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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", "Materials and Methods", "Results", "Discussion" ]	[ "viral vaccines", "virology", "emerging viral diseases", "biology", "microbiology" ]	IRES-driven Expression of the Capsid Protein of the Venezuelan Equine Encephalitis Virus TC-83 Vaccine Strain Increases Its Attenuation and Safety	journal.pntd.0002197	null	[ [ "Arboviruses ( Arthropod-Borne viruses ) comprise a group of viruses transmitted among vertebrates by hematophagous arthropods .", "They include members of a wide range of viral families , such as Rhabdoviridae , Bunyaviridae , Flaviviridae and Togaviridae , with a worldwide distribution .", "The pres...	[ "The live-attenuated TC-83 strain is the only licensed veterinary vaccine available to protect equids against Venezuelan equine encephalitis virus ( VEEV ) and to protect humans indirectly by preventing equine amplification .", "However , TC-83 is reactogenic due to its reliance on only two attenuating point muta...	[ "Venezuelan equine encephalitis virus ( VEEV ) is transmitted by mosquitoes and widely distributed in Central and South America , causing regular outbreaks in horses and humans .", "Often misdiagnosed as dengue , VEEV infection in humans can lead to lifelong neurological sequelae and is fatal in up to >80% of equ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Buruli Ulcer Disease and Its Association with Land Cover in Southwestern Ghana	journal.pntd.0003840	null	[ [ "Buruli ulcer ( BU ) , a neglected emerging infectious disease , is a skin and soft tissue infection caused by Mycobacterium ulcerans ( MU ) .", "The infection is characterized by painless nodules with necrotizing toxins that produce lesions in the skin , and which may lead to scarring , contractual defor...	[ "Buruli ulcer ( BU ) , one of 17 neglected tropical diseases , is a debilitating skin and soft tissue infection caused by Mycobacterium ulcerans .", "In tropical Africa , changes in land use and proximity to water have been associated with the disease .", "This study presents the first analysis of BU at the vil...	[ "We studied the relationship between a neglected tropical disease , Buruli Ulcer ( BU ) , and landscape disturbance .", "We hypothesized that the increased presence of BU was related to landscape disturbance , especially alluvial mining , in endemic areas of the disease .", "We characterized recent cases of BU ...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "mycobacterium leprae", "medicine and health sciences", "clinical research design", "tropical diseases", "plasmid construction", "bacterial diseases", "research design", "pharmaceutics", "neglected tropical diseases", "dna", "molecular biology techniques", "dna construction", "pharmacology",...	DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae	journal.pntd.0005013	null	[ [ "Leprosy is no longer an incurable disease .", "Since the introduction of Multidrug Therapy ( MDT ) by the World Health Organization in the 1980s , the number of registered leprosy cases has decreased dramatically .", "However , leprosy still remains a public health problem with more than 210 , 000 ne...	[ "Fluoroquinolones are a class of antibacterial agents used for leprosy treatment .", "Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin , the fluoroquinolone currently recommended for treatment of leprosy .", "For example , D...	[ "Leprosy is now recognized as a disease curable by chemotherapy .", "Although the number of leprosy cases has dramatically decreased as a result of multidrug therapy , there are still more than 210 , 000 new cases reported worldwide every year .", "Recurrence is a major concern in the control of leprosy .", "...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "geomorphology", "medicine and health sciences", "wallis and futuna", "landforms", "topography", "tropical diseases", "geographical locations", "health care", "north america", "treponematoses", "bacterial diseases", "global health", "neglected tropical diseases", "infectious disease contro...	Prioritizing surveillance activities for certification of yaws eradication based on a review and model of historical case reporting	journal.pntd.0006953	null	[ [ "The endemic treponematoses are a group of chronic bacterial infections .", "This group is made up of: yaws , caused by Treponema pallidum subsp .", "pertenue; endemic syphilis ( also known as bejel ) , caused by T . pallidum subsp .", "endemicum; and pinta , caused by T . carateum .", "Of the...	[ "The World Health Organization ( WHO ) has targeted yaws for global eradication .", "Eradication requires certification that all countries are yaws-free .", "While only 14 Member States currently report cases to WHO , many more are known to have a history of yaws and some of them may have ongoing transmission ....	[ "Yaws is a disabling and disfiguring disease .", "When the World Health Organization ( WHO ) was established in 1948 , yaws was among the major public health problems that the new health agency chose to prioritize .", "In 2013 , it formally targeted yaws for global eradication .", "While only 14 Member States...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "eubacteria", "microbiology" ]	The OmpA-Like Protein Loa22 Is Essential for Leptospiral Virulence	journal.ppat.0030097	null	[ [ "Leptospira interrogans is a spirochete responsible for leptospirosis .", "This disease , which is considered the most geographically widespread zoonosis , has emerged as a major public health problem in developing countries [1–3] .", "Numerous mammalian species , including rodents , excrete the patho...	[ "Pathogenic mechanisms of Leptospira interrogans , the causal agent of leptospirosis , remain largely unknown .", "This is mainly due to the lack of tools for genetic manipulations of pathogenic species .", "In this study , we characterized a mutant obtained by insertion of the transposon Himar1 into a gene enc...	[ "The spirochetes , which include medically important pathogens such as the causative agents of Lyme disease , syphilis , and leptospirosis , constitute an evolutionarily unique group of bacteria .", "Leptospirosis is a zoonotic disease that causes a high rate of mortality and morbidity in humans and animals throu...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "dengue virus", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "immunology", "microbiology", "alphaviruses", "cell differentiation", "viruses", "multivariate analysis", "developmenta...	Longitudinal Analysis of Natural Killer Cells in Dengue Virus-Infected Patients in Comparison to Chikungunya and Chikungunya/Dengue Virus-Infected Patients	journal.pntd.0004499	null	[ [ "Dengue virus ( DENV ) , the most widespread arbovirus worldwide , is transmitted by Ae .", "aegypti and Ae .", "albopictus mosquitoes and is responsible for major outbreaks causing serious health and economical problems .", "Dengue is endemic in at least 100 countries in Southeast Asia , the paci...	[ "Dengue virus ( DENV ) is the most prominent arbovirus worldwide , causing major epidemics in South-East Asia , South America and Africa .", "In 2010 , a major DENV-2 outbreak occurred in Gabon with cases of patients co-infected with chikungunya virus ( CHIKV ) .", "Although the innate immune response is though...	[ "Dengue fever is the most important arthropod-borne viral disease worldwide , affecting 50 to 100 million individuals annually .", "The clinical picture associated with acute dengue virus ( DENV ) infections ranges from classical febrile illness to life-threatening disease .", "The innate immunity is the first ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders/prion diseases", "infectious diseases/prion diseases", "biophysics", "biophysics/protein folding" ]	Early Onset Prion Disease from Octarepeat Expansion Correlates with Copper Binding Properties	journal.ppat.1000390	null	[ [ "Prion diseases are infectious neurodegenerative disorders that arise from accumulation of PrPSc ( scrapie conformer ) , a misfolded form of the normal cellular prion protein ( PrPC ) that is found ubiquitously throughout the central nervous system [1]–[3] .", "PrPC is a GPI anchored glycoprotein possessi...	[ "Insertional mutations leading to expansion of the octarepeat domain of the prion protein ( PrP ) are directly linked to prion disease .", "While normal PrP has four PHGGGWGQ octapeptide segments in its flexible N-terminal domain , expanded forms may have up to nine additional octapeptide inserts .", "The type ...	[ "Prion diseases are neurodegenerative disorders involving the prion protein , a normal component of the central nervous system .", "An unusual class of inherited mutations giving rise to prion disease involves elongation of the so-called octarepeat domain , near the protein's N-terminus .", "Research from our l...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "chemical bonding", "chemical characterization", "neurochemistry", "medicine and health sciences", "electrostatic bonding", "electricity", "radii", "electrophysiology", "neuroscience", "geometry", "simulation and modeling", "ion channels", "electrostatics", "mathematics", "neurotransmitt...	An Electrostatic Funnel in the GABA-Binding Pathway	journal.pcbi.1004831	null	[ [ "The neurotransmitter γ-aminobutyric acid ( GABA ) is the brain’s major inhibitory neurotransmitter , which binds to the GABA type A receptors ( GABAA-Rs ) .", "These GABAA-Rs are ‘Cys-loop receptors’ in the pentameric ligand-gated ion channel ( pLGIC ) superfamily .", "Cys-loop receptors are so named...	[ "The γ-aminobutyric acid type A receptor ( GABAA-R ) is a major inhibitory neuroreceptor that is activated by the binding of GABA .", "The structure of the GABAA-R is well characterized , and many of the binding site residues have been identified .", "However , most of these residues are obscured behind the C-l...	[ "Neurotransmitters convey signals from one neuron to the next and are indispensable to the functioning of the nervous system .", "These small molecules bind to receptors to exert their action .", "One of the most important neurotransmitters is γ-aminobutyric acid ( GABA ) , which binds to its type A receptor to...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "vesicles", "cell processes", "vertebrates", "electrophysiology", "neuroscience", "animals", "macroglial cells", "animal models", "osteichthyes", "developmental biology", "ion channels", "model organisms", "nerve fibers", "embryos", "cellular structures ...	Neuronal Ndrg4 Is Essential for Nodes of Ranvier Organization in Zebrafish	journal.pgen.1006459	null	[ [ "Myelination is a vertebrate adaptation that ensures the fast propagation of action potentials along the axons .", "Schwann Cells ( SCs ) are one of the myelinating glial cells of the Peripheral Nervous System ( PNS ) while Oligodendrocytes ( OLs ) are responsible for myelin wrapping in the Central Nervou...	[ "Axon ensheathment by specialized glial cells is an important process for fast propagation of action potentials .", "The rapid electrical conduction along myelinated axons is mainly due to its saltatory nature characterized by the accumulation of ion channels at the nodes of Ranvier .", "However , how these ion...	[ "Myelination is an important process that enables fast propagation of action potential along the axons .", "Schwann cells ( SCs ) are the specialized glial cells that ensure the ensheathment of the corresponding axons in the Peripheral Nervous System .", "In order to do so , SCs and axons need to communicate to...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "vesicles", "pathology and laboratory medicine", "pathogens", "microbiology", "membrane proteins", "molecular motors", "sexually transmitted diseases", "chlamydia", "cellular structures and organelles", "bacteria", "bacterial pathogens", "motor proteins", "e...	Acquisition of Rab11 and Rab11-Fip2—A novel strategy for Chlamydia pneumoniae early survival	journal.ppat.1006556	null	[ [ "Chlamydia pneumoniae is the causative agent of a variety of acute and chronic diseases of the upper and lower respiratory tract including pneumonia , asthma , bronchitis and sinusitis , and is associated with ~50% of cases of chronic obstructive pulmonary disease [1] .", "C . pneumoniae , like all other ...	[ "The initial steps in chlamydial infection involve adhesion and internalization into host cells and , most importantly , modification of the nascent inclusion to establish the intracellular niche .", "Here , we show that Chlamydia pneumoniae enters host cells via EGFR-dependent endocytosis into an early endosome ...	[ "Here , we show for the first time how Chlamydia pneumoniae an obligate intracellular pathogen establishes its intracellular niche .", "After EGFR-dependent endocytosis into host cells , the nascent chlamydial inclusion acquires early endosomal membrane identity and the Rab GTPases Rab4 , Rab5 and Rab7 , as well ...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "anatomical pathology", "surgical pathology", "diagnostic medicine", "pathology" ]	Sensitive and Specific Immunohistochemical Diagnosis of Human Alveolar Echinococcosis with the Monoclonal Antibody Em2G11	journal.pntd.0001877	null	[ [ "Echinococcosis is a zoonosis caused by larval stages ( metacestodes ) of tapeworms of the genus Echinococcus .", "In humans , alveolar echinococcosis ( AE ) , provoked by E . multilocularis , and cystic echinococcosis ( CE ) , induced by E . granulosus sensu lato ( a complex of several genotypes or speci...	[ "Alveolar echinococcosis ( AE ) is caused by the metacestode stage of Echinococcus multilocularis .", "Differential diagnosis with cystic echinococcosis ( CE ) caused by E . granulosus and AE is challenging .", "We aimed at improving diagnosis of AE on paraffin sections of infected human tissue by immunohistoch...	[ "Echinococcosis is a life-threatening disease in humans that is caused by the larval stages of the tapeworms Echinococcus multilocularis and Echinococcus granulosus .", "The eggs of the parasites are released with faeces of canids , and humans are aberrantly infected .", "In humans , the larval stages of the pa...	2012
[ "Introduction", "Methods", "Results", "Discussion", "Conclusion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "nervous system", "tropical diseases", "geographical locations", "india", "sports and exercise medicine", "physical activity", "bacterial diseases", "signs and symptoms", "neglected tropical diseases", "public and occupationa...	Does appreciative inquiry decrease false positive diagnosis during leprosy case detection campaigns in Bihar, India? An operational research study	journal.pntd.0007004	null	[ [ "Leprosy is a chronic infectious disease caused by the bacteria—Mycobacterium Leprae .", "It usually affects the peripheral sensory nerves and has a wide range of clinical manifestations .", "The disease is characterized by long incubation period generally 5–7 years .", "Leprosy is completely cura...	[ "India contributes ~60% to the global leprosy burden .", "The country implements 14-day community-based leprosy case detection campaigns ( LCDC ) periodically in all high endemic states .", "Paramedical staff screen the population and medical officers of primary health centres ( PHCs ) diagnose and treat lepros...	[ "India is the highest leprosy burden country in the world .", "Government of India’s National Leprosy Eradication Programme ( NLEP ) launched Leprosy Case Detection Campaign ( LCDC ) —an active community-based case detection campaign—in 2016 in all high burden areas to detect undiagnosed cases .", "Following th...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "vesicular stomatitis virus", "antiviral immune response", "pathology and laboratory medicine", "viral transmission and infection", "molecular probe techniques", "pathogens", "immunology", "microbiology", "immunoblotting", "viruses", "rna viruses", "signalosom...	Induction of OTUD1 by RNA viruses potently inhibits innate immune responses by promoting degradation of the MAVS/TRAF3/TRAF6 signalosome	journal.ppat.1007067	null	[ [ "The innate immune response is the first line of host defense against viral infection .", "Viral nucleic acids can be recognized by host pattern recognition receptors ( PRRs ) , including RIG-I-like receptors ( RLRs ) , Toll-like receptors ( TLRs ) and cytosolic dsDNA sensors ( STING ) [1–5] .", "PRRs...	[ "During RNA virus infection , the adaptor protein MAVS recruits TRAF3 and TRAF6 to form a signalosome , which is critical to induce the production of type I interferons ( IFNs ) and proinflammatory cytokines .", "While activation of the MAVS/TRAF3/TRAF6 signalosome is well studied , the negative regulation of the...	[ "Extensive studies have demonstrated redundant roles of multiple antiviral signaling pathways in host defense against viral infection .", "However , the strategies viruses have evolved to efficiently antagonize the complementary effect of alternative IFNs-inducing signaling remain largely unknown .", "Here we r...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/systems biology", "cell biology/cytoskeleton" ]	An Experimental and Computational Study of the Effect of ActA Polarity on the Speed of Listeria monocytogenes Actin-based Motility	journal.pcbi.1000434	null	[ [ "Listeria monocytogenes is a rod-shaped bacterial pathogen that can infect cells and spread from cell to cell directly , thus evading the host's normal immune response [1] .", "L . monocytogenes expresses the surface protein , ActA , which interacts with the host-cell actin-polymerization machinery , to p...	[ "Listeria monocytogenes is a pathogenic bacterium that moves within infected cells and spreads directly between cells by harnessing the cell's dendritic actin machinery .", "This motility is dependent on expression of a single bacterial surface protein , ActA , a constitutively active Arp2 , 3 activator , and has...	[ "Cells tightly regulate the branched actin networks involved in motility , division , and other important cellular functions through localized activation of the Arp2 , 3 protein , which nucleates new actin filaments off the sides of existing ones .", "The pathogenic bacterium , Listeria monocytogenes , expresses ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell physiology", "cell motility", "dictyosteliomycota", "directed cell migration", "developmental biology", "receptor physiology", "model organisms", "chemotaxis assay", "bioassays and physiological analysis", "population biology", "research and analysis methods", "cell analysis", "slime m...	Self-Generated Chemoattractant Gradients: Attractant Depletion Extends the Range and Robustness of Chemotaxis	journal.pbio.1002404	A combination of experiment and simulation reveals self-generated chemotaxis—an emergent, fundamental, and widespread mechanism of directed cell migration that depends on removal or destruction of the chemotactic signal by the migrating cells themselves.	[ [ "Eukaryotic chemotaxis is a key mechanism in many biological processes , including wound healing , development , and the metastasis of cancers [1] .", "In spite of its profound biological and medical importance , we frequently do not know enough about the environments of cells to predict their chemotactic...	[ "Chemotaxis is fundamentally important , but the sources of gradients in vivo are rarely well understood .", "Here , we analyse self-generated chemotaxis , in which cells respond to gradients they have made themselves by breaking down globally available attractants , using both computational simulations and exper...	[ "Cells move in response to chemical gradients .", "This is chemotaxis , a fundamental process that is crucial for embryonic development , immune response , and the progression of cancer .", "How the environment dictates cell movement has been studied extensively , but most studies do not account for how cells a...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "immunology", "microbiology", "host-pathogen interaction", "parasitic diseases", "parasitology", "parastic protozoans", "model organisms", "leishmania", "neglected tropical diseases", "infectious diseases", "biology", "leishmaniasis", "genetics", "protozoology", "genetics a...	Genetics of Host Response to Leishmania tropica in Mice – Different Control of Skin Pathology, Chemokine Reaction, and Invasion into Spleen and Liver	journal.pntd.0001667	null	[ [ "Several hundred million people in 88 countries are living in areas where they can contract leishmaniasis , a disease caused by intracellular protozoan parasites of the genus Leishmania and transmitted to vertebrates by phlebotomine sand flies .", "Leishmania parasites infect professional phagocytes ( neu...	[ "Leishmaniasis is a disease caused by protozoan parasites of genus Leishmania .", "The frequent involvement of Leishmania tropica in human leishmaniasis has been recognized only recently .", "Similarly as L . major , L . tropica causes cutaneous leishmaniasis in humans , but can also visceralize and cause syste...	[ "Several hundred million people are exposed to the risk of leishmaniasis , a disease caused by intracellular protozoan parasites of several Leishmania species and transmitted by phlebotomine sand flies .", "In humans , L . tropica causes cutaneous form of leishmaniasis with painful and long-persisting lesions in ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "genome analysis tools", "diabetic endocrinology", "endocrinology", "biology", "genomics", "diabetes and endocrinology", "genetics and genomics" ]	The Human Pancreatic Islet Transcriptome: Expression of Candidate Genes for Type 1 Diabetes and the Impact of Pro-Inflammatory Cytokines	journal.pgen.1002552	null	[ [ "Type 1 diabetes ( T1D ) is an autoimmune disease with a strong genetic component [1] .", "We have previously proposed that insulitis , the pancreatic islet inflammation present in T1D , results from a “dialog” between immune cells homing into the islets and the target beta cells .", "Beta cells contr...	[ "Type 1 diabetes ( T1D ) is an autoimmune disease in which pancreatic beta cells are killed by infiltrating immune cells and by cytokines released by these cells .", "Signaling events occurring in the pancreatic beta cells are decisive for their survival or death in diabetes .", "We have used RNA sequencing ( R...	[ "Pancreatic beta cells are destroyed by the immune system in type 1 diabetes mellitus , causing insulin dependence for life .", "Candidate genes for diabetes contribute to this process by acting both at the immune system and , as we suggest here , at the pancreatic beta cell level .", "We have utilized a novel ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "cell death", "medicine and health sciences", "autophagic cell death", "fungal genetics", "cell processes", "tropical diseases", "variant genotypes", "genetic mapping", "bacterial diseases", "genetic predisposition", "neglected tropical diseases", "bacteria", "infectious diseases", "buruli...	Genetic Variation in Autophagy-Related Genes Influences the Risk and Phenotype of Buruli Ulcer	journal.pntd.0004671	null	[ [ "Buruli ulcer ( BU ) is a severe necrotizing human skin disease caused by Mycobacterium ulcerans , representing the third most common mycobacteriosis worldwide [1] .", "At least 33 countries from Africa , South America and Western Pacific , with tropical , subtropical and temperate climates , have reporte...	[ "Buruli ulcer ( BU ) is a severe necrotizing human skin disease caused by Mycobacterium ulcerans .", "Clinically , presentation is a sum of these diverse pathogenic hits subjected to critical immune-regulatory mechanisms .", "Among them , autophagy has been demonstrated as a cellular process of critical importa...	[ "Buruli ulcer ( BU ) is a neglected tropical disease caused by Mycobacterium ulcerans .", "Because the exact trigger is still under investigation , current treatment options rely mostly on the surgical excision of the affected site .", "There is therefore a pressing demand for improved risk prediction and tailo...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell growth and division", "cell biology/chemical biology of the cell" ]	Plk1 Self-Organization and Priming Phosphorylation of HsCYK-4 at the Spindle Midzone Regulate the Onset of Division in Human Cells	journal.pbio.1000111	Self-regulated movement of Polo-like kinase 1 to the midzone of the mitotic spindle initiates a local signaling cascade that activates the cell division machinery at the cell's equator.	[ [ "At the end of mitosis , a physical barrier must be established between the segregated sister genomes to produce two distinct cells .", "This process , termed cytokinesis , involves the assembly and constriction of an actomyosin ring at the cell equator [1]–[3] .", "In addition to its fundamental role...	[ "Animal cells initiate cytokinesis in parallel with anaphase onset , when an actomyosin ring assembles and constricts through localized activation of the small GTPase RhoA , giving rise to a cleavage furrow .", "Furrow formation relies on positional cues provided by anaphase spindle microtubules ( MTs ) , but how...	[ "During mitosis , the separation of duplicated chromosomes and subsequent cytokinesis ( cell division ) are tightly coupled processes .", "Cytokinesis must occur not only after chromosomes have separated but also in the physical space between the chromosomes , so that each daughter cell inherits the appropriate g...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "body fluids", "population genetics", "habits", "twins", "developmental biology", "epigenetics", "dna", "population biology", "smoking habits", "dna methylation", "chromatin", "sex chromosomes", "genetic polymorphism", "chromosome biology", "behavior", ...	Characterizing genetic and environmental influences on variable DNA methylation using monozygotic and dizygotic twins	journal.pgen.1007544	null	[ [ "The study of twins provides an opportunity for exploring the extent to which heritable and environmental factors contribute to phenotypic variation in human populations [1] .", "By comparing concordance rates between monozygotic ( MZ ) and dizygotic ( DZ ) twins it has been shown that most human traits a...	[ "Variation in DNA methylation is being increasingly associated with health and disease outcomes .", "Although DNA methylation is hypothesized to be a mechanism by which both genetic and non-genetic factors can influence the regulation of gene expression , little is known about the extent to which DNA methylation ...	[ "The study of monozygotic ( MZ ) and dizygotic ( DZ ) twins provides an opportunity for exploring the extent to which heritable and environmental factors contribute to phenotypic variation in human populations .", "We exploit the twin study design to explore the factors influencing epigenetic variation between in...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "genetic networks", "toxins", "heavy metals", "pathology and laboratory medicine", "rna interference", "animals", "toxicology", "toxic agents", "lead (element)", "animal models", "toxicity", "drosophila melanogaster", "model organisms", ...	A Drosophila model for toxicogenomics: Genetic variation in susceptibility to heavy metal exposure	journal.pgen.1006907	null	[ [ "Studies on the genetics of susceptibility to environmental toxins are challenging in human populations , due to the variety of clinical symptoms and difficulty in determining which symptoms causally result from toxic exposure; uncontrolled environments , often with exposure to multiple toxicants; and difficu...	[ "The genetic factors that give rise to variation in susceptibility to environmental toxins remain largely unexplored .", "Studies on genetic variation in susceptibility to environmental toxins are challenging in human populations , due to the variety of clinical symptoms and difficulty in determining which sympto...	[ "Although physiological effects of environmental toxins are well documented , we know little about the genetic factors that determine individual variation in susceptibility to toxins .", "Such information is difficult to obtain in human populations due to heterogeneity in genetic background and environmental expo...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology and life sciences" ]	Toward Understanding the Functional Role of Ss-riok-1, a RIO Protein Kinase-Encoding Gene of Strongyloides stercoralis	journal.pntd.0003062	null	[ [ "Strongyloides stercoralis is a parasitic nematode infecting human beings and dogs , and causes a fatal , disseminated hyperinfection in immuno-compromised patients [1] , [2] .", "The life cycle of S . stercoralis , like other members of Strongyloides and related genera , is more complicated than that of ...	[ "Some studies of Saccharomyces cerevisiae and mammals have shown that RIO protein kinases ( RIOKs ) are involved in ribosome biogenesis , cell cycle progression and development .", "However , there is a paucity of information on their functions in parasitic nematodes .", "We aimed to investigate the function of...	[ "Parasitic nematodes cause serious global health problems and enormous economic losses .", "Control of these parasites is difficult due to their complicated life cycle and the lack of knowledge of their developmental biology at the molecular level .", "Protein kinases are key molecules regulating a range of bio...	2014
[ "Introduction", "Materials & Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "tropical diseases", "geographical locations", "microbiology", "blood groups", "alphaviruses", "health care", "north america", "viruses", "chikungunya ...	Epidemiology of Chikungunya Virus Outbreaks in Guadeloupe and Martinique, 2014: An Observational Study in Volunteer Blood Donors	journal.pntd.0005254	null	[ [ "Chikungunya virus ( CHIKV ) , an Aedes-borne alphavirus first identified in Tanzania in the early 1950's , infects humans through a \"zoonotic cycle\" ( i . e . , starting from a non-human primate reservoir and sylvatic mosquitoes ) or a \"dengue-like cycle\" ( i . e . , via direct human-mosquito-human trans...	[ "During Dec-2013 , a chikungunya virus ( CHIKV ) outbreak was first detected in the French-West Indies .", "Subsequently , the virus dispersed to other Caribbean islands , continental America and many islands in the Pacific Ocean .", "Previous estimates of the attack rate were based on declaration of clinically...	[ "Chikungunya virus ( CHIKV ) is an emerging mosquito-borne arbovirus responsible of a large outbreak since December 2013 in the Americas from French islands in the Caribbean .", "Documentation of the epidemic was based on the survey of clinically suspected cases , providing limited information on the incidence of...	2017
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "genome sequencing", "plant science", "genomics", "plant biology", "plant pathogens", "plant pathology", "biology", "evolutionary biology", "comparative genomics", "genetics and genomics" ]	Genomic Insights into the Origin of Parasitism in the Emerging Plant Pathogen Bursaphelenchus xylophilus	journal.ppat.1002219	null	[ [ "The nematode Caenorhabditis elegans was the first multicellular organism for which a complete genome sequence was available , and subsequent genomics research on a wider range of nematodes has provided information on many important biological processes and is underpinned by the information developed for C . ...	[ "Bursaphelenchus xylophilus is the nematode responsible for a devastating epidemic of pine wilt disease in Asia and Europe , and represents a recent , independent origin of plant parasitism in nematodes , ecologically and taxonomically distinct from other nematodes for which genomic data is available .", "As well...	[ "Bursaphelenchus xylophilus is an important plant pathogen , responsible for an epidemic of pine wilt disease in Asia and Europe .", "B . xylophilus has acquired the ability to parasitise plants independently from other economically important nematodes and has a complex life cycle that includes fungal feeding and...	2011
[ "Introduction", "Results", "Discussion", "Conclusion", "Materials and methods" ]	[ "genetic networks", "population genetics", "mathematics", "network analysis", "molecular biology techniques", "population biology", "discrete mathematics", "combinatorics", "research and analysis methods", "computer and information sciences", "genetic polymorphism", "gene mapping", "gene exp...	Gene co-expression network connectivity is an important determinant of selective constraint	journal.pgen.1006402	null	[ [ "A central aim of biology is to understand how emergent phenotypes are encoded in the genome and how genetic variation engenders phenotypic variation within populations .", "While much emphasis was , and is , placed on studying the genetics of those emergent phenotypes , less attention has been paid to th...	[ "While several studies have investigated general properties of the genetic architecture of natural variation in gene expression , few of these have considered natural , outbreeding populations .", "In parallel , systems biology has established that a general feature of biological networks is that they are scale-f...	[ "Numerous studies have shown that many genomic polymorphisms contributing to phenotypic variation are located outside of protein coding regions , suggesting that they act by modulating gene expression .", "Furthermore , phenotypes are seldom explained by individual genes , but rather emerge from networks of inter...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "medicine", "neurological tumors", "gene expression", "genetics", "biology", "cancers and neoplasms", "genetics and genomics", "dna transcription" ]	SIRT1 Promotes N-Myc Oncogenesis through a Positive Feedback Loop Involving the Effects of MKP3 and ERK on N-Myc Protein Stability	journal.pgen.1002135	null	[ [ "Neuroblastoma , which originates from precursor neuroblast cells , is the most common solid tumor in early childhood .", "MYCN oncogene amplification and consequent N-Myc mRNA and protein over-expression , are seen as a clonal feature in a quarter of tumors , and correlate with poorer prognosis in patien...	[ "The N-Myc oncoprotein is a critical factor in neuroblastoma tumorigenesis which requires additional mechanisms converting a low-level to a high-level N-Myc expression .", "N-Myc protein is stabilized when phosphorylated at Serine 62 by phosphorylated ERK protein .", "Here we describe a novel positive feedback ...	[ "The class III histone deacetylase SIRT1 is repressed by tumor suppressor genes and exerts divergent effects on tumorigenesis depending on its down-stream targets .", "Small molecule SIRT1 inhibitors have shown promising anti-cancer effects both in vitro and in vivo .", "Here we identified SIRT1 as a gene direc...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal genetics", "gene regulation", "dna transcription", "histone modification", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "molecular development", "molecular genetics", "pattern formation", "chromatin", "chromosome biology", "gene expression...	Preferential Genome Targeting of the CBP Co-Activator by Rel and Smad Proteins in Early Drosophila melanogaster Embryos	journal.pgen.1002769	null	[ [ "CREB-binding protein ( CBP ) and its paralog p300 are widely used transcriptional co-regulators with histone acetyltransferase ( HAT ) activity ( reviewed in [1] ) .", "Over 400 interaction partners have been described for these proteins , including transcription factors of all major families , and they ...	[ "CBP and the related p300 protein are widely used transcriptional co-activators in metazoans that interact with multiple transcription factors .", "Whether CBP/p300 occupies the genome equally with all factors or preferentially binds together with some factors is not known .", "We therefore compared Drosophila ...	[ "Development of an embryo into different cell types relies on regulation of gene expression , whereby genes are coordinately turned on or off .", "CBP and the related p300 protein are central regulators of gene expression in animal cells .", "These co-activator proteins facilitate gene activation by a multitude...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/neuronal and glial cell biology", "molecular biology/rna-protein interactions", "genetics and genomics/gene expression", "molecular biology/mrna stability", "molecular biology/rna splicing", "biochemistry/biomacromolecule-ligand interactions", "molecular biology/translational regulation", ...	Quaking Regulates Hnrnpa1 Expression through Its 3′ UTR in Oligodendrocyte Precursor Cells	journal.pgen.1001269	null	[ [ "Myelin is a lipid-rich structure that facilitates the propagation of electrical impulses along neuronal axons and protects them from degeneration [1]–[3] .", "In the central nervous system ( CNS ) , myelin is produced by oligodendrocytes , glial cells that ensheathe nearby axons with specialized cytoplas...	[ "In mice , Quaking ( Qk ) is required for myelin formation; in humans , it has been associated with psychiatric disease .", "QK regulates the stability , subcellular localization , and alternative splicing of several myelin-related transcripts , yet little is known about how QK governs these activities .", "Her...	[ "Myelin is a lipid-rich structure that insulates neuronal axons , facilitating electrical conductance and protecting neurons from degeneration .", "Myelin comprises multiple compact layers of phospholipid bilayer and specific myelin proteins that occupy distinct positions within the structure .", "In the centra...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "circuit models", "mathematics", "neural networks", "computational neuroscience", "single neuron function", "biology", "computational biology", "neuroscience", "nonlinear dynamics" ]	Impact of Adaptation Currents on Synchronization of Coupled Exponential Integrate-and-Fire Neurons	journal.pcbi.1002478	null	[ [ "Synchronized oscillating neural activity has been shown to be involved in a variety of cognitive functions [1] , [2] such as multisensory integration [3] , [4] , conscious perception [5] , [6] , selective attention [7] , and memory [9] , [10] , as well as in pathological states including Parkinson's disease ...	[ "The ability of spiking neurons to synchronize their activity in a network depends on the response behavior of these neurons as quantified by the phase response curve ( PRC ) and on coupling properties .", "The PRC characterizes the effects of transient inputs on spike timing and can be measured experimentally ."...	[ "Synchronization of neuronal spiking in the brain is related to cognitive functions , such as perception , attention , and memory .", "It is therefore important to determine which properties of neurons influence their collective behavior in a network and to understand how .", "A prominent feature of many cortic...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "neural networks", "statistics", "geographical locations", "visual object recognition", "social sciences", "neuroscience", "animals", "learning and memory", "perception", "regression analysis", "developmental biology", "cognitive psychology"...	Large scale detailed mapping of dengue vector breeding sites using street view images	journal.pntd.0007555	null	[ [ "In their review of dengue risk mapping modeling tools , Louis et al . [25] showed that social predictors such as education level , occupational status , and income are often used as proxies to assess local environmental conditions and hygiene , which are normally difficult to assess directly .", "Housing...	[ "Targeted environmental and ecosystem management remain crucial in control of dengue .", "However , providing detailed environmental information on a large scale to effectively target dengue control efforts remains a challenge .", "An important piece of such information is the extent of the presence of potentia...	[ "Providing detailed environmental information on a large scale to effectively target dengue control efforts remains a challenge .", "In this paper we present the design and implementation of a pipeline to detect outdoor open containers which constitute potential dengue vector breeding sites from geotagged images ...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "computational biology/metagenomics", "ecology/environmental microbiology", "marine and aquatic sciences/bioinformatics" ]	The GAAS Metagenomic Tool and Its Estimations of Viral and Microbial Average Genome Size in Four Major Biomes	journal.pcbi.1000593	null	[ [ "Metagenomic approaches to the study of microbial and viral communities have revealed previously undiscovered diversity on a tremendous scale [1] , [2] .", "Metagenomic sequences are typically compared to sequences from known genomes using BLAST to estimate the taxonomic and functional composition of the ...	[ "Metagenomic studies characterize both the composition and diversity of uncultured viral and microbial communities .", "BLAST-based comparisons have typically been used for such analyses; however , sampling biases , high percentages of unknown sequences , and the use of arbitrary thresholds to find significant si...	[ "Metagenomics uses DNA or RNA sequences isolated directly from the environment to determine what viruses or microorganisms exist in natural communities and what metabolic activities they encode .", "Typically , metagenomic sequences are compared to annotated sequences in public databases using the BLAST search to...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "deletion mutation", "insertion mutation", "population genetics", "mutation", "phylogenetics", "data management", "phylogenetic analysis", "dna", "population biology", "gene conversion", "haplogroups", "computer and information sciences", "sex chromosomes", "chromosome biolog...	Analysis of 62 hybrid assembled human Y chromosomes exposes rapid structural changes and high rates of gene conversion	journal.pgen.1006834	null	[ [ "The human Y chromosome shares around 3 Mb of sequence with the X chromosome—the telomeric pseudoautosomal regions , where recombination occurs .", "The remainder of the Y chromosome , the male-specific region ( MSY ) is inherited from father to son without recombination and its evolution therefore reflec...	[ "The human Y-chromosome does not recombine across its male-specific part and is therefore an excellent marker of human migrations .", "It also plays an important role in male fertility .", "However , its evolution is difficult to fully understand because of repetitive sequences , inverted repeats and the potent...	[ "The Y chromosome is extraordinary in many respects; it is non-recombining along most of its length , it carries many testis-expressed genes that are often found in palindromes and thus in several copies , and it is generally highly repetitive with very few unique genes .", "Its evolutionary process is not well u...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "animal models of infection", "biology and life sciences", "microbiology" ]	Insights into Vibrio cholerae Intestinal Colonization from Monitoring Fluorescently Labeled Bacteria	journal.ppat.1004405	null	[ [ "Cholera , a severe and potentially fatal diarrheal disease , is caused by ingestion of food or water contaminated with the highly motile gram-negative rod Vibrio cholerae .", "Although the disease has been recognized for centuries , cholera still causes significant morbidity and mortality in several part...	[ "Vibrio cholerae , the agent of cholera , is a motile non-invasive pathogen that colonizes the small intestine ( SI ) .", "Most of our knowledge of the processes required for V . cholerae intestinal colonization is derived from enumeration of wt and mutant V . cholerae recovered from orogastrically infected infan...	[ "Vibrio cholerae is a highly motile bacterium that causes the diarrheal disease cholera .", "Despite our extensive knowledge of the genes and processes that enable this non-invasive pathogen to colonize the small intestine , there is limited knowledge of the pathogen's fine localization within the intestine .", ...	2014
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "computer and information sciences", "evolutionary processes", "virology", "genetics", "biology and life sciences", "molecular evolution", "microbiology", "computational biology", "evolutionary biology", "biophysics", "evolutionary genetics", "biophysical simulations" ]	Payoffs, Not Tradeoffs, in the Adaptation of a Virus to Ostensibly Conflicting Selective Pressures	journal.pgen.1004611	null	[ [ "The relationship between genotype and phenotype is complicated by genetic interactions such as pleiotropy , in which genes contribute to multiple traits thereby influencing multiple phenotypes [1] , [2] .", "Such pleiotropic effects of mutations often manifest as tradeoffs between traits where improvemen...	[ "The genetic architecture of many phenotypic traits is such that genes often contribute to multiple traits , and mutations in these genes can therefore affect multiple phenotypes .", "These pleiotropic interactions often manifest as tradeoffs between traits where improvement in one property entails a cost in anot...	[ "One of the most fundamental tradeoffs in evolutionary biology is between survival and reproduction .", "Many parasites experience distinct selective pressures during different stages of their life cycles; mutations arising during one stage may be beneficial , but come at a cost during another .", "For example ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "biophysics", "biology and life sciences" ]	Logarithmic and Power Law Input-Output Relations in Sensory Systems with Fold-Change Detection	journal.pcbi.1003781	null	[ [ "Biological sensory systems have been quantitatively studied for over 150 years .", "In many sensory systems , the response to a step increase in signal rises , reaches a peak response , and then falls , adapting back to a baseline level , ( Fig . 1a upper panel ) .", "Consider a step increase in inpu...	[ "Two central biophysical laws describe sensory responses to input signals .", "One is a logarithmic relationship between input and output , and the other is a power law relationship .", "These laws are sometimes called the Weber-Fechner law and the Stevens power law , respectively .", "The two laws are found ...	[ "One of the first measurements an experimentalist makes to understand a sensory system is to explore the relation between input signal and the systems response amplitude .", "Here , we show using mathematical models that this measurement can give important clues about the possible mechanism of sensing .", "We u...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "luciferase", "enzymes", "enzymology", "microbiology", "neuroscience", "mammalian genomics", "microbial genetics", "microbial genomics", "viral genomics", "animal cells", "proteins", "oxidoreductases", "gene expression", "viral replication", "animal genomics", "viral genetics", "bioc...	The HSV-1 Latency-Associated Transcript Functions to Repress Latent Phase Lytic Gene Expression and Suppress Virus Reactivation from Latently Infected Neurons	journal.ppat.1005539	null	[ [ "Herpes simplex viruses 1 ( HSV-1 ) and 2 ( HSV-2 ) are ancient human pathogens that are most commonly associated with sub-clinical and mild infections but can occasionally cause severe life threatening disease [1] .", "HSV-1 is most commonly associated with infection of the oral mucosa , and following pr...	[ "Herpes simplex virus 1 ( HSV-1 ) establishes life-long latent infection within sensory neurons , during which viral lytic gene expression is silenced .", "The only highly expressed viral gene product during latent infection is the latency-associated transcript ( LAT ) , a non-protein coding RNA that has been str...	[ "Like all herpesviruses , herpes simplex virus 1 ( HSV-1 ) persistently infects an individual for their entire life .", "This persistent—or latent—virus is maintained as silenced DNA within the nuclei of sensory neurons , from which only the virus latency-associated transcript RNA is abundantly transcribed .", ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Machine Learning Methods Enable Predictive Modeling of Antibody Feature:Function Relationships in RV144 Vaccinees	journal.pcbi.1004185	null	[ [ "Antibodies provide the correlate of protection for most vaccines [1] .", "This correlation is often thought to be mechanistic , as in numerous disease settings passively transferred antibodies provide protection from infection [2] .", "Yet , the fact that some vaccines that induce an antibody respons...	[ "The adaptive immune response to vaccination or infection can lead to the production of specific antibodies to neutralize the pathogen or recruit innate immune effector cells for help .", "The non-neutralizing role of antibodies in stimulating effector cell responses may have been a key mechanism of the protectio...	[ "Antibodies are one of the central mechanisms that the human immune system uses to eliminate infection: an antibody can recognize a pathogen or infected cell using its Fab region while recruiting additional immune cells through its Fc that help destroy the offender .", "This mechanism may have been key to the red...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "gene regulation", "animals", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "epigenetics", "chromatin", "drosophila", "research and analysis methods", "transcriptional control", "chromosome biology", "proteins", "animal s...	Thermodynamic model of gene regulation for the Or59b olfactory receptor in Drosophila	journal.pcbi.1006709	null	[ [ "The variety of ways in which the information of the genetic code is expressed in different multicellular organisms depends upon a broad spectrum of regulatory mechanisms .", "These regulatory mechanisms determine which of the genes are “turned on” and which are “turned off” under specific sets of circums...	[ "Complex eukaryotic promoters normally contain multiple cis-regulatory sequences for different transcription factors ( TFs ) .", "The binding patterns of the TFs to these sites , as well as the way the TFs interact with each other and with the RNA polymerase ( RNAp ) , lead to combinatorial problems rarely unders...	[ "The paper proposes and validates experimentally a model for the fine-graded regulation of a gene , called Or59b , coding for an olfactory receptor in Drosophila .", "The model is based on statistical thermodynamical theory , theory that so far has been mostly used for prokaryotes .", "In order to apply it to o...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "gene regulation", "molecular genetics", "biology", "computational biology" ]	Computational Assessment of the Cooperativity between RNA Binding Proteins and MicroRNAs in Transcript Decay	journal.pcbi.1003075	null	[ [ "Transcript degradation is an important mechanism for regulating the levels of proteins in a time or space-dependent manner [1] .", "One mechanism through which transcript degradation can be controlled is via miRNAs , short RNAs approximately 21–23 nucleotides in length that regulate diverse biological pr...	[ "Transcript degradation is a widespread and important mechanism for regulating protein abundance .", "Two major regulators of transcript degradation are RNA Binding Proteins ( RBPs ) and microRNAs ( miRNAs ) .", "We computationally explored whether RBPs and miRNAs cooperate to promote transcript decay .", "We...	[ "Transcript degradation represents an important mechanism of regulation used in diverse biological processes , including during development to eliminate maternally inherited transcripts , in adult tissues to define cell lineages , and as part of signaling pathways to down-regulate unneeded transcripts .", "RNA bi...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "physiology", "biology", "anatomy and physiology", "molecular cell biology" ]	Transcriptional Corepressors HIPK1 and HIPK2 Control Angiogenesis Via TGF-β–TAK1–Dependent Mechanism	journal.pbio.1001527	During angiogenesis, endothelial cells in nascent blood vessels use the transcriptional cofactors HIPK1 and HIPK2 to transduce TGF-β signals and control cell proliferation and adhesion.	[ [ "Vascular morphogenesis is controlled by an intricate interplay of extrinsic factors and their downstream signaling mechanisms [1] , [2] .", "At the early stage of vascular development , several critical events dictate the successful establishment of nascent vasculature in yolk sac and in the developing e...	[ "Several critical events dictate the successful establishment of nascent vasculature in yolk sac and in the developing embryos .", "These include aggregation of angioblasts to form the primitive vascular plexus , followed by the proliferation , differentiation , migration , and coalescence of endothelial cells ."...	[ "An essential step during early embryonic development is to establish elaborate vascular networks that provide nutrients to ensure the proper growth of the embryos .", "This process , known as angiogenesis , requires coordinated regulation of cell proliferation , migration , and differentiation in endothelial cel...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Predictive Modeling of In Vivo Response to Gemcitabine in Pancreatic Cancer	journal.pcbi.1003231	null	[ [ "We aim to quantify the link between pancreatic tumor growth observed in-vitro and that observed in-vivo by providing a novel integrated experimental/computational approach to predict the cancer drug response .", "The most common chemotherapy drug , Difluorodeoxycytidine ( dFdC , or gemcitabine ) , is a c...	[ "A clear contradiction exists between cytotoxic in-vitro studies demonstrating effectiveness of Gemcitabine to curtail pancreatic cancer and in-vivo studies failing to show Gemcitabine as an effective treatment .", "The outcome of chemotherapy in metastatic stages , where surgery is no longer viable , shows a 5-y...	[ "There are few treatment options for advanced pancreatic cancer .", "The chemotherapeutic drug Gemcitabine is routinely used , yet 95% of patients die within 5 years of diagnosis .", "Surprisingly , Gemcitabine experiments with pancreatic tumor cells in the laboratory dish show that most cells will be killed by...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology/environmental microbiology" ]	First Description of a Cluster of Acute/Subacute Paracoccidioidomycosis Cases and Its Association with a Climatic Anomaly	journal.pntd.0000643	null	[ [ "Paracoccidioidomycosis ( PCM ) is the most important endemic deep mycosis in Latin America [1] .", "Infection is acquired through inhalation of airborne propagules released by the filamentous forms of the fungus P . brasiliensis present in the soil of endemic areas .", "Although it has been estimated...	[ "Identifying clusters of acute paracoccidioidomycosis cases could potentially help in identifying the environmental factors that influence the incidence of this mycosis .", "However , unlike other endemic mycoses , there are no published reports of clusters of paracoccidioidomycosis .", "A retrospective cluster...	[ "Paracoccocidioidomycosis is acquired through inhalation of spores released from filamentous forms of Paracoccidioides brasiliensis presumably present in the soil of endemic areas .", "However , successful isolation of the fungus from these areas has been rare , making it difficult to determine the fungus's ecolo...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "infectious diseases/fungal infections", "computational biology/comparative sequence analysis", "microbiology/microbial evolution and genomics", "evolutionary biology/genomics", "genetics and genomics/genome projects", "computational biology/genom...	Genomic Analysis of the Basal Lineage Fungus Rhizopus oryzae Reveals a Whole-Genome Duplication	journal.pgen.1000549	null	[ [ "The fungal kingdom comprises an estimated 1 . 5 million diverse members spanning over 1 billion years of evolutionary history .", "Within the fungal kingdom , four major groups ( “Phyla” ) —the Chytridiomycota , Zygomycota , Ascomycota and Basidiomycota— are traditionally recognized [1] , [2] ( Figure 1 ...	[ "Rhizopus oryzae is the primary cause of mucormycosis , an emerging , life-threatening infection characterized by rapid angioinvasive growth with an overall mortality rate that exceeds 50% .", "As a representative of the paraphyletic basal group of the fungal kingdom called “zygomycetes , ” R . oryzae is also use...	[ "Rhizopus oryzae is a widely dispersed fungus that can cause fatal infections in people with suppressed immune systems , especially diabetics or organ transplant recipients .", "Antibiotic therapy alone is rarely curative , particularly in patients with disseminated infection .", "We sequenced the genome of a p...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "carbohydrate metabolism", "medicine and health sciences", "protein metabolism", "pathology and laboratory medicine", "pathogens", "microbiology", "cell metabolism", "glucose metabolism", "viruses", "physiological processes", "metabolites", "dna viruses", "pharmacology",...	The Human Cytomegalovirus UL38 protein drives mTOR-independent metabolic flux reprogramming by inhibiting TSC2	journal.ppat.1007569	null	[ [ "Viruses depend on cellular energy and macromolecules to support their replication .", "Several studies have identified specific virally-induced metabolic activities that are important for the production of viral progeny [1–9] .", "Further , many successful anti-viral treatments target virally-induced...	[ "Human Cytomegalovirus ( HCMV ) infection induces several metabolic activities that are essential for viral replication .", "Despite the important role that this metabolic modulation plays during infection , the viral mechanisms involved are largely unclear .", "We find that the HCMV UL38 protein is responsible...	[ "Viruses are parasites that usurp the energy and molecular building blocks of their hosts to support their replication .", "In the past few years , numerous studies have shown that a wide variety of viruses induce cellular metabolic activities that are essential for successful infection .", "However , the viral...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "insulin", "animal behavior", "sexual selection", "evolutionary biology", "physiology", "endocrine system", "pheromones", "biology", "anatomy and physiology", "evolutionary processes", "endocrine physiology" ]	Insulin Signaling Mediates Sexual Attractiveness in Drosophila	journal.pgen.1002684	null	[ [ "Organismal fitness is influenced by social interactions , which drive sexual selection and individual attractiveness .", "In nature , a myriad of specialized signals and cues are used for intraspecific communication and mate choice , and many attractiveness traits are known to reflect an individual's hea...	[ "Sexually attractive characteristics are often thought to reflect an individual's condition or reproductive potential , but the underlying molecular mechanisms through which they do so are generally unknown .", "Insulin/insulin-like growth factor signaling ( IIS ) is known to modulate aging , reproduction , and s...	[ "In nature , a myriad of specialized traits have evolved that are used for intraspecific communication and mate choice .", "We postulated that certain traits may have evolved to be attractive by virtue of their accurate representation of molecular pathways that are critical for determining evolutionary fitness ."...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "genome analysis tools", "mathematics", "statistics", "genetics", "biology", "genomics", "biostatistics", "statistical methods", "genetics and genomics" ]	Beyond Missing Heritability: Prediction of Complex Traits	journal.pgen.1002051	null	[ [ "Few examples exist of findings from Genome Wide Association Studies ( GWAS ) being applied to preventive and personalized medicine .", "Despite the success of GWAS in the discovery of many novel disease variants , the variants identified as being statistically significant typically account for minimal fr...	[ "Despite rapid advances in genomic technology , our ability to account for phenotypic variation using genetic information remains limited for many traits .", "This has unfortunately resulted in limited application of genetic data towards preventive and personalized medicine , one of the primary impetuses of genom...	[ "While previous genome-wide association studies have implicated numerous loci associated with complex traits , such loci typically account for a very small proportion of phenotypic variation .", "However , a recent study using height as a model trait has illustrated that common single nucleotide polymorphisms can...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci	journal.pgen.1005202	null	[ [ "Recent large-scale GWAS have identified 46 genome-wide significant CAD loci and a further 104 independent variants associated at a 5% false discovery rate ( FDR ) , yet the biological and disease-relevant mechanisms for these associations remain largely unknown [1] .", "It is estimated that at least two-...	[ "To functionally link coronary artery disease ( CAD ) causal genes identified by genome wide association studies ( GWAS ) , and to investigate the cellular and molecular mechanisms of atherosclerosis , we have used chromatin immunoprecipitation sequencing ( ChIP-Seq ) with the CAD associated transcription factor TC...	[ "While coronary artery disease ( CAD ) is due in part to environmental and metabolic factors , about half of the risk is genetically predetermined .", "Genome-wide association studies in human populations have identified approximately 150 sites in the genome that appear to be associated with CAD .", "The mechan...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Trichinella spiralis Paramyosin Binds Human Complement C1q and Inhibits Classical Complement Activation	journal.pntd.0004310	null	[ [ "Trichinellosis is a serious zoonotic disease caused by the ingestion of undercooked meat contaminated with the larvae of Trichinella spiralis .", "Heavy infection can result in death [1] .", "Recently , trichinellosis has been regarded as an emerging or re-emerging disease in some countries due to im...	[ "Trichinella spiralis expresses paramyosin ( Ts-Pmy ) as a defense mechanism .", "Ts-Pmy is a functional protein with binding activity to human complement C8 and C9 and thus plays a role in evading the attack of the host’s immune system .", "In the present study , the binding activity of Ts-Pmy to human complem...	[ "Trichinellosis is one of the most important food-borne parasitic zoonoses worldwide .", "The key factor for Trichinella spiralis to survive in its host is evading from the attacks by the immune defense system .", "Our previous study revealed that paramyosin from Trichinella spiralis ( Ts-Pmy ) played a role in...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "organismal evolution", "protein metabolism", "enzymes", "metabolic networks", "enzymology", "microbiology", "network analysis", "enzyme metabolism", "microbial evolution", "membrane metabolism", "enzyme kinetics", "cellular structures and organelles", "enzyme chemistry", "computer and inf...	The number of active metabolic pathways is bounded by the number of cellular constraints at maximal metabolic rates	journal.pcbi.1006858	null	[ [ "Fitter microorganisms drive competitors to extinction by synthesising more viable offspring [1 , 2] .", "The rate of offspring-cell synthesis per cell , i . e . , the specific growth rate , is a common determinant of evolutionary success across microbial species [1] .", "A high growth rate requires h...	[ "Growth rate is a near-universal selective pressure across microbial species .", "High growth rates require hundreds of metabolic enzymes , each with different nonlinear kinetics , to be precisely tuned within the bounds set by physicochemical constraints .", "Yet , the metabolic behaviour of many species is ch...	[ "The microbial genome encodes for a large network of enzyme-catalyzed reactions .", "The reaction rates depend on concentrations of enzymes and metabolites , which in turn depend on those rates .", "Cells face a number of biophysical constraints on enzyme expression , for example due to a limited membrane area ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/viral infections", "virology/host antiviral responses", "immunology/immunity to infections", "immunology/innate immunity" ]	An Accessory to the ‘Trinity’: SR-As Are Essential Pathogen Sensors of Extracellular dsRNA, Mediating Entry and Leading to Subsequent Type I IFN Responses	journal.ppat.1000829	null	[ [ "There is a ‘trinity’ of pattern recognition receptors ( PRRs ) used by the innate immune system to sense pathogens .", "These include the toll-like receptors ( TLRs ) , retinoic acid-inducible gene-I ( RIG-I ) -like receptors ( RLRs ) and nucleotide oligomerization domain ( NOD ) -like receptors ( NLRs )...	[ "Extracellular RNA is becoming increasingly recognized as a signaling molecule .", "Virally derived double stranded ( ds ) RNA released into the extracellular space during virus induced cell lysis acts as a powerful inducer of classical type I interferon ( IFN ) responses; however , the receptor that mediates thi...	[ "Nearly all viruses produce dsRNA during their replication cycle .", "This molecule is not normally found in a healthy host cell and thus functions as a flag , alerting the host to a viral infection .", "Cells can die by lysis during virus infections , and the intracellular dsRNA is then released into the extra...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "drosophila melanogaster", "model organisms", "molecular cell biology", "transposons", "cell biology", "chromosome biology", "nucleic acids", "genetics", "molecular genetics", "biology", "molecular biology", "genetics and genomics" ]	Competition between Replicative and Translesion Polymerases during Homologous Recombination Repair in Drosophila	journal.pgen.1002659	null	[ [ "DNA double-strand breaks ( DSBs ) pose a serious threat to cell viability and genome integrity .", "DSBs can be repaired either by non-homologous end joining , in which the DSB ends are processed and directly ligated , potentially leading to loss of information and mutagenesis ( reviewed in [1] ) , or by...	[ "In metazoans , the mechanism by which DNA is synthesized during homologous recombination repair of double-strand breaks is poorly understood .", "Specifically , the identities of the polymerase ( s ) that carry out repair synthesis and how they are recruited to repair sites are unclear .", "Here , we have inve...	[ "DNA polymerases are required during both DNA replication and various types of DNA repair .", "DNA double-strand breaks are frequently repaired by homologous recombination , a conservative process in which DNA is copied into the break site from a similar template .", "The specific polymerases that operate durin...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "crystal structure", "chemical compounds", "phosphates", "enzymes", "condensed matter physics", "enzymology", "enzyme metabolism", "crystallography", "cellular structures and organelles", "enzyme chemistry", "solid state physics", "proteins", "zinc", "chemistry", "physics", "biochemist...	The Structural Basis of Coenzyme A Recycling in a Bacterial Organelle	journal.pbio.1002399	This study describes the structure of a novel phosphotransacylase enzyme that facilitates the recycling of the essential cofactor acetyl-CoA within a bacterial organelle and discusses the properties of the enzyme's active site and how it is packaged into the organelle.	[ [ "Bacterial Microcompartments ( BMCs ) are organelles that encapsulate enzymes for sequential biochemical reactions within a protein shell [1–4] .", "The shell is typically composed of three types of protein subunits , which form either hexagonal ( BMC-H and BMC-T ) or pentagonal ( BMC-P ) tiles that assem...	[ "Bacterial Microcompartments ( BMCs ) are proteinaceous organelles that encapsulate critical segments of autotrophic and heterotrophic metabolic pathways; they are functionally diverse and are found across 23 different phyla .", "The majority of catabolic BMCs ( metabolosomes ) compartmentalize a common core of e...	[ "In metabolism , molecules with “high-energy” bonds ( e . g . , ATP and Acetyl~CoA ) are critical for both catabolic and anabolic processes .", "Accordingly , the retention of these bonds during biochemical transformations is incredibly important .", "The phosphotransacylase ( Pta ) enzyme catalyzes the convers...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell biology", "computational biology", "computational biology/systems biology" ]	Nonidentifiability of the Source of Intrinsic Noise in Gene Expression from Single-Burst Data	journal.pcbi.1000192	null	[ [ "The regulation of gene activity is essential for the proper functioning of cells ,", "which employ a variety of molecular mechanisms to control gene expression .", "Despite", "this , there is considerable variation in the precise number and timing of protein", "molecules that are produced for...	[ "Over the last few years , experimental data on the fluctuations in gene activity", "between individual cells and within the same cell over time have confirmed that", "gene expression is a “noisy” process .", "This variation is in", "part due to the small number of molecules taking part in some of the key",...	[ "Recent experimental data showing fluctuations in gene activity between individual", "cells and within the same cell over time confirm that gene expression is a", "“noisy” process .", "This variation is partly due to the small", "number of molecules involved in gene expression .", "One consequence is that...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "coronaviruses", "pathology and laboratory medicine", "statistics", "pathogens", "sars coronavirus", "microbiology", "viruses", "statistical data", "probability distribution", "mathematics", "rna viruses", "genome analysis", "genetic epidemiology", "infect...	Bayesian inference of transmission chains using timing of symptoms, pathogen genomes and contact data	journal.pcbi.1006930	null	[ [ "Inferring chains of transmission in an infectious disease outbreak can provide valuable epidemiological insights into transmission dynamics , which can be used to guide infection control policy .", "For example , reconstructed outbreaks have been used to identify drivers of ongoing infection [1] , charac...	[ "There exists significant interest in developing statistical and computational tools for inferring ‘who infected whom’ in an infectious disease outbreak from densely sampled case data , with most recent studies focusing on the analysis of whole genome sequence data .", "However , genomic data can be poorly inform...	[ "Reconstructing the history of transmission events in an infectious disease outbreak provides valuable information for informing infection control policy .", "Recent years have seen considerable progress in the development of statistical tools for the inference of such transmission trees from outbreak data , with...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/genomics", "computational biology/transcriptional regulation" ]	A Quantitative Model of Transcriptional Regulation Reveals the Influence of Binding Location on Expression	journal.pcbi.1000773	null	[ [ "Control of gene expression programs across diverse tissues and developmental stages is achieved through networks of proteins interacting with specific regulatory sites in the genome .", "Pioneering work on several individual promoters , including those of beta-interferon [1] and endo16 [2] have revealed ...	[ "Understanding the mechanistic basis of transcriptional regulation has been a central focus of molecular biology since its inception .", "New high-throughput chromatin immunoprecipitation experiments have revealed that most regulatory proteins bind thousands of sites in mammalian genomes .", "However , the func...	[ "Gene expression is controlled , in large part , by regulatory proteins called transcription factors that bind specific sites in the genome .", "A major focus of molecular biology has been understanding how these transcription factors interact with the cell's transcriptional machinery , the genome , and with each...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "phosphorylation", "meiosis", "cell cycle and cell division", "cell processes", "chromatids", "dna", "homologous recombination", "chromosome biology", "proteins", "recombinant proteins", "biochemistry", "cell biology", "post-translational modification", "nucleic acids", "genetics", "bi...	Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1	journal.pgen.1006226	null	[ [ "In mitotically dividing cells , DNA damage such as double strand breaks ( DSBs ) involves potentially lethal events that must be repaired to maintain the integrity of the genome .", "The most accurate and conservative way to repair such breaks is by homologous recombination , in which the conserved recom...	[ "During meiosis , programmed double strand breaks ( DSBs ) are repaired preferentially between homologs to generate crossovers that promote proper chromosome segregation at Meiosis I .", "In many organisms , there are two strand exchange proteins , Rad51 and the meiosis-specific Dmc1 , required for interhomolog (...	[ "Sexual reproduction requires the formation of haploid gametes by a highly conserved , specialized cell division called meiosis .", "Failures in meiotic chromosome segregation lead to chromosomally imbalanced gametes that cause infertility and birth defects such as Trisomy 21 in humans .", "Meiotic crossovers ,...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "helminths", "tropical diseases", "hookworms", "geographical locations", "parasitic diseases", "animals", "ascaris", "ascaris lumbricoides", "veterinary diagnostics", "tanzania", "internet", "neglected tropical diseases", "africa", "vete...	Diagnostic comparison between FECPAKG2 and the Kato-Katz method for analyzing soil-transmitted helminth eggs in stool	journal.pntd.0006562	null	[ [ "Approximately 1 . 5 billion people are infected with the soil-transmitted helminths ( STH ) Ascaris lumbricoides , hookworm and/or Trichuris trichiura [1] .", "While the majority of light infections remain asymptomatic , moderate and heavy infections are responsible for a considerable health burden , inc...	[ "Over one billion people are infected with soil-transmitted helminths ( STH ) , i . e . Ascaris lumbricoides , hookworm and Trichuris trichiura .", "For estimating drug efficacy and monitoring anthelminthic drug resistance , accurate diagnostic methods are critical .", "FECPAKG2 is a new remote-diagnostic tool ...	[ "About 1 . 5 billion people are infected with soil-transmitted helminths ( Ascaris lumbricoides , hookworm and Trichuris trichiura ) .", "Since morbidity correlates with the number of worms harbored by an infected individual , WHO aims to reduce moderate and heavy infections in pre- and school-aged children by 20...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viruses and cancer" ]	Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus	journal.ppat.1000578	null	[ [ "The Polyomaviridae are a diverse family of non-enveloped DNA viruses named for some family members' ability to cause various types of tumors in experimentally challenged animals .", "Although BK and JC polyomaviruses ( BKV and JCV ) are highly prevalent in human populations , neither virus has been clear...	[ "Merkel cell carcinoma ( MCC ) is a relatively uncommon but highly lethal form of skin cancer .", "A majority of MCC tumors carry DNA sequences derived from a newly identified virus called Merkel cell polyomavirus ( MCV or MCPyV ) , a candidate etiologic agent underlying the development of MCC .", "To further i...	[ "For more than 50 years it has been known that some polyomavirus types can induce cancer in experimental animals .", "However , associations between the various polyomaviruses known to chronically infect most humans and the development of cancer have been difficult to uncover .", "Last year , DNA from a new hum...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/plant-biotic interactions", "genetics and genomics/comparative genomics", "genetics and genomics/genome projects", "genetics and genomics/disease models", "biotechnology/bioengineering", "infectious diseases/respiratory infections", "infectious diseases/bacterial infections", "plant biol...	Complete Genome Sequence of the N2-Fixing Broad Host Range Endophyte Klebsiella pneumoniae 342 and Virulence Predictions Verified in Mice	journal.pgen.1000141	null	[ [ "Klebsiella pneumoniae 342 ( hereafter Kp342 ) is a mutualistic , diazotrophic ( nitrogen-fixing ) endophyte and as such is capable of providing small but critical amounts of fixed nitrogen in the form of ammonia by the colonization of the interior of their plant hosts while receiving vital nutrients and prot...	[ "We report here the sequencing and analysis of the genome of the nitrogen-fixing endophyte , Klebsiella pneumoniae 342 .", "Although K . pneumoniae 342 is a member of the enteric bacteria , it serves as a model for studies of endophytic , plant-bacterial associations due to its efficient colonization of plant tis...	[ "Bacterial endophytes are capable of inhabiting the living tissues of plants without causing them significant harm .", "Klebsiella pneumoniae 342 ( Kp342 ) is a model for this plant host-bacterial association , in part due to its capacity to colonize in high numbers the interior of plants including wheat and maiz...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics", "plant science", "biology", "genomics" ]	Generation of Tandem Direct Duplications by Reversed-Ends Transposition of Maize Ac Elements	journal.pgen.1003691	null	[ [ "In addition to generating additional copies of coding sequences that can be used as substrates for gene evolution [1] , gene duplication may also cause immediate phenotypic impacts such as human disease [2] .", "Segmental duplications ( SD ) –two or more chromosomal segments with high homology–are common...	[ "Tandem direct duplications are a common feature of the genomes of eukaryotes ranging from yeast to human , where they comprise a significant fraction of copy number variations .", "The prevailing model for the formation of tandem direct duplications is non-allelic homologous recombination ( NAHR ) .", "Here we...	[ "The recent explosion of genome sequence data has greatly increased the need to understand the forces that shape eukaryotic genomes .", "A common feature of higher plant genomes is the presence of large numbers of duplications , often occurring as tandem repeats of thousands of base pairs .", "Despite the impor...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	The Diagnosis of Human Fascioliasis by Enzyme-Linked Immunosorbent Assay (ELISA) Using Recombinant Cathepsin L Protease	journal.pntd.0002414	null	[ [ "Fascioliasis , or liver fluke disease , is a food-borne infection caused by trematodes of the genus Fasciola .", "The disease has been traditionally viewed as of mainly veterinary importance because of the substantial production and economic losses it causes in livestock , particularly sheep and cattle ....	[ "Fascioliasis is a worldwide parasitic disease of domestic animals caused by helminths of the genus Fasciola .", "In many parts of the world , particularly in poor rural areas where animal disease is endemic , the parasite also infects humans .", "Adult parasites reside in the bile ducts of the host and therefo...	[ "Fascioliasis is a food-borne human disease caused by helminth parasites of the genus Fasciola .", "It is a global disease of domestic animals but its increased recognition as a major zoonosis has led to the World Health Organization including fascioliasis on the list of important human parasitic diseases .", "...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "helminths", "enzymes", "metalloproteases", "immunology", "enzymology", "parasitic diseases", "animals", "parasitology", "serine proteases", "developmental biology", "gastropods", "sporocysts", "sn...	A metalloprotease produced by larval Schistosoma mansoni facilitates infection establishment and maintenance in the snail host by interfering with immune cell function	journal.ppat.1007393	null	[ [ "Compatibility between parasites and their hosts is influenced by a wide variety of immune and immunosuppressive factors that arise over the co-evolutionary history of a host/parasite relationship .", "This is evident when examining the parasitism of gastropod molluscs by digenean trematodes .", "Snai...	[ "Metalloproteases ( MPs ) have demonstrated roles in immune modulation .", "In some cases , these enzymes are produced by parasites to influence host immune responses such that parasite infection is facilitated .", "One of the best examples of parasite-mediated immune modulation is the matrix metalloprotease ( ...	[ "Parasitic flatworms , or digenetic trematodes , cause a wide range of diseases of both medical and agricultural importance .", "Nearly all species of digenea require specific species of snail for their larval development and transmission .", "The factors underpinning snail host specificity and how they dictate...	2018
[ "Introduction", "Discussion", "Methods" ]	[ "evolutionary selection", "protein folding", "divergent evolution", "biophysics simulations", "forms of evolution", "theoretical biology", "biology", "evolutionary theory", "biophysics", "adaptation", "biophysic al simulations", "natural selection", "computational biology", "evolutionary b...	Evolutionary Dynamics on Protein Bi-stability Landscapes can Potentially Resolve Adaptive Conflicts	journal.pcbi.1002659	null	[ [ "New functional proteins are likely to evolve from existing proteins .", "Most existing proteins , however , are under selection to conserve their existing native structure in order to maintain functionality ( and also to avoid aggregation and proteolysis ) .", "Without such selective constraints , th...	[ "Experimental studies have shown that some proteins exist in two alternative native-state conformations .", "It has been proposed that such bi-stable proteins can potentially function as evolutionary bridges at the interface between two neutral networks of protein sequences that fold uniquely into the two differe...	[ "Proteins are essential molecules for performing a majority of functions in all biological systems .", "These functions often depend on the three-dimensional structures of proteins .", "Here , we investigate a fundamental question in molecular evolution: how can proteins acquire new advantageous structures via ...	2012
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "chemical ecology", "ecology", "gene identification and analysis", "genetics", "olfactory system", "molecular genetics", "biology", "sensory systems", "neuroethology", "neuroscience", "genetics and genomics" ]	A Single Sex Pheromone Receptor Determines Chemical Response Specificity of Sexual Behavior in the Silkmoth Bombyx mori	journal.pgen.1002115	null	[ [ "In insects and other animals , intraspecific communication between individuals of opposite sex is mediated in part by chemical signals called sex pheromones .", "In most moth species , male moths heavily rely on species-specific sex pheromones emitted by female moths to identify and orient towards an app...	[ "In insects and other animals , intraspecific communication between individuals of the opposite sex is mediated in part by chemical signals called sex pheromones .", "In most moth species , male moths rely heavily on species-specific sex pheromones emitted by female moths to identify and orient towards an appropr...	[ "Like many animal species , moths use chemical signals called sex pheromones to communicate with conspecific individuals of the opposite sex in the context of reproduction .", "Typically , male moths depend on sex pheromones emitted by conspecific females to identify and locate their mates .", "Therefore , the ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "eukaryotes", "computational biology" ]	Stochastic Noise and Synchronisation during Dictyostelium Aggregation Make cAMP Oscillations Robust	journal.pcbi.0030218	null	[ [ "Dictyostelium discoideum are social amoebae which normally live in forest soil , where they feed on bacteria [1] .", "Under conditions of starvation , Dictyostelium cells begin a programme of development during which they aggregate to eventually form spores atop a stalk of vacuolated cells .", "At th...	[ "Stable and robust oscillations in the concentration of adenosine 3′ , 5′-cyclic monophosphate ( cAMP ) are observed during the aggregation phase of starvation-induced development in Dictyostelium discoideum .", "In this paper we use mathematical modelling together with ideas from robust control theory to identif...	[ "The molecular network , which underlies the oscillations in the concentration of adenosine 3′ , 5′-cyclic monophosphate ( cAMP ) during the aggregation phase of starvation-induced development in Dictyostelium discoideum , achieves remarkable levels of robust performance in the face of environmental variations and ...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "cellular stress responses", "rna interference", "caenorhabditis", "enzymes", "gene regulation", "cell processes", "enzymology", "animals", "animal models", "caenorhabditis elegans", "model organisms", "experimental organism systems", "sequence motif analysis", "molecula...	WDR23 regulates NRF2 independently of KEAP1	journal.pgen.1006762	null	[ [ "In response to environmental and cellular stress , organisms must activate specific pathways to defend and protect against damage[1–3] .", "Such stressors include electrophiles , pathogens , and xenobiotics , many of which are carcinogens and activate the conserved cap-n-collar transcription factor NRF2 ...	[ "Cellular adaptation to stress is essential to ensure organismal survival .", "NRF2/NFE2L2 is a key determinant of xenobiotic stress responses , and loss of negative regulation by the KEAP1-CUL3 proteasome system is implicated in several chemo- and radiation-resistant cancers .", "Advantageously using C . elega...	[ "Chronic exposure to environmental stressors throughout life ( “the exposome” ) has been tied to several cancers in humans .", "Cellular adaptation to stress is essential to ensure organismal survival , and NRF2 is an exceptionally well-studied and key determinant of cellular stress responses that plays complex r...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "genomics", "biology", "computational biology", "metabolism", "genetics and genomics" ]	The CanOE Strategy: Integrating Genomic and Metabolic Contexts across Multiple Prokaryote Genomes to Find Candidate Genes for Orphan Enzymes	journal.pcbi.1002540	null	[ [ "Approximately 27% of all enzymatic activities recognized by the IUBMB [www . iubmb . org] are still sequence-orphan metabolic activities ( dubbed “orphan enzymes” for short ) in the UniProt databank [1] , a number that has decreased slowly over the past years [2]–[4] .", "It would , of course , be too ti...	[ "Of all biochemically characterized metabolic reactions formalized by the IUBMB , over one out of four have yet to be associated with a nucleic or protein sequence , i . e . are sequence-orphan enzymatic activities .", "Few bioinformatics annotation tools are able to propose candidate genes for such activities by...	[ "The discovery of the various metabolic functions catalyzed by enzymes encoded by the genes from the exponentially increasing number of sequenced genomes is one of the main focuses of bioinformatics tools today .", "However , most of these tools rely on already identified enzyme-coding gene or protein sequence in...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetic networks", "chemical compounds", "gene regulation", "organic compounds", "dna transcription", "fungi", "model organisms", "network analysis", "genome analysis", "acidic amino acids", "amino acids", "research and analysis methods", "saccharomyces", "computer and information science...	Elucidation of Genetic Interactions in the Yeast GATA-Factor Network Using Bayesian Model Selection	journal.pcbi.1004784	null	[ [ "Decades of research on gene regulatory networks have provided us with a wealth of knowledge on their topologies .", "However , even the best characterized networks contain many ambiguous interactions , discovered using a variety of experimental techniques that often cannot validate their presence conclus...	[ "Understanding the structure and function of complex gene regulatory networks using classical genetic assays is an error-prone procedure that frequently generates ambiguous outcomes .", "Even some of the best-characterized gene networks contain interactions whose validity is not conclusively proven .", "Founded...	[ "Gene regulatory networks underlie all key processes that enable a cell to maintain long-term homeostasis in a changing environment .", "Understanding the structure and function of complex gene networks is an experimentally difficult and error-prone procedure .", "Mechanistic mathematical modeling promises to a...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "biochemistry/protein chemistry" ]	Identification of Proteins Targeted by the Thioredoxin Superfamily in Plasmodium falciparum	journal.ppat.1000383	null	[ [ "The malarial parasite Plasmodium falciparum ( Pf ) possesses two major functional redox systems: The thioredoxin system [1] , [2] comprising NADPH , thioredoxin reductase , thioredoxin ( Trx ) [2] , [3] , and thioredoxin-dependent peroxiredoxins [4]–[8] , and a glutathione system comprising NADPH , glutathio...	[ "The malarial parasite Plasmodium falciparum possesses a functional thioredoxin and glutathione system comprising the dithiol-containing redox proteins thioredoxin ( Trx ) and glutaredoxin ( Grx ) , as well as plasmoredoxin ( Plrx ) , which is exclusively found in Plasmodium species .", "All three proteins belong...	[ "Protection from oxidative stress and efficient redox regulation are essential for malarial parasites which have to grow and multiply rapidly in various environments .", "As shown by glucose-6 phosphate dehydrogenase deficiency , a genetic variation protecting from malaria , the parasite–host cell unit is very su...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell death", "animal models", "caenorhabditis elegans", "model organisms", "apoptotic signaling", "radiobiology", "signaling in cellular processes", "ras signaling", "biology", "molecular biology", "signal transduction", "cell biology", "molecular cell biology" ]	Regulation of Caenorhabditis elegans p53/CEP-1–Dependent Germ Cell Apoptosis by Ras/MAPK Signaling	journal.pgen.1002238	null	[ [ "The p53 family of transcription factors is conserved throughout animal evolution [1] , [2] .", "In vertebrates the founding member , p53 , is a key tumour suppressor and is the most commonly mutated gene in human tumours .", "Two paralogues , p63 and p73 , have diverse roles in development and in res...	[ "Maintaining genome stability in the germline is thought to be an evolutionarily ancient role of the p53 family .", "The sole Caenorhabditis elegans p53 family member CEP-1 is required for apoptosis induction in meiotic , late-stage pachytene germ cells in response to DNA damage and meiotic recombination failure ...	[ "Germ cell apoptosis helps to ensure that only healthy germ cells contribute to the next generation .", "The C . elegans p53 family member CEP-1 plays an important role in inducing apoptosis in damaged germ cells .", "CEP-1 protein is maximally expressed in late-stage pachytene cells , which are the only cells ...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "chemical compounds", "chromosome structure and function", "molecular probe techniques", "dna-binding proteins", "galactose", "carbohydrates", "organic compounds", "telomeres", "dna replication", "dna", "molecular biology techniques", "research and analysis methods", "probe hybridization", ...	Ku Binding on Telomeres Occurs at Sites Distal from the Physical Chromosome Ends	journal.pgen.1006479	null	[ [ "The Ku proteins , initially identified as an auto-antigen in sera from patients suffering of scleroderma-polymyositis overlap syndrome [1] , are highly conserved in eukaryotes and there are also prokaryotic equivalents [2] .", "In eukaryotes , two subunits , Ku70 and Ku80 , form a complex and its crystal...	[ "The Ku complex binds non-specifically to DNA breaks and ensures repair via NHEJ .", "However , Ku is also known to bind directly to telomeric DNA ends and its presence there is associated with telomere capping , but avoiding NHEJ .", "How the complex discriminates between a DNA break and a telomeric extremity ...	[ "The Ku complex binds to and mediates the rejoining of two DNA ends that were generated by a double-stranded DNA break in the genome .", "However , Ku is known to be present at telomeres as well .", "If it would induce end-to-end joining there , it would create chromosome end-fusions that inevitably will lead t...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "onchocerca volvulus", "diagnostic radiology", "ultrasound imaging", "helminths", "vertebrates", "parasitic diseases", "dogs", "onchocerca", "animals", "mammals", "nematode infections", "pharmaceutics", "research and analy...	Evaluation of oxfendazole in the treatment of zoonotic Onchocerca lupi infection in dogs	journal.pntd.0006218	null	[ [ "The genus Onchocerca ( Spirurida , Onchocercidae ) encompasses parasitic nematodes mainly associated to ungulates , with the exception of Onchocerca volvulus in humans and Onchocerca lupi in carnivores [1–3] .", "While O . volvulus is a well-known parasite estimated to infect 37 million people globally (...	[ "The genus Onchocerca encompasses parasitic nematodes including Onchocerca volvulus , causative agent of river blindness in humans , and the zoonotic Onchocerca lupi infecting dogs and cats .", "In dogs , O . lupi adult worms cause ocular lesions of various degrees while humans may bear the brunt of zoonotic onch...	[ "The genus Onchocerca ( Spirurida , Onchocercidae ) includes Onchocerca volvulus , which is estimated to infect at least 37 million people globally , and zoonotic Onchocerca lupi in carnivores .", "Infection by O . lupi has been reported in dogs and cats from several European countries and recently also in the U ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computer science/applications", "computational biology/comparative sequence analysis", "virology/immunodeficiency viruses", "computational biology/evolutionary modeling", "mathematics/statistics" ]	An Evolutionary Model-Based Algorithm for Accurate Phylogenetic Breakpoint Mapping and Subtype Prediction in HIV-1	journal.pcbi.1000581	null	[ [ "Many RNA viruses have evolutionary rates that hover near the mutational speed limit [1] permitting them to generate incredible sequence variability among circulating strains in a relatively short time [2] .", "Bottleneck events , such as viral introduction to new populations or species of hosts , followe...	[ "Genetically diverse pathogens ( such as Human Immunodeficiency virus type 1 , HIV-1 ) are frequently stratified into phylogenetically or immunologically defined subtypes for classification purposes .", "Computational identification of such subtypes is helpful in surveillance , epidemiological analysis and detect...	[ "There are nine different subtypes of the main group of HIV-1 , each originating as a distinct subepidemic of HIV-1 .", "The distribution of subtypes is often unique to a given geographic region of the world and constitutes a useful epidemiological and surveillance resource .", "The effects of viral subtype on ...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "infectious diseases/epidemiology and control of infectious diseases" ]	Effect of Village-wide Use of Long-Lasting Insecticidal Nets on Visceral Leishmaniasis Vectors in India and Nepal: A Cluster Randomized Trial	journal.pntd.0000587	null	[ [ "Visceral leishmaniasis ( VL ) , also known as kala azar , is a life-threatening vector-borne disease with a fatal outcome if left untreated .", "A large proportion of the 500 , 000 annual cases and 60 , 000 deaths occur in the poor rural communities within the Indian subcontinent [1] .", "In this reg...	[ "Visceral leishmaniasis ( VL ) control in the Indian subcontinent is currently based on case detection and treatment , and on vector control using indoor residual spraying ( IRS ) .", "The use of long-lasting insecticidal nets ( LN ) has been postulated as an alternative or complement to IRS .", "Here we tested...	[ "Visceral leishmaniasis ( VL ) is a vector-borne disease causing at least 60 , 000 deaths each year amongst an estimated half million cases , and until recently there have been no significant initiatives to reduce this burden .", "However , in 2005 , the governments of India , Bangladesh and Nepal signed a memora...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "gram positive bacteria", "acute cardiovascular problems", "heart failure", "infectious diseases", "bacterial diseases", "medicine and health sciences", "arrhythmia", "cell biology", "biology and life sciences", "cardiovascular diseases", "microbiology", "molecular cell biolo...	Streptococcus pneumoniae Translocates into the Myocardium and Forms Unique Microlesions That Disrupt Cardiac Function	journal.ppat.1004383	null	[ [ "Severe community-acquired pneumonia ( CAP ) carries an extensively documented risk for adverse cardiac events such as congestive heart failure , arrhythmias , and myocardial infarction .", "A meta-analysis of 19 observational studies determined that the pooled incidence rate for cardiac complications dur...	[ "Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia .", "Herein , we describe previously unrecognized microscopic lesions ( microlesions ) formed within t...	[ "Hospitalization for community-acquired pneumonia carries a documented risk for adverse cardiac events .", "These occur during infection and contribute to elevated mortality rates in convalescent individuals up to 1 year thereafter .", "We describe a previously unrecognized pathogenic mechanism by which Strepto...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "neuromuscular junctions", "nervous system", "neurodegenerative diseases", "animal models of disease", "electrophysiology", "neuroscience", "animals", "motor neurons", "animal models", "drosophila melanogaster", "model organisms", "experimen...	Comparison of independent screens on differentially vulnerable motor neurons reveals alpha-synuclein as a common modifier in motor neuron diseases	journal.pgen.1006680	null	[ [ "The term “motor neuron disease” refers to a group of disorders in which motor neurons are a prominent pathological target .", "Such disorders are generally severely disabling and frequently fatal within months to years of diagnosis .", "Effective treatments for many motor neuron diseases are currentl...	[ "The term “motor neuron disease” encompasses a spectrum of disorders in which motor neurons are the primary pathological target .", "However , in both patients and animal models of these diseases , not all motor neurons are equally vulnerable , in that while some motor neurons are lost very early in disease , oth...	[ "The term “motor neuron disease” refers to a group of disorders , causing progressive paralysis of affected patients due to the degeneration of motor neurons cells which control voluntary movements .", "Importantly , not all motor neurons appear to be affected in the same way , with those that control the face be...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/bacterial infections", "microbiology/applied microbiology", "microbiology/environmental microbiology", "microbiology" ]	Asymptomatic Renal Colonization of Humans in the Peruvian Amazon by Leptospira	journal.pntd.0000612	null	[ [ "Leptospirosis is a zoonotic disease caused by spirochetes of the genus Leptospira .", "Found worldwide , leptospirosis is more common in tropical and sub-tropical areas where environmental and socioeconomic conditions favor its transmission .", "It has been identified in recent years as a global publ...	[ "Renal carriage and shedding of leptospires is characteristic of carrier or maintenance animal hosts .", "Sporadic reports indicate that after infection , humans may excrete leptospires for extended periods .", "We hypothesized that , like mammalian reservoir hosts , humans develop asymptomatic leptospiruria in...	[ "Leptospirosis is a bacterial disease commonly transmitted from animals to humans .", "The more than 200 types of spiral-shaped bacteria ( spirochetes ) in the genus Leptospira are classified as pathogenic , intermediately pathogenic , or saprophytic ( meaning not causing infection in any mammal ) based on their ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "plant growth and development", "plant biology", "biology" ]	Short Day–Mediated Cessation of Growth Requires the Downregulation of AINTEGUMENTALIKE1 Transcription Factor in Hybrid Aspen	journal.pgen.1002361	null	[ [ "The ability to adapt to changes in the environment is crucial to the survival of both animals and plants .", "Plants , unlike animals , are sessile organisms and have therefore evolved highly sophisticated mechanisms to anticipate seasonal changes and modulate their patterns of growth and development .",...	[ "Day length is a key environmental cue regulating the timing of major developmental transitions in plants .", "For example , in perennial plants such as the long-lived trees of the boreal forest , exposure to short days ( SD ) leads to the termination of meristem activity and bud set ( referred to as growth cessa...	[ "Day length is a critical and robust environmental cue utilised by plants to modulate their patterns of growth to adapt to changing seasonal conditions .", "In perennial plants such as long-lived trees of the boreal forest , reduction in day length ( short day signal/SD ) induces the cessation of growth prior to ...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Why Latrines Are Not Used: Communities’ Perceptions and Practices Regarding Latrines in a Taenia solium Endemic Rural Area in Eastern Zambia	journal.pntd.0003570	null	[ [ "Taenia solium taeniosis/cysticercosis is an important neglected parasitic zoonosis prevailing in many developing countries .", "The adult tapeworm lives in the intestines of humans , causing taeniosis , while the metacestode larval stage ( cysticercus ) usually develops in pigs following the ingestion of...	[ "Taenia solium cysticercosis is a neglected parasitic zoonosis occurring in many developing countries .", "Socio-cultural determinants related to its control remain unclear .", "Studies in Africa have shown that the underuse of sanitary facilities and the widespread occurrence of free-roaming pigs are the major...	[ "Livestock owners from small scale farms are most vulnerable for Neglected Zoonotic Diseases ( NZD ) in developing countries and their risk behavior leads to more intense and complex transmission patterns .", "Studies in Africa have shown that the underuse of sanitary facilities and the widespread occurrence of f...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Is Model Fitting Necessary for Model-Based fMRI?	journal.pcbi.1004237	null	[ [ "The advent of fMRI revolutionized psychology as it allowed , for the first time , the noninvasive mapping of human cognition .", "Despite this progress , traditional fMRI analyses are limited in that they can , for the most part , only ascertain the involvement of an area in a task but not its precise ro...	[ "Model-based analysis of fMRI data is an important tool for investigating the computational role of different brain regions .", "With this method , theoretical models of behavior can be leveraged to find the brain structures underlying variables from specific algorithms , such as prediction errors in reinforcemen...	[ "In recent years , model-based fMRI has emerged as a powerful technique in psychology and neuroscience .", "With this method , computational models of behavior can be leveraged to identify where , whether and how different algorithms are implemented in the brain .", "Yet this approach seems to have an Achilles ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Zinc Piracy as a Mechanism of Neisseria meningitidis for Evasion of Nutritional Immunity	journal.ppat.1003733	null	[ [ "The outer membrane of Gram-negative bacteria functions as a protective barrier against harmful compounds from the environment , including many antibiotics .", "Most nutrients can pass the outer membrane by passive diffusion via pore-forming proteins , known as porins .", "However , diffusion can only...	[ "The outer membrane of Gram-negative bacteria functions as a permeability barrier that protects these bacteria against harmful compounds in the environment .", "Most nutrients pass the outer membrane by passive diffusion via pore-forming proteins known as porins .", "However , diffusion can only satisfy the gro...	[ "The sequestration of essential nutrient metals is a first line of defense used by vertebrates to limit the growth of invading pathogens , a process termed “nutritional immunity . ”", "As a part of this defense mechanism , neutrophils and other cells produce massive amounts of calprotectin , a protein that limits...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virulence factors and mechanisms", "pathology/pathophysiology", "virology/animal models of infection", "virology", "virology/mechanisms of resistance and susceptibility, including host genetics" ]	Transforming Growth Factor-β: Activation by Neuraminidase and Role in Highly Pathogenic H5N1 Influenza Pathogenesis	journal.ppat.1001136	null	[ [ "Transforming growth factor-β1 ( TGF-β ) is the prototypic member of a family of multifunctional cytokines that modulate diverse cellular , developmental , and immunological processes ( reviewed in [1]–[3] ) .", "TGF-β is secreted by virtually all cells as a biologically inactive molecule termed latent TG...	[ "Transforming growth factor-beta ( TGF-β ) , a multifunctional cytokine regulating several immunologic processes , is expressed by virtually all cells as a biologically inactive molecule termed latent TGF-β ( LTGF-β ) .", "We have previously shown that TGF-β activity increases during influenza virus infection in ...	[ "Transforming growth factor-beta ( TGF-β ) is a multifunctional protein that serves as a global regulator of immunity by controlling the initiation and resolution of inflammatory responses .", "A pathogen that can regulate TGF-β activation could promote an immune-privileged state for itself within its host .", ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "neuroscience/motor systems", "computer science/systems and control theory", "neuroscience/theoretical neuroscience" ]	Bayesian Integration and Non-Linear Feedback Control in a Full-Body Motor Task	journal.pcbi.1000629	null	[ [ "Recent studies have shown that , for many motor tasks , human subjects take uncertainty in their sensory feedback into account .", "They often use knowledge of uncertainty in a way that is close to optimal in a statistical sense both in their perception of the world [c . f . 1] , [2] , [3] and for severa...	[ "A large number of experiments have asked to what degree human reaching movements can be understood as being close to optimal in a statistical sense .", "However , little is known about whether these principles are relevant for other classes of movements .", "Here we analyzed movement in a task that is similar ...	[ "There is a growing body of work demonstrating that humans are close to statistically optimal in both their perception of the world and their actions on it .", "That is , we seem to combine information from our sensors with the constraints and costs of moving to minimize our errors and effort .", "Most of the e...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Efficacy of Recombinant Canine Distemper Virus Expressing Leishmania Antigen against Leishmania Challenge in Dogs	journal.pntd.0003914	null	[ [ "Leishmaniasis is a major infectious disease caused by the parasitic protozoan Leishmania in both humans and dogs .", "It occurs across 88 countries and affects 12 million people in tropical and subtropical regions .", "The World Health Organization reported that in 1993 , leishmaniasis was one of the...	[ "Canine distemper virus ( CDV ) vaccination confers long-term protection against CDV reinfection .", "To investigate the utility of CDV as a polyvalent vaccine vector for Leishmania , we generated recombinant CDVs , based on an avirulent Yanaka strain , that expressed Leishmania antigens: LACK , TSA , or LmSTI1 (...	[ "More than 1 million new cases of leishmaniasis occur throughout the world every year .", "Leishmaniasis typically presents as one of two clinical forms , either cutaneous or visceral .", "Dogs harboring Leishmania act as reservoirs , and are closely associated with human infections in South America and souther...	2015
[ "Introduction", "Methods", "Results", "Discussion", "Supporting Information" ]	[ "viruses", "animals", "infectious diseases", "virology" ]	Effective Post-Exposure Treatment of Ebola Infection	journal.ppat.0030002	null	[ [ "Editor's Note: The potential efficacy of pre- and post-exposure prophylaxis against Ebola virus infection , as well as the fundamentally important question of whether neutralizing antibodies are important for Ebola virus resistance , is addressed by a related manuscript in this issue of PLoS Pathogens .", ...	[ "Ebola viruses are highly lethal human pathogens that have received considerable attention in recent years due to an increasing re-emergence in Central Africa and a potential for use as a biological weapon .", "There is no vaccine or treatment licensed for human use .", "In the past , however , important advanc...	[ "Being highly pathogenic for humans and monkeys and the subject of former weapons programs makes Ebola virus one of the most feared pathogens worldwide today .", "Due to a lack of licensed pre- and post-exposure intervention , our current response depends on rapid diagnostics , proper isolation procedures , and s...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "physics", "systems biology", "developmental biology", "computer science", "mathematics", "applied mathematics", "biology", "computational biology", "computerized simulations", "biophysics", "neuroscience", "nonlinear dynamics" ]	A BMP-FGF Morphogen Toggle Switch Drives the Ultrasensitive Expression of Multiple Genes in the Developing Forebrain	journal.pcbi.1003463	null	[ [ "The formation of borders between compartments and body parts is crucial for embryonic development [1] , [2] , [3] , [4] , [5] .", "A challenge in understanding border formation is the elucidation of mechanisms that convert shallow morphogen gradients into sharp expression domains [3] , [6] .", "Such ...	[ "Borders are important as they demarcate developing tissue into distinct functional units .", "A key challenge is the discovery of mechanisms that can convert morphogen gradients into tissue borders .", "While mechanisms that produce ultrasensitive cellular responses provide a solution , how extracellular morph...	[ "During development , morphogen gradients play a crucial role in transforming a uniform field of cells into regions with distinct cell identities ( marked by the expression of specific genes ) .", "Finding mechanisms that convert morphogen gradients into sharp borders of gene expression , however , remains a chal...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "genome sequencing", "genomics", "genetic polymorphism", "genetic association studies", "genetics", "population genetics", "biology", "human genetics", "genetics of disease", "genetic drift" ]	Re-sequencing Expands Our Understanding of the Phenotypic Impact of Variants at GWAS Loci	journal.pgen.1004147	null	[ [ "Genome-wide association studies ( GWAS ) based on common single nucleotide polymorphisms ( SNPs ) have unequivocally demonstrated the contribution of thousands of loci to risk for common diseases and to variation in quantitative traits .", "However for most such complex phenotypes , the variants identifi...	[ "Genome-wide association studies ( GWAS ) have identified >500 common variants associated with quantitative metabolic traits , but in aggregate such variants explain at most 20–30% of the heritable component of population variation in these traits .", "To further investigate the impact of genotypic variation on m...	[ "Abnormal serum levels of various metabolites , including measures relevant to cholesterol , other fats , and sugars , are known to be risk factors for cardiovascular disease and type 2 diabetes .", "Identification of the genes that play a role in generating such abnormalities could advance the development of new...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "antimicrobials", "medicine and health sciences", "rna interference", "nucleobases", "drugs", "microbiology", "antifungals", "nucleotides", "mutation", "uracils", "genome analysis", "pharmacology", "epigenetics", "molecular biology techniques", "nucleotide mapping", "research and analy...	Broad antifungal resistance mediated by RNAi-dependent epimutation in the basal human fungal pathogen Mucor circinelloides	journal.pgen.1007957	null	[ [ "Mucormycosis , an emerging fungal infection , is notable for very high mortality , ranging from 50% for rhino-orbital-cerebral infections to 90% in disseminated infections [1] .", "Mucormycosis primarily affects immunocompromised patients: most commonly patients with diabetes , followed by those with hem...	[ "Mucormycosis—an emergent , deadly fungal infection—is difficult to treat , in part because the causative species demonstrate broad clinical antifungal resistance .", "However , the mechanisms underlying drug resistance in these infections remain poorly understood .", "Our previous work demonstrated that one ma...	[ "The emerging infection mucormycosis causes high mortality in part because the major causative fungi , including Mucor circinelloides , are resistant to most clinically available antifungal drugs .", "We previously discovered an RNA interference-based resistance mechanism , epimutation , through which M . circine...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	AKTIP/Ft1, a New Shelterin-Interacting Factor Required for Telomere Maintenance	journal.pgen.1005167	null	[ [ "Mammalian telomeres consist of double stranded TTAGGG repeats that terminate with a single stranded 3' overhang .", "These repeats are added to chromosome ends by telomerase to compensate for the terminal DNA loss that occurs at each replication cycle due to the intrinsic inability of the DNA replication...	[ "Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes from incomplete replication , degradation and detection as DNA breaks .", "Mammalian telomeres are protected by shelterin , a multiprotein complex that binds the TTAGGG telomeric repeats and recruits a series of additional factors ...	[ "Chromosome ends are capped by specialized structures called telomeres , which protect chromosomes from deterioration , incomplete replication and end-to-end fusion .", "Defects in telomere structure and/or function may have a strong impact on human health , leading to premature aging and a variety of diseases in...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/embryology", "dermatology/pediatric skin diseases, including genetic diseases", "developmental biology", "cell biology/developmental molecular mechanisms", "cell biology/extra-cellular matrix" ]	Genetic Analysis of Fin Development in Zebrafish Identifies Furin and Hemicentin1 as Potential Novel Fraser Syndrome Disease Genes	journal.pgen.1000907	null	[ [ "Fraser Syndrome ( FS ) is a recessive polygenic , multisystem congenital human disorder characterised largely by syndactyly of the soft tissue of the digits , cryptophthalmos ( fusion of the eye lids ) and renal agenesis , although a myriad of other variable epithelial malformations have been reported , unde...	[ "Using forward genetics , we have identified the genes mutated in two classes of zebrafish fin mutants .", "The mutants of the first class are characterized by defects in embryonic fin morphogenesis , which are due to mutations in a Laminin subunit or an Integrin alpha receptor , respectively .", "The mutants o...	[ "There are a large number of human genetic syndromes with limb and digit deformities .", "It has been shown that the genes underlying these syndromes are well conserved in evolution , and most perform the same role even in the fins of fish .", "One such human syndrome is Fraser Syndrome , characterized by a num...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "brain electrophysiology", "vertebrates", "electrophysiology", "mice", "neuroscience", "animals", "mammals", "materials science", "bioassays and physiological analysis", "oligomers", "research and analysis methods", "infectious diseases", "size-exclusion chr...	Early existence and biochemical evolution characterise acutely synaptotoxic PrPSc	journal.ppat.1007712	null	[ [ "Prion diseases are transmissible neurodegenerative disorders with human phenotypes including Creutzfeldt-Jakob disease ( CJD ) , Gerstmann-Sträussler-Scheinker syndrome ( GSS ) and Kuru , while the principal animal diseases comprise scrapie in sheep and goats , bovine spongiform encephalopathy ( “mad cow” di...	[ "Although considerable evidence supports that misfolded prion protein ( PrPSc ) is the principal component of “prions” , underpinning both transmissibility and neurotoxicity , clear consensus around a number of fundamental aspects of pathogenesis has not been achieved , including the time of appearance of neurotoxi...	[ "Although evidence clearly supports that misfolded prion protein ( PrPSc ) is the principal component of “prions” , underpinning both transmissibility and neurotoxicity , consensus is lacking around the time of appearance and biochemical profile of neurotoxic species during disease evolution .", "Employing an ele...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell walls", "cryptococcus neoformans", "medicine and health sciences", "cryptococcus", "pathology and laboratory medicine", "pathogens", "cell cycle and cell division", "population genetics", "ploidy", "microbiology", "cell processes", "fungi", "experimental organism systems", "populatio...	The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis	journal.ppat.1006978	null	[ [ "Fungi change shape in response to environmental stimuli .", "These morphogenic transitions drive pathogenesis and allow fungi to occupy different environmental niches .", "Dimorphic fungi undergo a yeast-to-hyphal transition in response to changing temperature , while the pleomorphic gut resident fun...	[ "Fungal cells change shape in response to environmental stimuli , and these morphogenic transitions drive pathogenesis and niche adaptation .", "For example , dimorphic fungi switch between yeast and hyphae in response to changing temperature .", "The basidiomycete Cryptococcus neoformans undergoes an unusual m...	[ "Changes in cell shape underlie fungal pathogenesis by allowing immune evasion and dissemination .", "Aspergillus and Candida albicans hyphae drive tissue penetration .", "Histoplasma capsulatum and C . albicans yeast growth allows evasion and dissemination .", "As major virulence determinants , morphogenic t...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	NLRC5 Exclusively Transactivates MHC Class I and Related Genes through a Distinctive SXY Module	journal.pgen.1005088	null	[ [ "Nucleotide-binding oligomerization domain ( NOD ) -like receptors ( NLRs ) constitute a family of innate immune receptors involved mainly in inflammatory responses and cell death .", "The NLR family member CIITA instead functions as the master transcriptional regulator of major histocompatibility complex...	[ "MHC class II ( MHCII ) genes are transactivated by the NOD-like receptor ( NLR ) family member CIITA , which is recruited to SXY enhancers of MHCII promoters via a DNA-binding “enhanceosome” complex .", "NLRC5 , another NLR protein , was recently found to control transcription of MHC class I ( MHCI ) genes .", ...	[ "Major histocompatibility complex class I ( MHCI ) molecules are central to immunity and immunological disorders , and constitute a major obstacle in organ transplantation .", "It is therefore vital to gain insight into the regulation of their expression .", "NLRC5 was recently found to regulate MHCI gene trans...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "parastic protozoans", "medicine", "infectious diseases", "trypanosoma", "neglected tropical diseases", "protozoology", "biology", "microbiology" ]	Neopterin Is a Cerebrospinal Fluid Marker for Treatment Outcome Evaluation in Patients Affected by Trypanosoma brucei gambiense Sleeping Sickness	journal.pntd.0002088	null	[ [ "Sleeping sickness , also known as human African trypanosomiasis ( HAT ) , is a neglected parasitic disease widespread in sub-Saharan Africa where it mainly afflicts rural communities [1] .", "According to the most recent published data , 10'000 new cases were reported in 2009 [2] .", "More than ninet...	[ "Post-therapeutic follow-up is essential to confirm cure and to detect early treatment failures in patients affected by sleeping sickness ( HAT ) .", "Current methods , based on finding of parasites in blood and cerebrospinal fluid ( CSF ) and counting of white blood cells ( WBC ) in CSF , are imperfect .", "Ne...	[ "The reduction of the number of lumbar punctures performed during the follow-up of patients affected by sleeping sickness ( HAT ) is considered a research priority .", "Follow-up , consisting of the examination of cerebrospinal fluid ( CSF ) for presence of parasites and for the number of leukocytes , is necessar...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "antimicrobials", "medicine and health sciences", "gut bacteria", "microbiome", "immune cells", "melioidosis", "drugs", "immunology", "microbiology", "animal models", "bacterial diseases", "model organisms", "antibiotics", "experimental organism systems", "pharmacology",...	The gut microbiota as a modulator of innate immunity during melioidosis	journal.pntd.0005548	null	[ [ "Melioidosis is a frequent cause of community-acquired sepsis in Southeast Asia and northern Australia [1 , 2] .", "Pneumonia is the presenting symptom in most adult patients [3] and results in a rapidly progressive illness with a high mortality up to 40% [1 , 3] .", "The disease is caused by Burkhold...	[ "Melioidosis , caused by the Gram-negative bacterium Burkholderia pseudomallei , is an emerging cause of pneumonia-derived sepsis in the tropics .", "The gut microbiota supports local mucosal immunity and is increasingly recognized as a protective mediator in host defenses against systemic infection .", "Here ,...	[ "Melioidosis is a common cause of community-acquired pneumonia and sepsis in Asia .", "The causative agent , Burkholderia pseudomallei , is listed as a potential bioterror weapon .", "The intestinal microbiota has been suggested to be a modulator of innate immune defenses against bacterial infections .", "Her...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fourier analysis", "medicine and health sciences", "engineering and technology", "signal processing", "brain", "random variables", "neuroscience", "covariance", "simulation and modeling", "mathematics", "brain mapping", "white noise", "neuroimaging", "research and analysis methods", "im...	Dynamic decomposition of spatiotemporal neural signals	journal.pcbi.1005540	null	[ [ "Human neocortex has an impressively complex organization .", "Cortical electrical activity is determined by dynamic properties of neurons that are wired together in large cortical networks .", "These neuronal networks generate measurable time series with characteristic spatial and temporal structure ...	[ "Neural signals are characterized by rich temporal and spatiotemporal dynamics that reflect the organization of cortical networks .", "Theoretical research has shown how neural networks can operate at different dynamic ranges that correspond to specific types of information processing .", "Here we present a dat...	[ "In neuroscience , researchers are often interested in the modulations of specific signal components ( e . g . , oscillations in a particular frequency band ) , that have to be extracted from a background of both rhythmic and non-rhythmic activity .", "As the interfering background signals often have higher ampli...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "neuroscience/theoretical neuroscience", "neuroscience/sensory systems", "computational biology/computational neuroscience" ]	Spike-Based Population Coding and Working Memory	journal.pcbi.1001080	null	[ [ "Our senses furnish us with information about the external world that is ambiguous and corrupted by noise .", "Taking this uncertainty into account is crucial for a successful interaction with our environment .", "Psychophysical studies have shown that animals and humans can behave as optimal Bayesian...	[ "Compelling behavioral evidence suggests that humans can make optimal decisions despite the uncertainty inherent in perceptual or motor tasks .", "A key question in neuroscience is how populations of spiking neurons can implement such probabilistic computations .", "In this article , we develop a comprehensive ...	[ "Most of our daily actions are subject to uncertainty .", "Behavioral studies have confirmed that humans handle this uncertainty in a statistically optimal manner .", "A key question then is what neural mechanisms underlie this optimality , i . e . how can neurons represent and compute with probability distribu...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "methods and resources", "multivariate analysis", "fungi", "model organisms", "mathematics", "statistics (mathematics)", "genome analysis", "experimental organism systems", "molecular biology techniques", "mutagenesis and gene deletion techniques", "research and analysis methods", "saccharomyc...	High-dimensional single-cell phenotyping reveals extensive haploinsufficiency	journal.pbio.2005130	null	[ [ "The concepts of dominance and recessiveness were originally formulated by Gregor Mendel [1] and are still fundamental to modern genetics .", "Loss-of-function mutations are mostly recessive and rarely dominant in diploid organisms .", "Haploinsufficiency is a rare manifestation of the dominant phenot...	[ "Haploinsufficiency , a dominant phenotype caused by a heterozygous loss-of-function mutation , has been rarely observed .", "However , high-dimensional single-cell phenotyping of yeast morphological characteristics revealed haploinsufficiency phenotypes for more than half of 1 , 112 essential genes under optimal...	[ "Diploid organisms harboring a wild-type gene and a loss-of-function mutation are called heterozygotes .", "They are expected to have weak or no individual phenotypes because the mutation is compensated for by the intact allele .", "The dominant inheritance of phenotypes in heterozygotes is an exceptional pheno...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational neuroscience", "single neuron function", "biology", "computational biology" ]	Location-Dependent Effects of Inhibition on Local Spiking in Pyramidal Neuron Dendrites	journal.pcbi.1002550	null	[ [ "The sensory , motor , and cognitive functions of neocortical circuits depend critically on synaptic interactions between pyramidal neurons ( PN ) , the principal excitatory neurons of the neocortex , and a multitude of inhibitory interneuron types [1] , [2] .", "Understanding the “arithmetic” governing t...	[ "Cortical computations are critically dependent on interactions between pyramidal neurons ( PNs ) and a menagerie of inhibitory interneuron types .", "A key feature distinguishing interneuron types is the spatial distribution of their synaptic contacts onto PNs , but the location-dependent effects of inhibition a...	[ "Establishing how inhibitory neurons shape the computing functions of neural circuits is crucial to understanding both normal function and dysfunction in the human brain .", "It has been known for over a century that different classes of inhibitory interneurons project to different sub-regions of the neurons they...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	A Power-Law Dependence of Bacterial Invasion on Mammalian Host Receptors	journal.pcbi.1004203	null	[ [ "Pathogenic bacteria such as Yersinia pseudotuberculosis and Listeria monocytogenes exploit a latent phagocytic activity in gut epithelia to pass into deeper tissues that are optimal for survival and proliferation [1] .", "Particularly well studied is the 'zipper' phagocytic process used by Yersinia: Enve...	[ "Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization .", "Bacterial uptake entails successive , increasingly strong associations between receptors on the surface of bacteria and hosts .", "Even with genetically identical cell...	[ "Uptake of bacteria by mammalian cells is highly variable within a population of host cells and between host cell types .", "A detailed but unwieldy mechanistic model describing individual host-pathogen receptor binding events is captured by a simple power-law dependence on the concentration of the host receptors...	2015

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