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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", "Methods" ]	[ "medicine", "public health and epidemiology", "geriatrics", "epidemiology", "endocrinology", "genetics", "biology", "genomics", "diabetes and endocrinology", "genetics and genomics" ]	Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms	journal.pgen.1002025	null	[ [ "Dehydroepiandrosterone sulphate ( DHEAS ) , mainly secreted by the adrenal gland , is the most abundant circulating steroid in humans .", "It acts as an inactive precursor which is converted initially into DHEA and thereafter into active androgens and estrogens in peripheral target tissues [1] .", "I...	[ "Dehydroepiandrosterone sulphate ( DHEAS ) is the most abundant circulating steroid secreted by adrenal glands—yet its function is unknown .", "Its serum concentration declines significantly with increasing age , which has led to speculation that a relative DHEAS deficiency may contribute to the development of co...	[ "Dehydroepiandrosterone sulphate ( DHEAS ) , mainly secreted by the adrenal gland , is the most abundant circulating steroid in humans .", "It shows a significant physiological decline after the age of 25 and diminishes about 95% by the age of 85 years , which has led to speculation that a relative DHEAS deficien...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Theory of Choice in Bandit, Information Sampling and Foraging Tasks	journal.pcbi.1004164	null	[ [ "Decision making has been studied with a wide array of tasks .", "Choices in many of these tasks either do not affect future choices or are modeled as if they do not affect future choices .", "For example , when asked to choose between gambles ( e . g . 50% chance of $20 or 100% chance of $11 ) , the ...	[ "Decision making has been studied with a wide array of tasks .", "Here we examine the theoretical structure of bandit , information sampling and foraging tasks .", "These tasks move beyond tasks where the choice in the current trial does not affect future expected rewards .", "We have modeled these tasks usin...	[ "Numerous choice tasks have been used to study decision processes .", "Some of these choice tasks , specifically n-armed bandit , information sampling and foraging tasks , pose choices that trade-off immediate and future reward .", "Specifically , the best choice may not be the choice that pays off the highest ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "influenza", "virology" ]	Influenza in Migratory Birds and Evidence of Limited Intercontinental Virus Exchange	journal.ppat.0030167	null	[ [ "Long-term surveillance of influenza in migratory waterfowl in North America [1–4] from 1976 to the present and more intensive surveillance in Europe from 1998 to the present [5 , 6] have established the importance of Anseriformes ( waterfowl ) and Charadriiformes ( gull and shorebird ) in the perpetuation of...	[ "Migratory waterfowl of the world are the natural reservoirs of influenza viruses of all known subtypes .", "However , it is unknown whether these waterfowl perpetuate highly pathogenic ( HP ) H5 and H7 avian influenza viruses .", "Here we report influenza virus surveillance from 2001 to 2006 in wild ducks in A...	[ "Influenza surveillance in wild migratory birds has been done at two sites in North America:", "1 ) in Alberta , Canada , for the past 31 years , and", "2 ) along Delaware Bay , United States , for the past 22 years .", "These studies support the concept that wild migratory birds are the reservoirs of all inf...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/plant-biotic interactions", "plant biology/plant-biotic interactions", "genetics and genomics/gene expression" ]	Pep1, a Secreted Effector Protein of Ustilago maydis, Is Required for Successful Invasion of Plant Cells	journal.ppat.1000290	null	[ [ "The initial step of pathogenic development for both necrotrophic and biotrophic fungal pathogens is the successful penetration of the plant surface .", "Penetration can occur directly via specialized infection structures , called appressoria , which promote the localized secretion of plant cell wall degr...	[ "The basidiomycete Ustilago maydis causes smut disease in maize .", "Colonization of the host plant is initiated by direct penetration of cuticle and cell wall of maize epidermis cells .", "The invading hyphae are surrounded by the plant plasma membrane and proliferate within the plant tissue .", "We identifi...	[ "For many fungi that infect plants , successful invasion is coupled to a series of differentiation steps that are necessary to breach the plant cuticle .", "Such fungi form specialized infection structures which allow direct penetration of the plant cuticle .", "The smut fungus Ustilago maydis establishes a bio...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "applied mathematics", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "algorithms", "simulation and modeling", "optimization", "mathematics", "rna ...	Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting	journal.ppat.1006148	null	[ [ "The HIV-1 Env glycoprotein , the sole target of antibody responses on the surface of the virus , exhibits extreme levels of sequence diversity [1–3] , possibly explaining why antibodies capable of broad and potent neutralization of the virus have been found to target only a small set of conserved Env sites o...	[ "Computational neutralization fingerprinting , NFP , is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection .", "Here , we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enabl...	[ "HIV-1 remains a significant global health threat , with no effective vaccine against the virus currently available .", "Since traditional vaccine design efforts have had limited success , much effort in recent years has focused on gaining a better understanding of the ways select individuals are able to effectiv...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "developmental biology/stem cells", "molecular biology/transcription initiation and activation", "developmental biology/aging", "molecular biology/transcription elongation", "developmental biology/developmental molecular mechanisms" ]	A Transcription Elongation Factor That Links Signals from the Reproductive System to Lifespan Extension in Caenorhabditis elegans	journal.pgen.1000639	null	[ [ "When the germline of C . elegans is removed , either by laser ablation or by mutations that block germline-stem cell proliferation , the animals live approximately 60% longer than normal [1] , [2] .", "This longevity is not a simple consequence of sterility , as removing the entire gonad ( the germ cells...	[ "In Caenorhabditis elegans and Drosophila melanogaster , the aging of the soma is influenced by the germline .", "When germline-stem cells are removed , aging slows and lifespan is increased .", "The mechanism by which somatic tissues respond to loss of the germline is not well-understood .", "Surprisingly , ...	[ "The reproductive status and longevity of animals are strongly interlinked .", "Increasing age influences the reproductive capacities of most animals .", "However , little is known about how reproductive status might affect lifespan .", "Experiments in worms and flies have shown that removing cells that give ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "ecology" ]	Specialization Does Not Predict Individual Efficiency in an Ant	journal.pbio.0060285	The assumption that the success of social insects rests on the increased efficiency of dividing tasks within the colony is challenged by evidence that specialists are not always better at their jobs.	[ [ "Social insects are enormously successful ecologically .", "Ants , social bees , social wasps , and termites may make up 75% of the world's insect biomass , they play a major role in soil turnover and nutrient cycling , and they often surpass vertebrates in their biomass in a habitat [1] .", "Division...	[ "The ecological success of social insects is often attributed to an increase in efficiency achieved through division of labor between workers in a colony .", "Much research has therefore focused on the mechanism by which a division of labor is implemented , i . e . , on how tasks are allocated to workers .", "H...	[ "Social insects , including ants , bees , and termites , may make up 75% of the world's insect biomass .", "This success is often attributed to their complex colony organization .", "Each individual is thought to specialize in a particular task and thus become an “expert” for this task .", "Researchers have l...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Toxoplasmosis and Epilepsy — Systematic Review and Meta Analysis	journal.pntd.0003525	null	[ [ "Epilepsy is a major chronic neurological disorder that affects about 70 million people worldwide [1] .", "However , its importance goes beyond mere numbers [2] .", "Most of its burden is felt in low- and middle-income tropical countries , where a number of infections that are important risk factors f...	[ "Toxoplasmosis is an important , widespread , parasitic infection caused by Toxoplasma gondii .", "The chronic infection in immunocompetent patients , usually considered as asymptomatic , is now suspected to be a risk factor for various neurological disorders , including epilepsy .", "We aimed to conduct a syst...	[ "Toxoplasmosis is a common parasitic infection and affects one-third of the global population .", "The burden this figure represents clearly signifies the public health relevance of toxoplasmosis .", "Epilepsy , another chronic condition , is often caused by a variety of infections that affect numerous low- and...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "emerging infectious diseases", "gene identification and analysis", "genetics", "microbial pathogens", "molecular genetics", "host-pathogen interaction", "biology", "microbiology", "pathogenesis" ]	Fine Analysis of Genetic Diversity of the tpr Gene Family among Treponemal Species, Subspecies and Strains	journal.pntd.0002222	null	[ [ "Non-cultivable pathogenic treponemes include three subspecies of Treponema pallidum: T . pallidum subsp .", "pallidum ( T . p . pallidum ) , T . pallidum subsp .", "pertenue ( T . p . pertenue ) and T . pallidum subsp .", "endemicum ( T . p . endemicum ) .", "These subspecies are human pathog...	[ "The pathogenic non-cultivable treponemes include three subspecies of Treponema pallidum ( pallidum , pertenue , endemicum ) , T . carateum , T . paraluiscuniculi , and the unclassified Fribourg-Blanc treponeme ( Simian isolate ) .", "These treponemes are morphologically indistinguishable and antigenically and ge...	[ "Pathogenic treponemes include three subspecies of Treponema pallidum ( pallidum , pertenue , endemicum ) , T . carateum , T . paraluiscuniculi , and the unclassified Fribourg-Blanc treponeme .", "Although they share morphology and have very similar antigenic profiles , they have traditionally been distinguished ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "affinity chromatography", "gene regulation", "regulatory proteins", "immunology", "cell processes", "dna-binding proteins", "plasmid construction", "dna transcription", "immunoprecipitation", "transcription factors", "dna cons...	EBV Nuclear Antigen 3C Mediates Regulation of E2F6 to Inhibit E2F1 Transcription and Promote Cell Proliferation	journal.ppat.1005844	null	[ [ "EBV nuclear antigen 3C ( EBNA3C ) is expressed in latent infection and essential for EBV-mediated B-cell transformation , which plays an intricate role in regulation of viral as well as cellular gene transcription [1 , 2] .", "A large proportion of cellular transcription factors are genes encoded by onco...	[ "Epstein–Barr virus ( EBV ) is considered a ubiquitous herpesvirus with the ability to cause latent infection in humans worldwide .", "EBV-association is evidently linked to different types of human malignancies , mainly of epithelial and lymphoid origin .", "Of interest is the EBV nuclear antigen 3C ( EBNA3C )...	[ "EBV is associated with a broad range of human cancers .", "EBV-encoded nuclear antigen 3C ( EBNA3C ) is one of the essential latent antigens important for deregulating the functions of numerous host transcription factors which play vital roles in B-cell immortalization .", "The family of E2F transcription fact...	2016
[ "Introduction", "Methods", "Results and discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "helminths", "geographical locations", "parasitic diseases", "animals", "parasitology", "seasons", "developmental biology", "ascaris", "ascaris lumbricoides", "population biology", "africa", "life cycles", "nigeria", "pe...	Seasonally timed treatment programs for Ascaris lumbricoides to increase impact—An investigation using mathematical models	journal.pntd.0006195	null	[ [ "Soil-transmitted helminth infections affect approximately 1 . 5 billion people worldwide [1] , with periodic mass deworming playing a key role in control and elimination efforts .", "More efficient allocation of control effort resources therefore has the potential to improve the lives of many millions of...	[ "There is clear empirical evidence that environmental conditions can influence Ascaris spp .", "free-living stage development and host reinfection , but the impact of these differences on human infections , and interventions to control them , is variable .", "A new model framework reflecting four key stages of ...	[ "Soil-transmitted helminth infections affect 1 . 5 billion people worldwide and mass drug adminstration ( MDA ) is one of the key public health measures for reducing the burden of infection .", "A number of experimental studies have demonstrated links between temperature and the dynamics of Ascaris spp .", "egg...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Arabidopsis RCC1 Family Protein TCF1 Regulates Freezing Tolerance and Cold Acclimation through Modulating Lignin Biosynthesis	journal.pgen.1005471	null	[ [ "Freezing temperature is an important environmental factor that determines the natural geographical distribution of plants and limits crop productivity [1] .", "Sudden exposure to freezing temperature causes intracellular freezing , membrane damage and cell death [1–3] .", "To better survive freezing ...	[ "Cell water permeability and cell wall properties are critical to survival of plant cells during freezing , however the underlying molecular mechanisms remain elusive .", "Here , we report that a specifically cold-induced nuclear protein , Tolerant to Chilling and Freezing 1 ( TCF1 ) , interacts with histones H3 ...	[ "Cold acclimation is a well-known adaptive process through which plants can dramatically increase their tolerance to freezing temperature .", "Modifications of cell wall have been recognized as a key characteristic during plant acclimation to low temperature .", "However , the molecular mechanism responsible fo...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viruses", "biochemistry", "infectious diseases", "virology", "in vitro" ]	Newly Synthesized APOBEC3G Is Incorporated into HIV Virions, Inhibited by HIV RNA, and Subsequently Activated by RNase H	journal.ppat.0030015	null	[ [ "APOBEC3G ( A3G ) is a highly active antiretroviral deoxycytidine deaminase that greatly impairs HIV spread in cultures of activated CD4 T cells provided the HIV Vif protein is absent [1] .", "In these activated cells , the antiviral action of A3G involves its effective incorporation into budding virions ...	[ "APOBEC3G ( A3G ) is a potent antiretroviral deoxycytidine deaminase that , when incorporated into HIV virions , hypermutates nascent viral DNA formed during reverse transcription .", "HIV Vif counters the effect of A3G by depleting intracellular stores of the enzyme , thereby blocking its virion incorporation ."...	[ "APOBEC3G ( A3G ) is a cellular enzyme that promotes DNA mutagenesis and can restrict infection by HIV-1 .", "However , HIV counters the antiviral effects of A3G through the action of its Vif protein .", "In the absence of Vif , A3G is effectively incorporated into virions , where it mutagenizes the first DNA c...	2007
[ "Introduction", "Model", "Results", "Discussion", "Supporting Information" ]	[]	Short-Range Guiding Can Result in the Formation of Circular Aggregates in Myxobacteria Populations	journal.pcbi.1004213	null	[ [ "Myxobacteria are social bacteria that upon starvation form multicellular fruiting bodies whose shape in different species can range from simple mounds to elaborate tree-like structures consisting of 105 − 106 cells [1 , 2] .", "The development of fruiting bodies is a result of collective movement of flex...	[ "Myxobacteria are social bacteria that upon starvation form multicellular fruiting bodies whose shape in different species can range from simple mounds to elaborate tree-like structures .", "The formation of fruiting bodies is a result of collective cell movement on a solid surface .", "In the course of develop...	[ "Myxobacteria are social bacteria that upon starvation form multicellular fruiting bodies whose shape in different species can range from simple mounds to elaborate tree-like structures .", "The formation of fruiting bodies is a result of collective cell movement on a solid surface .", "Since collective cell mo...	2015
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Genetic Evidence for Function of the bHLH-PAS Protein Gce/Met As a Juvenile Hormone Receptor	journal.pgen.1005394	null	[ [ "Arthropods possess unique sesquiterpenoid hormones , represented by the juvenile hormones ( JHs ) of insects [1] and their non-epoxidized precursor , methyl farnesoate ( MF ) in crustaceans [2 , 3] .", "JHs regulate insect metamorphosis , polymorphism and social caste determination , and adult reproducti...	[ "Juvenile hormones ( JHs ) play a major role in controlling development and reproduction in insects and other arthropods .", "Synthetic JH-mimicking compounds such as methoprene are employed as potent insecticides against significant agricultural , household and disease vector pests .", "However , a receptor me...	[ "Juvenile hormones ( JHs ) play critical roles in the development of arthropods , comprising half the animal biomass of the oceans and over a million insect species , which have an enormous impact on ecosystems , agriculture ( pollinators and pests ) and health of mankind ( disease vectors ) .", "Despite decades ...	2015
[ "Introduction", "Results", "Discussion" ]	[ "neuroscience" ]	Mapping the Structural Core of Human Cerebral Cortex	journal.pbio.0060159	Mapping of major structural connections of the human cortex reveals a core of brain regions that are highly interconnected and highly central with respect to the rest of the brain.	[ [ "Human cerebral cortex consists of approximately 1010 neurons that are organized into a complex network of local circuits and long-range fiber pathways .", "This complex network forms the structural substrate for distributed interactions among specialized brain systems [1–3] .", "Computational network...	[ "Structurally segregated and functionally specialized regions of the human cerebral cortex are interconnected by a dense network of cortico-cortical axonal pathways .", "By using diffusion spectrum imaging , we noninvasively mapped these pathways within and across cortical hemispheres in individual human particip...	[ "In the human brain , neural activation patterns are shaped by the underlying structural connections that form a dense network of fiber pathways linking all regions of the cerebral cortex .", "Using diffusion imaging techniques , which allow the noninvasive mapping of fiber pathways , we constructed connection ma...	2008
[ "Introduction", "Methods", "Results/Discussion" ]	[ "computer science/natural and synthetic vision", "neuroscience/natural and synthetic vision", "neuroscience/sensory systems", "computational biology/computational neuroscience" ]	Robust Models for Optic Flow Coding in Natural Scenes Inspired by Insect Biology	journal.pcbi.1000555	null	[ [ "There are four main classes of motion detection models , namely: ( 1 ) differential methods; ( 2 ) region-based matching; ( 3 ) phase-based and ( 4 ) energy-based techniques ( for review see [11] ) .", "All four consist of three basic components ( pre-filtering , local motion estimation and integration o...	[ "The extraction of accurate self-motion information from the visual world is a difficult problem that has been solved very efficiently by biological organisms utilizing non-linear processing .", "Previous bio-inspired models for motion detection based on a correlation mechanism have been dogged by issues that ari...	[ "Building artificial vision systems that work robustly in a variety of environments has been difficult , with systems often only performing well under restricted conditions .", "In contrast , animal vision operates effectively under extremely variable situations .", "Many attempts to emulate biological vision h...	2009
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "chitin", "medicine and health sciences", "pathology and laboratory medicine", "enzymes", "pathogens", "vibrio", "enzymology", "microbiology", "pili and fimbriae", "phosphatases", "pseudomonas aeruginosa", "vibrio cholerae", "materials science", "genetic elements", "cellular structures a...	The type IV pilus protein PilU functions as a PilT-dependent retraction ATPase	journal.pgen.1008393	null	[ [ "Type IV pili ( T4P ) are a widespread class of cell surface polymers found throughout the bacteria and archaea [1–3] .", "In bacteria , they allow cells to physically sense and interact with the environment around them [4] .", "Consequently they play critical roles in environmental survival and patho...	[ "Type IV pili are dynamic cell surface appendages found throughout the bacteria .", "The ability of these structures to undergo repetitive cycles of extension and retraction underpins their crucial roles in adhesion , motility and natural competence for transformation .", "In the best-studied systems a dedicate...	[ "Bacteria interact with their surroundings using micrometre scale polymers called type IV pili .", "They allow bacteria to physically sense , attach and move on surfaces , and even to take up DNA .", "Consequently they represent important mechanisms of environmental survival and pathogenesis .", "The versatil...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Acquisition Order of Ras and p53 Gene Alterations Defines Distinct Adrenocortical Tumor Phenotypes	journal.pgen.1002700	null	[ [ "Cancer is an heterogeneous disease .", "Thus , tumors in different organs display markedly different clinical behaviors and tumors that arise in a single tissue can even exhibit an array of pathologies , ranging from benign adenomas to highly invasive malignancies [1] , [2] .", "The phenotypic divers...	[ "Sporadic adrenocortical carcinomas ( ACC ) are rare endocrine neoplasms with a dismal prognosis .", "By contrast , benign tumors of the adrenal cortex are common in the general population .", "Whether benign tumors represent a separate entity or are in fact part of a process of tumor progression ultimately lea...	[ "A sequential acquisition of genetic events is critical in tumorigenesis , and a dysregulation of a limited set of pathways has been demonstrated as sufficient to progressively transform normal cells into tumor cells in several human tissues .", "However , in the case of adrenocortical tumorigenesis , whether ben...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Male-Biased Aganglionic Megacolon in the TashT Mouse Line Due to Perturbation of Silencer Elements in a Large Gene Desert of Chromosome 10	journal.pgen.1005093	null	[ [ "The enteric nervous system ( ENS ) is the intrinsic neural network of the gastrointestinal tract .", "One of its essential roles is to regulate intestinal motility .", "The ENS is made up of interconnected neural ganglia , themselves composed of neurons and supporting glial cells , forming two main p...	[ "Neural crest cells ( NCC ) are a transient migratory cell population that generates diverse cell types such as neurons and glia of the enteric nervous system ( ENS ) .", "Via an insertional mutation screen for loci affecting NCC development in mice , we identified one line—named TashT—that displays a partially p...	[ "Hirschsprung’s disease ( also known as aganglionic megacolon ) is a severe congenital defect of the enteric nervous system ( ENS ) resulting in complete failure to pass stools .", "It is characterized by the absence of neural ganglia ( aganglionosis ) in the distal gut due to incomplete colonization of the embry...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "public health and epidemiology", "ecology", "plasmodium", "anopheles", "homo (human)" ]	Revisiting the Basic Reproductive Number for Malaria and Its Implications for Malaria Control	journal.pbio.0050042	A new mathematical approach applied to 121 human populations infected with malaria revises the basic reproductive number--an indication of the transmission intensity--up by an order of magnitude, with serious implications for effective malaria control.	[ [ "Each year , Plasmodium falciparum causes approximately 515 million clinical malaria cases [1] and over one million deaths [2 , 3] .", "Most malaria-related mortality and a large fraction of malaria cases occur in sub-Saharan Africa , where transmission can be very intense [4] .", "Strategic planning ...	[ "The prospects for the success of malaria control depend , in part , on the basic reproductive number for malaria , R0 .", "Here , we estimate R0 in a novel way for 121 African populations , and thereby increase the number of R0 estimates for malaria by an order of magnitude .", "The estimates range from around...	[ "Each year malaria results in more than a million deaths .", "Controlling this disease involves understanding its transmission .", "For all infectious disease , the basic reproductive number , R0 , describes the most important aspects of transmission .", "This is the expected number of hosts that can trace th...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission	journal.ppat.1005000	null	[ [ "The development of highly potent antiretroviral therapy ( ART ) for HIV means that the virus can be effectively controlled in most treated patients .", "However , ART must be taken continuously , as interruption of ART is followed by the rapid recrudescence of virus from a quiescent ‘latent reservoir’ of...	[ "HIV infection can be effectively controlled by anti-retroviral therapy ( ART ) in most patients .", "However therapy must be continued for life , because interruption of ART leads to rapid recrudescence of infection from long-lived latently infected cells .", "A number of approaches are currently being develop...	[ "During treatment of HIV infection the virus persists in infected cells in a quiescent or ‘latent’ state .", "If treatment is stopped , then virus rebounds to detectable levels usually within 2–3 weeks .", "This is thought to occur due to release of infectious virus from a reservoir of long-lived latently infec...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "circuit models", "mathematics", "neural homeostasis", "neural networks", "computational neuroscience", "biology", "nonlinear dynamics", "neuroscience", "learning and memory" ]	Spatiotemporal Computations of an Excitable and Plastic Brain: Neuronal Plasticity Leads to Noise-Robust and Noise-Constructive Computations	journal.pcbi.1003512	null	[ [ "Neuronal plasticity , both homeostatic and synaptic , is the central ingredient for the generation and adaptation of neural function and computation [1] .", "However , it remains mostly unclear how neurons in recurrent neural networks utilize neuronal plasticity to self-organize and to learn computing on...	[ "It is a long-established fact that neuronal plasticity occupies the central role in generating neural function and computation .", "Nevertheless , no unifying account exists of how neurons in a recurrent cortical network learn to compute on temporally and spatially extended stimuli .", "However , these stimuli...	[ "The world is not perceived as a chain of segmented sensory still lifes .", "Instead , it appears that the brain is capable of integrating the temporal dependencies of the incoming sensory stream with the spatial aspects of that input .", "It then transfers the resulting whole in a useful manner , in order to r...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Signatures of Adaptation in Human Invasive Salmonella Typhimurium ST313 Populations from Sub-Saharan Africa	journal.pntd.0003611	null	[ [ "Salmonella enterica isolates can infect a range of animals and humans , causing a spectrum of disease syndromes ranging from gastroenteritis through to typhoid and an asymptomatic carrier state [1] .", "From a clinical perspective S . enterica serovars have been classically assigned to two broad groups ,...	[ "Two lineages of Salmonella enterica serovar Typhimurium ( S . Typhimurium ) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan Africa .", "The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage ."...	[ "Salmonella enterica is a diverse species , isolates of which can colonise or infect many different animals , including humans and can cause different disease syndromes .", "S . enterica can be sub-typed using serology into serovars .", "Isolates from some serovars , known as generalists , can infect multiple h...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "rna interference", "gene regulation", "oxygen", "animals", "animal models", "developmental biology", "micrornas", "model organisms", "drosophila melanogaster", "hypoxia", "molecular biology techniques", "epigenetics", "embryos", "drosophila", "research and analysis me...	miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga	journal.pgen.1006073	null	[ [ "Cells and organisms exposed to environmental stress mount complex adaptive responses in order to maintain homeostasis .", "In mammals , hypoxic stress triggers cellular and systemic modifications , such as metabolic switches [1 , 2] , erythropoiesis [3 , 4] , angiogenesis and vasodilation [5 , 6] , resul...	[ "Cellular and systemic responses to low oxygen levels are principally mediated by Hypoxia Inducible Factors ( HIFs ) , a family of evolutionary conserved heterodimeric transcription factors , whose alpha- and beta-subunits belong to the bHLH-PAS family .", "In normoxia , HIFα is hydroxylated by specific prolyl-4-...	[ "Sufficient oxygen supply is essential for animal survival .", "When cells or organisms are exposed to low oxygen levels ( hypoxia ) , a complex molecular response is triggered , enabling adaptation to this stressful condition .", "A key mediator of this response is HIF , a transcription factor that induces the...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Triglyceride-Increasing Alleles Associated with Protection against Type-2 Diabetes	journal.pgen.1005204	null	[ [ "Along with age , body weight , family history , and other characteristics , triglyceride ( TG ) level is a major risk factor for cardiovascular disease and type-2 diabetes ( T2D ) .", "In many prospective studies , TG at baseline is positively associated with T2D incidence , independently of body mass in...	[ "Elevated plasma triglyceride ( TG ) levels are an established risk factor for type-2 diabetes ( T2D ) .", "However , recent studies have hinted at the possibility that genetic risk for TG may paradoxically protect against T2D .", "In this study , we examined the association of genetic risk for TG with incident...	[ "An elevated triglyceride level is generally considered a risk factor for the development of type-2 diabetes .", "However , recent studies suggest , somewhat paradoxically , that genetic risk for elevated triglycerides may protect against type-2 diabetes .", "In this study , we test the relationship of triglyce...	2015
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	HOMER2, a Stereociliary Scaffolding Protein, Is Essential for Normal Hearing in Humans and Mice	journal.pgen.1005137	null	[ [ "Targeted genomic enrichment and massively parallel sequencing ( TGE+MPS ) have revolutionized the field of hereditary hearing loss ( HHL ) by making comprehensive genetic testing for deafness a clinical reality and by accelerating the discovery of novel deafness-causing genes [1 , 2] .", "To date over 80...	[ "Hereditary hearing loss is a clinically and genetically heterogeneous disorder .", "More than 80 genes have been implicated to date , and with the advent of targeted genomic enrichment and massively parallel sequencing ( TGE+MPS ) the rate of novel deafness-gene identification has accelerated .", "Here we repo...	[ "The most frequent sensory disorder worldwide is hearing impairment .", "It impacts over 5% of the world population ( 360 million persons ) , and is characterized by extreme genetic heterogeneity .", "Over 80 genes have been implicated in isolated ( also referred to as ‘non-syndromic’ ) hearing loss , and abund...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunodeficiency viruses", "virology", "biology", "microbiology" ]	Mechanism of HIV-1 Virion Entrapment by Tetherin	journal.ppat.1003483	null	[ [ "Cells have evolved numerous defense measures to inhibit the replication of infectious agents .", "In animal cells , sensing of viruses by pattern recognition receptors leads to interferon production and signaling , which induces the expression of hundreds of interferon-stimulated genes ( ISGs ) in infect...	[ "Tetherin , an interferon-inducible membrane protein , inhibits the release of nascent enveloped viral particles from the surface of infected cells .", "However , the mechanisms underlying virion retention have not yet been fully delineated .", "Here , we employ biochemical assays and engineered tetherin protei...	[ "The cellular restriction factor , tetherin , prevents HIV-1 and other enveloped virus particles from being disseminated into the extracellular milieu by infiltrating their envelopes and by physically crosslinking them to the cell surface .", "It is known that tetherin consists of pairs of membrane anchors , situ...	2013
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "medicine and health sciences", "luciferase", "protein interactions", "pathology and laboratory medicine", "enzymes", "pathogens", "protein interaction networks", "immunology", "microbiology", "enzymology", "viruses", "rna viruses", "network analysis", "mapk signaling cascades", "rabies ...	Regulation of NF-κB by the p105-ABIN2-TPL2 complex and RelAp43 during rabies virus infection	journal.ppat.1006697	null	[ [ "Depending on specific stimuli , the transcription factors of the NF-κB family are major regulators of cellular physiology .", "They regulate apoptosis , cell survival , proliferation and immune response , which requires each step of the cell signaling cascade to be highly regulated [1] .", "The NF-κB...	[ "At the crossroad between the NF-κB and the MAPK pathways , the ternary complex composed of p105 , ABIN2 and TPL2 is essential for the host cell response to pathogens .", "The matrix protein ( M ) of field isolates of rabies virus was previously shown to disturb the signaling induced by RelAp43 , a NF-κB protein ...	[ "Rabies virus is a recurring zoonosis responsible for about 60 , 000 deaths per year .", "A key feature of rabies virus is its stealth , allowing it to spread within the host and escape the immune response .", "To do so , rabies virus developed several mechanisms , including a thorough interference with cell si...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "inflammatory diseases", "urology", "medicine and health sciences", "immune cells", "body fluids", "pathology and laboratory medicine", "maternal health", "blood counts", "immunology", "tropical diseases", "throat", "treponematoses", "bacterial diseases", "women's health",...	Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?	journal.pntd.0005456	null	[ [ "Neutropenia is a condition marked by an absolute neutrophil count ( ANC ) below 1 . 5×109/L in adults [1] , which can be further categorized as mild ( 1×109/L≤ANC<1 . 5×109/L ) , moderate ( 0 . 5×109/L≤ANC<1×109/L ) and severe type ( ANC<0 . 5×109/L ) [1 , 2] .", "There are many causes including drug-ind...	[ "Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae .", "However , life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other dise...	[ "High-dose intravenous benzylpenicillin is an effective treatment for neurosyphilis although it can cause potentially life-threatening drug-induced neutropenia .", "We investigated the incidence , presentation , management and prognosis of benzylpenicillin-induced neutropenia among neurosyphilis patients treated ...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "computer applications", "genome expression analysis", "cellular structures", "subcellular organelles", "genome evolution", "evolutionary biology", "molecular genetics", "information technology", "sequence analysis", "comparative genomics", "biology", "databases", "computer science", "web-...	Thousands of Rab GTPases for the Cell Biologist	journal.pcbi.1002217	null	[ [ "Intracellular compartmentalisation is found in all cellular lifeforms , yet eukaryotes have evolved extensive membranous compartments unique to this domain of life .", "Protein trafficking pathways accomplish the movement of cellular components like proteins and lipids between the cellular compartments ....	[ "Rab proteins are small GTPases that act as essential regulators of vesicular trafficking .", "44 subfamilies are known in humans , performing specific sets of functions at distinct subcellular localisations and tissues .", "Rab function is conserved even amongst distant orthologs .", "Hence , the annotation ...	[ "Intracellular compartmentalisation via membrane-delimited organelles is a fundamental feature of the eukaryotic cell .", "Understanding its origins and specialisation into functionally distinct compartments is a major challenge in evolutionary cell biology .", "We focus on the Rab enzymes , critical organisers...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "oncology", "computer and information sciences", "medicine and health sciences", "machine learning", "drug research and development", "pharmaceutics", "artificial intelligence", "cancer drug discovery", "dose prediction methods", "cancer treatment", "pharmacology", "drug discovery", "basic c...	Drug combination sensitivity scoring facilitates the discovery of synergistic and efficacious drug combinations in cancer	journal.pcbi.1006752	null	[ [ "Despite great advances in the understanding of cancer , there remains a major challenge to develop more effective anti-cancer treatments .", "Next generation sequencing has revealed the intrinsic heterogeneity in cancer genomes , which partly explains why patients respond differently to the same therapy ...	[ "High-throughput drug screening has facilitated the discovery of drug combinations in cancer .", "Many existing studies adopted a full matrix design , aiming for the characterization of drug pair effects for cancer cells .", "However , the full matrix design may be suboptimal as it requires a drug pair to be co...	[ "Cancer is one of the main causes of death worldwide .", "Although new treatment strategies have been achieved , they still have limited efficacy as cancer cells can easily develop drug resistance .", "To achieve more sustainable therapies to treat cancer , we need multi-targeted drug combinations that can inhi...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/theoretical neuroscience", "neuroscience/sensory systems" ]	Innate Visual Learning through Spontaneous Activity Patterns	journal.pcbi.1000137	null	[ [ "The classic debates of nature vs . nurture , or innate vs . learned , are pervasive in the literature of early visual development .", "A variety of studies have shown that the visual system requires external experience to mature ( e . g . , [1]–[3] ) .", "On the other hand , many animals are able to ...	[ "Patterns of spontaneous activity in the developing retina , LGN , and cortex are necessary for the proper development of visual cortex .", "With these patterns intact , the primary visual cortices of many newborn animals develop properties similar to those of the adult cortex but without the training benefit of ...	[ "Before many animals first open their eyes , neurons in the retina , thalamus , and visual cortex fire spontaneously in highly structured , patterned ways .", "Experimental manipulations have demonstrated that this activity is necessary for proper function , but it is difficult to answer certain fundamental quest...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "arrhythmias", "neurology", "genetics", "biology", "human genetics", "genetics of disease", "autonomic nervous system", "cardiovascular" ]	A Nonsynonymous Polymorphism in Semaphorin 3A as a Risk Factor for Human Unexplained Cardiac Arrest with Documented Ventricular Fibrillation	journal.pgen.1003364	null	[ [ "Unexpected sudden death in healthy individuals remains a daunting problem .", "Unexplained cardiac arrest with documented ventricular fibrillation ( UCA ) including idiopathic ventricular fibrillation ( IVF ) is defined as spontaneous VF that is not associated with a known structural or electrical heart ...	[ "Unexplained cardiac arrest ( UCA ) with documented ventricular fibrillation ( VF ) is a major cause of sudden cardiac death .", "Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation .", "Further , adequate expression of SEMA3A was reported to be critical for normal patt...	[ "Unexplained cardiac arrest with documented ventricular fibrillation ( UCA ) is defined as spontaneous ventricular fibrillation ( VF ) that is not associated with known structural or electrical heart diseases and is one of the major causes of sudden cardiac death .", "Identification of the genes responsible for U...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "leptospira", "pathology and laboratory medicine", "ruminants", "pathogens", "geographical locations", "microbiology", "vertebrates", "tropical diseases", "buffaloes", "animals", "mammals", "bacterial diseases", "neglected tropical diseases", ...	Investigation on predominant Leptospira serovars and its distribution in humans and livestock in Thailand, 2010-2015	journal.pntd.0005228	null	[ [ "Leptospirosis is a worldwide zoonotic bacterial disease particularly in tropical and subtropical countries [1] .", "Pathogenic Leptospira species are causative agents of the disease , specifically Leptospira interrogans sensu lato .", "There are approximately more than 250 recognized pathogenic serov...	[ "Leptospirosis is a worldwide zoonotic bacterial disease caused by infection with leptospires .", "Leptospirosis in humans and livestock is an endemic and epidemic disease in Thailand .", "Livestock may act as reservoirs for leptospires and source for human infection .", "Data on leptospirosis infection in hu...	[ "Leptospirosis is an important worldwide zoonotic disease , particularly in tropical and subtropical countries .", "The infection in humans is caused by either direct contact with products of infected animals , mainly urine , or by indirect contact via a contaminated environment .", "The animal hosts are thus c...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	South African Ebola diagnostic response in Sierra Leone: A modular high biosafety field laboratory	journal.pntd.0005665	null	[ [ "Ebola virus ( EBOV ) was previously only identified to cause outbreaks of Ebola virus disease ( EVD ) in central equatorial Africa [1] , but emerged in West Africa in late 2013 in Guinea [2] , and spread into Liberia in March , Sierra Leone in May , and Nigeria in late July 2014 [3] .", "The EVD outbreak...	[ "In August 2014 , the National Institute for Communicable Diseases ( NICD ) in South Africa established a modular high-biosafety field Ebola diagnostic laboratory ( SA FEDL ) near Freetown , Sierra Leone in response to the rapidly increasing number of Ebola virus disease ( EVD ) cases .", "The SA FEDL operated in...	[ "In response to Ebola virus disease outbreak in West Africa , the National Institute for Communicable Diseases in South Africa established a modular high-biosafety field Ebola diagnostic laboratory ( FEDL ) near Freetown , Sierra Leone .", "This was the sole diagnostic capacity available to respond to the overwhe...	2017
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "medicinal chemistry", "chemical biology", "chemistry", "biology", "microbiology", "parasitology", "parasite physiology" ]	SCYX-7158, an Orally-Active Benzoxaborole for the Treatment of Stage 2 Human African Trypanosomiasis	journal.pntd.0001151	null	[ [ "Human African trypanosomiasis ( HAT ) , commonly known as sleeping sickness , is a neglected disease caused by the kinetoplastid parasite Trypanosoma brucei and is fatal if left untreated .", "[1] , [2] The parasite is transmitted through the bite of the tsetse fly , and is endemic in sub-Saharan Africa ...	[ "Human African trypanosomiasis ( HAT ) is an important public health problem in sub-Saharan Africa , affecting hundreds of thousands of individuals .", "An urgent need exists for the discovery and development of new , safe , and effective drugs to treat HAT , as existing therapies suffer from poor safety profiles...	[ "Human African trypanosomiasis ( HAT ) is caused by infection with the parasite Trypanosoma brucei and is an important public health problem in sub-Saharan Africa .", "New , safe , and effective drugs are urgently needed to treat HAT , particularly stage 2 disease where the parasite infects the brain .", "Exist...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "population modeling", "biology", "computational biology", "infectious disease modeling" ]	The Dynamics of Naturally Acquired Immunity to Plasmodium falciparum Infection	journal.pcbi.1002729	null	[ [ "Plasmodium falciparum ( Pf ) malaria in holoendemic areas is characterized by high level parasitaemia and symptomatic infections in early childhood , followed by the development of semi-protective immunity that allows the persistence of low level asymptomatic infections and appears to reduce the likelihood o...	[ "Severe malaria occurs predominantly in young children and immunity to clinical disease is associated with cumulative exposure in holoendemic settings .", "The relative contribution of immunity against various stages of the parasite life cycle that results in controlling infection and limiting disease is not well...	[ "Human malaria infections resulting in serious complications and death occur predominantly in young children , and resistance is gradually acquired with repeated exposure .", "Malaria parasites have two major stages within the human host during its life cycle: an initial liver stage , and the subsequent blood sta...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models of infection", "bacterial diseases", "infectious diseases", "medicine and health sciences", "women's health", "medical microbiology", "microbial pathogens", "biology and life sciences", "superinfection", "microbiology" ]	Uropathogenic Escherichia coli Superinfection Enhances the Severity of Mouse Bladder Infection	journal.ppat.1004599	null	[ [ "Nearly nine million people present each year to primary care physicians with a urinary tract infection ( UTI ) , costing nearly $2 billion yearly [1] , [2] .", "Women suffer the majority of these infections , with the lifetime risk approaching 50% [3] .", "Furthermore , 25–40% of these women will suf...	[ "Urinary tract infections ( UTIs ) afflict over 9 million women in America every year , often necessitating long-term prophylactic antibiotics .", "One risk factor for UTI is frequent sexual intercourse , which dramatically increases the risk of UTI .", "The mechanism behind this increased risk is unknown; howe...	[ "Urinary tract infections ( UTIs ) affect millions of women each year resulting in substantial morbidity and lost wages .", "Approximately 1 . 5 million women are referred to urology clinics suffering from chronic recurrent UTI on a yearly basis necessitating the use of prophylactic antibiotics .", "Frequent an...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms	journal.pntd.0004173	null	[ [ "Filarial parasites belonging to the family Onchocercidae remain a significant global burden , endemic in over 80 countries worldwide , particularly India and sub-Saharan Africa [1] , and infecting up to 120 million individuals [2] .", "The major human diseases caused by filaria are Lymphatic Filariasis (...	[ "Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite .", "Targeting Wolbachia for elimination is a therapeut...	[ "Infection with the filarial endoparasites Brugia malayi and its symbiotic bacteria Wolbachia represent a significant burden to both humans and animals .", "Current treatment protocols include use of multiple drugs over a course of months to years , resulting in high costs , undesirable side effects , and poor pa...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "cell biology", "immunology", "mus (mouse)", "hematology" ]	Aging Hematopoietic Stem Cells Decline in Function and Exhibit Epigenetic Dysregulation	journal.pbio.0050201	In highly purified hematopoietic stem cells from mice aged 2 to 21 months, gene expression analysis indicates a deficit in function yet an increase in stem cell number with advancing age.	[ [ "Somatic stem cells replenish many tissues throughout life .", "In general , they have slow turnover and reside in specialized niches , protected from the environment , so that only a few are activated at a time .", "Thus , stem cells are a defense against aging , replacing cells lost through attritio...	[ "Age-related defects in stem cells can limit proper tissue maintenance and hence contribute to a shortened lifespan .", "Using highly purified hematopoietic stem cells from mice aged 2 to 21 mo , we demonstrate a deficit in function yet an increase in stem cell number with advancing age .", "Expression analysis...	[ "Aging is marked by a decline in function of the entire organism .", "The effect of age on the regenerative capacity of adult stem cells , which should rejuvenate tissues throughout life , is poorly understood .", "Bone marrow stem cells , also known as hematopoietic stem cells ( HSCs ) , continuously regenerat...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "complement system", "medicine and health sciences", "coronaviruses", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "respiratory infections", "pathogens", "immunology", "microbiology", "rabbits", "vertebrates", "animals", "mammals", "pulmonology"...	Enhanced inflammation in New Zealand white rabbits when MERS-CoV reinfection occurs in the absence of neutralizing antibody	journal.ppat.1006565	null	[ [ "Since its discovery in 2012 , the Middle East respiratory syndrome coronavirus ( MERS-CoV ) has caused at least 2 , 040 human infections and 712 deaths worldwide [1 , 2] .", "Like other human coronaviruses ( 229E , OC43 , NL63 and HKU1 ) , MERS-CoV is associated with respiratory tract infection .", "...	[ "The Middle East respiratory syndrome coronavirus ( MERS-CoV ) is a zoonotic betacoronavirus that was first detected in humans in 2012 as a cause of severe acute respiratory disease .", "As of July 28 , 2017 , there have been 2 , 040 confirmed cases with 712 reported deaths .", "While many infections have been ...	[ "New Zealand white rabbits display an increase in lung inflammation following reinfection with MERS-CoV that is associated with non-neutralizing antibodies and complement proteins .", "The development of neutralizing antibodies resulted in protection from infection .", "These findings may have implications for ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biophysics/theory and simulation", "computational biology/systems biology", "cell biology/cell signaling" ]	A Cell-Based Model for Quorum Sensing in Heterogeneous Bacterial Colonies	journal.pcbi.1000819	null	[ [ "Bacteria have evolved signaling networks enabling them to sense the environment by producing , exporting and importing small signaling molecules called autoinducers .", "By using autoinducers that can rapidly diffuse across cell populations and accumulate over time , bacterial cells can receive informati...	[ "Although bacteria are unicellular organisms , they have the ability to act in concert by synthesizing and detecting small diffusing autoinducer molecules .", "The phenomenon , known as quorum sensing , has mainly been proposed to serve as a means for cell-density measurement .", "Here , we use a cell-based mod...	[ "Unicellular organisms have the ability to communicate with each other via signaling molecules , leading to correlated behaviors resembling that of higher organisms .", "This process , called quorum sensing , allows the cells to monitor the population size or density in a decentralized fashion and perform a commo...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "epizootics", "sequencing techniques", "genome evolution", "parasite evolution", "rna analysis", "nucleic acid sequencing", "parasitology", "phylogenetic analysis", "genome analysis", "molecular biology techniques", "veterinary science", "sequence analysis", "veterinary diseases", "rna seq...	A Virulent Strain of Deformed Wing Virus (DWV) of Honeybees (Apis mellifera) Prevails after Varroa destructor-Mediated, or In Vitro, Transmission	journal.ppat.1004230	null	[ [ "Host-pathogen interactions can be broadly divided into asymptomatic or symptomatic infections [1] .", "In the former , the absence of symptomatic disease is typically due to restricted pathogen replication , which reduces the opportunities for horizontal transmission within its host population .", "C...	[ "The globally distributed ectoparasite Varroa destructor is a vector for viral pathogens of the Western honeybee ( Apis mellifera ) , in particular the Iflavirus Deformed Wing Virus ( DWV ) .", "In the absence of Varroa low levels DWV occur , generally causing asymptomatic infections .", "Conversely , Varroa-in...	[ "Honeybees are the most important managed pollinating insect , contributing billions of dollars to annual global agricultural production .", "Over the last century a parasitic mite , Varroa , has spread worldwide , with significant impacts on honeybee colony health as a consequence of its transmission of a cockta...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics", "biology", "genomics", "microbiology", "genetics and genomics" ]	Approaching the Functional Annotation of Fungal Virulence Factors Using Cross-Species Genetic Interaction Profiling	journal.pgen.1003168	null	[ [ "Diseases produced by fungal infections are challenging to diagnose and treat , making these infections a major cause of morbidity and mortality worldwide [1] , [2] .", "Genetics and genomics have led to the identification of numerous pathogen genes required for replication in the mammalian host [3]–[7] ....	[ "In many human fungal pathogens , genes required for disease remain largely unannotated , limiting the impact of virulence gene discovery efforts .", "We tested the utility of a cross-species genetic interaction profiling approach to obtain clues to the molecular function of unannotated pathogenicity factors in t...	[ "HIV/AIDS patients , cancer chemotherapy patients , and organ transplant recipients are highly susceptible to infection by opportunistic fungal pathogens , organisms common in the environment that are harmless to normal individuals .", "Understanding how these pathogens cause disease requires the identification o...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "developmental biology" ]	Visualisation and Quantification of Morphogen Gradient Formation in the Zebrafish	journal.pbio.1000101	Gradients of nodal signalling in developing zebrafish embryos are visualized using a novel biofluorescence complementation reporter and quantified, demonstrating a role for nodal signalling in dorso-ventral patterning in addition to specifying the animal-vegetal axis.	[ [ "During embryonic development , secreted molecules known as morphogens generate a concentration gradient of positional information that instructs developing tissues to adopt particular cell fates [1] .", "One example of this phenomenon is the patterning of the early zebrafish embryo by the nodal/TGF-β sig...	[ "During embryonic development , signalling molecules known as morphogens act in a concentration-dependent manner to provide positional information to responding tissues .", "In the early zebrafish embryo , graded signalling by members of the nodal family induces the formation of mesoderm and endoderm , thereby pa...	[ "One of the earliest events in vertebrate embryonic development is the patterning of the embryo into three germ layers: the ectoderm , mesoderm , and endoderm .", "Morphogens are signalling molecules that act in a concentration-dependent manner to induce the formation of different cell types .", "Members of the...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "sequencing techniques", "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "bac cloning", "pathogens", "microbiology", "vertebrates", "cloning", "animals", "vector cloning", "viruses", "rna viruses", "molecular biology techniques", "re...	Attenuation of a very virulent Marek's disease herpesvirus (MDV) by codon pair bias deoptimization	journal.ppat.1006857	null	[ [ "The attenuation by codon pair ( bias ) deoptimization ( CPBD ) has enabled rapid and highly efficient attenuation of a wide variety of RNA viruses , including Enterovirus C ( poliovirus ) [1] , Influenza A virus ( IAV ) [2–4] , Human immunodeficiency virus type 1 ( HIV-1 ) [5] , Human respiratory syncytial v...	[ "Codon pair bias deoptimization ( CPBD ) has enabled highly efficient and rapid attenuation of RNA viruses .", "The technique relies on recoding of viral genes by increasing the number of codon pairs that are statistically underrepresented in protein coding genes of the viral host without changing the amino acid ...	[ "Codon pair bias deoptimization ( CPBD ) enables highly efficient attenuation of viruses .", "In contrast to other methods , live attenuated virus vaccine candidates can be rationally designed and produced within days .", "The technique involves recoding of viral genes , while preserving their codon bias and am...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "dengue virus", "invertebrates", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "geographical locations", "microbiology", "tropical diseases", "spatial epidemiology", "australia", "animals", "viruses", "rna viruses", ...	Serological evidence for transmission of multiple dengue virus serotypes in Papua New Guinea and West Papua prior to 1963	journal.pntd.0005488	null	[ [ "Dengue is a mosquito-borne disease of humans caused by infection with the dengue viruses ( DENV ) .", "An estimated 390 million infections occur each year in tropical and subtropical countries of which about 98 million are symptomatic; in endemic countries dengue is associated with significant morbidity ...	[ "Little is known about the natural history of dengue in Papua New Guinea ( PNG ) .", "We assessed dengue virus ( DENV ) -specific neutralizing antibody profiles in serum samples collected from northern and southern coastal areas and the highland region of New Guinea between 1959 and 1963 .", "Neutralizing antib...	[ "Dengue is a mosquito-borne disease caused by infection with any of the four dengue virus serotypes ( DENV-1 –DENV-4 ) , which are transmitted in more than 100 tropical and subtropical countries .", "The current global dengue burden , and dengue mortality , is greatest in the southeast Asian and western Pacific r...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "cell biology/nuclear structure and function", "cell biology/cell signaling", "immunology/leukocyte signaling and gene expression", "cell biology/gene expression" ]	Global Regulator SATB1 Recruits β-Catenin and Regulates TH2 Differentiation in Wnt-Dependent Manner	journal.pbio.1000296	Chromatin organizer SATB1 and Wnt transducer β-catenin form a complex and regulate expression of GATA3 and TH2 cytokines in Wnt-dependent manner and orchestrate TH2 lineage commitment.	[ [ "Wnt growth factors regulate a variety of developmental processes by altering specific gene expression patterns [1] .", "Wnt proteins are secreted molecules that coordinate cell-to-cell interactions in many different cell types by binding to a member of the Frizzled ( Fz ) family of transmembrane receptor...	[ "In vertebrates , the conserved Wnt signalling cascade promotes the stabilization and nuclear accumulation of β-catenin , which then associates with the lymphoid enhancer factor/T cell factor proteins ( LEF/TCFs ) to activate target genes .", "Wnt/β -catenin signalling is essential for T cell development and diff...	[ "In vertebrates the canonical Wnt signalling culminates in β-catenin moving into the nucleus where it activates transcription of target genes .", "Wnt/β-catenin signalling is essential for the thymic maturation and differentiation of naïve T cells .", "Here we show that SATB1 , a T cell lineage-enriched chromat...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "rna extraction", "microbiology", "cloning", "fungi", "model organisms", "fungal evolution", "microbial evolution", "molecular biology techniques", "extraction techniques", "research and analysis met...	XRN1 Is a Species-Specific Virus Restriction Factor in Yeasts	journal.ppat.1005890	null	[ [ "Degradation of mRNAs is a process essential to cell viability .", "Degradation pathways eliminate aberrant mRNAs , and also act to control gene expression levels .", "This process typically begins with host enzymes that perform either deadenylation or decapping on mRNAs targeted for degradation [1] ....	[ "In eukaryotes , the degradation of cellular mRNAs is accomplished by Xrn1 and the cytoplasmic exosome .", "Because viral RNAs often lack canonical caps or poly-A tails , they can also be vulnerable to degradation by these host exonucleases .", "Yeast lack sophisticated mechanisms of innate and adaptive immunit...	[ "Like other eukaryotes , Saccharomyces cerevisiae is chronically infected with viruses .", "It is fascinating to consider how S . cerevisiae deals with viral infection , because yeast have limited mechanisms of immunity .", "Our paper focuses on Xrn1p , an enzyme that is important for the destruction of irregul...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/rna structure", "microbiology/immunity to infections", "infectious diseases/bacterial infections", "biochemistry/transcription and translation", "microbiology/cellular microbiology and pathogenesis" ]	A Staphylococcus aureus Small RNA Is Required for Bacterial Virulence and Regulates the Expression of an Immune-Evasion Molecule	journal.ppat.1000927	null	[ [ "Staphylococcus aureus is a member of the commensal flora that can be an opportunistic pathogen and a cause of nosocomial and community-acquired infections [1] .", "With the widespread use of antimicrobials , the incidence and spread of highly antibiotic-resistant S . aureus strains have increased rapidly...	[ "Staphylococcus aureus , a pathogen responsible for hospital and community-acquired infections , expresses many virulence factors under the control of numerous regulatory systems .", "Here we show that one of the small pathogenicity island RNAs , named SprD , contributes significantly to causing disease in an ani...	[ "Bacteria possess numerous and diverse means of gene regulation using RNA molecules , including small RNAs ( sRNAs ) .", "Here we show that one sRNA is essential for a major human bacterial pathogen , Staphylococcus aureus , to cause a disease in an animal model of infection .", "Our study provides evidence tha...	2010
[ "Introduction", "Results", "Discussion", "Models" ]	[ "mathematics", "developmental biology/pattern formation", "biophysics/biomacromolecule-ligand interactions", "developmental biology/developmental molecular mechanisms", "computational biology/systems biology" ]	Somitogenesis Clock-Wave Initiation Requires Differential Decay and Multiple Binding Sites for Clock Protein	journal.pcbi.1000728	null	[ [ "Somitogenesis is the process by which vertebrate embryos develop somites , which are transient , repeated blocks of cells arising from the presomitic mesoderm ( PSM ) that differentiate further into vertebrae , ribs , musculature , and dorsal dermis .", "The tailbud is a proliferative zone at the posteri...	[ "Somitogenesis is a process common to all vertebrate embryos in which repeated blocks of cells arise from the presomitic mesoderm ( PSM ) to lay a foundational pattern for trunk and tail development .", "Somites form in the wake of passing waves of periodic gene expression that originate in the tailbud and sweep ...	[ "The vertebral column is a characteristic structure of all vertebrates .", "Individual vertebrae , together with ribs and attached muscles , develop from repeated embryonic structures called somites .", "The somite pattern forms in the embryo during somitogenesis .", "We know that this process uses periodic g...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "chemical compounds", "gene regulation", "nucleotides", "organic compounds", "mutation", "plant science", "pyrimidines", "amino acids", "epigenetics", "dna", "molecular biology techniques", "dna methylation", "chromatin", "research and analysis methods", "gene silencin...	Cotton Leaf Curl Multan virus C4 protein suppresses both transcriptional and post-transcriptional gene silencing by interacting with SAM synthetase	journal.ppat.1007282	null	[ [ "In the course of plant-virus interactions , plants have evolved ingenious counter-attack mechanisms to diminish or eliminate invading viral pathogens .", "Of various plant antiviral defenses , gene silencing can target either viral RNAs for degradation through post-transcriptional gene silencing ( PTGS )...	[ "Gene silencing is a natural antiviral defense mechanism in plants .", "For effective infection , plant viruses encode viral silencing suppressors to counter this plant antiviral response .", "The geminivirus-encoded C4 protein has been identified as a gene silencing suppressor , but the underlying mechanism of...	[ "Geminiviruses are single-stranded DNA ( ssDNA ) viruses that infect a wide range of plant species and are responsible for substantial crop damage worldwide .", "However , how geminiviruses inhibit plant antiviral gene silencing defense is unclear .", "Here , we report that a single geminiviral protein CLCuMuV ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immediate-early promoter", "medicine and health sciences", "immunology", "microbiology", "infectious disease immunology", "protein structure", "nuclear bodies", "cellular structures and organelles", "immune system proteins", "protein structure determination", "viral immune evasion", "proteins...	Crystal Structure of Cytomegalovirus IE1 Protein Reveals Targeting of TRIM Family Member PML via Coiled-Coil Interactions	journal.ppat.1004512	null	[ [ "Promyelocytic leukemia protein PML is the organizer of small nuclear matrix structures termed nuclear bodies ( NBs ) or nuclear domain 10 ( ND10 ) [1] .", "PML , also named TRIM19 , is a member of the tripartite motif ( TRIM ) family of proteins , which are characterized by the presence of RING , B-box a...	[ "PML nuclear bodies ( PML-NBs ) are enigmatic structures of the cell nucleus that act as key mediators of intrinsic immunity against viral pathogens .", "PML itself is a member of the E3-ligase TRIM family of proteins that regulates a variety of innate immune signaling pathways .", "Consequently , viruses have ...	[ "Research of the last few years has revealed that microbial infections are not only controlled by innate and adaptive immune mechanisms , but also by cellular restriction factors , which give cells the capacity to resist pathogens .", "PML nuclear bodies ( PML-NBs ) are dot-like nuclear structures representing mu...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "cell biology", "plasmodium", "gastroenterology and hepatology", "in vitro", "immunology", "microbiology", "mus (mouse)" ]	Release of Hepatic Plasmodium yoelii Merozoites into the Pulmonary Microvasculature	journal.ppat.0030171	null	[ [ "Two billion people , more than one third of the world's population , live at risk for malaria and about 1 billion are infected .", "Each year there are 300 million to 500 million new cases with 2–3 million deaths , the vast majority young children in Africa .", "We are now forty years past the discov...	[ "Plasmodium undergoes one round of multiplication in the liver prior to invading erythrocytes and initiating the symptomatic blood phase of the malaria infection .", "Productive hepatocyte infection by sporozoites leads to the generation of thousands of merozoites capable of erythrocyte invasion .", "Merozoites...	[ "The malaria parasite Plasmodium undergoes one large round of multiplication in the liver before beginning the blood phase of the life cycle , the phase that causes the typical episodes of fever and chills .", "Using intravital microscopy and fluorescent parasites , we studied the mode and dynamics of parasite re...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	The Anti-Sigma Factor TcdC Modulates Hypervirulence in an Epidemic BI/NAP1/027 Clinical Isolate of Clostridium difficile	journal.ppat.1002317	null	[ [ "C . difficile is the causative agent of a spectrum of gastrointestinal diseases , collectively known as C . difficile infections , or CDI , that are induced by treatment with antibiotics that disrupt the normal gastrointestinal microbiota .", "CDI can range from mild diarrhoea , through moderately seriou...	[ "Nosocomial infections are increasingly being recognised as a major patient safety issue .", "The modern hospital environment and associated health care practices have provided a niche for the rapid evolution of microbial pathogens that are well adapted to surviving and proliferating in this setting , after which...	[ "Hospital infections are increasingly being recognised as a major patient safety issue with the hospital environment providing a niche for the rapid evolution of microbial pathogens that are well adapted to infecting susceptible patients .", "The spore-forming Clostridium difficile is one such bacterium , which c...	2011
[ "Introduction", "Discussion" ]	[ "computational biology/evolutionary modeling", "computational biology/metabolic networks", "computational biology/systems biology" ]	On the Accessibility of Adaptive Phenotypes of a Bacterial Metabolic Network	journal.pcbi.1000472	null	[ [ "During adaptation , a population “moves” in genotype space in search of genotypes associated with high-fitness phenotypes .", "The success of adaptation depends crucially on the accessibility of such adaptive phenotypes .", "While adaptive phenotypes rely on natural selection for their fixation , the...	[ "The mechanisms by which adaptive phenotypes spread within an evolving population after their emergence are understood fairly well .", "Much less is known about the factors that influence the evolutionary accessibility of such phenotypes , a pre-requisite for their emergence in a population .", "Here , we inves...	[ "Adaptation involves the discovery by mutation and spread through populations of traits ( or “phenotypes” ) that have high fitness under prevailing environmental conditions .", "While the spread of adaptive phenotypes through populations is mediated by natural selection , the likelihood of their discovery by muta...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "body fluids", "pathology and laboratory medicine", "immunology", "opportunistic infections", "animal models", "model organisms", "signs and symptoms", "research and analysis methods", "infectious diseases", "...	Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response	journal.pgen.1005935	null	[ [ "Endoglin was originally described as a type I integral membrane protein with an extracellular domain of 561 amino acids , a hydrophobic transmembrane domain , and a 47-residue cytosolic domain [1] .", "It is mainly expressed in endothelial cells and plays a pivotal role modulating cellular responses to T...	[ "Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall .", "Mutations in endoglin gene ( ENG ) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia , the Hereditary Hemo...	[ "Endoglin is a transmembrane protein and an auxiliary receptor for TGF-β with an important role in the homeostasis of the vessel wall .", "However , endoglin was originally identified as a human cell surface antigen expressed in a pre-B leukemic cell line .", "Mutations in ENG are responsible for the Hereditary...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "nuclear import", "gene regulation", "cell processes", "microbiology", "light microscopy", "viral structure", "neuroscience", "virus effects on host gene expression", "microscopy", "research and analysis methods", "small interfering rnas", "animal cells", "fluorescence microscopy", "gene e...	Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons	journal.ppat.1006823	null	[ [ "Herpesviruses such as herpes simplex virus ( HSV ) , human cytomegalovirus or Epstein-Barr virus cause human diseases ranging from minor ailments to life threatening acute infections , blindness or cancers , particularly in immunocompromised patients .", "They are complex DNA viruses that depend on many ...	[ "Herpesviruses are large DNA viruses which depend on many nuclear functions , and therefore on host transport factors to ensure specific nuclear import of viral and host components .", "While some import cargoes bind directly to certain transport factors , most recruit importin β1 via importin α .", "We identif...	[ "Nuclear pore complexes are highly selective gateways that penetrate the nuclear envelope for bidirectional trafficking between the cytoplasm and the nucleoplasm .", "Viral and host cargoes have to engage specific transport factors to achieve active nuclear import and export .", "Like many human and animal DNA ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Splice Region Variant in LDLR Lowers Non-high Density Lipoprotein Cholesterol and Protects against Coronary Artery Disease	journal.pgen.1005379	null	[ [ "The low-density lipoprotein receptor ( LDLR ) is a cell-surface receptor responsible for binding and uptake of circulating cholesterol-containing lipoprotein particles .", "This uptake is the primary pathway for removal of cholesterol from the circulation [1] .", "It is well established that high lev...	[ "Through high coverage whole-genome sequencing and imputation of the identified variants into a large fraction of the Icelandic population , we found four independent signals in the low density lipoprotein receptor gene ( LDLR ) that associate with levels of non-high density lipoprotein cholesterol ( non-HDL-C ) an...	[ "Cholesterol levels in the bloodstream , in particular elevated low-density lipoprotein cholesterol ( LDL-C ) , are strong risk factors for cardiovascular disease , and LDL-C reduction reduces mortality in people at risk .", "One of the major determinants of plasma LDL-C levels is the low density lipoprotein rece...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "genetics and genomics/functional genomics", "computational biology/metabolic networks", "microbiology/microbial physiology and metabolism", "computational biology/systems biology" ]	Epistatic Interaction Maps Relative to Multiple Metabolic Phenotypes	journal.pgen.1001294	null	[ [ "An epistatic interaction between two genes occurs when the phenotypic impact of at least one of the genes is dependent on the other [1] .", "This dependence is often a consequence of an underlying functional relationship between the two genes [2] , [3] .", "By extending the study of epistasis from in...	[ "An epistatic interaction between two genes occurs when the phenotypic impact of one gene depends on another gene , often exposing a functional association between them .", "Due to experimental scalability and to evolutionary significance , abundant work has been focused on studying how epistasis affects cellular...	[ "An epistatic interaction between two genes occurs when the phenotypic impact of one gene is dependent on the other .", "While different phenotypes have been used to uncover epistasis in different contexts , little is known about how cell-scale genetic interaction networks vary across multiple phenotypes .", "H...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "action potentials", "medicine and health sciences", "ecology and environmental sciences", "nervous system", "membrane potential", "vertebrates", "electrophysiology", "neuroscience", "animals", "physiological parameters", "body temperature", "computational neuroscience", "interneurons", "e...	Temperature manipulation of neuronal dynamics in a forebrain motor control nucleus	journal.pcbi.1005699	null	[ [ "Coordinated motor behaviors require a delicate sequence of gestures .", "Their precise timing depends on instructions coming from motor control areas in the brain .", "Differentiated regions or nuclei are interconnected forming a motor pathway .", "However , little is known about how the detailed...	[ "Different neuronal types within brain motor areas contribute to the generation of complex motor behaviors .", "A widely studied songbird forebrain nucleus ( HVC ) has been recognized as fundamental in shaping the precise timing characteristics of birdsong .", "This is based , among other evidence , on the stre...	[ "The study of the neuronal mechanisms that give rise to the complex behavior of singing in birds has been hotly debated lately .", "Many models have been tested and novel tools have been developed to try to understand the role of a key brain nucleus in the song pathway: HVC .", "It is believed that it is highly...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "aspergillus", "fungal genetics", "gene regulation", "dna-binding proteins", "dna transcription", "aspergillus nidulans", "fungi", "model organisms", "epigenetics", "chromatin", "research and analysis methods", "mycology", "genomics", "chromosome biology", "proteins", "gene expression"...	KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans	journal.pgen.1006222	null	[ [ "Chromatin is the natural substrate for all eukaryotic nuclear processes such as transcription , replication , recombination or DNA repair .", "Chromatin structure is necessarily dynamic and the underlying mechanisms involve remodeling of nucleosomes as well as depositing and removing posttranslational mo...	[ "Histone posttranslational modifications ( HPTMs ) are involved in chromatin-based regulation of fungal secondary metabolite biosynthesis ( SMB ) in which the corresponding genes—usually physically linked in co-regulated clusters—are silenced under optimal physiological conditions ( nutrient-rich ) but are activate...	[ "In this work we monitored by proteomic analysis and ChIP-seq the genome-wide distribution of several key modifications on histone H3 in the model fungus Aspergillus nidulans cultivated either under optimal physiological conditions ( active growth ) or less favourable conditions which are known to promote the produ...	2016
[ "Introduction", "Methods", "Results and Discussion" ]	[ "virology/immune evasion", "virology/viral replication and gene regulation", "infectious diseases/neglected tropical diseases", "computational biology/protein homology detection", "molecular biology/bioinformatics", "infectious diseases/viral infections", "computational biology/protein structure predict...	Mapping Protein Interactions between Dengue Virus and Its Human and Insect Hosts	journal.pntd.0000954	null	[ [ "With over 50 million cases per year , dengue virus ( DENV ) is a significant and growing threat to world-wide human health .", "Wide-spread among tropical and sub-tropical regions , this NIAID Category A pathogen consists of four serotypes , DENV1 to DENV4 , and is a member of the family Flaviviridae [1]...	[ "Dengue fever is an increasingly significant arthropod-borne viral disease , with at least 50 million cases per year worldwide .", "As with other viral pathogens , dengue virus is dependent on its host to perform the bulk of functions necessary for viral survival and replication .", "To be successful , dengue m...	[ "Dengue virus ( DENV ) represents a major disease burden in tropical and subtropical regions of the world , and has shown an increase in the number of cases in recent years .", "DENV is transmitted to humans through the bite of an infected mosquito , typically Aedes aegypti , after which it begins the infection a...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "developmental biology/morphogenesis and cell biology", "cell biology/cell signaling", "molecular biology/bioinformatics", "biotechnology/bioengineering", "computational biology/molecular dynamics", "cell biology/cytoskeleton" ]	Quantification of Local Morphodynamics and Local GTPase Activity by Edge Evolution Tracking	journal.pcbi.1000223	null	[ [ "Cell morphological change is a key process in the development and homeostasis of multicellular organisms [1] , [2] .", "Various types of morphological change appear during migration and differentiation; essential events occurring as part of these processes usually accompany morphologically different phen...	[ "Advances in time-lapse fluorescence microscopy have enabled us to directly observe dynamic cellular phenomena .", "Although the techniques themselves have promoted the understanding of dynamic cellular functions , the vast number of images acquired has generated a need for automated processing tools to extract s...	[ "Morphological change is a key indicator of various cellular functions such as migration and construction of specific structures .", "Time-lapse image microscopy permits the visualization of changes in morphology and spatio-temporal protein activity related to dynamic cellular functions .", "However , an unsolv...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell death", "medicine and health sciences", "luciferase", "immune cells", "gene regulation", "granulomas", "enzymes", "immunology", "cell processes", "enzymology", "tropical diseases", "bacterial diseases", "bacteria", "small interfering rnas", "infectious diseases", ...	PPARγ is critical for Mycobacterium tuberculosis induction of Mcl-1 and limitation of human macrophage apoptosis	journal.ppat.1007100	null	[ [ "Nuclear receptors are a large family of structurally conserved , ligand activated transcription factors , which have a range of functions related to development , homeostasis , metabolism and immunity .", "Nuclear receptors include receptors for fatty acids such as peroxisome proliferator-activated recep...	[ "Peroxisome proliferator-activated receptor ( PPAR ) γ is a global transcriptional regulator associated with anti-inflammatory actions .", "It is highly expressed in alveolar macrophages ( AMs ) , which are unable to clear the intracellular pathogen Mycobacterium tuberculosis ( M . tb ) .", "Although M . tb inf...	[ "The bacterium Mycobacterium tuberculosis is the causative agent of the disease tuberculosis ( TB ) , which is a global health problem and a leading cause of death world-wide .", "There is a clear need for better therapies for this disease , the design of which is predicated on better understanding of how M . tub...	2018
[ "Introduction", "Results", "Methods", "Discussion" ]	[ "invertebrates", "applied mathematics", "animals", "circadian oscillators", "simulation and modeling", "algorithms", "animal models", "drosophila melanogaster", "model organisms", "probability distribution", "mathematics", "experimental organism systems", "chronobiology", "drosophila", "...	Long-time analytic approximation of large stochastic oscillators: Simulation, analysis and inference	journal.pcbi.1005676	null	[ [ "Dynamic cellular oscillating systems such as the cell cycle , circadian clock and other signaling and regulatory systems have complex structures , highly nonlinear dynamics and are subject to both intrinsic and extrinsic stochasticity .", "Moreover , current models of these systems have high-dimensional ...	[ "In order to analyse large complex stochastic dynamical models such as those studied in systems biology there is currently a great need for both analytical tools and also algorithms for accurate and fast simulation and estimation .", "We present a new stochastic approximation of biological oscillators that addres...	[ "Many cellular and molecular systems such as the circadian clock and the cell cycle are oscillators that are modelled using nonlinear dynamical systems .", "Moreover , oscillatory systems are ubiquitous elsewhere in science .", "There is an extensive theory for perfectly noise-free dynamical systems and very ef...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "ecology and environmental sciences", "microbiome", "chemical compounds", "split-decomposition method", "microbiology", "plant physiology", "diazo compounds", "organic compounds", "multiple alignment calculation", "cereal crops", "plant science", "model organisms", "experimental organism sys...	Nitrogen fixation in a landrace of maize is supported by a mucilage-associated diazotrophic microbiota	journal.pbio.2006352	null	[ [ "Plants grow in close association with microbial communities that influence plant traits related to nutrient acquisition , plant development , plant defenses , and abiotic stress responses .", "The root-associated microbiota of plants has been characterized and shown to be much less complex than the micro...	[ "Plants are associated with a complex microbiota that contributes to nutrient acquisition , plant growth , and plant defense .", "Nitrogen-fixing microbial associations are efficient and well characterized in legumes but are limited in cereals , including maize .", "We studied an indigenous landrace of maize gr...	[ "Nitrogen is an essential nutrient for plants , and for many nonlegume crops , the requirement for nitrogen is primarily met by the use of inorganic fertilizers .", "These fertilizers are produced from fossil fuel by energy-intensive processes that are estimated to use 1% to 2% of the total global energy supply a...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/biocatalysis", "biochemistry/biomacromolecule-ligand interactions", "infectious diseases/bacterial infections", "microbiology/microbial physiology and metabolism", "microbiology/cellular microbiology and pathogenesis" ]	Studies of a Ring-Cleaving Dioxygenase Illuminate the Role of Cholesterol Metabolism in the Pathogenesis of Mycobacterium tuberculosis	journal.ppat.1000344	null	[ [ "Mycobacterium tuberculosis , the leading cause of mortality among bacterial pathogens , infects one-third of the human population and is responsible for approximately 2 million deaths annually .", "The global threat of TB has risen alarmingly due to two factors: the bacterium's deadly synergy with HIV [1...	[ "Mycobacterium tuberculosis , the etiological agent of TB , possesses a cholesterol catabolic pathway implicated in pathogenesis .", "This pathway includes an iron-dependent extradiol dioxygenase , HsaC , that cleaves catechols .", "Immuno-compromised mice infected with a ΔhsaC mutant of M . tuberculosis H37Rv ...	[ "Mycobacterium tuberculosis , the etiological agent of TB , is the most devastating infectious agent of mortality worldwide: it is carried by one-third of all humans and kills nearly two million people annually .", "Recent work has established that the pathogen metabolizes cholesterol , although the role of this ...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "ears", "pathogens", "immunology", "microbiology", "parasitic diseases", "staphylococcus aureus", "animal models", "otology", "model organisms", "ear infections", "experimental organism sy...	Coinfection with Leishmania major and Staphylococcus aureus enhances the pathologic responses to both microbes through a pathway involving IL-17A	journal.pntd.0007247	null	[ [ "Leishmaniasis constitutes a spectrum of diseases with distinct clinical forms usually caused by different species of Leishmania protozoa [1] .", "Each of the Leishmania species can also lead to highly variable clinical outcomes in different individuals , ranging from asymptomatic to severe infection .", ...	[ "Cutaneous leishmaniasis ( CL ) is a parasitic disease causing chronic , ulcerating skin lesions .", "Most humans infected with the causative Leishmania protozoa are asymptomatic .", "Leishmania spp .", "are usually introduced by sand flies into the dermis of mammalian hosts in the presence of bacteria from e...	[ "Cutaneous leishmaniasis ( CL ) is a vector-borne ulcerating skin disease affecting several million people worldwide .", "The causative Leishmania spp .", "protozoa are transmitted by infected phlebotomine sand flies .", "During a sand fly bite , bacteria can be coincidentally inoculated into the dermis with ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "chromosome structure and function", "centromeres", "pathogens", "microbiology", "dna transcription", "fungi", "model organisms", "genome analysis", "fungal pathogens", "research and analysis methods", "mycology", "genomi...	Neocentromeres Provide Chromosome Segregation Accuracy and Centromere Clustering to Multiple Loci along a Candida albicans Chromosome	journal.pgen.1006317	null	[ [ "Genome stability requires accurate chromosome segregation .", "Faithful chromosome segregation requires the assembly of a kinetochore complex on the centromere DNA region of each chromosome .", "The kinetochore is a large complex of more than 100 proteins and is essential for the attachment of the sp...	[ "Assembly of kinetochore complexes , involving greater than one hundred proteins , is essential for chromosome segregation and genome stability .", "Neocentromeres , or new centromeres , occur when kinetochores assemble de novo , at DNA loci not previously associated with kinetochore proteins , and they restore c...	[ "The accurate segregation of chromosomes during cell division is essential for maintaining genome integrity .", "The centromere is the DNA region on each chromosome where assembly of a large protein complex , the kinetochore , is required to maintain proper chromosome segregation .", "In addition , active centr...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "homo (human)", "genetics and genomics" ]	Power to Detect Risk Alleles Using Genome-Wide Tag SNP Panels	journal.pgen.0030170	null	[ [ "Researchers have used several approaches to identify genetic variation that predispose individuals to common diseases .", "For Mendelian disease traits , the method of choice has been linkage analysis in families [1] .", "For many complex disease traits where many alleles contribute to the trait , th...	[ "Advances in high-throughput genotyping and the International HapMap Project have enabled association studies at the whole-genome level .", "We have constructed whole-genome genotyping panels of over 550 , 000 ( HumanHap550 ) and 650 , 000 ( HumanHap650Y ) SNP loci by choosing tag SNPs from all populations genoty...	[ "Advances in high-throughput genotyping technology and the International HapMap Project have enabled genetic association studies at the whole-genome level .", "Our paper describes two genome-wide SNP panels that contain tag SNPs derived from the International HapMap Project .", "Tag SNPs are proxies for groups ...	2007
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "pathology and laboratory medicine", "maternal health", "obstetrics and gynecology", "drugs", "geographical locations", "microbiology", "antifungals", "surgical and invasive medical procedures", "women's health", "sporotrichosis", "signs and ...	Cryosurgery for the treatment of cutaneous sporotrichosis in four pregnant women	journal.pntd.0006434	null	[ [ "Sporotrichosis is caused by dimorphic fungi of the genus Sporothrix , found in its filamentous form as saprophytes on decaying and living vegetation , and soil [1] .", "However , since the late 1990s , sporotrichosis in the state of Rio de Janeiro , Brazil , has become an urban-epidemic phenomenon , bein...	[ "Pregnant women with sporotrichosis should not receive systemic antifungal therapy except in severe cases when amphotericin B is recommended .", "Thermotherapy is the most reported treatment described in this group of patients .", "It entails weeks of daily self-application of heat to the lesions , requires tha...	[ "Sporotrichosis is a cosmopolitan disease , considered the most important subcutaneous mycosis in Latin America .", "Since 1998 , there is an ongoing cat-transmitted zoonotic epidemic of sporotrichosis occurring in Rio de Janeiro , Brazil .", "Pregnant women are a vulnerable population occasionally affected tha...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Axon Regeneration Is Regulated by Ets–C/EBP Transcription Complexes Generated by Activation of the cAMP/Ca2+ Signaling Pathways	journal.pgen.1005603	null	[ [ "The ability of a neuron to regenerate following injury is dependent on both its intrinsic growth capacity and the extracellular environment .", "When an axon is injured , intracellular levels of calcium ( Ca2+ ) and cyclic adenosine monophosphate ( cAMP ) increase [1] .", "The increase in cAMP levels...	[ "The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways .", "In Caenorhabditis elegans , the JNK and p38 MAPK pathways are important for axon regeneration .", "Axonal injury induces expression of the svh-2 gene encoding a receptor tyrosine kina...	[ "An axon’s ability to regenerate after injury is governed by cell-intrinsic regeneration pathways .", "In C . elegans , the JNK and p38 MAPK pathways play an important role in axon regeneration .", "The JNK pathway is activated by growth factor SVH-1 , which signals through its receptor SVH-2 .", "It is known...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "medicine and health sciences", "model organisms", "genetics", "biology and life sciences", "research and analysis methods", "clinical genetics" ]	Abnormal Type I Collagen Post-translational Modification and Crosslinking in a Cyclophilin B KO Mouse Model of Recessive Osteogenesis Imperfecta	journal.pgen.1004465	null	[ [ "Type I collagen , the most abundant protein component of the extracellular matrix of skin , tendon and bone , is a heterotrimer consisting of two α1 ( I ) and one α2 ( I ) chains encoded by the COL1A1 and COL1A2 genes , respectively .", "The pro-alpha chains of type I collagen contain an uninterrupted he...	[ "Cyclophilin B ( CyPB ) , encoded by PPIB , is an ER-resident peptidyl-prolyl cis-trans isomerase ( PPIase ) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex .", "CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding .", "Muta...	[ "Osteogenesis imperfecta ( OI ) , or brittle bone disease , is characterized by susceptibility to fractures from minimal trauma and growth deficiency .", "Deficiency of components of the collagen prolyl 3-hydroxylation complex , CRTAP , P3H1 and CyPB , cause recessive types VII , VIII and IX OI , respectively .",...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "small intestine", "clinical research design", "biota", "statistics", "microbiology", "algorithms", "metagenomics", "mathematics", "gastroenterology and hepatology", "genetics and genomics", "computer inferencing", "ecological metrics", "ecosystems", "medical microbiology", ...	Inferring Dynamic Signatures of Microbes in Complex Host Ecosystems	journal.pcbi.1002624	null	[ [ "The human gut harbors a dense and complex microbial ecosystem .", "Our ability to extensively characterize the microbiota has greatly increased in the last several years , due to lower costs and technical improvements in both DNA sequencing [1] and bioinformatics tools [2] , [3] .", "High-throughput ...	[ "The human gut microbiota comprise a complex and dynamic ecosystem that profoundly affects host development and physiology .", "Standard approaches for analyzing time-series data of the microbiota involve computation of measures of ecological community diversity at each time-point , or measures of dissimilarity b...	[ "Microbes colonize the human body soon after birth and propagate to form rich ecosystems .", "These ecosystems play essential roles in health and disease .", "Recent advances in DNA sequencing technologies make possible comprehensive studies of the time-dependent behavior of microbes throughout the body .", "...	2012
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "evolutionary biology", "mammals" ]	Proboscidean Mitogenomics: Chronology and Mode of Elephant Evolution Using Mastodon as Outgroup	journal.pbio.0050207	The first complete mitochondrial DNA genome for the mastodon extends the age range for genomic analyses by almost a complete glacial cycle and resolves the relationships among African and Asian elephants and mammoths.	[ [ "An accurate and well-supported phylogeny is the basis for understanding the evolution of species .", "With the appropriate and adequate amount of data , it is possible not only to determine relationships among species , but also to date divergence events between lineages .", "In turn , divergence eve...	[ "We have sequenced the complete mitochondrial genome of the extinct American mastodon ( Mammut americanum ) from an Alaskan fossil that is between 50 , 000 and 130 , 000 y old , extending the age range of genomic analyses by almost a complete glacial cycle .", "The sequence we obtained is substantially different ...	[ "We determined the complete mitochondrial genome of the mastodon ( Mammut americanum ) , a recently extinct relative of the living elephants that diverged about 26 million years ago .", "We obtained the sequence from a tooth dated to 50 , 000–130 , 000 years ago , increasing the specimen age for which such palaeo...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "gene regulation", "antigen-presenting cells", "drugs", "immunology", "microbiology", "immunosuppressives", "dendritic cells", "cytotoxic t cells", "pharmacology", "immune system proteins", "white blood c...	Lassa virus activates myeloid dendritic cells but suppresses their ability to stimulate T cells	journal.ppat.1007430	null	[ [ "Viral hemorrhagic fevers ( VHF ) are an important global health problem with a significant yearly death toll .", "Among VHFs , Lassa fever ( LF ) is endemic in West Africa , with an estimated 300 , 000 to 500 , 000 cases and 3 , 000 to 5 , 000 deaths every year [1] .", "Populations living from Senega...	[ "Lassa virus ( LASV ) is responsible for a viral hemorrhagic fever in humans and the death of 3 , 000 to 5 , 000 people every year .", "The immune response to LASV is poorly understood , but type I interferon ( IFN-I ) and T-cell responses appear to be critical for the host .", "We studied the response of myelo...	[ "Lassa fever is a viral hemorrhagic fever and a major public health issue in West Africa .", "Lassa virus , the causative agent of Lassa fever , is listed by the World Health Organization as one of the emerging pathogens likely to cause severe outbreaks in the near future .", "Indeed , there is currently no vac...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "theoretical biology", "biology and life sciences", "developmental biology", "computational biology" ]	Fast Synchronization of Ultradian Oscillators Controlled by Delta-Notch Signaling with Cis-Inhibition	journal.pcbi.1003843	null	[ [ "Adaption to the day-and-night-cycle on earth provides an evolutionary advantage for organisms that can adjust their gene activity to this 24-hour rhythm .", "Therefore many metabolic processes show a circadian periodicity because they are all controlled by a GRN forming the so-called circadian clock [1] ...	[ "While it is known that a large fraction of vertebrate genes are under the control of a gene regulatory network ( GRN ) forming a clock with circadian periodicity , shorter period oscillatory genes like the Hairy-enhancer-of split ( Hes ) genes are discussed mostly in connection with the embryonic process of somito...	[ "During vertebrate embryonic development , the segmented structure of the axial skeleton is laid down by the process of somitogenesis .", "Periodically , blocks of cells separate at the anterior end of a mesenchymal tissue ( PSM ) on either side of the neural tube and develop later into spinal vertebrae .", "Ce...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "genetics and genomics", "evolutionary biology" ]	X Chromosome Inactivation during Drosophila Spermatogenesis	journal.pbio.0050273	Genes expressed in the Drosophila testes are under-represented on the X chromosome to avoid the global inactivation of the X chromosome that occurs in the male germ line.	[ [ "Sex chromosomes , such as the X and Y chromosomes of Drosophila , are thought to have evolved from a pair of homologous autosomes that lost their ability to recombine with each other [1 , 2] .", "Over evolutionary time , the sex chromosome that is present only in the heterogametic sex ( the Y in Drosophi...	[ "Genes with male- and testis-enriched expression are under-represented on the Drosophila melanogaster X chromosome .", "There is also an excess of retrotransposed genes , many of which are expressed in testis , that have “escaped” the X chromosome and moved to the autosomes .", "It has been proposed that inacti...	[ "During spermatogenesis , the X chromosome is inactivated in the male germline ( sperm cells ) , thereby silencing , or inactivating , genes residing on the X chromosome .", "X chromosome silencing is thought to be common among species with XY sex determination and has important implications for genome evolution ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "developmental biology", "infectious diseases", "genetics", "biology", "microbiology" ]	Global Analysis of the Sporulation Pathway of Clostridium difficile	journal.pgen.1003660	null	[ [ "Clostridium difficile is a Gram-positive , spore-forming , obligate anaerobe that causes gastrointestinal diseases including diarrhea , pseudomembranous colitis , and toxic megacolon [1]–[3] .", "C . difficile infections and C . difficile-related deaths have risen dramatically in the past decade , increa...	[ "The Gram-positive , spore-forming pathogen Clostridium difficile is the leading definable cause of healthcare-associated diarrhea worldwide .", "C . difficile infections are difficult to treat because of their frequent recurrence , which can cause life-threatening complications such as pseudomembranous colitis ....	[ "C . difficile is the leading cause of healthcare-associated infectious diarrhea in the United States in large part because of its ability to form spores .", "Since spores are resistant to most disinfectants and antibiotics , C . difficile infections frequently recur and are easily spread .", "Despite the impor...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "archaea", "ecology", "virology", "microbiology", "computational biology", "evolutionary biology", "genetics and genomics", "eubacteria" ]	The Sorcerer II Global Ocean Sampling Expedition: Northwest Atlantic through Eastern Tropical Pacific	journal.pbio.0050077	TheSorcerer II GOS expedition, data sampling, and analysis is described. The immense diversity in the sequence data required novel comparative genomic assembly methods, which uncovered genomic differences that marker-based methods could not.	[ [ "The concept of microbial diversity is not well defined .", "It can either refer to the genetic", "( taxonomic or phylogenetic ) diversity as commonly measured by molecular genetics methods , or", "to the biochemical ( physiological ) diversity measured in the laboratory with pure or mixed", "...	[ "The world's oceans contain a complex mixture of micro-organisms that are for the most", "part , uncharacterized both genetically and biochemically .", "We report here a metagenomic", "study of the marine planktonic microbiota in which surface ( mostly marine ) water samples", "were analyzed as part of the ...	[ "Marine microbes remain elusive and mysterious , even though they are the most abundant", "life form in the ocean , form the base of the marine food web , and drive energy and", "nutrient cycling .", "We know so little about the vast majority of microbes because only a", "small percentage can be cultivated ...	2007
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "antigen presentation", "lysosomes", "immune cells", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "enzymes", "pathogens", "immunology", "tropical diseases", "microbiology", "enzymology"...	Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein	journal.pntd.0006036	null	[ [ "The mosquito-borne Chikungunya virus ( CHIKV ) , a member of the Alphavirus genus of the Togaviridae family , causes an acute febrile infection in patients that leads to debilitating arthralgia and arthritis .", "Identified in the former Tanganyika territory in 1952 [1–3] , this arboviral pathogen caused...	[ "The adaptive cytotoxic T lymphocyte ( CTL ) -mediated immune response is critical for clearance of many viral infections .", "These CTL recognize naturally processed short viral antigenic peptides bound to human leukocyte antigen ( HLA ) class I molecules on the surface of infected cells .", "This specific rec...	[ "The arboviral pathogen Chikungunya virus ( CHIKV ) is a serious threat to global health , and is considered a priority re-emerging virus .", "This pathogen causes acute febrile infection in patients , leading to debilitating arthralgia and arthritis .", "In recent years , CHIKV has spread quickly in tropical a...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "pollen", "epistasis", "plant anatomy", "plant science", "fitness epistasis", "cell biology", "quantitative trait loci", "chromosome biology", "heredity", "genetics", "biology and life sciences", "introgression", "evolutionary biology", "seeds", "evolutionary processes", "genetic loci"...	Pervasive antagonistic interactions among hybrid incompatibility loci	journal.pgen.1006817	null	[ [ "Intrinsic postzygotic isolation ( hybrid inviability and sterility that occurs independently of the environment ) is often due to deleterious genetic interactions between loci that have functionally diverged during the evolution of new species ( i . e . , Dobzhansky-Muller incompatibilities , or DMIs; [1] ) ...	[ "Species barriers , expressed as hybrid inviability and sterility , are often due to epistatic interactions between divergent loci from two lineages .", "Theoretical models indicate that the strength , direction , and complexity of these genetic interactions can strongly affect the expression of interspecific rep...	[ "A characteristic feature of new species is their inability to produce fertile or viable hybrids with other lineages .", "This post-zygotic reproductive isolation is caused by dysfunctional interactions between genes that have newly evolved changes in the diverging lineages .", "Whether these interactions occur...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "model organisms", "genetic mutation", "neurospora crassa", "genetics", "yeast and fungal models", "biology", "microbial growth and development", "microbiology", "genetics and genomics" ]	A New Mutation Affecting FRQ-Less Rhythms in the Circadian System of Neurospora crassa	journal.pgen.1002151	null	[ [ "Circadian rhythms are approximately 24 h cycles of behavior , physiology , etc . that are driven by an endogenous biological clock .", "They are found at all levels of eukaryotic life , and in some prokaryotes .", "Molecular models for the endogenous oscillators that drive these rhythms in eukaryotes...	[ "We are using the fungus Neurospora crassa as a model organism to study the circadian system of eukaryotes .", "Although the FRQ/WCC feedback loop is said to be central to the circadian system in Neurospora , rhythms can still be seen under many conditions in FRQ-less ( frq knockout ) strains .", "To try to ide...	[ "All eukaryotes ( including humans ) , and some bacteria , have evolved internal biological clocks that control activity and physiology in a daily ( circadian ) cycle .", "The molecular oscillators that drive these circadian rhythms are said to depend on rhythmic expression and feedback regulation of a small set ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/chromatin structure", "genetics and genomics/bioinformatics", "genetics and genomics/chromosome biology" ]	Quantitative Test of the Barrier Nucleosome Model for Statistical Positioning of Nucleosomes Up- and Downstream of Transcription Start Sites	journal.pcbi.1000891	null	[ [ "The long DNA molecules of eukaryotic genomes are packaged into a compact structure with the help of histone proteins [1] .", "The fundamental unit of this structure , a nucleosome , comprises almost 150 base pairs ( bp ) of DNA wrapped around a histone octamer [2] , [3] .", "Individual nucleosomes ar...	[ "The positions of nucleosomes in eukaryotic genomes determine which parts of the DNA sequence are readily accessible for regulatory proteins and which are not .", "Genome-wide maps of nucleosome positions have revealed a salient pattern around transcription start sites , involving a nucleosome-free region ( NFR )...	[ "Within the last five years , knowledge about nucleosome organization on the genome has grown dramatically .", "To a large extent , this has been achieved by an increasing number of experimental studies determining nucleosome positions at high resolution over entire genomes .", "Particular attention has been pa...	2010
[ "Introduction", "Results", "Discussion", "Methods", "Note added in proof" ]	[ "hematologic cancers and related disorders", "oncology", "medicine", "genomics", "chromosome biology", "basic cancer research", "genetics", "genetics and genomics", "biology", "computational biology", "gene networks", "hematology" ]	Genomic Hallmarks of Genes Involved in Chromosomal Translocations in Hematological Cancer	journal.pcbi.1002797	null	[ [ "Chromosomal translocations are genomic rearrangements in which reciprocal exchange of genetic material between two non-homologous chromosomes results in the formation of novel fusion genes .", "Some of these fusion genes display oncogenic properties and have a strong impact on cancer progression and prog...	[ "Reciprocal chromosomal translocations ( RCTs ) leading to the formation of fusion genes are important drivers of hematological cancers .", "Although the general requirements for breakage and fusion are fairly well understood , quantitative support for a general mechanism of RCT formation is still lacking .", "...	[ "A common genetic lesion leading to hematological cancer is the creation of fusion genes as a result of reciprocal translocations between chromosomes .", "Such translocations are non-random , in the sense that certain genes are more likely to be fused than others , and they appear to be tissue-specific .", "Cur...	2012
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genome sequencing", "genetics", "biology", "genomics", "genetics and genomics" ]	Whole-Exome Sequencing and Homozygosity Analysis Implicate Depolarization-Regulated Neuronal Genes in Autism	journal.pgen.1002635	null	[ [ "Autism is a neurodevelopmental disorder characterized by impaired communication skills , social behavior abnormalities , and stereotypies , with a prevalence of ∼1/150 children [1] .", "It is considered to be one of the most highly genetic neuropsychiatric disorders with a heritability of 40–80% [2] , [3...	[ "Although autism has a clear genetic component , the high genetic heterogeneity of the disorder has been a challenge for the identification of causative genes .", "We used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence of distant shared ancestry , suggesting potent...	[ "Autism spectrum disorders are neurodevelopmental disorders that are genetically highly heterogeneous , with no single gene accounting for more than 1% of cases .", "In order to identify recessive mutations , we selected probands from an outbred population based on abundance of homozygosity in their genomes .", ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "medicine and health sciences", "infectious disease epidemiology", "malacology", "spatial epidemiology", "tropical diseases", "parasitic diseases", "parasitology", "global health", "neglected tropical diseases", "infectious disease control", "zoology", "...	Reduction Patterns of Acute Schistosomiasis in the People's Republic of China	journal.pntd.0002849	null	[ [ "Schistosomiasis japonica , caused by Schistosoma japonicum , is a serious parasitic zoonosis threatening millions of people in the Southeast Asia , including the Peoples' Republic of China ( P . R . China ) [1] .", "Despite the great achievements made during the last six decades in the control of the dis...	[ "Despite significant , steady progress in schistosomiasis control in the People's Republic of China over the past 50 years , available data suggest that the disease has re-emerged with several outbreaks of acute infections in the early new century .", "In response , a new integrated strategy was introduced .", ...	[ "A retrospective study on the incidence of acute schistosomiasis in the People's Republic of China ( P . R . China ) was performed , in order to assess the new integrated control strategy that was implemented through the national control program from 2005 to 2012 .", "The lake and marshland regions have been iden...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "engineering and technology", "transportation", "tropical diseases", "geographical locations", "social sciences", "census", "parasitic diseases", "research design", "neglected tropical diseases", "onchocerciasis", "infectious disease control", "africa", "res...	Programmatic factors associated with the limited impact of Community-Directed Treatment with Ivermectin to control Onchocerciasis in three drainage basins of South West Cameroon	journal.pntd.0005966	null	[ [ "Cameroon health system is coordinated by a Ministry of Public Health headed by a Minister , who works through ten ( 10 ) Regional Delegations of Public Health headed by medical doctors .", "A region is divided into Health Districts , headed by district medical officers who are also medical doctors; there...	[ "The CDTI model is known to have enhanced community participation in planning and resource mobilization toward the control of onchocerciasis .", "These effects were expected to translate into better individual acceptance of the intervention and hence high Treatment Coverage , leading to a sustainable community-le...	[ "River blindness is caused by a very tiny , thread-like worm .", "The disease is better controlled when affected communities are included in the planning and carrying out of distribution of Ivermectin used to treat the disease .", "For a community to be able to prevent people from getting this disease , members...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "histology", "genetics", "biology", "genetics and genomics" ]	Regulation of Neurod1 Contributes to the Lineage Potential of Neurogenin3+ Endocrine Precursor Cells in the Pancreas	journal.pgen.1003278	null	[ [ "The destruction or dysfunction of the insulin-producing beta cells of the pancreas contributes to a family of metabolic diseases known as diabetes mellitus .", "Given that the specification of the three major cell types in the pancreas , endocrine , exocrine and ductal cells , occurs in the embryo , unde...	[ "During pancreatic development , transcription factor cascades gradually commit precursor populations to the different endocrine cell fate pathways .", "Although mutational analyses have defined the functions of many individual pancreatic transcription factors , the integrative transcription factor networks requi...	[ "Diabetes mellitus is a family of metabolic diseases that can result from either destruction or dysfunction of the insulin-producing beta cells of the pancreas .", "Recent studies have provided hope that generating insulin-producing cells from alternative cell sources may be a possible treatment for diabetes; thi...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "european union", "evolutionary biology", "neurodegenerative diseases", "population genetics", "geographical locations", "genetic mapping", "ethnicities", "african american people", "population biology", "alzheimer's disease", "proteins", "lipoproteins", "de...	Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations	journal.pgen.1007791	null	[ [ "Late-onset Alzheimer disease ( LOAD ) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive functions .", "It is the most common form of dementia worldwide [1] , with prevalence increasing with age ( e . g . , ~30–40% by 85–89 years ) [2] .", "The etiology of...	[ "The ApoE ε4 allele is the most significant genetic risk factor for late-onset Alzheimer disease .", "The risk conferred by ε4 , however , differs across populations , with populations of African ancestry showing lower ε4 risk compared to those of European or Asian ancestry .", "The cause of this heterogeneity ...	[ "The strongest risk gene identified for late-onset Alzheimer disease is ApoE .", "However , the risk for Alzheimer disease due to ApoE is not consistent across populations .", "For example , individuals with African ancestry experience less risk from ApoE ε4 than individuals of European or Asian ancestry .", ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biochemistry", "systems ecology", "computer and information sciences", "ecology", "network analysis", "metabolic pathways", "biology and life sciences", "metabolic networks", "microbiology", "metabolism", "microbial ecology" ]	A Novel Nutritional Predictor Links Microbial Fastidiousness with Lowered Ubiquity, Growth Rate, and Cooperativeness	journal.pcbi.1003726	null	[ [ "Microbial nutrition influences global ecosystems , food production , and human disease .", "However , most microbes in nature are difficult or impossible to cultivate , and have thus traditionally been nearly impossible to study [1] .", "Recent cultivation-independent methods such as metagenomic sequ...	[ "Understanding microbial nutritional requirements is a key challenge in microbiology .", "Here we leverage the recent availability of thousands of automatically generated genome-scale metabolic models to develop a predictor of microbial minimal medium requirements , which we apply to thousands of species to study...	[ "Understanding microbial nutrition is critical for understanding microbial life , and thus has a major influence in many areas of biology .", "In recent years , the traditional methods of studying microbial nutrition , which rely on culturing bacteria and assessing their nutritional needs through extensive experi...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "medicine and health sciences", "pathology and laboratory medicine", "evolutionary biology", "viral transmission and infection", "pathogens", "population genetics", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "rna viruses", "phylo...	Estimating the Respective Contributions of Human and Viral Genetic Variation to HIV Control	journal.pcbi.1005339	null	[ [ "There are differences in the rate of disease progression among individuals infected with HIV .", "An easy to measure and reliable correlate of disease progression is the mean log viral load ( HIV RNA copies per ml of plasma ) .", "The viral load measured during the chronic phase of infection ( referr...	[ "We evaluated the fraction of variation in HIV-1 set point viral load attributable to viral or human genetic factors by using joint host/pathogen genetic data from 541 HIV infected individuals .", "We show that viral genetic diversity explains 29% of the variation in viral load while host factors explain 8 . 4% ....	[ "Viral loads of Human Immunodeficiency Virus infections are correlated between the donor and the recipient of the transmission pair .", "Similarly , human genetic factors may modulate viral load .", "In this study we estimate the extents to which viral load is heritable either via the viral genotype ( from dono...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/macromolecular sequence analysis", "computational biology/protein homology detection", "computational biology/sequence motif analysis", "computational biology" ]	The Construction and Use of Log-Odds Substitution Scores for Multiple Sequence Alignment	journal.pcbi.1000852	null	[ [ "Protein and DNA sequence alignment is a fundamental tool of computational molecular biology .", "It is used for functional prediction , genome annotation , the discovery of functional elements and motifs , homology-based structure prediction and modeling , phylogenetic reconstruction , and in numerous ot...	[ "Most pairwise and multiple sequence alignment programs seek alignments with optimal scores .", "Central to defining such scores is selecting a set of substitution scores for aligned amino acids or nucleotides .", "For local pairwise alignment , substitution scores are implicitly of log-odds form .", "We now ...	[ "Multiple sequence alignment is a fundamental tool of biological research , widely used to identify important regions of DNA or protein molecules , to infer their biological functions , to reconstruct ancestries , and in numerous other applications .", "The effectiveness and accuracy of sequence comparison progra...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "global health", "epidemiology", "drugs and devices", "public health" ]	Comparison of Individual and Pooled Stool Samples for the Assessment of Soil-Transmitted Helminth Infection Intensity and Drug Efficacy	journal.pntd.0002189	null	[ [ "The soil-transmitted helminths ( STHs ) Ascaris lumbricoides , Trichuris trichiura , and the two hookworm species , Necator americanus and Ancylostoma duodenale , cause the highest burden among all neglected tropical diseases ( NTDs ) , with school-aged children and pregnant women being at highest risk [1]–[...	[ "In veterinary parasitology samples are often pooled for a rapid assessment of infection intensity and drug efficacy .", "Currently , studies evaluating this strategy in large-scale drug administration programs to control human soil-transmitted helminths ( STHs; Ascaris lumbricoides , Trichuris trichiura , and ho...	[ "Since the last decade , growing awareness of the control of neglected tropical diseases ( NTDs ) has resulted in worldwide increased pledges of drug donations .", "However , health care decision makers have a limited repertoire of strategies for a rapid assessment of infection intensity and for checking of drug ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna replication", "cell biology/cellular death and stress responses", "dermatology/skin cancers, including melanoma and lymphoma", "molecular biology/chromosome structure", "genetics and genomics/chromosome biology", "genetics and genomics/cancer genetics", "molecular biology/chromati...	Human Telomeres Are Hypersensitive to UV-Induced DNA Damage and Refractory to Repair	journal.pgen.1000926	null	[ [ "Telomeric DNA consists , in all eukaryotes examined to date , of a tandemly repeated sequence located at each end of each chromosome .", "In humans , it is constituted of 5–10 kb of a repeated hexamer ( 5′TTAGGG/5′CCCTAA ) .", "Telomeres are required for chromosomal stability and integrity ( reviewed...	[ "Telomeric repeats preserve genome integrity by stabilizing chromosomes , a function that appears to be important for both cancer and aging .", "In view of this critical role in genomic integrity , the telomere's own integrity should be of paramount importance to the cell .", "Ultraviolet light ( UV ) , the pre...	[ "Telomeres consist of a repeated sequence located at each end of each chromosome .", "This repeated sequence is required for chromosomal stability and integrity , a function important for both cancer and aging .", "The DNA sequence of human telomeres is 5–10 kb of a repeated double-strand hexamer ( 5′TTAGGG/5′C...	2010
[ "Introduction", "Models", "Results", "Discussion" ]	[ "computational biology/transcriptional regulation", "computational biology/evolutionary modeling", "evolutionary biology/developmental evolution" ]	An End to Endless Forms: Epistasis, Phenotype Distribution Bias, and Nonuniform Evolution	journal.pcbi.1000202	null	[ [ "The tremendous diversity of shapes and forms observed in nature is truly remarkable", "and yet it represents only a small fraction of the ‘space’ of", "the possible .", "One reason for this is that the space of possible genotypes has been", "incompletely sampled over the course of the history...	[ "Studies of the evolution of development characterize the way in which gene", "regulatory dynamics during ontogeny constructs and channels phenotypic", "variation .", "These studies have identified a number of evolutionary regularities:", "( 1 ) phenotypes occupy only a small subspace of possible phenotypes...	[ "At the very end of his On the Origin of Species , Charles Darwin", "wrote , “from so simple a beginning endless forms most beautiful and", "most wonderful have been , and are being , evolved .", "” Nature truly", "displays a bewildering variety of shapes and forms .", "Yet , with all its", "magnificenc...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Design Principles of the Yeast G1/S Switch	journal.pbio.1001673	Single-cell microscopy and computational modeling offer novel mechanistic insight into the G1/S switch that initiates DNA replication in budding yeast, revealing a Clb5/6-Cdk1 and Sic1 feedback loop and new rules of biochemical circuit design.	[ [ "In the cell cycle of the budding yeast Saccharomyces cerevisiae , DNA replication initiation is driven by a sharp rise of Clb5/6-Cdk1 activity [1]–[3] .", "As the cell passes Start [4] , [5] , the commitment to the next round of cell division , the transcriptional inhibitor Whi5 , is phosphorylated and t...	[ "A hallmark of the G1/S transition in budding yeast cell cycle is the proteolytic degradation of the B-type cyclin-Cdk stoichiometric inhibitor Sic1 .", "Deleting SIC1 or altering Sic1 degradation dynamics increases genomic instability .", "Certain key facts about the parts of the G1/S circuitry are established...	[ "In eukaryotic organisms , genome replication starts simultaneously from many sites on the DNA , called origins of replication .", "In budding yeast , these origins are activated by a kinase , Clb5/6-Cdk1 .", "Until the start of S-phase , when the replication origins are activated , this kinase is kept inactive...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mechanisms of signal transduction", "membrane proteins", "membrane structures", "biophysics simulations", "cell membrane", "cytochemistry", "proteins", "biophysics theory", "biology", "biophysics", "molecular biology", "biochemistry", "signal transduction", "transmembrane proteins", "mo...	Ligand-Dependent Conformations and Dynamics of the Serotonin 5-HT2A Receptor Determine Its Activation and Membrane-Driven Oligomerization Properties	journal.pcbi.1002473	null	[ [ "Serotonin 2A receptors ( 5-HT2AR ) are a very well characterized family of G-protein coupled receptors ( GPCRs ) in the amine sub-class of rhodopsin-like class A GPCRs [1] , [2] .", "The 5-HT2ARs are targeted by chemically and pharmacologically distinct classes of ligands which include antidepressants , ...	[ "From computational simulations of a serotonin 2A receptor ( 5-HT2AR ) model complexed with pharmacologically and structurally diverse ligands we identify different conformational states and dynamics adopted by the receptor bound to the full agonist 5-HT , the partial agonist LSD , and the inverse agonist Ketanseri...	[ "The 5-HT2A receptor for the neurotransmitter serotonin ( 5-HT ) belongs to family A ( rhodopsin-like ) G-protein coupled receptors ( GPCRs ) , one of the most important classes of membrane proteins that are targeted by an extensive and diverse collection of external stimuli .", "Recently we learned that differen...	2012

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