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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "learning", "decision making", "social sciences", "neuroscience", "learning and memory", "optimization", "analysis of variance", "cognitive psychology", "mathematics", "statistics (mathematics)", "cognition", "research and analysis methods", "learning curves", "human learning", "behavior...	Confirmation bias in human reinforcement learning: Evidence from counterfactual feedback processing	journal.pcbi.1005684	null	[ [ "Goal-directed behaviour is composed of two core components [1]: one component is the decision-making process that starts with representing the available options and terminates in selecting the option with the highest expected value; the second component is reinforcement learning ( RL ) , through which outcom...	[ "Previous studies suggest that factual learning , that is , learning from obtained outcomes , is biased , such that participants preferentially take into account positive , as compared to negative , prediction errors .", "However , whether or not the prediction error valence also affects counterfactual learning ,...	[ "While the investigation of decision-making biases has a long history in economics and psychology , learning biases have been much less systematically investigated .", "This is surprising as most of the choices we deal with in everyday life are recurrent , thus allowing learning to occur and therefore influencing...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurobiology of disease and regeneration", "animal genetics", "gene regulation", "neuroscience", "animal models", "histology", "behavioral neuroscience", "model organisms", "molecular genetics", "gene expression", "biology", "mouse", "genotypes", "phenotypes", "protein translation", "...	ATXN2-CAG42 Sequesters PABPC1 into Insolubility and Induces FBXW8 in Cerebellum of Old Ataxic Knock-In Mice	journal.pgen.1002920	null	[ [ "Spinocerebellar Ataxia Type 2 ( SCA2 ) is one of 9 currently known inherited neurodegenerative diseases ( e . g . Huntington's disease , SCA1 , SCA3 , SBMA ) that are caused by an expanded CAG trinucleotide repeat within the coding region of the disease gene , which expands its size from generation to genera...	[ "Spinocerebellar Ataxia Type 2 ( SCA2 ) is caused by expansion of a polyglutamine encoding triplet repeat in the human ATXN2 gene beyond ( CAG ) 31 .", "This is thought to mediate toxic gain-of-function by protein aggregation and to affect RNA processing , resulting in degenerative processes affecting preferentia...	[ "Frequent age-associated neurodegenerative disorders like Alzheimer's , Parkinson's , and Lou Gehrig's disease are being elucidated molecularly by studying rare heritable variants .", "Various hereditary neurodegenerative disorders are caused by polyglutamine expansions in different proteins .", "In spite of th...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/cognitive neuroscience", "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Neurobiological Models of Two-Choice Decision Making Can Be Reduced to a One-Dimensional Nonlinear Diffusion Equation	journal.pcbi.1000046	null	[ [ "The response behavior in two-choice decision making tasks is well described by so-called sequential sampling models [6] , of which Ratcliff's Diffusion model [7] , [8] is a particularly successful variant .", "According to the Diffusion model there is a decision variable X , the evolution in time of whic...	[ "The response behaviors in many two-alternative choice tasks are well described by so-called sequential sampling models .", "In these models , the evidence for each one of the two alternatives accumulates over time until it reaches a threshold , at which point a response is made .", "At the neurophysiological l...	[ "The brain holds a central position in scientific theories of rational behavior .", "For example , brain activity is thought to stand in a causal relation to the decision making behavior observed in two-choice perceptual discrimination tasks .", "Although a lot is known about both the brain activity and the res...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "disease mapping", "public health and epidemiology", "epidemiology", "spatial epidemiology" ]	Geostatistical Model-Based Estimates of Schistosomiasis Prevalence among Individuals Aged ≤20 Years in West Africa	journal.pntd.0001194	null	[ [ "Schistosomiasis is a water-based disease caused by trematodes of the genus Schistosoma .", "The five schistosome species that are known to infect humans are Schistosoma mansoni , S . haematobium , S . intercalatum , S . mekongi , and S . japonicum .", "School-aged children are at highest risk of infe...	[ "Schistosomiasis is a water-based disease that is believed to affect over 200 million people with an estimated 97% of the infections concentrated in Africa .", "However , these statistics are largely based on population re-adjusted data originally published by Utroska and colleagues more than 20 years ago .", "...	[ "Schistosomiasis is a parasitic disease caused by a blood fluke that mainly occurs in Africa .", "Current prevalence estimates of schistosomiasis are based on historical data , and hence might be outdated due to control programs , improved sanitation , and water resources development and management ( e . g . , co...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal models", "caenorhabditis elegans", "behavioral neuroscience", "model organisms", "genetic polymorphism", "genetics", "population genetics", "biology", "neurotransmitters", "neuroethology", "neuroscience", "genetics and genomics", "gene function" ]	Long-Range Regulatory Polymorphisms Affecting a GABA Receptor Constitute a Quantitative Trait Locus (QTL) for Social Behavior in Caenorhabditis elegans	journal.pgen.1003157	null	[ [ "Most animal and human behaviors are variable , in part due to genetic variation between individuals .", "Genetic mapping of strain differences in anxiety , learning , activity levels , and the response to addictive drugs in mice , as well as aggression , locomotor activity , and sensory behaviors in Dros...	[ "Aggregation is a social behavior that varies between and within species , providing a model to study the genetic basis of behavioral diversity .", "In the nematode Caenorhabditis elegans , aggregation is regulated by environmental context and by two neuromodulatory pathways , one dependent on the neuropeptide re...	[ "In both animals and humans , normal individuals can behave differently in the same environment .", "Natural variation in behavior is partly due to genetic differences between individuals and partly due to experience .", "Mapping studies have demonstrated that the genetic component of natural behavioral variati...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/membranes and sorting", "virology/immunodeficiency viruses", "virology/virion structure, assembly, and egress" ]	The ESCRT-0 Component HRS is Required for HIV-1 Vpu-Mediated BST-2/Tetherin Down-Regulation	journal.ppat.1001265	null	[ [ "The assembly and release of HIV-1 particles requires a highly orchestrated series of interactions between proteins encoded by the virus and key cellular components , including elements of the cellular membrane trafficking apparatus and the ESCRT ( Endosomal Sorting Complexes Required for Transport ) machiner...	[ "The Endosomal Sorting Complexes Required for Transport ( ESCRT ) machinery , a highly conserved set of four hetero-oligomeric protein complexes , is required for multivesicular body formation , sorting ubiquitinylated membrane proteins for lysosomal degradation , cytokinesis and the final stages of assembly of a n...	[ "The release of HIV-1 particles requires a series of interactions between proteins encoded by the virus and key cellular components , including elements of the cellular membrane trafficking apparatus such as the Endosomal Sorting Complexes Required for Transport ( ESCRT ) machinery .", "This machinery is composed...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Oct4 Is Required ∼E7.5 for Proliferation in the Primitive Streak	journal.pgen.1003957	null	[ [ "Oct4 is a homeodomain-containing transcription factor ( TF ) of the POU family required for pluripotency in ES cells and preimplantation embryos [1] .", "It has been extensively characterized in ES cells , and established as a hub of the signaling network that maintains pluripotency [2]–[5] .", "Embr...	[ "Oct4 is a widely recognized pluripotency factor as it maintains Embryonic Stem ( ES ) cells in a pluripotent state , and , in vivo , prevents the inner cell mass ( ICM ) in murine embryos from differentiating into trophectoderm .", "However , its function in somatic tissue after this developmental stage is not w...	[ "Embryogenesis is an intricate process requiring that division , differentiation and position of cells are coordinated .", "During mammalian development early pluripotent populations are canalized or restricted in potency during embryogenesis .", "Due to considerable interest in how this fundamental state of pl...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immune activation", "immunology", "host-pathogen interaction", "microbiology", "animal models", "adaptive immunity", "model organisms", "immune defense", "immunoregulation", "animal models of infection", "biology", "immune response", "macaque", "immunity", "virology", "innate immunity...	Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure	journal.pntd.0002171	null	[ [ "Lassa virus ( LASV ) is a segmented negative-strand RNA virus and a member of the Arenavirus genus .", "LASV is a human pathogen that is endemic to several countries in West Africa .", "It is estimated to infect more than 300 , 000 people each year , killing over 3 , 000 with fatality rate for Lassa ...	[ "Lassa virus ( LASV ) is a significant human pathogen that is endemic to several countries in West Africa .", "Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases , and it is estimated that thousands die each year from the disease .", "Little is known about the com...	[ "Lassa virus ( LASV ) , a member of the Arenaviridae family , is a viral hemorrhagic fever causing virus endemic to several countries in West Africa with a history of sporadic importation into the United States .", "It has been characterized as a Category A agent , and despite the significant public health issues...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal genetics", "functional genomics", "genetic screens", "genetics", "molecular genetics", "biology", "genomics", "genetics and genomics", "gene function" ]	Cofilin-1: A Modulator of Anxiety in Mice	journal.pgen.1002970	null	[ [ "Exploiting naturally occurring genetic variation to identify mechanisms that give rise to behavioural phenotypes in mammals has proved to be extremely difficult [1] .", "The abundance and small size of loci that contribute to behavioural variation frustrate gene identification and make it difficult to kn...	[ "The genes involved in conferring susceptibility to anxiety remain obscure .", "We developed a new method to identify genes at quantitative trait loci ( QTLs ) in a population of heterogeneous stock mice descended from known progenitor strains .", "QTLs were partitioned into intervals that can be summarized by ...	[ "Thousands of small effect loci are believed to contribute to behavioural variation in mammals .", "Their abundance and small size frustrate gene identification and make it difficult to know which among them are central to the responsible biological mechanisms .", "Using imputed genome sequences from 2 , 000 ou...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Type I-E CRISPR-Cas Systems Discriminate Target from Non-Target DNA through Base Pairing-Independent PAM Recognition	journal.pgen.1003742	null	[ [ "There are several prokaryotic defense systems that confer innate immunity against invading mobile genetic elements , such as receptor masking , blocking DNA injection , restriction/modification ( R-M ) and abortive infection ( reviewed in [1]–[3] ) .", "In addition , half of the bacteria , and most of th...	[ "Discriminating self and non-self is a universal requirement of immune systems .", "Adaptive immune systems in prokaryotes are centered around repetitive loci called CRISPRs ( clustered regularly interspaced short palindromic repeat ) , into which invader DNA fragments are incorporated .", "CRISPR transcripts a...	[ "CRISPR loci and their associated genes form a diverse set of adaptive immune systems that are widespread among prokaryotes .", "In these systems , the CRISPR-associated genes ( cas ) encode for proteins that capture fragments of invading DNA and integrate these sequences between repeat sequences of the host's CR...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "evolutionary biology/evolutionary and comparative genetics", "microbiology/microbial physiology and metabolism", "cell biology/cell growth and division", "molecular biology/molecular evolution", "microbiology/microbial growth and development", "cell biology/cell...	The Protein Kinase Tor1 Regulates Adhesin Gene Expression in Candida albicans	journal.ppat.1000294	null	[ [ "Coordinated cell–cell adhesion is an essential biological process widely employed by organisms throughout the tree of life .", "In metazoans , cellular adhesion is important for numerous processes ranging from establishment of body plans and maintenance of differentiated tissues to regulation of cancer p...	[ "Eukaryotic cell growth is coordinated in response to nutrient availability , growth factors , and environmental stimuli , enabling cell–cell interactions that promote survival .", "The rapamycin-sensitive Tor1 protein kinase , which is conserved from yeasts to humans , participates in a signaling pathway central...	[ "Living organisms have an intrinsic ability to coordinate their growth and proliferation in response to nutrient availability .", "In organisms ranging from yeasts to humans , the Tor1 signaling pathway responds to nutrient-derived signals and orchestrates cell growth .", "Accordingly , we find that in the huma...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "veterinary diseases", "veterinary epidemiology", "zoonotic diseases", "veterinary science" ]	Use of Oxfendazole to Control Porcine Cysticercosis in a High-Endemic Area of Mozambique	journal.pntd.0001651	null	[ [ "Taenia solium is the etiologic agent of cysticercosis , an important zoonotic infection involving humans and pigs .", "The life cycle of this parasite includes pigs as the normal intermediate hosts , harbouring the larval cysts in many parts of the body causing cysticercosis , and humans as definitive ho...	[ "A randomized controlled field trial to evaluate the effectiveness of a single oral dose of 30 mg/kg of oxfendazole ( OFZ ) treatment for control of porcine cysticercosis was conducted in 4 rural villages of Angónia district , north-western Mozambique .", "Two hundred and sixteen piglets aged 4 months were select...	[ "Porcine cysticercosis is an infection of pigs caused by the larval stage of Taenia solium , a tapeworm that causes taeniosis in humans .", "The disease is very common in developing countries where it is a serious public health risk and causes significant economic losses in pig production .", "Many control stra...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "immunology", "microbiology", "host-pathogen interaction", "parasitic diseases", "parasitology", "cardiovascular", "neglected tropical diseases", "signaling pathways", "calcium signaling", "infectious diseases", "signaling in cellular processes", "biology", "pathogenesis", "a...	Trypanosoma cruzi Infection and Endothelin-1 Cooperatively Activate Pathogenic Inflammatory Pathways in Cardiomyocytes	journal.pntd.0002034	null	[ [ "Chagas' disease , caused by the infection with the protozoan parasite Trypanosoma cruzi , constitutes the major cause of infectious heart disease in Latin America .", "It is estimated that 10 million people are infected with T . cruzi in the Central and South America , 100–120 million are at potential ri...	[ "Trypanosoma cruzi , the causative agent of Chagas' disease , induces multiple responses in the heart , a critical organ of infection and pathology in the host .", "Among diverse factors , eicosanoids and the vasoactive peptide endothelin-1 ( ET-1 ) have been implicated in the pathogenesis of chronic chagasic car...	[ "Chronic cardiomyopathy is the most common and severe manifestation of human Chagas' disease , caused by the protozoan parasite Trypanosoma cruzi .", "Among diverse inflammation-promoting moieties , eicosanoids and the vasoactive peptide endothelin-1 ( ET-1 ) have been implicated in its pathogenesis .", "Nevert...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna repair", "biochemistry/replication and repair", "molecular biology/dna replication", "genetics and genomics/chromosome biology" ]	Mismatch Repair–Independent Increase in Spontaneous Mutagenesis in Yeast Lacking Non-Essential Subunits of DNA Polymerase ε	journal.pgen.1001209	null	[ [ "The accuracy by which DNA polymerases synthesize DNA is essential for maintaining genome stability and preventing carcinogenesis .", "Eukaryotes utilize many DNA polymerases , with different properties , during DNA replication and in DNA repair [1] .", "DNA polymerase δ ( Pol δ ) , DNA polymerase ε (...	[ "Yeast DNA polymerase ε ( Pol ε ) is a highly accurate and processive enzyme that participates in nuclear DNA replication of the leading strand template .", "In addition to a large subunit ( Pol2 ) harboring the polymerase and proofreading exonuclease active sites , Pol ε also has one essential subunit ( Dpb2 ) a...	[ "The high fidelity of DNA replication is safeguarded by the accuracy of nucleotide selection by DNA polymerases , proofreading activity of the replicative polymerases , and the DNA mismatch repair system .", "Errors made by replicative polymerases are corrected by mismatch repair , and inactivation of the mismatc...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunopathology", "immunity", "immunology", "host-pathogen interaction", "biology", "microbiology", "pathogenesis", "parasitology", "immune system" ]	The Malnutrition-Related Increase in Early Visceralization of Leishmania donovani Is Associated with a Reduced Number of Lymph Node Phagocytes and Altered Conduit System Flow	journal.pntd.0002329	null	[ [ "Protein-energy malnutrition ( PEM ) is thought to be the most frequent cause of human immunodeficiency [1] , and greatly predisposes individuals to infectious diseases in resource-poor regions of the world [2] .", "In its synergy with infection , under-nutrition contributes to approximately 50% of childh...	[ "In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4–5-fold increase in early visceralization of L . donovani ( 3 days post-infection ) following cutaneous infection and a 16-fold decrease in lymph node barrier function ( p<0 . 04 for all ) .", "To begin to unders...	[ "The impact of malnutrition in the world is staggering .", "Malnutrition is thought to directly or indirectly contribute to more than half of all childhood deaths , most of them related to heightened susceptibility to infection .", "Visceral leishmaniasis ( VL ) , caused by the intracellular protozoan Leishmani...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "allosteric regulation", "enzymes", "dna clamps", "enzymology", "phosphatases", "mutation", "network analysis", "mismatch repair", "dna", "dna structure", "enzyme chemistry", "computer and information sciences", "proteins", "enzyme regulation", "biophysics", "molecular biology", "ade...	Long-Range Signaling in MutS and MSH Homologs via Switching of Dynamic Communication Pathways	journal.pcbi.1005159	null	[ [ "Allostery is a fundamental part of many if not most biological processes .", "It is classically defined as the induced regulation at one site by an event at another distal site .", "Venerable models for allostery , such as the MWC ( Monod-Wyman-Changeux ) [1] and KNF ( Koshland-Nemethy-Filmer ) [2] m...	[ "Allostery is conformation regulation by propagating a signal from one site to another distal site .", "This study focuses on the long-range communication in DNA mismatch repair proteins MutS and its homologs where intramolecular signaling has to travel over 70 Å to couple lesion detection to ATPase activity and ...	[ "We are proposing a new model for how long-range allosteric communication may be accomplished via switching of pre-existing pathway as a result of only minor structural perturbations .", "The systems studied here are the bacterial mismatch repair enzyme MutS and its eukaryotic homologs where we identified strong ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/molecular evolution", "virology/virulence factors and mechanisms", "virology/virus evolution and symbiosis", "immunology/immunomodulation", "immunology/immune response", "immunology/innate immunity", "infectious diseases/viral infections", "biophysics/biomacromolecule-ligand interactions...	Structure of the HCMV UL16-MICB Complex Elucidates Select Binding of a Viral Immunoevasin to Diverse NKG2D Ligands	journal.ppat.1000723	null	[ [ "Human cytomegalovirus ( HCMV ) is a β-herpesvirus that causes lifelong asymptomatic infections in healthy individuals but endangers the lives of immunocompromised individuals and very young children [1] .", "Cytotoxic lymphocytes such as CD8 T cells and natural killer ( NK ) cells are essential for the c...	[ "The activating immunoreceptor NKG2D promotes elimination of infected or malignant cells by cytotoxic lymphocytes through engagement of stress-induced MHC class I-related ligands .", "The human cytomegalovirus ( HCMV ) -encoded immunoevasin UL16 subverts NKG2D-mediated immune responses by retaining a select group...	[ "Cytotoxic lymphocytes such as natural killer ( NK ) cells or CD8 T cells have the ability to detect and destroy cells infected by viruses .", "They therefore are tools on which the human immune system critically depends in order to control viral infections .", "To avoid discovery by cytotoxic lymphocytes and t...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "vertebrates", "viruses", "infectious diseases", "virology", "eukaryotes", "microbiology", "mus (mouse)", "animals" ]	Interfering Residues Narrow the Spectrum of MLV Restriction by Human TRIM5α	journal.ppat.0030200	null	[ [ "Retroelements constitute important evolutionary forces for the genome of higher organisms , yet their uncontrolled spread , whether from endogenous loci or within the context of retroviral infections , can cause diseases such as cancer , autoimmunity and immunodeficiency , including AIDS .", "Correspondi...	[ "TRIM5α is a restriction factor that limits infection of human cells by so-called N- but not B- or NB-tropic strains of murine leukemia virus ( MLV ) .", "Here , we performed a mutation-based functional analysis of TRIM5α-mediated MLV restriction .", "Our results reveal that changes at tyrosine336 of human TRIM...	[ "Mammalian cells are endowed with intrinsic lines of defence against retroviruses , which notably contribute to limiting the cross-species transmission of these pathogens .", "TRIM5α is one such restriction factor , which acts by recognizing the capsid of incoming retroviruses through its C-terminal PRYSPRY domai...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Epigenetic Dominance of Prion Conformers	journal.ppat.1003692	null	[ [ "Prion-mediated phenotypes and diseases result from the conformationally protean characteristics of particular amyloidogenic proteins .", "The prion state has the property of interacting with proteins in their non-prion conformation , thus inducing further prion conversion .", "The prion phenomenon ha...	[ "Although they share certain biological properties with nucleic acid based infectious agents , prions , the causative agents of invariably fatal , transmissible neurodegenerative disorders such as bovine spongiform encephalopathy , sheep scrapie , and human Creutzfeldt Jakob disease , propagate by conformational te...	[ "Prions are infectious proteins , originally discovered as the cause of a group of transmissible , fatal mammalian neurodegenerative diseases .", "Propagation results from conversion of the host-encoded cellular form of the prion protein to a self-propagating disease-associated conformation .", "It is believed ...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[]	Physical constraints on accuracy and persistence during breast cancer cell chemotaxis	journal.pcbi.1006961	null	[ [ "Chemotaxis plays a crucial role in many biological phenomena such as organism development , immune system targeting , and cancer progression [1–4] .", "Specifically , recent studies indicate that chemotaxis occurs during metastasis in many different types of cancer [2 , 5–9] .", "At the onset of meta...	[ "Directed cell motion in response to an external chemical gradient occurs in many biological phenomena such as wound healing , angiogenesis , and cancer metastasis .", "Chemotaxis is often characterized by the accuracy , persistence , and speed of cell motion , but whether any of these quantities is physically co...	[ "One of the most ubiquitous and important cell behaviors is chemotaxis: the ability to move in the direction of a chemical gradient .", "Due to its importance , key aspects of chemotaxis have been quantified for a variety of cells , including the accuracy , persistence , and speed of cell motion .", "However , ...	2019
[ "Introduction", "Results and discussion", "Material and methods" ]	[ "taxonomy", "invertebrates", "animals", "trichoplax adhaerens", "placozoa", "phylogenetics", "data management", "phylogenetic analysis", "energy-producing organelles", "mitochondria", "bioenergetics", "cellular structures and organelles", "research and analysis methods", "sequence analysis...	Comparative genomics and the nature of placozoan species	journal.pbio.2005359	null	[ [ "Placozoans Grell , 1971 , are small , benthic marine animals found worldwide in various habitats [1–6] .", "To date , only a single species has been described , Trichoplax adhaerens Schulze 1883 .", "Animals are flat and have a typically disc-like morphology but have the capacity to change shape [7–9...	[ "Placozoans are a phylum of nonbilaterian marine animals currently represented by a single described species , Trichoplax adhaerens , Schulze 1883 .", "Placozoans arguably show the simplest animal morphology , which is identical among isolates collected worldwide , despite an apparently sizeable genetic diversity...	[ "Placozoans are a phylum of tiny ( approximately 1 mm ) marine animals that are found worldwide in temperate and tropical waters .", "They are characterized by morphological simplicity , with only a handful of cell types , no neurons , no tissue organization , and even no axial polarity .", "Since the original ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/microbial physiology and metabolism", "cell biology/cellular death and stress responses", "cell biology/cell signaling", "infectious diseases/fungal infections", "microbiology/microbial growth and development", "microbiology/medical microbiology" ]	A Role for the Unfolded Protein Response (UPR) in Virulence and Antifungal Susceptibility in Aspergillus fumigatus	journal.ppat.1000258	null	[ [ "Aspergillus fumigatus is a soil-dwelling filamentous fungus that has become the predominant mold pathogen of the immunocompromised population [1] , [2] , [3] .", "The infection is acquired through the inhalation of aerosolized conidia ( spores ) , which are small enough to reach the distal airways [4] ."...	[ "Filamentous fungi rely heavily on the secretory pathway , both for the delivery of cell wall components to the hyphal tip and the production and secretion of extracellular hydrolytic enzymes needed to support growth on polymeric substrates .", "Increased demand on the secretory system exerts stress on the endopl...	[ "The pathogenic mold Aspergillus fumigatus is the leading cause of airborne fungal infections in immunocompromised patients .", "The fungus normally resides in compost , an environment that challenges the organism to obtain nutrients by degrading complex organic polymers .", "This is accomplished by secreted en...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "protein metabolism", "engineering and technology", "metabolic processes", "cancers and neoplasms", "oncology", "industrial engineering", "genome analysis", "quality control", "network analysis", "polycystic ovary syndrome", "computer and information sciences", ...	Reactome from a WikiPathways Perspective	journal.pcbi.1004941	null	[ [ "Pathway diagrams are a common way to represent a wealth of information about biological molecules , interactions and processes .", "Currently , the Pathguide collection lists 45 freely available pathway databases with human data , out of which only 14 provide the data in a machine readable format [1 , 2]...	[ "Reactome and WikiPathways are two of the most popular freely available databases for biological pathways .", "Reactome pathways are centrally curated with periodic input from selected domain experts .", "WikiPathways is a community-based platform where pathways are created and continually curated by any intere...	[ "Biological pathways are descriptive diagrams that describe biological processes , i . e . interactions between genes , proteins , and metabolites .", "Pathways can therefore be used to integrate and visualize molecular measurements of genes , proteins , and metabolites in different biological conditions , e . g ...	2016
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[]	TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus	journal.ppat.1005253	null	[ [ "TRIM21 is a ubiquitously expressed high-affinity cytosolic antibody receptor and E3 ubiquitin ligase [1] .", "TRIM21 intercepts incoming antibody-opsonized virions during cellular infection , mediating efficient post-entry neutralization [2] and innate immune signaling [3 , 4] .", "Unlike Fc gamma re...	[ "Encapsidation is a strategy almost universally employed by viruses to protect their genomes from degradation and from innate immune sensors .", "We show that TRIM21 , which targets antibody-opsonized virions for proteasomal destruction , circumvents this protection , enabling the rapid detection and degradation ...	[ "Our cells have potent immune sensors that can detect the presence of viral nucleic acid in the cytosol .", "Unfortunately , almost all viruses utilize a strategy of encapsidation , comprising a protein shell that protects their genomes and impedes them from being sensed or degraded .", "In our study , we descr...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "biology", "evolutionary biology", "viral diseases", "vectors and hosts" ]	Additive Protection by Antioxidant and Apoptosis-Inhibiting Effects on Mosquito Cells with Dengue 2 Virus Infection	journal.pntd.0001613	null	[ [ "The dengue virus ( DENV ) , a flavivirus belonging to the family Flaviviridae , is the etiological agent of dengue fever ( DF ) , dengue hemorrhagic fever ( DHF ) , and dengue shock syndrome ( DSS ) [1] .", "The genome of the DENV consists of a single-stranded positive-sense RNA of ∼11 kilobases ( kb ) l...	[ "Cytopathic effects ( CPEs ) in mosquito cells are generally trivial compared to those that occur in mammalian cells , which usually end up undergoing apoptosis during dengue virus ( DENV ) infection .", "However , oxidative stress was detected in both types of infected cells .", "Despite this , the survival of...	[ "This study demonstrated an idea that mosquito cells can survive dengue virus ( or other arboviruses ) infection through antioxidant defense and an additional effect by induction of IAP expression for protection of infection .", "It makes mosquito eligible to support virus replication efficiently , leading to a g...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "molecular biology/mrna stability", "molecular biology/translational regulation", "microbiology", "molecular biology" ]	Staphylococcus aureus RNAIII Binds to Two Distant Regions of coa mRNA to Arrest Translation and Promote mRNA Degradation	journal.ppat.1000809	null	[ [ "Staphylococcus aureus is ubiquitous in the environment and is a commensal organism found on human skin .", "This major human pathogen is the most common cause of hospital- and community-acquired infections .", "Therefore , S . aureus has developed a plethora of strategies to survive in various enviro...	[ "Staphylococcus aureus RNAIII is the intracellular effector of the quorum sensing system that temporally controls a large number of virulence factors including exoproteins and cell-wall-associated proteins .", "Staphylocoagulase is one major virulence factor , which promotes clotting of human plasma .", "Like t...	[ "Staphylococcus aureus causes a wide spectrum of diseases in humans and is one of the main causes of community- as well as hospital-acquired infections .", "S . aureus produces a large number of virulence factors that are expressed in a coordinated manner and at appropriate time and space .", "To this end , a s...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "insulin-dependent signal transduction", "cellular stress responses", "anatomy and physiology", "physiological processes", "developmental biology", "organism development", "signaling pathways", "biology", "aging", "signal transduction", "cell biology", "physiology", "genetics",...	The GATA Transcription Factor egl-27 Delays Aging by Promoting Stress Resistance in Caenorhabditis elegans	journal.pgen.1003108	null	[ [ "Responses to various forms of stress play an important role in aging and longevity .", "Several types of stress result in damage that can accumulate over time ( e . g . oxidative stress results in damaged proteins that often accumulate with age ) [1]–[3] .", "Responses to these stresses have protecti...	[ "Stress is a fundamental aspect of aging , as accumulated damage from a lifetime of stress can limit lifespan and protective responses to stress can extend lifespan .", "In this study , we identify a conserved Caenorhabditis elegans GATA transcription factor , egl-27 , that is involved in several stress responses...	[ "Stress is a fundamental aspect of aging , but it is unclear whether the molecular mechanisms underlying stress response become altered during normal aging and whether these alterations can affect the aging process .", "In this study , we found a GATA transcription factor called egl-27 , whose targets are signifi...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene regulation", "regulatory proteins", "messenger rna", "dna-binding proteins", "circadian oscillators", "transcription factors", "chronobiology", "proteins", "gene expression", "biochemistry", "circadian rhythms", "genetic oscillators", "rna", "biochemical simulations", "nucleic acid...	Kernel Architecture of the Genetic Circuitry of the Arabidopsis Circadian System	journal.pcbi.1004748	null	[ [ "A variety of living organisms on Earth features built-in molecular clock machineries that control the organism’s daily activities [1] .", "These internal time-keepers , circadian clocks , generate endogenous oscillations of gene expression with ~24 h periodicity , enabling the anticipation of diurnal env...	[ "A wide range of organisms features molecular machines , circadian clocks , which generate endogenous oscillations with ~24 h periodicity and thereby synchronize biological processes to diurnal environmental fluctuations .", "Recently , it has become clear that plants harbor more complex gene regulatory circuits ...	[ "Sleep/wake cycles in animals exemplify daily biological rhythms driven by internal molecular clocks , circadian clocks , which are important for plant life as well .", "The plant circadian clock is highly complex , eluding our understanding of its design principle .", "Based on the computational simulation of ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Cutaneous Distribution and Circadian Rhythm of Onchocerca lupi Microfilariae in Dogs	journal.pntd.0002585	null	[ [ "Vector-borne nematodes of the family Onchocercidae ( Spirurida ) are of major medical concern .", "Among others , adult worms of Wuchereria bancrofti and Brugia malayi may live in the lymphatic system of humans causing obstruction ( i . e . , elephantiasis ) and those of Onchocerca volvulus in the subcut...	[ "Among the arthropod-borne nematodes infesting dogs , Onchocerca lupi ( Spirurida: Onchocercidae ) is of increasing zoonotic concern , with new human cases of infection diagnosed in Turkey , Tunisia , Iran and the USA .", "Knowledge of the biology of this nematode is meagre .", "This study aimed at assessing th...	[ "Onchocerca lupi is a little known arthropod-borne helminth infesting dogs of increasing interest to the scientific community due to the recent demonstration of its zoonotic potential .", "Nonetheless , knowledge of the biology of this nematode is exiguous .", "In this study the distribution and periodicity of ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Transgenic Fatal Familial Insomnia Mice Indicate Prion Infectivity-Independent Mechanisms of Pathogenesis and Phenotypic Expression of Disease	journal.ppat.1004796	null	[ [ "Prion strains with unique self-templating and neurotoxic properties are thought to emerge spontaneously in humans carrying genetic prion disease-associated PrP mutations , dictating the phenotypic expression of disease .", "Here we report that transgenic ( Tg ) mice carrying the PrP mutation associated w...	[ "Fatal familial insomnia ( FFI ) and a genetic form of Creutzfeldt-Jakob disease ( CJD178 ) are clinically different prion disorders linked to the D178N prion protein ( PrP ) mutation .", "The disease phenotype is determined by the 129 M/V polymorphism on the mutant allele , which is thought to influence D178N Pr...	[ "Genetic prion diseases are degenerative brain disorders caused by mutations in the gene encoding the prion protein ( PrP ) .", "Different PrP mutations cause different diseases , including Creutzfeldt-Jakob disease ( CJD ) and fatal familial insomnia ( FFI ) .", "The reason for this variability is not known , ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "autophagic cell death", "lysosomes", "vesicles", "vacuoles", "enzymes", "cell processes", "enzymology", "light microscopy", "fungi", "microscopy", "cellular structures and organelles", "endosomes", "research and analysis methods", "proteins", "fluorescence microscopy", ...	A Rab5 GTPase module is important for autophagosome closure	journal.pgen.1007020	null	[ [ "In autophagy , parts of the cytoplasm , including organelles , are engulfed by the phagophore ( or isolation ) membrane , which expands and closes to form the double-membrane autophagosomes ( APs ) .", "APs then fuse with the cellular degradative compartment termed lysosome , and the degradation products...	[ "In the conserved autophagy pathway , the double-membrane autophagosome ( AP ) engulfs cellular components to be delivered for degradation in the lysosome .", "While only sealed AP can productively fuse with the lysosome , the molecular mechanism of AP closure is currently unknown .", "Rab GTPases , which regul...	[ "In autophagy , a cellular recycling pathway , the double-membrane autophagosome ( AP ) engulfs excess or damaged cargo and delivers it for degradation in the lysosome for the reuse of its building blocks .", "While plenty of information is currently available regarding AP formation , expansion and fusion , not m...	2017
[ "Introduction", "Results", "Discussion" ]	[ "protons", "chemical bonding", "protein interactions", "cadherins", "materials science", "protein structure", "hydrogen bonding", "physical chemistry", "cell adhesion", "proteins", "chemistry", "salt bridges", "nucleons", "molecular biology", "adhesives", "physics", "biochemistry", ...	Exploring E-cadherin-peptidomimetics interaction using NMR and computational studies	journal.pcbi.1007041	null	[ [ "Classical cadherins constitute a subfamily of calcium-dependent cell–cell adhesion proteins that belong to the large and phylogenetically diverse cadherin superfamily .", "The various members of the classical cadherin subfamily show a tissue-dependent expression profile as well as a high sequence and str...	[ "Cadherins are homophilic cell-cell adhesion molecules whose aberrant expression has often been shown to correlate with different stages of tumor progression .", "In this work , we investigate the interaction of two peptidomimetic ligands with the extracellular portion of human E-cadherin using a combination of N...	[ "Classical cadherins are the main adhesive proteins at the intercellular junctions and play an essential role in tissue morphogenesis and homeostasis .", "A large number of studies have shown that cadherin aberrant expression and/or dysregulation often correlate with pathological processes , such as tumor develop...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "meiosis", "rna interference", "microtubules", "chromosome structure and function", "centromeres", "metaphase", "cell cycle and cell division", "atmospheric science", "cell processes", "animals", "germ cells", "animal models", "oocytes", "drosophila melanogaster", "mod...	Sister centromere fusion during meiosis I depends on maintaining cohesins and destabilizing microtubule attachments	journal.pgen.1008072	null	[ [ "The necessity of sister kinetochores to co-orient toward the same pole for co-segregation at anaphase I differentiates the first meiotic division from the second division .", "A meiosis-specific mechanism exists that ensures sister chromatid co-segregation by rearranging sister kinetochores , aligning th...	[ "Sister centromere fusion is a process unique to meiosis that promotes co-orientation of the sister kinetochores , ensuring they attach to microtubules from the same pole during metaphase I .", "We have found that the kinetochore protein SPC105R/KNL1 and Protein Phosphatase 1 ( PP1-87B ) regulate sister centromer...	[ "Meiosis involves two cell divisions .", "In the first division , pairs of homologous chromosomes segregate , in the second division , the sister chromatids segregate .", "These patterns of division are mediated by regulating microtubule attachments to the kinetochores and stepwise release of cohesion between t...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbial mutation", "vector biology", "microbial pathogens", "microbial control", "genetics and genomics", "biology", "genomics", "microbiology", "ticks", "host-pathogen interaction", "bacterial pathogens", "microbial growth and development" ]	Targeted and Random Mutagenesis of Ehrlichia chaffeensis for the Identification of Genes Required for In vivo Infection	journal.ppat.1003171	null	[ [ "Ehrlichia chaffeensis , an alpha-proteobacterium , is an intracellular pathogen that is transmitted through an infected Lone Star tick , Amblyomma americanum , to humans and several other vertebrate hosts [1]–[8] .", "The pathogen is responsible for causing human monocytic ehrlichiosis ( HME ) [6] , [7] ...	[ "Ehrlichia chaffeensis is a tick transmitted pathogen responsible for the disease human monocytic ehrlichiosis .", "Research to elucidate gene function in rickettsial pathogens is limited by the lack of genetic manipulation methods .", "Mutational analysis was performed , targeting to specific and random insert...	[ "The tick-transmitted bacterium , Ehrlichia chaffeensis , causes human monocytic ehrlichiosis , an acute febrile illness that can progress to a fatal outcome .", "This and other related pathogens have evolved to establish infections in vertebrate and tick hosts for completing their lifecycle .", "Our recent stu...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Structure of UreG/UreF/UreH Complex Reveals How Urease Accessory Proteins Facilitate Maturation of Helicobacter pylori Urease	journal.pbio.1001678	Structural and biochemical study of urease accessory protein complex provides mechanistic insights into the delivery of nickel to metalloenzyme urease, an enzyme enabling the survival of Helicobacter pylori in the human stomach.	[ [ "More than a quarter of the cellular proteins are metalloproteins [1] .", "Homeostatic regulation on the incorporation of specific metal ions to these metalloproteins is essential to life .", "Metal ions that occupy the top of the Irving-Williams series [2] , such as nickel , copper , and zinc , form ...	[ "Urease is a metalloenzyme essential for the survival of Helicobacter pylori in acidic gastric environment .", "Maturation of urease involves carbamylation of Lys219 and insertion of two nickel ions at its active site .", "This process requires GTP hydrolysis and the formation of a preactivation complex consist...	[ "Catalytic activities of many important enzymes depend upon metal cofactors .", "Ensuring each enzyme acquires the proper type of metal cofactor is essential to life .", "One such example is urease , which is a nickel containing metalloenzyme catalyzing the hydrolysis of urea to ammonia .", "The survival of H...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular neuroscience", "adenylyl cyclase signaling pathway", "second messenger system", "mechanisms of signal transduction", "neuroscience", "neurotransmitter receptor signaling", "membrane receptor signaling", "signaling pathways", "neurotransmitters", "biology", "molecular biology", "sign...	The Circadian Neuropeptide PDF Signals Preferentially through a Specific Adenylate Cyclase Isoform AC3 in M Pacemakers of Drosophila	journal.pbio.1001337	To synchronize a network of pacemakers in the Drosophila brain, a neuropeptide receptor specifically associates with adenylate cyclase 3 to create a “circadian signalosome.”	[ [ "The importance of biological rhythms in the anticipation and response to daily environmental changes is underscored by their conservation throughout nature .", "In eukaryotes , these rhythms are generated by a set of core clock genes that contrive to produce interlocked feedback loops .", "Both mamma...	[ "The neuropeptide Pigment Dispersing Factor ( PDF ) is essential for normal circadian function in Drosophila .", "It synchronizes the phases of M pacemakers , while in E pacemakers it decelerates their cycling and supports their amplitude .", "The PDF receptor ( PDF-R ) is present in both M and subsets of E cel...	[ "In the fruit fly Drosophila melanogaster , the neuropeptide Pigment Dispersing Factor ( PDF ) supports circadian function by synchronizing two types of pacemaker cells , M cells and E cells .", "The PDF receptor ( PDF-R ) is a G protein coupled receptor ( GPCR ) whose activation stimulates adenylate cyclase ( AC...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "algorithms", "systems biology", "computer applications", "computer science", "mathematics", "algebra", "genetics", "applied mathematics", "computing methods", "biology", "genomics", "computational biology", "numerical analysis" ]	Multi-tissue Analysis of Co-expression Networks by Higher-Order Generalized Singular Value Decomposition Identifies Functionally Coherent Transcriptional Modules	journal.pgen.1004006	null	[ [ "The increasingly cheaper and rapid accumulation of large -omics datasets across several experimental conditions has prompted generation of a wealth of data on biological networks .", "This growth of network data now permits their large scale applications to biomedical research , including analysis of gen...	[ "Recent high-throughput efforts such as ENCODE have generated a large body of genome-scale transcriptional data in multiple conditions ( e . g . , cell-types and disease states ) .", "Leveraging these data is especially important for network-based approaches to human disease , for instance to identify coherent tr...	[ "Complex biological interactions and processes can be modelled as networks , for instance metabolic pathways or protein-protein interactions .", "The growing availability of large high-throughput data in several experimental conditions now permits the full-scale analysis of biological interactions and processes ....	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "virology/immune evasion", "evolutionary biology/microbial evolution and genomics", "virology/virus evolution and symbiosis", "evolutionary biology/evolutionary and comparative genetics" ]	Positive Selection Results in Frequent Reversible Amino Acid Replacements in the G Protein Gene of Human Respiratory Syncytial Virus	journal.ppat.1000254	null	[ [ "Human respiratory syncytial virus ( HRSV ) is a leading cause of severe acute respiratory infection in childhood worldwide [1] and an important agent of acute respiratory infection in the elderly and immunocompromised [2] , [3] .", "Initial studies with monoclonal antibodies to the HRSV F and G proteins ...	[ "Human respiratory syncytial virus ( HRSV ) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly , causing annual disease outbreaks during the fall and winter .", "Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and disp...	[ "As part of the Viral Genetic Diversity Network ( VGDN ) , we sequenced the second variable region ( G2 ) of the G protein of human respiratory syncytial virus ( HRSV ) A and B from 568 patients sampled during 11 consecutive HRSV seasons ( 1995–2005 ) in the state of São Paulo , Brazil .", "A total of 933 HRSVA a...	2009
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "pathogens", "biological cultures", "cancers and neoplasms", "microbiology", "genomic library construction", "histone modification", "oncology", "viruses", "dna viruses", "cell cultures", "dna construct...	Epigenetic Landscape of Kaposi's Sarcoma-Associated Herpesvirus Genome in Classic Kaposi's Sarcoma Tissues	journal.ppat.1006167	null	[ [ "Kaposi's sarcoma-associated herpesvirus ( KSHV ) was first identified in Kaposi's sarcoma ( KS ) biopsies by Chang and Moore in 1994 and has been proven to be the etiological agent of several human cancers including KS , primary effusion lymphoma ( PEL ) and multicentric Castleman's disease ( MCD ) [1–3] .",...	[ "Kaposi's sarcoma-associated herpesvirus ( KSHV ) is etiologically related to Kaposi's sarcoma ( KS ) , primary effusion lymphoma ( PEL ) and multicentric Castleman's disease ( MCD ) .", "It typically displays two different phases in its life cycle , the default latency and occasional lytic replication .", "The...	[ "Epigenetic modifications are thought to determine the fate of KSHV infection .", "The epigenetic landscape of KSHV genome in in vitro cell culture systems was well studied previously .", "However , the physiologically relevant scenario in clinical KS tissues is unclear .", "In this study , we performed ChIP-...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "leptospira", "body fluids", "pathology and laboratory medicine", "ruminants", "pathogens", "tropical diseases", "microbiology", "vertebrates", "animals", "mammals", "urine", "bacterial diseases", "neglected tropical diseases", "bacteria", ...	High Leptospira Diversity in Animals and Humans Complicates the Search for Common Reservoirs of Human Disease in Rural Ecuador	journal.pntd.0004990	null	[ [ "Leptospirosis is an infectious disease that causes morbidity in about 1 . 03 million people each year [1] .", "Severe disease produces multisystem complications such as acute renal or hepatic failure , or severe pulmonary hemorrhage that can lead to death [2 , 3] .", "Leptospirosis has a widespread d...	[ "Leptospirosis is a zoonotic disease responsible for high morbidity around the world , especially in tropical and low income countries .", "Rats are thought to be the main vector of human leptospirosis in urban settings .", "However , differences between urban and low-income rural communities provide additional...	[ "Leptospirosis is a febrile disease responsible for high morbidity rates all around the world .", "It is caused by spirochete bacteria in the genus Leptospira and transmitted to humans through animal urine or contaminated soil or water .", "The epidemiology of leptospirosis has been extensively studied in urban...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/chromatin structure", "molecular biology/rna-protein interactions", "computational biology/transcriptional regulation", "genetics and genomics/gene expression", "biochemistry/transcription and translation", "genetics and genomics/epigenetics", "developmental biology/developmental mole...	HP1 Recruitment in the Absence of Argonaute Proteins in Drosophila	journal.pgen.1000880	null	[ [ "In D . melanogaster , an estimated one-third of the genome is composed of repetitive and noncoding sequences associated with a condensed form of chromatin known as heterochromatin .", "Heterochromatin is characterized by repeat-rich sequences , hypoacetylation of histone tails , and dimethylation of hist...	[ "Highly repetitive and transposable element rich regions of the genome must be stabilized by the presence of heterochromatin .", "A direct role for RNA interference in the establishment of heterochromatin has been demonstrated in fission yeast .", "In metazoans , which possess multiple RNA–silencing pathways th...	[ "One role for silent heterochromatin is to preserve the integrity of the genome by stabilizing regions rich in repetitive sequence and mobile elements .", "Compaction of repetitive sequences by heterochromatin is needed to prevent genome rearrangement and loss of genetic material .", "Furthermore , uncontrolled...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "chemical compounds", "plant cell biology", "vascular bundles", "microbiology", "phloem", "plant physiology", "cloning", "viral structure", "organic compounds", "plant science", "amino acids", "sequence motif analysis", "molecular biology techniques", "cellular structure...	An aromatic amino acid and associated helix in the C-terminus of the potato leafroll virus minor capsid protein regulate systemic infection and symptom expression	journal.ppat.1007451	null	[ [ "Potato leafroll virus ( PLRV ) is the type member of the Poleroviruses , in the family Luteoviridae .", "These viruses and the related Luteoviruses , collectively referred to here as luteovirids , are phloem limited viruses and transmitted by aphids in a circulative , nonpropagative manner [1 , 2] .", ...	[ "The C-terminal region of the minor structural protein of potato leafroll virus ( PLRV ) , known as the readthrough protein ( RTP ) , is involved in efficient virus movement , tissue tropism and symptom development .", "Analysis of numerous C-terminal deletions identified a five-amino acid motif that is required ...	[ "Protein function is often dependent on its structure that is determined by the composition and chemistry of its amino acids .", "The C-terminal ~200 amino acids of the PLRV RTP are characteristically disordered yet this protein domain is involved in virus movement , tissue tropism and symptom development .", "...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "cell biology", "biology and life sciences", "computational biology", "evolutionary biology" ]	Differential Responses to Wnt and PCP Disruption Predict Expression and Developmental Function of Conserved and Novel Genes in a Cnidarian	journal.pgen.1004590	null	[ [ "A major challenge in biology is to understand how the current extraordinary diversity of animal forms has been generated during evolution .", "Specific goals are to determine which genes were employed to regulate developmental processes in the earliest multi-cellular animals , and how this set of regulat...	[ "We have used Digital Gene Expression analysis to identify , without bilaterian bias , regulators of cnidarian embryonic patterning .", "Transcriptome comparison between un-manipulated Clytia early gastrula embryos and ones in which the key polarity regulator Wnt3 was inhibited using morpholino antisense oligonuc...	[ "The recent wave of genome sequencing from many species has revealed that most of the gene families known to regulate animal development are shared not only between humans and laboratory favorites such as mice , flies and worms , but also by evolutionarily more distant animals such as jellyfish and sponges .", "I...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neurobiology of disease and regeneration", "behavioral neuroscience", "cognitive neuroscience", "computational neuroscience", "biology", "neuroscience", "animal cognition" ]	Disentangling the Roles of Approach, Activation and Valence in Instrumental and Pavlovian Responding	journal.pcbi.1002028	null	[ [ "The functional architecture of responding involves two fundamental components that are behaviourally [1] and computationally [2] separable: Pavlovian and instrumental .", "The instrumental component respects the stimulus-dependent contingency between responses and their outcomes ( stimulus-response and a...	[ "Hard-wired , Pavlovian , responses elicited by predictions of rewards and punishments exert significant benevolent and malevolent influences over instrumentally-appropriate actions .", "These influences come in two main groups , defined along anatomical , pharmacological , behavioural and functional lines .", ...	[ "Beautiful background music in a shop may well tempt us to buy something we neither need nor want .", "Valenced stimuli have broad and profound influences on ongoing choice behaviour .", "After replicating known findings whereby approach is enhanced by appetitive Pavlovian stimuli and inhibited by aversive ones...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Doubly Bayesian Analysis of Confidence in Perceptual Decision-Making	journal.pcbi.1004519	null	[ [ "Humans and other animals use estimates about the reliability of their sensory data to guide behaviour ( e . g . [1–3] ) .", "For instance , a monkey will wait until its sensory data is deemed sufficiently reliable before taking a risky decision [3] .", "Humans can go further than other animals: they ...	[ "Humans stand out from other animals in that they are able to explicitly report on the reliability of their internal operations .", "This ability , which is known as metacognition , is typically studied by asking people to report their confidence in the correctness of some decision .", "However , the computatio...	[ "Confidence plays a key role in group interactions: when people express an opinion , they almost always communicate—either implicitly or explicitly—their confidence , and the degree of confidence has a strong effect on listeners .", "Understanding both how confidence is generated and how it is interpreted are the...	2015
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative	journal.ppat.1005114	null	[ [ "Despite difficulties in interrupting wild poliovirus transmission in the last few remaining endemic countries and recent drawbacks due to international spread of poliovirus in central Asia , central Africa and the Middle East [1] , the global polio eradication appears to be within reach .", "Four of the ...	[ "There are currently huge efforts by the World Health Organization and partners to complete global polio eradication .", "With the significant decline in poliomyelitis cases due to wild poliovirus in recent years , rare cases related to the use of live-attenuated oral polio vaccine assume greater importance .", ...	[ "The global polio eradication initiative is the most ambitious and complex public health programme directed at a single disease in history with a projected cost of $16 . 5 billion .", "Of the three serotypes types 2 and 3 appear to have been eradicated in the wild and type 1 is mostly confined to a region of Paki...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/mrna transport and localization", "virology/viral replication and gene regulation", "virology" ]	Recruitment of the Complete hTREX Complex Is Required for Kaposi's Sarcoma–Associated Herpesvirus Intronless mRNA Nuclear Export and Virus Replication	journal.ppat.1000194	null	[ [ "The nuclear export of mRNA composes one part of a larger network of molecular events that begin with transcription of the mRNA in the nucleus and end with its translation and degradation in the cytoplasm .", "During trafficking to the cytoplasm , a nascent mRNA undergoes numerous co-transcriptional proce...	[ "A cellular pre-mRNA undergoes various post-transcriptional processing events , including capping , splicing and polyadenylation prior to nuclear export .", "Splicing is particularly important for mRNA nuclear export as two distinct multi-protein complexes , known as human TREX ( hTREX ) and the exon-junction com...	[ "Following gene expression in the nucleus , newly transcribed messenger RNA ( mRNA ) is exported to the cytoplasm , where it is translated into protein .", "In mammals the vast majority of mRNAs contain introns that must be removed by the spliceosome prior to nuclear export .", "In addition to excising introns ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "hepatitis c", "medicine", "infectious hepatitis", "immunity", "gastroenterology and hepatology", "innate immunity", "immunity to infections", "immunology", "biology", "liver diseases" ]	Hepatitis C Virus Pathogen Associated Molecular Pattern (PAMP) Triggers Production of Lambda-Interferons by Human Plasmacytoid Dendritic Cells	journal.ppat.1003316	null	[ [ "Pathogens are sensed by host pattern recognition receptors ( PRR ) that recognize molecular motifs .", "Two major receptor systems sense the presence of viral infection to mount an immune response: toll-like receptors ( TLRs ) 3 , 7 , 8 , and 9 are major PRRs that respond to different types of viral nucl...	[ "Plasmacytoid Dendritic Cells ( pDCs ) represent a key immune cell in the defense against viruses .", "Through pattern recognition receptors ( PRRs ) , these cells detect viral pathogen associated molecular patterns ( PAMPs ) and initiate an Interferon ( IFN ) response .", "pDCs produce the antiviral IFNs inclu...	[ "Hepatitis C Virus ( HCV ) is the most common bloodborne pathogen for which no vaccine is available .", "Infection with the virus often leads to persistent ( or chronic ) infection .", "Patients with chronic HCV infection can develop progressive liver disease and liver failure , leading to the need for a transp...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "biology", "genomics", "molecular cell biology", "genetics and genomics" ]	REST–Mediated Recruitment of Polycomb Repressor Complexes in Mammalian Cells	journal.pgen.1002494	null	[ [ "Polycomb group ( PcG ) proteins are epigenetic regulators of gene expression and play an essential role during embryonic development [1] .", "The Polycomb repressive complex 2 ( PRC2 ) is the only known enzyme that mediates di- and tri-methylation of histone H3 on lysine 27 ( H3K27Me2/3 ) , modifications...	[ "Polycomb Repressive Complex ( PRC ) 1 and PRC2 regulate genes involved in differentiation and development .", "However , the mechanism for how PRC1 and PRC2 are recruited to genes in mammalian cells is unclear .", "Here we present evidence for an interaction between the transcription factor REST , PRC1 , and P...	[ "Multicellular organisms are composed of a large number of specialized cell types that all originate from the Embryonic Stem cell ( ES cell ) .", "It is crucial for the maintenance of naïve ES cells that developmental genes are kept in an off-state until appropriate differentiation stimuli are received .", "Pol...	2012
[ "Introduction", "Results/Discussion", "Methods" ]	[ "animal models", "systems biology", "computer and information sciences", "model organisms", "systems science", "mathematics", "biology and life sciences", "mouse models", "physical sciences", "nonlinear dynamics", "research and analysis methods" ]	Mouse Hair Cycle Expression Dynamics Modeled as Coupled Mesenchymal and Epithelial Oscillators	journal.pcbi.1003914	null	[ [ "The miniorgan of the hair follicle represents a complex biological system that undergoes repeated phases of death and regeneration over its lifetime [1]–[3] .", "Understanding of the hair cycle and its regulation would shed light on many other complex systems relevant to biological and medical research i...	[ "The hair cycle is a dynamic process where follicles repeatedly move through phases of growth , retraction , and relative quiescence .", "This process is an example of temporal and spatial biological complexity .", "Understanding of the hair cycle and its regulation would shed light on many other complex system...	[ "The hair cycle represents a complex process of particular interest in the study of regulated proliferation , apoptosis and differentiation .", "While various modeling strategies are presented in the literature , none attempt to link extensive molecular details , provided by high-throughput experiments , with hig...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Canonical Poly(A) Polymerase Activity Promotes the Decay of a Wide Variety of Mammalian Nuclear RNAs	journal.pgen.1005610	null	[ [ "Eukaryotic messenger RNAs ( mRNAs ) undergo a series of maturation events before they are exported to the cytoplasm and translated .", "The complexity of alternative processing increases the likelihood of mistakes that produce aberrant mRNAs encoding defective proteins .", "In addition , pervasive tr...	[ "The human nuclear poly ( A ) -binding protein PABPN1 has been implicated in the decay of nuclear noncoding RNAs ( ncRNAs ) .", "In addition , PABPN1 promotes hyperadenylation by stimulating poly ( A ) -polymerases ( PAPα/γ ) , but this activity has not previously been linked to the decay of endogenous transcript...	[ "Cells control gene expression by balancing the rates of RNA synthesis and decay .", "While the mechanisms of transcription regulation are extensively studied , the parameters that control nuclear RNA stability remain largely unknown .", "Previously , we and others reported that poly ( A ) tails may stimulate R...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/molecular evolution", "molecular biology/chromosome structure", "genetics and genomics/chromosome biology", "genetics and genomics/genetics of disease", "genetics and genomics/population genetics" ]	Linkage Disequilibrium between Two High-Frequency Deletion Polymorphisms: Implications for Association Studies Involving the glutathione-S transferase (GST) Genes	journal.pgen.1000472	null	[ [ "Copy number variation ( CNV ) is a significant source of genetic variation in the genome of humans [1]–[11] .", "A large number of CNVs has been identified , and span more than 10% of the human genome in total [12] , although the estimate is dependent on the frequency of the event under consideration .",...	[ "Copy number variations ( CNVs ) represent a large source of genetic variation in humans and have been increasingly studied for disease association .", "A deletion polymorphism of the gene encoding the cytosolic detoxification enzyme glutathione S-transferase theta 1 ( GSTT1 ) has been extensively studied for can...	[ "Common diseases such as cancer are caused by interactions between multiple genetic and environmental factors .", "Glutathione S-transferases ( GST ) are key enzymes in eliminating carcinogens and harmful macromolecules from cells .", "Based on the assumption that individuals who do not have a particular type o...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Highly Sensitive In Vivo Imaging of Trypanosoma brucei Expressing “Red-Shifted” Luciferase	journal.pntd.0002571	null	[ [ "African sleeping sickness , or human African trypanosomiasis ( HAT ) , currently infects around 10 , 000 people per year and threatens the lives of a further 70 million people living in 36 countries of sub-Saharan Africa [1] .", "Infections of domestic livestock are also a major economic problem througho...	[ "Human African trypanosomiasis is caused by infection with parasites of the Trypanosoma brucei species complex , and threatens over 70 million people in sub-Saharan Africa .", "Development of new drugs is hampered by the limitations of current rodent models , particularly for stage II infections , which occur onc...	[ "Parasites of the Trypanosoma brucei species complex are the causative agents of human African trypanosomiasis .", "There is an urgent need for new drugs to treat this debilitating and potentially fatal infection , especially in its late stage , when parasites have entered the central nervous system .", "Factor...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	A Retrospective Study of the Epidemiology of Leprosy in Cebu: An Eleven-Year Profile	journal.pntd.0002444	null	[ [ "For over a century , Cebu has been one of the most leprosy endemic areas in the Philippines .", "With the establishment of a centralized leprosy settlement in the island of Culion , compulsory notification of leprosy cases was introduced in 1906; ever since , a large proportion of leprosy cases have been...	[ "Cebu has been one of the most leprosy endemic areas in the Philippines .", "Despite the high coverage rates of multiple drug therapy ( MDT ) and high BCG-vaccine coverage in children , leprosy control authorities believe that leprosy transmission and incidence ( as evidence by continuing new case detection in bo...	[ "The island of Cebu is one of the most leprosy-endemic areas in the Philippines .", "Multiple drug therapy ( MDT ) , improved BCG-vaccine coverage and active case finding have significantly lowered the adult case notification rates ( CNRs ) , but the CNR in children ( which is a proxy indicator of ongoing transmi...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "crystal structure", "monomers", "condensed matter physics", "materials science", "network analysis", "sequence motif analysis", "crystallography", "oligomers", "research and analysis methods", "sequence analysis", "polymer chemistry", "computer and information sciences", ...	Conformational coupling by trans-phosphorylation in calcium calmodulin dependent kinase II	journal.pcbi.1006796	null	[ [ "The calcium calmodulin-dependent protein kinase ( CaMKII ) is a multifunctional , multi-subunit eukaryotic protein kinase ( EPK ) .", "It has key roles in calcium regulation of neuronal and cardiovascular physiology [1–3] .", "EPKs mediate reactions whose malfunction promotes disease across a broad p...	[ "The calcium calmodulin-dependent protein kinase II ( CaMKII ) is a dodecameric holoenzyme important for encoding memory .", "Its activation , triggered by binding of calcium-calmodulin , persists autonomously after calmodulin dissociation .", "One ( receiver ) kinase captures and subsequently phosphorylates th...	[ "Protein kinases play central roles in intracellular signalling .", "Auto-phosphorylation by bound nucleotide typically precedes phosphate transfer to multiple substrates .", "Protein conformational changes are central to kinase function , altering binding affinities to change cellular location and shunt from o...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	What Drives the Occurrence of the Melioidosis Bacterium Burkholderia pseudomallei in Domestic Gardens?	journal.pntd.0003635	null	[ [ "Southeast Asia and tropical Australia have recently experienced a surge in melioidosis , an often fatal infectious disease caused by the saprophytic environmental bacterium Burkholderia pseudomallei [1 , 2] .", "Case numbers in the Top End of Australia have substantially increased in recent years .", ...	[ "Melioidosis is an often fatal infectious disease affecting humans and animals in tropical regions and is caused by the saprophytic environmental bacterium Burkholderia pseudomallei .", "Domestic gardens are not only a common source of exposure to soil and thus to B . pseudomallei , but they also have been found ...	[ "Melioidosis cases are on the rise in endemic areas of northern Australia and Thailand .", "This potentially severe infectious disease affecting humans and animals in the tropical belt is caused by the gram negative bacterium Burkholderia pseudomallei .", "Domestic gardens are a common point of exposure to thes...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	A Population Growth Trend Analysis for Neotricula aperta, the Snail Intermediate Host of Schistosoma mekongi, after Construction of the Pak-Mun Dam	journal.pntd.0002539	null	[ [ "The Pak-Mun dam in Northeast Thailand , has been the focus of much controversy since the announcement of plans for its construction in 1982 .", "Demonstrations and protests against the dam became more pronounced in 1989 when the project received government approval [1] .", "Construction of the dam be...	[ "The Pak-Mun dam is a controversial hydro-power project on the Mun River in Northeast Thailand .", "The dam is sited in a habitat of the freshwater snail Neotricula aperta , which is the intermediate host for the parasitic blood-fluke Schistosoma mekongi causing Mekong schistosomiasis in humans in Cambodia and La...	[ "There is much controversy over the effects of water resource development on the transmission of schistosomiasis in the lower Mekong Basin .", "Impact assessments are urgently required because there are currently 12 such projects planned in the region .", "The key to understanding the effects of impoundment is ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "medicine and health sciences", "body fluids", "population genetics", "dna transcription", "urine", "sequence motif analysis", "molecular biology techniques", "population biology", "mammalian genomics", "research and analysis methods", "sequence analysis", "sequence ...	Selection on Coding and Regulatory Variation Maintains Individuality in Major Urinary Protein Scent Marks in Wild Mice	journal.pgen.1005891	null	[ [ "Animals produce complex blends of scents that can provide information on species , age , sex and individual identity [1] .", "As arguably the most complex and subtle form of recognition , individual recognition has attracted considerable attention from the perspective of neurobiology [2–4] and chemical e...	[ "Recognition of individuals by scent is widespread across animal taxa .", "Though animals can often discriminate chemical blends based on many compounds , recent work shows that specific protein pheromones are necessary and sufficient for individual recognition via scent marks in mice .", "The genetic nature of...	[ "Individual recognition via scent is critical for many aspects of behavior including parental care , competition , cooperation and mate choice .", "While animal scents can differ in a huge number of dimensions , recent work has shown that only some specialized semiochemicals in scent marks are behaviorally releva...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "medicine and health sciences", "biological data management", "infectious disease epidemiology", "population dynamics", "applied mathematics", "epidemiological methods and statistics", "plant science", "systems science", "mathematics", "probability distribut...	Pattern of Tick Aggregation on Mice: Larger Than Expected Distribution Tail Enhances the Spread of Tick-Borne Pathogens	journal.pcbi.1003931	null	[ [ "Several ecological studies have shown that the distribution of ticks on their hosts is often highly aggregated , with a large number of hosts harbouring few parasites and a small number harbouring a large number of them ( [1]–[5]; other interesting references could be found in [6] ) .", "In addition , th...	[ "The spread of tick-borne pathogens represents an important threat to human and animal health in many parts of Eurasia .", "Here , we analysed a 9-year time series of Ixodes ricinus ticks feeding on Apodemus flavicollis mice ( main reservoir-competent host for tick-borne encephalitis , TBE ) sampled in Trentino (...	[ "Our work analyses a 9-year time series of tick co-feeding patterns on Yellow-necked mice .", "Our data shows a strong heterogeneity , where most mice are parasitised by a small number of ticks while few host a much larger number .", "We describe the number of ticks per host by the commonly used Negative Binomi...	2014
[ "Introduction", "Nonnegative sparse coding as a modern variant of the efficient coding hypothesis", "Empirical evidence for NSC in the brain", "Discussion", "Conclusion", "Data availability" ]	[ "medicine and health sciences", "neurochemistry", "face", "chemical compounds", "brain", "social sciences", "neuroscience", "learning and memory", "organic compounds", "hormones", "face recognition", "perception", "review", "cognitive psychology", "cognition", "computational neuroscien...	Neural correlates of sparse coding and dimensionality reduction	journal.pcbi.1006908	null	[ [ "Brains face the fundamental challenge of extracting relevant information from high-dimensional external stimuli in order to form the neural basis that can guide an organism's behavior and its interaction with the world .", "To support complex patterns of behavior , populations of interconnected neurons m...	[ "Supported by recent computational studies , there is increasing evidence that a wide range of neuronal responses can be understood as an emergent property of nonnegative sparse coding ( NSC ) , an efficient population coding scheme based on dimensionality reduction and sparsity constraints .", "We review evidenc...	[ "Brains face the fundamental challenge of extracting relevant information from high-dimensional external stimuli in order to form the neural basis that can guide an organism's behavior and its interaction with the world .", "One potential approach to addressing this challenge is to reduce the number of variables ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immune cells", "immune activation", "retrovirology and hiv immunopathogenesis", "immunity to infections", "immunology", "adaptive immunity", "sexually transmitted diseases", "immunomodulation", "infectious diseases", "aids", "hiv", "t cells", "biology", "immune response", ...	CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction	journal.ppat.1002840	null	[ [ "Mounting evidence supports the notion that CD8 T cells contribute to the control of HIV viral replication [1] .", "The emergence in early infection of viral variants bearing escape mutations within sequences targeted by HIV-specific T lymphocytes is consistent with CD8 T cells exerting selective antivira...	[ "Chronic viral infections lead to persistent CD8 T cell activation and functional exhaustion .", "Expression of programmed cell death-1 ( PD-1 ) has been associated to CD8 T cell dysfunction in HIV infection .", "Herein we report that another negative regulator of T cell activation , CD160 , was also upregulate...	[ "HIV infection is widely known to cause generalized immune activation and immune exhaustion ultimately leading to HIV disease progression .", "Several studies have suggested over the years that the accumulation of inhibitory signalling proteins on the surface of responding cells is linked to immune exhaustion in ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/nosocomial and healthcare-associated infections", "genetics and genomics/gene expression", "infectious diseases/bacterial infections", "genetics and genomics/epigenetics", "microbiology/microbial growth and development" ]	Epigenetic Control of Virulence Gene Expression in Pseudomonas aeruginosa by a LysR-Type Transcription Regulator	journal.pgen.1000779	null	[ [ "The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen of humans .", "It can cause infection in a wide variety of tissues in the immunocompromised host , and is the leading cause of morbidity and mortality in cystic fibrosis ( CF ) patients [1] .", "This breadth of infectious...	[ "Phenotypic variation within an isogenic bacterial population is thought to ensure the survival of a subset of cells in adverse conditions .", "The opportunistic pathogen Pseudomonas aeruginosa variably expresses several phenotypes , including antibiotic resistance , biofilm formation , and the production of CupA...	[ "Bistable switches allow the expression of a gene , or set of genes , to switch from one stable expression state to another and can generate cells with different phenotypes in an isogenic population .", "In this work we uncover a previously unidentified bistable switch that controls virulence gene expression in t...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "pharmacologic analysis", "medicine and health sciences", "antibiotic susceptibility testing", "dose prediction methods", "cancer treatment", "biological cultures", "cancers and neoplasms", "drug screening", "simulation and modeling", "oncology", "systems science", "mathematics", "pharmaceut...	A Computational Approach for Identifying Synergistic Drug Combinations	journal.pcbi.1005308	null	[ [ "Targeted therapies designed to specifically target molecules involved in carcinogenesis have achieved remarkable antitumor efficacy .", "In melanoma , over half of patients are reported to harbor activating mutations in the BRAF oncogene [1 , 2] .", "BRAF inhibitors , such as vemurafenib , have been ...	[ "A promising alternative to address the problem of acquired drug resistance is to rely on combination therapies .", "Identification of the right combinations is often accomplished through trial and error , a labor and resource intensive process whose scale quickly escalates as more drugs can be combined .", "To...	[ "While targeted therapies have achieved remarkable antitumor responses , resistance to targeted agents frequently develops and renders the targeted drug ineffective .", "Combination therapies have been successful in delaying resistance and overcoming resistance .", "Additional goals of combination therapy are t...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "parastic protozoans", "mycology", "genomics", "protozoology", "host-pathogen interaction", "microbiology", "biology", "proteomics", "parasitology" ]	The Genome of Spraguea lophii and the Basis of Host-Microsporidian Interactions	journal.pgen.1003676	null	[ [ "Microsporidia are a diverse phylum of obligate intracellular parasites related to fungi .", "Over 1300 species have been described in approximately 160 genera and , as is the case for other microbial eukaryotes , a vast undescribed diversity is thought to exist in the environment [1] .", "Microsporid...	[ "Microsporidia are obligate intracellular parasites with the smallest known eukaryotic genomes .", "Although they are increasingly recognized as economically and medically important parasites , the molecular basis of microsporidian pathogenicity is almost completely unknown and no genetic manipulation system is c...	[ "Microsporidia are unusual intracellular parasites that infect a broad range of animal cells .", "In comparison to their fungal relatives , microsporidian genomes have shrunk during evolution , encoding as few as 2000 proteins .", "This minimal molecular repertoire makes them a reduced model system for understa...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "biochemistry", "plant biochemistry", "plant science", "plant genomics", "genetics", "biology and life sciences", "plant genetics", "plant biotechnology" ]	Genome-wide Association Mapping Identifies a New Arsenate Reductase Enzyme Critical for Limiting Arsenic Accumulation in Plants	journal.pbio.1002009	A genome-wide association study identifies the enzyme in plants that transforms arsenate into arsenite, allowing its extrusion into the soil and thereby controlling arsenic accumulation.	[ [ "Inorganic arsenic is a non-threshold class-1 chronic exposure human carcinogen [1] , and its elevated level in rice ( Oryza sativa ) produced in Bangladesh , China , and India is known to pose a significantly elevated cancer risk in these populations , which eat rice at the high levels typical of many Southe...	[ "Inorganic arsenic is a carcinogen , and its ingestion through foods such as rice presents a significant risk to human health .", "Plants chemically reduce arsenate to arsenite .", "Using genome-wide association ( GWA ) mapping of loci controlling natural variation in arsenic accumulation in Arabidopsis thalian...	[ "Arsenic is a human carcinogen that accumulates from soil into many different food crops , where it presents a significantly increased cancer risk when foods derived from these crops are consumed .", "Plants naturally control the amount of arsenic they accumulate by first chemically converting arsenate into arsen...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "mathematics", "statistics (mathematics)", "genome analysis", "genetics", "biology and life sciences", "physical sciences", "computational biology", "human genetics" ]	GPA: A Statistical Approach to Prioritizing GWAS Results by Integrating Pleiotropy and Annotation	journal.pgen.1004787	null	[ [ "Hundreds of genome-wide association studies ( GWAS ) have been conducted to study the genetic bases of complex human traits .", "As of January , 2014 , more than 12 , 000 single-nucleotide polymorphisms ( SNPs ) have been reported to be significantly associated with at least one complex trait ( see the w...	[ "Results from Genome-Wide Association Studies ( GWAS ) have shown that complex diseases are often affected by many genetic variants with small or moderate effects .", "Identifications of these risk variants remain a very challenging problem .", "There is a need to develop more powerful statistical methods to le...	[ "In the past 10 years , many genome wide association studies ( GWAS ) have been conducted to identify the genetic bases of complex human traits .", "As of January , 2014 , more than 12 , 000 single-nucleotide polymorphisms ( SNPs ) have been reported to be significantly associated with at least one complex trait/...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "viruses", "infectious diseases", "virology", "mus (mouse)", "insects" ]	A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential	journal.ppat.0030201	null	[ [ "The large-scale epidemic of the mosquito-transmitted alphavirus , Chikungunya virus ( CHIKV ) , began in Kenya in 2004 and spread to several Indian Ocean islands including the Comoros , Mauritius , the Seychelles , Madagascar , Mayotte and Reunion .", "On Reunion island alone there were approximately 266...	[ "Chikungunya virus ( CHIKV ) is an emerging arbovirus associated with several recent large-scale epidemics .", "The 2005–2006 epidemic on Reunion island that resulted in approximately 266 , 000 human cases was associated with a strain of CHIKV with a mutation in the envelope protein gene ( E1-A226V ) .", "To te...	[ "Chikungunya virus ( CHIKV ) is an emerging arbovirus associated with several recent large-scale epidemics of arthritic disease , including one on Reunion island , where there were approximately 266 , 000 cases ( 34% of the total island population ) .", "CHIKV is transmitted by Aedes species mosquitoes , primaril...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology", "emerging viral diseases", "genetics", "molecular genetics", "host-pathogen interaction", "biology", "microbiology", "evolutionary biology", "evolutionary genetics" ]	Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein	journal.pbio.1001571	Relentless selective pressures exerted by viruses trigger arms race dynamics that shape the evolution of even critical host genes like those involved in iron homeostasis.	[ [ "Transferrin receptor ( TfR1 ) is the cell-surface receptor for iron-loaded transferrin circulating in the blood [1] .", "TfR1-transferrin complexes are internalized via clathrin-mediated endocytosis and iron is released in acidic endosomes .", "Besides transferrin , the other major binding partner of...	[ "Transferrin Receptor ( TfR1 ) is the cell-surface receptor that regulates iron uptake into cells , a process that is fundamental to life .", "However , TfR1 also facilitates the cellular entry of multiple mammalian viruses .", "We use evolutionary and functional analyses of TfR1 in the rodent clade , where two...	[ "Genetic differences between mammalian species dictate the patterns of viral infection observed in nature .", "They also define how viruses must evolve in order to infect new mammalian hosts , giving rise to new and sometimes pandemic diseases .", "Because viruses must enter cells before they can replicate , ne...	2013
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "genetics and genomics/complex traits", "genetics and genomics/genetics of disease", "neurological disorders/neurogenetics", "neurological disorders/neuropsychiatric disorders", "computational biology/genomics", "genetics and genomics/bioinformatics", "genetics and genomics/medical genetics" ]	Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function	journal.pgen.1001097	null	[ [ "Multiple recent studies have demonstrated a convincing and statistically significant excess of rare CNVs in individuals affected by schizophrenia compared to unaffected individuals [1]–[4] .", "Similar observations have now been made separately in autism [5]–[7] and bipolar disorder [8] .", "However ...	[ "Investigators have linked rare copy number variation ( CNVs ) to neuropsychiatric diseases , such as schizophrenia .", "One hypothesis is that CNV events cause disease by affecting genes with specific brain functions .", "Under these circumstances , we expect that CNV events in cases should impact brain-functi...	[ "Specific rare deletion and duplication events in the genome have now been shown to be associated with neuropsychiatric diseases such as 16p11 . 2 to autism and 22q11 . 21 to schizophrenia .", "However , controversy remains as to whether rare events impacting certain pathways as a group increase the risk of disea...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/sexually transmitted diseases", "public health and epidemiology/infectious diseases", "physics/interdisciplinary physics", "public health and epidemiology/epidemiology" ]	Simulated Epidemics in an Empirical Spatiotemporal Network of 50,185 Sexual Contacts	journal.pcbi.1001109	null	[ [ "Spatiotemporal heterogeneities in sexual contact patterns are thought to influence the spread of sexually transmitted infections ( STIs ) .", "Since epidemics can be a society-wide phenomenon , and sexual contact patterns can have structure at all scales , we need population-level sexual network data to ...	[ "Sexual contact patterns , both in their temporal and network structure , can influence the spread of sexually transmitted infections ( STI ) .", "Most previous literature has focused on effects of network topology; few studies have addressed the role of temporal structure .", "We simulate disease spread using ...	[ "Human sexual contacts form a spatiotemporal network—the underlying structure over which sexually transmitted infections ( STI ) spread .", "By understanding the structure of this system we can better understand the dynamics of STIs .", "So far , there has been much focus on the static network structure of sexu...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "neglected tropical diseases", "infectious diseases", "trachoma" ]	A Randomized Trial of Two Coverage Targets for Mass Treatment with Azithromycin for Trachoma	journal.pntd.0002415	null	[ [ "Trachoma , caused by ocular Chlamydia trachomatis , is the leading infectious cause of blindness world-wide [1] .", "In addition to the heavy personal and societal burden inflicted by loss of vision , there are significant economic impacts as well .", "The 3 . 8 million cases of blindness and 5 . 3 m...	[ "The World Health Organization recommends at least 3 annual antibiotic mass drug administrations ( MDA ) where the prevalence of trachoma is >10% in children ages 1–9 years , with coverage at least at 80% .", "However , the additional value of higher coverage targeted at children with multiple rounds is unknown ....	[ "The World Health Organization recommends at least 3 annual antibiotic mass drug administrations ( MDA ) where the prevalence of trachoma is >10% in children ages 1–9 years , with coverage at least at 80% .", "However , the additional value of higher coverage targeted at children with multiple rounds is unknown ....	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "genetics and genomics/gene discovery", "cell biology/cell signaling", "genetics and genomics/gene expression", "cell biology/microbial growth and development", "genetics and genomics/gene function", "cell biology/extra-cellular matri...	Connecting Quorum Sensing, c-di-GMP, Pel Polysaccharide, and Biofilm Formation in Pseudomonas aeruginosa through Tyrosine Phosphatase TpbA (PA3885)	journal.ppat.1000483	null	[ [ "Pseudomonas aeruginosa , an opportunistic pathogen , is often used to elucidate how biofilms form because persistence of this bacterium is linked to its ability to form biofilms [1] .", "Biofilms are formed by the attachment of bacteria to submerged surfaces in aquatic environments through their producti...	[ "With the opportunistic pathogen Pseudomonas aeruginosa , quorum sensing based on homoserine lactones was found to influence biofilm formation .", "Here we discern a mechanism by which quorum sensing controls biofilm formation by screening 5850 transposon mutants of P . aeruginosa PA14 for altered biofilm formati...	[ "Most bacteria live in biofilms , which are complex communities of microorganisms attached to a surface via polysaccharides; these biofilms are responsible for most human bacterial diseases .", "The pathogen Pseudomonas aeruginosa is best-studied for biofilm formation .", "Currently , it is recognized that cell...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "saccharomyces", "drosophila", "computational biology" ]	In Search of the Biological Significance of Modular Structures in Protein Networks	journal.pcbi.0030107	null	[ [ "Many complex networks are naturally divided into communities or modules , where links within modules are much denser than those across modules [1] ( Figure 1 ) .", "For example , human individuals belonging to the same ethnic groups interact more than those from different ethnic groups [2] .", "Study...	[ "Many complex networks such as computer and social networks exhibit modular structures , where links between nodes are much denser within modules than between modules .", "It is widely believed that cellular networks are also modular , reflecting the relative independence and coherence of different functional uni...	[ "Many complex networks are naturally divided into communities or modules , where links within modules are much denser than those across modules .", "For example , human individuals belonging to the same ethnic groups interact more than those from different ethnic groups .", "Cellular functions are also organize...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "fish", "skeletal muscles", "vertebrates", "animals", "animal models", "osteichthyes", "muscle regeneration", "developmental biology", "model organisms", "organism development", "stem cells", "experimental organism systems", "immunologic techniques", "morp...	RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes	journal.pgen.1007226	null	[ [ "Ribosome biogenesis is fundamental to all life forms and is the primary determinant of translational capacity of the cell .", "Ribosome biogenesis is a complex process that involves transcription , modification and processing of ribosomal RNA , production of ribosomal proteins and auxiliary factors and c...	[ "Gene expression in a tissue-specific context depends on the combined efforts of epigenetic , transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity .", "Ribosomes are a central component of the protein biosynthesis ...	[ "Inherited skeletal muscle diseases are the most common form of genetic disorders with primary abnormalities in the structure and function of skeletal muscle resulting in the impaired locomotion in affected patients .", "A major hindrance to the development of effective therapies is a lack of understanding of bio...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "developmental neuroscience", "synaptic plasticity", "neuroanatomy", "neural networks", "computational neuroscience", "biology", "neuroscience", "learning and memory" ]	Spike-Timing Dependence of Structural Plasticity Explains Cooperative Synapse Formation in the Neocortex	journal.pcbi.1002689	null	[ [ "The structure of neocortical networks of neurons changes in time: new synapses are formed , maturate , and eventually are pruned again , in the adult as well as in the developing animal [1] , [2] , for recent reviews see [3] , [4] , [5] .", "The majority ( about ) of excitatory synaptic contacts terminat...	[ "Structural plasticity governs the long-term development of synaptic connections in the neocortex .", "While the underlying processes at the synapses are not fully understood , there is strong evidence that a process of random , independent formation and pruning of excitatory synapses can be ruled out .", "Inst...	[ "Structural plasticity has been observed even in the adult mammalian neocortex – in seemingly static neuronal circuits structural remodeling is continuously at work .", "Still , it has been shown that the connection patterns between pairs of neurons are not random .", "In contrast , there is evidence that the s...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "test evaluation", "diagnostic medicine", "neglected tropical diseases", "leptospirosis" ]	Sensitivity and Specificity of a New Vertical Flow Rapid Diagnostic Test for the Serodiagnosis of Human Leptospirosis	journal.pntd.0002289	null	[ [ "Leptospirosis is a bacterial disease of high incidence in many tropical and sub-tropical areas [1] , [2] .", "Its clinical presentation is both highly variable and most often characterized by non-specific signs and symptoms; the complete triad of Weil's disease ( hepatic failure , renal failure and hemor...	[ "This RDT might be used as a point of care diagnostic tool in limited resources countries .", "An evaluation in field conditions and in other epidemiological contexts should be considered to assess its validity over a wider range of serogroups or when facing different endemic pathogens .", "It might prove usefu...	[ "The major burden of leptospirosis happens in low-income populations from tropical or subtropical regions .", "Because of nonspecific symptoms in human leptospirosis , the biological confirmation is needed to ascertain the disease .", "However , this biological diagnosis relies on sophisticated and time-consumi...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Integrative Analysis of Circadian Transcriptome and Metabolic Network Reveals the Role of De Novo Purine Synthesis in Circadian Control of Cell Cycle	journal.pcbi.1004086	null	[ [ "The circadian clock represents a key time-keeping mechanism for many fundamental physiological processes such as cell cycle and metabolism .", "The cell cycle and the circadian clock are both well-studied periodic processes and their interaction has been a recent focus of circadian research .", "Unti...	[ "Metabolism is the major output of the circadian clock in many organisms .", "We developed a computational method to integrate both circadian gene expression and metabolic network .", "Applying this method to zebrafish circadian transcriptome , we have identified large clusters of metabolic genes containing mos...	[ "The circadian timing system gates cell cycle progression in various organisms from unicellular microorganisms to mammals .", "Although a number of factors have been implicated in linking the circadian clock with the cell cycle , little is known about the contribution of metabolic processes to this interaction ."...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "livestock", "medicine and health sciences", "ecology and environmental sciences", "onchocerca volvulus", "rivers", "ruminants", "tropical diseases", "geographical locations", "vertebrates", "vector-borne diseases", "parasitic diseases", "animals", "mammals", "onchocerca...	Ongoing Transmission of Onchocerca volvulus after 25 Years of Annual Ivermectin Mass Treatments in the Vina du Nord River Valley, in North Cameroon	journal.pntd.0004392	null	[ [ "The interruption of transmission of Onchocerca volvulus , the causing agent of river blindness or onchocerciasis , has been confirmed for a growing number of endemic foci on the American continent [1 , 2 , 3] and in West [4] and East Africa [5 , 6 , 7] .", "The recent success in onchocerciasis control ca...	[ "Recent reports of transmission interruption of Onchocerca volvulus , the causing agent of river blindness , in former endemic foci in the Americas , and more recently in West and East Africa , raise the question whether elimination of this debilitating disease is underway after long-term treatment of the populatio...	[ "Over the past decades the Fight against river blindness , a tropical disease caused by a nematode worm , has been relatively successful , and a number of countries have been reported to be free of parasite transmission .", "In North Cameroon , we checked the occurrence of infective stages of Onchocerca volvulus ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Characterisation of a Multi-ligand Binding Chemoreceptor CcmL (Tlp3) of Campylobacter jejuni	journal.ppat.1003822	null	[ [ "Campylobacter jejuni is the one of the prevalent causes of acute human bacterial gastroenteritis worldwide [1]–[3] .", "C . jejuni is commonly found in the gastrointestinal tract of birds and poultry as commensal microbial flora [1] , with infections in humans usually occurring from consumption of underc...	[ "Campylobacter jejuni is the leading cause of human gastroenteritis worldwide with over 500 million cases annually .", "Chemotaxis and motility have been identified as important virulence factors associated with C . jejuni colonisation .", "Group A transducer-like proteins ( Tlps ) are responsible for sensing t...	[ "Bacterial chemotaxis is an important part in initiation of colonisation and subsequent pathogenicity .", "In this study , we report direct evidence supporting the involvement of C . jejuni transducer-like protein Cj1564 ( Tlp3 ) in the chemotaxis signalling pathway via small molecule arrays , surface plasmon and...	2014
[ "Introduction", "Conclusions", "Materials and Methods" ]	[ "biotechnology", "flight mechanics (biology)", "x-radiation", "engineering and technology", "nervous system", "neuroscience", "biological locomotion", "biomechanics", "electromagnetic radiation", "materials science", "zoology", "bioengineering", "musculoskeletal system", "biomaterials", ...	In Vivo Time-Resolved Microtomography Reveals the Mechanics of the Blowfly Flight Motor	journal.pbio.1001823	Time-resolved X-ray microtomography permits a real-time view of the blowfly in flight at a previously unprecedented level of detail, revealing how the tiny steering muscles work.	[ [ "We undertook time-resolved microtomographic imaging of the thorax of tethered blowflies flying in the TOMCAT beamline of the Swiss Light Source [29] .", "We used single exposure phase retrieval to increase contrast by an order of magnitude over standard absorption-based imaging [30] .", "This was imp...	[ "Dipteran flies are amongst the smallest and most agile of flying animals .", "Their wings are driven indirectly by large power muscles , which cause cyclical deformations of the thorax that are amplified through the intricate wing hinge .", "Asymmetric flight manoeuvres are controlled by 13 pairs of steering m...	[ "A blowfly's wingbeat is 50 times shorter than a blink of a human eye , and is controlled by numerous tiny steering muscles—some of which are as thin as a human hair .", "To visualize the movements of these muscles and the deformations of the surrounding exoskeleton , we developed a technique to allow us to look ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "genetics and genomics/genetics of disease", "genetics and genomics/medical genetics" ]	The IG-DMR and the MEG3-DMR at Human Chromosome 14q32.2: Hierarchical Interaction and Distinct Functional Properties as Imprinting Control Centers	journal.pgen.1000992	null	[ [ "Human chromosome 14q32 . 2 carries a cluster of protein-coding paternally expressed genes ( PEGs ) such as DLK1 and RTL1 and non-coding maternally expressed genes ( MEGs ) such as MEG3 ( alias , GTL2 ) , RTL1as ( RTL1 antisense ) , MEG8 , snoRNAs , and microRNAs [1] , [2] .", "Consistent with this , pate...	[ "Human chromosome 14q32 . 2 harbors the germline-derived primary DLK1-MEG3 intergenic differentially methylated region ( IG-DMR ) and the postfertilization-derived secondary MEG3-DMR , together with multiple imprinted genes .", "Although previous studies in cases with microdeletions and epimutations affecting bot...	[ "Genomic imprinting is a process causing genes to be expressed in a parent-of-origin specific manner—some imprinted genes are expressed from maternally inherited chromosomes and others from paternally inherited chromosomes .", "Imprinted genes are often located in clusters regulated by regions that are differenti...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "genome-wide association studies", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "body fluids", "immune cells", "pathogens", "immunology", "microbiology", "alleles", "retroviruses", "viruses",...	Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1	journal.ppat.1006703	null	[ [ "The discovery of the protective deletion variant , CCR5-delta32 , in the chemokine receptor 5 gene , encoding a HIV-1 co-receptor [1–3] , generated great enthusiasm to search for additional host genetic variants and pathways associated with HIV-1 acquisition as a means of identifying targets for new HIV-1 pr...	[ "Host genetic variation modifying HIV-1 acquisition risk can inform development of HIV-1 prevention strategies .", "However , associations between rare or intermediate-frequency variants and HIV-1 acquisition are not well studied .", "We tested for the association between variation in genic regions and extreme ...	[ "Antiretroviral drugs for pre-exposure prophylaxis ( PrEP ) or treatment significantly reduce risk of HIV-1 acquisition and transmission , but face challenges of increasing access , maintaining high adherence , and selecting viral resistance .", "Improved understanding of the molecular determinants of HIV-1 sexua...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biotechnology", "oncology", "biochemistry", "homo (human)", "genetics and genomics", "saccharomyces" ]	Function-Altering SNPs in the Human Multidrug Transporter Gene ABCB1 Identified Using a Saccharomyces-Based Assay	journal.pgen.0030039	null	[ [ "Patients vary widely in their drug responses including unpredicted adverse drug reactions that cause a significant loss of lives and a huge toll on health-care costs [1] .", "Rational selection and dosage optimization of anticancer agents are particularly important due to their narrow therapeutic index a...	[ "The human ABCB1 ( MDR1 ) -encoded multidrug transporter P-glycoprotein ( P-gp ) plays a major role in disposition and efficacy of a broad range of drugs including anticancer agents .", "ABCB1 polymorphisms could therefore determine interindividual variability in resistance to these drugs .", "To test this hypo...	[ "Patients often show varied drug responses ranging from lack of therapeutic efficacy to life-threatening adverse drug reactions .", "Drug therapy would be greatly improved if it were possible to predict individual drug sensitivity and tailor drugs to patients' genetic makeup .", "Like all other organisms , huma...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "clinical research design", "vomiting", "statistics", "metaanalysis", "tropical diseases", "database searching", "parasitic diseases", "toxicology", "research design", "physiological processes", "toxicity", "mathematics",...	The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia – A review and meta-analysis	journal.pntd.0007173	null	[ [ "Post-Kala-Azar Dermal Leishmaniasis ( PKDL ) is a dermal complication of visceral leishmaniasis ( VL ) caused by the Leishmania donovani parasite , which is transmitted by phlebotomine sandflies .", "The PKDL disease can appear weeks to years after the successful cure of VL and is characterised by skin l...	[ "Miltefosine ( MF ) is the only oral drug available for treatment of visceral leishmaniasis ( VL ) and post-kala-azar dermal leishmaniasis ( PKDL ) .", "Although the drug is effective and well tolerated in treatment of VL , the efficacy and safety of MF for longer treatment durations ( >28 days ) in PKDL remains ...	[ "In this study , we reviewed the available literature on the subject of safety and efficacy of the oral drug miltefosine in the treatment of post-kala-azar dermal leishmaniasis ( PKDL ) .", "Literature was searched systematically in the PubMed database and eight articles , with a total of 324 PKDL patients , were...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Optimal Prediction of Moving Sound Source Direction in the Owl	journal.pcbi.1004360	null	[ [ "Predicting the future position of an object in the environment is a common and critical component of many tasks that involve reaching or orienting toward moving targets [1–4] .", "To execute these prediction tasks successfully , motor plans must extrapolate beyond accumulated sensory input to account for...	[ "Capturing nature’s statistical structure in behavioral responses is at the core of the ability to function adaptively in the environment .", "Bayesian statistical inference describes how sensory and prior information can be combined optimally to guide behavior .", "An outstanding open question of how neural co...	[ "Many behaviors require predictive movements .", "Predictive movements are especially important in prey capture where a predator must predict the future location of moving prey .", "How sensory information is transformed to motor commands for predictive behaviors is an important open question .", "Bayesian st...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/disease models", "genetics and genomics/complex traits" ]	The Genetic Interpretation of Area under the ROC Curve in Genomic Profiling	journal.pgen.1000864	null	[ [ "Genome-wide association studies in human populations have facilitated the creation of genomic profiles which combine the effects of many associated genetic variants to predict risk of disease .", "Genetic testing has long been available for Mendelian genetic diseases for which variants within one gene ar...	[ "Genome-wide association studies in human populations have facilitated the creation of genomic profiles which combine the effects of many associated genetic variants to predict risk of disease .", "The area under the receiver operator characteristic ( ROC ) curve is a well established measure for determining the ...	[ "Genome-wide association studies in human populations have facilitated the creation of genomic profiles that combine the effects of many associated genetic variants to predict risk of disease .", "However , genomic profiles are inherently constrained in their ability to classify diseased from non-diseased individ...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "mathematics", "immunology/immune response", "immunology/innate immunity", "public health and epidemiology/infectious diseases", "immunology/immunity to infections", "infectious diseases/epidemiology and control of infectious diseases" ]	The Effect of Ongoing Exposure Dynamics in Dose Response Relationships	journal.pcbi.1000399	null	[ [ "Microbial risk assessment models are valuable tools for estimating the risks", "associated with exposures to pathogens in the environment pathogens [1] .", "Central", "to this estimate is a dose-response model that predicts the probability of infection", "given a dose exposure magnitude .", ...	[ "Characterizing infectivity as a function of pathogen dose is integral to", "microbial risk assessment .", "Dose-response experiments usually administer doses to", "subjects at one time .", "Phenomenological models of the resulting data , such as the", "exponential and the Beta-Poisson models , ignore dos...	[ "We model the relationship between the temporal patterns of pathogen exposure and", "infection take off within people .", "Since different routes of transmission ( e . g . ,", "airborne versus surface transfer routes ) may result in different temporal", "patterns of exposure , this model helps to better com...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "genomics", "biology", "computational biology", "evolutionary biology", "genetics and genomics" ]	Evidence for Positive Selection on a Number of MicroRNA Regulatory Interactions during Recent Human Evolution	journal.pgen.1002578	null	[ [ "microRNAs ( miRNAs ) are endogenous small RNAs that bind to their target mRNAs to post-transcriptionally repress protein production .", "They recognize their target mRNAs primarily through sequence complementarity between the seed region of a miRNA ( usually defined as the 2nd to the 7th or 8th nucleotid...	[ "MicroRNA ( miRNA ) –mediated gene regulation is of critical functional importance in animals and is thought to be largely constrained during evolution .", "However , little is known regarding evolutionary changes of the miRNA network and their role in human evolution .", "Here we show that a number of miRNA bi...	[ "MicroRNAs ( miRNAs ) are endogenous small RNAs that bind to their target mRNAs to post-transcriptionally repress protein production .", "miRNA–mediated gene regulation is usually considered to be strongly conserved among and within species , and thus alteration of such regulations is usually considered as detrim...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "dna metabolism", "microbiology", "telomeres", "model organisms", "dna", "chromosome biology", "biology", "molecular biology", "cell biology", "nucleic acids", "yeast and fungal models", "saccharomyces cerevisiae", "dna recombination", "molecular cell biology" ]	Rif1 Supports the Function of the CST Complex in Yeast Telomere Capping	journal.pgen.1002024	null	[ [ "Telomeres , the specialized nucleoprotein complexes at the ends of eukaryotic chromosomes , are essential for genome integrity .", "They protects chromosome ends from fusions , DNA degradation and recognition as DNA double-strand breaks ( DSBs ) that would otherwise lead to chromosome instability and cel...	[ "Telomere integrity in budding yeast depends on the CST ( Cdc13-Stn1-Ten1 ) and shelterin-like ( Rap1-Rif1-Rif2 ) complexes , which are thought to act independently from each other .", "Here we show that a specific functional interaction indeed exists among components of the two complexes .", "In particular , u...	[ "Protection of chromosome ends is crucial for maintaining chromosome stability and genome integrity , and its failure leads to genome rearrangements that may facilitate carcinogenesis .", "This protection is achieved by the packaging of chromosome ends into protective structures called telomeres that prevent DNA ...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "immune cells", "immunology", "parasitic diseases", "parasitic protozoans", "collagens", "developmental biology", "lymph nodes", "protozoans", "si...	Morinda citrifolia Linn. Reduces Parasite Load and Modulates Cytokines and Extracellular Matrix Proteins in C57BL/6 Mice Infected with Leishmania (Leishmania) amazonensis	journal.pntd.0004900	null	[ [ "Leishmaniasis is one of the seventeen neglected diseases prioritized by the World Health Organization .", "Although most cases of neglected diseases are in underdeveloped countries , leishmaniasis is spreading worldwide [1] .", "The infection caused by Leishmania parasites may remain asymptomatic or ...	[ "The absence of an effective vaccine and the debilitating chemotherapy for Leishmaniasis demonstrate the need for developing alternative treatments .", "Several studies conducted with Morinda citrifolia have shown various biological activities , including antileishmanial activity , however its mechanisms of actio...	[ "Leishmaniasis is a complex of diseases caused by parasites of the Leishmania genus , which affects thousands of people around the world .", "The parasite lives within the cells and the disease manifests itself in different ways , one of them is wound-like lesions on the skin that do not heal .", "The treatment...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/theoretical neuroscience", "biophysics/theory and simulation", "neuroscience/sensory systems", "computational biology/computational neuroscience" ]	Specific Entrainment of Mitral Cells during Gamma Oscillation in the Rat Olfactory Bulb	journal.pcbi.1000551	null	[ [ "Recent experiments under awake conditions indicate that there is little effective spatial contrast in the firing rate of neurons in olfactory structures [1] and even in auditory primary sensory structures [2] , which suggests a limited role for the mean firing rate in sensory function .", "In addition , ...	[ "Local field potential ( LFP ) oscillations are often accompanied by synchronization of activity within a widespread cerebral area .", "Thus , the LFP and neuronal coherence appear to be the result of a common mechanism that underlies neuronal assembly formation .", "We used the olfactory bulb as a model to inv...	[ "Olfactory function relies on a chain of neural relays that extends from the periphery to the central nervous system and implies neural activity with various timescales .", "A central question in neuroscience is how information is encoded by the neural activity .", "In the mammalian olfactory bulb , local neura...	2009
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "physics", "biochemistry", "research design", "proteins", "protein folding", "protein structure", "longitudinal studies", "biology and life sciences", "physical sciences", "biomarkers", "biophysics", "research and analysis methods" ]	Optimal Reaction Coordinate as a Biomarker for the Dynamics of Recovery from Kidney Transplant	journal.pcbi.1003685	null	[ [ "Here we present a general framework that allows us to determine such an optimal coordinate or biomarker from longitudinal cohort studies directly , without constructing the Markov state model .", "The method was originally developed to describe complex dynamics of protein folding [7]–[9] .", "Briefly...	[ "The evolution of disease or the progress of recovery of a patient is a complex process , which depends on many factors .", "A quantitative description of this process in real-time by a single , clinically measurable parameter ( biomarker ) would be helpful for early , informed and targeted treatment .", "Organ...	[ "The evolution of disease or the progress of recovery of a patient is usually monitored by collecting physical parameters , which may be simply the body temperature for a common cold or properties of tissue samples for e . g . , cancer .", "Most often clinical decisions are taken based on the current value or bec...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "gene regulation", "regulatory proteins", "messenger rna", "dna-binding proteins", "animals", "dna transcription", "circadian oscillators", "animal models", "drosophila melanogaster", "model organisms", "transcription factors", "chronobiology", "drosophila", "research an...	CLOCKWORK ORANGE Enhances PERIOD Mediated Rhythms in Transcriptional Repression by Antagonizing E-box Binding by CLOCK-CYCLE	journal.pgen.1006430	null	[ [ "Almost all organisms from Cyanobacteria to humans have internal circadian clocks that drive daily rhythms in physiology , metabolism and behavior , thereby synchronizing internal processes with the external environment .", "In eukaryotes , the circadian clock keeps time via one or more transcriptional fe...	[ "The Drosophila circadian oscillator controls daily rhythms in physiology , metabolism and behavior via transcriptional feedback loops .", "CLOCK-CYCLE ( CLK-CYC ) heterodimers initiate feedback loop function by binding E-box elements to activate per and tim transcription .", "PER-TIM heterodimers then accumula...	[ "Circadian clocks control daily rhythms in animal , plant and fungal physiology , metabolism and behavior via transcriptional feedback loops .", "In Drosophila , the CLOCK-CYCLE ( CLK-CYC ) activator complex binds E-box regulatory sequences to initiate transcription of hundreds of effector genes including their o...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "neglected tropical diseases", "infectious disease control", "public health" ]	Effect of a Control Project on Clinical Profiles and Outcomes in Buruli Ulcer: A Before/After Study in Bas-Congo, Democratic Republic of Congo	journal.pntd.0001402	null	[ [ "Buruli ulcer ( BU ) is a necrotizing bacterial infection of skin , subcutaneous tissue and bone , caused by an environmental pathogen , Mycobacterium ulcerans [1] .", "Although the functional impairment caused by BU results in severe suffering and in socio-economic problems [2] , the disease remains larg...	[ "Buruli ulcer ( BU ) is a necrotizing bacterial infection of skin , subcutaneous tissue and bone caused by Mycobacterium ulcerans .", "Although the functional impairment caused by BU results in severe suffering and in socio-economic problems , the disease remains largely neglected in Africa .", "The province of...	[ "Buruli ulcer ( BU ) , which is caused by Mycobacterium ulcerans , is an important disabling skin disease .", "However , BU has been neglected in many endemic African countries , including in the Democratic Republic of Congo .", "The province of Bas-Congo contains one of the most important BU foci of the countr...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Combining Public Health Education and Disease Ecology Research: Using Citizen Science to Assess Chagas Disease Entomological Risk in Texas	journal.pntd.0004235	null	[ [ "Citizen science—the engagement of non-scientists in collecting scientific data—has long been used in ecological and wildlife research [1–3] , resulting in an engaged public and providing researchers access to data from large geographic and temporal scales .", "We pose that citizen science is a powerful y...	[ "Chagas disease is a zoonotic parasitic disease well-documented throughout the Americas and transmitted primarily by triatomine ‘kissing bug’ vectors .", "In acknowledgment of the successful history of vector control programs based on community participation across Latin America , we used a citizen science approa...	[ "We created a kissing bug citizen science program in Texas to educate the public about Chagas disease , a vector-borne disease of humans and dogs , and to create a mechanism for the public to submit triatomine ‘kissing bug’ vectors to our research program .", "From May 2013 to December 2014 , we designed an inter...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	HTLV-1 Tax Stimulates Ubiquitin E3 Ligase, Ring Finger Protein 8, to Assemble Lysine 63-Linked Polyubiquitin Chains for TAK1 and IKK Activation	journal.ppat.1005102	null	[ [ "Human T-lymphotropic virus type 1 ( HTLV-1 ) is the etiological agent of adult T-cell leukemia/lymphoma ( ATL ) and HTLV-1-associated myelopathy/tropical spastic paraparesis ( HAM/TSP ) .", "The HTLV-1 genome encodes a trans-activator/oncoprotein known as Tax , which is crucial for viral transcription an...	[ "Human T lymphotropic virus type 1 ( HTLV-1 ) trans-activator/oncoprotein , Tax , impacts a multitude of cellular processes , including I-κB kinase ( IKK ) /NF-κB signaling , DNA damage repair , and mitosis .", "These activities of Tax have been implicated in the development of adult T-cell leukemia ( ATL ) in HT...	[ "Activation of the NF-κB family of transcription factors by the HTLV-1 oncoprotein , Tax , is causally linked to adult T cell leukemia ( ATL ) development in HTLV-1-infected individuals , but the underlying mechanisms are not fully understood .", "NF-κB activation requires the phosphorylation of its inhibitor , I...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "systems biology", "genome complexity", "plant science", "genomics", "phenotypes", "plant genomics", "genetics", "biology and life sciences", "population genetics", "plant genetics", "computational biology", "evolutionary biology", "population biology", "plant biotechnol...	Genetic Variation in the Nuclear and Organellar Genomes Modulates Stochastic Variation in the Metabolome, Growth, and Defense	journal.pgen.1004779	null	[ [ "The link between genotype and phenotype is often considered to be deterministic such that a single genotype functions to yield a specific phenotypic value .", "This deterministic relationship is a central tenet of the desire to develop predictive models allowing an organism's phenotype to be forecasted u...	[ "Recent studies are starting to show that genetic control over stochastic variation is a key evolutionary solution of single celled organisms in the face of unpredictable environments .", "This has been expanded to show that genetic variation can alter stochastic variation in transcriptional processes within mult...	[ "Systems biology is largely based on the principal that the link between genotype and phenotype is deterministic , and , if we know enough , can be predicted with high accuracy .", "In contrast , recent work studying transcription within single celled organisms has shown that the genotype to phenotype link is sto...	2015
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "plasmodium falciparum", "medicine", "biotechnology", "agrochemicals", "infectious diseases", "chagas disease", "tropical diseases (non-neglected)", "african trypanosomiasis", "leishmaniasis", "neglected tropical diseases", "malaria", "agriculture" ]	Agrochemicals against Malaria, Sleeping Sickness, Leishmaniasis and Chagas Disease	journal.pntd.0001805	null	[ [ "The Protozoan parasites of the genera Plasmodium spp .", ", Leishmania spp .", ", Trypanosoma brucei spp .", "and Trypanosoma cruzi , are the disease causative agents threatening entire populations in mainly resource poor countries around the world .", "Malaria , due to infection with Plasmod...	[ "In tropical regions , protozoan parasites can cause severe diseases with malaria , leishmaniasis , sleeping sickness , and Chagas disease standing in the forefront .", "Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects ....	[ "Even though agrochemistry and infectious disease control have the same principle goal – the suppression of harmful organisms without harming human health and the environment – there have been only very limited activities to exploit this overlap for the development of new antiinfectious drugs so far .", "In this ...	2012
[ "Introduction", "Results", "Discussion" ]	[ "metabolic networks", "enzymology", "database searching", "reactants", "genomic databases", "plant science", "metabolites", "network analysis", "genome analysis", "enzyme metabolism", "photosynthesis", "plants", "enzyme chemistry", "research and analysis methods", "computer and informati...	Meneco, a Topology-Based Gap-Filling Tool Applicable to Degraded Genome-Wide Metabolic Networks	journal.pcbi.1005276	null	[ [ "Metabolic knowledge is crucial to understand physiology and biotic interactions .", "Supported by an unprecedented rise of sequencing technologies , the last decade saw the increasing understanding of metabolic capacities using genomic knowledge .", "In particular , in 2010 , Thiele and Palsson [1] d...	[ "Increasing amounts of sequence data are becoming available for a wide range of non-model organisms .", "Investigating and modelling the metabolic behaviour of those organisms is highly relevant to understand their biology and ecology .", "As sequences are often incomplete and poorly annotated , draft networks ...	[ "In the era of fast and massive genome sequencing , one challenge is to transform sequence information into biological knowledge .", "Reconstructing metabolic networks that include all biochemical reactions of a cell is a way to infer reactions from genomic data .", "Unfortunately , those data are usually incom...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "immune physiology", "body fluids", "education", "sociology", "immunology", "geographical locations", "social sciences", "parasitic diseases", "animals", "filariasis", "antibodies", "insect vectors", "public and occupational health", "im...	Reassessment of areas with persistent Lymphatic Filariasis nine years after cessation of mass drug administration in Sri Lanka	journal.pntd.0006066	null	[ [ "Lymphatic filariasis ( LF , caused by the filarial nematodes Wuchereria bancrofti , Brugia malayi , and B . timori ) , is a major public-health problem in many tropical and subtropical countries .", "The global program to eliminate Lymphatic Filariasis ( GPELF ) has made significant progress by providing...	[ "Sri Lanka was one of the first countries to initiate a lymphatic filariasis ( LF ) elimination program based on WHO guidelines .", "The Anti-Filariasis Campaign provided 5 annual rounds of mass drug administration ( MDA ) with diethylcarbamazine plus albendazole in all 8 endemic districts from 2002–2006 .", "M...	[ "Lymphatic Filariasis ( LF , also known as “elephantiasis” ) is a disabling and deforming tropical disease caused by parasitic worms that are transmitted by mosquitoes .", "The Sri Lankan Anti-Filariasis Campaign provided 5 annual rounds of mass drug administration ( MDA ) with diethylcarbamazine and albendazole ...	2017

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