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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "chemical compounds", "organic compounds", "toluene", "physiological parameters", "aromatic hydrocarbons", "pharmacology", "drug metabolism", "hydrocarbons", "chemistry", "iodides", "hematology", "xylenes", "pharmacokinetics", "blood", "...	Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction	journal.pcbi.1004495	null	[ [ "Developing physiologically-based pharmacokinetic ( PBPK ) models for chemicals can be resource-intensive , as the formulation of new PBPK models is dictated by multiple factors .", "These factors include intended use for the model , target organism , target subpopulation ( e . g . , life stage , gender )...	[ "Developing physiologically-based pharmacokinetic ( PBPK ) models for chemicals can be resource-intensive , as neither chemical-specific parameters nor in vivo pharmacokinetic data are easily available for model construction .", "Previously developed , well-parameterized , and thoroughly-vetted models can be a gr...	[ "Physiologically-based pharmacokinetic ( PBPK ) models are complex kinetic models describing the absorption , distribution , metabolism and excretion of chemicals in humans or animals in vivo .", "They can be utilized in many applications , such as dosimetry testing , toxicological investigations , and chemical r...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "recreation", "decision theory", "decision making", "engineering and technology", "applied mathematics", "social sciences", "mathematical models", "neuroscience", "problem solving", "decision analysis", "cognitive psychology", "mathematics", "statistics (mathematics)", "management engineer...	An entropic barriers diffusion theory of decision-making in multiple alternative tasks	journal.pcbi.1005961	null	[ [ "Decision-making has been studied in great detail relying on binary choices by the Two-Alternative Forced-Choice paradigm ( 2AFC ) .", "In 2AFC tasks , choices are made between two alternatives with limited information while speed and accuracy are registered .", "In addition , for simplicity , in the ...	[ "We present a theory of decision-making in the presence of multiple choices that departs from traditional approaches by explicitly incorporating entropic barriers in a stochastic search process .", "We analyze response time data from an on-line repository of 15 million blitz chess games , and show that our model ...	[ "Decision-making has been studied in great detail relying on binary choices , modeled as the noisy accumulation of a decision variable to a threshold .", "We show that it breaks down when used to describe real-life human decision involving multiple options .", "We show instead that including obstacles in the di...	2018
[ "Introduction", "Models", "Results", "Discussion" ]	[]	A General Framework for Thermodynamically Consistent Parameterization and Efficient Sampling of Enzymatic Reactions	journal.pcbi.1004195	null	[ [ "Since the seminal work of Michaelis and Menten [1] , enzyme kinetics theory has been developed for most catalytic mechanisms , captured as a series of elementary reactions representing events at molecular level , i . e . binding and release of reactants from enzyme intermediates and catalysis .", "The pa...	[ "Kinetic models provide the means to understand and predict the dynamic behaviour of enzymes upon different perturbations .", "Despite their obvious advantages , classical parameterizations require large amounts of data to fit their parameters .", "Particularly , enzymes displaying complex reaction and regulato...	[ "Kinetic models enable understanding and prediction of the dynamic behaviour of enzymatic reactions .", "Different frameworks have been proposed to parameterize enzymatic reactions using approximate expressions while maintaining thermodynamic consistency .", "Approximate expressions have been particularly sough...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "transfection", "luciferase", "enzymes", "messenger rna", "microbiology", "enzymology", "dna damage", "immunoprecipitation", "dna", "molecular biology techniques", "research and analysis methods", "genome complexity", "genomics", "proteins", "oxidoreductases", "ubiquitination", "vira...	Ring finger protein 121 is a potent regulator of adeno-associated viral genome transcription	journal.ppat.1007988	null	[ [ "Adeno-associated viruses ( AAVs ) rely on co-infection of the host cell by a helper virus as well as several host factors for replication [1] .", "The 4 . 7kb single stranded DNA AAV genome contains two open reading frames flanked by two inverted terminal repeats ( ITRs ) packaged into an icosahedral cap...	[ "Adeno-associated viruses ( AAV ) are Dependoparvoviruses that have shown promise as recombinant vectors for gene therapy .", "While infectious pathways of AAV are well studied , gaps remain in our understanding of host factors affecting vector genome expression .", "Here , we map the role of ring finger protei...	[ "Recombinant AAV vectors are at the forefront of clinical gene therapy .", "There is a need to better understand the mechanisms dictating AAV transduction in the host .", "Here , we identify a network of host proteins involving RNF121 , p97 and the DNA damage machinery as potent factors regulating AAV genome tr...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "immunology", "biology", "immune response" ]	A Lipopeptide Facilitate Induction of Mycobacterium leprae Killing in Host Cells	journal.pntd.0001401	null	[ [ "The introduction of multidrug therapy in 1982 and the WHO campaign for the ‘elimination of leprosy as a public health problem’ , have contributed greatly to the decrease in the prevalence rate over the past three decades .", "But leprosy still remains to be a public health problem in some countries , and...	[ "Little is known of the direct microbicidal activity of T cells in leprosy , so a lipopeptide consisting of the N-terminal 13 amino acids lipopeptide ( LipoK ) of a 33-kD lipoprotein of Mycobacterium leprae , was synthesized .", "LipoK activated M . leprae infected human dendritic cells ( DCs ) to induce the prod...	[ "We observed that LipoK ( Mycobacterium leprae lipopeptide with 13 amino acids ) is capable of inducing a good immune response in M . leprae infected human dendritic cells ( DCs ) .", "These activated DCs had up-regulated expression of costimulatory molecule CD86 as well as CD83 ( well known maturation marker ) o...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "microbiology", "biophysics" ]	VirE2: A Unique ssDNA-Compacting Molecular Machine	journal.pbio.0060044	Combining single-molecule techniques and biological assays, the authors show that VirE2 proteins could mediate the active translocation ofAgrobacterium's genetic material into plant cells.	[ [ "Agrobacterium tumefaciens is a Gram-negative pathogenic bacterium able to transfer and integrate up to 150 , 000-bases-long single-stranded DNA ( ssDNA ) into the infected cell nuclear genome [1] .", "In Agrobacterium pathogenesis , the sequence of ssDNA to be transferred ( T-DNA ) and the genes encoding...	[ "The translocation of single-stranded DNA ( ssDNA ) across membranes of two cells is a fundamental biological process occurring in both bacterial conjugation and Agrobacterium pathogenesis .", "Whereas bacterial conjugation spreads antibiotic resistance , Agrobacterium facilitates efficient interkingdom transfer ...	[ "The importation of genetic material into cells is a common and fundamental mechanism occurring in bacterial conjugation , DNA uptake , and Agrobacterium plant infection and is , for instance , responsible for antibiotic resistance spread .", "Previous studies suggested that this process relied only on the activi...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "bacterial diseases", "infectious diseases", "immunity", "innate immunity", "immunology", "biology" ]	Shigella Type III Secretion Protein MxiI Is Recognized by Naip2 to Induce Nlrc4 Inflammasome Activation Independently of Pkcδ	journal.ppat.1003926	null	[ [ "Recognition of intracellular pathogenic bacteria by members of the nucleotide-binding domain and leucine-rich repeat containing ( NLR ) family triggers immune responses against bacterial infection [1] , [2] .", "A major response against several pathogenic Gram-negative bacteria , including Salmonella , L...	[ "Recognition of intracellular pathogenic bacteria by members of the nucleotide-binding domain and leucine-rich repeat containing ( NLR ) family triggers immune responses against bacterial infection .", "A major response induced by several Gram-negative bacteria is the activation of caspase-1 via the Nlrc4 inflamm...	[ "Shigella are bacterial pathogens that are the cause of bacillary dysentery .", "An important feature of Shigella is their ability to invade the cytoplasm of host epithelial cells and macrophages .", "A major component of host recognition of Shigella invasion is the activation of the inflammasome , a molecular ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "immune cells", "clinical immunology", "immunity", "hiv", "immunology", "biology", "viral diseases" ]	Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection	journal.ppat.1002529	null	[ [ "A major challenge to the development of effective vaccines against highly variable viruses is their ability to adapt to evade host immune responses [1]–[4] .", "During HIV-1 infection , for example , immune escape mutations develop which impair the ability of both CD8+ T cell responses and neutralizing a...	[ "Deep sequencing technologies have the potential to transform the study of highly variable viral pathogens by providing a rapid and cost-effective approach to sensitively characterize rapidly evolving viral quasispecies .", "Here , we report on a high-throughput whole HIV-1 genome deep sequencing platform that co...	[ "The ability of HIV-1 and other highly variable pathogens to rapidly mutate to escape vaccine-induced immune responses represents a major hurdle to the development of effective vaccines to these highly persistent pathogens .", "Application of next-generation or deep sequencing technologies to the study of host pa...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "nucleic acid synthesis", "pathology and laboratory medicine", "bacteriophages", "pathogens", "messenger rna", "microbiology", "dna transcription", "viruses", "bacterial diseases", "enterobacteriaceae", "molecular biology techniques", "rna synthesis", "bacte...	Gifsy-1 Prophage IsrK with Dual Function as Small and Messenger RNA Modulates Vital Bacterial Machineries	journal.pgen.1005975	null	[ [ "The first systematic searches for bacterial sRNA were based on bio-computational identification of conserved genes in intergenic regions [1] .", "The subsequent characterization of these conserved sRNAs identified them as important players in many adaptive and physiological responses .", "These conse...	[ "While an increasing number of conserved small regulatory RNAs ( sRNAs ) are known to function in general bacterial physiology , the roles and modes of action of sRNAs from horizontally acquired genomic regions remain little understood .", "The IsrK sRNA of Gifsy-1 prophage of Salmonella belongs to the latter cla...	[ "As the function of conserved core-genome-encoded small RNAs ( sRNA ) reflects the basic lifestyle of bacteria , the function of non-conserved island-encoded sRNAs remains enigmatic .", "The island-encoded sRNA IsrK belongs to Gifsy-1 prophage of Salmonella .", "Here , we report a complex mechanism in which the...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/bacterial infections", "infectious diseases/neglected tropical diseases", "immunology/immunity to infections", "immunology/innate immunity" ]	Human Complement Regulators C4b-Binding Protein and C1 Esterase Inhibitor Interact with a Novel Outer Surface Protein of Borrelia recurrentis	journal.pntd.0000698	null	[ [ "B . recurrentis , the causative agent of louse-borne relapsing fever is transmitted to humans by contamination of abraded skin with either hemolymph from crushed , infected lice ( Pediculus humanus humanus ) or excreted feces thereof [1] , [2] .", "The last century has seen multiple epidemics of louse-bo...	[ "The spirochete Borrelia recurrentis is the causal agent of louse-borne relapsing fever and is transmitted to humans by the infected body louse Pediculus humanus .", "We have recently demonstrated that the B . recurrentis surface receptor , HcpA , specifically binds factor H , the regulator of the alternative pat...	[ "Borrelia recurrentis , the causal agent of louse-borne relapsing fever is transmitted to humans via infected body lice .", "Infection with B . recurrentis has been achieved only in humans and is accompanied by a systemic inflammatory disease , multiple relapses of fever and massive spirochetemia .", "A key vir...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Modeling the Evolution of Beliefs Using an Attentional Focus Mechanism	journal.pcbi.1004558	null	[ [ "A typical problem that humans encounter , in our complex environment , is to identify those environmental features that are relevant for achieving a desired outcome in a given task .", "This is computationally difficult because the real-world environment displays a large number of environmental features ...	[ "For making decisions in everyday life we often have first to infer the set of environmental features that are relevant for the current task .", "Here we investigated the computational mechanisms underlying the evolution of beliefs about the relevance of environmental features in a dynamical and noisy environment...	[ "When making decisions in our everyday life ( e . g . where to eat ) we first have to identify a set of environmental features that are relevant for the decision ( e . g . the distance to the place , current time or the price ) .", "Although we are able to make such inferences almost effortlessly , this type of p...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "skin", "cell death", "medicine and health sciences", "reproductive system", "integumentary system", "cell processes", "developmental biology", "respiratory system", "pupae", "epidermis", "trachea", "lipids", "fats", "gene expression", "life cycles", "biochemistry", "anatomy", "cel...	Inhibition of a NF-κB/Diap1 Pathway by PGRP-LF Is Required for Proper Apoptosis during Drosophila Development	journal.pgen.1006569	null	[ [ "In Drosophila , bacteria infection triggers NF-κB cascades ( called Toll and IMD ( Immune Deficiency ) ) leading to the production of immune effectors and regulators [1–3] [4] .", "This activation relies on the previous recognition of bacteria derived peptidoglycan ( PGN ) by host Peptidoglycan Recogniti...	[ "NF-κB pathways are key signaling cascades of the Drosophila innate immune response .", "One of them , the Immune Deficiency ( IMD ) pathway , is under a very tight negative control .", "Although molecular brakes exist at each step of this signaling module from ligand availability to transcriptional regulation ...	[ "In multicellular organism such as mammals or insects , activation of innate immune responses occurs following detection of microbes by dedicated receptors called pattern recognition receptors .", "Such immune activation is taking place in immune competent tissue such as the skin , the digestive and respiratory e...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Sm29, but Not Sm22.6 Retains its Ability to Induce a Protective Immune Response in Mice Previously Exposed to a Schistosoma mansoni Infection	journal.pntd.0003537	null	[ [ "The development of a vaccine against schistosomiasis together with chemotherapy would have a great impact in the disease control and elimination .", "The ability of the parasite to evade the host immune system and its complex life cycle make the development of a vaccine against schistososmiasis a difficu...	[ "A vaccine against schistosomiasis would have a great impact in disease elimination .", "Sm29 and Sm22 . 6 are two parasite tegument proteins which represent promising antigens to compose a vaccine .", "These antigens have been associated with resistance to infection and reinfection in individuals living in end...	[ "The development of a vaccine against schistosomiasis together with chemotherapy would have a great impact in the disease control and elimination .", "Sm29 and Sm22 . 6 are two promising antigens that have been associated with resistance to infection/reinfection in humans and also successfully induce protection i...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/comparative genomics", "genetics and genomics/genome projects", "computational biology/genomics", "computer science/information technology", "genetics and genomics/bioinformatics" ]	A Survey of Genomic Traces Reveals a Common Sequencing Error, RNA Editing, and DNA Editing	journal.pgen.1000954	null	[ [ "With the exception of infrequent random somatic mutations , it is widely believed that the same genomic content should be fixed in an organism throughout its lifetime .", "This information will also serve as a template for exact RNA copies .", "Proteins that can modify genomic content , nevertheless ...	[ "While it is widely held that an organism's genomic information should remain constant , several protein families are known to modify it .", "Members of the AID/APOBEC protein family can deaminate DNA .", "Similarly , members of the ADAR family can deaminate RNA .", "Characterizing the scope of these events i...	[ "Most biomedical , genomic research begins with the painstaking assembly of a “reference genome” for the organism of interest .", "Implicit in this process is an assumption that genomic information is constant throughout an organism .", "There are enzymes , however , that can change , or “edit , ” genomic infor...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "applied microbiology", "emerging infectious diseases", "virology", "biology", "microbiology", "viral disease diagnosis" ]	International External Quality Assessment of Molecular Detection of Rift Valley Fever Virus	journal.pntd.0002244	null	[ [ "Rift Valley fever ( RVF ) is a mosquito-borne viral zoonosis that primarily affects animals but also has the capacity to infect humans .", "An epizootic of RVF is usually first indicated by a wave of unexplained abortions as infected pregnant livestock abort virtually 100% of fetuses .", "The disease...	[ "Rift Valley fever ( RVF ) is a viral zoonosis that primarily affects animals resulting in considerable economic losses due to death and abortions among infected livestock .", "RVF also affects humans with clinical symptoms ranging from an influenza-like illness to a hemorrhagic fever .", "Over the past years ,...	[ "Rift Valley fever ( RVF ) is a zoonotic viral disease posing an increasing threat to animals and humans worldwide .", "Recent severe outbreaks of the disease in animal and human populations in endemic regions and outside the disease's traditional geographic boundaries necessitate the need for evaluating the diag...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/social and behavioral determinants of health", "public health and epidemiology/infectious diseases", "public health and epidemiology/health services research and economics", "public health and epidemiology/health policy" ]	“It Is Me Who Endures but My Family That Suffers”: Social Isolation as a Consequence of the Household Cost Burden of Buruli Ulcer Free of Charge Hospital Treatment	journal.pntd.0000321	null	[ [ "Buruli ulcer disease ( henceforth , Bu ) is the third most common mycobacterial disease in humans , after tuberculosis and leprosy [1]; nonetheless , despite the dramatic increase in incidence rates in West Africa during the last decade , it remains largely neglected [2] .", "Its causative agent , Mycoba...	[ "Despite free of charge biomedical treatment , the cost burden of Buruli ulcer disease ( Bu ) hospitalisation in Central Cameroon accounts for 25% of households' yearly earnings , surpassing the threshold of 10% , which is generally considered catastrophic for the household economy , and calling into question the s...	[ "The cost burden of free of charge Buruli ulcer disease ( Bu ) hospital treatment is not sustainable for a majority of patients and their families in Central Cameroon .", "The long term nature of Bu taxes the patients' and their families' resources often to a breaking point , consequently often leading to the aba...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "developmental biology", "menstrual abnormalities", "reproductive system", "obstetrics and gynecology", "genetics", "epigenetics", "biology", "dna modification", "anatomy and physiology", "sexual reproduction", "cell differentiation", "reproductive physiology" ]	Genome-Wide DNA Methylation Analysis Predicts an Epigenetic Switch for GATA Factor Expression in Endometriosis	journal.pgen.1004158	null	[ [ "Endometriosis is a painful and chronic gynecological disease that affects approximately 10% of reproductive-age women , causing infertility and development of adhesions due to the extrauterine growth of endometrium-like tissue [1] , [2] .", "The molecular cause of endometriosis is multifactorial , with d...	[ "Endometriosis is a gynecological disease defined by the extrauterine growth of endometrial-like cells that cause chronic pain and infertility .", "The disease is limited to primates that exhibit spontaneous decidualization , and diseased cells are characterized by significant defects in the steroid-dependent gen...	[ "Women develop endometriosis when endometrial tissue with altered sensitivity to ovarian hormones grows outside the uterus .", "The persistent survival of these cells results in chronic pelvic pain and infertility .", "Although the origin of the disease remains a mystery , it only occurs in women and menstruati...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "chemical compounds", "pathogens", "immunology", "microbiology", "organic compounds", "electromagnetic radiation", "dna transcription", "acidic amino acids", "amino acids", "bacterial pathog...	L-glutamine Induces Expression of Listeria monocytogenes Virulence Genes	journal.ppat.1006161	null	[ [ "Listeria monocytogenes is a Gram-positive facultative intracellular bacterial pathogen and the causative agent of listeriosis in humans , a disease with deleterious impacts , such as increased risk of meningitis and miscarriage [1] .", "L . monocytogenes invades mammalian cells by expressing surface prot...	[ "The high environmental adaptability of bacteria is contingent upon their ability to sense changes in their surroundings .", "Bacterial pathogen entry into host poses an abrupt and dramatic environmental change , during which successful pathogens gauge multiple parameters that signal host localization .", "The ...	[ "To thrive in the human body and cause disease , bacterial pathogens rely on the expression of a battery of genes , termed virulence genes .", "However , to activate these genes , the bacterium must “know” that it is no longer free-roaming , and has invaded a host .", "Like all life forms , bacterial pathogens ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicinal chemistry", "virology", "chemistry", "chemical reactions", "biology", "antivirals", "microbiology", "photochemical reactions" ]	A Mechanistic Paradigm for Broad-Spectrum Antivirals that Target Virus-Cell Fusion	journal.ppat.1003297	null	[ [ "Advances in antiviral therapeutics have allowed for effective management of specific viral infections , most notably human immunodeficiency virus ( HIV ) [1] .", "Yet , the one-bug-one-drug paradigm of drug discovery is insufficient to meet the looming threat of emerging and re-emerging viral pathogens t...	[ "LJ001 is a lipophilic thiazolidine derivative that inhibits the entry of numerous enveloped viruses at non-cytotoxic concentrations ( IC50≤0 . 5 µM ) , and was posited to exploit the physiological difference between static viral membranes and biogenic cellular membranes .", "We now report on the molecular mechan...	[ "The threat of emerging and re-emerging viruses underscores the need to develop broad-spectrum antivirals .", "LJ001 is a non-cytotoxic , membrane-targeted , broad-spectrum antiviral previously reported to inhibit the entry of many lipid-enveloped viruses .", "Here , we delineate the molecular mechanism that un...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immunology", "microbiology", "parasitic diseases", "protozoan life cycles", "parasitic protozoans", "membrane proteins", "developmental biology", "protozoans", "leishmania", "promastigotes", "cellular structures and organelles...	L-arginine availability and arginase activity: Characterization of amino acid permease 3 in Leishmania amazonensis	journal.pntd.0006025	null	[ [ "Leishmania is the causative agent of leishmaniasis , a complex disease characterized by cutaneous , mucocutaneous or visceral lesions [1–3] .", "It is currently endemic in 98 countries and territories around the world , with an annual incidence estimated at 1 million cases of cutaneous leishmaniasis and ...	[ "Leishmania uses the amino acid L-arginine as a substrate for arginase , enzyme that produces urea and ornithine , last precursor of polyamine pathway .", "This pathway is used by the parasite to replicate and it is essential to establish the infection in the mammalian host .", "L-arginine is not synthesized by...	[ "Leishmania alternates its life cycle between the invertebrate host , in which the promastigote forms reside at pH 7 . 0 and approximately 25°C; and the mammalian host , in which the amastigote forms reside at pH 5 . 0 and approximately 37°C .", "These environmental changes submit the parasite to dynamic undergo ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "genetics and genomics/functional genomics", "genetics and genomics/genetics of the immune system", "genetics and genomics/complex traits", "immunology/immune response", "immunology/innate immunity", "genetics and genomics/genetics of disease", ...	Polymorphisms in Anopheles gambiae Immune Genes Associated with Natural Resistance to Plasmodium falciparum	journal.ppat.1001112	null	[ [ "Human malaria is transmitted by female Anopheles mosquitoes , which vary in vector competence at both the species and individual level [1] .", "In Anopheles gambiae , the main malaria vector in Africa , it has been possible to select laboratory strains for their resistance or susceptibility to Plasmodium...	[ "Many genes involved in the immune response of Anopheles gambiae , the main malaria vector in Africa , have been identified , but whether naturally occurring polymorphisms in these genes underlie variation in resistance to the human malaria parasite , Plasmodium falciparum , is currently unknown .", "Here we carr...	[ "Anopheles gambiae is the main malaria vector in Africa , transmitting the parasite when it blood feeds on human hosts .", "The parasite undergoes several developmental stages in the mosquito to complete its life cycle , during which time it is confronted by the mosquito's immune system .", "The resistance of m...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "medicinal chemistry", "chemistry", "biology", "microbiology" ]	Broad Spectrum Pro-Quorum-Sensing Molecules as Inhibitors of Virulence in Vibrios	journal.ppat.1002767	null	[ [ "Quorum sensing ( QS ) is a process of bacterial cell-cell communication that relies on the production , release , detection , and response to extracellular signaling molecules called autoinducers .", "QS allows groups of bacteria to synchronously alter behavior in response to changes in the population de...	[ "Quorum sensing ( QS ) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers .", "QS allows bacteria to perform collective activities .", "Vibrio cholerae , a pathogen that causes an acute disease , uses QS to repress vir...	[ "The disease cholera , caused by the pathogenic bacterium Vibrio cholerae , is a major health concern in developing regions .", "In order to be virulent , V . cholerae must precisely control the timing of production of virulence factors .", "To do this , V . cholerae uses a cell-cell communication process calle...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "caulobacter", "cell cycle and cell division", "cell processes", "microbiology", "genomic databases", "prokaryotic models", "model organisms", "genome analysis", "bacteria", "research and analysis methods", "genome complexity", "caulobacter crescentus", "syste...	The Coding and Noncoding Architecture of the Caulobacter crescentus Genome	journal.pgen.1004463	null	[ [ "The C . crescentus genome encodes instructions to perform asymmetric cell division using a genetic circuit that integrates transcriptional control from differential chromosome methylation , activation of transcription factors by phosphosignaling pathways , specific proteolysis events , and the subcellular lo...	[ "Caulobacter crescentus undergoes an asymmetric cell division controlled by a genetic circuit that cycles in space and time .", "We provide a universal strategy for defining the coding potential of bacterial genomes by applying ribosome profiling , RNA-seq , global 5′-RACE , and liquid chromatography coupled with...	[ "Caulobacter crescentus is a model system for studying asymmetric cell division , a fundamental process that , through differential gene expression in the two daughter cells , enables the generation of cells with different fates .", "To explore how the genome directs and maintains asymmetry upon cell division , w...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "mathematics", "ecology", "biology", "nonlinear dynamics" ]	Early Warning Signals for Critical Transitions: A Generalized Modeling Approach	journal.pcbi.1002360	null	[ [ "Critical transitions are sudden , long-term changes in complex systems that occur when a threshold is crossed [1] .", "Many systems are known to be at risk of such transitions , including systems in ecology [2] , climate research [3] , economics [4] , sociology [5] and human physiology [6] .", "Examp...	[ "Critical transitions are sudden , often irreversible , changes that can occur in a large variety of complex systems; signals that warn of critical transitions are therefore highly desirable .", "We propose a new method for early warning signals that integrates multiple sources of information and data about the s...	[ "Fisheries , coral reefs , productive farmland , planetary climate , neural activity in the brain , and financial markets are all complex systems that can be susceptible to sudden changes leading to drastic re-organization or collapse .", "A variety of signals based on analysis of time-series data have been propo...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "functional genomics", "genetics", "biology", "evolutionary biology", "evolutionary genetics", "genetics and genomics" ]	Biochemical Diversification through Foreign Gene Expression in Bdelloid Rotifers	journal.pgen.1003035	null	[ [ "Bdelloid rotifers ( Rotifera , Bdelloidea ) are abundant , ubiquitous microinvertebrates that inhabit aqueous habitats [1] .", "They possess an extraordinary and unique combination of characteristics among the Metazoa: they have survived for tens of millions of years without sexual reproduction , while s...	[ "Bdelloid rotifers are microinvertebrates with unique characteristics: they have survived tens of millions of years without sexual reproduction; they withstand extreme desiccation by undergoing anhydrobiosis; and they tolerate very high levels of ionizing radiation .", "Recent evidence suggests that subtelomeric ...	[ "Bdelloid rotifers are tiny invertebrates with unusual characteristics: they withstand stresses , such as desiccation and high levels of ionising radiation , that kill other animals , and they have survived over millions of years without sexual reproduction , which contradicts theories on the evolutionary advantage...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "synthetic biotechnology", "medicine and health sciences", "pathology and laboratory medicine", "fibrinogen", "engineering and technology", "pathogens", "synthetic biology", "microbiology", "peptide libraries", "molecular biology techniques", "glycoproteins", "bacteria", "...	The Structure of Treponema pallidum Tp0751 (Pallilysin) Reveals a Non-canonical Lipocalin Fold That Mediates Adhesion to Extracellular Matrix Components and Interactions with Host Cells	journal.ppat.1005919	null	[ [ "Syphilis is a chronic , multistage disease caused by Treponema pallidum subsp .", "pallidum , with a global burden of 36 million cases and 11 million new infections per year [1] .", "Syphilis remains prevalent in resource-poor settings and the incidence rate is rising in Europe and Britain , the Unit...	[ "Syphilis is a chronic disease caused by the bacterium Treponema pallidum subsp .", "pallidum .", "Treponema pallidum disseminates widely throughout the host and extravasates from the vasculature , a process that is at least partially dependent upon the ability of T . pallidum to interact with host extracellula...	[ "The Treponema pallidum protein , Tp0751 , possesses adhesive properties and has been previously reported to mediate attachment to the host extracellular matrix components laminin , fibronectin , and fibrinogen .", "Herein we demonstrate that Tp0751 adopts an eight-stranded beta barrel-containing lipocalin struct...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience", "neuroscience/theoretical neuroscience", "neuroscience/sensory systems" ]	Cortical Gamma Rhythms Modulate NMDAR-Mediated Spike Timing Dependent Plasticity in a Biophysical Model	journal.pcbi.1000602	null	[ [ "In many systems , synaptic plasticity is believed to depend on the spike timing of the pre- and postsynaptic cells [1] , [2] .", "This spike timing dependent plasticity ( STDP ) has been observed in vivo [3] and has been studied in many in vitro preparations in the context of learning and sensory process...	[ "Spike timing dependent plasticity ( STDP ) has been observed experimentally in vitro and is a widely studied neural algorithm for synaptic modification .", "While the functional role of STDP has been investigated extensively , the effect of rhythms on the precise timing of STDP has not been characterized as well...	[ "Rhythms are well studied phenomena in many animal species .", "Brain rhythms in the gamma frequency range ( 30–90 Hz ) are thought to play a role in attention and memory .", "In this paper , we are interested in how cortical gamma rhythms interact with information specific inputs that also have a significant g...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell motility", "medicine and health sciences", "vesicles", "actin filaments", "vacuoles", "microtubules", "cellular structures and organelles", "cytoskeleton", "digestive system", "endosomes", "contractile proteins", "actins", "proteins", "cell membranes", "gastrointestinal tract", "...	RAB-10 Promotes EHBP-1 Bridging of Filamentous Actin and Tubular Recycling Endosomes	journal.pgen.1006093	null	[ [ "Transmembrane proteins enter cells via several endocytic pathways including clathrin-dependent endocytosis ( CDE ) and a variety of less well understood clathrin-independent endocytosis ( CIE ) mechanisms [1–3] .", "After internalization some receptors will be recycled back to the plasma membrane via the...	[ "EHBP-1 ( Ehbp1 ) is a conserved regulator of endocytic recycling , acting as an effector of small GTPases including RAB-10 ( Rab10 ) .", "Here we present evidence that EHBP-1 associates with tubular endosomal phosphatidylinositol-4 , 5-bisphosphate [PI ( 4 , 5 ) P2] enriched membranes through an N-terminal C2-li...	[ "Endosomes are intracellular organelles that sort protein and lipid components integral to the membrane , as well as more loosely associated lumenal content , for delivery to distinct intracellular destinations .", "Endosomes associated with recycling cargo back to the plasma membrane are often tubular in morphol...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology", "microbiology", "zoology", "parasitology", "helminthology" ]	Detection of Echinococcus multilocularis in Carnivores in Razavi Khorasan Province, Iran Using Mitochondrial DNA	journal.pntd.0001379	null	[ [ "Echinococcus multilocularis is the agent of alveolar echinococcosis , a potentially fatal zoonotic disease [1] , [2] .", "The life cycle of E . multilocularis is sylvatic; adult worms are found in wild carnivores , principally foxes , and in the raccoon dog , wolf , coyote , and jackal , while their meta...	[ "Echinococcus multilocularis is the source of alveolar echinococcosis , a potentially fatal zoonotic disease .", "This investigation assessed the presence of E . multilocularis infection in definitive hosts in the Chenaran region of Razavi Khorasan Province , northeastern Iran .", "Fecal samples from 77 domesti...	[ "Echinococcus multilocularis causes alveolar echinococcosis , a serious zoonotic disease present in many areas of the world .", "The parasite is maintained in nature through a life cycle in which adult worms in the intestine of carnivores transmit infection to small mammals , predominantly rodents , via eggs in t...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Metabolic Constraint-Based Refinement of Transcriptional Regulatory Networks	journal.pcbi.1003370	null	[ [ "The inference of transcriptional regulatory networks ( TRNs ) from high-throughput data is a central challenge in systems biology .", "TRN models provide a mechanistic framework for describing interactions between transcription factors and their target genes .", "Cellular phenotypes are influenced by...	[ "There is a strong need for computational frameworks that integrate different biological processes and data-types to unravel cellular regulation .", "Current efforts to reconstruct transcriptional regulatory networks ( TRNs ) focus primarily on proximal data such as gene co-expression and transcription factor ( T...	[ "Cellular networks , such as metabolic and transcriptional regulatory networks ( TRNs ) , do not operate independently but work together in unison to determine cellular phenotypes .", "Further , the phenotype and architecture of one network constrains the topology of other networks .", "Hence , it is critical t...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Regulatory T Cells in Peripheral Blood and Cerebrospinal Fluid of Syphilis Patients with and without Neurological Involvement	journal.pntd.0002528	null	[ [ "China has experienced an expanding epidemic of syphilis infection in the last 10 years [1] , [2] .", "In 2011 , the national incidence rate was 32 . 04 per 100 , 000 population and 429 , 677 new cases were reported [3] .", "This sexually transmitted disease has reemerged as a significant public healt...	[ "Syphilis , a sexually transmitted disease caused by spirochetal bacterium Treponema pallidum , can progress to affect the central nervous system , causing neurosyphilis .", "Accumulating evidence suggest that regulatory T cells ( Tregs ) may play an important role in the pathogenesis of syphilis .", "However ,...	[ "Syphilis , caused by the bacterium Treponema pallidum , can progress to affect the central nervous system ( CNS ) and cause damage in the brain and spinal cord , which is called neurosyphilis .", "While many affected neurosyphilis patients may not have any symptoms , some of the patients will develop severe symp...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "yeast and fungi", "eukaryotes", "molecular biology", "genetics and genomics" ]	H2A.Z-Mediated Localization of Genes at the Nuclear Periphery Confers Epigenetic Memory of Previous Transcriptional State	journal.pbio.0050081	Recruitment of active genes to the periphery of the yeast nucleus does not require concurrent transcription.	[ [ "The subnuclear localization of DNA has important roles in regulating transcription [1 , 2] .", "In particular , localization of chromatin near the nuclear periphery has well-documented effects on transcription .", "Heterochromatin and developmentally repressed genes localize at the nuclear periphery ...	[ "Many genes are recruited to the nuclear periphery upon transcriptional activation .", "The mechanism and functional significance of this recruitment is unclear .", "We find that recruitment of the yeast INO1 and GAL1 genes to the nuclear periphery is rapid and independent of transcription .", "Surprisingly ,...	[ "Eukaryotic cells control the spatial arrangement of chromosomes; the localization of genes can both reflect and contribute to their transcriptional state .", "A number of genes in the simple eukaryote brewer's yeast are “recruited” to the nuclear periphery through interactions with the nuclear pore complex when ...	2007
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "biotechnology", "taxonomy", "plant anatomy", "stem anatomy", "ferns", "stomata", "phylogenetics", "plant science", "data management", "plant genomics", "plants", "flowering plants", "leaf veins", "computer and information sciences", "plant genetics", "leaves", "short reports", "ev...	Genome downsizing, physiological novelty, and the global dominance of flowering plants	journal.pbio.2003706	null	[ [ "The flowering plants are highly competitive in almost every terrestrial ecosystem , and their rapid rise during the early Cretaceous period irrevocably altered terrestrial primary productivity and global climate [1–3] .", "Terrestrial primary productivity is ultimately determined by the photosynthetic ca...	[ "The abrupt origin and rapid diversification of the flowering plants during the Cretaceous has long been considered an “abominable mystery . ”", "While the cause of their high diversity has been attributed largely to coevolution with pollinators and herbivores , their ability to outcompete the previously dominant...	[ "The angiosperms , commonly referred to as the flowering plants , are the dominant plants in most terrestrial ecosystems , but how they came to be so successful is considered one of the most profound mysteries in evolutionary biology .", "Prevailing hypotheses have suggested that the angiosperms rose to dominance...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure	journal.ppat.1004894	null	[ [ "Naturally acquired immunity is vital in reducing morbidity and mortality from Plasmodium falciparum malaria in endemic areas , where some individuals receive hundreds of infectious mosquito bites per year .", "Humoral responses to P . falciparum may be a critical component of this immunity , and P . falc...	[ "Exposure to Plasmodium falciparum is associated with circulating “atypical” memory B cells ( atMBCs ) , which appear similar to dysfunctional B cells found in HIV-infected individuals .", "Functional analysis of atMBCs has been limited , with one report suggesting these cells are not dysfunctional but produce pr...	[ "A subset of “atypical” memory B cells found in individuals with high exposure to P . falciparum has been hypothesized to be dysfunctional , based on phenotypic similarities to analogous cells found in HIV-infected individuals .", "However , the functional capabilities of these cells have been poorly characterize...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immune cells", "cytokines", "immune activation", "immunity to infections", "immunology", "microbiology", "lymphoid organs", "host-pathogen interaction", "animal models", "adaptive immunity", "mechanisms of resistance and susceptibility", "model organisms", "immune defense", "bacterial pat...	Inflammatory Monocytes and Neutrophils Are Licensed to Kill during Memory Responses In Vivo	journal.ppat.1002457	null	[ [ "Immunological memory is a central feature of the adaptive immune system and relies on the maintenance of antigen-experienced B cells and T cells .", "In general , a memory immune response is faster and stronger than a primary response because of the increased frequency , improved functional characteristi...	[ "Immunological memory is a hallmark of B and T lymphocytes that have undergone a previous encounter with a given antigen .", "It is assumed that memory cells mediate better protection of the host upon re-infection because of improved effector functions such as antibody production , cytotoxic activity and cytokine...	[ "The immune system comprises white blood cells that belong to the innate or the adaptive immune arms .", "Adaptive immune cells such as T and B lymphocytes can give rise to memory cells which mediate long-lived immunity against pathogens .", "During a recall infection , innate immune phagocytic cells such as mo...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "reproductive system", "dna-binding proteins", "nucleotides", "animal models", "germ cells", "model organisms", "molecular biology techniques", "genotyping", "extraction techniques", "sperm", "research and analysis methods", "protein extraction", "artificial...	A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?	journal.pgen.1006190	null	[ [ "The fragile X ( FX ) -related disorders ( FXDs ) are repeat expansion diseases that result from an increase in the length of a CGG/CCG-repeat tract in the 5’ UTR of the FMR1 gene ( reviewed in [1] ) .", "This expansion occurs from an unstable premutation ( PM ) allele that contains 55–200 repeats .", ...	[ "The fragile X-related disorders result from expansion of a CGG/CCG microsatellite in the 5’ UTR of the FMR1 gene .", "We have previously demonstrated that the MSH2/MSH3 complex , MutSβ , that is important for mismatch repair , is essential for almost all expansions in a mouse model of these disorders .", "Here...	[ "The repeat expansion diseases are a group of human genetic disorders that are caused by expansion of a specific microsatellite in a single affected gene .", "How this expansion occurs is unknown , but previous work in various models for different diseases in the group , including the fragile X-related disorders ...	2016
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "mathematics", "biochemistry/chemical biology of the cell", "biochemistry/bioinformatics", "computational biology/metabolic networks", "biotechnology/bioengineering", "biochemistry/theory and simulation" ]	Top-Down Analysis of Temporal Hierarchy in Biochemical Reaction Networks	journal.pcbi.1000177	null	[ [ "The network of interactions that occur between biological components on a range of various spatial and temporal scales confer hierarchical functionality in living cells .", "In order to determine how molecular events organize themselves into coherent physiological functions , in silico approaches are nee...	[ "The study of dynamic functions of large-scale biological networks has intensified in recent years .", "A critical component in developing an understanding of such dynamics involves the study of their hierarchical organization .", "We investigate the temporal hierarchy in biochemical reaction networks focusing ...	[ "Cellular metabolism describes the complex web of biochemical transformations that are necessary to build the structural components , to convert nutrients into “usable energy” by the cell , and to degrade or excrete the by-products .", "A critical aspect toward understanding metabolism is the set of dynamic inter...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna interference", "animal models", "caenorhabditis elegans", "model organisms", "epigenetics", "gene expression", "biology", "molecular biology", "systems biology", "rna", "rna processing", "nucleic acids", "genetics", "molecular cell biology", "genetics and genomics" ]	The ERI-6/7 Helicase Acts at the First Stage of an siRNA Amplification Pathway That Targets Recent Gene Duplications	journal.pgen.1002369	null	[ [ "Small RNA pathways regulate gene expression , chromatin structure and defense against invading elements such as transposons and viruses .", "Three general classes of small RNAs can be distinguished in animals: piwi-interacting RNAs ( piRNAs ) , microRNAs ( miRNAs ) and small interfering RNAs ( siRNAs ) ....	[ "Endogenous small interfering RNAs ( siRNAs ) are a class of naturally occuring regulatory RNAs found in fungi , plants , and animals .", "Some endogenous siRNAs are required to silence transposons or function in chromosome segregation; however , the specific roles of most endogenous siRNAs are unclear .", "The...	[ "Endogenous small interfering RNAs ( siRNAs ) are a class of small RNAs present in fungi , plants , and animals .", "Small RNAs , including microRNAs , are known to regulate the expression levels of genes , silence invading elements such as transposons , and act in cell division .", "However , the function of m...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "invertebrates", "medicine and health sciences", "immune cells", "immunology", "invertebrate genomics", "animals", "animal models", "nucleosome mapping", "insulators", "drosophila melanogaster", "model organisms", "materials science", "epigenetics", "molecular biology tech...	Genome-Wide Mapping Targets of the Metazoan Chromatin Remodeling Factor NURF Reveals Nucleosome Remodeling at Enhancers, Core Promoters and Gene Insulators	journal.pgen.1005969	null	[ [ "The organization of DNA in nucleosomes has a major function in controlling accessibility of DNA to the protein complexes that process genetic information .", "By altering nucleosome dynamics , targets for the transcription , replication and repair machineries can be rendered inaccessible or made availabl...	[ "NURF is a conserved higher eukaryotic ISWI-containing chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding .", "By sliding nucleosomes , NURF is able to alter chromatin dynamics to control transcription and genome organization .", "Previous biochemical and genetic analysis of the specif...	[ "In eukaryotes DNA is folded and compacted into manageable units by wrapping around a protein spool of histone proteins to form nucleosomes .", "By varying the position and dynamics of nucleosomes using energy-dependent chromatin remodeling enzymes , genes can be selectively turned off or on in cells , controllin...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "circuit models", "computational neuroscience", "biology", "neuroscience" ]	LTS and FS Inhibitory Interneurons, Short-Term Synaptic Plasticity, and Cortical Circuit Dynamics	journal.pcbi.1002248	null	[ [ "Low threshold-spiking ( LTS ) neurons are a specific subtype of interneuron in the neocortex .", "Their somata are located in layers 2–6 [1] , and they include the Martinotti cells of layer 5 [2] , [3] , [4] , [5] and the green fluorescent protein ( GFP ) -expressing neurons of the GIN line of transgenic...	[ "Somatostatin-expressing , low threshold-spiking ( LTS ) cells and fast-spiking ( FS ) cells are two common subtypes of inhibitory neocortical interneuron .", "Excitatory synapses from regular-spiking ( RS ) pyramidal neurons to LTS cells strongly facilitate when activated repetitively , whereas RS-to-FS synapses...	[ "The brain consists of circuits of neurons that signal to one another via synapses .", "There are two classes of neurons: excitatory cells , which cause other neurons to become more active , and inhibitory neurons , which cause other neurons to become less active .", "It is thought that the activity of excitato...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/infectious diseases" ]	Rabies Situation in Cambodia	journal.pntd.0000511	null	[ [ "Rabies is a viral zoonotic infection of the nervous central system caused by a lyssavirus and is fatal without proper post exposure treatment [1] .", "Despite the existence of an effective vaccine , rabies remains a public health problem worldwide , particularly in developing countries where dogs continu...	[ "Rabies , a fatal but preventable zoonosis , is a major public health problem in developing countries .", "In Cambodia the disease burden is largely underestimated because patients with encephalitis following dog bites are rarely hospitalized and die at home .", "Since 1998 Institut Pasteur in Cambodia ( IPC ) ...	[ "In Cambodia , rabies still elicits fear in the communities .", "Since 1998 the Institut Pasteur in Cambodia ( IPC ) , Phnom Penh has been the only source of free post-exposure prophylaxis ( PEP ) and post mortem diagnosis .", "During 1998–2007 , on average ∼12 , 400 patients received PEP annually at IPC ( rang...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "cell binding", "flow cytometry", "cell physiology", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "viral transmission and infection", "293t cells", "pathogens", "biological cultures", "tropical diseases", "microbiology", "alph...	Identification of Functional Determinants in the Chikungunya Virus E2 Protein	journal.pntd.0005318	null	[ [ "The Chikungunya virus ( CHIKV ) is a mosquito-transmitted alphavirus that causes high fever , rash , and recurrent arthritis in humans .", "The majority of symptoms disappear after about one week .", "However , in about 30% of cases , arthritis can last for months or even years , which may cause subs...	[ "Chikungunya virus ( CHIKV ) is a mosquito-transmitted alphavirus that causes high fever , rash , and recurrent arthritis in humans .", "It has efficiently adapted to Aedes albopictus , which also inhabits temperate regions , including Europe and the United States of America .", "In the past , CHIKV has mainly ...	[ "The chikungunya virus ( CHIKV ) glycoprotein E2 mediates cell attachment and consists of three domains A , B and C . Since the cell entry process of CHIKV is not understood in detail , we analyzed the binding properties of the three E2 domains with proteins expressed in E . coli or as Fc-fusion proteins and the ro...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "global health", "parasitic diseases" ]	Substance P Causes Seizures in Neurocysticercosis	journal.ppat.1002489	null	[ [ "Neurocysticercosis ( NCC ) is a parasitic infection of the human central nervous system that is caused by the pig tapeworm Taenia solium .", "NCC is the major cause of acquired seizures worldwide and now accounts for up to 10% of emergency room visits for seizures in the southwestern United States [1]–[7...	[ "Neurocysticercosis ( NCC ) , a helminth infection of the brain , is a major cause of seizures .", "The mediators responsible for seizures in NCC are unknown , and their management remains controversial .", "Substance P ( SP ) is a neuropeptide produced by neurons , endothelial cells and immunocytes .", "The ...	[ "Neurocysticercosis ( NCC ) , is a helminth infection of the brain that is caused by Taenia solium .", "NCC is the major cause of acquired seizures worldwide .", "Live Taenia solium parasites in the brain of NCC patients are surrounded by little or no inflammation .", "Seizures are thought to result not from ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "innate immune system", "medicine and health sciences", "parasite groups", "immune physiology", "cytokines", "pathology and laboratory medicine", "plasmodium", "pathogens", "immunology", "tropical diseases", "microbiology", "biomarkers", "parasitic diseases", "hepatitis b virus", "parasi...	Chronic hepatitis B virus infection drives changes in systemic immune activation profile in patients coinfected with Plasmodium vivax malaria	journal.pntd.0007535	null	[ [ "Malaria still rises major concerns in public health worldwide .", "The burden caused by the disease is noticeable , as it leads to more than 200 million cases and billions of dollars invested each year [1] .", "Despite all the investments and increased interest in the pursuit of new interventions [1 ...	[ "Plasmodium vivax and Hepatitis B virus ( HBV ) are globally outspread in similar geographic regions .", "The concurrence of both infections and its association with some degree of protection against symptomatic and/or severe vivax malaria has been already described .", "Nevertheless , data on how host response...	[ "The determinants of the diverse clinical presentations of Plasmodium vivax malaria are not completely understood .", "Previous studies have reported that P . vivax-HBV coinfection is associated with increased odds of presenting with asymptomatic malaria , but little is known about the immune mechanisms driving s...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "innate immune system", "medicine and health sciences", "toxins", "immune physiology", "pathology and laboratory medicine", "cytokines", "engineering and technology", "nervous system", "lasers", "immunology", "tropical diseases", "hyperalgesia", "neuroscience", "toxic agents", "toxicolog...	Analgesic Effect of Photobiomodulation on Bothrops Moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition, Cytokines and Kinin Receptors Modulation	journal.pntd.0004998	null	[ [ "Bothropic envenomation is characterized by severe local manifestation associated with oedema , myonecrosis , hemorrhage and intense pain [1–4] caused by the toxic action of venom components and aggravated by induced-inflammation .", "The local effects induced by bothropic venoms are the result of multifa...	[ "Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment .", "Herein , the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia i...	[ "Envenoming caused by Bothrops snakes is characterized by drastic local tissue damage involving hemorrhage , blistering , myonecrosis , prominent inflammatory response and intense pain .", "The most effective treatment for Bothrops snakebites is antivenom therapy , which is very efficient in reversing systemic ef...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "genetics and genomics/comparative genomics", "genetics and genomics/gene expression", "genetics and genomics/gene function", "genetics and genomics" ]	Missense Mutation in Exon 2 of SLC36A1 Responsible for Champagne Dilution in Horses	journal.pgen.1000195	null	[ [ "Many horse breeders value animals with variation in coat color .", "Several genes are known which diminish the intensity of the coloration and are phenotypically described as “dilutions” .", "Two of these are a result of the Cream ( CR ) locus and Silver ( Z ) locus .", "The molecular basis for C...	[ "Champagne coat color in horses is controlled by a single , autosomal-dominant gene ( CH ) .", "The phenotype produced by this gene is valued by many horse breeders , but can be difficult to distinguish from the effect produced by the Cream coat color dilution gene ( CR ) .", "Three sires and their families seg...	[ "The purpose of this study was to uncover the molecular basis for the champagne hair color dilution phenotype in horses .", "Here , we report a DNA base substitution in the second exon of the horse gene SLC36A1 that changes an amino acid in the transmembrane domain of the protein from threonine to arginine .", ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chromosome structure and function", "gene regulation", "dna transcription", "gene function", "histone modification", "genome sequencing", "developmental biology", "stem cells", "epigenetics", "molecular genetics", "chromatin", "chromosome biology", "embryonic stem cells", "gene expression...	High-Resolution Mapping of H1 Linker Histone Variants in Embryonic Stem Cells	journal.pgen.1003417	null	[ [ "In all eukaryotes , nuclear DNA is packaged into chromatin by its association with histones [1] .", "The nucleosome , the building block of chromatin , consists of an octamer of four core histones ( H2A , H2B , H3 and H4 ) wrapped by 147 bp of DNA [2] .", "Linker histone H1 binds to DNA entering and ...	[ "H1 linker histones facilitate higher-order chromatin folding and are essential for mammalian development .", "To achieve high-resolution mapping of H1 variants H1d and H1c in embryonic stem cells ( ESCs ) , we have established a knock-in system and shown that the N-terminally tagged H1 proteins are functionally ...	[ "Embryonic stem cells ( ESCs ) possess unique chromatin and epigenetic signatures , which are important in defining the identity and genome plasticity of pluripotent stem cells .", "Although ESC epigenomes have been extensively characterized , the genome localization of histone H1 variants , the chromatin structu...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "ecology/behavioral ecology", "infectious diseases/neglected tropical diseases", "infectious diseases/viral infections", "public health and epidemiology/social and behavioral determinants of health", "ecology/spatial and landscape ecology", "infectious diseases/protozoal infection...	The Role of Human Movement in the Transmission of Vector-Borne Pathogens	journal.pntd.0000481	null	[ [ "Historically epidemiologists have viewed human movement from the perspective of populations of susceptible hosts moving into high risk areas or infected hosts moving into susceptible populations as explanation for disease occurrence and spread .", "Indeed , across different scales and diseases , movement...	[ "Human movement is a key behavioral factor in many vector-borne disease systems because it influences exposure to vectors and thus the transmission of pathogens .", "Human movement transcends spatial and temporal scales with different influences on disease dynamics .", "Here we develop a conceptual model to eva...	[ "Vector-borne diseases constitute a largely neglected and enormous burden on public health in many resource-challenged environments , demanding efficient control strategies that could be developed through improved understanding of pathogen transmission .", "Human movement—which determines exposure to vectors—is a...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genome-wide association studies", "medicine and health sciences", "crohn's disease", "gene regulation", "immunology", "ulcerative colitis", "colitis", "cell signaling", "clinical medicine", "mathematics", "gastroenterology and hepatology", "genome analysis", "inflammatory bowel disease", ...	Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease	journal.pcbi.1005934	null	[ [ "Genome-wide association studies ( GWAS ) have considerable untapped potential to reveal new mechanisms of disease[1] .", "Variants associated with disease are over-represented in regulatory , rather than protein-coding , sequence; this enrichment is particularly strong in promoters and enhancers[2–4] .",...	[ "Genetic variants underlying complex traits , including disease susceptibility , are enriched within the transcriptional regulatory elements , promoters and enhancers .", "There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional ac...	[ "We discover that genetic variants associated with specific diseases have more in common with each other than we have previously seen .", "Specifically , variants associated with the same disease tend to be in parts of the genome that are turned on or off in similar complex patterns across many different cell typ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "signal transduction", "functional genomics", "cell biology", "genetics", "biology and life sciences", "genomics", "molecular cell biology", "computational biology" ]	Revealing Molecular Mechanisms by Integrating High-Dimensional Functional Screens with Protein Interaction Data	journal.pcbi.1003801	null	[ [ "Genome-scale functional genetics screens using technologies such as RNA interference ( RNAi ) have recently started to generate high-dimensional datasets by measuring either the same parameter in different cell lines [1] , [2] or different features in the same cell line [3]–[5] .", "Such high-dimensional...	[ "Functional genomics screens using multi-parametric assays are powerful approaches for identifying genes involved in particular cellular processes .", "However , they suffer from problems like noise , and often provide little insight into molecular mechanisms .", "A bottleneck for addressing these issues is the...	[ "Genome-scale functional genomics screens are important tools for investigating the function of genes .", "Technological progress allows for the simultaneous measurement of multiple parameters quantifying the response of cells to gene perturbations such as RNA interference .", "Such multi-dimensional screens pr...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "yellow fever", "immunizations", "medicine", "infectious diseases", "veterinary diseases", "veterinary virology", "zoonotic diseases", "viral diseases", "public health", "veterinary science" ]	Yellow Fever Outbreaks in Unvaccinated Populations, Brazil, 2008–2009	journal.pntd.0002740	null	[ [ "Yellow fever is an acute viral hemorrhagic disease transmitted by mosquitoes .", "Severity ranges from self-limited febrile illness to hemorrhagic syndrome with jaundice , multiple organ failure and death; severe cases are more likely to be detected and reported to passive surveillance systems [1] , [2] ...	[ "Due to the risk of severe vaccine-associated adverse events , yellow fever vaccination in Brazil is only recommended in areas considered at risk for disease .", "From September 2008 through June 2009 , two outbreaks of yellow fever in previously unvaccinated populations resulted in 21 confirmed cases with 9 deat...	[ "Yellow fever is a viral hemorrhagic disease transmitted by mosquitos , endemic in tropical regions of Africa and South America .", "Large urban outbreaks of yellow fever have been eliminated in the Americas , where most yellow fever cases result from human exposure to jungle or forested environments .", "Vacci...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "drugs and devices", "viral enzymes", "microbiology", "hepatitis", "pharmacology", "infectious diseases", "proteins", "hiv", "biology", "recombinant proteins", "viral replication", "drug discovery", "biochemistry", "hiv diagnosis and management", "hepatitis b", "drug rese...	The Hepatitis B Virus Ribonuclease H Is Sensitive to Inhibitors of the Human Immunodeficiency Virus Ribonuclease H and Integrase Enzymes	journal.ppat.1003125	null	[ [ "Hepatitis B virus ( HBV ) is a hepatotropic DNA virus that replicates by reverse transcription [1] .", "It chronically infects >350 million people world-wide and kills up to 1 . 2 million patients annually by inducing liver failure and liver cancer [2]–[4] .", "Reverse transcription is catalyzed by a...	[ "Nucleos ( t ) ide analog therapy blocks DNA synthesis by the hepatitis B virus ( HBV ) reverse transcriptase and can control the infection , but treatment is life-long and has high costs and unpredictable long-term side effects .", "The profound suppression of HBV by the nucleos ( t ) ide analogs and their abili...	[ "Current therapy for HBV blocks DNA synthesis by the viral reverse transcriptase and can control the infection indefinitely , but treatment rarely cures patients .", "More patients could be cured by suppressing HBV replication further using a new drug in combination with the existing ones .", "The HBV RNAseH is...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "heat shock response", "cellular stress responses", "medicine and health sciences", "cell biology", "proteins", "protein structure", "biology and life sciences", "cell processes", "cystic fibrosis transmembrane conductance regulator", "molecular cell biology", "protein misfoldi...	Modulation of the Maladaptive Stress Response to Manage Diseases of Protein Folding	journal.pbio.1001998	This study shows how chronic stress and heat shock response exacerbate the phenotype in protein misfolding diseases by triggering a Maladaptive Stress Response; this pathway represents a promising therapeutic target for multiple genetic disorders.	[ [ "The transition from protein folding to misfolding , in both normal physiology and disease , is dynamically managed by multiple proteostatic pathways [1] , [2] .", "The heat shock response ( HSR ) is a central signaling pathway managing the malleable composition of the proteostasis network ( PN ) of foldi...	[ "Diseases of protein folding arise because of the inability of an altered peptide sequence to properly engage protein homeostasis components that direct protein folding and function .", "To identify global principles of misfolding disease pathology we examined the impact of the local folding environment in alpha-...	[ "The function of all proteins is dependent on achieving the correct folded state , a process referred to as protein homeostasis or proteostasis .", "Cellular proteostasis is maintained by diverse signaling pathways , including the heat shock response ( HSR ) , which protects proteins in the face of acute stress ....	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "immunology", "signaling networks", "neurites", "neuroscience", "collagens", "developmental biology", "signal inhibition", "signs and symptoms", "network analysis"...	Control of neurite growth and guidance by an inhibitory cell-body signal	journal.pcbi.1006218	null	[ [ "The development of the nervous system requires the precise wiring of billions of cells .", "To achieve this considerable feat , growing axons navigate over long distances to reach their synaptic targets , and hence establish appropriate patterns of connectivity .", "Dysregulation of this process cont...	[ "The development of a functional nervous system requires tight control of neurite growth and guidance by extracellular chemical cues .", "Neurite growth is astonishingly sensitive to shallow concentration gradients , but a widely observed feature of both growth and guidance regulation , with important consequence...	[ "For the brain to become wired up during development , growing nerve fibres use molecular guidance factors to navigate over long distances and find their appropriate targets .", "However , the ability of nerve fibres to do this is severely limited by the loss of both growth and guidance as the concentration of gu...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "flow cytometry", "anatomical pathology", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "cytokines", "immunology", "cytopathology", "animal models", "developmental biology", "model organisms"...	An NK Cell Perforin Response Elicited via IL-18 Controls Mucosal Inflammation Kinetics during Salmonella Gut Infection	journal.ppat.1005723	null	[ [ "The intestinal mucosa is a key site limiting microbial access to the body [1 , 2] .", "Nonetheless , some enteropathogenic bacteria , including Salmonella enterica subspecies 1 serovar Typhimurium ( S . Tm ) , have the capacity to overcome the mucosal defenses and utilize the gut as a port of entry .", ...	[ "Salmonella Typhimurium ( S . Tm ) is a common cause of self-limiting diarrhea .", "The mucosal inflammation is thought to arise from a standoff between the pathogen's virulence factors and the host's mucosal innate immune defenses , particularly the mucosal NAIP/NLRC4 inflammasome .", "However , it had remaine...	[ "Salmonella Typhimurium is a common cause of foodborne diarrhea .", "The disease symptoms arise already a few hours after infection .", "However , it had remained unclear how the immune system can mount the responses eliciting the disease symptoms so quickly .", "Earlier work in a mouse model had shown that t...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology", "science policy", "evolutionary biology" ]	Persistent Leatherback Turtle Migrations Present Opportunities for Conservation	journal.pbio.0060171	Satellite tracking data from female leatherback turtles reveal their migration routes in the eastern Pacific and demonstrate how oceanic currents shape their migration corridors, providing a biological basis for conservation strategies.	[ [ "Leatherback turtles ( Dermochelys coriacea ) in the eastern Pacific ( EP ) have exhibited population declines of up to 90% during the past two decades [1 , 2] .", "These declines have been driven by a number of factors , including incidental mortality in fisheries , loss of nesting habitats , and unsusta...	[ "Effective transboundary conservation of highly migratory marine animals requires international management cooperation as well as clear scientific information about habitat use by these species .", "Populations of leatherback turtles ( Dermochelys coriacea ) in the eastern Pacific have declined by >90% during the...	[ "Highly migratory marine animals routinely cross international borders during extensive migrations over thousands of kilometers , thus requiring conservation strategies with information about habitat use and movement patterns .", "Critically endangered leatherback turtles ( Dermochelys coriacea ) in the eastern P...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biology and life sciences", "immunology", "microbiology", "medicine and health sciences" ]	G3BP1, G3BP2 and CAPRIN1 Are Required for Translation of Interferon Stimulated mRNAs and Are Targeted by a Dengue Virus Non-coding RNA	journal.ppat.1004242	null	[ [ "The critical roles of type I interferon ( IFN ) in detecting and clearing a wide range of viral infections have been well established [1] .", "IFNs are produced and released into the extracellular space by virtually all cell types upon recognition of pathogen-associated molecular patterns .", "Secret...	[ "Viral RNA-host protein interactions are critical for replication of flaviviruses , a genus of positive-strand RNA viruses comprising major vector-borne human pathogens including dengue viruses ( DENV ) .", "We examined three conserved host RNA-binding proteins ( RBPs ) G3BP1 , G3BP2 and CAPRIN1 in dengue virus (...	[ "Dengue virus is the most prevalent arbovirus in the world and an increasingly significant public health problem .", "Development of vaccines and therapeutics has been slowed by poor understanding of viral pathogenesis .", "Especially , how the virus subverts the host interferon response , a powerful branch of ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "biology", "computational biology" ]	A Network Characteristic That Correlates Environmental and Genetic Robustness	journal.pcbi.1003474	null	[ [ "Biological systems in general show various types and degrees of robustness to environmental changes , meaning that they continue to function even when changes in the environment occur .", "This imperturbability is often accompanied by robustness to genetic perturbations , meaning that progeny function ev...	[ "As scientific advances in perturbing biological systems and technological advances in data acquisition allow the large-scale quantitative analysis of biological function , the robustness of organisms to both transient environmental stresses and inter-generational genetic changes is a fundamental impediment to the ...	[ "Advances in the ways that living systems can be perturbed in order to study how they function and sharp reductions in the cost of computer resources have allowed the collection of large amounts of data .", "The aim of biological system modeling is to analyze this data in order to pin down the precise interaction...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	Requirement for Drosophila SNMP1 for Rapid Activation and Termination of Pheromone-Induced Activity	journal.pgen.1004600	null	[ [ "Pheromones are chemicals that trigger or inhibit stereotyped social behaviors , such as aggregation , courtship and mating [1] , [2] , [3] .", "Studies on insects have contributed enormously to our understanding of pheromones [2] , [3] .", "The first pheromone characterized was bombykol— a volatile 1...	[ "Pheromones are used for conspecific communication by many animals .", "In Drosophila , the volatile male-specific pheromone 11-cis vaccenyl acetate ( cVA ) supplies an important signal for gender recognition .", "Sensing of cVA by the olfactory system depends on multiple components , including an olfactory rec...	[ "Pheromones are chemicals produced and released by animals for social communication with other members of their species .", "For example , male fruit flies produce a volatile pheromone that is sensed by both males and females , and which functions in gender recognition .", "This volatile male pheromone , called...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "medicine", "chronic kidney disease", "quantitative traits", "tubulointerstitial disease", "biology", "heredity", "genetic association studies", "genetics", "human genetics", "genetics of disease", "nephrology", "genetics and genomics", "complex traits" ]	Genetic Association for Renal Traits among Participants of African Ancestry Reveals New Loci for Renal Function	journal.pgen.1002264	null	[ [ "Chronic kidney disease ( CKD ) affects approximately 15% of U . S adults [1] .", "Due in part to increasing rates of diabetes and obesity , the prevalence of CKD continues to rise [1] .", "Marked variability in the incidence of CKD suggests that factors other than diabetes and hypertension contribute...	[ "Chronic kidney disease ( CKD ) is an increasing global public health concern , particularly among populations of African ancestry .", "We performed an interrogation of known renal loci , genome-wide association ( GWA ) , and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Con...	[ "Chronic kidney disease ( CKD ) is an increasing global public health problem and disproportionately affects populations of African ancestry .", "Many studies have shown that genetic variants are associated with the development of CKD; however , similar studies are lacking in African ancestry populations .", "T...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell death", "molecular neuroscience", "neurobiology of disease and regeneration", "gene regulation", "neuroscience", "animal models", "model organisms", "molecular genetics", "biology", "mouse", "visual system", "cellular neuroscience", "neuronal morphology", "neurons", "genetics", "...	Distinct and Atypical Intrinsic and Extrinsic Cell Death Pathways between Photoreceptor Cell Types upon Specific Ablation of Ranbp2 in Cone Photoreceptors	journal.pgen.1003555	null	[ [ "The disintegration of neuronal networks owing to the non-autonomous death of neurons without primary damage is a hallmark manifestation of many neurodegenerative diseases and contributes determinately to their onset or progression [1]–[3] .", "Cone or rod photoreceptor neurons employ cell type-specific s...	[ "Non-autonomous cell-death is a cardinal feature of the disintegration of neural networks in neurodegenerative diseases , but the molecular bases of this process are poorly understood .", "The neural retina comprises a mosaic of rod and cone photoreceptors .", "Cone and rod photoreceptors degenerate upon rod-sp...	[ "The secondary demise of healthy neurons upon the degeneration of neurons harboring primary genetic defect ( s ) is hallmark to neurodegenerative diseases .", "However , the factors and mechanisms driving these cell-death processes are not understood , a severe limitation which has hampered the therapeutic develo...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "clinical immunology", "immunology" ]	Circulating Microbial Products and Acute Phase Proteins as Markers of Pathogenesis in Lymphatic Filarial Disease	journal.ppat.1002749	null	[ [ "Although two-thirds of the 120 million people infected with Wuchereria bancrofti—the major causative agent of human lymphatic filariasis—have subclinical infections , ∼40 million have lymphedema and/or other pathologic manifestations including hydroceles ( and other forms of urogenital disease ) , episodic a...	[ "Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema , hydrocele , and elephantiasis in a subset of infected patients .", "Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathog...	[ "Lymphatic filariasis afflicts over 120 million people worldwide .", "While the infection is mostly clinically asymptomatic , approximately 40 million people suffer from overt , morbid clinical pathology , characterized by swelling of the scrotal area and lower limbs ( hydrocele and lymphedema ) .", "Host immun...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology", "viral vaccines", "biology", "microbiology" ]	Genetic and Phenotypic Characterization of Manufacturing Seeds for a Tetravalent Dengue Vaccine (DENVax)	journal.pntd.0002243	null	[ [ "The dengue virus ( DENV ) complex , genus Flavivirus , comprises four distinct serotypes of viruses ( DENV-1 to -4 ) .", "DENV causes the most rapidly spreading mosquito-borne human viral disease in the world .", "About 50–100 million new dengue infections occur each year in more than 100 endemic cou...	[ "We have developed a manufacturing strategy that can improve the safety and genetic stability of recombinant live-attenuated chimeric dengue vaccine ( DENVax ) viruses .", "These viruses , containing the pre-membrane ( prM ) and envelope ( E ) genes of dengue serotypes 1–4 in the replicative background of the att...	[ "Transmitted by Aedes spp .", "mosquitoes found worldwide , dengue is the most important mosquito-borne viral disease in the world .", "The incidence of dengue has increased 30-fold over the past 50 years , and is now endemic in over 100 countries .", "Vaccination is believed to be one of the most effective s...	2013
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biochemistry", "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "infectious diseases/fungal infections", "microbiology/microbial physiology and metabolism", "microbiology/microbial growth and development", "cell biology/chemical biology of the cell", "microbiology...	HapX-Mediated Adaption to Iron Starvation Is Crucial for Virulence of Aspergillus fumigatus	journal.ppat.1001124	null	[ [ "Iron is an essential nutrient for virtually every organism .", "The ability to exist in two redox states makes this metal an essential cofactor of proteins involved in numerous major cellular processes including respiration , amino acid metabolism and DNA metabolism .", "However , excess iron has the...	[ "Iron is essential for a wide range of cellular processes .", "Here we show that the bZIP-type regulator HapX is indispensable for the transcriptional remodeling required for adaption to iron starvation in the opportunistic fungal pathogen Aspergillus fumigatus .", "HapX represses iron-dependent and mitochondri...	[ "Due to its requirement for a wide range of cellular processes , iron is an essential nutrient for virtually every organism .", "The mammalian immune system utilizes iron-withholding mechanisms to deny access to free iron .", "Therefore , pathogens must overcome extreme iron limitation .", "Patients with supp...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Convergence and Extrusion Are Required for Normal Fusion of the Mammalian Secondary Palate	journal.pbio.1002122	A study of the mouse palate shows that the fusion of tissues during development involves convergence and displacement of epithelial cells, coupled with cell extrusion driven by the contractile activity of actomyosin.	[ [ "Tissue fusion is required for the morphogenesis of numerous vertebrate organ systems , including neural tube closure , heart morphogenesis , urogenital development , and craniofacial development , and failure of tissue fusion leads to birth defects in these contexts [1] .", "In craniofacial development ,...	[ "The fusion of two distinct prominences into one continuous structure is common during development and typically requires integration of two epithelia and subsequent removal of that intervening epithelium .", "Using confocal live imaging , we directly observed the cellular processes underlying tissue fusion , usi...	[ "Tissue fusion , the process by which two independent prominences become united to form one continuous structure , is common during development , and its failure leads to multiple structural birth defects .", "In this study , we directly examine the cellular and molecular mechanisms by which tissue fusion occurs ...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "ecology", "viral transmission and infection", "vector biology", "virology", "biology", "microbiology" ]	Genetic and Anatomic Determinants of Enzootic Venezuelan Equine Encephalitis Virus Infection of Culex (Melanoconion) taeniopus	journal.pntd.0001606	null	[ [ "Venezuelan equine encephalitis virus ( VEEV ) has been recognized as an etiologic agent of neurologic disease in humans and equids for nearly 80 years .", "Closely related to eastern ( EEEV ) and western equine encephalitis viruses ( WEEV ) , VEEV belongs to the family Togaviridae , genus Alphavirus .", ...	[ "Venezuelan equine encephalitis ( VEE ) is a re-emerging , mosquito-borne viral disease with the potential to cause fatal encephalitis in both humans and equids .", "Recently , detection of endemic VEE caused by enzootic strains has escalated in Mexico , Peru , Bolivia , Colombia and Ecuador , emphasizing the imp...	[ "Venezuelan equine encephalitis virus ( VEEV ) is transmitted to humans and horses by mosquitoes in Mexico , Central and South America .", "These infections can lead to fatal encephalitis in humans as well as horses , donkeys and mules , and there are no licensed vaccines or treatments available for humans .", ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Hsp70-Hsp40 Chaperone Complex Functions in Controlling Polarized Growth by Repressing Hsf1-Driven Heat Stress-Associated Transcription	journal.pgen.1003886	null	[ [ "Sensing ecological parameters and mounting an appropriate adaptive response allows organisms to thrive in changing habitats .", "Free-living microorganisms , such as yeast , can maintain regular patterns of growth over a relatively wide range of environmental temperatures .", "Cellular adaptation to ...	[ "How the molecular mechanisms of stress response are integrated at the cellular level remains obscure .", "Here we show that the cellular polarity machinery in the fission yeast Schizosaccharomyces pombe undergoes dynamic adaptation to thermal stress resulting in a period of decreased Cdc42 activity and altered ,...	[ "Heat stress , caused by fluctuations in ambient temperature , occurs frequently in nature .", "How organisms adapt and maintain regular patterns of growth over a range of environmental conditions remain poorly understood .", "Our work in the simple unicellular yeast Schizosaccharomyces pombe suggests that the ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "evolutionary biology", "neuroscience", "molecular biology", "genetics and genomics" ]	Drosophila Neurotrophins Reveal a Common Mechanism for Nervous System Formation	journal.pbio.0060284	Members of the neurotrophin superfamily mediate critical roles in neuronal survival and targeting in the fruit flyDrosophila. Although this is an accepted role for neurotrophins in vertebrates, scant previous evidence has been able to demonstrate such a conserved role in invertebrates.	[ [ "In vertebrate brain development , neurons are produced in excess , and surplus neurons are eliminated through apoptosis ( cell death ) , adjusting innervation , targeting , and connectivity to target size [1] .", "Neurotrophins ( NTs ) are the major class of molecules promoting neuronal survival in verte...	[ "Neurotrophic interactions occur in Drosophila , but to date , no neurotrophic factor had been found .", "Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival , targeting , synaptic plasticity , memory and cognition ."...	[ "Neurotrophins are secreted proteins that link nervous system structure and function in vertebrates .", "They regulate neuronal survival , thus adjusting cell populations , and connectivity , enabling the formation of neuronal circuits .", "They also regulate patterns of dendrites and axons , synaptic function ...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "infectious disease immunology", "medicine and health sciences", "infectious hepatitis", "hepatitis b", "hepatitis", "clinical immunology", "gastroenterology and hepatology", "biology and life sciences", "immunology", "viral diseases", "liver diseases", "hepatocellular...	Primary Seronegative but Molecularly Evident Hepadnaviral Infection Engages Liver and Induces Hepatocarcinoma in the Woodchuck Model of Hepatitis B	journal.ppat.1004332	null	[ [ "It is estimated that 370 million people have serologically evident chronic hepatitis B virus ( HBV ) infection and over 2 billion have been exposed to this virus [1] .", "Chronic hepatitis B ( CHB ) frequently ( 20–25% ) advances to cirrhosis and liver failure , while hepatocellular carcinoma ( HCC ) dev...	[ "Hepadnavirus at very low doses establishes in woodchucks asymptomatic , serologically undetectable but molecularly evident persistent infection .", "This primary occult infection ( POI ) preferentially engages the immune system and initiates virus-specific T cell response in the absence of antiviral antibody ind...	[ "Introduction of highly sensitive molecular assays for detection of hepatitis B virus ( HBV ) identified the existence of persistent occult HBV infection years after recovery from an episode of hepatitis B and in individuals exposed to HBV but without symptoms and classical markers of infection .", "Because HBV i...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genome expression analysis", "functional genomics", "gene regulation", "anatomy and physiology", "rna stability", "muscle", "molecular genetics", "musculoskeletal system", "cell adhesion", "extracellular matrix", "gene expression", "biology", "molecular biology", "muscle cel...	The PARN Deadenylase Targets a Discrete Set of mRNAs for Decay and Regulates Cell Motility in Mouse Myoblasts	journal.pgen.1002901	null	[ [ "The poly ( A ) tail added to mRNAs during processing in the nucleus stimulates mRNA export and translation through its association with poly ( A ) -binding proteins .", "In contrast , the removal of the poly ( A ) tail renders transcripts translationally silent and is also the first step in decay of the ...	[ "PARN is one of several deadenylase enzymes present in mammalian cells , and as such the contribution it makes to the regulation of gene expression is unclear .", "To address this , we performed global mRNA expression and half-life analysis on mouse myoblasts depleted of PARN .", "PARN knockdown resulted in the...	[ "Almost all cellular mRNAs terminate in a 3′ poly ( A ) tail , the removal of which can induce both translational silencing and mRNA decay .", "Mammalian cells encode many poly ( A ) -specific exoribonucleases , but their individual roles are poorly understood .", "Here , we undertook an analysis of the role of...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Population Pharmacokinetics of an Indian F(ab')2 Snake Antivenom in Patients with Russell's Viper (Daboia russelii) Bites	journal.pntd.0003873	null	[ [ "Snake envenoming is a major health issue in South and South-eastern Asia [1] .", "Although antivenom is the most important treatment for snake envenoming , it can cause early systemic hypersensitivity reactions [2 , 3] , and there is limited evidence to support currently practiced dosing schedules .", ...	[ "There is limited information on antivenom pharmacokinetics .", "This study aimed to investigate the pharmacokinetics of an Indian snake antivenom in humans with Russell’s viper bites .", "Patient data and serial blood samples were collected from patients with Russell’s viper ( Daboia russelii ) envenoming in S...	[ "Snake envenoming is a neglected tropical disease that affects hundreds of thousands of people in the rural tropics .", "Antivenom is the main treatment for snake bites but there is limited information on the pharmacokinetics and appropriate dosing regimen .", "Most studies have been done in animals and dosing ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "global positioning system", "engineering and technology", "pathogens", "tropical diseases", "geographical locations", "social sciences", "vertebrates", "human mobility", "animals", "ma...	Fine-scale GPS tracking to quantify human movement patterns and exposure to leptospires in the urban slum environment	journal.pntd.0006752	null	[ [ "Household characteristics are frequently used as a measure of the risk of pathogen exposure .", "However , these household risk factors are static proxies for exposure , which is a dynamic function of movement through a contaminated environment .", "Many neglected tropical diseases—including schistos...	[ "Human movement is likely an important risk factor for environmentally-transmitted pathogens .", "While epidemiologic studies have traditionally focused on household risk factors , individual movement data could provide critical additional information about risk of exposure to such pathogens .", "We conducted g...	[ "Environmental features of urban slums including inadequate sanitation , substandard housing , and population crowding predispose residents to numerous infections .", "Despite this shared environment , not all slum residents , even within households , have equal risk of infection with specific pathogens and we do...	2018
[ "Introduction", "Models and methods", "Results and discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "vibrio", "microbiology", "cryptosporidium", "parasitic protozoans", "physiological processes", "statistical data", "vibrio cholerae", "protozoans", "mathematics", "statistics (mathematics)", "materials scien...	Dose-response relationships for environmentally mediated infectious disease transmission models	journal.pcbi.1005481	null	[ [ "Modeling infectious disease transmission by person-to-person contact has a long history in the scientific community .", "Environmentally mediated transmission modeling , on the other hand , has only recently been explored , notably including", "i ) the Codeço model [1] ( based on an older model by Ca...	[ "Environmentally mediated infectious disease transmission models provide a mechanistic approach to examining environmental interventions for outbreaks , such as water treatment or surface decontamination .", "The shift from the classical SIR framework to one incorporating the environment requires codifying the re...	[ "Many infectious disease interventions , including water treatment , hand hygiene , and surface decontamination , target pathogens in the environment .", "Explicitly modeling the concentration of pathogens in the environment within transmission models can be a useful way to consider not only the impact of such mi...	2017
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "veterinary diseases", "emerging infectious diseases", "veterinary microbiology", "virology", "microbial pathogens", "biology", "evolutionary biology", "microbiology", "host-pathogen interaction", "evolutionary genetics", "animal management", "veterinary science" ]	Histo-Blood Group Antigens Act as Attachment Factors of Rabbit Hemorrhagic Disease Virus Infection in a Virus Strain-Dependent Manner	journal.ppat.1002188	null	[ [ "Rabbit hemorrhagic disease virus ( RHDV ) , a single stranded positive-sense RNA virus belonging to the Lagovirus genus of the Caliciviridae family , is the cause of rabbit hemorrhagic disease ( RHD ) , a disease affecting wild and domestic rabbits of the Oryctolagus cuniculus species .", "RHD was first ...	[ "Rabbit Hemorrhagic disease virus ( RHDV ) , a calicivirus of the Lagovirus genus , and responsible for rabbit hemorrhagic disease ( RHD ) , kills rabbits between 48 to 72 hours post infection with mortality rates as high as 50–90% .", "Caliciviruses , including noroviruses and RHDV , have been shown to bind hist...	[ "Rabbit hemorrhagic disease virus ( RHDV ) , detected as late as 1984 , has spread to large parts of the world , threatening rabbit populations and other species dependent on rabbits in many European countries .", "Mortality has been shown to be as high as 90% and rabbits are killed 48 to 72 hours after infection...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "leptospira", "pathology and laboratory medicine", "infectious disease epidemiology", "pathogens", "tropical diseases", "geographical locations", "microbiology", "census", "bacterial diseases", "research design", "signs and symptoms", "tanzania", "neglected ...	Comparison of the Estimated Incidence of Acute Leptospirosis in the Kilimanjaro Region of Tanzania between 2007–08 and 2012–14	journal.pntd.0005165	null	[ [ "Leptospirosis is a major cause of illness worldwide with an estimated 1 . 03 million cases , 59 , 000 deaths , and 2 . 90 million disability adjusted life years lost annually [1 , 2] .", "The burden of disease is thought to be greatest in tropical countries , although reported estimates of incidence in c...	[ "The sole report of annual leptospirosis incidence in continental Africa of 75–102 cases per 100 , 000 population is from a study performed in August 2007 through September 2008 in the Kilimanjaro Region of Tanzania .", "To evaluate the stability of this estimate over time , we estimated the incidence of acute le...	[ "Leptospirosis is an infectious disease that causes a fever .", "It can be severe or fatal .", "Understanding how many people get leptospirosis helps to determine priorities in allocating resources for disease diagnosis , treatment , and prevention .", "There are few data about leptospirosis incidence in sub-...	2016
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "ecology" ]	Climate Change, Humans, and the Extinction of the Woolly Mammoth	journal.pbio.0060079	Climate models together with population models provide quantitative evidence that the combined effects of climate change and anthropogenic pressures can explain the extinction of the woolly mammoths.	[ [ "The woolly mammoth , Mammuthus primigenius , was an herbivorous mammal that lived in the cool and dry open steppe-tundras of the Northern Hemisphere from late Middle Pleistocene ( 300 thousand years before presend [ky BP] ) , or even earlier [1] .", "They are thought to have finally become extinct 3 . 7 ...	[ "Woolly mammoths inhabited Eurasia and North America from late Middle Pleistocene ( 300 ky BP [300 , 000 years before present] ) , surviving through different climatic cycles until they vanished in the Holocene ( 3 . 6 ky BP ) .", "The debate about why the Late Quaternary extinctions occurred has centred upon env...	[ "What caused the woolly mammoth's extinction ?", "Climate warming in the Holocene might have driven the extinction of this cold-adapted species , yet the species had survived previous warming periods , suggesting that the more-plausible cause was human expansion .", "Testing these competing hypotheses has been ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "virology", "biology and life sciences", "microbiology", "molecular cell biology", "cellular structures and organelles" ]	GAPDH-A Recruits a Plant Virus Movement Protein to Cortical Virus Replication Complexes to Facilitate Viral Cell-to-Cell Movement	journal.ppat.1004505	null	[ [ "Eukaryotic positive-strand RNA viruses replicate their genomes using membrane-bound virus replication complexes ( VRC ) , which contain viral replicase proteins , viral RNA templates , and host-factor proteins [1]–[5] .", "Viral replicase proteins modify the host intracellular membrane morphology , inclu...	[ "The formation of virus movement protein ( MP ) -containing punctate structures on the cortical endoplasmic reticulum is required for efficient intercellular movement of Red clover necrotic mosaic virus ( RCNMV ) , a bipartite positive-strand RNA plant virus .", "We found that these cortical punctate structures c...	[ "Intercellular movement of plant viruses is the crucial step during systemic viral infections .", "Red clover necrotic mosaic virus ( RCNMV ) , a bipartite positive-strand RNA plant virus , forms movement protein ( MP ) -containing punctate structures on the cortical endoplasmic reticulum in infected cells , whic...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/macromolecular structure analysis", "biophysics/macromolecular assemblies and machines", "biophysics/structural genomics", "computational biology/protein structure prediction" ]	From Nonspecific DNA–Protein Encounter Complexes to the Prediction of DNA–Protein Interactions	journal.pcbi.1000341	null	[ [ "DNA-binding proteins play an essential role in many fundamental biological", "activities , including DNA transcription , replication , packaging , repair and", "rearrangement .", "Interactions relevant to these activities typically involve specific", "binding sites on both proteins and DNA ."...	[ "DNA–protein interactions are involved in many essential biological", "activities .", "Because there is no simple mapping code between DNA base pairs and", "protein amino acids , the prediction of DNA–protein interactions is a", "challenging problem .", "Here , we present a novel computational approach fo...	[ "Many essential biological activities require interactions between DNA and", "proteins .", "These proteins usually use certain amino acids , called DNA-binding", "sites , to recognize their specific DNA targets .", "To facilitate the search of its", "specific DNA targets , a DNA-binding protein often asso...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "spatial epidemiology", "phylogenetics", "rabies", "neglected tropical diseases", "population biology", "veterinary science", "infectious diseases", "veterinary diseases", "zoonotic diseases", "epidemiology", "biology", "evolutionary systematic...	The Spatial and Temporal Dynamics of Rabies in China	journal.pntd.0001640	null	[ [ "Rabies is an enzootic disease that causes severe dysfunction to the central nervous system [1] .", "While cases are relatively rare in developed countries , the virus has significant impact on a global scale , with more than 55 , 000 deaths reported annually [2] , and represents a major public health iss...	[ "Recent years have seen a rapid increase in the number of rabies cases in China and an expansion in the geographic distribution of the virus .", "In spite of the seriousness of the outbreak and increasing number of fatalities , little is known about the phylogeography of the disease in China .", "In this study ...	[ "Rabies is a major problem in developing countries and responsible for more than 55 , 000 deaths annually .", "More than half of the cases occur in Asia and China has the second highest incidence of rabies after India .", "Human rabies cases in China decreased during the early 1990s but the virus began to re-em...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "viral vaccines", "adaptive immunity", "viruslike particles", "emerging infectious diseases", "immunity", "virology", "neglected tropical diseases", "biology", "microbiology", "arboviral infections", "infectious disease control" ]	Effective Chikungunya Virus-like Particle Vaccine Produced in Insect Cells	journal.pntd.0002124	null	[ [ "Chikungunya virus ( CHIKV ) is a mosquito-borne , single-stranded , positive-sense RNA virus ( genus alphavirus ) that has caused sporadic outbreaks every 2–50 years of predominantly rheumatic disease , primarily in Africa and Asia .", "CHIKV recently ( 2004–2011 ) produced the largest epidemic recorded ...	[ "The emerging arthritogenic , mosquito-borne chikungunya virus ( CHIKV ) causes severe disease in humans and represents a serious public health threat in countries where Aedes spp mosquitoes are present .", "This study describes for the first time the successful production of CHIKV virus-like particles ( VLPs ) i...	[ "Viruses that are transmitted by mosquitoes represent major threats for human health all over the world .", "One of these viruses is the Chikungunya virus ( CHIKV ) .", "CHIKV is transmitted by the Asian Tiger mosquito , which is making ground to more temperate regions such as Europe , and thereby increasing th...	2013
[ "Introduction", "Discussion", "Materials and Methods" ]	[ "condensation", "gene regulation", "rna analysis", "condensed matter physics", "germ cells", "developmental biology", "oocytes", "epigenetics", "molecular biology techniques", "embryos", "mammalian genomics", "chromatin", "research and analysis methods", "small interfering rnas", "embryo...	Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice	journal.pgen.1006375	null	[ [ "A previous study using XmXm embryos ( parthenogenotes ) showed that loss of H3K9me3 via Kdm4b , which is a H3K9me3 demethylase [12] , or gain of histone acetylation by trichostatin A ( TSA ) treatment , induced Xm-Xist derepression [4] ( S1 Fig ) .", "More recently , chromatin decondensation was shown to...	[ "In female mammals , activation of Xist ( X-inactive specific transcript ) is essential for establishment of X chromosome inactivation .", "During early embryonic development in mice , paternal Xist is preferentially expressed whereas maternal Xist ( Xm-Xist ) is silenced .", "Unlike autosomal imprinted genes ,...	[ "X-inactive specific transcript ( Xist ) is essential a large non-coding RNA for establishment of X chromosome inactivation in female mammals .", "The aberrant X chromosome inactivation critically affects cellular viability .", "Therefore , spatiotemporal regulation of Xist expression is required for proper dev...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "children", "medicine and health sciences", "education", "african trypanosomiasis", "sociology", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "health care", "age groups", "human families", "neglected tropical diseases", "africa", "veterinary sci...	The socio-economic burden of human African trypanosomiasis and the coping strategies of households in the South Western Kenya foci	journal.pntd.0006002	null	[ [ "Human African trypanosomiasis ( HAT ) also known as sleeping sickness is one of the 17 neglected tropical diseases identified by the World Health Organization ( WHO ) and has also been marked for elimination by the year 2020 [1 , 2] .", "Two forms of the disease exist depending on the parasite involved; ...	[ "Human African Trypanosomiasis ( HAT ) , a disease caused by protozoan parasites transmitted by tsetse flies , is an important neglected tropical disease endemic in remote regions of sub-Saharan Africa .", "Although the determination of the burden of HAT has been based on incidence , mortality and morbidity rates...	[ "Sleeping sickness affects people often living in remote rural areas and those who mainly depend on subsistence agriculture .", "We carried out a study among former sleeping sickness patients in Kenya to find out the socio-economic challenges they faced in seeking treatment and the coping strategies they used to ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "genome evolution", "parasite evolution", "parasitology", "biology", "genomics", "microbiology", "drug discovery" ]	Asexual Populations of the Human Malaria Parasite, Plasmodium falciparum, Use a Two-Step Genomic Strategy to Acquire Accurate, Beneficial DNA Amplifications	journal.ppat.1003375	null	[ [ "The emergence of chloroquine and Fansidar resistance contributed to resurgence of malaria in the 1970s and 1980s [1] , [2] .", "Today , from an estimated 2 billion global clinical cases , ∼0 . 5 to 1 million individuals die of malaria every year [3] , [4] , [5] .", "There is a growing concern that de...	[ "Malaria drug resistance contributes to up to a million annual deaths .", "Judicious deployment of new antimalarials and vaccines could benefit from an understanding of early molecular events that promote the evolution of parasites .", "Continuous in vitro challenge of Plasmodium falciparum parasites with a nov...	[ "Malaria parasites kill up to a million people around the world every year .", "Emergence of resistance to drugs remains a key obstacle against elimination of malaria .", "In the laboratory , parasites can efficiently acquire resistance to experimental antimalarials by changing DNA at the target locus .", "Th...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "cancers and neoplasms", "cloning", "animals", "notch signaling", "cell differentiation", "oncology", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "stem cells", "experimental organism systems", "d...	A genetic framework controlling the differentiation of intestinal stem cells during regeneration in Drosophila	journal.pgen.1006854	null	[ [ "In metazoans , the digestive tract supports organismal growth and maintenance .", "Genetic disorders or microbial dysbiosis that prevent the digestion and absorption of nutrients are major causes of morbidity and mortality in humans .", "In mammals , mature intestinal cells are short-lived and consta...	[ "The speed of stem cell differentiation has to be properly coupled with self-renewal , both under basal conditions for tissue maintenance and during regeneration for tissue repair .", "Using the Drosophila midgut model , we analyze at the cellular and molecular levels the differentiation program required for robu...	[ "Adult tissue/organ function is maintained by stem cells .", "Key question in stem cell biology is how the pool of stem cells can be robustly expanded yet timely contracted through differentiation according to the need of a tissue .", "Over the last years , the mechanisms underlying stem cell activation have be...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/gene expression" ]	Tandem E2F Binding Sites in the Promoter of the p107 Cell Cycle Regulator Control p107 Expression and Its Cellular Functions	journal.pgen.1001003	null	[ [ "The retinoblastoma gene Rb was initially identified as a prototypic tumor suppressor through its association with hereditary retinoblastoma; mutations in Rb or in genes that play a role in the regulation of Rb function are found in virtually all types of human cancers .", "The best-described function of ...	[ "The retinoblastoma tumor suppressor ( Rb ) is a potent and ubiquitously expressed cell cycle regulator , but patients with a germline Rb mutation develop a very specific tumor spectrum .", "This surprising observation raises the possibility that mechanisms that compensate for loss of Rb function are present or a...	[ "The retinoblastoma tumor suppressor Rb belongs to a family of cell cycle inhibitors along with the related proteins p107 and p130 .", "Strong evidence indicates that the three family members have both specific and overlapping functions and expression patterns in mammalian cells , including in cancer cells .", ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "veterinary epidemiology", "veterinary microbiology", "medical microbiology", "epidemiology", "biology", "microbiology", "public health", "veterinary science" ]	Molecular Epidemiology and Antibiotic Susceptibility of Livestock Brucella melitensis Isolates from Naryn Oblast, Kyrgyzstan	journal.pntd.0002047	null	[ [ "Agriculture is a key component of Kyrgyzstan's economy and livestock play a major role in the daily lives of the population .", "Sixty four percents of the population live in rural areas and rely on agriculture for their livelihoods .", "Up to 76% of the rural population of the country is classified ...	[ "The incidence of human brucellosis in Kyrgyzstan has been increasing in the last years and was identified as a priority disease needing most urgent control measures in the livestock population .", "The latest species identification of Brucella isolates in Kyrgyzstan was carried out in the 1960s and investigated ...	[ "Brucellosis is a bacterial disease causing abortion in cattle , sheep , and goats .", "It is transmissible to humans by direct transmission and the consumption of untreated milk .", "Brucellosis has become more and more frequent in Kyrgyzstan in the last decades , and its control has been made a priority .", ...	2013
[ "Introduction", "Methods", "Data Archiving", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "rna extraction", "microbiology", "vertebrates", "geographical locations", "animals", "mammals", "viruses", "rna viruses", "phylogenetic analysis", "mitochondria", "molecular biology techniques", "bioenerge...	When Viruses Don’t Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses	journal.ppat.1006073	null	[ [ "Most emerging RNA virus infections originate from wild animals [1] .", "Fortunately , outbreaks of many such infections are geographically restricted , e . g . MERS coronavirus in the Middle East , Marburg filovirus in central and southern Africa , and Nipah henipavirus in south-east Asia .", "This r...	[ "Many emerging infections are RNA virus spillovers from animal reservoirs .", "Reservoir identification is necessary for predicting the geographic extent of infection risk , but rarely are taxonomic levels below the animal species considered as reservoir , and only key circumstances in nature and methodology allo...	[ "Reservoirs of zoonotic viruses are usually equated with a particular wildlife species .", "It is rarely assessed whether genetic groups below the species level may instead represent the actual reservoir , though this would have major implications on estimations of the zoonosis’ spatial distribution .", "Here w...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Over-Expression of Cysteine Leucine Rich Protein Is Related to SAG Resistance in Clinical Isolates of Leishmania donovani	journal.pntd.0003992	null	[ [ "Infection of Leishmania has several clinical manifestations as visceral , cutaneous and mucocutaneous forms of leishmaniasis and visceral leishmaniasis ( VL ) , among these , VL is the deadly form in the absence of proper treatment .", "In India , particularly the states of Bihar , adjoining areas of Wes...	[ "Resistance emergence against antileishmanial drugs , particularly Sodium Antimony Gluconate ( SAG ) has severely hampered the therapeutic strategy against visceral leishmaniasis , the mechanism of resistance being indistinguishable .", "Cysteine leucine rich protein ( CLrP ) , was recognized as one of the overex...	[ "Leishmania causes complex of pathologies called Leishmaniasis and among the several forms visceral leishmaniasis is the precarious one as being fatal , if left untreated .", "Emergence of resistance against several antileishmanials particularly Sodium Antimony Gluconate ( SAG ) has severely battered the therapeu...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Untangling Brain-Wide Dynamics in Consciousness by Cross-Embedding	journal.pcbi.1004537	null	[ [ "The brain is a complex system with restless activity dynamics [1] .", "These dynamics are generated and maintained by interactions among variety of neural populations inside the brain .", "How brain-wide interaction produces specific dynamics underlying cognitive functions is a central question in ne...	[ "Brain-wide interactions generating complex neural dynamics are considered crucial for emergent cognitive functions .", "However , the irreducible nature of nonlinear and high-dimensional dynamical interactions challenges conventional reductionist approaches .", "We introduce a model-free method , based on embe...	[ "Advances in recording technologies have enabled the acquisition of neuronal dynamics data at unprecedented scale and resolution , but the increase in data complexity challenges reductionist model-based approaches .", "Motivated by generic theorems of dynamical systems , we characterize model-free , nonlinear emb...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers	journal.pgen.1004922	null	[ [ "Lymphoma and angiosarcoma are both malignancies of the hematological system , originating from lymphocytes and hematopoietic stem cells , respectively .", "Lymphomas are a heterogeneous group of diseases , estimated to be the eighth leading cause of human cancer deaths in the US in 2014 [1] .", "The ...	[ "Dogs , with their breed-determined limited genetic background , are great models of human disease including cancer .", "Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma ,...	[ "To shed light on the genetic predisposition to cancers of the hematologic system , we performed genome-wide association analysis of affected and non-affected pet dogs .", "Dogs naturally develop the same diseases as humans , including cancer , and the relatively limited genetic diversity within different breeds ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "genome evolution", "population genetics", "oncology", "mutation", "nonsense mutation", "evolutionary adaptation", "population biology", "population density", "molecular evolution", "evolutionary genetics", "carcinogenesis", "population metrics", "evolutiona...	High mutation rates limit evolutionary adaptation in Escherichia coli	journal.pgen.1007324	null	[ [ "Mutation is fundamental to evolution .", "Without it , evolution cannot occur , because mutation provides the genetic variation necessary for selection and genetic drift .", "Each new mutation in an individual can increase its fitness , decrease its fitness , or have no effect on its fitness .", ...	[ "Mutation is fundamental to evolution , because it generates the genetic variation on which selection can act .", "In nature , genetic changes often increase the mutation rate in systems that range from viruses and bacteria to human tumors .", "Such an increase promotes the accumulation of frequent deleterious ...	[ "Mutation is of central importance in biology .", "It creates genetic variation , the raw material of evolution by natural selection , It can improve traits and organisms , but can also lead to phenomena like cancerous cells and antibiotic resistant pathogens .", "Increasing the mutation rate can accelerate evo...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "cost-effectiveness analysis", "infectious disease epidemiology", "economic analysis", "tropical diseases", "social sciences", "parasitic diseases", "health care", "research design", "global health", "neglected tropical diseases", "population biology", "infect...	Diagnostic Accuracy and Cost-Effectiveness of Alternative Methods for Detection of Soil-Transmitted Helminths in a Post-Treatment Setting in Western Kenya	journal.pntd.0002843	null	[ [ "The reliable mapping , surveillance and evaluation of infectious diseases relies upon two key factors:", "( i ) accurate methods of diagnosis and", "( ii ) optimal strategies to sample the population .", "For the soil-transmitted helminths ( STH: Ascaris lumbricoides , Trichuris trichiura and hoo...	[ "This study evaluates the diagnostic accuracy and cost-effectiveness of the Kato-Katz and Mini-FLOTAC methods for detection of soil-transmitted helminths ( STH ) in a post-treatment setting in western Kenya .", "A cost analysis also explores the cost implications of collecting samples during school surveys when c...	[ "Accurate methods of diagnosis and optimal strategies to sample the population are essential for the reliable mapping and surveillance of infectious diseases .", "The current standard for detection of soil-transmitted helminths ( STH ) entails use of the Kato-Katz diagnostic method .", "Alternative diagnostic m...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology", "viruses and cancer", "viral enzymes", "biology", "microbiology", "viral replication" ]	Dual Short Upstream Open Reading Frames Control Translation of a Herpesviral Polycistronic mRNA	journal.ppat.1003156	null	[ [ "Translation initiation of eukaryotic mRNAs is dependent on the 5′ mRNA cap and proceeds by ribosomal scanning until recognition of an AUG codon in a favorable context [1] , [2] .", "As a consequence of the translation machinery not engaging start codons at internal positions within the mRNA , eukaryotic ...	[ "The Kaposi's sarcoma-associated herpesvirus ( KSHV ) protein kinase , encoded by ORF36 , functions to phosphorylate cellular and viral targets important in the KSHV lifecycle and to activate the anti-viral prodrug ganciclovir .", "Unlike the vast majority of mapped KSHV genes , no viral transcript has been ident...	[ "Kaposi's sarcoma-associated herpesvirus ( KSHV ) is the etiologic agent of multicentric Castleman's disease , primary effusion lymphoma and Kaposi's sarcoma .", "KSHV expresses a number of transcripts with the potential to generate multiple proteins , yet relies on the cellular translation machinery that is prim...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "plant anatomy", "engineering and technology", "cell cycle and cell division", "cell processes", "trees", "mutation", "substitution mutation", "plant science", "peach trees", "plant genomics", "plants", "extraction techniques", "flower anatomy", "research and analysis me...	The architecture of intra-organism mutation rate variation in plants	journal.pbio.3000191	The rates of accumulation of mutations vary between different parts of a plant, with lower rates when mutations have greater potential longevity (such as in leaves) than in short-lived structures (such as petals).	[ [ "In some animals , the germline is segregated early in development , thereby preventing many ( i . e . , somatic ) mutations from being transmitted to progeny [1] .", "Given this , classical theory of senescence posits that organisms have no vested interest in keeping the somatic mutation rate under contr...	[ "Given the disposability of somatic tissue , selection can favor a higher mutation rate in the early segregating soma than in germline , as seen in some animals .", "Although in plants intra-organismic mutation rate heterogeneity is poorly resolved , the same selectionist logic can predict a lower rate in shoot t...	[ "Whereas there has been considerable attention paid to understanding differences in the mutation rate between different species , much less is known about variation in the mutation rate within individuals of multicellular species .", "In animals , evidence suggests that the segregated germline has a lower mutatio...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer	journal.pntd.0004158	null	[ [ "Buruli ulcer ( BU ) is a neglected necrotizing skin and bone disease caused by the enigmatic pathogen Mycobacterium ulcerans that occurs in riverine regions of West and Central Africa .", "The clonal nature of M . ulcerans has complicated molecular analyses of the epidemiology of the pathogen , as genoty...	[ "Increased availability of Next Generation Sequencing ( NGS ) techniques allows , for the first time , to distinguish relapses from reinfections in patients with multiple Buruli ulcer ( BU ) episodes .", "We compared the number and location of single nucleotide polymorphisms ( SNPs ) identified by genomic screeni...	[ "We compared the whole genomes of four pairs of Mycobacterium ulcerans isolates collected at the time of first diagnosis and at recurrence , derived from a collection of almost 5000 well characterized clinical samples from one BU treatment center in Benin .", "Our findings suggest that after surgical treatment—wi...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "agriculture" ]	Global Expression Profiling of Transcription Factor Genes Provides New Insights into Pathogenicity and Stress Responses in the Rice Blast Fungus	journal.ppat.1003350	null	[ [ "Fungal pathogenesis requires well-orchestrated regulation of multiple cellular and developmental processes in response to diverse stimuli from the host and the environment .", "Transcription factors ( TFs ) function as key regulators of such processes .", "Identification of TF genes , which typically...	[ "Because most efforts to understand the molecular mechanisms underpinning fungal pathogenicity have focused on studying the function and role of individual genes , relatively little is known about how transcriptional machineries globally regulate and coordinate the expression of a large group of genes involved in p...	[ "Rice blast disease , caused by Magnaporthe oryzae , destroys rice crop enough to feed 60 million people every year and has served as a model pathosystem for understanding host-parasite interactions .", "However , little is known about how M . oryzae globally regulates and coordinates its gene expression at the w...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mongolian gerbil (meriones unguiculatus)", "cell biology" ]	Meiotic Pairing and Segregation of Achiasmate Sex Chromosomes in Eutherian Mammals: The Role of SYCP3 Protein	journal.pgen.0030198	null	[ [ "The proper distribution of chromosomes into daughter cells during meiosis depends on the essential phenomena of pairing , synapsis , recombination , and segregation .", "During early prophase I homologous chromosomes associate in pairs and are held by a proteinaceous structure , the synaptonemal complex ...	[ "In most eutherian mammals , sex chromosomes synapse and recombine during male meiosis in a small region called pseudoautosomal region .", "However in some species sex chromosomes do not synapse , and how these chromosomes manage to ensure their proper segregation is under discussion .", "Here we present a stud...	[ "Meiosis is a special kind of cell division that leads to the formation of gametes .", "During meiosis the number of chromosomes must be halved in the daughter cells , and to do this properly , most organisms use an amazing strategy: during the first of the two meiotic divisions , homologous chromosomes associate...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Statistical analysis" ]	[ "phosphorylation", "antimicrobials", "trophozoites", "parasite groups", "medicine and health sciences", "chemical compounds", "oxidative stress", "drugs", "microbiology", "carbohydrates", "parasitic protozoans", "polyribosomes", "parasitology", "organic compounds", "glucose", "apicompl...	Phosphorylation of Eukaryotic Initiation Factor-2α during Stress and Encystation in Entamoeba Species	journal.ppat.1006085	null	[ [ "Entamoeba histolytica is an intestinal parasite that is the causative agent of amebic dysentery and amoebic liver abscesses .", "It is transmitted by the cyst form of the pathogen in fecally-contaminated food and water , making it prevalent in the developing world where sanitation practices are substanda...	[ "Entamoeba histolytica is an enteric pathogen responsible for amoebic dysentery and liver abscess .", "It alternates between the host-restricted trophozoite form and the infective environmentally-stable cyst stage .", "Throughout its lifecycle E . histolytica experiences stress , in part , from host immune pres...	[ "Entamoeba histolytica is the causative agent of amoebic dysentery and liver abscess and is prevalent in underdeveloped countries that lack proper sanitation .", "Infection is acquired by ingestion of the cyst form in contaminated food or water .", "During infection , the parasite experiences stress including d...	2016
[ "Introduction", "Results/Discussion", "Materials & methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "legs", "morphogenic segmentation", "limbs (anatomy)", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "animal anatomy", "experimental organism systems", "epigenetics", ...	Evolution and multiple roles of the Pancrustacea specific transcription factor zelda in insects	journal.pgen.1006868	null	[ [ "Gene regulatory networks ( GRNs ) depend on the coevolution of transcription factors ( TFs ) and their relationship with the cis-regulatory modules ( CRMs ) they bind [1 , 2] .", "In insects , the detailed role of a number of TFs and CRMs have been well-described , particularly during the embryogenesis o...	[ "Gene regulatory networks ( GRNs ) evolve as a result of the coevolutionary processes acting on transcription factors ( TFs ) and the cis-regulatory modules they bind .", "The zinc-finger TF zelda ( zld ) is essential for the maternal-to-zygotic transition ( MZT ) in Drosophila melanogaster , where it directly bi...	[ "Pioneer transcription factors ( TFs ) are considered the first regulators of chromatin accessibility in fruit flies and vertebrates , modulating the expression of a large number of target genes .", "In fruit flies , zelda resembles a pioneer TF , being essential during early embryogenesis .", "However , the ev...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "evolutionary biology", "3' utr", "oxidative stress", "messenger rna", "geographical locations", "population genetics", "reporter genes", "animals", "animal models", "drosophila melanogaster", "model organisms", "untranslated regions", "gene types", "population biology",...	An Indel Polymorphism in the MtnA 3' Untranslated Region Is Associated with Gene Expression Variation and Local Adaptation in Drosophila melanogaster	journal.pgen.1005987	null	[ [ "Natural populations adapt constantly to their changing environments , with alterations in protein sequences and gene expression providing the main sources of variation upon which natural selection can act .", "At present , understanding how changes in gene expression contribute to adaptation is one of th...	[ "Insertions and deletions ( indels ) are a major source of genetic variation within species and may result in functional changes to coding or regulatory sequences .", "In this study we report that an indel polymorphism in the 3’ untranslated region ( UTR ) of the metallothionein gene MtnA is associated with gene ...	[ "Although molecular variation is abundant in natural populations , understanding how this variation affects organismal phenotypes that are subject to natural selection remains a major challenge in the field of evolutionary genetics .", "Here we show that a deletion mutation in a noncoding region of the Drosophila...	2016

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