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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "hematology/acute lymphoblastic leukemia", "hematology/pediatric hematology", "molecular biology/transcription elongation", "oncology/hematological malignancies", "hematology/acute myeloid leukemia" ]	Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia	journal.pbio.1000249	Investigation of the activity of a family of fusion proteins that cause aggressive leukemia suggests transcriptional elongation as a new mechanism for oncogenic transformation.	[ [ "Mixed-lineage leukemia ( MLL ) is a particularly aggressive subtype of acute leukemia with a very dismal prognosis .", "This disease is caused by chromosomal aberrations , mostly translocations , affecting Chromosome 11 at band q23 .", "This chromosomal locus contains the gene for the histone H3 lysi...	[ "Fusion proteins composed of the histone methyltransferase mixed-lineage leukemia ( MLL ) and a variety of unrelated fusion partners are highly leukemogenic .", "Despite their prevalence , particularly in pediatric acute leukemia , many molecular details of their transforming mechanism are unknown .", "Here , w...	[ "The expression level of a gene needs to be precisely adjusted to ensure proper function .", "Adjustments can be imposed at different stages during the overall process of gene expression , including transcription initiation , transcript elongation , and transcript processing .", "If control of one of these mech...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "medicine and health sciences", "engineering and technology", "membrane potential", "electrophysiology", "endocrine physiology", "diabetes mellitus", "biological systems engineering", "bioengineering", "computer and information sciences", "biophysics", "metabolic disorders", ...	Phase Transitions in the Multi-cellular Regulatory Behavior of Pancreatic Islet Excitability	journal.pcbi.1003819	null	[ [ "Most biological systems exist as dynamic multicellular structures where distinct functionalities are generated through cellular interactions .", "While important for proper function , the complexity in network architecture , cellular dynamics , as well as the presence of heterogeneity , noise and biologi...	[ "The pancreatic islets of Langerhans are multicellular micro-organs integral to maintaining glucose homeostasis through secretion of the hormone insulin .", "β-cells within the islet exist as a highly coupled electrical network which coordinates electrical activity and insulin release at high glucose , but leads ...	[ "As science has successfully broken down the elements of many biological systems , the network dynamics of large-scale cellular interactions has emerged as a new frontier .", "One way to understand how dynamical elements within large networks behave collectively is via mathematical modeling .", "Diabetes , whic...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "systems biology", "biochemistry", "biochemical simulations", "computer and information sciences", "computer modeling", "biology and life sciences", "computational biology" ]	Exact Hybrid Particle/Population Simulation of Rule-Based Models of Biochemical Systems	journal.pcbi.1003544	null	[ [ "Cell signaling encompasses the collection of cellular processes that sample the extracellular environment , process and transmit that information to the interior of the cell , and regulate cellular responses .", "In a typical scenario , molecules outside of the cell bind to cognate receptors on the cell ...	[ "Detailed modeling and simulation of biochemical systems is complicated by the problem of combinatorial complexity , an explosion in the number of species and reactions due to myriad protein-protein interactions and post-translational modifications .", "Rule-based modeling overcomes this problem by representing m...	[ "Rule-based modeling is a modeling paradigm that addresses the problem of combinatorial complexity in biochemical systems .", "The key idea is to specify only those components of a biological macromolecule that are directly involved in a biochemical transformation .", "Until recently , this “pattern-based” appr...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "enzyme-linked immunoassays", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "animals", "parasitology", "vaccines", "preventive medicine", "parasitemia", "bacterial diseases", "protozoans", "vaccination an...	Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial	journal.pntd.0005070	null	[ [ "Although there has been a decrease in malaria incidence globally during the past 15 years ( ~37% ) [1] , this infection remains a major public health problem with 214 million cases and 438 , 000 deaths estimated in 2015 [1] .", "Plasmodium falciparum ( Pf ) causes the greatest malaria burden particularly...	[ "Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites ( RAS ) results in high-level protection against infection .", "Only two volunteers have been similarly immunized with P . vivax ( Pv ) RAS , and both were protected .", "A phase 2 controlled clinical trial...	[ "Despite the advances in Plasmodium falciparum ( Pf ) vaccine development , progress in developing P . vivax ( Pv ) vaccines lags far behind .", "Immunization via mosquito bites with Pf radiation-attenuated sporozoites ( RAS ) has been the gold standard model for induction of sterile protection against malaria in...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "neurochemistry", "chemical compounds", "decision making", "predator-prey dynamics", "population dynamics", "social sciences", "neuroscience", "organic compounds", "hormones", "cognitive psychology", "animal behavior", "cognition", "amines", "neurotr...	Interrupting behaviour: Minimizing decision costs via temporal commitment and low-level interrupts	journal.pcbi.1005916	null	[ [ "The full model of foraging under predation risk that we consider below includes a number of detailed components .", "Therefore , in order to illustrate and provide intuition for the workings of interruption , we start with a simple , stripped-down model .", "Consider an animal ( e . g . , a rat ) for...	[ "Ideal decision-makers should constantly assess all sources of information about opportunities and threats , and be able to redetermine their choices promptly in the face of change .", "However , perpetual monitoring and reassessment impose inordinate sensing and computational costs , making them impractical for ...	[ "Animals should ideally be able to monitor all relevant aspects of their environment constantly and be ever prepared to alter their course of action in the face of unexpected change .", "However , the impractically high costs of continual monitoring and deliberation mean that a more realistic strategy is required...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "cell biology", "eubacteria", "computational biology" ]	The Effect of Stochasticity on the Lac Operon: An Evolutionary Perspective	journal.pcbi.0030111	null	[ [ "Noise in gene expression , i . e . , the variation in gene expression in an isogenic population in a homogeneous environment , has drawn much attention in recent years .", "When two isogenic cells vary in gene expression , this can be due to variation in factors determining gene expression in these cells...	[ "The role of stochasticity on gene expression is widely discussed .", "Both potential advantages and disadvantages have been revealed .", "In some systems , noise in gene expression has been quantified , in among others the lac operon of Escherichia coli .", "Whether stochastic gene expression in this system ...	[ "Gene expression is a process that is inherently stochastic because of the low number of molecules that are involved .", "In recent years it has become possible to measure the amount of stochasticity in gene expression , which has inspired a debate about the importance of stochasticity in gene expression .", "L...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/motor systems", "neurological disorders/neuroimaging", "neurological disorders/movement disorders", "neurological disorders", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "genetics and genomics/gene function"...	RNA Gain-of-Function in Spinocerebellar Ataxia Type 8	journal.pgen.1000600	null	[ [ "Spinocerebellar ataxia type 8 ( SCA8 ) , is a slowly progressive neurodegenerative disease caused by a CTG•CAG expansion that primarily affects the cerebellum [1] , [2] .", "The disease is transmitted in an autosomal dominant pattern with reduced penetrance and the expansion mutation was originally shown...	[ "Microsatellite expansions cause a number of dominantly-inherited neurological diseases .", "Expansions in coding-regions cause protein gain-of-function effects , while non-coding expansions produce toxic RNAs that alter RNA splicing activities of MBNL and CELF proteins .", "Bi-directional expression of the spi...	[ "We describe several lines of evidence that RNA gain-of-function effects play a significant role in spinocerebellar ataxia type 8 ( SCA8 ) and has broader implications for understanding the CNS effects of other trinucleotide expansion disorders including myotonic dystrophy type 1 , Huntington disease like-2 , and s...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "plant anatomy", "chemical compounds", "brassica", "animals", "organic compounds", "plant science", "model organisms", "crops", "volatile organic compounds", "plants", "flowering plants", "bees", "arabidopsis thaliana", "research and analysis methods", "hymenoptera", ...	Virus Infection of Plants Alters Pollinator Preference: A Payback for Susceptible Hosts?	journal.ppat.1005790	null	[ [ "Insects pollinate many plant species , including several major crops [1] .", "Bees are the single most important insect pollinator group and can be a limiting factor for the success of plant reproduction [1–3] .", "Consequently , there is strong inter- and intra-specific competition among plants for ...	[ "Plant volatiles play important roles in attraction of certain pollinators and in host location by herbivorous insects .", "Virus infection induces changes in plant volatile emission profiles , and this can make plants more attractive to insect herbivores , such as aphids , that act as viral vectors .", "Howeve...	[ "Cucumber mosaic virus , an important pathogen of tomato , causes plants to emit volatile chemicals that attract bumblebees .", "Bumblebees are important tomato pollinators , but do not transmit this virus .", "We propose that under natural conditions , helping host reproduction by encouraging bee visitation mi...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "mathematical computing", "mathematics", "neurological disorders", "neurology", "mathematical economics" ]	The Impact of Neurocysticercosis in California: A Review of Hospitalized Cases	journal.pntd.0001480	null	[ [ "Neurocysticercosis ( NCC ) is associated with severe disease morbidity and mortality across the globe , including the United States where its impact has been studied primarily in the states of California [1] , [2] , [3] , [4] , Texas [5] and Oregon [6] .", "Though NCC mortality is rare in the United Stat...	[ "To assess the burden of neurocysticercosis ( NCC ) in California we examined statewide hospital discharge data for 2009 .", "There were 304 cases hospitalized with NCC identified ( incidence = 0 . 8 per 100 , 000 ) .", "Cases were mostly Latino ( 84 . 9% ) , slightly more likely to be male than female ( men 57...	[ "Neurocysticercosis ( NCC ) is considered one of the major neglected infections of poverty in the United States , with mortality studies indicating that California bears the highest burden of this disease .", "Although NCC is a reportable disease in California , studies indicate that this disease goes largely und...	2012
[ "Introduction", "Results", "Discussion" ]	[ "machine learning algorithms", "medicine and health sciences", "china", "atmospheric science", "applied mathematics", "geographical locations", "simulation and modeling", "algorithms", "regression analysis", "mathematics", "forecasting", "statistics (mathematics)", "artificial intelligence",...	Developing a dengue forecast model using machine learning: A case study in China	journal.pntd.0005973	null	[ [ "Dengue is a serious infectious disease and remains rampant across tropical and subtropical regions [1] .", "Primary dengue infection in humans often leads to a variety of clinical symptoms , from mild fever to potentially fatal dengue shock syndrome , and effective antiviral agents capable of treating de...	[ "In China , dengue remains an important public health issue with expanded areas and increased incidence recently .", "Accurate and timely forecasts of dengue incidence in China are still lacking .", "We aimed to use the state-of-the-art machine learning algorithms to develop an accurate predictive model of deng...	[ "Dengue epidemics have posed a great burden expanding of disease , with areas expanding and incidence increasing in China recently .", "It has remained challenging to develop a robust and accurate forecast model and enhance predictability of dengue incidence .", "Several state-of-the-art machine learning algori...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Integration of Genome-Wide SNP Data and Gene-Expression Profiles Reveals Six Novel Loci and Regulatory Mechanisms for Amino Acids and Acylcarnitines in Whole Blood	journal.pgen.1005510	null	[ [ "High-throughput metabolomics experiments using mass spectrometry platforms are becoming an integral part of clinical and systems biology research .", "Profiling of amino acids and acylcarnitine species in dried whole blood samples of newborns is used worldwide in neonatal screening programs to identify r...	[ "Profiling amino acids and acylcarnitines in whole blood spots is a powerful tool in the laboratory diagnosis of several inborn errors of metabolism .", "Emerging data suggests that altered blood levels of amino acids and acylcarnitines are also associated with common metabolic diseases in adults .", "Thus , th...	[ "Human metabolite levels differ between individuals due to environmental and genetic factors .", "In the present work , we analyzed whole blood levels of amino acids and acylcarnitines , reflecting disease relevant metabolic pathways , in a cohort of 2 , 107 individuals .", "We then performed a genome wide asso...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Maternal Filaggrin Mutations Increase the Risk of Atopic Dermatitis in Children: An Effect Independent of Mutation Inheritance	journal.pgen.1005076	null	[ [ "Atopic dermatitis ( AD , eczema ) is a chronic inflammatory skin disease with 10–20% prevalence in industrialized countries .", "The etiology of AD is complex , with multiple genetic and environmental factors influencing disease risk .", "Genome-wide association studies ( GWAS ) have successfully ide...	[ "Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers .", "This can be due to genomic imprinting , where the phenotype effect of an allele depends on its parental origin , or due to maternal effects reflecting the maternal genome's influence on the child during prenatal ...	[ "Most human diseases are caused by a combination of multiple environmental and genetic influences .", "The widely used case/control approach aims to identify disease risk genes by comparing the genetic constitution of affected and healthy individuals .", "Although successful , this approach ignores additional m...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "infectious diseases/neglected tropical diseases", "infectious diseases/antimicrobials and drug resistance" ]	In Vitro and In Vivo High-Throughput Assays for the Testing of Anti-Trypanosoma cruzi Compounds	journal.pntd.0000740	null	[ [ "Chagas disease , caused by the protozoan parasite Trypanosoma cruzi , is the leading cause of cardiac disease in many countries of Latin America .", "The World Health Organization has estimated that 16–18 million people are currently infected and 90 million are at risk of acquiring the infection [1]–[2] ...	[ "The two available drugs for treatment of T . cruzi infection , nifurtimox and benznidazole ( BZ ) , have potential toxic side effects and variable efficacy , contributing to their low rate of use .", "With scant economic resources available for antiparasitic drug discovery and development , inexpensive , high-th...	[ "The treatment of Trypanosoma cruzi infection ( the cause of human Chagas disease ) remains a significant challenge .", "Only two drugs , both with substantial toxicity , are available and the efficacy of these dugs is often questioned – in many cases due to the limitations of the methods for assessing efficacy r...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "vibrio", "cell processes", "cell cycle and cell division", "microbiology", "operons", "vibrio cholerae", "rrna operons", "dna replication", "bacterial genetics", "dna", "microbial genetics"...	Synchronous termination of replication of the two chromosomes is an evolutionary selected feature in Vibrionaceae	journal.pgen.1007251	null	[ [ "The diversity of regulatory systems of DNA replication has been studied in multiple bacteria [1–4] .", "An especially interesting group of bacteria with regard to DNA replication are those with multiple chromosomes .", "While a single chromosome is the norm in bacteria , about 10% of species in a div...	[ "Vibrio cholerae , the causative agent of the cholera disease , is commonly used as a model organism for the study of bacteria with multipartite genomes .", "Its two chromosomes of different sizes initiate their DNA replication at distinct time points in the cell cycle and terminate in synchrony .", "In this st...	[ "Most bacteria encode their genetic information on a single chromosome .", "The pathogenic bacterium Vibrio cholerae is an exception to this rule and carries two chromosomes of different sizes , each having one origin of replication .", "A very basic research question is how the replication of the two chromosom...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/microbial growth and development", "microbiology/medical microbiology" ]	The Pel Polysaccharide Can Serve a Structural and Protective Role in the Biofilm Matrix of Pseudomonas aeruginosa	journal.ppat.1001264	null	[ [ "Biofilms are surface associated communities embedded within an extracellular matrix [1] , [2] , [3] .", "Biofilm communities exhibit enhanced antibiotic tolerance [4] , [5] , [6] .", "As a result , biofilm infections tend to be chronic and difficult to eradicate [2] , [7] .", "This enhanced toler...	[ "Bacterial extracellular polysaccharides are a key constituent of the extracellular matrix material of biofilms .", "Pseudomonas aeruginosa is a model organism for biofilm studies and produces three extracellular polysaccharides that have been implicated in biofilm development , alginate , Psl and Pel .", "Sign...	[ "Most bacteria live within biofilm communities , which are a complex population of microorganisms that attach to surfaces and produce copious amounts of extracellular matrix material .", "Exopolysaccharides are a key feature of the extracellular matrix and are found in many forms , ranging from structurally simpl...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "pathology/immunology", "immunology/immunity to infections", "immunology/innate immunity" ]	Parasite-Derived Plasma Microparticles Contribute Significantly to Malaria Infection-Induced Inflammation through Potent Macrophage Stimulation	journal.ppat.1000744	null	[ [ "Severe malaria in humans is a leading cause of morbidity and mortality , especially in sub-Saharan Africa [1] .", "The clinical manifestations of severe malaria are directly correlated with the induction of strong pro-inflammatory type-1 immune responses .", "Thus , whilst it is clear that early inna...	[ "There is considerable debate as to the nature of the primary parasite-derived moieties that activate innate pro-inflammatory responses during malaria infection .", "Microparticles ( MPs ) , which are produced by numerous cell types following vesiculation of the cellular membrane as a consequence of cell death or...	[ "Although parasite materials are responsible for the activation of the immune system during malaria infection , exactly how the immune response is initiated during infection is extremely unclear .", "In this study we demonstrate that sub micron particles ( microparticles ) are produced by malaria infected red blo...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "drosophila", "genetics and genomics" ]	Molecular Landscape of Modified Histones in Drosophila Heterochromatic Genes and Euchromatin-Heterochromatin Transition Zones	journal.pgen.0040016	null	[ [ "Constitutive heterochromatin is a nearly universal component of eukaryotic genomes .", "It was first defined in the 1920′s as distinct from euchromatin by its densely stained cytological appearance [1] .", "It was also associated with modulation of gene expression in Drosophila chromosome rearrangeme...	[ "Constitutive heterochromatin is enriched in repetitive sequences and histone H3-methylated-at-lysine 9 .", "Both components contribute to heterochromatin's ability to silence euchromatic genes .", "However , heterochromatin also harbors hundreds of expressed genes in organisms such as Drosophila .", "Recent ...	[ "The chromosomal domain “heterochromatin” was first defined at the cytological level by its deeply staining appearance compared to more lightly stained domains called “euchromatin . ”", "Abnormal juxtaposition of these two domains by chromosome rearrangements results in silencing of the nearby euchromatic genes ....	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "neurochemistry", "action potentials", "neural networks", "engineering and technology", "nervous system", "electrical circuits", "membrane potential", "electrophysiology", "neuroscience", "ion channels", "computer and information sciences", "animal cells", "...	Switchable slow cellular conductances determine robustness and tunability of network states	journal.pcbi.1006125	null	[ [ "Neuronal processing is constantly shaped by fluctuations in population rhythmic activities , each defining distinctive brain states [1–4] .", "Neuromodulators organize the switch between different brain states [5 , 6] , changing the way networks process neural signals [7 , 8] .", "Precise temporal an...	[ "Neuronal information processing is regulated by fast and localized fluctuations of brain states .", "Brain states reliably switch between distinct spatiotemporal signatures at a network scale even though they are composed of heterogeneous and variable rhythms at a cellular scale .", "We investigated the mechan...	[ "Brain information processing involves electrophysiological signals at multiple temporal and spatial timescales , from the single neuron level to whole brain areas .", "A fast and local control of these signals by neurochemicals called neuromodulators is essential in complex tasks such as movement initiation and ...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "small molecules", "microbiology", "host-pathogen interaction", "parasitology", "parastic protozoans", "leishmania", "neglected tropical diseases", "infectious diseases", "microbial pathogens", "biology", "drug discovery", "biochemistry", "leishmaniasis", "protozoology" ]	A Screen against Leishmania Intracellular Amastigotes: Comparison to a Promastigote Screen and Identification of a Host Cell-Specific Hit	journal.pntd.0001253	null	[ [ "Leishmaniasis is caused by protozoan parasites of the genus Leishmania .", "The disease is endemic in the tropics , subtropics and the Mediterranean basin .", "There are three main clinical syndromes caused by different species of Leishmania .", "Cutaneous and muccocutaneous leishmaniasis result ...	[ "The ability to screen compounds in a high-throughput manner is essential in the process of small molecule drug discovery .", "Critical to the success of screening strategies is the proper design of the assay , often implying a compromise between ease/speed and a biologically relevant setting .", "Leishmaniasis...	[ "Leishmaniasis , a disease caused by protozoan parasites of the genus Leishmania , is a poverty-related disease threatening 350 million people throughout the world .", "Drugs currently available to treat this disease are toxic to the patient and drug-resistant parasites are emerging .", "New therapeutics are th...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "rna-binding proteins", "rna", "rna structure", "rna folding", "protein structure determination", "rna processing", "molecular complexes", "proteins", "enzymes", "protein structure", "biology and life sciences", "enzymology", "rna splicing", "molecular biology", "ribozy...	Evolution of RNA-Protein Interactions: Non-Specific Binding Led to RNA Splicing Activity of Fungal Mitochondrial Tyrosyl-tRNA Synthetases	journal.pbio.1002028	Studies of tRNA synthetases that adapted to assist the splicing of group I introns provide insight into how proteins can evolve new RNA-binding functions.	[ [ "RNA-binding proteins play critical roles in post-transcriptional regulation of gene expression in all domains of life [1] .", "However , the complexity of this regulation is far greater in eukaryotes than in prokaryotes , reflecting both the larger number of RNAs requiring regulation and the evolution of...	[ "The Neurospora crassa mitochondrial tyrosyl-tRNA synthetase ( mtTyrRS; CYT-18 protein ) evolved a new function as a group I intron splicing factor by acquiring the ability to bind group I intron RNAs and stabilize their catalytically active RNA structure .", "Previous studies showed:", "( i ) CYT-18 binds grou...	[ "The acquisition of new modes of post-transcriptional gene regulation played an important role in the evolution of eukaryotes and was achieved by an increase in the number of RNA-binding proteins with new functions .", "RNA-binding proteins bind directly to double- or single-stranded RNA and regulate many cellula...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "parasitology", "biology", "microbiology" ]	Schistosoma japonicum Egg Specific Protein SjE16.7 Recruits Neutrophils and Induces Inflammatory Hepatic Granuloma Initiation	journal.pntd.0002703	null	[ [ "Schistosomiasis is a neglected tropical disease caused by trematode parasites of the genus Schistosoma .", "It is estimated to affect 200 million people globally and cause nearly 280 , 000 deaths reported annually [1] .", "S . japonicum is the major causative agent of schistosomiasis in South East As...	[ "Neutrophils are known to play a major role in the egg granulomatous lesions caused by Schistosoma japonicum , but the precise mechanism by which eggs recruit or active neutrophil is unknown .", "Here we report S . japonicum egg specific EF-hand protein-SjE16 . 7 is a potent neutrophil recruiter and initiates the...	[ "As a neglected disease , schistosomiasis continues to be a significant cause of parasitic morbidity and mortality worldwide .", "Schistosoma japonicum is one of the major causative agents of human schistosomiasis .", "Trapped in the liver or intestinal tissue , S . japonicum eggs are the main cause of patholog...	2014
[ "Introduction", "Results", "Discussion" ]	[ "medicine and health sciences", "geographical locations", "tropical diseases", "parasitic diseases", "parasitic protozoans", "health care", "organisms", "age groups", "adults", "protozoans", "pharmaceutics", "neglected tropical diseases", "infectious disease control", "infectious diseases"...	A strategy for scaling up access to comprehensive care in adults with Chagas disease in endemic countries: The Bolivian Chagas Platform	journal.pntd.0005770	null	[ [ "The prevention and control of CD in Bolivia was declared a national priority in Law 3374 dated March 23 , 2006 [12] .", "However , no additional regulations were developed .", "The Chagas National Programme ( ChNP ) , the responsible body for the prevention , diagnosis and treatment of CD in the coun...	[ "Bolivia has the highest prevalence of Chagas disease ( CD ) in the world ( 6 . 1% ) , with more than 607 , 186 people with Trypanosoma cruzi infection , most of them adults .", "In Bolivia CD has been declared a national priority .", "In 2009 , the Chagas National Program ( ChNP ) had neither a protocol nor a ...	[ "Bolivia has the highest prevalence of Chagas disease ( CD ) in the world ( 6 . 1% ) , with more than 607 , 186 people with Trypanosoma cruzi infection .", "In Bolivia , the management of CD has been declared a national priority .", "In 2009 , the Chagas National Program ( ChNP ) had neither a protocol nor a cl...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "vesicles", "nervous system", "enzymes", "protein interaction networks", "enzymology", "electrophysiology", "neuroscience", "phosphatases", "synaptic vesicles", "synaptosomes", "network analysis", "cellular structures and organelles", "c...	The temporal profile of activity-dependent presynaptic phospho-signalling reveals long-lasting patterns of poststimulus regulation	journal.pbio.3000170	Analysis of activity-dependent phosphorylation-based signalling in synaptosomes revealed six patterns of long-lasting presynaptic regulation from 1,917 phosphopeptides. The authors identified patterns most likely to be regulated by CamKII and MAPK/ERK and showed the active zone scaffold protein bassoon to be a major si...	[ [ "Depolarization of the presynaptic plasma membrane stimulates the opening of voltage-gated Ca2+ channels , and Ca2+ rapidly enters at the active zone .", "Increased Ca2+ triggers neurotransmitter release by binding to Ca2+ sensors such as synaptotagmin 1 , which facilitates fast synchronous fusion of dock...	[ "Depolarization of presynaptic terminals stimulates calcium influx , which evokes neurotransmitter release and activates phosphorylation-based signalling .", "Here , we present the first global temporal profile of presynaptic activity-dependent phospho-signalling , which includes two KCl stimulation levels and an...	[ "Neurobiological processes are altered by linking neuronal activity to regulated changes in protein phosphorylation levels that influence protein function .", "Although some of the major targets of activity-dependent phospho-signalling have been identified , a large number of substrates remain unknown .", "Here...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "genetic polymorphism", "genome evolution", "genetics", "population genetics", "comparative genomics", "biology", "human genetics", "evolutionary biology", "population biology", "structural genomics" ]	Validation and Genotyping of Multiple Human Polymorphic Inversions Mediated by Inverted Repeats Reveals a High Degree of Recurrence	journal.pgen.1004208	null	[ [ "Different types of structural variants ( SVs ) , including deletions , duplications , insertions , inversions , and translocations , have been recently discovered in the human genome and there is growing evidence of their importance in human diseases , complex traits , and evolution [1]–[4] .", "Specific...	[ "In recent years different types of structural variants ( SVs ) have been discovered in the human genome and their functional impact has become increasingly clear .", "Inversions , however , are poorly characterized and more difficult to study , especially those mediated by inverted repeats or segmental duplicati...	[ "Inversions have been an evolutionary biology model for almost a century , and recently the discovery of a high amount of structural variation in multiple organisms , including humans , has renewed the interest in them .", "Since early on , it was shown that they were adaptive and that they were involved in human...	2014
[ "Introduction", "Results/Discussion", "Methods" ]	[ "genome evolution", "plant biology", "microbiology", "genome sequencing", "plant science", "fungal evolution", "microbial evolution", "plant pathology", "genome complexity", "mycology", "microbial pathogens", "comparative genomics", "biology", "plant pathogens", "genomics", "computatio...	Comparative Genomics Yields Insights into Niche Adaptation of Plant Vascular Wilt Pathogens	journal.ppat.1002137	null	[ [ "Vascular wilts caused by fungal pathogens are widespread and very destructive plant diseases , causing enormous economic losses .", "The survival structures produced by wilt pathogens may remain viable in the soil for more than 20 years [1] , making them a major constraint on agricultural production .", ...	[ "The vascular wilt fungi Verticillium dahliae and V . albo-atrum infect over 200 plant species , causing billions of dollars in annual crop losses .", "The characteristic wilt symptoms are a result of colonization and proliferation of the pathogens in the xylem vessels , which undergo fluctuations in osmolarity ....	[ "Vascular wilts are chronic and very often severe plant diseases that cause billions of dollars in annual crop losses .", "The characteristic wilt symptom is a result of water blockage caused by the colonization and proliferation of pathogenic microbes in the plant xylem , a water-conducting system .", "We sequ...	2011
[ "Introduction", "Results", "Discussion", "Conclusions", "Materials and methods" ]	[ "cell motility", "medicine and health sciences", "neurogenesis", "nervous system", "electrophysiology", "neuroscience", "developmental biology", "cellular structures and organelles", "neuronal dendrites", "cytoskeleton", "contractile proteins", "actins", "developmental neuroscience", "anim...	RhoGEF9 splice isoforms influence neuronal maturation and synapse formation downstream of α2 GABAA receptors	journal.pgen.1007073	null	[ [ "During CNS development , GABAergic transmission regulates key steps of neurogenesis and neuronal circuit formation [1 , 2] .", "A similar role has been observed also for the regulation of adult neurogenesis [3–5] .", "The diverse effects of GABA can be observed best upon inactivation of specific GABA...	[ "In developing brain neuronal migration , dendrite outgrowth and dendritic spine outgrowth are controlled by Cdc42 , a small GTPase of the Rho family , and its activators .", "Cdc42 function in promoting actin polymerization is crucial for glutamatergic synapse regulation .", "Here , we focus on GABAergic synap...	[ "GABAergic inhibition regulates distinct stages of brain development; however , cellular mechanisms downstream of GABAA receptors ( GABAARs ) that influence neuronal migration , maturation and synaptogenesis are less clear .", "ArfGEF9 encodes for RhoGEF with Cdc42 and TC10 GTPase as its substrates .", "Interes...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "microbiology/parasitology", "infectious diseases/protozoal infections", "cell biology/cell adhesion" ]	Targeted Disruption of py235ebp-1: Invasion of Erythrocytes by Plasmodium yoelii Using an Alternative Py235 Erythrocyte Binding Protein	journal.ppat.1001288	null	[ [ "Despite the recent renewed onslaught to tackle a disease that infects 300-660 million", "people and kills one million each year worldwide [1] , the malaria parasite remains an", "elusive target .", "During the asexual blood stage , which is responsible for the", "disease , the parasite invade...	[ "Plasmodium yoelii YM asexual blood stage parasites express", "multiple members of the py235 gene family , part of the", "super-family of genes including those coding for Plasmodium", "vivax reticulocyte binding proteins and Plasmodium", "falciparum RH proteins .", "We previously identified a Py235", "e...	[ "Malaria parasites invade erythrocytes where they develop and multiply before", "bursting out and invading fresh cells .", "There are sequential steps to invasion;", "early in the process , specific parasite proteins bind to molecules on the", "surface of the erythrocyte .", "Tight binding forms a junctio...	2011
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "genetics and genomics/gene discovery", "cell biology/gene expression", "cell biology", "cell biology/cell adhesion", "genetics and genomics", "genetics and genomics/bioinformatics" ]	An Integrated Strategy to Study Muscle Development and Myofilament Structure in Caenorhabditis elegans	journal.pgen.1000537	null	[ [ "Muscle tissue is important for humans in a myriad of processes including movement , digestion , and the pumping of blood through the cardiovascular system .", "Afflictions that affect muscle can be debilitating in any of these processes .", "The underlying cause of many myopathies lies within the cel...	[ "A crucial step in the development of muscle cells in all metazoan animals is the assembly and anchorage of the sarcomere , the essential repeat unit responsible for muscle contraction .", "In Caenorhabditis elegans , many of the critical proteins involved in this process have been uncovered through mutational sc...	[ "Muscular diseases affect many people worldwide .", "While we have learned much about the sarcomere , the basic building block of muscle cells , there are still numerous questions that remain to be answered .", "We must learn more about proteins expressed in muscle and how they interact so that better treatment...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genome expression analysis", "medicine and health sciences", "functional genomics", "animal genetics", "pathology and laboratory medicine", "tropical diseases", "microbiology", "parasitic diseases", "parasitology", "parasite physiology", "genomic databases", "genome analysis", "quantitative...	Imatinib Treatment Causes Substantial Transcriptional Changes in Adult Schistosoma mansoni In Vitro Exhibiting Pleiotropic Effects	journal.pntd.0002923	null	[ [ "Schistosomiasis is an infectious disease of worldwide importance caused by parasitic platyhelminthes of the class trematoda such as Schistosoma haematobium , S . intercalatum , S . japonicum , S . mansoni , or S . mekongi .", "About 780 million people are at risk of schistosomiasis , and more than 240 mi...	[ "Schistosome parasites cause schistosomiasis , one of the most important infectious diseases worldwide .", "For decades Praziquantel ( PZQ ) is the only drug widely used for controlling schistosomiasis .", "The absence of a vaccine and fear of PZQ resistance have motivated the search for alternatives .", "Stu...	[ "Schistosomiasis is an infectious disease caused by schistosome parasites , affecting millions of people worldwide .", "The pathogenic consequences of schistosomiasis are caused by the eggs inducing severe organ inflammations .", "Praziquantel is widely used to treat schistosomiasis; however , there is fear of ...	2014
[ "Introduction", "Results", "Materials and methods", "Discussion" ]	[ "medicine and health sciences", "microtubules", "nervous system", "cell processes", "neuroscience", "macroglial cells", "motor neurons", "nerve regeneration", "developmental biology", "dyneins", "molecular motors", "organism development", "schwann cells", "nerve fibers", "morphogenesis",...	Dynein promotes sustained axonal growth and Schwann cell remodeling early during peripheral nerve regeneration	journal.pgen.1007982	null	[ [ "Axons of the mature peripheral nervous system have retained a remarkable ability for regeneration .", "Although simple in concept , peripheral nerve regeneration is a complex process that requires extrinsic as well as intrinsic mechanisms .", "Chief amongst the intracellular mechanisms that contribut...	[ "Following injury , axons of the peripheral nervous system have retained the capacity for regeneration .", "While it is well established that injury signals require molecular motors for their transport from the injury site to the nucleus , whether kinesin and dynein motors play additional roles in peripheral nerv...	[ "Nerve regeneration requires coordinated responses from multiple cell types after injury .", "Axons must extend from the neuronal cell body back towards their targets , while surrounding Schwann cells enter a repair cell state in which they promote regeneration .", "While nerves of the peripheral nervous system...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "adaptive immunity", "immune cells", "monocytes", "immunity", "innate immunity", "antigen-presenting cells", "parasitology", "immunology", "biology", "microbiology", "host-pathogen interaction", "immune response" ]	Leishmania mexicana Induces Limited Recruitment and Activation of Monocytes and Monocyte-Derived Dendritic Cells Early during Infection	journal.pntd.0001858	null	[ [ "Infection with Leishmania results in a variety of outcomes , depending on the parasite species and immune response mounted by the host [1] .", "Murine disease models resemble human disease , with some infections being self-healing and others chronic .", "Resolution of leishmaniasis requires the produ...	[ "While C57BL/6 mice infected in the ear with L . major mount a vigorous Th1 response and resolve their lesions , the Th1 response in C57BL/6 mice infected with L . mexicana is more limited , resulting in chronic , non-healing lesions .", "The aim of this study was to determine if the limited immune response follo...	[ "Leishmaniasis , caused by protozoan parasites belonging to the genus , Leishmania , exhibits clinical symptoms ranging from mild cutaneous lesions to more severe cutaneous or visceral disease .", "Here , we focus on L . major and L . mexicana , two species that lead to self-resolving and chronic cutaneous lesion...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "developmental biology", "genetics", "biology", "genomics", "evolutionary biology", "clinical genetics" ]	Comparative Anatomy of Chromosomal Domains with Imprinted and Non-Imprinted Allele-Specific DNA Methylation	journal.pgen.1003622	null	[ [ "Evidence from genome-wide association studies ( GWAS ) and cross-species comparisons suggests that many inter-individual phenotypic differences result from genetic variants in non-coding DNA sequences .", "Thus a major challenge in the post-genomic era is to define the mechanisms by which non-coding sequ...	[ "Allele-specific DNA methylation ( ASM ) is well studied in imprinted domains , but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci , where the ASM is dictated not by parent-of-origin but instead by the local haplotype .", "We identified loci with strong ASM in human tissue...	[ "Allele-specific DNA methylation ( ASM ) is a central mechanism of gene regulation in humans , which can influence inter-individual differences in physical and mental traits and disease susceptibility .", "ASM is mediated either by parental imprinting , in which the repressed copy ( allele ) of the gene is determ...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "cellular stress responses", "neurodegenerative diseases", "cell processes", "endoplasmic reticulum", "brain", "neuroscience", "animal models", "protein expression", "model organisms", "experimental organism systems", "molecular biology tech...	Bidirectional interplay of HSF1 degradation and UPR activation promotes tau hyperphosphorylation	journal.pgen.1006849	null	[ [ "Neurofibrillary tangles ( NFTs ) of phosphorylated tau aggregates and senile plaques of amyloid beta ( Aβ ) are the pathological hallmarks of Alzheimer’s disease ( AD ) patients .", "Aβ toxicity has been known to contribute to synaptic loss and cognitive impairment , the mechanism of which appears to be ...	[ "The unfolded protein response ( UPR ) in the endoplasmic reticulum ( ER ) and the cytoplasmic heat stress response are two major stress response systems necessary for maintaining proteostasis for cellular health .", "Failure of either of these systems , such as in sustained UPR activation or in insufficient heat...	[ "Tauopathy including Alzheimer’s disease ( AD ) is characterized by a build-up of tau aggregates in the brain , highly associated with failure of cellular protein homeostasis .", "Proteostasis can be achieved by protein quality control system to cope with numerous stresses such as proteotoxic stress from misfolde...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "japanese encephalitis virus", "dengue virus", "medicine and health sciences", "vesicular stomatitis virus", "pathology and laboratory medicine", "pathogens", "biological cultures", "microbiology", "toxicology", "viruses", "rna viruses", "cell cultures", "research and analysis methods", "p...	Limited Effects of Type I Interferons on Kyasanur Forest Disease Virus in Cell Culture	journal.pntd.0004871	null	[ [ "Kyasanur Forest disease virus ( KFDV ) is a tick-borne flavivirus that was identified in 1957 following a monkey epizootic and a coinciding human outbreak in south-west India [1] .", "KFDV cases previously were localized within the Shimoga district of Karnataka; however KFDV has been recently discovered ...	[ "The tick-borne flavivirus , Kyasanur Forest disease virus ( KFDV ) causes seasonal infections and periodic outbreaks in south-west India .", "The current vaccine offers poor protection with reported issues of coverage and immunogenicity .", "Since there are no approved prophylactic therapeutics for KFDV , type...	[ "Since 1957 Kyasanur Forest disease virus ( KFDV ) has caused seasonal infections and periodic outbreaks in south-west India .", "It is estimated that nearly 500 people acquire KFDV annually and 3–5% of those infected succumb to the disease .", "The vaccine strategy is complicated by the lack of coverage , comp...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genome projects", "genetics and genomics", "genetics and genomics/plant genomes and evolution", "genetics and genomics/genomics" ]	Exceptional Diversity, Non-Random Distribution, and Rapid Evolution of Retroelements in the B73 Maize Genome	journal.pgen.1000732	null	[ [ "Transposable elements ( TEs ) were first discovered in maize ( Zea mays ) [1] , but have subsequently been found in almost every organism investigated , from archaea and eubacteria to animals , plants , fungi and protists [2] .", "TEs are dynamic , abundant and diverse components of higher eukaryotic gen...	[ "Recent comprehensive sequence analysis of the maize genome now permits detailed discovery and description of all transposable elements ( TEs ) in this complex nuclear environment .", "Reiteratively optimized structural and homology criteria were used in the computer-assisted search for retroelements , TEs that t...	[ "Although TEs are a major component of all studied plant genomes , and are the most significant contributors to genome structure and evolution in almost all eukaryotes that have been investigated , their properties and reasons for existence are not well understood in any eukaryotic genome .", "In order to begin a...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "structural characterization", "medicine and health sciences", "cell biology", "macromolecular crystallography", "genetics", "x-ray crystallography", "biology and life sciences", "immunology", "congenital disorders", "molecular biology", "crystallographic techniques", ...	Structural Basis for the Recognition of Human Cytomegalovirus Glycoprotein B by a Neutralizing Human Antibody	journal.ppat.1004377	null	[ [ "Human cytomegalovirus ( HCMV ) belongs to the family of β-herpes viruses and is a clinically important pathogen .", "While infection in hosts with a functional immune system is usually clinically asymptomatic , the virus can cause significant morbidity and mortality in individuals with an immature or sup...	[ "Human cytomegalovirus ( HCMV ) infections are life-threating to people with a compromised or immature immune system .", "Upon adhesion , fusion of the virus envelope with the host cell is initiated .", "In this step , the viral glycoprotein gB is considered to represent the major fusogen .", "Here , we prese...	[ "Human cytomegalovirus ( HCMV ) belongs to the family of β-herpes viruses .", "HCMV infections are not only life threatening to people with a compromised immune system but also the most common viral cause of congenital defects in newborns .", "Hence , the development of HCMV vaccines was ranked top priority by ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "immunity", "genetics", "population genetics", "biology", "immunology", "genetics and genomics" ]	High-Density SNP Mapping of the HLA Region Identifies Multiple Independent Susceptibility Loci Associated with Selective IgA Deficiency	journal.pgen.1002476	null	[ [ "The major histocompatibility complex ( MHC ) locus has been one of the most intensively studied regions in the vertebrate genome since it was first discovered in the mouse in 1936 [1] .", "In humans , gene products from the MHC were initially identified as surface markers on leucocytes , which led to its...	[ "Selective IgA deficiency ( IgAD; serum IgA<0 . 07 g/l ) is the most common form of human primary immune deficiency , affecting approximately 1∶600 individuals in populations of Northern European ancestry .", "The polygenic nature of IgAD is underscored by the recent identification of several new risk genes in a ...	[ "The human leukocyte antigen ( HLA ) locus is robustly associated with many immune-mediated conditions .", "However , identification of the genetic variants contributing to the disease pathophysiology has been greatly hampered by the extensive chromosomal conservation within this genomic region .", "To better u...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fish", "neuromuscular junctions", "medicine and health sciences", "hela cells", "nervous system", "biological cultures", "vertebrates", "electrophysiology", "neuroscience", "animals", "biological locomotion", "animal models", "osteichthyes", "developmental biology", "mutation", "model...	Biallelic mutations in nucleoporin NUP88 cause lethal fetal akinesia deformation sequence	journal.pgen.1007845	null	[ [ "The nucleoporin NUP88 [MIM 602552] is a constituent of the nuclear pore complex ( NPC ) , the gate for all trafficking between the nucleus and the cytoplasm [1] .", "NUP88 resides on both the cytoplasmic and the nuclear side of NPCs [2] and it is found in distinct sub-complexes: on the cytoplasmic face i...	[ "Nucleoporins build the nuclear pore complex ( NPC ) , which , as sole gate for nuclear-cytoplasmic exchange , is of outmost importance for normal cell function .", "Defects in the process of nucleocytoplasmic transport or in its machinery have been frequently described in human diseases , such as cancer and neur...	[ "Fetal movement is a prerequisite for normal fetal development and growth .", "Fetal akinesia deformation sequence ( FADS ) is the result of decreased fetal movement coinciding with congenital malformations related to impaired fetal movement .", "FADS may be caused by heterogenous defects at any point along the...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Control, Elimination, and Eradication of River Blindness: Scenarios, Timelines, and Ivermectin Treatment Needs in Africa	journal.pntd.0003664	null	[ [ "Elimination of neglected tropical diseases ( NTDs ) has recently emerged on the global health agenda and gained prominence with the release of the global plan to combat NTDs by the World Health Organization ( WHO ) [1] .", "In 2012 , WHO issued a roadmap towards the elimination of 17 NTDs [2] , and stake...	[ "River blindness ( onchocerciasis ) causes severe itching , skin lesions , and vision impairment including blindness .", "More than 99% of all current cases are found in sub-Saharan Africa .", "Fortunately , vector control and community-directed treatment with ivermectin have significantly reduced morbidity .",...	[ "River blindness ( onchocerciasis ) is transmitted by blackflies and causes severe itching , skin lesions , and vision impairment including blindness .", "More than 99% of all current cases are found in sub-Saharan Africa where the disease has historically hindered socioeconomic development in endemic areas .", ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "chromosome structure and function", "histone modification", "chromosome mapping", "mathematics", "materials science", "algebra", "epigenetics", "molecular biology techniques", "macromolecules", "structural genomics", "chromatin", "research and analysis methods", "polymers", "polymer chemi...	Predicting three-dimensional genome organization with chromatin states	journal.pcbi.1007024	null	[ [ "The human genome contains about 2 meters of DNA that is packaged as chromatin inside a nucleus of only 10 micrometers in diameter [1] .", "The way in which chromatin is organized in the three-dimensional space , i . e . , the chromatin structure , has been shown to play important roles for all DNA-templa...	[ "We introduce a computational model to simulate chromatin structure and dynamics .", "Starting from one-dimensional genomics and epigenomics data that are available for hundreds of cell types , this model enables de novo prediction of chromatin structures at five-kilo-base resolution .", "Simulated chromatin st...	[ "Three-dimensional genome organization is expected to play crucial roles in regulating gene expression and establishing cell fate , and has inspired the development of numerous innovative experimental techniques for its characterization .", "Though significant progress has been made , it remains challenging to co...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "neurodegenerative diseases", "biomarkers", "diabetes mellitus", "endocrine disorders", "coronary heart disease", "mathematics", "statistics (mathematics)", "alzheimer disease", "cardiology", "research and analysis methods", "stroke", "endocrinology", "mathe...	Pleiotropic Associations of Allelic Variants in a 2q22 Region with Risks of Major Human Diseases and Mortality	journal.pgen.1006314	null	[ [ "The demographic transition on aging of populations in developed countries requires strategies , which could extend healthspan and lifespan , and compress morbidity [1–3] .", "Breakthroughs in genome-wide sequencing and high-throughput genotyping raised enthusiasm for advancing the progress in the field b...	[ "Gaining insights into genetic predisposition to age-related diseases and lifespan is a challenging task complicated by the elusive role of evolution in these phenotypes .", "To gain more insights , we combined methods of genome-wide and candidate-gene studies .", "Genome-wide scan in the Atherosclerosis Risk i...	[ "Biomedical research and medical care are traditionally focused on individual health conditions in order to postpone , ameliorate , or prevent the accumulation of morbidities in late life .", "An attractive idea is to find factors , which could reduce burden of not just one disease but a major subset of them to e...	2016
[ "Introduction", "Results", "Discussion", "Supporting Information" ]	[ "eukaryotes", "computational biology" ]	DNA Familial Binding Profiles Made Easy: Comparison of Various Motif Alignment and Clustering Strategies	journal.pcbi.0030061	null	[ [ "Transcription factor ( TF ) proteins usually recognize a small number of DNA targets via the formation of sequence-specific and nonspecific molecular interactions .", "Understanding the evolution of TF DNA-binding preferences will not only provide useful insights on the mechanism of DNA recognition , it ...	[ "Transcription factor ( TF ) proteins recognize a small number of DNA sequences with high specificity and control the expression of neighbouring genes .", "The evolution of TF binding preference has been the subject of a number of recent studies , in which generalized binding profiles have been introduced and use...	[ "Transcription factors are primary regulators of gene expression .", "They usually recognize short DNA sequences in gene promoters and subsequently alter their transcription rate .", "It is known that structurally related transcription factors often recognize similar DNA-binding patterns ( or motifs ) .", "Co...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	The Mating Competence of Geographically Diverse Leishmania major Strains in Their Natural and Unnatural Sand Fly Vectors	journal.pgen.1003672	null	[ [ "Protozoan parasites of the genus Leishmania present a remarkable epidemiologic and clinical diversity , producing a spectrum of human diseases that pose serious health concerns throughout tropical and sub-tropical regions .", "Leishmania have a dimorphic asexual life cycle consisting of extracellular pro...	[ "Invertebrate stages of Leishmania are capable of genetic exchange during their extracellular growth and development in the sand fly vector .", "Here we explore two variables: the ability of diverse L . major strains from across its natural range to undergo mating in pairwise tests; and the timing of the appearan...	[ "Leishmania are pathogenic protozoa characterized by substantial diversity in the sand fly species that can transmit them , in the mammalian species that can serve as their reservoir hosts , and in the disease forms and severity of the clinical outcomes they can produce in humans .", "The possibility that this di...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "reproductive system", "rna interference", "animals", "cell differentiation", "germ cells", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "stem cells", "experimental organism systems", "epigenetics",...	Enhancer of polycomb coordinates multiple signaling pathways to promote both cyst and germline stem cell differentiation in the Drosophila adult testis	journal.pgen.1006571	null	[ [ "In physiological condition , adult stem cells are surrounded by other cell types and extracellular matrix .", "Recent studies have demonstrated a dynamic crosstalk between stem cells and their surrounding microenvironment termed as the stem cell niche [1] .", "Signaling molecules emanating from this ...	[ "Stem cells reside in a particular microenvironment known as a niche .", "The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity .", "Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by c...	[ "Tissue maintenance and repair rely on adult stem cells , which can divide to generate new stem cells as well as cells committed for becoming specific cell types .", "Stem cell activity needs to be tightly controlled because insufficient or unlimited stem cell division may lead to tissue degeneration or tumorigen...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	Microhomology Directs Diverse DNA Break Repair Pathways and Chromosomal Translocations	journal.pgen.1003026	null	[ [ "Chromosome structural variations such as deletions , duplications , inversions and chromosomal translocations contribute to evolution and genetic diseases [1] , [2] , [3] .", "A chromosomal translocation is a fusion between two non-homologous chromosomes .", "It contributes to cancer by forming a chi...	[ "Chromosomal structural change triggers carcinogenesis and the formation of other genetic diseases .", "The breakpoint junctions of these rearrangements often contain small overlapping sequences called “microhomology , ” yet the genetic pathway ( s ) responsible have yet to be defined .", "We report a simple ge...	[ "Cancer results from an accumulation of mutations that transform a normal cell into one that proliferates uncontrollably .", "DNA double-strand breaks ( DSBs ) can lead to genetic mutations and chromosome rearrangements , underscoring the importance of functional DNA DSB repair pathways in the maintenance of chro...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "signaling networks", "cell differentiation", "circadian oscillators", "simulation and modeling", "developmental biology", "mathematics", "network analysis", "chronobiology", "research and analysis methods", "computer and information sciences", "gene expression", "biophysics", "physics", "...	Stochastic Simulation of Biomolecular Networks in Dynamic Environments	journal.pcbi.1004923	null	[ [ "Dynamic simulation is an essential and widespread approach for studying biomolecular networks in cell biology [1] .", "However , the computational resources required can quickly become limiting for several reasons .", "Cellular networks are complex , containing many biomolecular species and reactions...	[ "Simulation of biomolecular networks is now indispensable for studying biological systems , from small reaction networks to large ensembles of cells .", "Here we present a novel approach for stochastic simulation of networks embedded in the dynamic environment of the cell and its surroundings .", "We thus sampl...	[ "Simulation algorithms have become indispensable tools in modern quantitative biology , providing deep insight into many biochemical systems , including gene regulatory networks .", "However , current stochastic simulation approaches handle the effects of fluctuating extracellular signals and upstream processes p...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal genetics", "gene regulation", "cell differentiation", "animal models", "developmental biology", "caenorhabditis elegans", "model organisms", "organism development", "molecular development", "molecular genetics", "pattern formation", "gene expression", "organogenesis", "biology", ...	The Caenorhabditis elegans Synthetic Multivulva Genes Prevent Ras Pathway Activation by Tightly Repressing Global Ectopic Expression of lin-3 EGF	journal.pgen.1002418	null	[ [ "Signaling by epidermal growth factor ( EGF ) family ligands and EGF receptor ( EGFR ) family tyrosine kinases controls many aspects of mammalian development and can drive cancers: EGFRs are commonly overexpressed or constitutively activated by mutations in tumor cells [1] , and EGF-family ligands can be misr...	[ "The Caenorhabditis elegans class A and B synthetic multivulva ( synMuv ) genes redundantly antagonize an EGF/Ras pathway to prevent ectopic vulval induction .", "We identify a class A synMuv mutation in the promoter of the lin-3 EGF gene , establishing that lin-3 is the key biological target of the class A synMu...	[ "Extracellular signals that drive cells to divide must be carefully restricted so that only the correct cells receive those signals .", "Failure to properly control the expression of signaling molecules can lead to aberrant development and cancer .", "Studies of vulval development in the nematode Caenorhabditis...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "cell biology/nuclear structure and function", "cell biology/cell signaling", "cell biology/cell growth and division", "genetics and genomics/nuclear structure and function", "cell biology/developmental molecular mechanisms", "genetics and genomics/chromosome biology"...	Spermatogenesis-Specific Features of the Meiotic Program in Caenorhabditis elegans	journal.pgen.1000611	null	[ [ "During either sperm or oocyte production , meiotic chromosomes undergo a continuum of similar events that are tightly regulated by the cell cycle .", "Meiosis starts with an extended G2 phase called meiotic prophase in which chromosomes first shorten ( leptotene ) , then pair and assemble synaptonemal co...	[ "In most sexually reproducing organisms , the fundamental process of meiosis is implemented concurrently with two differentiation programs that occur at different rates and generate distinct cell types , sperm and oocytes .", "However , little is known about how the meiotic program is influenced by such contrasti...	[ "Sperm and oocytes contribute equal but unique complements of DNA to each new life .", "Both types of cells arise from meiosis , a multi-step program during which chromosomes replicate , pair and recombine , then divide to generate haploid gametes .", "Simultaneously , each cell type also differentiates via dis...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "chagas disease", "neglected tropical diseases", "tropical diseases", "protozoan infections", "parasitic diseases" ]	Sources of Blood Meals of Sylvatic Triatoma guasayana near Zurima, Bolivia, Assayed with qPCR and 12S Cloning	journal.pntd.0003365	null	[ [ "Blood-feeding insects in the subfamily Triatominae are vectors of Trypanosoma cruzi , the parasite that causes Chagas disease .", "Approximately 140 species of Triatominae range across the Americas [1] and vary in their role in transmitting human Chagas disease in part because of their preference for syl...	[ "In this study we compared the utility of two molecular biology techniques , cloning of the mitochondrial 12S ribosomal RNA gene and hydrolysis probe-based qPCR , to identify blood meal sources of sylvatic Chagas disease insect vectors collected with live-bait mouse traps ( also known as Noireau traps ) .", "Four...	[ "The World Health Organization ( WHO ) estimates that 7 to 8 million people are currently infected with Trypanosoma cruzi , the parasite that causes Chagas disease .", "The WHO recommends insect vector control as the primary prevention method; and insecticide spraying is the most commonly used intervention techni...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/chromosome biology", "evolutionary biology/evolutionary and comparative genetics" ]	Turnover of Sex Chromosomes in the Stickleback Fishes (Gasterosteidae)	journal.pgen.1000391	null	[ [ "Genetic sex determination ( GSD ) is prevalent in vertebrates and is often accompanied by the presence of a heteromorphic chromosome pair in one sex .", "Birds and snakes have a ZW heteromorphic pair , where the W sex chromosome is female-limited; however , neither the bird nor the snake sex determinatio...	[ "Diverse sex-chromosome systems are found in vertebrates , particularly in teleost fishes , where different systems can be found in closely related species .", "Several mechanisms have been proposed for the rapid turnover of sex chromosomes , including the transposition of an existing sex-determination gene , the...	[ "Sex chromosomes have independently evolved many times in animals , plants , and fungi .", "Although some sex chromosomes have been maintained across different species for over a hundred million years , there are other systems in which sex chromosomes appear to turn over within a few million years .", "Because ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "psychology", "cognitive psychology", "social and behavioral sciences", "mental health", "computational neuroscience", "biology", "neuroscience" ]	Dual Process for Intentional and Reactive Decisions	journal.pcbi.1003013	null	[ [ "Research on human action control typically distinguishes between two types of action: re-actions issued in response to some external stimulus event and voluntary actions based on an internal decision to act [1] , [2] .", "There has been a long-standing debate on whether these two types of action are cont...	[ "Efficient cognitive decisions should be adjustable to incoming novel information .", "However , most current models of decision making have so far neglected any potential interaction between intentional and stimulus-driven decisions .", "We report here behavioral results and a new model on the interaction betw...	[ "The topic of our study is the interaction between intentional and externally-driven actions .", "The contemporary literature on motor control in primates clearly distinguishes two neural mechanisms for these two types of actions .", "We believe that this distinction is artefactual and comes in part from the fa...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	Mitosis Gives a Brief Window of Opportunity for a Change in Gene Transcription	journal.pbio.1001914	In mitotic nuclei transplant experiments, many genes undergo major changes in gene expression. This supports the idea that mitosis facilitates new cell fate decisions during normal development.	[ [ "Normal development , as well as nearly all cases of experimentally induced changes in gene transcription , is accompanied by cell division .", "It is therefore hard to distinguish those molecular events which prepare cells for , or engage them in , mitosis from those that are required specifically for tr...	[ "Cell differentiation is remarkably stable but can be reversed by somatic cell nuclear transfer , cell fusion , and iPS .", "Nuclear transfer to amphibian oocytes provides a special opportunity to test transcriptional reprogramming without cell division .", "We show here that , after nuclear transfer to amphibi...	[ "Cells are dividing very actively at a time in development when new gene expression and new cell lineages arise .", "At mitosis , most transcription factors are temporarily displaced from chromosomes .", "We show that , after transplantation to oocytes , somatic cell nuclei that have been synchronized in mitosi...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "honey bees", "applied mathematics", "sociology", "social sciences", "animals", "simulation and modeling", "social systems", "algorithms", "systems science", "mathematics", "animal behavior", "probability distribution", "zoology", "research and analysis methods", "bees...	Costs of task allocation with local feedback: Effects of colony size and extra workers in social insects and other multi-agent systems	journal.pcbi.1005904	null	[ [ "Many systems in biology and engineering , from cells to mobile networks and human societies , consist of several or many interacting units that contribute ‘work’ towards a central goal [1–6] .", "Each of these systems employs a ‘task allocation mechanism’ , i . e . , individual workers choose , or are al...	[ "Adaptive collective systems are common in biology and beyond .", "Typically , such systems require a task allocation algorithm: a mechanism or rule-set by which individuals select particular roles .", "Here we study the performance of such task allocation mechanisms measured in terms of the time for individual...	[ "Many complex systems have to allocate their units to different functions: cells in an embryo develop into different tissues , servers in a computer cluster perform different calculations , and insect workers choose particular tasks , such as brood care or foraging .", "Here we demonstrate that this process does ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "developmental biology", "model organisms", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	Transcriptional Control in Cardiac Progenitors: Tbx1 Interacts with the BAF Chromatin Remodeling Complex and Regulates Wnt5a	journal.pgen.1002571	null	[ [ "The second heart field ( SHF ) provides progenitor cells for the development of several segments of the mature heart , such as the outflow tract , right ventricles and atria [1] , [2] .", "Mouse models of congenital heart disease suggest that perturbation of SHF development may be the basis of relatively...	[ "Mutations of the Wnt5a gene , encoding a ligand of the non-canonical Wnt pathway , and the Ror2 gene , encoding its receptor , have been found in patients with cardiac outflow tract defects .", "We found that Wnt5a is expressed in the second heart field ( SHF ) , a population of cardiac progenitor cells destined...	[ "We have demonstrated a novel interaction between the Tbx1 gene , the mutation of which causes DiGeorge syndrome , and Wnt5a , another human disease gene , which is important for oriented cell migration and cell polarity .", "We found that , in mice , reduced dosage of each of the two genes enhances the phenotype...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "pathology and laboratory medicine", "hela cells", "gene regulation", "pathogens", "biological cultures", "cell processes", "condensed matter physics", "cell cultures", "research and analysis methods", "contractile proteins", "small interfer...	Enteropathogenic E. coli relies on collaboration between the formin mDia1 and the Arp2/3 complex for actin pedestal biogenesis and maintenance	journal.ppat.1007485	null	[ [ "Bacteria and viruses have historically been useful tools for studying the regulation of cytoskeletal dynamics [1] , as several intracellular pathogens rearrange host actin into comet tails , which propel them through the cytosol [2] and/or promote their transmission from cell-to-cell [3] .", "Pathogen mo...	[ "Enteropathogenic and enterohemorrhagic E . coli ( EPEC and EHEC ) are closely related extracellular pathogens that reorganize host cell actin into “pedestals” beneath the tightly adherent bacteria .", "This pedestal-forming activity is both a critical step in pathogenesis , and it makes EPEC and EHEC useful mode...	[ "Microbial pathogens that rearrange the host actin cytoskeleton have made valuable contributions to our understanding of cell signaling and movement .", "The assembly and organization of the actin cytoskeleton is driven by proteins called nucleators , which can be manipulated by bacteria including enteropathogeni...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "plant biology/plant genetics and gene expression", "developmental biology/plant growth and development", "developmental biology/pattern formation" ]	Regulation of Small RNA Accumulation in the Maize Shoot Apex	journal.pgen.1000320	null	[ [ "Small regulatory RNAs play fundamental roles in diverse aspects of animal and plant development [1]–[2] .", "However , few examples exist in which small RNAs direct early patterning events .", "Leaves provide a unique developmental system in which multiple small RNAs pattern the adaxial-abaxial ( dor...	[ "MicroRNAs ( miRNAs ) and trans-acting siRNAs ( ta-siRNAs ) are essential to the establishment of adaxial–abaxial ( dorsoventral ) leaf polarity .", "Tas3-derived ta-siRNAs define the adaxial side of the leaf by restricting the expression domain of miRNA miR166 , which in turn demarcates the abaxial side of leave...	[ "Small RNAs regulate many key developmental processes .", "Consistent with a prominent role in development , miRNAs exhibit complex and distinctive expression patterns .", "In this study , we identify regulatory mechanisms that allow for the precise spatial accumulation of developmentally important small RNAs i...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biotechnology", "bioengineering", "computer science", "computer modeling", "biology", "computational biology", "engineering" ]	Functional Inference of Complex Anatomical Tendinous Networks at a Macroscopic Scale via Sparse Experimentation	journal.pcbi.1002751	null	[ [ "Much attention is given to functional networks ( e . g . , scale-free , small world and others ) resulting from the complex interactions between their constituents [e . g . , 1–5] .", "For example , the mechanisms of module assembly in biological molecular networks [6]–[8] ( with underlying motifs [9] ) ...	[ "In systems and computational biology , much effort is devoted to functional identification of systems and networks at the molecular-or cellular scale .", "However , similarly important networks exist at anatomical scales such as the tendon network of human fingers: the complex array of collagen fibers that trans...	[ "In science and medicine alike , one of the critical steps to understand the working of organisms is to identify how a given individual is similar or different from others .", "Only then can the specific features of an individual be distinguished from the general properties of that species .", "However , doing ...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/systems biology", "neurological disorders" ]	Vulnerabilities in the Tau Network and the Role of Ultrasensitive Points in Tau Pathophysiology	journal.pcbi.1000997	null	[ [ "Despite the fidelity of protein folding and the operation of quality control mechanisms to eliminate misfolded and otherwise abnormal proteins , a number of diseases can be traced to defects in these processes [1] .", "Among them are many neurodegenerative disorders , including the tauopathies , which ar...	[ "The multifactorial nature of disease motivates the use of systems-level analyses to understand their pathology .", "We used a systems biology approach to study tau aggregation , one of the hallmark features of Alzheimer's disease .", "A mathematical model was constructed to capture the current state of knowled...	[ "Neurodegenerative disorders , particularly the tauopathy Alzheimer's disease , affect millions of people and cost billions of dollars a year in healthcare costs .", "Although effective treatments to delay or reverse cognitive decline are still unavailable , several approaches to address this medical need are bei...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "parasitic cell cycles", "split-decomposition method", "microbiology", "parasitic diseases", "protozoan life cycles", "parasitic protozoans", "parasitology", "multiple alignment calculation", "developmental biology", "protozoans", "leishmania", "mitochondria",...	The mitochondrial SIR2 related protein 2 (SIR2RP2) impacts Leishmania donovani growth and infectivity	journal.pntd.0005590	null	[ [ "Acetylation and deacetylation of proteins have recently emerged as a major post-translational modification [1] .", "Initially described for N-terminal tails of histones [2] , reversible acetylation of proteins in the cytoplasm and in the mitochondria , suggest a central role for acetylation in regulatory...	[ "Leishmania donovani , a protozoan parasite is the major causative agent of visceral leishmaniasis .", "Increased toxicity and resistance to the existing repertoire of drugs has been reported .", "Hence , an urgent need exists for identifying newer drugs and drug targets .", "Previous reports have shown sirtu...	[ "Sirtuins are present in most organisms , including plants , bacteria , and animals .", "They play a vital role in promoting an organism’s health and survival .", "These proteins are involved in the regulation of several functions in eukaryotic cells , including transcriptional repression , recombination , cell...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "parasite groups", "plasmodium", "tropical diseases", "parasitic diseases", "parasitic protozoans", "genetic mapping", "parasitology", "preventive medicine", "mutation", "apicomplexa", "protozoans", "public and occupational health", "malarial parasites", "...	The prevalence and antifolate drug resistance profiles of Plasmodium falciparum in study participants randomized to discontinue or continue cotrimoxazole prophylaxis	journal.pntd.0007223	null	[ [ "Despite the changes in the epidemiology and improvement in the control of HIV-infection and malaria , both remain important infectious diseases and global health priorities .", "Through immunosuppression , HIV infection affects the acquisition and persistence of immune response to malaria , causing subst...	[ "Cotrimoxazole prevents opportunistic infections including falciparum malaria in HIV-infected individuals but there are concerns of cross-resistance to other antifolate drugs such as sulphadoxine-pyrimethamine ( SP ) .", "In this study , we investigated the prevalence of antifolate-resistance mutations in Plasmod...	[ "Cotrimoxazole , an antifolate , is a fixed-dose trimethoprim-sulfamethoxazole used to prevent opportunistic infections including malaria in HIV-infected individuals .", "There are concerns that widespread use of cotrimoxazole for prophylaxis may result in selection of P . falciparum parasites with cross-resistan...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biogeography", "livestock", "medicine and health sciences", "ecology and environmental sciences", "ruminants", "population genetics", "vertebrates", "animals", "mammals", "farms", "population biology", "bacteria", "veterinary science", "genetic epidemiology", "swine", "veterinary dise...	Genotype diversity and distribution of Mycobacterium bovis from livestock in a small, high-risk area in northeastern Sicily, Italy	journal.pntd.0007546	null	[ [ "Bovine tuberculosis ( bTB ) is an infectious disease of worldwide distribution caused mainly by Mycobacterium bovis , one of the members of the Mycobacterium tuberculosis complex ( MTC ) .", "M . bovis has the broadest host range of any member of the MTC , and an intricate epidemiological pattern of infe...	[ "Bovine tuberculosis ( bTB ) caused by Mycobacterium bovis is an important re-emerging disease affecting livestock , wildlife and humans .", "Epidemiological studies are crucial to identifying the source of bTB infection , and its transmission dynamics and host preference , and thus to the implementation of effec...	[ "Bovine tuberculosis is a widespread infectious disease affecting both domestic and wild animals , as well as humans .", "In addition to being of public health concern , the disease , caused mainly by Mycobacterium bovis , has a significant economic impact on the farming industry due to the costs of eradication e...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "cell biology", "biology and life sciences", "molecular biology" ]	Rabies Virus Hijacks and Accelerates the p75NTR Retrograde Axonal Transport Machinery	journal.ppat.1004348	null	[ [ "Rabies virus ( RABV ) is a neurotropic negative-strand RNA virus of the Lyssavirus genus , belonging to the Rhabdoviridae family .", "It is transmitted mostly via bites of diseased animals and causes a fatal infection of the nervous system in both animals and humans .", "A key step in RABV pathogenes...	[ "Rabies virus ( RABV ) is a neurotropic virus that depends on long distance axonal transport in order to reach the central nervous system ( CNS ) .", "The strategy RABV uses to hijack the cellular transport machinery is still not clear .", "It is thought that RABV interacts with membrane receptors in order to i...	[ "Rabies virus ( RABV ) is a neurotropic virus that depends on long distance axonal transport in order to reach the central nervous system ( CNS ) .", "The strategy RABV uses to hijack the cellular transport machinery is unknown .", "Here we use live cell imaging to track RABV entry at nerve terminals and study ...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[]	Discovery and characterization of variance QTLs in human induced pluripotent stem cells	journal.pgen.1008045	null	[ [ "Robustness , or the ability to maintain a stable phenotype despite genetic mutations and environmental perturbations , is an important property of many key biological processes , such as those underlying embryogenesis and development [1 , 2] .", "Conversely , evolvability , or the ability to generate her...	[ "Quantification of gene expression levels at the single cell level has revealed that gene expression can vary substantially even across a population of homogeneous cells .", "However , it is currently unclear what genomic features control variation in gene expression levels , and whether common genetic variants m...	[ "Common genetic variation can alter the level of average gene expression in human tissues , and through changes in gene expression have downstream consequences on cell function , human development , and human disease .", "However , human tissues are composed of many cells , each with its own level of gene express...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "auditory cortex", "medicine and health sciences", "action potentials", "engineering and technology", "signal processing", "topographic maps", "membrane potential", "brain", "brain electrophysiology", "electrophysiology", "neuroscience", "signal filtering", "brain mapping", "computational ...	Topographic Distribution of Stimulus-Specific Adaptation across Auditory Cortical Fields in the Anesthetized Rat	journal.pbio.1002397	This study of higher-order auditory cortex strengthens the case for long-latency stimulus-specific adaptation as a genuine neural correlate of the mismatch negativity, which flags salient stimuli.	[ [ "A critical function of the brain is to identify uncommon and potentially important stimuli while ignoring irrelevant ambient backgrounds [1–3] .", "In humans , this ability is reflected by an electrophysiological brain response called mismatch negativity ( MMN ) , a mid-late ( 150–200 ms ) deflection of ...	[ "Stimulus-specific adaptation ( SSA ) in single neurons of the auditory cortex was suggested to be a potential neural correlate of the mismatch negativity ( MMN ) , a widely studied component of the auditory event-related potentials ( ERP ) that is elicited by changes in the auditory environment .", "However , se...	[ "Sensory systems automatically detect salient events in a monotonous ambient background .", "In humans , this change detection process is indexed by the mismatch negativity ( MMN ) , a mid-late component of the auditory-evoked potentials that has become a central tool in cognitive and clinical neuroscience over t...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "statistical mechanics", "neuroscience", "animal behavior", "animal management", "phase transformation", "biology", "agriculture", "behavioral ecology", "physics", "systems biology", "computer science", "condensed-matter physics", "computer modeling", "ecology", "biophysic al simulations...	Deciphering Interactions in Moving Animal Groups	journal.pcbi.1002678	null	[ [ "Collective motion occurs across a variety of scales in nature , offering a wealth of fascinating phenomena which have attracted a lot of attention [1]–[5] .", "The self-organized motion of social animals is particularly intriguing because the behavioral rules the individuals actually follow and from whic...	[ "Collective motion phenomena in large groups of social organisms have long fascinated the observer , especially in cases , such as bird flocks or fish schools , where large-scale highly coordinated actions emerge in the absence of obvious leaders .", "However , the mechanisms involved in this self-organized behav...	[ "Swarms of insects , schools of fish and flocks of birds display an impressive variety of collective patterns that emerge from local interactions among group members .", "These puzzling phenomena raise a variety of questions about the behavioral rules that govern the coordination of individuals' motions and the e...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model	journal.pntd.0003924	null	[ [ "Enterotoxigenic Escherichia coli ( ETEC ) is a significant cause of human morbidity due to infectious diarrhea and resultant malnutrition [1] .", "A recent Global Enteric Multicenter study conducted over a 3-year period to identify the etiology of pediatric diarrheal diseases in sub-Saharan Africa and So...	[ "Enterotoxigenic Escherichia coli ( ETEC ) is an endemic health threat in underdeveloped nations .", "Despite the significant effort extended to vaccine trials using ETEC colonization factors , these approaches have generally not been especially effective in mediating cross-protective immunity .", "We used quan...	[ "Diarrheal disease is an endemic health threat in underdeveloped nations .", "One of the major causative agents of diarrheal disease is a group of bacteria collectively known as enterotoxigenic Escherichia coli ( ETEC ) .", "These organisms can cause disease symptoms ranging from mild diarrhea to a more severe ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "dermatology/psoriasis and other inflammatory diseases", "genetics and genomics/complex traits", "genetics and genomics/genetics of disease", "genetics and genomics/medical genetics" ]	Multiple Loci within the Major Histocompatibility Complex Confer Risk of Psoriasis	journal.pgen.1000606	null	[ [ "Psoriasis ( Ps ) is a relatively common , T cell-mediated , inflammatory skin disease .", "Ps is typically manifested as thickened scaly red plaques , characterized by epidermal hyperplasia , increased vascularity in the dermis , and infiltration of inflammatory cells into the dermis and epidermis [1] , ...	[ "Psoriasis is a common inflammatory skin disease characterized by thickened scaly red plaques .", "Previously we have performed a genome-wide association study ( GWAS ) on psoriasis with 1 , 359 cases and 1 , 400 controls , which were genotyped for 447 , 249 SNPs .", "The most significant finding was for SNP rs...	[ "Psoriasis ( Ps ) is a chronic inflammatory disease of the skin , affecting approximately 2% of Europeans .", "The HLA-C gene , located within the major histocompatibility complex ( MHC ) region on chromosome 6 , is the major genetic determinant of psoriasis .", "However , multiple susceptibility genes within M...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "antibody-producing cells", "white blood cells", "immune evasion", "immune cells", "cell biology", "animal cells", "b cells", "parasitology", "biology and life sciences", "cellular types", "immunology", "immune suppression", "immunomodulation", "vaccination and immunizatio...	Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection	journal.pntd.0003170	null	[ [ "More than 1 billion people are infected with helminths worldwide , predominantly in the tropics and subtropics [1] .", "To avoid their elimination and to limit pathology , helminths have developed sophisticated strategies to dampen the immune response of their hosts [2] , [3] .", "This helminth-induc...	[ "One-third of the human population is infected with parasitic worms .", "To avoid being eliminated , these parasites actively dampen the immune response of their hosts .", "This immune modulation also suppresses immune responses to third-party antigens such as vaccines .", "Here , we used Litomosoides sigmodo...	[ "Parasitic worms , called helminths , infect one-third of the world population .", "Despite exposure to their host's immune system many helminths establish chronic infections and survive several years within their host .", "They avoid elimination by dampening the immune response of their hosts .", "This immun...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "cell motility", "actin filaments", "vesicles", "cell processes", "pollen", "plant science", "cellular structures and organelles", "dynamic actin filaments", "contractile proteins", "actins", "actin polymerization", "proteins", "pollen tube", "cell membranes", "biochem...	Arabidopsis class I formins control membrane-originated actin polymerization at pollen tube tips	journal.pgen.1007789	null	[ [ "The pollen tube is the passage for two non-motile sperm cells and its proper growth is essential for successful reproduction in flowering plants [1–3] .", "Pollen tube growth is tightly regulated , and this raises many fascinating questions .", "Numerous studies suggest that the actin cytoskeleton is...	[ "A population of dynamic apical actin filaments is required for rapid polarized pollen tube growth .", "However , the cellular mechanisms driving their assembly remain incompletely understood .", "It was postulated that formin is a major player in nucleating apical actin assembly , but direct genetic and cytolo...	[ "Actin polymerization has been implicated in the regulation of rapid polarized pollen tube growth .", "The important role of actin polymerization is well appreciated , but the mechanisms that regulate rapid actin polymerization in pollen tubes remain incompletely understood .", "It was postulated that one of th...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signal transduction", "signaling in cellular processes", "model organisms", "cellular stress responses", "adenylyl cyclase signaling pathway", "mechanisms of signal transduction", "genetics", "tor signaling", "ras signaling", "signaling pathways", "biology", "microbiology", "molecular cell ...	Serine- and Threonine/Valine-Dependent Activation of PDK and Tor Orthologs Converge on Sch9 to Promote Aging	journal.pgen.1004113	null	[ [ "Calorie restriction ( CR ) , which usually refers to a 20–40% reduction in calorie intake , can effectively prolong life span in taxonomically diverse organisms ranging from yeasts to mammals [1] .", "It is also known that selective restriction of carbohydrates or proteins , as well as alternate day fast...	[ "Dietary restriction extends longevity in organisms ranging from bacteria to mice and protects primates from a variety of diseases , but the contribution of each dietary component to aging is poorly understood .", "Here we demonstrate that glucose and specific amino acids promote stress sensitization and aging th...	[ "Calorie restriction ( CR ) , but also the restriction of specific components of the diet , has been known for decades to affect longevity .", "However , the understanding of how each component of the macronutrients affects longevity and stress resistance is poorly understood , in part because of the complexity o...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "engineering and technology", "molecular probe techniques", "probability distribution", "mathematics", "statistics (mathematics)", "industrial engineering", "quality control", "forms of dna", "bioassays and physiological analysis", "molecular biology techniques", "dna"...	Mixture models reveal multiple positional bias types in RNA-Seq data and lead to accurate transcript concentration estimates	journal.pcbi.1005515	null	[ [ "RNA-Seq has established itself as a popular alternative to microarrays for the quantification of RNA transcripts .", "In contrast to microarrays , which measure the quantity of an RNA transcript by hybridization to a transcript specific oligonucleotide , RNA-Seq generates cDNA for fragments of the RNA tr...	[ "Accuracy of transcript quantification with RNA-Seq is negatively affected by positional fragment bias .", "This article introduces Mix2 ( rd . “mixquare” ) , a transcript quantification method which uses a mixture of probability distributions to model and thereby neutralize the effects of positional fragment bia...	[ "RNA-Seq is a powerful tool for detecting and quantifying genes and gene isoforms .", "However , accurate quantification in genomic loci with multiple isoforms has proven difficult .", "This is due to the fact that the transcript generating an RNA-Seq fragment cannot be identified if multiple transcripts share ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immunology", "tropical diseases", "geographical locations", "south sudan", "vaccines", "preventive medicine", "bacterial diseases", "animal behavior", "neglected tropical diseases", "infectious disease control", "vaccination and immunization", "zoology", "a...	Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects	journal.pntd.0006257	null	[ [ "Vaccination campaigns with sufficiently high efficacy and coverage can ideally achieve herd immunity in the population .", "Herd immunity emerges when the indirect protection of vaccination reduces the per-case expected number of onward infections in a population ( i . e . , the effective reproductive nu...	[ "Oral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings .", "However , vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy .", "As the supply and utilization ...	[ "Cholera vaccination can be a relatively quick means to temporarily prevent cholera from spreading in an at-risk population .", "In order to understand how long this temporary protection remains and therefore the timeline for when we need to install longer-term water and sanitation solutions , we must know how lo...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	PCNA Ubiquitination Is Important, But Not Essential for Translesion DNA Synthesis in Mammalian Cells	journal.pgen.1002262	null	[ [ "Translesion DNA synthesis is a universal DNA damage tolerance mechanism , which enables continuous functioning of replication despite the presence of DNA lesions .", "While the replisome might be able to bypass lesions that cause minor changes in the structure of DNA , lesions which are bulky or cause si...	[ "Translesion DNA synthesis ( TLS ) is a DNA damage tolerance mechanism in which specialized low-fidelity DNA polymerases bypass replication-blocking lesions , and it is usually associated with mutagenesis .", "In Saccharomyces cerevisiae a key event in TLS is the monoubiquitination of PCNA , which enables recruit...	[ "DNA damage can block replication and lead to mutations , genomic instability , and cancer .", "In cases when the removal of DNA damage and restoration of the original sequence prior to replication is impossible , cells utilize DNA damage tolerance mechanisms , which help replication to bypass the lesions .", "...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "fungal genetics", "fungi", "genome analysis", "genome annotation", "research and analysis methods", "paracoccidioides", "mycology", "genomics", "biological databases", "comparative genomics", "fungal genomics", "eukaryota", "database and informatics methods", "genetics", "biology and li...	ParaDB: A manually curated database containing genomic annotation for the human pathogenic fungi Paracoccidioides spp.	journal.pntd.0007576	null	[ [ "The genus Paracoccidioides includes a series of thermodymorphic fungi responsible for causing a neglected tropical disease known as paracoccidioidomycosis ( PCM ) , which represents one of the most prevalent systemic mycoses in Latin America [1] .", "In fact , approximately 10 million people have been es...	[ "The genus Paracoccidioides consists of thermodymorphic fungi responsible for Paracoccidioidomycosis ( PCM ) , a systemic mycosis that has been registered to affect ~10 million people in Latin America .", "Biogeographical data subdivided the genus Paracoccidioides in five divergent subgroups , which have been rec...	[ "The genus Paracoccidioides comprises fungi responsible for Paracoccidioidomycosis ( PCM ) , a neglected tropical disease prevalent in South America that has been shown to affect approximately 10 million people and has great medical/social impact , since available treatments are poorly effective , frequently leadin...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "game theory", "medicine", "public health and epidemiology", "mathematics", "epidemiology", "infectious disease epidemiology", "applied mathematics", "biology", "computational biology", "public health" ]	The Impact of Imitation on Vaccination Behavior in Social Contact Networks	journal.pcbi.1002469	null	[ [ "Vaccination is the primary public health measure for preventing transmission of infectious diseases as well as reducing morbidity and mortality from infections [1] .", "An individual's decision-making with respect to vaccination may depend on perceived risk of infection , cost of infection , cost of vacc...	[ "Previous game-theoretic studies of vaccination behavior typically have often assumed that populations are homogeneously mixed and that individuals are fully rational .", "In reality , there is heterogeneity in the number of contacts per individual , and individuals tend to imitate others who appear to have adopt...	[ "Both infectious diseases and behavioral traits can spread via social contacts .", "Using network-based mathematical models , our study addresses the interplay between these two processes , as disease spreads through a population and individuals copy their social contacts when making vaccination decisions .", "...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "evolutionary biology", "genomic evolution", "evolutionary genetics" ]	The Hmr and Lhr Hybrid Incompatibility Genes Suppress a Broad Range of Heterochromatic Repeats	journal.pgen.1004240	null	[ [ "As populations diverge , their ability to reproduce with each other diminishes .", "Hybrid incompatibility ( HI ) , the reduced viability and fertility of interspecific hybrids , is a major cause of reproductive isolation between nascent species and thus an important contributor to speciation .", "Ma...	[ "Hybrid incompatibilities ( HIs ) cause reproductive isolation between species and thus contribute to speciation .", "Several HI genes encode adaptively evolving proteins that localize to or interact with heterochromatin , suggesting that HIs may result from co-evolution with rapidly evolving heterochromatic DNA ...	[ "Sister species capable of mating often produce hybrids that are sterile or die during development .", "This reproductive isolation is caused by incompatibilities between the two sister species' genomes .", "Some hybrid incompatibilities involve genes that encode rapidly evolving proteins that localize to heter...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Bayesian Estimation of Conditional Independence Graphs Improves Functional Connectivity Estimates	journal.pcbi.1004534	null	[ [ "In the early days of neuroscience much attention was devoted to identifying the functional specialization of different brain areas [1] .", "More recently , this focus has shifted towards revealing how these areas are organized into networks and how these networks , rather than their individual constituen...	[ "Functional connectivity concerns the correlated activity between neuronal populations in spatially segregated regions of the brain , which may be studied using functional magnetic resonance imaging ( fMRI ) .", "This coupled activity is conveniently expressed using covariance , but this measure fails to distingu...	[ "Significant neuroscientific effort is devoted to elucidating functional connectivity between spatially segregated brain regions .", "This requires that we are able to quantify the degree of dependence between the signals of different areas .", "Yet how this must be accomplished—using which measures , each with...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "histology", "dermatology", "clinical genetics", "model organisms", "ophthalmology", "genetics", "biology", "molecular cell biology", "genetics and genomics", "cardiovascular" ]	Microenvironmental Regulation by Fibrillin-1	journal.pgen.1002425	null	[ [ "Mutations in fibrillin-1 cause the pleiotropic features of the Marfan syndrome ( MFS , OMIM#154700 ) .", "MFS is recognized by its unique combination of skeletal , cardiovascular , and ocular features ( long bone overgrowth , aortic root dilatation and dissection , and ectopia lentis ) .", "More than...	[ "Fibrillin-1 is a ubiquitous extracellular matrix molecule that sequesters latent growth factor complexes .", "A role for fibrillin-1 in specifying tissue microenvironments has not been elucidated , even though the concept that fibrillin-1 provides extracellular control of growth factor signaling is currently app...	[ "The microenvironment is specified by cell-surface molecules , growth factors , and the extracellular matrix .", "Here we report genetic evidence that implicates fibrillin-1 , a ubiquitous extracellular matrix molecule that sequesters latent growth factor complexes , as a key determinant in the local control of m...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "transfection", "phosphorylation", "medicine and health sciences", "immune cells", "chemical compounds", "gene regulation", "immunology", "organic compounds", "micrornas", "tyrosine", "immunoprecipitation", "amino acids", "molecular biology techniques", "research and analy...	miR-126-5p by direct targeting of JNK-interacting protein-2 (JIP-2) plays a key role in Theileria-infected macrophage virulence	journal.ppat.1006942	null	[ [ "Theileria annulata is an apicomplexan parasite causing a widespread disease called tropical theileriosis that is endemic to North Africa , the Middle East , vast parts of India and China [1] .", "The parasite can infect bovine B cells , but in the natural environment , predominantly infects macrophages ....	[ "Theileria annulata is an apicomplexan parasite that infects and transforms bovine macrophages that disseminate throughout the animal causing a leukaemia-like disease called tropical theileriosis .", "Using deep RNAseq of T . annulata-infected B cells and macrophages we identify a set of microRNAs induced by infe...	[ "Theileria annulata-infected bovine macrophages lose their hyper-disseminating virulent phenotype during long-term culture and are used as attenuated live vaccines to fight tropical theileriosis .", "Deep microRNA sequencing revealed that infection of both B cells and macrophages alters the expression of a large ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "dendritic cells", "white blood cells", "medicine and health sciences", "immune cells", "protozoans", "cell biology", "animal cells", "t cells", "antigen-presenting cells", "biology and life sciences", "cellular types", "immunology", "tropical diseases", "neglected tropica...	Cathepsin B in Antigen-Presenting Cells Controls Mediators of the Th1 Immune Response during Leishmania major Infection	journal.pntd.0003194	null	[ [ "Worldwide , 2 million new cases of leishmaniasis occur every year .", "It is endemic in 98 countries , where 350 million people are considered to be at risk , largely affecting “the poorest of the poor” [1] , [2] .", "The cutaneous form of leishmaniasis is characterized by lesions that heal over the ...	[ "Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression .", "Previous reports involving the use of cysteine cathepsin inhibitors indicated that catheps...	[ "The emergence of resistance to the available drugs against cutaneous leishmaniasis emphasizes the need of new chemotherapeutic approaches .", "Cysteine proteases from Leishmania are important virulence factors and , therefore , interesting drug targets .", "Studies on inhibitors against these enzymes during Le...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "borrelia infection", "public health and epidemiology", "infectious disease epidemiology", "microbiology", "rickettsia", "relapsing fever", "bartonellosis", "bacterial diseases", "emerging infectious diseases", "neglected tropical diseases", "trench fever", "bacterial pathogens",...	Point-of-Care Laboratory of Pathogen Diagnosis in Rural Senegal	journal.pntd.0001999	null	[ [ "The POC immuno-chromatographic tests ( ICT ) tests for malaria and HIV diagnostics are extensively used in Africa [21] .", "The malaria RDT played a significant role in reducing of malaria morbidity [5] .", "Other diagnostic tests are either not available , or , as in case of trachoma , not suitable ...	[ "In tropical Africa , where the spectrum of the bacterial pathogens that cause fevers is poorly understood and molecular-based diagnostic laboratories are rare , the time lag between test results and patient care is a critical point for treatment of disease .", "We implemented POC laboratory in rural Senegal to r...	[ "In tropical Africa , clinical laboratories capable of performing complicated diagnostic studies like PCR are rare and are almost always found in large cities .", "Moreover , a number of infectious diseases , many of them are emerging and neglected , may be quickly and reliably diagnosed only by molecular biology...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "optimization", "mathematics", "fungal evolution", "molecular biology techniques", "genotyping", "bacteria", "bacterial pathogens", "research and analysis methods", "mycology", "genome complex...	ClassTR: Classifying Within-Host Heterogeneity Based on Tandem Repeats with Application to Mycobacterium tuberculosis Infections	journal.pcbi.1004475	null	[ [ "The genotyping technique known as MLVA ( multiple loci variable-number tandem repeats analysis ) , which identifies the number of copies of tandem repeat regions at specific pre-selected loci , has benefited the study of many bacteria .", "Data produced by MLVA can be used to glean information about bact...	[ "Genomic tools have revealed genetically diverse pathogens within some hosts .", "Within-host pathogen diversity , which we refer to as “complex infection” , is increasingly recognized as a determinant of treatment outcome for infections like tuberculosis .", "Complex infection arises through two mechanisms: wi...	[ "Within-host heterogeneity of an infection can arise through two distinct mechanisms: within-host mutation and reinfection .", "While current genotyping techniques based on MLVA ( multiple loci variable-number tandem repeat analysis ) can identify within-host diversity , standard methods for classifying the mecha...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "cancer genetics", "genome scans", "population genetics", "genome analysis tools", "trait locus analysis", "population biology", "genetic polymorphism", "biology", "genetics", "genomics", "genetics of disease", "genetics and genomics", "human genetics" ]	Susceptibility Loci Associated with Specific and Shared Subtypes of Lymphoid Malignancies	journal.pgen.1003220	null	[ [ "Lymphoid malignancies represent clonal proliferations occurring at various stages of differentiation of B and T cells .", "B-cell differentiation is characterized by a canonical set of DNA modifications , including somatic hypermutation , class switching , and VDJ recombination .", "If aberrant , the...	[ "The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype .", "However , multiple subtypes of lymphoma are observed in some families , suggesting shared pathways of genetic predisposition to these pathologically distinct entities .", "Using a two-st...	[ "B-cell lymphomas comprise several diseases representing aberrant proliferations of immune cells at various stages of maturation .", "It might be expected that dissimilar subtypes of lymphoma will have different etiologic and pathogenic mechanisms , reflecting the distinct histologic and clinical characteristics ...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "reproductive system", "rna interference", "gonads", "cell cycle and cell division", "cell processes", "cell differentiation", "developmental biology", "stem cells", "epigenetics", "research and analysis methods", "specimen preparation and treatment", "stainin...	A switch in the mode of Wnt signaling orchestrates the formation of germline stem cell differentiation niche in Drosophila	journal.pgen.1007154	null	[ [ "Stem cell self-renewal and differentiation are critical for maintaining the organ systems of multicellular organisms .", "Loss of stem cell self-renewal leads to aging , due to an inability to replenish these organs; while loss of differentiation leads to tumors , which can progress toward diseases such ...	[ "Germline stem cell ( GSC ) self-renewal and differentiation into gametes is regulated by both intrinsic factors in the germ line as well as extrinsic factors from the surrounding somatic niche .", "dWnt4 , in the escort cells of the adult somatic niche promotes GSC differentiation using the canonical β-catenin-d...	[ "Germ line association with the somatic cells is critical for various aspects of germ cell biology , including migration , self-renewal and differentiation .", "In Drosophila females , soma–germ line association begins during embryogenesis and continues until the mature egg is formed .", "In the adult , the som...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signal transduction", "cell biology", "cell cycle and cell division", "biology and life sciences", "cell processes", "molecular cell biology", "cellular structures and organelles", "cell signaling", "cytoskeleton", "parasitology" ]	The Apical Complex Provides a Regulated Gateway for Secretion of Invasion Factors in Toxoplasma	journal.ppat.1004074	null	[ [ "Apicomplexans are obligate parasites of metazoans that non-destructively enter their host cells .", "Here they feed and replicate before destructively escaping in search of further cells to invade .", "Apicomplexa comprises over 6000 species that parasitize virtually every animal group [1] .", "T...	[ "The apical complex is the definitive cell structure of phylum Apicomplexa , and is the focus of the events of host cell penetration and the establishment of intracellular parasitism .", "Despite the importance of this structure , its molecular composition is relatively poorly known and few studies have experimen...	[ "Apicomplexan parasites comprise major human pathogens , including the malaria-causing parasites Plasmodium spp .", ", and Toxoplasma gondii that causes birth defects and neurological disorders .", "Key to the success of this group was the evolution of the apical complex , a structure at the focus of the events...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "united states", "medicine and health sciences", "engineering and technology", "transportation", "tropical diseases", "geographical locations", "social sciences", "north america", "bacterial diseases", "research design", "data management", "eye diseases", "neglected tropical diseases", "su...	The cost of mapping trachoma: Data from the Global Trachoma Mapping Project	journal.pntd.0006023	null	[ [ "An estimated 285 million people worldwide live with visual impairment , including 39 million who are blind [1] .", "Trachoma is the leading infectious cause of avoidable blindness , responsible for the visual impairment of about 1 . 9 million people , of whom 0 . 5 million are irreversibly blind [2] .", ...	[ "The Global Trachoma Mapping Project ( GTMP ) was implemented with the aim of completing the baseline map of trachoma globally .", "Over 2 . 6 million people were examined in 1 , 546 districts across 29 countries between December 2012 and January 2016 .", "The aim of the analysis was to estimate the unit cost a...	[ "There are currently few data sets available to aid programmes in planning and budgeting for population-based surveys in low- and middle- income countries .", "With the objective of identifying cost drivers and key variables influencing prevalence survey costs , the authors collected expenses incurred during the ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	The bZIP Transcription Factor Rca1p Is a Central Regulator of a Novel CO2 Sensing Pathway in Yeast	journal.ppat.1002485	null	[ [ "Atmospheric carbon dioxide ( CO2 ) with a concentration of 0 . 039% is not only central to the Earth's biogeochemical carbon cycle but is also sensed as a signal by many organisms .", "The nematode and parasite of insects Neoaplectana carpocapsae localizes its prey via a CO2 gradient [1] , while avoidanc...	[ "Like many organisms the fungal pathogen Candida albicans senses changes in the environmental CO2 concentration .", "This response involves two major proteins: adenylyl cyclase and carbonic anhydrase ( CA ) .", "Here , we demonstrate that CA expression is tightly controlled by the availability of CO2 and identi...	[ "Skin infection , oral and vaginal thrush , or bloodstream candidiasis are some of the diseases caused by the human pathogen Candida albicans .", "The high versatility of infection niches reflects the capacity of this yeast to respond to strong variations in its environment such as CO2 concentration .", "This m...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	DNA Detection of Schistosoma japonicum: Diagnostic Validity of a LAMP Assay for Low-Intensity Infection and Effects of Chemotherapy in Humans	journal.pntd.0003668	null	[ [ "Schistosomiasis remains one of the most important chronic parasitic diseases in tropical regions and affects approximately 200 million people , despite the continued implementation of control measures [1] .", "Schistosomiasis japonica , caused by infection with Schistosoma japonicum , is mainly endemic i...	[ "Schistosomiasis has decreased significantly in prevalence and intensity of infection in China , thus more accurate and sensitive methods are desperately needed for the further control of schistosomiasis .", "The present work aimed to assess the utility of the loop-mediated isothermal amplification ( LAMP ) for d...	[ "Accurate diagnostic tests play a key role in patient management and control of schistosomiasis , especially in China where the prevalence and intensity of Schistosoma japonicum infection is low in recent years .", "The present study aimed to assess the utility of the loop-mediated isothermal amplification ( LAMP...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "biochemical simulations", "theoretical biology", "biology", "computational biology", "signaling networks" ]	Trade-Offs and Constraints in Allosteric Sensing	journal.pcbi.1002261	null	[ [ "Sensing is fundamental to life .", "All cells detect chemicals in their environment and modify their physiology in response to the chemicals detected .", "Yet fluctuations in the concentrations of extracellular chemicals and stochasticity in intracellular biochemistry confound the cellular “decision”...	[ "Sensing extracellular changes initiates signal transduction and is the first stage of cellular decision-making .", "Yet relatively little is known about why one form of sensing biochemistry has been selected over another .", "To gain insight into this question , we studied the sensing characteristics of one of...	[ "Sensing environmental changes is the first step in the process of cellular decision-making , but many different biochemical sensors exist and why one sensor is selected for a particular task over another is not known .", "Here we study the sensing properties of a simple and generic allosteric sensor to understan...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "infectious diseases", "virology", "immunology" ]	The Bacterial Symbiont Wolbachia Induces Resistance to RNA Viral Infections in Drosophila melanogaster	journal.pbio.1000002	Wolbachia are one of the most widespread intracellular bacteria. InDrosophila melanogaster, the presence ofWolbachia increases resistance to infection by RNA viruses.	[ [ "Wolbachia are obligatory , intracellular α-proteobacteria that infect a wide range of arthropods and filarial nematodes .", "They are found in 17% to 76% of surveyed arthropods and have recently been estimated to be present in 66% of all arthropod species [1–3]; therefore Wolbachia are one of the most wi...	[ "Wolbachia are vertically transmitted , obligatory intracellular bacteria that infect a great number of species of arthropods and nematodes .", "In insects , they are mainly known for disrupting the reproductive biology of their hosts in order to increase their transmission through the female germline .", "In D...	[ "Many symbiotic bacteria confer fitness benefits to the organisms that they infect .", "Wolbachia are one of the most widespread intracellular bacteria , infecting a great number of species of insects .", "Here we show that in the fruit fly Drosophila melanogaster , infection with Wolbachia increases resistance...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biofilms", "cell walls", "ecology and environmental sciences", "genomic library screening", "genomic library construction", "model organisms", "dna construction", "molecular biology techniques", "cellular structures and organelles", "research and analysis methods", "hyperexpression techniques",...	Targeted Changes of the Cell Wall Proteome Influence Candida albicans Ability to Form Single- and Multi-strain Biofilms	journal.ppat.1004542	null	[ [ "Candida albicans is the most predominant human fungal pathogen , causing both superficial and hematogenously disseminated infections [1] .", "These infections are complicated by C . albicans' ability to form biofilms , which are complex three-dimensional microbial structures attached to either biotic or ...	[ "Biofilm formation is an important virulence trait of the pathogenic yeast Candida albicans .", "We have combined gene overexpression , strain barcoding and microarray profiling to screen a library of 531 C . albicans conditional overexpression strains ( ∼10% of the genome ) for genes affecting biofilm developmen...	[ "Candida albicans is the most prevalent human fungal pathogen .", "Its ability to cause disease relies , in part , on the formation of biofilms , a protective structure of highly adherent cells tolerant to antifungal agents and the host immune response .", "The biofilm is considered as a persistent root of infe...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "biophysics", "virology" ]	Structure and Function of A41, a Vaccinia Virus Chemokine Binding Protein	journal.ppat.0040005	null	[ [ "Chemokines ( chemotactic cytokines ) comprise a large family of small ( ∼ 7–14 kDa ) , secreted proteins that direct the migration of leukocytes into areas of infection and inflammation , as part of the innate immune response [1 , 2] .", "They function by binding to cell surface glycosaminoglycans ( GAGs...	[ "The vaccinia virus ( VACV ) A41L gene encodes a secreted 30 kDa glycoprotein that is nonessential for virus replication but affects the host response to infection .", "The A41 protein shares sequence similarity with another VACV protein that binds CC chemokines ( called vCKBP , or viral CC chemokine inhibitor , ...	[ "As part of the innate immune response ( for example to virus infection ) , the body produces proteins called chemokines , which act by directing white blood cells ( leukocytes ) to the areas of infection and inflammation .", "Viruses have evolved mechanisms to fight this immune response .", "Indeed , so import...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "organismal evolution", "evolutionary biology", "synthetic biology", "microbiology", "neuroscience", "model organisms", "molecular genetics", "environmental biotechnology", "forms of evolution", "signaling in cellular processes", "biology", "molecular biology", "agricultur...	Induction of Biogenic Magnetization and Redox Control by a Component of the Target of Rapamycin Complex 1 Signaling Pathway	journal.pbio.1001269	null	[ [ "In biology , magnetism is a unique and virtually orthogonal physical property .", "As magnetic interactions can be contactless , remote , and permeable , integration of magnetic properties into biological systems provides another dimension for bioengineering and therapy .", "Magnetic functions may pr...	[ "Most organisms are simply diamagnetic , while magnetotactic bacteria and migratory animals are among organisms that exploit magnetism .", "Biogenic magnetization not only is of fundamental interest , but also has industrial potential .", "However , the key factor ( s ) that enable biogenic magnetization in coo...	[ "Most organisms do not respond to magnetic fields .", "However , “magnetotactic” bacteria and migratory animals can sense geomagnetic fields and alter their behavior accordingly .", "These organisms often contain small magnetic particles that may be responsible for sensing magnetic fields .", "In magnetotacti...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gram negative", "biology", "microbiology", "host-pathogen interaction", "bacterial pathogens" ]	Near Surface Swimming of Salmonella Typhimurium Explains Target-Site Selection and Cooperative Invasion	journal.ppat.1002810	null	[ [ "Salmonella enterica subspecies 1 serovar Typhimurium ( referred to as S . Typhimurium in this study ) is a common food-borne pathogen .", "Central to the pathogenesis of S . Typhimurium is its ability to invade intestinal cells , namely M-cells , epithelial cells and possibly dendritic cells [1] , [2] , ...	[ "Targeting of permissive entry sites is crucial for bacterial infection .", "The targeting mechanisms are incompletely understood .", "We have analyzed target-site selection by S . Typhimurium .", "This enteropathogenic bacterium employs adhesins ( e . g . fim ) and the type III secretion system 1 ( TTSS-1 ) ...	[ "The animal body is protected by physical , chemical and immunological barriers .", "Identification of “promising” target sites is therefore of importance for any pathogen .", "This crucial step of the infection is still poorly understood .", "Here , we have studied target site selection by the flagellated Gr...	2012
[ "Introduction", "Models", "Results", "Discussion" ]	[ "physics", "computational neuroscience", "single neuron function", "biophysics theory", "biology and life sciences", "physical sciences", "computational biology", "biophysics", "neuroscience", "biophysical simulations" ]	Power Laws from Linear Neuronal Cable Theory: Power Spectral Densities of the Soma Potential, Soma Membrane Current and Single-Neuron Contribution to the EEG	journal.pcbi.1003928	null	[ [ "The apparent ubiquity of power laws in nature and society , i . e . , that quantities or probability distributions satisfy the relationship ( 1 ) where α is the power-law exponent , has for a long time intrigued scientists [1] .", "Power laws in the tails of distributions have been reported in a wide ran...	[ "Power laws , that is , power spectral densities ( PSDs ) exhibiting behavior for large frequencies f , have been observed both in microscopic ( neural membrane potentials and currents ) and macroscopic ( electroencephalography; EEG ) recordings .", "While complex network behavior has been suggested to be at the ...	[ "The common observation of power laws in nature and society , that is , quantities or probabilities that follow distributions , has for long intrigued scientists .", "In the brain , power laws in the power spectral density ( PSD ) have been reported in electrophysiological recordings , both at the microscopic ( s...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience" ]	Cdk5 Regulates Accurate Maturation of Newborn Granule Cells in the Adult Hippocampus	journal.pbio.0060272	New neurons are born throughout life in the hippocampus. Cell-type-specific, single-gene ablation in newborn neurons reveals that the kinase cdk5 regulates growth of neuronal processes, identifying a key mechanism of neuronal integration within the adult brain.	[ [ "New granule cells are added into the dentate circuitry throughout life , as neurogenic neural stem and progenitor cells ( NPCs ) persist in the adult hippocampus [1] .", "Hippocampal NPCs give rise to only one neuronal subtype , excitatory dentate granule cells , in contrast to the other neurogenic area ...	[ "Newborn granule cells become functionally integrated into the synaptic circuitry of the adult dentate gyrus after a morphological and electrophysiological maturation process .", "The molecular mechanisms by which immature neurons and the neurites extending from them find their appropriate position and target are...	[ "Neural stem cells divide and generate new neurons throughout life in the mammalian hippocampus .", "After a distinct maturation process , newborn neurons become functionally integrated into the preexisting circuitry and appear to participate in hippocampal function , which is critically involved in certain forms...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "ecology", "microbiology" ]	The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing	journal.pbio.0060280	The most complete survey to date of bacterial diversity in the human gut shows extensive but temporary changes in the microbial community following ciprofloxacin treatment.	[ [ "Specialized microbial communities inhabit the skin , mucosal surfaces , and gastrointestinal tract of humans ( and other vertebrates ) from birth until death , with by far the largest populations in the colon [1 , 2] .", "Humans rely on their native microbiota for nutrition and resistance to colonization...	[ "The human intestinal microbiota is essential to the health of the host and plays a role in nutrition , development , metabolism , pathogen resistance , and regulation of immune responses .", "Antibiotics may disrupt these coevolved interactions , leading to acute or chronic disease in some individuals .", "Our...	[ "The intestinal microbiota is essential to human health , with effects on nutrition , metabolism , pathogen resistance , and other processes .", "Antibiotics may disrupt these interactions and cause acute disease , as well as contribute to chronic health problems , although technical challenges have hampered rese...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "gene regulation", "microbiology", "bacterial biochemistry", "gene function", "prokaryotic models", "model organisms", "molecular genetics", "microbial growth and development", "microbial physiology", "cell adhesion", "caulobacter crescentus", "biology", "bacterial physiolo...	A Cell Cycle and Nutritional Checkpoint Controlling Bacterial Surface Adhesion	journal.pgen.1004101	null	[ [ "The majority of bacteria in the biosphere exist within surface-attached communities [1]–[3] that facilitate metabolic cooperation , sharing of genetic information , and protect cells against stress ( reviewed in [1] ) .", "Environmental signals including nutrient availability , pH , and ion concentration...	[ "In natural environments , bacteria often adhere to surfaces where they form complex multicellular communities .", "Surface adherence is determined by the biochemical composition of the cell envelope .", "We describe a novel regulatory mechanism by which the bacterium , Caulobacter crescentus , integrates cell ...	[ "Bacteria predominantly exist within surface-attached communities that facilitate metabolic cooperation , sharing of genetic information , and protect cells against stress .", "The freshwater bacterium , Caulobacter crescentus elaborates an adhesive structure known as the holdfast , which enables surface attachme...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical characterization", "protein interactions", "hela cells", "enzymes", "cell cycle and cell division", "biological cultures", "cell processes", "enzymology", "in vivo imaging", "dna damage", "immunoprecipitation", "cell cultures", "dna", "co-immunoprecipitation", "ligases", "res...	Identification of UHRF2 as a novel DNA interstrand crosslink sensor protein	journal.pgen.1007643	null	[ [ "DNA interstrand crosslinks ( ICLs ) can obstruct the critical processes of transcription and replication [1] .", "If unrepaired , an ICL can perturb accurate chromosome segregation during mitosis when replication has not been completed due to the crosslink , this can additionally lead to replication fork...	[ "The Fanconi Anemia ( FA ) pathway is important for repairing interstrand crosslinks ( ICLs ) between the Watson-Crick strands of the DNA double helix .", "An initial and essential stage in the repair process is the detection of the ICL .", "Here , we report the identification of UHRF2 , a paralogue of UHRF1 , ...	[ "Fanconi Anemia is a genetic disease where patients typically have congenital abnormalities , develop bone marrow failure and suffer from cancer predisposition .", "The cells in patients have a reduced ability to repair a type of DNA damage where the two strands of the DNA double helix are physically linked toget...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "neurological disorders/epilepsy", "infectious diseases/neglected tropical diseases" ]	Epilepsy in Onchocerciasis Endemic Areas: Systematic Review and Meta-analysis of Population-Based Surveys	journal.pntd.0000461	null	[ [ "Recent surveys , based on rapid epidemiological mapping of onchocerciasis ( REMO ) , have revealed that the number of people infected with Onchocerca volvulus , the causative agent of onchocerciasis , had been largely underestimated .", "According to the latest REMO results obtained as part of the Africa...	[ "We sought to evaluate the relationship between onchocerciasis prevalence and that of epilepsy using available data collected at community level .", "We conducted a systematic review and meta-regression of available data .", "Electronic and paper records on subject area ever produced up to February 2008 .", "...	[ "Epilepsy is particularly common in tropical areas .", "One main reason is that many endemic infections have neurological consequences .", "In addition , the medical , social and demographic burden of epilepsy remains substantial in these countries where it is often seen as a contagious condition and where the ...	2009

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