their daughter cells .", "In eukaryotes , elaborate regulatory controls ensure that each of these processes occur with great fidelity .", "Because DNA replication and chromosome seg...	[ "The faithful inheritance of chromosomes during cell division requires their precise replication and segregation .", "Numerous mechanisms ensure that each of these fundamental cell cycle events is performed with a high degree of fidelity .", "The fidelity of chromosomal replication is maintained in part by re-r...	[ "The stable inheritance of genetic information requires an elaborate mitotic machinery that acts on the centromeres of chromosomes to ensure their precise segregation .", "Errors in this segregation can lead to aneuploidy , an unbalanced chromosomal state in which some chromosomes have different copy number than ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "ecology and environmental sciences", "onchocerca volvulus", "rivers", "helminths", "tropical diseases", "geographical locations", "parasitic diseases", "animals", "onchocerca", "filariasis", "aquatic environments", "pharmaceutics", "drug ...	Evaluation of Lymphatic Filariasis and Onchocerciasis in Three Senegalese Districts Treated for Onchocerciasis with Ivermectin	journal.pntd.0005198	null	[ [ "Lymphatic filariasis ( LF ) is an infection caused by the parasitic nematodes Wuchereria bancrofti , Brugia malayi , and Brugia timori and transmitted by mosquitoes .", "LF is endemic in 73 countries with an estimated 1 . 1 billion people at risk who required mass drug administration ( MDA ) in 2014 [1] ...	[ "In Africa , onchocerciasis and lymphatic filariasis ( LF ) are co-endemic in many areas .", "Current efforts to eliminate both diseases are through ivermectin-based mass drug administration ( MDA ) .", "Years of ivermectin distribution for onchocerciasis may have interrupted LF transmission in certain areas ."...	[ "Onchocerciasis and lymphatic filariasis ( LF ) are neglected tropical diseases caused by infection with filarial parasites , Onchocerca volvulus and Wuchereria bancrofti or Brugia species respectively .", "Efforts to eliminate both diseases are through ivermectin-based mass drug administration ( MDA ) for onchoc...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "natural antisense transcripts", "gene regulation", "ears", "alleles", "cell differentiation", "physiological processes", "developmental biology", "mutation", "micrornas", "embryos", "embryology", "gene expression", "head", "genetic loci", "biochemistry"...	Hypomorphic mutation of the mouse Huntington’s disease gene orthologue	journal.pgen.1007765	null	[ [ "Huntington’s Disease ( HD ) is a dominantly inherited neurodegenerative disorder characterized by motor , cognitive and behavioral signs , generally of mid-life onset [1] .", "HD is caused by an unstable CAG trinucleotide repeat expansion in the 4p16 . 3 gene HTT ( previously HD ) [2] .", "The size o...	[ "Rare individuals with inactivating mutations in the Huntington’s disease gene ( HTT ) exhibit variable abnormalities that imply essential HTT roles during organ development .", "Here we report phenotypes produced when increasingly severe hypomorphic mutations in the murine HTT orthologue Htt , ( HdhneoQ20 , Hdhn...	[ "The HTT gene mutated in Huntington’s Disease ( HD ) has essential roles during normal development .", "However , still not fully understood are the functional consequences of its partial inactivation .", "Our genetic study provides a comprehensive description of the effects of progressively more severe decreas...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology/global change ecology", "public health and epidemiology", "infectious diseases/neglected tropical diseases", "public health and epidemiology/global health", "public health and epidemiology/infectious diseases", "computational biology" ]	Climate Change and Risk of Leishmaniasis in North America: Predictions from Ecological Niche Models of Vector and Reservoir Species	journal.pntd.0000585	null	[ [ "Leishmaniasis is a vector-borne parasitic disease endemic in most tropical regions of the world with approximately two million new human cases reported each year [1] , [2] .", "In the Americas , parasite species belonging to the genus Leishmania are responsible for different clinical pathologies , includ...	[ "Climate change is increasingly being implicated in species' range shifts throughout the world , including those of important vector and reservoir species for infectious diseases .", "In North America ( México , United States , and Canada ) , leishmaniasis is a vector-borne disease that is autochthonous in México...	[ "We explored the consequences of climate change for the spread of leishmaniasis in North America .", "We modeled the distribution of two sand fly vector and four rodent reservoir species found in northern México and the southern United States .", "Models were based on occurrence data and environmental and topog...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	A Data-Driven Mathematical Model of CA-MRSA Transmission among Age Groups: Evaluating the Effect of Control Interventions	journal.pcbi.1003328	null	[ [ "Staphylococcus aureus is one of the most common bacterial pathogens in humans and the most frequent cause of skin and soft tissue infections ( SSTIs ) [1] .", "Strains of health care-associated methicillin-resistant S . aureus ( HA-MRSA ) were first identified among hospitalized patients in 1960 [2] and ...	[ "Community associated methicillin-resistant Staphylococcus aureus ( CA-MRSA ) has become a major cause of skin and soft tissue infections ( SSTIs ) in the US .", "We developed an age-structured compartmental model to study the spread of CA-MRSA at the population level and assess the effect of control intervention...	[ "Community associated methicillin-resistant Staphylococcus aureus ( CA-MRSA ) is a bacteria that causes skin infections in the US .", "We developed a mathematical model of CA-MRSA transmission among different age groups at the population level .", "We parameterized the model using monthly time series data on nu...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "microbiology/cellular microbiology and pathogenesis", "molecular biology/dna methylation", "genetics and genomics/gene expression" ]	Phasevarions Mediate Random Switching of Gene Expression in Pathogenic Neisseria	journal.ppat.1000400	null	[ [ "The pathogenic Neisseria are host-adapted human pathogens that pose a significant health problem worldwide .", "Neisseria meningitidis colonizes the upper respiratory tract and causes meningitis and septicemia .", "Neisseria gonorrhoeae colonizes the genitourinary tract and can cause a spectrum of di...	[ "Many host-adapted bacterial pathogens contain DNA methyltransferases ( mod genes ) that are subject to phase-variable expression ( high-frequency reversible ON/OFF switching of gene expression ) .", "In Haemophilus influenzae , the random switching of the modA gene controls expression of a phase-variable regulon...	[ "The pathogenic Neisseria are bacterial pathogens that cause meningitis and gonorrhoea .", "They have adapted to life exclusively in humans and have developed unique strategies to colonize the host and to evade the immune response .", "Central among these strategies are genetic switches that randomly turn genes...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A DIseAse MOdule Detection (DIAMOnD) Algorithm Derived from a Systematic Analysis of Connectivity Patterns of Disease Proteins in the Human Interactome	journal.pcbi.1004120	null	[ [ "In the recent years , there is increasing evidence that proteins associated with a particular disease have distinct interactions within the Human Interactome , representing the cellular network of all physical molecular interactions [1–7] .", "The pathobiological properties of a disease and its clinical ...	[ "The observation that disease associated proteins often interact with each other has fueled the development of network-based approaches to elucidate the molecular mechanisms of human disease .", "Such approaches build on the assumption that protein interaction networks can be viewed as maps in which diseases can ...	[ "Diseases are rarely the result of an abnormality in a single gene , but involve a whole cascade of interactions between several cellular processes .", "To disentangle these complex interactions it is necessary to study genotype-phenotype relationships in the context of protein-protein interaction networks .", ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genomics", "biology", "computational biology" ]	Shining a Light on Dark Sequencing: Characterising Errors in Ion Torrent PGM Data	journal.pcbi.1003031	null	[ [ "The last decade has seen dramatic advances in sequencing technology that have relied on highly-parallel optical sensing of polymerisation reactions .", "These advances have substantially reduced sequencing costs , however further reduction in cost is limited by the dependence of these platforms on photo-...	[ "The Ion Torrent Personal Genome Machine ( PGM ) is a new sequencing platform that substantially differs from other sequencing technologies by measuring pH rather than light to detect polymerisation events .", "Using re-sequencing datasets , we comprehensively characterise the biases and errors introduced by the ...	[ "DNA sequencing is used routinely within biology to reveal the genetic information of living organisms .", "In recent years , technological advances have led to the availability of high-throughput , low-cost DNA sequencing machines ( ‘sequencers’ ) .", "In 2011 , Life Sciences released a new sequencer , the Ion...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/prion diseases" ]	Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation	journal.ppat.1000206	null	[ [ "Prions are proteinaceous infectious particles that cause invariably fatal neurodegenerative diseases , including Creutzfeldt-Jakob disease ( CJD ) and kuru in humans , bovine spongiform encephalopathy ( BSE ) , chronic wasting disease ( CWD ) in deer and elk , and scrapie in sheep and goats .", "The only...	[ "Distinct prion strains often exhibit different incubation periods and patterns of neuropathological lesions .", "Strain characteristics are generally retained upon intraspecies transmission , but may change on transmission to another species .", "We investigated the inactivation of two related prions strains: ...	[ "“Mad cow” disease , formally known as bovine spongiform encephalopathy ( BSE ) , belongs to a family of diseases affecting humans and a number of commercially important animal species .", "These diseases are not spread by bacteria or viruses , but by infectious proteins , termed “prions . ”", "Prions are known...	2008
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "leptospira", "pathology and laboratory medicine", "pathogens", "tropical diseases", "microbiology", "vertebrates", "animals", "mammals", "dogs", "bacterial diseases", "neglected tropical diseases", "kidneys", "bacteria", "bacterial pathogens", "research...	Leptospira diversity in animals and humans in Tahiti, French Polynesia	journal.pntd.0005676	null	[ [ "Leptospirosis is a disease caused by leptospires , bacteria belonging to the order Spirochaetales , family Leptospiraceae , genus Leptospira [1] .", "Leptospirosis is the most widespread zoonosis worldwide [2] , but a neglected disease in most of the tropics , especially in the Pacific region [3] .", ...	[ "Leptospirosis is a highly endemic bacterial zoonosis in French Polynesia ( FP ) .", "Nevertheless , data on the epidemiology of leptospirosis in FP are scarce .", "We conducted molecular studies on Leptospira isolated from humans and the potential main animal reservoirs in order to identify the most likely sou...	[ "Leptospirosis , a zoonosis caused by Leptospira spp .", "bacteria , is an important but neglected disease in the Pacific region .", "The bacteria can lead to human infections , either through direct contact with infected animals or through water and soil contaminated with urine .", "Although animals play a k...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	The Biting Midge Culicoides sonorensis (Diptera: Ceratopogonidae) Is Capable of Developing Late Stage Infections of Leishmania enriettii	journal.pntd.0004060	null	[ [ "The leishmaniases are widespread protozoan diseases with dermal or visceral clinical symptoms that affect humans and animals worldwide .", "Members of the genus Leishmania ( Trypanosomatidae: Kinetoplastida ) follow a digenetic life cycle , alternating between a vertebrate host and insect vector .", ...	[ "Despite their importance in animal and human health , the epidemiology of species of the Leishmania enriettii complex remains poorly understood , including the identity of their biological vectors .", "Biting midges of the genus Forcipomyia ( Lasiohelea ) have been implicated in the transmission of a member of t...	[ "This study investigates the laboratory infection of two species of Culicoides biting midges ( Diptera: Ceratopogonidae ) and one species of sand fly ( Diptera: Psychodidae ) with two species of Leishmania .", "These members of the L . enriettii complex were demonstrated to colonize the stomodeal valve of Culicoi...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "hela cells", "enzymes", "chlamydia trachomatis", "pathogens", "cell processes", "biological cultures", "microbiology", "enzymology", "phosphatases", "membrane proteins", "molecular motors", "actin motors", "sexually tr...	Chlamydia trachomatis inclusion membrane protein MrcA interacts with the inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) to regulate extrusion formation	journal.ppat.1006911	null	[ [ "Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium that causes a variety of human and veterinary infections .", "Distinct serological variants , or serovars , are responsible for different diseases such as trachoma , the leading cause of infectious blindness worldwide ( serovars A-...	[ "Chlamydia trachomatis is an obligate intracellular bacterium that replicates within a vacuole termed an inclusion .", "At the end of their intracellular developmental cycle , chlamydiae are released either by lysis of the host cell or extrusion of the intact inclusion .", "The inclusion membrane is extensively...	[ "At the end of their intracellular developmental cycle , chlamydiae exit host cells by one of two mechanisms; lysis of the host cell or extrusion of a membrane bound vesicle containing viable chlamydiae .", "Sequestration of infectious organisms within a vesicle is believed to aid in dissemination of the bacteria...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "squamous cell lung carcinoma", "cancer risk factors", "carcinomas", "cancers and neoplasms", "endometrial carcinoma", "dna transcription", "oncology", "adenocarcinomas", "head and neck tumors", "epigenetics", "dna", "medical risk factors", "dna methylation"...	Aberrant DNA methylation defines isoform usage in cancer, with functional implications	journal.pcbi.1007095	null	[ [ "More than 90% of human protein coding genes are capable of producing multiple isoforms , either by adopting alternative transcription start or termination sites ( TSSs or TTSs , respectively ) or by switching internal splice sites to generate alternative exons [1] .", "Utilizing these approaches , gene f...	[ "Alternative transcript isoforms are common in tumors and act as potential drivers of cancer .", "Mechanisms determining altered isoform expression include somatic mutations in splice regulatory sites or altered splicing factors .", "However , since DNA methylation is known to regulate transcriptional isoform a...	[ "In eukaryotes , one gene can be transcribed into multiple RNA sequences ( or isoforms ) that are subsequently translated into proteins with different functions in response to specific cellular needs .", "Recent studies showed that cancer cells can obtain abnormal functions via expressing different isoforms .", ...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology/epidemiology", "public health and epidemiology/infectious diseases", "infectious diseases/bacterial infections", "infectious diseases/epidemiology and control of infectious diseases" ]	The Natural History of Trachoma Infection and Disease in a Gambian Cohort with Frequent Follow-Up	journal.pntd.0000341	null	[ [ "The scarring and blindness that result from repeated infection of the eye with Chlamydia trachomatis represent a significant public health burden in some of the poorest parts of the world [1] .", "Community-wide treatment with antibiotics can significantly reduce the prevalence of infection and active in...	[ "The natural history of ocular Chlamydia trachomatis infections in endemic communities has not been well characterised and is an important determinant of the effectiveness of different mass treatment strategies to prevent blindness due to trachoma .", "A multistate hidden Markov model was fitted to data on infect...	[ "Trachoma is an infectious disease of the eye that causes blindness in many of the poorest parts of the world .", "In this paper , we use a novel statistical approach to estimate the characteristics of this disease among people living in The Gambia who were examined every 2 weeks over a 6-month period .", "We f...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "oncology/breast cancer", "cell biology/nuclear structure and function", "genetics and genomics/nuclear structure and function", "cell biology", "genetics and genomics/chromosome biology", "genetics and genomics/epigenetics", "molec...	Activation of Estrogen-Responsive Genes Does Not Require Their Nuclear Co-Localization	journal.pgen.1000922	null	[ [ "Chromatin organisation in the vertebrate nucleus is non random: chromosomes adopt preferential positions with regard to the centre or edge of the nucleus and genes adopt preferential positions with regard to their own chromosome territory [1] .", "Moreover , preferential long-range associations have been...	[ "The spatial organization of the genome in the nucleus plays a role in the regulation of gene expression .", "Whether co-regulated genes are subject to coordinated repositioning to a shared nuclear space is a matter of considerable interest and debate .", "We investigated the nuclear organization of estrogen re...	[ "Whether co-regulated genes relocalize in a coordinated fashion to a shared nuclear space is a matter of considerable interest and debate .", "We investigated the spatial organization of estrogen receptor alpha ( ERα ) target genes in three human breast epithelial cell lines , human epithelial cells ( HMEC ) , th...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "biogeography", "ecology and environmental sciences", "medicine and health sciences", "pathology and laboratory medicine", "giardia", "pathogens", "population dynamics", "population genetics", "geographical locations", "microbiology", "cryptosporidium", "parasitic protozoans", "protozoans", ...	Local and global genetic diversity of protozoan parasites: Spatial distribution of Cryptosporidium and Giardia genotypes	journal.pntd.0005736	null	[ [ "Infectious diseases are the major leading causes of death and disability worldwide [1] .", "Classical public health and sanitation measures have long served to minimize dissemination and human exposure to many pathogens that are spread by routes such as contaminated water or via vectors [2] but the recen...	[ "Cryptosporidiosis and giardiasis are recognized as significant enteric diseases due to their long-term health effects in humans and their economic impact in agriculture and medical care .", "Molecular analysis is essential to identify species and genotypes causing these infectious diseases and provides a potenti...	[ "Infectious diseases threaten the health and well-being of wildlife , livestock and human populations and contribute to significant economic impact in agriculture and medical care .", "Cryptosporidium and Giardia are enteric protozoan pathogens that cause diarrhea and nutritional disorders on a global level .", ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "neuroscience", "dna transcription", "sequence motif analysis", "molecular biology techniques", "rna sequencing", "research and analysis methods", "sequence analysis", "exon mapping", "genome complexity", "gene mapping", "bioinformatics", "animal cells", "sequence ...	The temporal landscape of recursive splicing during Pol II transcription elongation in human cells	journal.pgen.1007579	null	[ [ "Recursive splicing ( RS ) —a multi-step process to excise long introns from pre-mRNAs—was first identified in the Ultrabithorax ( Ubx ) gene of Drosophila melanogaster [1] .", "Each recursive splice site ( RS site; also called a ratchet site in Drosophila ) contains a pair of juxtaposed 3′ and 5′ splice ...	[ "Recursive splicing ( RS ) is an evolutionarily conserved process of removing long introns via multiple steps of splicing .", "It was first discovered in Drosophila and recently proven to occur also in humans .", "The detailed mechanism of recursive splicing is not well understood , in particular , whether it i...	[ "Nascent precursor RNAs newly transcribed from a DNA template are processed into mature RNAs by splicing out introns and ligating exons .", "Recursive splicing ( RS ) is a special kind of splicing whereby long introns are removed piecewise in multiple consecutive steps .", "Only nine human introns are known to ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mathematics", "neuroscience/neurodevelopment", "neuroscience/theoretical neuroscience" ]	Subbarrel Patterns in Somatosensory Cortical Barrels Can Emerge from Local Dynamic Instabilities	journal.pcbi.1000537	null	[ [ "Mechanisms underlying the attainment of the central nervous system's highly structured organization are varied and numerous .", "The identification of developmentally regulated molecular signals are critically important for understanding neural function as well as fundamental processes of disease and rep...	[ "Complex spatial patterning , common in the brain as well as in other biological systems , can emerge as a result of dynamic interactions that occur locally within developing structures .", "In the rodent somatosensory cortex , groups of neurons called “barrels” correspond to individual whiskers on the contralate...	[ "Complex spatial patterning , common in the brain as well as in other biological systems , can emerge as a result of dynamic interactions that occur locally within developing structures .", "In rodent somatosensory cortex , groups of neurons called “barrels” correspond to individual whiskers on the contralateral ...	2009
[ "Introduction", "Materials and Methods", "Discussion" ]	[ "public health", "medicine", "echinococcosis", "infectious diseases", "veterinary epidemiology", "neglected tropical diseases", "parasitic diseases", "veterinary science" ]	A Systematic Review of the Epidemiology of Echinococcosis in Domestic and Wild Animals	journal.pntd.0002249	null	[ [ "Echinococcosis is a zoonotic parasitic infection caused by the larval stage of several species belonging to the genus Echinococcus .", "Human echinococcosis results following the direct or indirect infection from canid hosts , which are themselves infected by various domestic and wild mammals .", "Ec...	[ "Human echinococcosis is a neglected zoonosis caused by parasites of the genus Echinococcus .", "The most frequent clinical forms of echinococcosis , cystic echinococcosis ( CE ) and alveolar echinococcosis ( AE ) , are responsible for a substantial health and economic burden , particularly to low-income societie...	[ "Echinococcosis is considered a neglected zoonotic disease caused by the larval form of Echinococcus spp .", "tapeworms .", "Humans become infected through the accidental intake of parasitic eggs excreted by the faeces of definitive hosts ( dogs , foxes and other canids ) .", "Infection involves the developme...	2013
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "infectious diseases/neglected tropical diseases", "biochemistry", "microbiology/applied microbiology" ]	Control of Pyrethroid-Resistant Chagas Disease Vectors with Entomopathogenic Fungi	journal.pntd.0000434	null	[ [ "Chagas disease is currently the most important parasitic disease of the Americas representing a serious health and social burden for most Latin-American countries , with current estimates of about 10 million people infected and 40 million at risk [1] .", "The causative agent of this disease , Trypanosoma...	[ "Triatoma infestans-mediated transmission of Tripanosoma cruzi , the causative agent of Chagas disease , remains as a major health issue in southern South America .", "Key factors of T . infestans prevalence in specific areas of the geographic Gran Chaco region—which extends through northern Argentina , Bolivia ,...	[ "Chagas disease , also known as American Trypanosomiasis , is the most relevant parasitic disease in Latin America , being a major burden that affects mostly poor human populations living in rural areas .", "The kissing-bugs of the Triatominae family transmit the parasite Trypanosoma cruzi by infectious blood-suc...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "ocular anatomy", "microbiology", "saliva", "pili and fimbriae", "epithelial cells", "pseudomonas aeruginosa", "analysis of variance", "mathematics", "statistics (mathematics)", "cellular struc...	Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of the opportunistic pathogen Pseudomonas aeruginosa	journal.ppat.1006392	null	[ [ "Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen ubiquitous in our environment .", "It is a leading cause of life-threatening infections in debilitated individuals in the hospital setting [1] , and of sight-threatening corneal disease in healthy people who wear contact lenses [2 , 3] .", ...	[ "It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity .", "However , our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriosta...	[ "Pseudomonas aeruginosa is an opportunistic pathogen that causes life-threatening infections .", "P . aeruginosa disease is increasing in prevalence while bacteria continue to evolve antibiotic resistance .", "It is not clear how mucosal fluids usually protect against opportunistic pathogens .", "Knowing the ...	2017
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "livestock", "medicine and health sciences", "ruminants", "african trypanosomiasis", "geographical locations", "tropical diseases", "vertebrates", "parasitic diseases", "animals", "mammals", "neglected tropical diseases", "infectious disease control", "africa", "veterinary science", "vet...	Past and Ongoing Tsetse and Animal Trypanosomiasis Control Operations in Five African Countries: A Systematic Review	journal.pntd.0005247	null	[ [ "Animal African Trypanosomiasis ( AAT ) and its primary vector , the tsetse , are among the biggest constraints to sustainable livestock production in Africa [1] .", "Although extensive trypanosomiasis and tsetse ( T&T ) control operations have been running since the beginning of the 20th century , tsetse...	[ "Control operations targeting Animal African Trypanosomiasis and its primary vector , the tsetse , were covering approximately 128 , 000 km2 of Africa in 2001 , which is a mere 1 . 3% of the tsetse infested area .", "Although extensive trypanosomiasis and tsetse ( T&T ) control operations have been running since ...	[ "Despite decades of control efforts targeting Animal African Trypanosomiasis , its distribution has hardly receded and the situation in sub-Saharan Africa has recently been described as “serious and deteriorating” .", "This disease of livestock affects farmers’ livelihood and welfare , food security and poses a t...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "neural networks", "neuroscience", "surgical and invasive medical procedures", "mathematics", "signs and symptoms", "algebra", "network analysis", "epilepsy", "computer and information sciences", "lesions", "surgical resect...	Controlling seizure propagation in large-scale brain networks	journal.pcbi.1006805	null	[ [ "Propagation of activity through a network is a non-stationary spatiotemporal process and is the most fundamental representation of information processing in the brain [1 , 2] .", "In task conditions , as the behavioral dynamics unfold , brain activity simultaneously evolves in a hierarchy of characterist...	[ "Information transmission in the human brain is a fundamentally dynamic network process .", "In partial epilepsy , this process is perturbed and highly synchronous seizures originate in a local network , the so-called epileptogenic zone ( EZ ) , before recruiting other close or distant brain regions .", "We stu...	[ "Epilepsy is characterized by perturbed dynamics that originate in a local network before spreading to other brain regions .", "We studied patient-specific brain network models of epilepsy patients , comprising 88 nodes equipped with region specific neural mass models capable of demonstrating epileptiform dischar...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computer applications", "biomacromolecule-ligand interactions", "protein interactions", "molecular dynamics", "small molecules", "macromolecular assemblies", "regulatory proteins", "computer-aided design", "chemical biology", "molecular mechanics", "computerized simulations", "protein structu...	Surface Dynamics in Allosteric Regulation of Protein-Protein Interactions: Modulation of Calmodulin Functions by Ca2+	journal.pcbi.1003028	null	[ [ "Elucidating the basic principles governing molecular recognition in biological systems is important for advancing our understanding of the organization and functioning of biological networks , both metabolic and signaling , and hence for the development of pharmacological tools for the correction of aberrant...	[ "Knowledge of the structural basis of protein-protein interactions ( PPI ) is of fundamental importance for understanding the organization and functioning of biological networks and advancing the design of therapeutics which target PPI .", "Allosteric modulators play an important role in regulating such interacti...	[ "Protein-protein interactions ( PPI ) play an essential role in virtually all physiological processes .", "Knowledge of the principles governing PPI is of fundamental importance for understanding the organization and functioning of biological systems .", "Furthermore , a number of human diseases intractable to ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral persistence and latency", "virology", "biology", "microbiology" ]	Unbiased Mutagenesis of MHV68 LANA Reveals a DNA-Binding Domain Required for LANA Function In Vitro and In Vivo	journal.ppat.1002906	null	[ [ "Rhadinovirus infections are associated with a number of lymphoproliferative diseases .", "In the case of the human virus , Kaposi's sarcoma-associated herpesvirus ( KSHV , HHV-8 ) , there is tight association between KSHV and Kaposi's sarcoma ( sporadic , endemic and HIV-associated forms of Kaposi's sarc...	[ "The Latency-Associated Nuclear Antigen ( LANA ) , encoded by ORF73 , is a conserved gene among the γ2-herpesviruses ( rhadinoviruses ) .", "The Kaposi's Sarcoma-Associated Herpesvirus ( KSHV ) LANA is consistently expressed in KSHV-associated malignancies .", "In the case of the rodent γ2-herpesvirus , murine ...	[ "The human gammaherpesviruses Epstein-Barr virus ( EBV ) and Kaposi's sarcoma-associated herpesvirus ( KSHV ) are tightly associated with a number of different cancers .", "Unfortunately , due to their very narrow host tropism , characterizing the pathogenesis of these viruses has been difficult .", "Infection ...	2012
[ "Introduction", "Results and Discussion", "Conclusions", "Methods" ]	[]	Predicting Epidemic Risk from Past Temporal Contact Data	journal.pcbi.1004152	null	[ [ "Being able to promptly identify who , in a system , is at risk of infection during an outbreak is key to the efficient control of the epidemic .", "The explicit pattern of potential disease-transmission contacts has been extensively used to this purpose in the framework of theoretical studies of epidemic...	[ "Understanding how epidemics spread in a system is a crucial step to prevent and control outbreaks , with broad implications on the system’s functioning , health , and associated costs .", "This can be achieved by identifying the elements at higher risk of infection and implementing targeted surveillance and cont...	[ "Following the emergence of a transmissible disease epidemic , interventions and resources need to be prioritized to efficiently control its spread .", "While the knowledge of the pattern of disease-transmission contacts among hosts would be ideal for this task , the continuously changing nature of such pattern m...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemical compounds", "molecular probe techniques", "293t cells", "enzymes", "biological cultures", "immunoblotting", "enzymology", "protein abundance", "organic compounds", "immunoprecipitation", "basic amino acids", "amino acids", "molecular biology techniques", "cellular structures and ...	Regulation of the Abundance of Kaposi’s Sarcoma-Associated Herpesvirus ORF50 Protein by Oncoprotein MDM2	journal.ppat.1005918	null	[ [ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) , also referred to as human herpesvirus-8 ( HHV-8 ) , is the etiologic agent of Kaposi’s sarcoma ( KS ) , primary effusion lymphomas ( PELs ) and multicentric Castleman’s disease [1–3] .", "Numerous lines of evidence have shown that both KSHV latent and ly...	[ "The switch between latency and the lytic cycle of Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is controlled by the expression of virally encoded ORF50 protein .", "Thus far , the regulatory mechanism underlying the protein stability of ORF50 is unknown .", "Our earlier studies have demonstrated that a pro...	[ "The switch of Kaposi’s sarcoma-associated herpesvirus ( KSHV ) from latency to lytic replication is an essential process for controlling viral dissemination and the pathogenesis of KSHV-associated diseases .", "The virally encoded ORF50 protein is known as the master controller of viral reactivation .", "We pr...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "animal types", "medicine and health sciences", "health education and awareness", "pathology and laboratory medicine", "statistics", "pathogens", "tropical diseases", "geographical locations", "vertebrates", "india", "microbiology", "pets and companion animals", "dogs", "animals", "mamma...	Knowledge, attitudes and practices (KAP) towards rabies and free roaming dogs (FRD) in Panchkula district of north India: A cross-sectional study of urban residents	journal.pntd.0007384	null	[ [ "An estimated 59 , 000 human deaths occur annually due to rabies in the world , and 99% of this global mortality is attributed to the transmission of the virus through dog-bites [1] .", "The disease is endemic in Asia with India reporting the highest number of human deaths within the region , primarily am...	[ "Canine rabies is endemic in urban India .", "A questionnaire was administered to 204 residents of the urbanised municipality of Panchkula in north India to assess the influence of gender , age , family size , social status and dog ownership , over the knowledge , attitudes and practices ( KAP ) towards rabies co...	[ "An enhanced level of awareness regarding rabies and management of dog-bite wounds is usually expected of urban residents owing to improved health care facilities and superior avenues for information dissemination .", "This perception can be misleading as gaps were found in the knowledge of residents of the Munic...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "cell biology/cell adhesion", "microbiology/parasitology" ]	Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process	journal.ppat.1000322	null	[ [ "Invasion of red blood cells ( RBCs ) is one of the critical points in the erythrocytic life cycle of the malaria parasite Plasmodium falciparum .", "The invasive form of the parasite , the merozoite , harbours a set of specialized secretory organelles , in particular two varieties called rhoptries and mi...	[ "A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes .", "Entry into the host cell requires the apical membrane antigen 1 ( AMA-1 ) , a type I transmembrane protein located in the micronemes of the merozoite .", "Although AMA-1 is evolving into...	[ "Malaria is one of the most lethal parasitic diseases worldwide , causing more than 1 million fatalities per annum .", "Drug resistance is widespread , and a vaccine is not available .", "One of the leading blood stage vaccine candidates is the apical membrane antigen 1 ( AMA-1 ) , which is well-conserved among...	2009
[ "Introduction", "Results", "Discussion", "Materials & methods" ]	[ "biotechnology", "plant anatomy", "population genetics", "ploidy", "brassica", "plant science", "model organisms", "genetically modified plants", "experimental organism systems", "sequence motif analysis", "population biology", "plants", "genetic engineering", "arabidopsis thaliana", "re...	Fruit weight is controlled by Cell Size Regulator encoding a novel protein that is expressed in maturing tomato fruits	journal.pgen.1006930	null	[ [ "Rapid morphological diversification among closely related organisms often arise in response to strong selection pressures such as those imposed by domestication .", "Starting approximately 10 , 000 years ago , during the Neolithic period , human societies began the transformation from a hunting and gathe...	[ "Increases in fruit weight of cultivated vegetables and fruits accompanied the domestication of these crops .", "Here we report on the positional cloning of a quantitative trait locus ( QTL ) controlling fruit weight in tomato .", "The derived allele of Cell Size Regulator ( CSR-D ) increases fruit weight predo...	[ "Starting about 10 , 000 years ago , during the Neolithic period , human societies began the transformation from a hunting and gathering-dependent lifestyle to an agrarian lifestyle .", "This transformation was accompanied by plant and animal domestication .", "Tomato shows a huge increase in fruit weight that ...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "parastic protozoans", "medicine", "trypanosoma", "drug research and development", "drugs and devices", "protozoology", "biology", "microbiology" ]	Benznidazole and Posaconazole in Experimental Chagas Disease: Positive Interaction in Concomitant and Sequential Treatments	journal.pntd.0002367	null	[ [ "The use of a DNA probe targeted against Trypanosoma cruzi kinetoplast DNA extracted from mummified Andean humans demonstrated that Chagas disease was highly prevalent in the Southern Andean coastal area 9 , 000 years ago [1] .", "Currently , an estimated 8 to 10 million people are infected with T . cruzi...	[ "Current chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy , particularly in the chronic phase , with frequent side effects that can lead to treatment discontinuation .", "Combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxi...	[ "In this study , we investigated the efficacy of posaconazole in combination with benznidazole against Trypanosoma cruzi acute infections in mice , to support the potential clinical evaluation of such combination therapy for Chagas disease .", "The curative action of benznidazole/posaconazole combinations was exp...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "virology/host antiviral responses", "immunology/innate immunity" ]	Ebola Zaire Virus Blocks Type I Interferon Production by Exploiting the Host SUMO Modification Machinery	journal.ppat.1000493	null	[ [ "Ebola Zaire virus ( EBOV ) causes severe hemorrhagic fever in humans , with case fatality rates as high as 90% in large outbreaks in Africa [1] .", "Dendritic cells ( DCs ) and macrophages are the main initial targets of EBOV infection [2]–[4] .", "A series of studies have shown that EBOV inhibits th...	[ "Ebola Zaire virus is highly pathogenic for humans , with case fatality rates approaching 90% in large outbreaks in Africa .", "The virus replicates in macrophages and dendritic cells ( DCs ) , suppressing production of type I interferons ( IFNs ) while inducing the release of large quantities of proinflammatory ...	[ "Ebola Zaire virus causes severe hemorrhagic fever in humans that is fatal in almost 90% of cases .", "The rapid spread of the virus to macrophages and dendritic cells results in the release of high levels of inflammatory cytokines , causing shock and bleeding .", "The ability of Ebola virus to overwhelm host d...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "innate immune system", "medicine and health sciences", "neurochemistry", "immune physiology", "cytokines", "pathology and laboratory medicine", "parasite replication", "immunology", "tropical diseases", "microbiology", "parasitic diseases", "protozoan life cycles", "neuroscience", "parasi...	Human Neutrophil Peptide 1 as immunotherapeutic agent against Leishmania infected BALB/c mice	journal.pntd.0006123	null	[ [ "Leishmaniasis is as an important neglected tropical disease in poverty-stricken countries of Africa , South America , and Asia [1 , 2] .", "Leishmaniasis has three major manifestations: Visceral leishmaniasis , cutaneous leishmaniasis and mucocutaneous leishmaniasis [3] .", "Considering the complex l...	[ "Human Neutrophil Peptide 1 ( HNP1 ) produced by neutrophils , is a well-known antimicrobial peptide which plays a role both in innate as well as in adaptive immunity and is under intensive investigation as a potential therapeutic agent .", "Previous in vitro experiments have indicated the leishmaniacidal effect ...	[ "The outbreak level of cutaneous leishmaniasis is approximated between one and 1 . 5 million individuals per year .", "Owning to several disadvantages of current therapies , special attention to expand novel and efficient therapies has been demanded .", "Among Anti-Microbial Peptides ( AMPs ) , Human Neutrophil...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "structural genomics", "cell biology", "chromosome biology", "chromosome structure and function", "gene expression", "genetics", "biology and life sciences", "epigenetics", "genomics", "chromatin", "cell differentiation", "chromosomes", "histone modification" ]	Copy Number Variation Is a Fundamental Aspect of the Placental Genome	journal.pgen.1004290	null	[ [ "While the accumulation of somatic copy number variations ( CNVs ) has been proposed to be a result of the aging process , predisposing cell types to cancer progression and neurological diseases , an alternate hypothesis is that they are a normal—or even essential—part of cell biology [1] , [2] .", "In su...	[ "Discovery of lineage-specific somatic copy number variation ( CNV ) in mammals has led to debate over whether CNVs are mutations that propagate disease or whether they are a normal , and even essential , aspect of cell biology .", "We show that 1 , 000N polyploid trophoblast giant cells ( TGCs ) of the mouse pla...	[ "Generally , every mammalian cell has the same complement of each part of its genome .", "However , copy number variation ( CNV ) can occur , where , compared to the rest of its genome , a cell has either more or less of a specific genomic region .", "It is unknown whether CNVs cause disease , or whether they a...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dengue virus", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "viral transmission and infection", "statistics", "pathogens", "metaanalysis", "immunology", "microbiology", "viruses", "developmental biology", ...	Does prior dengue virus exposure worsen clinical outcomes of Zika virus infection? A systematic review, pooled analysis and lessons learned	journal.pntd.0007060	null	[ [ "Zika virus is a flavivirus primarily transmitted by Aedes aegypti mosquitos and is the causative agent of a recent global outbreak of exanthematous febrile illness complicated by Guillain-Barre syndrome ( GBS ) , microcephaly and other birth defects [1] .", "ZIKV was first discovered in Uganda in 1947 an...	[ "Zika virus ( ZIKV ) recently caused a pandemic complicated by Guillain-Barre syndrome ( GBS ) and birth defects .", "ZIKV is structurally similar to the dengue viruses ( DENV ) and in vitro studies suggest antibody dependent enhancement occurs in ZIKV infections preceded by DENV; however , the clinical significa...	[ "Zika virus ( ZIKV ) is a mosquito borne virus that recently caused a large epidemic with some cases complicated by ascending paralysis ( Guillain-Barre syndrome ) and birth defects .", "One major concern is that such complications may be more common in those who have had previous infection with the closely relat...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "immunology", "biology", "microbiology", "molecular cell biology" ]	Late Repression of NF-κB Activity by Invasive but Not Non-Invasive Meningococcal Isolates Is Required to Display Apoptosis of Epithelial Cells	journal.ppat.1002403	null	[ [ "The exclusive human bacterium Neisseria meningitidis ( the meningococcus ) is a major cause of infectious diseases worldwide , including meningitis and fulminant sepsis that are associated with significant morbidity and case fatality rates ranging from 10 to 50% in patients with severe septicaemia [1] , [2] ...	[ "Meningococcal invasive isolates of the ST-11 clonal complex are most frequently associated with disease and rarely found in carriers .", "Unlike carriage isolates , invasive isolates induce apoptosis in epithelial cells through the TNF-α signaling pathway .", "While invasive and non-invasive isolates are both ...	[ "Strains of Neisseria meningitidis isolated from patients induce apoptotic cell death through the TNF-α pathway , whereas strains isolated from healthy carriage isolates do not .", "Part of the difference has been shown to arise from differential shedding of the type 1 TNF-α receptor ( TNFR1 ) from the surface of...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Escherichia coli α-Hemolysin Counteracts the Anti-Virulence Innate Immune Response Triggered by the Rho GTPase Activating Toxin CNF1 during Bacteremia	journal.ppat.1004732	null	[ [ "Bacteremia caused by extraintestinal strains of pathogenic Escherichia coli is a leading cause of death worldwide [1 , 2] .", "Among these pathogens , uropathogenic E . coli ( UPEC ) is a major etiological agent of bacteremia [1 , 2] .", "Therefore , it is essential to define the mechanisms by which ...	[ "The detection of the activities of pathogen-encoded virulence factors by the innate immune system has emerged as a new paradigm of pathogen recognition .", "Much remains to be determined with regard to the molecular and cellular components contributing to this defense mechanism in mammals and importance during i...	[ "The pathogenic potentials of most microbes depend on a repertoire of virulence factors .", "Despite major progress in the understanding of the molecular mechanisms underlying the activities of bacterial effectors , little is known about how they cooperate during infection to overcome host immune defenses and pro...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "cell physiology", "medicine and health sciences", "enzymes", "metabolic networks", "enzymology", "microbiology", "cell metabolism", "metabolites", "network analysis", "enzyme metabolism", "bacterial genetics", "pharmacology", "microbial genetics", "drug metabolism", "e...	Cellular determinants of metabolite concentration ranges	journal.pcbi.1006687	null	[ [ "Advances in systems biology studies have been propelled by the availability of high-quality genome-scale metabolic reconstructions for many organisms across all kingdoms of life [1] .", "Metabolic network reconstructions contain information about metabolites and reactions through which they are transform...	[ "Cellular functions are shaped by reaction networks whose dynamics are determined by the concentrations of underlying components .", "However , cellular mechanisms ensuring that a component’s concentration resides in a given range remain elusive .", "We present network properties which suffice to identify compo...	[ "We present a computational approach for inferring concentration ranges from genome-scale metabolic models .", "The approach specifies a determinant and molecular mechanism underling facile control of concentration ranges for components in large-scale cellular networks .", "Most importantly , the predictions ab...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "heme", "medicine and health sciences", "parasite groups", "plasmodium", "drugs", "population genetics", "microbiology", "parasitology", "antimalarials", "apicomplexa", "metabolites", "pharmacology", "population biology", "drug metabolism", "antimicrobial resistance", "proteins", "ch...	Evolution of Fitness Cost-Neutral Mutant PfCRT Conferring P. falciparum 4-Aminoquinoline Drug Resistance Is Accompanied by Altered Parasite Metabolism and Digestive Vacuole Physiology	journal.ppat.1005976	null	[ [ "Human malaria remains a leading global health scourge in part due to multidrug resistance mechanisms evolved by Plasmodium falciparum , the protozoan species responsible for the most severe forms of disease [1] .", "Artemisinin-based combination therapies ( ACTs ) are the current first-line means of cont...	[ "Southeast Asia is an epicenter of multidrug-resistant Plasmodium falciparum strains .", "Selective pressures on the subcontinent have recurrently produced several allelic variants of parasite drug resistance genes , including the P . falciparum chloroquine resistance transporter ( pfcrt ) .", "Despite signific...	[ "Point mutations in the Plasmodium falciparum chloroquine resistance transporter ( PfCRT ) earlier thwarted the clinical efficacy of chloroquine , the former gold standard , and constitute a major determinant of parasite susceptibility to antimalarial drugs .", "Recently , we reported that the highly mutated Camb...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "plant science", "medicine and health sciences", "infectious disease epidemiology", "epidemiology", "disease dynamics", "disease surveillance", "plant pathology", "biology and life sciences", "spatial epidemiology", "disease vectors", "disease informatics" ]	International Dispersal of Dengue through Air Travel: Importation Risk for Europe	journal.pntd.0003278	null	[ [ "Dengue has emerged as the most important viral mosquito-borne disease globally , taking on pandemic proportions with a 30-fold increase in disease burden over the last half-century [1]–[4] .", "The global burden of dengue is difficult to estimate but ranges from 50 to 390 million infections per year [4] ...	[ "The worldwide distribution of dengue is expanding , in part due to globalized traffic and trade .", "Aedes albopictus is a competent vector for dengue viruses ( DENV ) and is now established in numerous regions of Europe .", "Viremic travellers arriving in Europe from dengue-affected areas of the world can bec...	[ "The global disease burden of dengue is staggering .", "Continuous expansion and vaccine failures illustrate the limitations of current dengue control efforts .", "Novel approaches and additional tools are required to combat and contain the disease .", "In Europe , dengue infections are rare and the last outb...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "cell binding", "cell physiology", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "vertebrates", "cloning", "animals", "mammals", "retroviruses", "viruses", "immunodef...	Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability	journal.ppat.1005537	null	[ [ "Generating protective antibody responses by vaccination is the ultimate goal of an effective HIV vaccine [1–4] .", "As such , a number of highly potent bnAbs targeting major sites of HIV-1 Env vulnerability such as the CD4bs [5–8] , peptido-glycans of variable loops V1 , V2 and V3 [9–12] , the membrane-p...	[ "The simian immunodeficiency virus ( SIV ) challenge model of lentiviral infection is often used as a model to human immunodeficiency virus type 1 ( HIV-1 ) for studying vaccine mediated and immune correlates of protection .", "However , knowledge of the structure of the SIV envelope ( Env ) glycoprotein is limit...	[ "An antibody-based approach targeting human immunodeficiency virus ( HIV ) envelope ( Env ) protein may eventually prove to be effective in treating or preventing HIV infection .", "However , before any candidate HIV treatment or vaccine can be tested in humans , it must first be evaluated in nonhuman primates ( ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "immunology", "biology", "microbiology", "protozoology" ]	Progressive Visceral Leishmaniasis Is Driven by Dominant Parasite-induced STAT6 Activation and STAT6-dependent Host Arginase 1 Expression	journal.ppat.1002417	null	[ [ "In humans , active visceral leishmaniasis ( VL ) , caused by the intracellular protozoan Leishmania donovani , is a progressive , potentially fatal infection characterized by chronic , fever , hepatosplenomegaly , pancytopenia , and profound cachexia .", "VL remains a significant cause of morbidity and m...	[ "The clinicopathological features of the hamster model of visceral leishmaniasis ( VL ) closely mimic active human disease .", "Studies in humans and hamsters indicate that the inability to control parasite replication in VL could be related to ineffective classical macrophage activation .", "Therefore , we hyp...	[ "Visceral leishmaniasis ( VL ) , caused by the intracellular protozoan Leishmania donovani , is a progressive , potentially fatal infection found in many resource-poor regions of the world .", "We initiated these studies of an experimental model of VL to better understand the molecular and cellular determinants u...	2012

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