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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "genetics and genomics/cancer genetics", "genetics and genomics/bioinformatics" ]	p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair	journal.pgen.1000680	null	[ [ "p53 acts as a tumor suppressor gene by transcriptionally regulating a multitude of target genes in response to DNA damage [1] .", "Induction of these genes results in multiple cellular fates including apoptosis and cell cycle arrest .", "p63 and p73 share some of the same functions as p53; however , ...	[ "The p53 family activates many of the same genes in response to DNA damage .", "Because p63 and p73 have structural differences from p53 and play distinct biological functions in development and metastasis , it is likely that they activate a unique transcriptional network .", "Therefore , we performed a genome-...	[ "p63 and p73 have been identified as important suppressors of tumorigenesis and metastasis .", "Although they are structurally similar to p53 , they have many functions that are unique including roles in development and metastasis .", "Here we show , using a genome-wide analysis of cells lacking p63 and p73 ind...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "genetics and genomics/nuclear structure and function", "genetics and genomics/chromosome biology", "biochemistry/replication and repair", "genetics and genomics/gene function" ]	Mouse TRIP13/PCH2 Is Required for Recombination and Normal Higher-Order Chromosome Structure during Meiosis	journal.pgen.1001062	null	[ [ "Meiosis generates haploid gametes from a diploid progenitor in order for proper ploidy to be restored after fertilization .", "Meiocytes accomplish haploidization by performing two rounds of chromosome segregation after a single round of replication .", "During prophase of the first meiotic division ...	[ "Accurate chromosome segregation during meiosis requires that homologous chromosomes pair and become physically connected so that they can orient properly on the meiosis I spindle .", "These connections are formed by homologous recombination closely integrated with the development of meiosis-specific , higher-ord...	[ "Meiosis is the specialized cell division that gives rise to reproductive cells such as sperm and eggs .", "During meiosis in most organisms , genetic information is exchanged between homologous maternal and paternal chromosomes through the process of homologous recombination .", "This recombination forms conne...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune activation", "immunity to infections", "immunology", "vaccination and immunization", "white blood cells", "inflammation", "animal cells", "t cells", "immune response", "immune system", "cell biology", "clinical immuno...	Dynamic Functional Modulation of CD4+ T Cell Recall Responses Is Dependent on the Inflammatory Environment of the Secondary Stimulus	journal.ppat.1004137	null	[ [ "During acute viral and bacterial infections , antigen-specific naïve T cells clonally expand and acquire effector functions that contribute to pathogen clearance .", "Upon elimination of the pathogen , a small proportion of effector T cells survive and differentiate into long-lived memory cells that prov...	[ "The parameters that modulate the functional capacity of secondary Th1 effector cells are poorly understood .", "In this study , we employ a serial adoptive transfer model system to show that the functional differentiation and secondary memory potential of secondary CD4+ effector T cells are dependent on the infl...	[ "A key to the development of strategies for manipulating immune responses is the identification of the factors that regulate the generation of memory T cells .", "Many vaccination strategies rely on multiple injections to boost memory cell numbers , yet the factors that regulate the function and survival of memor...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell growth and division", "cell biology", "cell biology/cytoskeleton" ]	Bicaudal D2, Dynein, and Kinesin-1 Associate with Nuclear Pore Complexes and Regulate Centrosome and Nuclear Positioning during Mitotic Entry	journal.pbio.1000350	Mammalian Bicaudal D2 is the missing molecular link between cytoplasmic motor proteins and the nucleus during nuclear positioning prior to the onset of mitosis.	[ [ "Spatial organization of eukaryotic cells requires active transport of proteins , macromolecular assemblies , and membrane organelles along cytoskeletal fibers .", "Transport is driven by motor proteins , which use actin and microtubules ( MTs ) as tracks for their movement .", "Cytoskeletal elements ...	[ "BICD2 is one of the two mammalian homologues of the Drosophila Bicaudal D , an evolutionarily conserved adaptor between microtubule motors and their cargo that was previously shown to link vesicles and mRNP complexes to the dynein motor .", "Here , we identified a G2-specific role for BICD2 in the relative posit...	[ "Bidirectional microtubule-based transport is responsible for the positioning of a large variety of cellular organelles , but the molecular mechanisms underlying the recruitment of microtubule-based motors to their cargoes and their activation remain poorly understood .", "In particular , the molecular players in...	2010
[ "Introduction", "Results", "Discussion", "Methods and Materials" ]	[]	Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape	journal.pgen.1005203	null	[ [ "Pathogens constantly drive the evolution of populations they infect [1 , 2] .", "The burden of pathogens on host fitness results in selective pressure on both genes involved in immunity and host factors that are hijacked to promote infection .", "Therefore , alleles providing some measure of resistan...	[ "A diverse subset of pattern recognition receptors ( PRRs ) detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms .", "Reflecting their importance for host defense , pathogens encode various countermeasures to evade or inhibit these immune effectors .", "PRRs di...	[ "A pathogen’s ability to infect new individuals within and across species is largely driven by its capacity to hijack cellular machinery and overcome the immune system .", "Pathogens have evolved multiple means to evade and shut down host immunity .", "Typically , mechanisms of inactivation involve direct inter...	2015
[ "Introduction", "Methods", "Household Risk factors Survey", "Statistical Analysis", "Ethical Considerations", "Results", "Clinical Yaws", "Treponemal RDT Results", "Risk Factors Associated with TF", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "chlamydia trachomatis", "pathogens", "immunology", "tropical diseases", "geographical locations", "vanuatu", "microbiology", "health care", "treponematoses", "bacterial diseases", "signs and symptoms", "eye diseases", ...	Integrated Mapping of Yaws and Trachoma in the Five Northern-Most Provinces of Vanuatu	journal.pntd.0005267	null	[ [ "The World Health Assembly has targeted yaws and trachoma for global eradication and elimination-as-a-public-health-problem , respectively , by the year 2020[1] .", "Both are neglected tropical diseases found in rural areas of the world’s poorest countries .", "Trachoma is the world’s most common infe...	[ "Yaws and trachoma are targeted for eradication and elimination as public health problems .", "In trachoma-endemic populations mass administration of azithromycin can simultaneously treat yaws .", "We conducted a population-based prevalence survey in the five northernmost provinces of Vanuatu , where trachoma a...	[ "Yaws and trachoma are infectious diseases targeted by the World Health Organization ( WHO ) for eradication and elimination as a public health problem , respectively .", "Both diseases are found in the rural , isolated and underserved communities of the world’s poorest countries .", "The WHO strategy for trach...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "public health and epidemiology", "chemical biology/biocatalysis", "infectious diseases/neglected tropical diseases", "biochemistry/protein chemistry", "biochemistry/macromolecular chemistry", "molecular biology/bioinformatics", "computational biology/protein structure prediction", "...	Purification and Functional Characterisation of Rhiminopeptidase A, a Novel Aminopeptidase from the Venom of Bitis gabonica rhinoceros	journal.pntd.0000796	null	[ [ "A detailed understanding of the components of snake venom is important both for acquiring a more complete understanding of the pathology of envenoming and to aid in the development of improved treatments for snake bites , which are the cause of many deaths throughout the world each year .", "Snake venoms...	[ "Snake bite is a major neglected public health issue within poor communities living in the rural areas of several countries throughout the world .", "An estimated 2 . 5 million people are bitten by snakes each year and the cost and lack of efficacy of current anti-venom therapy , together with the lack of detaile...	[ "Snake bite is a major neglected public health issue causing an estimated 125 , 000 deaths each year , predominantly within poor communities living in rural areas of countries in South East Asia and Africa .", "Current treatments for snake bites are costly and have limited effectiveness , thus there is a need to ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "physics/interdisciplinary physics", "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Efficient Physical Embedding of Topologically Complex Information Processing Networks in Brains and Computer Circuits	journal.pcbi.1000748	null	[ [ "Since the publication of Watts and Strogatz's seminal article , “Collective dynamics of ‘small-world’ networks” , network science , as it has now come to be called , has extensively pervaded the scientific community , transcending previously impermeable boundaries between disciplines at every turn [1] .", ...	[ "Nervous systems are information processing networks that evolved by natural selection , whereas very large scale integrated ( VLSI ) computer circuits have evolved by commercially driven technology development .", "Here we follow historic intuition that all physical information processing systems will share key ...	[ "Brains are often compared to computers but , apart from the trivial fact that both process information using a complex physical pattern of connections , it has been unclear whether this is more than just a metaphor .", "In our work , we rigorously uncover novel quantitative organizational principles that underli...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mechanisms of resistance and susceptibility", "plant science", "virology", "plant pathogens", "plant biology", "plant pathology", "biology", "microbiology" ]	Viral Infection Induces Expression of Novel Phased MicroRNAs from Conserved Cellular MicroRNA Precursors	journal.ppat.1002176	null	[ [ "RNA-mediated gene silencing is a widespread mechanism of host defense against viral [1]–[6] and bacterial [7] infections .", "The 21–24 nt small RNAs , produced from DICER processing of double-stranded RNAs ( dsRNAs ) or RNA transcripts with stem-loop structures , are broadly defined as small interfering...	[ "RNA silencing , mediated by small RNAs including microRNAs ( miRNAs ) and small interfering RNAs ( siRNAs ) , is a potent antiviral or antibacterial mechanism , besides regulating normal cellular gene expression critical for development and physiology .", "To gain insights into host small RNA metabolism under in...	[ "Small RNA-mediated RNA silencing is a widespread antiviral or antibacterial mechanism in different organisms .", "Although the host and pathogen factors involved in this mode of host defense and pathogen counter-defense have been extensively investigated , much less is known about how a pathogen alters the small...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/gene expression", "computational biology/transcriptional regulation", "biophysics/theory and simulation", "computational biology/macromolecular sequence analysis", "biophysics/transcription and translation" ]	Thermodynamics-Based Models of Transcriptional Regulation by Enhancers: The Roles of Synergistic Activation, Cooperative Binding and Short-Range Repression	journal.pcbi.1000935	null	[ [ "We began by examining whether our models agree with existing data on transcriptional gene regulation during Drosophila embryonic development ( anterior–posterior axis specification ) .", "This involved training our model on 37–44 experimentally characterized CRMs and 6–8 transcription factors .", "Th...	[ "Quantitative models of cis-regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation .", "However , the few models available today have been based on simplistic assumptions about the sequences being modeled , or heuristic approximations of the underlying regula...	[ "The development of complex multicellular organisms requires genes to be expressed at specific stages and in specific tissues .", "Regulatory DNA sequences , often called cis-regulatory modules , drive the desired gene expression patterns by integrating information about the environment in the form of the activit...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders", "neuroscience", "genetics and genomics" ]	Neto1 Is a Novel CUB-Domain NMDA Receptor–Interacting Protein Required for Synaptic Plasticity and Learning	journal.pbio.1000041	Spatial learning and memory depend on the N-methyl-D-aspartic acid receptor, a synaptic ion channel regulated by Neto1. Impaired cognition due to the absence of Neto1 can be rescued pharmacologically, a finding with implications for the therapy of inherited learning defects in humans.	[ [ "In the mammalian central nervous system , excitatory transmission at synapses is mediated primarily by the amino acid glutamate , acting through the postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors ( AMPARs ) and N-methyl-D-aspartic acid receptors ( NMDARs ) [1] .", "Basal syna...	[ "The N-methyl-D-aspartate receptor ( NMDAR ) , a major excitatory ligand-gated ion channel in the central nervous system ( CNS ) , is a principal mediator of synaptic plasticity .", "Here we report that neuropilin tolloid-like 1 ( Neto1 ) , a complement C1r/C1s , Uegf , Bmp1 ( CUB ) domain-containing transmembran...	[ "The fundamental unit for information processing in the brain is the synapse , a highly specialized site of communication between the brain's multitude of individual neurons .", "The strength of the communication at each synapse changes in response to neuronal activity—a process called synaptic plasticity—allowin...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry/drug discovery", "genetics and genomics/gene expression", "biotechnology/chemical biology of the cell", "pharmacology/drug development", "molecular biology/bioinformatics", "computational biology/systems biology" ]	Transcriptional Profiling of the Dose Response: A More Powerful Approach for Characterizing Drug Activities	journal.pcbi.1000512	null	[ [ "The necessity of dose information in interpreting drug effects has been recognized since the 16th century , when Paracelsus observed: “All things are poison , and nothing is without poison: the dose alone makes a thing not poison” [1] .", "Today , dose-response models are routinely used to evaluate drug ...	[ "The dose response curve is the gold standard for measuring the effect of a drug treatment , but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis .", "One barrier to examining transcriptional dose responses is that existing methods for microarray data analy...	[ "Transcriptional profiling is arguably the most powerful hypothesis-free method for investigating biological effects of drugs—so why do the experiments typically use outmoded single-dose designs ?", "Such single-dose experiments will co-mingle effects that can occur with different potency ( e . g . , effects on t...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "immunology/innate immunity" ]	Potentiation of Epithelial Innate Host Responses by Intercellular Communication	journal.ppat.1001194	null	[ [ "Intestinal epithelial cells line the enteric mucosal surface and provide a physical barrier to maintain the integrity of this vulnerable body surface and prevent invasive infection by luminal microorganisms .", "Like professional immune cells , intestinal epithelial cells express receptors of the innate ...	[ "The epithelium efficiently attracts immune cells upon infection despite the low number of pathogenic microbes and moderate levels of secreted chemokines per cell .", "Here we examined whether horizontal intercellular communication between cells may contribute to a coordinated response of the epithelium .", "Li...	[ "All body surfaces are covered by a single layer of epithelial cells .", "Epithelial cells form a physical barrier to separate the underlying sterile tissue from the environment .", "In addition , epithelial cells actively sense bacterial and viral infection .", "The recognition of pathogenic microorganisms r...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "circuit models", "neurobiology of disease and regeneration", "medicine and health sciences", "computational neuroscience", "neurology", "biology and life sciences", "computational biology", "neuroscience" ]	Combined Role of Seizure-Induced Dendritic Morphology Alterations and Spine Loss in Newborn Granule Cells with Mossy Fiber Sprouting on the Hyperexcitability of a Computer Model of the Dentate Gyrus	journal.pcbi.1003601	null	[ [ "Several evidences have shown that prolonged seizures such as those in the animal models of Status Epilepticus ( SE ) induced by kainic acid or pilocarpine [1] act as a strong insult with consequent anatomical and functional sequelae .", "The neuroplastic changes associated to these alterations include ce...	[ "Temporal lobe epilepsy strongly affects hippocampal dentate gyrus granule cells morphology .", "These cells exhibit seizure-induced anatomical alterations including mossy fiber sprouting , changes in the apical and basal dendritic tree and suffer substantial dendritic spine loss .", "The effect of some of thes...	[ "Neurogenesis is currently a well known phenomenon in the adult brain , in special in some areas such as the subventricular zone and the dentate gyrus in the hippocampus , in which different endogenous and exogenous factors provoke cell proliferation .", "In the specific case of the dentate gyrus , granule cells ...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "medicine and health sciences", "pathology and laboratory medicine", "plant growth and development", "enzymes", "distillation", "plant embryo anatomy", "enzymology", "fungal structure", "developmental biology", "fungi", "plant science", "model organisms", "experimental org...	The morphogenesis-related NDR kinase pathway of Colletotrichum orbiculare is required for translating plant surface signals into infection-related morphogenesis and pathogenesis	journal.ppat.1006189	null	[ [ "Colletotrichum orbiculare ( syn . C . lagenarium ) is a plant pathogenic fungus causing anthracnose disease in cucumber ( Cucumis sativus ) .", "Like other Colletotrichum species , C . orbiculare infects host plants hemibiotrophically: first , C . orbiculare forms melanized appressoria that mediate the d...	[ "Plant infection by pathogenic fungi involves the differentiation of appressoria , specialized infection structures , initiated by fungal sensing and responding to plant surface signals .", "How plant fungal pathogens control infection-related morphogenesis in response to plant-derived signals has been unclear ."...	[ "Phytopathogenic fungi cause many of the most serious crop diseases .", "Many fungal pathogens form specialized infection structures , called appressoria in response to plant surface signals .", "Networks of protein kinase-based signaling pathways regulate a wide variety of key morphological processes including...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/rna-protein interactions", "genetics and genomics/functional genomics", "molecular biology/nucleolus and nuclear bodies", "molecular biology/translation mechanisms", "computational biology/molecular genetics", "genetics and genomics/bioinformatics", "cell biology/microbial growth and ...	Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics	journal.pbio.1000213	Gene networks are an efficient route for associating candidate genes with biological processes. Here, networks are used to discover more than 15 new genes for ribosomal subunit maturation, rRNA processing, and ribosomal export from the nucleus.	[ [ "In eukaryotic cells , the synthesis of ribosomes is a complex process involving several hundred genes whose functions span transcription of precursor ribosomal ribonucleic acids ( pre-rRNAs ) , processing of pre-rRNAs , assembly of ribosomal proteins ( r-proteins ) with pre-rRNAs , and nuclear export of the ...	[ "Biogenesis of ribosomes is an essential cellular process conserved across all eukaryotes and is known to require >170 genes for the assembly , modification , and trafficking of ribosome components through multiple cellular compartments .", "Despite intensive study , this pathway likely involves many additional g...	[ "Ribosomes are the extremely complex cellular machines responsible for constructing new proteins .", "In eukaryotic cells , such as yeast , each ribosome contains more than 80 protein or RNA components .", "These complex machines must themselves be assembled by an even more complex machinery spanning multiple c...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mathematics/statistics", "cell biology/cell growth and division", "computational biology/systems biology", "oncology/gastrointestinal cancers" ]	Tumor Growth Rate Determines the Timing of Optimal Chronomodulated Treatment Schedules	journal.pcbi.1000712	null	[ [ "Neurons located in the suprachiasmatic nuclei ( SCN ) of the hypothalamus form a dominant circadian pacemaker that controls timing of many physiological processes , including cell cycle .", "The pacemaker integrates environmental cues and communicates timing information to peripheral organs , which respo...	[ "In host and cancer tissues , drug metabolism and susceptibility to drugs vary in a circadian ( 24 h ) manner .", "In particular , the efficacy of a cell cycle specific ( CCS ) cytotoxic agent is affected by the daily modulation of cell cycle activity in the target tissues .", "Anti-cancer chronotherapy , in wh...	[ "Chronotherapy of cancers aims at exploiting daily physiological rhythms to improve anti-cancer efficacy and tolerance to drugs by administering treatments at a specific time of the day .", "Recent clinical trials have shown that chronotherapy can be beneficial in improving quality of life and median life span in...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "dengue virus", "medicine and health sciences", "parasite groups", "pathology and laboratory medicine", "plasmodium", "engineering and technology", "transportation", "pathogens", "vector-borne diseases", "microbiology", "tropical diseases", "parasitic diseases", "animals",...	Mosquitoes on a plane: Disinsection will not stop the spread of vector-borne pathogens, a simulation study	journal.pntd.0005683	null	[ [ "Mosquito-borne diseases such as malaria [1] and dengue [2] are major causes of morbidity and mortality globally .", "While these pathogens are endemic only in tropical and subtropical environments , modern air travel has broken down traditional geographic barriers to the extent that infected humans and m...	[ "Mosquito-borne diseases are increasingly being recognized as global threats , with increased air travel accelerating their occurrence in travelers and their spread to new locations .", "Since the early days of aviation , concern over the possible transportation of infected mosquitoes has led to recommendations t...	[ "Vector-borne diseases such as malaria , dengue , yellow fever , and Zika are global challenges to public health .", "International policies , such as the International Health Regulations , call for controlling mosquitoes on aircraft to prevent the introduction of mosquito-borne pathogens and invasive mosquito sp...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "veterinary diseases", "clinical immunology", "zoonotic diseases", "allergy and hypersensitivity", "parasitic diseases", "veterinary science", "helminth infection", "foodborne diseases" ]	Anti-Anisakis IgE Seroprevalence in the Healthy Croatian Coastal Population and Associated Risk Factors	journal.pntd.0002673	null	[ [ "Anisakidosis is a zoonotic disease caused by members of the nematode family Anisakidae , whereas anisakiasis ( = anisakiosis ) is caused by members of the genus Anisakis [1] .", "It is considered one of the most significant emerging food-borne diseases [2] , [3] , [4] because the more stringent measures ...	[ "The main objective of the study was to determine the degree of sensitization to Anisakis spp .", "antigens in healthy coastal population of Dalmatia given the high thermally unprocessed fish intake rate present in this area , suggested as a significant risk factor for anisakiasis .", "We performed a monocenter...	[ "Anisakiasis is a zoonosis induced by infection with the Anisakis third-stage larvae , contracted through consumption of thermally unprocessed or lightly processed seafood .", "Its diagnosis is difficult to suspect in countries where the illness was not previously reported , where it is infrequent , or in the cas...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "hematology/disorders of red cell metabolism", "mathematics", "computational biology/metabolic networks", "biochemistry/theory and simulation", "computational biology/systems biology" ]	Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles	journal.pcbi.1000319	null	[ [ "Robustness , the notion that biological systems must be able to withstand a variety of perturbations is becoming a cornerstone of research in systems biology .", "Indeed , several approaches have been developed to understand this concept .", "These approaches tend to focus on the levels of genotype ,...	[ "Robustness of organisms is widely observed although difficult to precisely characterize .", "Performance can remain nearly constant within some neighborhood of the normal operating regime , leading to homeostasis , but then abruptly break down with pathological consequences beyond this neighborhood .", "Curren...	[ "The ability of organisms to survive under a multitude of conditions is readily apparent .", "This robustness in performance is difficult to precisely characterize and quantify .", "At a biochemical level , it leads to physiological behavior when the parameters of the system remain within some neighborhood of t...	2009
[ "Introduction", "Model", "Results", "Discussion" ]	[]	Electrodiffusive Model for Astrocytic and Neuronal Ion Concentration Dynamics	journal.pcbi.1003386	null	[ [ "The interaction between neurons and glial cells has been the topic of many recent studies within the field of neuroscience ( see reviews in [1]–[3] ) .", "Astrocytes ( a species of glial cells ) play an important role in modulating excitatory and inhibitory synapses by removal , metabolism , and release ...	[ "The cable equation is a proper framework for modeling electrical neural signalling that takes place at a timescale at which the ionic concentrations vary little .", "However , in neural tissue there are also key dynamic processes that occur at longer timescales .", "For example , endured periods of intense neu...	[ "When neurons generate electrical signals they release potassium ions ( K+ ) into the extracellular space .", "During periods of intense neural activity , the local extracellular K+ may increase drastically .", "If it becomes too high , it can lead to neural dysfunction .", "Astrocytes ( a kind of glial cells...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	In Vivo MRI Assessment of Hepatic and Splenic Disease in a Murine Model of Schistosmiasis	journal.pntd.0004036	null	[ [ "Present in many tropical and subtropical countries , schistosomiasis ( or bilharzia ) , the second most prevalent parasitic disease in the world after malaria , affects more than 260 million people and leads to 200 000 deaths per year [1] .", "This helminthic disease is caused by trematodes of the Schist...	[ "Schistosomiasis ( or bilharzia ) , a major parasitic disease , affects more than 260 million people worldwide .", "In chronic cases of intestinal schistosomiasis caused by trematodes of the Schistosoma genus , hepatic fibrosis develops as a host immune response to the helminth eggs , followed by potentially leth...	[ "Schistosomiasis ( or bilharzia ) , a major helminth disease , affects more than 260 million people worldwide .", "While the adult worms survive for years within veins of the gastrointestinal system , symptoms are due to inflammatory reactions to their eggs in several organs .", "Hepatic fibrosis may develop in...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/neuronal signaling mechanisms", "neuroscience/theoretical neuroscience" ]	A New Approach for Determining Phase Response Curves Reveals that Purkinje Cells Can Act as Perfect Integrators	journal.pcbi.1000768	null	[ [ "Cerebellar Purkinje cells exhibit a wide range of dynamical phenomena .", "They are intrinsic neural oscillators , firing spontaneously and highly rhythmically in the absence of synaptic input , at a rate of 10–180 Hz [1]–[5] .", "They also exhibit intrinsic bistability [2] , [3] , which influences t...	[ "Cerebellar Purkinje cells display complex intrinsic dynamics .", "They fire spontaneously , exhibit bistability , and via mutual network interactions are involved in the generation of high frequency oscillations and travelling waves of activity .", "To probe the dynamical properties of Purkinje cells we measur...	[ "By observing how brief current pulses injected at different times between spikes change the phase of spiking of a neuron ( and thus obtaining the so-called phase response curve ) , it should be possible to predict a full spike train in response to more complex stimulation patterns .", "When we applied this tradi...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "genome expression analysis", "cardiovascular", "animal models", "model organisms", "chromosomal disorders", "biology", "down syndrome", "congenital heart disease", "clinical genetics", "genetic screens", "genetics", "genomics", "genetics of disease", "genetics and genomics",...	Over-Expression of DSCAM and COL6A2 Cooperatively Generates Congenital Heart Defects	journal.pgen.1002344	null	[ [ "The Online Inheritance in Man ( OMIM ) lists over 3500 loci which when mutated give rise to heritable human disease .", "Approximately one third of these disorders are dominant , most of these cases being due to dosage sensitive requirements for gene function ( i . e . , haploinsufficiency or elevated ge...	[ "A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders .", "One of the best characterized polygenic diseases is Down syndrome ( DS ) , which results from an extra copy of part or all of chromosome 21 .", "A short interval near t...	[ "A large fraction of human genes may contribute to polygenic disorders , yet few experimental methods for identifying such genes are currently available .", "For example , with regard to congenital heart defects ( CHD ) caused by extra copies of genes on chromosome 21 in Down syndrome patients , it is not known w...	2011
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "immunodeficiency viruses", "viruslike particles", "population modeling", "evolutionary modeling", "virology", "synthetic biology", "biology", "computational biology", "infectious disease modeling", "microbiology", "molecular biology" ]	Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies	journal.pcbi.1002015	null	[ [ "The TIP concept capitalizes upon and extends the phenomenon of interfering particles that occur naturally in many viruses , spread along with the viral pathogen [15] , and have demonstrated potential therapeutic efficacy against HIV [16] , [17] , [18] , [19] .", "TIPs are minimal versions of the pathogen...	[ "Infectious disease treatments , both pharmaceutical and vaccine , face three universal challenges: the difficulty of targeting treatments to high-risk ‘superspreader’ populations who drive the great majority of disease spread , behavioral barriers in the host population ( such as poor compliance and risk disinhibi...	[ "We introduce a proposed intervention against infectious diseases that extends and optimizes the recognized benefit of ‘transmissible immunization’ that occurs with live-attenuated vaccines such as Oral Polio Vaccine ( OPV ) , the vaccine chosen for the worldwide polio eradication campaign .", "The intervention p...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "developmental biology", "biology and life sciences", "gene regulatory networks", "computational biology" ]	Reconstruction of the Gene Regulatory Network Involved in the Sonic Hedgehog Pathway with a Potential Role in Early Development of the Mouse Brain	journal.pcbi.1003884	null	[ [ "Pattern formation in early animal development is controlled by signal transduction cascades , in which transcription factors ( TFs ) play crucially important roles as downstream effectors .", "The signal transduction cascades together with the gene regulatory networks they activate determine the temporal...	[ "The Sonic hedgehog ( Shh ) signaling pathway is crucial for pattern formation in early central nervous system development .", "By systematically analyzing high-throughput in situ hybridization data of E11 . 5 mouse brain , we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expre...	[ "Recent large-scale projects of high-throughput in situ hybridization ( ISH ) have generated a wealth of spatiotemporal information on gene expression patterns in the early mouse brain .", "We have developed a computational approach that combines publicly available high-throughput ISH data with our own experiment...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Genetic Incompatibility Accelerates Adaptation in Yeast	journal.pgen.1005407	null	[ [ "DNA mismatch repair ( MMR ) acts primarily during DNA replication in prokaryotes and eukaryotes to correct DNA polymerase misincorporation errors that include base substitutions , frameshift mutations , and insertions/deletions [1–3] .", "In S . cerevisiae MutS homolog ( MSH ) heterodimers can track with...	[ "During mismatch repair ( MMR ) MSH proteins bind to mismatches that form as the result of DNA replication errors and recruit MLH factors such as Mlh1-Pms1 to initiate excision and repair steps .", "Previously , we identified a negative epistatic interaction involving naturally occurring polymorphisms in the MLH1...	[ "In nature , bacterial populations with high mutation rates can adapt faster to new environments by acquiring beneficial mutations .", "However , such populations also accumulate harmful mutations that reduce their fitness .", "We show that the model eukaryote baker’s yeast can use a similar mutator strategy to...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "vesicles", "classical mechanics", "protein interactions", "membrane proteins", "materials science", "damage mechanics", "protein structure", "oligomers", "cellular structures and organelles", "polymer chemistry", "proteins", "deformation", "chemistry", "liposomes", "molecular biology", ...	ACAP1 assembles into an unusual protein lattice for membrane deformation through multiple stages	journal.pcbi.1007081	null	[ [ "Membrane deformation is needed for a wide range of cellular processes , including intracellular transport , organelle biogenesis , cell division , and cell motility [1 , 2] .", "Some of the best characterized proteins that deform membrane possess a Bin-Amphiphysin-Rvs ( BAR ) domain [3–8] .", "Studie...	[ "Studies on the Bin-Amphiphysin-Rvs ( BAR ) domain have advanced a fundamental understanding of how proteins deform membrane .", "We previously showed that a BAR domain in tandem with a Pleckstrin Homology ( PH domain ) underlies the assembly of ACAP1 ( Arfgap with Coil-coil , Ankryin repeat , and PH domain I ) i...	[ "Membrane remodeling is needed for a wide range of cellular events .", "Our current understanding of how proteins bend membrane to achieve such remodeling has come , in large part , from studies on proteins that contain the BAR domain .", "These studies have elucidated that the BAR domain dimerize to form a cre...	2019
[ "Introduction", "Methods", "Results and discussion" ]	[ "computer applications", "education", "decision making", "sociology", "social sciences", "neuroscience", "age groups", "adults", "cognitive psychology", "cognition", "computer and information sciences", "behavior", "educational attainment", "people and places", "psychology", "reasoning...	Human behavioral complexity peaks at age 25	journal.pcbi.1005408	null	[ [ "Knowledge forming the content of several academic fields , including mathematics , follows from precocious core knowledge [1–3] , and then follows a specific developmental course along the lifespan [4] .", "Numerosity ( our approximate implicit sense of quantity ) has been a privileged target of recent r...	[ "Random Item Generation tasks ( RIG ) are commonly used to assess high cognitive abilities such as inhibition or sustained attention .", "They also draw upon our approximate sense of complexity .", "A detrimental effect of aging on pseudo-random productions has been demonstrated for some tasks , but little is a...	[ "It has been unclear how this ability evolves over a person’s lifetime and it had not been possible to be assessed with previous classical tools for statistical randomness .", "To better understand how age impacts behavior , we have assessed more than 3 , 400 people aged 4 to 91 years old .", "Each participant ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biology and life sciences", "microbiology", "computational biology" ]	Genome-Scale Metabolic Network Validation of Shewanella oneidensis Using Transposon Insertion Frequency Analysis	journal.pcbi.1003848	null	[ [ "Transposon mutant analysis has been extensively used to generate genome-wide mutant libraries and to define gene essentiality [1] , [2] .", "With the introduction of parallel sequencing , transposon-based methods have developed into phenotype information gathering tools , rather than forward genetic scre...	[ "Transposon mutagenesis , in combination with parallel sequencing , is becoming a powerful tool for en-masse mutant analysis .", "A probability generating function was used to explain observed miniHimar transposon insertion patterns , and gene essentiality calls were made by transposon insertion frequency analysi...	[ "Metabolic modeling techniques play a central role in rational design of industrial strains , personalized medicine , and automated network reconstruction .", "However , due to the large size of models , very few have been comprehensively tested using single gene knockout mutants for every gene in the model .", ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "clinical laboratory sciences", "geographical locations", "tropical diseases", "neglected tropical diseases", "infectious disease control", "research facilities", "research and analysis methods", "infectious diseases", "sri lanka", "dengue fever", "epidemiology"...	Laboratory-Enhanced Dengue Sentinel Surveillance in Colombo District, Sri Lanka: 2012-2014	journal.pntd.0004477	null	[ [ "Dengue is one of the most important vector-borne viral disease worldwide , transmitted by Aedes mosquitoes and caused by any of the four dengue virus serotypes [1] .", "The extent of dengue transmission and therefore the risk of outbreaks is determined by a combination of various factors; these include t...	[ "Dengue has emerged as a significant public health problem in Sri Lanka .", "Historically surveillance was passive , with mandatory dengue notifications based on clinical diagnosis with only limited laboratory confirmation .", "To obtain more accurate data on the disease burden of dengue , we set up a laborator...	[ "The dramatic spread of epidemic dengue underscores the urgent need for better surveillance and control of this disease .", "The main purpose of surveillance is to provide timely and more accurate information to institute preventive or control measures for epidemic dengue .", "Dengue has emerged as a major publ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunity", "virology", "biology", "microbiology" ]	Dengue Virus Infection of the Aedes aegypti Salivary Gland and Chemosensory Apparatus Induces Genes that Modulate Infection and Blood-Feeding Behavior	journal.ppat.1002631	null	[ [ "With 2 . 5 billion people now living in areas at risk for epidemic transmission , dengue has become the most important mosquito-borne viral disease affecting humans [1] .", "Dengue virus ( DENV ) is a positive-strand RNA virus of the family Flaviviridae , genus Flavivirus .", "It exists as four close...	[ "The female Aedes aegypti salivary gland plays a pivotal role in bloodmeal acquisition and reproduction , and thereby dengue virus ( DENV ) transmission .", "It produces numerous immune factors , as well as immune-modulatory , vasodilatory , and anti-coagulant molecules that facilitate blood-feeding .", "To ass...	[ "Dengue virus ( DENV ) is transmitted between humans through the bite of infected Aedes aegypti mosquitoes .", "Since the virus is inoculated in saliva , infection of the mosquito salivary gland is an essential requirement for transmission .", "In addition , the gland also produces numerous biologically active ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biogeography", "livestock", "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "population genetics", "vertebrates", "animals", "mammals", "primates", "population biology", "infectious diseases", "swine", "geography", "zoonoses", ...	Clonal Evolution of Enterocytozoon bieneusi Populations in Swine and Genetic Differentiation in Subpopulations between Isolates from Swine and Humans	journal.pntd.0004966	null	[ [ "Microsporidia are obligate intracellular eukaryotic parasites that infect a wide range of animals and are closely related to fungi [1 , 2] .", "Genome analyses conducted in several recent studies strongly suggest that some species of microsporidia could have a diploid or polyploid stage and a sexual cycl...	[ "Enterocytozoon bieneusi is a widespread parasite with high genetic diversity among hosts .", "Its natural reservoir remains elusive and data on population structure are available only in isolates from primates .", "Here we describe a population genetic study of 101 E . bieneusi isolates from pigs using sequenc...	[ "This study explored the genetic characteristics of the ITS and four mini- and microsatellite markers and assessed the population structure and substructures in 101 E . bieneusi isolates from pigs in China .", "The measures of LD and recombination events supported the occurrence of clonal evolution among the isol...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "physics", "computational neuroscience", "interdisciplinary physics", "biology", "biophysics", "neuroscience" ]	Diversity and Noise Effects in a Model of Homeostatic Regulation of the Sleep-Wake Cycle	journal.pcbi.1002650	null	[ [ "Disorder , which originates from both noise and diversity , is naturally present in all biological systems .", "In neuronal systems some examples are the random opening and closing of ion channels , the multitude of stochastic input currents in the neurons , and the diversity of shapes , sizes , and elec...	[ "Recent advances in sleep neurobiology have allowed development of physiologically based mathematical models of sleep regulation that account for the neuronal dynamics responsible for the regulation of sleep-wake cycles and allow detailed examination of the underlying mechanisms .", "Neuronal systems in general ,...	[ "All biological systems are inherently noisy and heterogeneous .", "Disorder is mostly expected to disturb proper functioning of a system , like it can be the case with noise in a radio signal .", "However , it has been demonstrated by numerous studies that noise can actually improve signal encoding – the so-ca...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mathematics", "animal behavior", "statistics", "biology", "biostatistics", "zoology" ]	Leadership and Path Characteristics during Walks Are Linked to Dominance Order and Individual Traits in Dogs	journal.pcbi.1003446	null	[ [ "Groups that are not able to coordinate their actions and cannot reach a consensus on important events , such as where to go , will destabilise , and individuals will lose the benefits associated with being part of a group [1] , [2] .", "Decision-making usually involves some form of leadership , i . e . ‘...	[ "Movement interactions and the underlying social structure in groups have relevance across many social-living species .", "Collective motion of groups could be based on an “egalitarian” decision system , but in practice it is often influenced by underlying social network structures and by individual characteristi...	[ "How does a group of family dogs decide the direction of their collective movements ?", "Is there a leader , or is decision-making based on an egalitarian system ?", "Is leadership related to social dominance status ?", "We collected GPS trajectory data from an owner and her six dogs during several walks .", ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	An Enhancer Element Harboring Variants Associated with Systemic Lupus Erythematosus Engages the TNFAIP3 Promoter to Influence A20 Expression	journal.pgen.1003750	null	[ [ "TNFAIP3 encodes A20 , an ubiquitin-editing enzyme with a key role in negatively regulating NF-κB pathway activity downstream of activating cell surface receptors [1]–[4] .", "Murine models have been illustrative in demonstrating the importance of A20 in limiting immune responses .", "For example , mi...	[ "Functional characterization of causal variants present on risk haplotypes identified through genome-wide association studies ( GWAS ) is a primary objective of human genetics .", "In this report , we evaluate the function of a pair of tandem polymorphic dinucleotides , 42 kb downstream of the promoter of TNFAIP3...	[ "A key objective of human genetics is the identification and characterization of variants responsible for association with complex diseases .", "A pair of single nucleotide polymorphisms ( rs148314165 , rs200820567 ) 42 kb downstream from the promoter of TNFAIP3 , have been proposed as the variants responsible fo...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "bacterial diseases", "infectious diseases", "innate immune system", "medicine and health sciences", "immunity", "neglected tropical diseases", "biology and life sciences", "immunology", "microbiology", "tropical diseases", "leprosy", "immune system" ]	Differential Dermal Expression of CCL17 and CCL18 in Tuberculoid and Lepromatous Leprosy	journal.pntd.0003263	null	[ [ "Leprosy is a spectrum of illnesses involving the nerves , skin and upper airways of humans [1] .", "Depending on the host response to Mycobacterium leprae , the clinical presentation can vary widely between individuals [2] .", "Histologic features of these lesions can be quantitated on a 5 point clas...	[ "Leprosy is characterized by polar clinical , histologic and immunological presentations .", "Previous immunologic studies of leprosy polarity were limited by the repertoire of cytokines known at the time .", "We used a candidate gene approach to measure mRNA levels in skin biopsies from leprosy lesions .", "...	[ "Leprosy presents with a polarized spectrum , with lepromatous leprosy having high bacillary numbers and TH2 dermal cytokines , versus tuberculoid leprosy showing very few bacilli and TH1 cytokines .", "The mechanism underlying this polarized presentation is largely unknown .", "In the following study , we isol...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Lateral and End-On Kinetochore Attachments Are Coordinated to Achieve Bi-orientation in Drosophila Oocytes	journal.pgen.1005605	null	[ [ "It is well established that oocyte spindle assembly in many organisms occurs in the absence of centrosomes [1–3] .", "Instead , chromatin-based mechanisms play an important role in spindle assembly .", "The interactions between chromosomes and microtubules are paramount in oocytes , necessary for bot...	[ "In oocytes , where centrosomes are absent , the chromosomes direct the assembly of a bipolar spindle .", "Interactions between chromosomes and microtubules are essential for both spindle formation and chromosome segregation , but the nature and function of these interactions is not clear .", "We have examined ...	[ "In acentrosomal oocytes , spindle assembly depends on the chromosomes .", "The nature of the chromosome-microtubule interactions in oocytes that organize spindle bipolarity and orientation of the homologs has been unclear .", "We have found that several types of functional chromosome-microtubule interactions e...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "taxonomy", "applied mathematics", "split-decomposition method", "database searching", "simulation and modeling", "algorithms", "multiple alignment calculation", "optimization", "phylogenetics", "data management", "mathematics", "molecular biology techniques", "seq...	rasbhari: Optimizing Spaced Seeds for Database Searching, Read Mapping and Alignment-Free Sequence Comparison	journal.pcbi.1005107	null	[ [ "k-mers , i . e . words of length k , are used in many basic algorithms for biological sequence comparison .", "Word matches are used , for example , as seeds in the hit-and-extend approach to database searching and read mapping [1–3] .", "Here , fast algorithms are applied to find pairs of identical ...	[ "Many algorithms for sequence analysis rely on word matching or word statistics .", "Often , these approaches can be improved if binary patterns representing match and don’t-care positions are used as a filter , such that only those positions of words are considered that correspond to the match positions of the p...	[ "We propose a fast algorithm to generate spaced seeds for database searching , read mapping and alignment-free sequence comparison .", "Spaced seeds—i . e . patterns of match and don’t-care positions—are used by many algorithms for sequence analysis; designing optimal seeds is therefore an active field of researc...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "medicine and health sciences" ]	Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4+ T Cell Immunity	journal.ppat.1004085	null	[ [ "Whether viewed as a threat to human health in anthrax endemic regions , as a bioweapon , or as a potentially devastating pathogen of livestock , there is pressing need to gain better insights into the immune response to Bacillus anthracis .", "The urgency has been underlined by recent clusters of fatal a...	[ "Bacillus anthracis produces a binary toxin composed of protective antigen ( PA ) and one of two subunits , lethal factor ( LF ) or edema factor ( EF ) .", "Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity , in contrast to which understanding of cell...	[ "Anthrax is of concern with respect to human exposure in endemic regions , concerns about bioterrorism and the considerable global burden of livestock infections .", "The immunology of this disease remains poorly understood .", "Vaccination has been based on B . anthracis filtrates or attenuated spore-based vac...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "animal types", "medicine and health sciences", "zoonotic pathogens", "animal pathogens", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "vertebrates", "animals", "mammals", "vaccines", "preventive medicine", "viruses", "rabies", ...	A little goes a long way: Weak vaccine transmission facilitates oral vaccination campaigns against zoonotic pathogens	journal.pntd.0007251	null	[ [ "Zoonotic pathogens represent a global threat to human welfare .", "Rabies circulating in domestic dogs in Asia and Africa , for example , results in 59 , 000 human deaths each year [1] .", "Ebola , a disease that circulates in non-human primates and bats , killed over 11 , 000 people during the 2014 ...	[ "Zoonotic pathogens such as Ebola and rabies pose a major health risk to humans .", "One proven approach to minimizing the impact of a pathogen relies on reducing its prevalence within animal reservoir populations using mass vaccination .", "However , two major challenges remain for vaccination programs that ta...	[ "Zoonotic pathogens pose a significant health risk to humans .", "Mass vaccination programs have shown promise for controlling zoonoses in reservoir populations and , in turn , lessening the health burden posed to neighboring human populations .", "Despite some significant successes , major logistical challenge...	2019
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "developmental biology/developmental evolution", "computational biology/signaling networks", "computational biology/systems biology" ]	Predicting Phenotypic Diversity and the Underlying Quantitative Molecular Transitions	journal.pcbi.1000354	null	[ [ "During development , regulatory signaling networks instruct cell populations to form", "multicellular patterns and structures .", "To what extent perturbations in the", "quantitative performance of these networks may lead to phenotypic changes remains", "unclear .", "Experimental genetics...	[ "During development , signaling networks control the formation of multicellular", "patterns .", "To what extent quantitative fluctuations in these complex networks may", "affect multicellular phenotype remains unclear .", "Here , we describe a", "computational approach to predict and analyze the phenotypi...	[ "The diversity of metazoan life forms that we experience today arose as", "multicellular systems continually sampled new phenotypes that withstood ever", "changing selective pressures .", "This phenotypic diversification is driven by", "variations in the underlying regulatory network that instructs cells to...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "microbiology/parasitology", "infectious diseases/protozoal infections", "ecology/population ecology", "genetics and genomics/population genetics" ]	Additional Haplogroups of Toxoplasma gondii out of Africa: Population Structure and Mouse-Virulence of Strains from Gabon	journal.pntd.0000876	null	[ [ "Toxoplasma gondii is a worldwide haploid protozoan parasite , and distribution of its genotypes varies across the continents ( e . g . [1] ) .", "In Europe and the USA , T . gondii has a low genetic diversity with three main lineages , Type I , II and III , based on clonal population structure and virule...	[ "Toxoplasma gondii is found worldwide , but distribution of its genotypes as well as clinical expression of human toxoplasmosis varies across the continents .", "Several studies in Europe , North America and South America argued for a role of genotypes in the clinical expression of human toxoplasmosis .", "Gene...	[ "Prevalence of human toxoplasmosis in tropical African countries usually exceeds 50% .", "Its role as a major opportunistic infection of AIDS patients is regularly described .", "Due to the lack of investigation , congenital infection is certainly underestimated in Africa .", "Incidence of Toxoplasma ocular d...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "flow cytometry", "cell physiology", "medicine and health sciences", "respiratory infections", "293t cells", "biological cultures", "egfr signaling", "pulmonology", "epithelial cells", "animal models", "model organisms", "research and analysis methods", "animal cells", "proteins", "biolo...	EGFR Interacts with the Fusion Protein of Respiratory Syncytial Virus Strain 2-20 and Mediates Infection and Mucin Expression	journal.ppat.1005622	null	[ [ "Respiratory syncytial virus ( RSV ) is a human pathogen of the Pneumovirus genus within the Paramyxoviridae family .", "Worldwide , the virus causes over 30 million lower respiratory tract illnesses per year in children and is a leading cause of infant pneumonia mortality [1 , 2] .", "Despite a subst...	[ "Respiratory syncytial virus ( RSV ) is the major cause of viral lower respiratory tract illness in children .", "In contrast to the RSV prototypic strain A2 , clinical isolate RSV 2–20 induces airway mucin expression in mice , a clinically relevant phenotype dependent on the fusion ( F ) protein of the RSV strai...	[ "Respiratory syncytial virus ( RSV ) is responsible for severe lower respiratory disease in infants and young children .", "Overabundant airway mucus contributes to airway obstruction in RSV bronchiolitis , and a better understanding of RSV pathogenesis may contribute to needed therapies and vaccines .", "We re...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "animals", "dung beetles", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism systems", "epigenetics", "drosophila", "research and analysis methods", "genetic in...	Rhinoceros beetle horn development reveals deep parallels with dung beetles	journal.pgen.1007651	null	[ [ "A variety of morphological novelties have arisen and diversified through the course of animal evolution .", "Where studied , preexisting genetic networks redeployed in new developmental contexts have often been found to underlie the origin of these novel morphological traits , helping explain how a restr...	[ "Beetle horns are attractive models for studying the evolution of novel traits , as they display diverse shapes , sizes , and numbers among closely related species within the family Scarabaeidae .", "Horns radiated prolifically and independently in two distant subfamilies of scarabs , the dung beetles ( Scarabaei...	[ "Goliath and Hercules beetles include some of the largest insects known , and the horns they wield are spectacular .", "These ‘rhinoceros’ beetles form a subfamily within the Scarabaeidae , a clade containing ~35 , 000 primarily hornless species .", "The other subfamily of horned scarabs , dung beetles , is dis...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "theoretical biology", "disease dynamics", "population dynamics", "biology", "population biology" ]	Dynamics of Mutant Cells in Hierarchical Organized Tissues	journal.pcbi.1002290	null	[ [ "Many tissues have a hierarchical multi compartment structure in which each compartment represents a cell type at a certain stage of differentiation .", "This architecture has been well described for hematopoiesis [1] , [2] and epidermal cell turnover in the skin [3] , [4] or in the colonic crypt [5] .", ...	[ "Most tissues in multicellular organisms are maintained by continuous cell renewal processes .", "However , high turnover of many cells implies a large number of error-prone cell divisions .", "Hierarchical organized tissue structures with stem cell driven cell differentiation provide one way to prevent the acc...	[ "We investigate the average stem cell driven dynamics of cell counts in an abstract multi compartment model .", "Within this framework one can represent different tissue structures , as for example hematopoiesis , the skin or the colonic crypt .", "Our analysis is based on an individual cell model in which cell...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "microbiology", "mus (mouse)", "homo (human)", "eubacteria" ]	Hemophagocytic Macrophages Harbor Salmonella enterica during Persistent Infection	journal.ppat.0030193	null	[ [ "Salmonella enterica are Gram-negative bacteria that are acquired from contaminated food or water .", "Certain S . enterica subspecies can traverse the gut lumen of some mammals and then colonize lymphatic tissue , causing systemic infection .", "S . enterica subspecies Typhi colonize the human liver ...	[ "Salmonella enterica subspecies can establish persistent , systemic infections in mammals , including human typhoid fever .", "Persistent S . enterica disease is characterized by an initial acute infection that develops into an asymptomatic chronic infection .", "During both the acute and persistent stages , th...	[ "Microbes that establish persistent infections present serious problems for world health but are not well understood .", "The bacteria Salmonella enterica cause asymptomatic chronic infection in humans .", "Carriers shed the bacteria into the environment , leading to periodic acute typhoid fever epidemics .", ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "evolutionary biology", "population modeling", "population genetics", "biology", "computational biology", "microbiology", "genetics and genomics" ]	Highly Sensitive and Specific Detection of Rare Variants in Mixed Viral Populations from Massively Parallel Sequence Data	journal.pcbi.1002417	null	[ [ "Genetic differences can arise among individual viral particles within an infected host , and detecting these viral genetic variants can reveal how viruses adapt to challenges such as host immune responses , antiviral medications , and transmission bottlenecks .", "However , detecting rare variants is dif...	[ "Viruses diversify over time within hosts , often undercutting the effectiveness of host defenses and therapeutic interventions .", "To design successful vaccines and therapeutics , it is critical to better understand viral diversification , including comprehensively characterizing the genetic variants in viral i...	[ "New sequencing technologies provide unprecedented resolution to study pathogen populations , such as the single stranded RNA viruses HIV , dengue ( DENV ) , and West Nile ( WNV ) , and how they evolve within infected individuals in response to immune , therapeutic , and vaccine pressures .", "While these new tec...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome evolution", "chemical compounds", "salts", "fungi", "model organisms", "fungal evolution", "experimental organism systems", "saccharomyces", "research and analysis methods", "mycology", "sulfates", "molecular evolution", "chemistry", "comparative genomics", "evolutionary genetics...	Differential paralog divergence modulates genome evolution across yeast species	journal.pgen.1006585	null	[ [ "Understanding how organisms adapt to their environment is a fundamental goal of evolutionary biology .", "This goal has been complicated by the dependence on the reconstruction of historical events to make inferences about selective pressures and evolutionary mechanisms .", "Furthermore , it can be d...	[ "Evolutionary outcomes depend not only on the selective forces acting upon a species , but also on the genetic background .", "However , large timescales and uncertain historical selection pressures can make it difficult to discern such important background differences between species .", "Experimental evolutio...	[ "Both comparative genomics and experimental evolution are powerful tools that can be used to make inferences about evolutionary processes .", "Together , these approaches provide the opportunity to observe evolutionary adaptation over millions of years where selective history is largely unknown , and over short t...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "vaccines", "medicine", "vaccination", "clinical immunology", "immunity", "vaccine development", "biology", "microbiology", "immunology", "bacterial pathogens" ]	Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development	journal.pntd.0001302	null	[ [ "For more than 100 years devastating epidemics of meningococcal disease have occurred in sub-Saharan Africa [1] .", "In the decade 1988 to 1997 , more than 700 , 000 cases and over 100 , 000 deaths were reported .", "Public health responses were limited by scarce resources [2] .", "Further , the o...	[ "Factor H binding protein ( fHbp ) is an important antigen for vaccines against meningococcal serogroup B disease .", "The protein binds human factor H ( fH ) , which enables the bacteria to resist serum bactericidal activity .", "Little is known about the vaccine-potential of fHbp for control of meningococcal ...	[ "Epidemics of meningococcal meningitis are common in sub-Saharan Africa .", "Most are caused by encapsulated serogroup A strains , which rarely cause disease in industrialized countries .", "A serogroup A polysaccharide protein conjugate vaccine recently was introduced in some countries in sub-Saharan Africa ."...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "homo (human)", "genetics and genomics", "computational biology" ]	A Universal Mechanism Ties Genotype to Phenotype in Trinucleotide Diseases	journal.pcbi.0030235	null	[ [ "Trinucleotide diseases are hereditary disorders in which a gene that harbors a trinucleotide repeat is inherited with a number of repeats that exceeds a disease-specific threshold [1 , 2] .", "In the so-called polyglutamine diseases , including Huntington disease ( HD ) [3] , spinocerebellar ataxia ( SCA...	[ "Trinucleotide hereditary diseases such as Huntington disease and Friedreich ataxia are cureless diseases associated with inheriting an abnormally large number of DNA trinucleotide repeats in a gene .", "The genes associated with different diseases are unrelated and harbor a trinucleotide repeat in different func...	[ "Trinucleotide diseases are a broad family of hereditary diseases characterized genetically by an expanded DNA region consisting of a repeated three-letter code .", "Patients inheriting such an abnormal DNA region experience sudden disease onset at an age that inversely depends on the size of the expanded region ...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biotechnology", "developmental biology", "fisheries science", "ecology", "agriculture", "ecosystems", "coastal ecosystems", "aquaculture", "life cycles", "biology and life sciences", "intestinal parasites", "freshwater ecology", "marine biology", "parasitology", "shrimp farming", "par...	The Prawn Macrobrachium vollenhovenii in the Senegal River Basin: Towards Sustainable Restocking of All-Male Populations for Biological Control of Schistosomiasis	journal.pntd.0003060	null	[ [ "Schistosomiasis is a chronic parasitic disease caused by blood flukes of the genus Schistosoma , which are dependent on two hosts to complete their life cycle , an intermediate host ( a freshwater snail ) and a definitive host ( a vertebrate ) .", "The adult parasites can live for decades and cause incre...	[ "Early malacological literature suggests that the outbreak of schistosomiasis , a parasitic disease transmitted by aquatic snails , in the Senegal River basin occurred due to ecological changes resulting from the construction of the Diama dam .", "The common treatment , the drug praziquantel , does not protect fr...	[ "Schistosomiasis is a chronic parasitic disease that infects millions of people , especially in Africa .", "Schistosomes are transmitted by direct contact with water sources infested by freshwater snails , which are intermediate hosts for the parasite .", "The cure in humans is a drug , praziquantel , that kill...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "luciferase assay", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "hela cells", "molecular probe techniques", "biological cultures", "immunology", "biochemical analysis", "developmental biology", "enzyme assays", "immunoprecipitation", "molecular...	SNX8 modulates innate immune response to DNA virus by mediating trafficking and activation of MITA	journal.ppat.1007336	null	[ [ "Innate immune response is pivotal for host defense against microbial pathogens .", "Cytosolic DNA derived from invading pathogens triggers signaling events that lead to induction of downstream anti-microbial effector genes [1–3] .", "It has been demonstrated that the nucleotidyltransferase family mem...	[ "MITA ( also called STING ) is a central adaptor protein in innate immune response to cytosolic DNA .", "Cellular trafficking of MITA from the ER to perinuclear microsomes after DNA virus infection is critical for MITA activation and onset of innate antiviral response .", "Here we found that SNX8 is a component...	[ "Infection by virus , such as the DNA virus herpes simplex virus 1 , induces the host cells to express proteins that mediate antiviral immune response .", "The protein called MITA plays an essential role in the process of antiviral immune response .", "After viral infection , MITA traffics from the endoplasmic ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "women's health", "biology", "microbiology", "molecular cell biology" ]	Chlamydia trachomatis Co-opts GBF1 and CERT to Acquire Host Sphingomyelin for Distinct Roles during Intracellular Development	journal.ppat.1002198	null	[ [ "Chlamydia species are obligate intracellular pathogens that cause a wide range of diseases in humans , including sexually transmitted , ocular , and respiratory tract infections [1] .", "The capacity of Chlamydia infections to lead to infertility and blindness , their association with chronic diseases su...	[ "The obligate intracellular pathogen Chlamydia trachomatis replicates within a membrane-bound inclusion that acquires host sphingomyelin ( SM ) , a process that is essential for replication as well as inclusion biogenesis .", "Previous studies demonstrate that SM is acquired by a Brefeldin A ( BFA ) -sensitive ve...	[ "C . trachomatis is the leading cause of non-congenital blindness in developing countries and is the number one cause of sexually transmitted disease and non-congenital infertility in Western countries .", "The capacity of Chlamydia infections to lead to infertility and blindness , their association with chronic ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant anatomy", "panicles", "floral meristem", "plant physiology", "hormones", "cereal crops", "plant science", "rice", "model organisms", "plant hormones", "crops", "inflorescences", "plants", "research and analysis methods", "cytokinins", "grasses", "crop science", "gibberellins...	The QTL GNP1 Encodes GA20ox1, Which Increases Grain Number and Yield by Increasing Cytokinin Activity in Rice Panicle Meristems	journal.pgen.1006386	null	[ [ "Rice panicle architecture , a valuable composite agronomic trait that includes grain number per panicle ( GNP ) , panicle length and so on , is strongly associated with rice grain yield .", "GNP is one of the most important agronomic characteristics of ideal plant architecture [1] .", "To improve ric...	[ "Cytokinins and gibberellins ( GAs ) play antagonistic roles in regulating reproductive meristem activity .", "Cytokinins have positive effects on meristem activity and maintenance .", "During inflorescence meristem development , cytokinin biosynthesis is activated via a KNOX-mediated pathway .", "Increased c...	[ "Grain number per panicle , a valuable agronomic trait for rice yield improvement , is profoundly affected by reproductive meristem activity .", "This activity , in turn , is controlled by transcriptional and plant hormone regulators , especially KNOX proteins and cytokinins .", "However , little is known about...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "parasitic diseases", "parasitic protozoans", "protozoans", "leishmania", "neglected tropical diseases", "immunologic techniques", "research and ana...	Performance of serological tests available in Brazil for the diagnosis of human visceral leishmaniasis	journal.pntd.0007484	null	[ [ "Human visceral leishmaniasis ( VL ) is a neglected tropical disease ( NTD ) endemic to more than 65 countries with an average of 25 , 000 new cases reported per year from 2013–2017 .", "Over 90% of global VL cases were reported from seven countries: Brazil , Ethiopia , India , Kenya , Somalia , South Sud...	[ "Visceral leishmaniasis ( VL ) is the most severe form of leishmaniasis and is potentially fatal if not diagnosed and treated .", "Accurate and timely diagnosis is considered one of the pillars needed for the reduction in disease-related lethality .", "Brazil is currently one of the three eco-epidemiological ho...	[ "Visceral leishmaniasis ( VL ) is a tropical disease distributed worldwide .", "In the Americas , Brazil reports about 96% of VL cases , which has been highlighted by the increase in lethality in last years .", "Accurate VL diagnosis is of utmost importance .", "Despite this , the performance of some commerci...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "safranin staining", "gene regulation", "regulatory proteins", "dna-binding proteins", "cytoplasmic staining", "developmental biology", "transcription factors", "embryos", "cellular structures and organelles", "research and analysis methods", "separation processes", "ectoderm", "specimen pre...	Craniofacial Ciliopathies Reveal Specific Requirements for GLI Proteins during Development of the Facial Midline	journal.pgen.1006351	null	[ [ "Midfacial disorders encompass a spectrum of conditions that affect the development of the facial midline .", "The full spectrum of medial craniofacial dysplasias range from conditions that exhibit tissue deficiencies or agenesis ( hypotelorism , cyclopia ) to those that exhibit tissue excess or duplicati...	[ "Ciliopathies represent a broad class of disorders that affect multiple organ systems .", "The craniofacial complex is among those most severely affected when primary cilia are not functional .", "We previously reported that loss of primary cilia on cranial neural crest cells , via a conditional knockout of the...	[ "Primary cilia are ubiquitous organelles that serve to transduce molecular signals within a cell .", "Loss of functional primary cilia results in a disease class called ciliopathies .", "Ciliopathies have a broad range of phenotypes; however , severe facial anomalies are commonly associated with this disease cl...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biomacromolecule-ligand interactions", "biochemistry", "antivirals", "proteins", "virology", "enzymes", "protein structure", "emerging viral diseases", "viral enzymes", "biology", "microbiology" ]	Crystal Structure and Functional Analysis of the SARS-Coronavirus RNA Cap 2′-O-Methyltransferase nsp10/nsp16 Complex	journal.ppat.1002059	null	[ [ "Most eukaryotic cellular and viral mRNAs are modified by the addition of a polyadenine tail at the 3′- terminal and a cap structure at the 5′-terminal .", "The RNA cap protects mRNA from degradation by 5′ exoribonucleases , ensures efficient mRNA translation , and prevents recognition of viral RNA via in...	[ "Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism , detoxification , signal transduction , chromatin remodeling , nucleic acid processing , and mRNA capping .", "The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a S-a...	[ "A novel coronavirus emerged in 2003 and was identified as the etiological agent of the deadly disease called Severe Acute Respiratory Syndrome .", "This coronavirus replicates and transcribes its giant genome using sixteen non-structural proteins ( nsp1-16 ) .", "Viral RNAs are capped to ensure stability , eff...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "medicine and health sciences", "reproductive system", "spermatocytes", "retrotransposons", "spermatogonia", "germ cells", "genetic elements", "epigenetics", "dna", "molecular biology techniques", "rna sequencing", "dna methylation", "chromatin", "sperm", "rese...	Switching of dominant retrotransposon silencing strategies from posttranscriptional to transcriptional mechanisms during male germ-cell development in mice	journal.pgen.1006926	null	[ [ "The mouse genome harbors millions of copies of transposable elements , the majority of which are retrotransposons .", "The retrotransposons include long terminal repeat ( LTR ) elements , long interspersed elements ( LINEs ) , and short interspersed elements ( SINEs ) [1] .", "The LTR elements includ...	[ "Mammalian genomes harbor millions of retrotransposon copies , some of which are transpositionally active .", "In mouse prospermatogonia , PIWI-interacting small RNAs ( piRNAs ) combat retrotransposon activity to maintain the genomic integrity .", "The piRNA system destroys retrotransposon-derived RNAs and guid...	[ "Retrotransposons are a class of transposable elements , of which mobility has mutagenic potential .", "Therefore , it is important to regulate the expression of retrotransposons for maintaining the genomic integrity .", "In male germ cells , DNA methylation and the piRNA system are thought to play roles in ret...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Dynamics of DNA Methylation in Recent Human and Great Ape Evolution	journal.pgen.1003763	null	[ [ "The genomic era is characterized by different comparative approaches to understand the effect of genomic changes upon phenotypes .", "In the context of human evolution , the genomes of all species of great apes have now been sequenced [1]–[4] allowing nucleotide resolution comparisons to understand the e...	[ "DNA methylation is an epigenetic modification involved in regulatory processes such as cell differentiation during development , X-chromosome inactivation , genomic imprinting and susceptibility to complex disease .", "However , the dynamics of DNA methylation changes between humans and their closest relatives a...	[ "Differences in protein coding sequences between humans and their closest relatives are too small to account for their phenotypic differences .", "It has been hypothesized that these differences may be explained by alterations of gene regulation rather than primary genome sequence .", "DNA methylation is an imp...	2013
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "biochemistry", "mutation", "deletion mutation", "haplotypes", "nucleic acids", "heredity", "germline mutation", "gene identification and analysis", "genetics", "mutation detection", "biology and life sciences", "dna", "dna repair", "alleles", "genetic loci", "genetic mapping" ]	Inference of Candidate Germline Mutator Loci in Humans from Genome-Wide Haplotype Data	journal.pgen.1006549	null	[ [ "The rate of germline mutation is a key parameter in molecular evolution and population genetics .", "As the ultimate source of genetic novelty , germline mutations provide the raw material on which selection acts and the basis for genetic drift over time .", "Mutation rates are known to differ substa...	[ "The rate of germline mutation varies widely between species but little is known about the extent of variation in the germline mutation rate between individuals of the same species .", "Here we demonstrate that an allele that increases the rate of germline mutation can result in a distinctive signature in the gen...	[ "Each time a genome is replicated there is the possibility of error resulting in the incorporation of an incorrect base or bases in the genome sequence .", "When these errors occur in cells that lead to the production of gametes they can be incorporated into the germline .", "Such germline mutations are the bas...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "statistical analysis of genetic association", "genetic networks", "genomics", "genome analysis", "trait locus analysis", "genetics", "biology and life sciences", "computational biology", "genomics statistics", "alleles", "genetic loci" ]	Detection of Pleiotropy through a Phenome-Wide Association Study (PheWAS) of Epidemiologic Data as Part of the Environmental Architecture for Genes Linked to Environment (EAGLE) Study	journal.pgen.1004678	null	[ [ "Genome-wide association studies ( GWAS ) have led to the discovery of thousands of variants associated with disease and phenotypic outcomes [1] .", "GWAS focus on investigating the association between hundreds of thousands to over a million single nucleotide polymorphisms ( SNPs ) and a single , or small...	[ "We performed a Phenome-wide association study ( PheWAS ) utilizing diverse genotypic and phenotypic data existing across multiple populations in the National Health and Nutrition Examination Surveys ( NHANES ) , conducted by the Centers for Disease Control and Prevention ( CDC ) , and accessed by the Epidemiologic...	[ "The Epidemiological Architecture for Genes Linked to Environment ( EAGLE ) study performed a Phenome-Wide Association Study ( PheWAS ) to investigate comprehensive associations between a wide range of phenotypes and single-nucleotide polymorphisms using the diverse genotypic and phenotypic data that exists across ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Effects of Argentilactone on the Transcriptional Profile, Cell Wall and Oxidative Stress of Paracoccidioides spp.	journal.pntd.0004309	null	[ [ "The genus Paracoccidioides , which comprises the species lutzii and brasiliensis , is the etiological agent of paracoccidioidomycosis ( PCM ) , an important systemic mycosis in Latin America .", "The inhalation of mycelia fragments , infectious forms of the fungus , is the common route of infection that ...	[ "Paracoccidioides spp .", ", a dimorphic pathogenic fungus , is the etiologic agent of paracoccidioidomycosis ( PCM ) .", "PCM is an endemic disease that affects at least 10 million people in Latin America , causing severe public health problems .", "The drugs used against pathogenic fungi have various side e...	[ "Paracoccidioidomycosis ( PCM ) is a neglected human systemic mycosis caused by Paracoccidioides spp .", "fungus that invades the host’s lungs and can disseminate to many other organs .", "Treatment usually involves amphotericin B , sulfadiazine , trimethoprim-sulfamethoxazole , itraconazole , ketoconazole or f...	2016
[ "Introduction", "Results", "Discussion", "Models", "Dynamical Mean-Field Theory of the Single Inhibitory Population", "Two-population networks", "Numerical simulations" ]	[]	Asynchronous Rate Chaos in Spiking Neuronal Circuits	journal.pcbi.1004266	null	[ [ "Single cell recordings [1] and electro-encephalography [2 , 3] suggest the existence of chaotic dynamics in the brain .", "Consistent with chaotic dynamics , in-vivo experiments have demonstrated that cortical circuits are sensitive to weak perturbations [4 , 5] .", "Remarkably , the misplacement of ...	[ "The brain exhibits temporally complex patterns of activity with features similar to those of chaotic systems .", "Theoretical studies over the last twenty years have described various computational advantages for such regimes in neuronal systems .", "Nevertheless , it still remains unclear whether chaos requir...	[ "Cortical circuits exhibit complex temporal patterns of spiking and are exquisitely sensitive to small perturbations in their ongoing activity .", "These features are all suggestive of an underlying chaotic dynamics .", "Theoretical works have indicated that a rich dynamical reservoir can endow neuronal circuit...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "developmental biology/embryology", "genetics and genomics/animal genetics", "developmental biology", "genetics and genomics/functional genomics", "genetics and genomics/disease models", "genetics and genomics", "developmental biology/molecular development", "deve...	Loss of Mitogen-Activated Protein Kinase Kinase Kinase 4 (MAP3K4) Reveals a Requirement for MAPK Signalling in Mouse Sex Determination	journal.pbio.1000196	The boygirl (byg) mouse mutant reveals that MAP3K4-mediated signaling is necessary for normal SRY expression and testis specification in the developing mouse gonad.	[ [ "Sex determination is the process by which an embryo develops into a male or female , namely , the formation of testes in an XY embryo and ovaries in an XX embryo .", "In the mouse , this process begins with commitment of cells of the bipotential genital ridge to either the testicular or ovarian fate at 1...	[ "Sex determination in mammals is controlled by the presence or absence of the Y-linked gene SRY .", "In the developing male ( XY ) gonad , sex-determining region of the Y ( SRY ) protein acts to up-regulate expression of the related gene , SOX9 , a transcriptional regulator that in turn initiates a downstream pat...	[ "In mammals , whether an individual develops as a male or female depends on its sex chromosome constitution: those with a Y chromosome become males because of the development of the embryonic gonad into a testis .", "The Y-linked sex determining gene SRY regulates this process by initiating a pathway of gene and ...	2009
[ "Introduction", "Material and methods", "Results", "Discussion" ]	[ "antimicrobials", "body weight", "medicine and health sciences", "animal models of disease", "drugs", "tropical diseases", "microbiology", "animal models", "bacterial diseases", "model organisms", "physiological parameters", "pharmaceutics", "antibiotics", "drug administration", "neglect...	Sterilizing Activity of Fully Oral Intermittent Regimens against Mycobacterium Ulcerans Infection in Mice	journal.pntd.0005066	null	[ [ "Buruli Ulcer ( BU ) , is an infectious disease caused by Mycobacterium ulcerans that is mostly prevalent in Africa , but also found in Australia , Southeast Asia and South America [1] .", "Recently , cases have also been reported in Japan [2] .", "Until 2004 , surgery to remove infected tissue follow...	[ "The treatment of Buruli ulcer ( BU ) that is caused by Mycobacterium ulcerans , is currently based on a daily administration of rifampin and streptomycin ( RIF-STR ) .", "A fully oral intermittent regimen would greatly simplify its treatment on the field .", "The objective of this study was to assess the bacte...	[ "Buruli ulcer , caused by Mycobacterium ulcerans , is the third most frequent disease due to a bacteria of the mycobacteria family , after tuberculosis and leprosy .", "The disease consists of a cutaneous infection leading to skin ulcerations that can cause severe and debilitating scars .", "It occurs mostly in...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "genetics", "biology", "microbiology", "genetics and genomics" ]	The Three Faces of Riboviral Spontaneous Mutation: Spectrum, Mode of Genome Replication, and Mutation Rate	journal.pgen.1002832	null	[ [ "Riboviruses ( RNA viruses with no DNA replication intermediates ) infect organisms from prokaryotes to higher eukaryotes and frequently cause deadly diseases .", "The mortality , morbidity , and economic burden of ribovirus-borne diseases strongly impact human society , especially in developing countries...	[ "Riboviruses ( RNA viruses without DNA replication intermediates ) are the most abundant pathogens infecting animals and plants .", "Only a few riboviral infections can be controlled with antiviral drugs , mainly because of the rapid appearance of resistance mutations .", "Little reliable information is availab...	[ "Viral disease is a subject of major concern in public health .", "Diseases produced by riboviruses ( RNA viruses sensu stricto ) represent a special urgency , because these viruses display an exceptional capability to generate resistance mutations against antiviral drugs .", "Unfortunately , little is known ab...	2012
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Partial Deletion of Chromosome 8 β-defensin Cluster Confers Sperm Dysfunction and Infertility in Male Mice	journal.pgen.1003826	null	[ [ "β-defensins are cationic peptides with a canonical six cysteines in their mature secreted peptide that were first isolated as antimicrobials and their presumed function is host defence .", "The β-defensin gene family consists of 40 family members at 5 gene loci in human and more than 50 genes over 4 loci...	[ "β-defensin peptides are a family of antimicrobial peptides present at mucosal surfaces , with the main site of expression under normal conditions in the male reproductive tract .", "Although they kill microbes in vitro and interact with immune cells , the precise role of these genes in vivo remains uncertain .",...	[ "β-defensins are small molecules , considered primarily to be antimicrobials and important in the first defence response to invading organisms .", "They are predominantly produced at surfaces in contact with the outside environment and these include skin , airway and reproductive tract .", "We show here that wh...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "taeniasis", "medicine", "infectious diseases", "public health and epidemiology", "zoonoses", "epidemiology", "infectious disease epidemiology", "cysticercosis", "neglected tropical diseases", "parasitic diseases" ]	The Incidence of Human Cysticercosis in a Rural Community of Eastern Zambia	journal.pntd.0002142	null	[ [ "Human ( neuro ) cysticercosis , an infection caused by the metacestode larval stage of the pork tapeworm Taenia solium , is a serious but neglected zoonotic disease and a major public health problem in many developing countries of Latin America , Asia and Africa [1] , [2] .", "Humans are the definitive h...	[ "A community-based longitudinal study was performed in the Eastern Province of Zambia , in which repeated serological samplings were done to determine the incidence of human cysticercosis .", "Three sampling rounds were carried out at six months intervals .", "A total of 867 participants presented for all three...	[ "Human neurocysticercosis is an infection of the central nervous system caused by the larval stage of the pork tapeworm ( Taenia solium ) .", "The infection occurs mainly in developing countries and is associated with poverty , poor sanitation and free-range pig management .", "It is estimated to be responsible...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virion structure, assembly, and egress", "virology/effects of virus infection on host gene expression", "virology/immunodeficiency viruses", "virology/viral replication and gene regulation" ]	The Gag Cleavage Product, p12, is a Functional Constituent of the Murine Leukemia Virus Pre-Integration Complex	journal.ppat.1001183	null	[ [ "Reverse transcription and integration are the hallmarks of the retroviral life cycle .", "These steps include reverse transcription of the genomic RNA into a linear double-stranded DNA and the subsequent integration of this DNA into the genome of the infected cell .", "These events are part of the ‘e...	[ "The p12 protein is a cleavage product of the Gag precursor of the murine leukemia virus ( MLV ) .", "Specific mutations in p12 have been described that affect early stages of infection , rendering the virus replication-defective .", "Such mutants showed normal generation of genomic DNA but no formation of circ...	[ "All retroviruses reverse transcribe their RNA genome to a DNA copy in the cytoplasm of the infected cell .", "To be expressed , the viral genomic DNA has to travel to the cell nucleus and to integrate into the cellular chromosomes .", "This trafficking is governed by cellular and viral proteins that associate ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "nuclear import", "medicine and health sciences", "pathology and laboratory medicine", "hela cells", "gene regulation", "pathogens", "biological cultures", "cell processes", "microbiology", "viral structure", "retroviruses", "viruses", "immunodeficiency viruses", "cytoplasmic staining", ...	KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection	journal.ppat.1005700	null	[ [ "Human Immunodeficiency Virus Type-1 ( HIV-1 ) , like all primate lentiviruses , possesses the ability to infect non-dividing cells .", "The ability to infect non-dividing cells is conveyed by the viral capsid ( CA ) protein which makes up the viral core that houses the viral genome [1 , 2 , 3] .", "C...	[ "Following envelope mediated fusion , the HIV-1 core is released into the cytoplasm of the target cell and undergoes a series of trafficking and replicative steps that result in the nuclear import of the viral genome , which ultimately leads to the integration of the proviral DNA into the host cell genome .", "Pr...	[ "Fusion of viral and target cell membranes releases the HIV-1 viral capsid , which houses the viral RNA and proteins necessary for viral reverse transcription and integration , into the cytoplasm of target cells .", "To complete infection , the viral capsid must ultimately traffic to the nucleus and undergo a pro...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutagenesis", "signal transduction", "kinetoplastids", "cell biology", "molecular biology", "genetics", "biology and life sciences", "molecular genetics", "microbiology", "protozoology", "microbial genetics", "cell signaling", "mapk signaling cascades", "parasitology", "signaling cascad...	Transgenic Analysis of the Leishmania MAP Kinase MPK10 Reveals an Auto-inhibitory Mechanism Crucial for Stage-Regulated Activity and Parasite Viability	journal.ppat.1004347	null	[ [ "Leishmaniasis is an infectious disease characterized by a variety of pathologies , affecting more than 12 million people worldwide and ranging from self-healing cutaneous lesions to fatal visceral infection [1] .", "This disease is caused by pathogenic protozoa of the genus Leishmania , which show two ma...	[ "Protozoan pathogens of the genus Leishmania have evolved unique signaling mechanisms that can sense changes in the host environment and trigger adaptive stage differentiation essential for host cell infection .", "The signaling mechanisms underlying parasite development remain largely elusive even though Leishma...	[ "Leishmaniasis is an important human disease caused by Leishmania parasites .", "A crucial aspect of Leishmania infectivity is its capacity to sense different environments and adapt for survival inside insect vector and vertebrate host by stage differentiation .", "This process is triggered by environmental cha...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "ecology", "epidemiology", "vector biology", "dengue fever", "neglected tropical diseases", "biology and life sciences", "vector-borne diseases", "viral diseases", "tropical diseases", "parasitic diseases", "disease vectors", "parasito...	Urbanization Increases Aedes albopictus Larval Habitats and Accelerates Mosquito Development and Survivorship	journal.pntd.0003301	null	[ [ "Aedes albopictus ( Skuse ) ( Diptera: Culicidae ) , the Asian tiger mosquito , is an aggressive , strongly anthropophilic , exophagic , and exophilic mosquito .", "As an important vector of dengue fever , chikungunya disease , and yellow fever , Ae .", "albopictus has emerged as a global public healt...	[ "Aedes albopictus is a very invasive and aggressive insect vector that causes outbreaks of dengue fever , chikungunya disease , and yellow fever in many countries .", "Vector ecology and disease epidemiology are strongly affected by environmental changes .", "Urbanization is a worldwide trend and is one of the ...	[ "Aedes albopictus has expanded its ecological habitat range throughout the world .", "Although Ae .", "albopictus was previously considered a rural vector , this species has adapted well to suburban and urban environments , and it has become the most important and sometimes the sole vector of dengue virus trans...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "action potentials", "body fluids", "chemical compounds", "diabetic endocrinology", "membrane potential", "electrophysiology", "carbohydrates", "neuroscience", "organic compounds", "glucose", "hormones", "ion channels", "cellular structures and organelles", ...	Upregulation of an inward rectifying K+ channel can rescue slow Ca2+ oscillations in K(ATP) channel deficient pancreatic islets	journal.pcbi.1005686	null	[ [ "Insulin is secreted from pancreatic islet β-cells in response to elevated blood glucose .", "Islet activity is oscillatory , with periods ranging from tens of seconds to several minutes , and this is reflected in the reported periods of pulsatile insulin secretion [1–4] .", "Plasma insulin oscillatio...	[ "Plasma insulin oscillations are known to have physiological importance in the regulation of blood glucose .", "In insulin-secreting β-cells of pancreatic islets , K ( ATP ) channels play a key role in regulating glucose-dependent insulin secretion .", "In addition , they convey oscillations in cellular metabol...	[ "Pulsatile insulin secretion is important for the proper regulation of blood glucose , and disruption of this pulsatility is a hallmark of type II diabetes .", "An ion channel was discovered more than three decades ago that conveys the metabolic state of insulin-secreting β-cells to the plasma membrane because it...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biochemistry", "proteins", "macromolecular assemblies", "biology", "computational biology", "molecular cell biology" ]	Structural Disorder Provides Increased Adaptability for Vesicle Trafficking Pathways	journal.pcbi.1003144	null	[ [ "The well-organized network of vesicle trafficking pathways is the basic communication mechanism between the different intracellular compartments and the environment , and as such it is crucial for the efficient transport of macromolecules within and between cells and their environment .", "Transport vesi...	[ "Vesicle trafficking systems play essential roles in the communication between the organelles of eukaryotic cells and also between cells and their environment .", "Endocytosis and the late secretory route are mediated by clathrin-coated vesicles , while the COat Protein I and II ( COPI and COPII ) routes stand fo...	[ "Vesicle trafficking systems are fundamental among cellular transport mechanisms; various cargo molecules are transported via different coated vesicles to their specific destinations in every eukaryotic cell .", "Clathrin-coated vesicles mediate endocytosis and the late secretory route , while the COat Protein I ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms	journal.ppat.1005254	null	[ [ "The type I interferons ( IFNs ) are critical players in the innate immune response against viral infections .", "Shortly after infection , these cytokines are rapidly induced , stimulating an antiviral state through the induction of hundreds of interferon-stimulated genes ( ISGs ) [1] .", "This famil...	[ "HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection .", "The type I interferons ( IFNs ) likely serve as a first line of defense , but the relative expression and antiviral properties of the 12 IFNα subtypes against HIV-1 infection of muc...	[ "The therapeutic potential of recombinant IFNα against HIV-1 infection has been explored for 25 years , but its effectiveness was inconsistent .", "However , these clinical trials administered IFNα2 , which is only one member of a 12-protein family of IFNα subtypes .", "More recently , IFNα was found to activat...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "action potentials", "medicine and health sciences", "neural networks", "population dynamics", "membrane potential", "electrophysiology", "neuroscience", "systems science", "mathematics", "algebra", "computational neuroscience", "population biology", "computer and information sciences", "s...	Recovery of Dynamics and Function in Spiking Neural Networks with Closed-Loop Control	journal.pcbi.1004720	null	[ [ "Open-loop brain stimulation has emerged as a common tool to restore aberrant neuronal activity .", "The most successful example is the application of high-frequency deep-brain-stimulation ( DBS ) used to ameliorate motor symptoms in Parkinson’s disease ( PD ) .", "However , even in this case the stim...	[ "There is a growing interest in developing novel brain stimulation methods to control disease-related aberrant neural activity and to address basic neuroscience questions .", "Conventional methods for manipulating brain activity rely on open-loop approaches that usually lead to excessive stimulation and , crucial...	[ "Brain stimulation is being used to ease symptoms in several neurological disorders in cases where pharmacological treatment is not effective ( anymore ) .", "The most common way for stimulation so far has been to apply a fixed , predetermined stimulus irrespective of the actual state of the brain or the conditio...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physics", "thermodynamics", "biophysics theory", "biology and life sciences", "physical sciences", "biophysics" ]	Thermodynamic Costs of Information Processing in Sensory Adaptation	journal.pcbi.1003974	null	[ [ "In order to perform a variety of tasks , living organisms continually respond and adapt to their changing surroundings through diverse electrical , chemical and mechanical signaling pathways , called sensory systems [1] .", "In mammals , prominent examples are the neurons involved in the visual , olfacto...	[ "Biological sensory systems react to changes in their surroundings .", "They are characterized by fast response and slow adaptation to varying environmental cues .", "Insofar as sensory adaptive systems map environmental changes to changes of their internal degrees of freedom , they can be regarded as computati...	[ "The ability to process information is a ubiquitous feature of living organisms .", "Indeed , in order to survive , every living being , from the smallest bacterium to the biggest mammal , has to gather and process information about its surrounding environment .", "In the same way as our everyday computers need...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetic networks", "chromosome structure and function", "messenger rna", "telomeres", "dna replication", "network analysis", "genome analysis", "protein structure", "dna", "molecular biology techniques", "research and analysis methods", "computer and information sciences", "genomics", "ch...	Excess of Yra1 RNA-Binding Factor Causes Transcription-Dependent Genome Instability, Replication Impairment and Telomere Shortening	journal.pgen.1005966	null	[ [ "Messenger RNA ( mRNA ) is coated by RNA-binding proteins ( RBPs ) forming large messenger ribonucleoprotein particles ( mRNPs ) .", "Many mRNA processing factors that participate in 5′-end capping , splicing , 3′-end processing , and polyadenylation are loaded co-transcriptionally to the pre-mRNA through...	[ "Yra1 is an essential nuclear factor of the evolutionarily conserved family of hnRNP-like export factors that when overexpressed impairs mRNA export and cell growth .", "To investigate further the relevance of proper Yra1 stoichiometry in the cell , we overexpressed Yra1 by transforming yeast cells with YRA1 intr...	[ "Yra1 is an essential nuclear RNA-binding protein that plays a role in mRNA export in Saccharomyces cerevisiae .", "The cellular levels of Yra1 are tightly auto-regulated by splicing of an unusual intron in its pre-mRNA , removal of which causes Yra1 overexpression that results in a dominant-negative growth defec...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/morphogenesis and cell biology", "genetics and genomics/functional genomics", "genetics and genomics/gene expression", "developmental biology/developmental evolution", "developmental biology/pattern formation", "genetics and genomics/gene function", "developmental biology/molecula...	Ancestral Regulatory Circuits Governing Ectoderm Patterning Downstream of Nodal and BMP2/4 Revealed by Gene Regulatory Network Analysis in an Echinoderm	journal.pgen.1001259	null	[ [ "It is becoming increasingly apparent that most developmental processes are controlled by dozens or hundreds of regulatory genes assembled into complex gene regulatory networks ( GRNs ) , rather than by a small number of master genes .", "By describing the functional relationships between these genes , GR...	[ "Echinoderms , which are phylogenetically related to vertebrates and produce large numbers of transparent embryos that can be experimentally manipulated , offer many advantages for the analysis of the gene regulatory networks ( GRN ) regulating germ layer formation .", "During development of the sea urchin embryo...	[ "Echinoderms ( sea urchins , starfish , etc . ) are marine invertebrates that share a close ancestry with vertebrates .", "Their embryos offer many advantages for the analysis of transcriptional circuits that control developmental programs .", "During early development of the common sea urchin Paracentrotus liv...	2010
[ "Introduction", "Results", "Discussion" ]	[]	Evolving Nutritional Strategies in the Presence of Competition: A Geometric Agent-Based Model	journal.pcbi.1004111	null	[ [ "Access to nutrients is one of the most influential factors affecting reproductive development and ultimately fitness ( e . g . [1–4] ) .", "A range of factors can influence nutrient access , but for many organisms interactions with conspecifics are pivotal .", "Group living animals in particular face...	[ "Access to nutrients is a key factor governing development , reproduction and ultimately fitness .", "Within social groups , contest-competition can fundamentally affect nutrient access , potentially leading to reproductive asymmetry among individuals .", "Previously , agent-based models have been combined with...	[ "Getting enough nutrients and at the right balance is among the primary challenges that an animal has to overcome .", "Animals that live in groups have the added complexity of competition among individuals over foods .", "We used an evolutionary simulation to explore how the intensity of such competition intera...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "immunology", "molecular biology/dna repair" ]	Genetic Evidence for Single-Strand Lesions Initiating Nbs1-Dependent Homologous Recombination in Diversification of Ig V in Chicken B Lymphocytes	journal.pgen.1000356	null	[ [ "Homologous recombination ( HR ) contributes to genome maintenance by repairing double-strand breaks ( DSBs ) and single-strand lesions .", "It accomplishes this by associating the damaged DNA with intact homologous sequences ( reviewed in [1] ) .", "Genetic studies of Escherichia coli indicate that D...	[ "Homologous recombination ( HR ) is initiated by DNA double-strand breaks ( DSB ) .", "However , it remains unclear whether single-strand lesions also initiate HR in genomic DNA .", "Chicken B lymphocytes diversify their Immunoglobulin ( Ig ) V genes through HR ( Ig gene conversion ) and non-templated hypermuta...	[ "An important class of chemotherapeutic drugs used in the treatment of cancer induces DNA damage that interferes with DNA replication .", "The resulting block to replication results in the formation of single-strand gaps in DNA .", "These gaps can be filled by specialized DNA polymerases , a process associated ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signal transduction", "molecular cell biology", "molecular biology", "genetics", "genetics and genomics", "biology", "evolutionary biology", "comparative genomics", "neuroscience", "evolutionary processes", "sensory perception", "gene function" ]	Evolution of Vertebrate Transient Receptor Potential Vanilloid 3 Channels: Opposite Temperature Sensitivity between Mammals and Western Clawed Frogs	journal.pgen.1002041	null	[ [ "Animals adapt to environmental temperature changes by sensing both their body and ambient temperatures .", "Thermal stimuli are detected by temperature receptors and transmitted by the peripheral nerves in which they reside [1]–[4] .", "Thus , temperature receptors must have served crucial roles in a...	[ "Transient Receptor Potential ( TRP ) channels serve as temperature receptors in a wide variety of animals and must have played crucial roles in thermal adaptation .", "The TRP vanilloid ( TRPV ) subfamily contains several temperature receptors with different temperature sensitivities .", "The TRPV3 channel is ...	[ "Evolution of temperature perception is crucial for adaptation to thermal environments; however , this process is poorly understood .", "Here we investigated the evolution of the vertebrate TRPV subfamily which contains several mammalian temperature receptors .", "We identified several novel TRPV genes that hav...	2011
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "in vitro", "immunology", "molecular biology" ]	DNA-Dependent Protein Kinase Inhibits AID-Induced Antibody Gene Conversion	journal.pbio.0050080	Affinity maturation and class switching of antibodies requires AID-dependent hypermutation of Ig V(D)J rearrangements. This process is shown here to involve double-strand DNA breaks that recruit repair machinery.	[ [ "In humans and mice , primary antibody ( Ig ) diversity is produced by V ( D ) J recombination , which is dependent on the RAG-1 and −2 proteins [1] .", "Over a lifetime , primary repertoires are largely re-shaped by the processes of Ig somatic hypermutation ( SHM ) and class switching [2] , independent p...	[ "Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase ( AID ) -dependent hypermutation of Ig V ( D ) J rearrangements and Ig S regions , respectively , in activated B cells .", "AID deaminates deoxycytidine bases in Ig genes , converting them into deoxyuridines .", ...	[ "To generate highly specific antibodies in response to an immune challenge , the antibody genes in activated B cells mutate at a very high rate over a period of several days .", "The enzyme that initiates antibody gene mutation is activation-induced cytidine deaminase ( AID ) , the first protein recognized to dir...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/bacterial infections", "ecology/environmental microbiology", "microbiology/medical microbiology", "infectious diseases/tropical and travel-associated diseases" ]	Landscape Changes Influence the Occurrence of the Melioidosis Bacterium Burkholderia pseudomallei in Soil in Northern Australia	journal.pntd.0000364	null	[ [ "Burkholderia pseudomallei is a Gram-negative bacterium whose main habitat is in moist tropical soil between latitudes 20° N and 20° S [1] .", "B . pseudomallei is not only a soil saprophyte but also a human and animal pathogen causing the severe disease melioidosis [1] , [2] .", "Clinical manifestati...	[ "The soil-dwelling saprophyte bacterium Burkholderia pseudomallei is the cause of melioidosis , a severe disease of humans and animals in southeast Asia and northern Australia .", "Despite the detection of B . pseudomallei in various soil and water samples from endemic areas , the environmental habitat of B . pse...	[ "Melioidosis is a severe disease affecting humans and animals in the tropics .", "It is caused by the bacterium Burkholderia pseudomallei , which lives in tropical soil and especially occurs in southeast Asia and northern Australia .", "Despite the recognition that melioidosis is an emerging infectious disease ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "animals", "animal models", "c-jun n-terminal kinase signaling cascade", "bacterial diseases", "drosophila melanogaster", "model organisms", "stem cells", "enterococcus", "bac...	Remote Control of Intestinal Stem Cell Activity by Haemocytes in Drosophila	journal.pgen.1006089	null	[ [ "Innate immunity provides the first line of defense against invading pathogens .", "This response is initiated by host pattern recognition receptors ( PRRs ) , which sense specific and conserved motifs called microbe associated molecular patterns ( MAMPs ) found in microbes , but not in the host .", "...	[ "The JAK/STAT pathway is a key signaling pathway in the regulation of development and immunity in metazoans .", "In contrast to the multiple combinatorial JAK/STAT pathways in mammals , only one canonical JAK/STAT pathway exists in Drosophila .", "It is activated by three secreted proteins of the Unpaired famil...	[ "Innate immunity acts as the primary line of defense to overcome invading organisms .", "This response starts through sensing of microbe-specific molecules such as lipopolysaccharide and peptidoglycan by host receptors .", "Metazoans can also recognize signals that are associated with tissue damage and wounding...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/recombination", "molecular biology/chromosome structure", "genetics and genomics/chromosome biology", "cell biology/plant genetics and gene expression", "molecular biology/dna repair" ]	The Arabidopsis BLAP75/Rmi1 Homologue Plays Crucial Roles in Meiotic Double-Strand Break Repair	journal.pgen.1000309	null	[ [ "From a diploid mother cell , meiosis generates four haploid products from which gametes differentiate .", "This ploidy reduction is a direct consequence of two rounds of chromosomal segregation ( meiosis I and meiosis II ) following a single S phase .", "The first meiotic division separates homologou...	[ "In human cells and in Saccharomyces cerevisiae , BLAP75/Rmi1 acts together with BLM/Sgs1 and TopoIIIα/Top3 to maintain genome stability by limiting crossover ( CO ) formation in favour of NCO events , probably through the dissolution of double Holliday junction intermediates ( dHJ ) .", "So far , very limited da...	[ "Recombination is a process by which cells can repair DNA damage .", "Such repair can either be crossovers ( CO ) , in which DNA molecules are submitted to major exchanges , or non-crossover ( NCO ) events .", "Eukaryotic cells have developed several mechanisms to maintain genome stability during vegetative dev...	2008
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "evolutionary biology/genomics", "evolutionary biology/developmental evolution" ]	A Gene-Based Linkage Map for Bicyclus anynana Butterflies Allows for a Comprehensive Analysis of Synteny with the Lepidopteran Reference Genome	journal.pgen.1000366	null	[ [ "With the need for a wider sampling of biological diversity [1]–[3] , the availability of tools for large-scale genetic and genomic analysis is rapidly being extended beyond a handful of classical model systems .", "Gene collections are growing for various species and with them , the need for methods to a...	[ "Lepidopterans ( butterflies and moths ) are a rich and diverse order of insects , which , despite their economic impact and unusual biological properties , are relatively underrepresented in terms of genomic resources .", "The genome of the silkworm Bombyx mori has been fully sequenced , but comparative lepidopt...	[ "Butterflies and moths ( called the Lepidoptera ) are a large and diverse group of insects that has long captured the attention of biologists and laymen .", "The colorful patterns on the wings of butterflies , in particular , offer an ideal system to investigate which genes and developmental mechanisms contribute...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "haplotypes", "chromosomal inheritance", "heredity", "genetics", "population genetics", "biology", "human genetics", "genetics and genomics" ]	Inference of Relationships in Population Data Using Identity-by-Descent and Identity-by-State	journal.pgen.1002287	null	[ [ "Single nucleotide polymorphism ( SNP ) genotyping is used to delineate the extent and nature of chromosomal variation , examine population genetic structure , and find loci that contribute to disease .", "SNPs are used as proxies for the unobserved sequence variants in the surrounding DNA , allowing meas...	[ "It is an assumption of large , population-based datasets that samples are annotated accurately whether they correspond to known relationships or unrelated individuals .", "These annotations are key for a broad range of genetics applications .", "While many methods are available to assess relatedness that invol...	[ "High-density microarrays measuring single nucleotide polymorphisms ( SNPs ) provide information about the genotypes across many loci .", "SNP genotypes observed for any two individuals can be compared in terms of identity-by-state ( IBS ) , in which two individuals are observed to have 0 , 1 , or 2 alleles in co...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/nosocomial and healthcare-associated infections", "microbiology/immunity to infections", "infectious diseases/fungal infections", "microbiology/innate immunity", "cell biology/microbial growth and development", "microbiology/cellular microbiology and pathogenesis", "microbiology/med...	Host Iron Withholding Demands Siderophore Utilization for Candida glabrata to Survive Macrophage Killing	journal.ppat.1001322	null	[ [ "Candida glabrata has emerged as an opportunistic fungal pathogen that causes life-threatening infectious disease in humans [1] .", "The dramatic rise in the number of immunocompromised individuals due to HIV infection and tuberculosis , and as a result of immunosuppressive regimens in cancer treatment an...	[ "The fungal pathogen Candida glabrata has risen from an innocuous commensal to a major human pathogen that causes life-threatening infections with an associated mortality rate of up to 50% .", "The dramatic rise in the number of immunocompromised individuals from HIV infection , tuberculosis , and as a result of ...	[ "Candida glabrata is a major human pathogen due to its low susceptibility to conventional antifungal drugs and the dramatic increase in the number of immunocompromised individuals suffering from HIV AIDS , cancer , and diabetes .", "Iron overload is one of the most common genetically inherited diseases and report...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Cathelicidin is a “fire alarm”, generating protective NLRP3-dependent airway epithelial cell inflammatory responses during infection with Pseudomonas aeruginosa	journal.ppat.1007694	null	[ [ "Pulmonary diseases caused by bacterial or viral infections are a common cause of morbidity and account for 1 in 5 deaths in the UK [1] .", "There is an increasing global threat from antibiotic-resistant bacterial infections and newly emerging viral infections .", "In this context , therapeutic interv...	[ "Pulmonary infections are a major global cause of morbidity , exacerbated by an increasing threat from antibiotic-resistant pathogens .", "In this context , therapeutic interventions aimed at protectively modulating host responses , to enhance defence against infection , take on ever greater significance .", "P...	[ "Lung infections are a common cause of death worldwide .", "As the threat of antibiotic-resistance becomes realised , new approaches are needed to treat disease-causing bacteria , such as multidrug-resistant Pseudomonas aeruginosa .", "Treatments that could enhance the body’s most effective natural defences can...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "sequence analysis", "biochemistry", "organismal evolution", "evolutionary modeling", "animal evolution", "biology and life sciences", "molecular biology techniques", "proteomics", "computational biology", "evolutionary biology", "molecular biology" ]	Coiled-Coil Proteins Facilitated the Functional Expansion of the Centrosome	journal.pcbi.1003657	null	[ [ "The transition from unicellularity to multicellularity occurred independently in many eukaryotic lineages [1] .", "Compared to other multicellular organisms , animals stand out with respect to the high number of cell types [1] , [2] , the complexity of body plans , and the necessity of cell migration for...	[ "Repurposing existing proteins for new cellular functions is recognized as a main mechanism of evolutionary innovation , but its role in organelle evolution is unclear .", "Here , we explore the mechanisms that led to the evolution of the centrosome , an ancestral eukaryotic organelle that expanded its functional...	[ "The centrosome helps cells to divide , and is important for the development of animals .", "It has its evolutionary origins in the basal body , which was present in the last common ancestor of all eukaryotes .", "Here , we study how the evolution of novel proteins helped the formation of the centrosome .", "...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "infectious diseases/neglected tropical diseases", "gastroenterology and hepatology/hepatology", "immunology/immune response", "infectious diseases/helminth infections", "infectious diseases/protozoal infections", "immunology/immunity to infections" ]	Cationic Amino Acid Transporter-2 Regulates Immunity by Modulating Arginase Activity	journal.ppat.1000023	null	[ [ "Tissue macrophages comprise a heterogeneous population of cells , recently separated into three major categories based on their unique functional capabilities .", "The TH2 cytokines IL-4 and IL-13 trigger a characteristic ‘alternative’ state of activation in macrophages that is distinct from the ‘classic...	[ "Cationic amino acid transporters ( CAT ) are important regulators of NOS2 and ARG1 activity because they regulate L-arginine availability .", "However , their role in the development of Th1/Th2 effector functions following infection has not been investigated .", "Here we dissect the function of CAT2 by studyin...	[ "Recent studies conducted with amino transporter Slc7a2-deficient mice ( CAT2 ) demonstrated that NOS2 activity in macrophages is regulated by CAT2 .", "NOS2 , which synthesizes nitric oxide , regulates numerous important activities , including resistance to infectious organisms , tumor development , and autoimmu...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "innate immune system", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "cytokines", "antiviral immune response", "immunology", "microbiology", "light microscopy", "viruses", "developmental biology", "rna viruses", "immunoprecipitation", "microscopy", "...	FAS-associated factor-1 positively regulates type I interferon response to RNA virus infection by targeting NLRX1	journal.ppat.1006398	null	[ [ "FAS-associated factor 1 ( FAF1 ) was originally identified as a member of the FAS death-inducing signaling complex [1] .", "FAF1 harbors several protein interaction domains , including FAS-interacting domains ( FID ) , a death effector domain-interacting domain ( DEDID ) , and multi-ubiquitin-related dom...	[ "FAS-associated factor-1 ( FAF1 ) is a component of the death-inducing signaling complex involved in Fas-mediated apoptosis .", "It regulates NF-κB activity , ubiquitination , and proteasomal degradation .", "Here , we found that FAF1 positively regulates the type I interferon pathway .", "FAF1gt/gt mice , wh...	[ "Type I interferon-mediated antiviral response is critical for controlling virus infections .", "However , interferon-mediated immune responses need to be tightly regulated to maintain host immune homeostasis .", "Recently , molecules involved in regulating interferon-mediated innate immune response are the sub...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "velocity", "medicine and health sciences", "body fluids", "classical mechanics", "fluid mechanics", "mechanical stress", "cellular structures and organelles", "mucus", "flow field", "fluid dynamics", "continuum mechanics", "fluid flow", "physics", "shear stresses", "cell biology", "an...	A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part II, modeling	journal.pcbi.1005552	null	[ [ "Mucociliary clearance is one of the major defense mechanisms of the respiratory airway system .", "The mucus layer coating the epithelial surface of the airways filters the inhaled air by trapping potentially harmful material ( fungi , bacteria and other particles ) [1–4] .", "This mucus layer is con...	[ "Mucociliary clearance is one of the major lines of defense of the human respiratory system .", "The mucus layer coating the airways is constantly moved along and out of the lung by the activity of motile cilia , expelling at the same time particles trapped in it .", "The efficiency of the cilia motion can expe...	[ "Mucociliary clearance is the first line of defense mechanisms of the human airways .", "The mucus transporting debris , particles , microorganisms and pollutants is carried away by the coordinated motion of cilia beating at the surface of the airway epithelium .", "We present here a mathematical and numerical ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "t helper cells", "flow cytometry", "medicine and health sciences", "immune cells", "immune physiology", "spleen", "immunology", "parasitic diseases", "parasitic protozoans", "protozoans", "anergy", "research and analysis methods", "immune system proteins", "spectrum analy...	GRAIL and Otubain-1 are Related to T Cell Hyporesponsiveness during Trypanosoma cruzi Infection	journal.pntd.0005307	null	[ [ "Chagas disease , caused by the intracellular protozoa Trypanosoma cruzi , is one of the major human health problems in Latin America .", "It evolves from an acute to a chronic phase , where subjects may be clinically asymptomatic or show progressive heart disease and leads to an end-stage dilated cardiom...	[ "Trypanosoma cruzi infection is associated with severe T cell unresponsiveness to antigens and mitogens and is characterized by decreased IL-2 synthesis .", "In addition , the acquisition of the anergic phenotype is correlated with upregulation of “gene related to anergy in lymphocytes” ( GRAIL ) protein in CD4 T...	[ "Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and is endemic in Central and South America , where it affects about 10 million people .", "In addition , migration has led to the disease being established in non-endemic countries .", "Infection involves an acute stage that evolves to a chr...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "larvicides", "invertebrates", "emulsions", "medicine and health sciences", "demography", "colloids", "animals", "reproductive physiology", "developmental biology", "waxes", "materials science", "pest control", "population biology", "insect vectors", "materials by struct...	Combining Attractants and Larvicides in Biodegradable Matrices for Sustainable Mosquito Vector Control	journal.pntd.0005043	null	[ [ "Mosquitoes transmit several serious pathogens in the tropics .", "Mosquito population control interventions are therefore frequently implemented to keep the diseases at bay , which are caused by those pathogens .", "The most targeted mosquito species include members of the mosquito genera Anopheles (...	[ "There is a global need for cost-effective and environmentally friendly tools for control of mosquitoes and mosquito-borne diseases .", "One potential way to achieve this is to combine already available tools to gain synergistic effects to reduce vector mosquito populations .", "Another possible way to improve ...	[ "Traditionally , a key intervention in mosquito control is the use of insecticides against the adult stage .", "However , various factors limit the long-term use of these control methods , including the development of insecticide resistance , changes in mosquito biting behaviour , and concerns regarding potential...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Histamine Recycling Is Mediated by CarT, a Carcinine Transporter in Drosophila Photoreceptors	journal.pgen.1005764	null	[ [ "Histamine is an important chemical messenger known to be involved in a broad spectrum of biological processes such as inflammation and gastric acid secretion .", "It is also recognized as an important neurotransmitter [1] .", "Recycling histamine at histaminergic synapses is a key event both in maint...	[ "Histamine is an important chemical messenger that regulates multiple physiological processes in both vertebrate and invertebrate animals .", "Even so , how glial cells and neurons recycle histamine remains to be elucidated .", "Drosophila photoreceptor neurons use histamine as a neurotransmitter , and the rele...	[ "Neurotransmitter transporters that remove neurotransmitters and recycle them after their release have particular importance at visual synapses , which must signal at high frequencies and therefore required rapid clearance of neurotransmitters from the synaptic cleft .", "In this study , we identified a SLC22 fam...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "guinea", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "vibrio", "tropical diseases", "geographical locations", "microbiology", "bacterial diseases", "vibrio cholerae", "benin", "neglected tropical diseases", "bacteria", "bacterial pathogens", "africa...	Dynamics of cholera epidemics from Benin to Mauritania	journal.pntd.0006379	null	[ [ "Seven cholera pandemics have been documented since 1817 [1] .", "The disease has plagued every continent , spreading along trade routes via both land and sea [1] .", "Current epidemics are however localized to South Asia , Haiti , and Sub-Saharan Africa [2] .", "Since the ongoing pandemic first r...	[ "The countries of West Africa are largely portrayed as cholera endemic , although the dynamics of outbreaks in this region of Africa remain largely unclear .", "To understand the dynamics of cholera in a major portion of West Africa , we analyzed cholera epidemics from 2009 to 2015 from Benin to Mauritania .", ...	[ "We analyzed cholera epidemics from Benin to Mauritania , during 2009 to 2015 , and performed a series of field visits as well as molecular epidemiology analyses of V . cholerae isolates from most recent epidemics throughout West Africa .", "We found that at least 54% of cases concerned populations living in the ...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "influenza", "sociology", "social sciences", "social media", "mathematics", "forecasting", "statistics (mathematics)", "internet", "network analysis", "social networks", "distribution curves", "social communication", "infectious disease control", "research...	Optimal multi-source forecasting of seasonal influenza	journal.pcbi.1006236	null	[ [ "Seasonal influenza epidemics annually result in significant global morbidity and mortality [1] , and influenza pandemics can cause catastrophic levels of death , social disruption , and economic loss [2] .", "Early detection and forecasting of both emergence and peak epidemic activity can inform an effec...	[ "Forecasting the emergence and spread of influenza viruses is an important public health challenge .", "Timely and accurate estimates of influenza prevalence , particularly of severe cases requiring hospitalization , can improve control measures to reduce transmission and mortality .", "Here , we extend a previ...	[ "In the United States , seasonal influenza causes thousands of deaths and hundreds of thousands of hospitalizations .", "The annual timing and burden of the flu season vary considerably with the severity of the circulating viruses .", "Epidemic forecasting can inform early and effective countermeasures to limit...	2018

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