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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "sequencing techniques", "heme", "taxonomy", "oxygen", "split-decomposition method", "multiple alignment calculation", "phylogenetics", "data management", "phylogenetic analysis", "molecular biology techniques", "chemical dissociation", "research and analysis methods", "sequence analysis", ...	Evolutionary and Functional Relationships in the Truncated Hemoglobin Family	journal.pcbi.1004701	null	[ [ "Predicting function from sequence and/or structure is one of the most important goals of structural biology , especially considering the increasing number of available sequences derived from multiple sequencing projects [1] .", "General function assignment or annotation , typically based on similarity wi...	[ "Predicting function from sequence is an important goal in current biological research , and although , broad functional assignment is possible when a protein is assigned to a family , predicting functional specificity with accuracy is not straightforward .", "If function is provided by key structural properties ...	[ "Globins are a superfamily of widely studied and diverse globular proteins whose function is tightly related to their oxygen affinity and reactivity .", "Two prominent members are the well-known tetrameric hemoglobin and the monomeric myoglobin , both involved in reversible oxygen storage and transport in mammals...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	HTLV-1 bZIP Factor Induces Inflammation through Labile Foxp3 Expression	journal.ppat.1003630	null	[ [ "Human T-cell leukemia virus type 1 ( HTLV-1 ) is known to be the causal agent of a neoplastic disease of CD4+ T cells , adult T-cell leukemia ( ATL ) [1] .", "In addition , this virus perturbs the host immune system , causing inflammatory diseases and immunodeficiency .", "Inflammatory diseases assoc...	[ "Human T-cell leukemia virus type 1 ( HTLV-1 ) causes both a neoplastic disease and inflammatory diseases , including HTLV-1-associated myelopathy/tropical spastic paraparesis ( HAM/TSP ) .", "The HTLV-1 basic leucine zipper factor ( HBZ ) gene is encoded in the minus strand of the proviral DNA and is constitutiv...	[ "Viral infection frequently induces tissue inflammation in the host .", "HTLV-1 infection is associated with chronic inflammation in the CNS , skin , and lung , but the inflammatory mechanism is not fully understood yet .", "Since HTLV-1 directly infects CD4+ T cells , central player of the host immune regulati...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "neuroscience" ]	Computational Phenotyping of Two-Person Interactions Reveals Differential Neural Response to Depth-of-Thought	journal.pcbi.1002841	null	[ [ "Here we write the model for how player forms an estimate of optimal play at each round t by calculating the values of their possible actions .", "The actions are the amounts to invest or to return .", "The values are the expected summed utilities over the next two rounds ( as a simplification , playe...	[ "Reciprocating exchange with other humans requires individuals to infer the intentions of their partners .", "Despite the importance of this ability in healthy cognition and its impact in disease , the dimensions employed and computations involved in such inferences are not clear .", "We used a computational th...	[ "Human social interactions are extraordinarily rich and complex .", "The ability to infer the intentions of others is essential for successful social interactions .", "Although most of our inferences about others are silent and subtle , traces of their effects can be found in the behavior we exhibit in various ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	New Routes to Phylogeography: A Bayesian Structured Coalescent Approximation	journal.pgen.1005421	null	[ [ "Phylogeographic methods aim to infer many aspects of population evolution from genetic data .", "The phylogeography term often encompasses methods that infer changes in population size ( phylodynamics ) and population divergence events ( see [1] ) .", "In this work , we focus on the inference of migr...	[ "Phylogeographic methods aim to infer migration trends and the history of sampled lineages from genetic data .", "Applications of phylogeography are broad , and in the context of pathogens include the reconstruction of transmission histories and the origin and emergence of outbreaks .", "Phylogeographic inferen...	[ "When studying infectious diseases it is often important to understand how germs spread from location-to-location , person-to-person , or even one part of the body to another .", "Using phylogeographic methods , it is possible to recover the history of spread of pathogens ( or other organisms ) by studying their ...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "medical doctors", "medical personnel", "biomarkers", "health care", "histology", "health care providers", "artificial intelligence", "research and analysis methods", "computer and information sciences", "imaging techniques", "deep learning", "support vector m...	Evaluating reproducibility of AI algorithms in digital pathology with DAPPER	journal.pcbi.1006269	null	[ [ "Artificial Intelligence ( AI ) methods for health data hold great promise but still have to deal with disease complexity: patient cohorts are most frequently an heterogeneous group of subtypes diverse for disease trajectories , with highly variable characteristics in terms of phenotypes ( e . g . bioimages i...	[ "Artificial Intelligence is exponentially increasing its impact on healthcare .", "As deep learning is mastering computer vision tasks , its application to digital pathology is natural , with the promise of aiding in routine reporting and standardizing results across trials .", "Deep learning features inferred ...	[ "In this study , we examine the issue of evaluating accuracy of predictive models from deep learning features in digital pathology , as an hallmark of reproducibility .", "It is indeed a top priority that reproducibility-by-design gets adopted as standard practice in building and validating AI methods in the heal...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational neuroscience", "biology", "neuroscience" ]	Spike-based Decision Learning of Nash Equilibria in Two-Player Games	journal.pcbi.1002691	null	[ [ "Neuroeconomics is an interdisciplinary research field that tries to explain human decision making in neuronal terms .", "Behavioral outcomes are construed as results of brain activity and the neuronal correlates of the quantities relevant for the decision making process are identified .", "Humans , a...	[ "Humans and animals face decision tasks in an uncertain multi-agent environment where an agent's strategy may change in time due to the co-adaptation of others strategies .", "The neuronal substrate and the computational algorithms underlying such adaptive decision making , however , is largely unknown .", "We ...	[ "Socio-economic interactions are captured in a game theoretic framework by multiple agents acting on a pool of goods to maximize their own reward .", "Neuroeconomics tries to explain the agent's behavior in neuronal terms .", "Classical models in neuroeconomics use temporal-difference ( TD ) -learning .", "Th...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computer and information sciences", "systems science", "mathematics", "network analysis", "regulatory networks", "biology and life sciences", "signaling networks", "computational biology", "nonlinear dynamics", "physical sciences" ]	Reciprocal Regulation as a Source of Ultrasensitivity in Two-Component Systems with a Bifunctional Sensor Kinase	journal.pcbi.1003614	null	[ [ "To rationalize the occurrence of concentration robustness in the EnvZ/OmpR system of E . coli , Batchelor and Goulian proposed a simple mathematical model based on the three activities of the bifunctional EnvZ ( denoted by HK in Fig . 2B ) .", "Guided by the observation that the total OmpR concentration ...	[ "Two-component signal transduction systems , where the phosphorylation state of a regulator protein is modulated by a sensor kinase , are common in bacteria and other microbes .", "In many of these systems , the sensor kinase is bifunctional catalyzing both , the phosphorylation and the dephosphorylation of the r...	[ "Bacteria often use two-component systems to sense and respond to environmental changes , which involves autophosphorylation of a sensor kinase and phosphotransfer to a cognate response regulator .", "However , despite conservation of this ‘classical’ scheme there exist substantial variations in the mechanism of ...	2014
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "genetics and genomics/animal genetics" ]	The Caenorhabditis elegans Elongator Complex Regulates Neuronal α-tubulin Acetylation	journal.pgen.1000820	null	[ [ "Microtubules ( MTs ) are polymers of α/β-tubulin heterodimers that associate head-to-tail and laterally to form hollow tubes .", "MTs are usually highly dynamic and undergo rapid turnover by exchange of subunits where the ends of MTs undergo transitions between growth and shrinkage .", "It has been p...	[ "Although acetylated α-tubulin is known to be a marker of stable microtubules in neurons , precise factors that regulate α-tubulin acetylation are , to date , largely unknown .", "Therefore , a genetic screen was employed in the nematode Caenorhabditis elegans that identified the Elongator complex as a possible r...	[ "We were able to demonstrate how a screen , that utilized the nematode model organism Caenorhabditis elegans , yielded the novel discovery that the Elongator protein complex is critical for neuronal development and microtubule acetylation .", "Other scientists have previously shown that the Elongator is important...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Osteopetrorickets due to Snx10 Deficiency in Mice Results from Both Failed Osteoclast Activity and Loss of Gastric Acid-Dependent Calcium Absorption	journal.pgen.1005057	null	[ [ "The function of the bone-resorbing osteoclast is highly dependent on vesicular trafficking pathways [1] .", "Endocytosis and intracellular trafficking of the endocytosed material are required for many osteoclast functions , including creation of the ruffled border; secretion of ions and proteases to dige...	[ "Mutations in sorting nexin 10 ( Snx10 ) have recently been found to account for roughly 4% of all human malignant osteopetrosis , some of them fatal .", "To study the disease pathogenesis , we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in...	[ "We found that Snx10 , a molecule expressed in osteoclasts , was also expressed in the stomach .", "Studies in tissue specific or global knock-down mice showed that Snx10 deficiency resulted in a phenotype that was a consequence of deficiencies in both osteoclasts and gastric zymogenic cells .", "Our studies ad...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genome expression analysis", "animal genetics", "genetic mutation", "immune cells", "antigen-presenting cells", "immunity to infections", "immunology", "microbiology", "host-pathogen interaction", "bacterial diseases", "genome analysis tools", "immune defense", "bacterial path...	Interferon Regulatory Factor 8 Regulates Pathways for Antigen Presentation in Myeloid Cells and during Tuberculosis	journal.pgen.1002097	null	[ [ "The defense mechanisms of mononuclear phagocytes that are circumvented by successful intracellular pathogens are poorly understood [1] .", "Genes and proteins in these pathways may represent valuable targets for therapeutic interventions in the corresponding diseases .", "Such host defense mechanisms...	[ "IRF8 ( Interferon Regulatory Factor 8 ) plays an important role in defenses against intracellular pathogens , including several aspects of myeloid cells function .", "It is required for ontogeny and maturation of macrophages and dendritic cells , for activation of anti-microbial defenses , and for production of ...	[ "IRF8 is a member of the Interferon Regulatory Factor family that is expressed in myeloid cells such as macrophages and dendritic cells and that activates or represses gene transcription upon stimulation with interferon gamma ( IFNγ ) , lipopolysaccharide ( LPS ) , and other microbial stimuli .", "IRF8 plays an i...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "genome-wide association studies", "medicine and health sciences", "population genetics", "carcinomas", "cancers and neoplasms", "endometrial carcinoma", "alleles", "oncology", "genome analysis", "sequence motif analysis", "epigenetics", "molecular biology techniques...	Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus	journal.pgen.1005893	null	[ [ "With the advent of genome-wide association studies ( GWASs ) , a large number of single nucleotide polymorphisms ( SNPs ) associated with human complex diseases have been discovered [1] .", "The findings from GWASs have provided previously unsuspected biological pathways relevant to the diseases [2] such...	[ "Genome-wide association studies ( GWASs ) have discovered numerous single nucleotide polymorphisms ( SNPs ) associated with human complex disorders .", "However , functional characterization of the disease-associated SNPs remains a formidable challenge .", "Here we explored regulatory mechanism of a SNP on chr...	[ "A large number of variants associated with human complex diseases have been discovered by genome-wide association studies ( GWASs ) .", "These discoveries have been anticipated to be translated into the definitive understanding of disease pathogeneses; however , functional characterization of the disease-associa...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurochemistry", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "molecular development", "neuropeptides", "erk signaling cascade", "neurochemicals", "nuclear receptor signaling", "biology", "molecular biology", "biochemistry", "signal transduction"...	Nuclear Receptor DHR4 Controls the Timing of Steroid Hormone Pulses During Drosophila Development	journal.pbio.1001160	Pulses of the steroid hormone ecdysone are turned off periodically through nucleo-cytoplasmic oscillations of a nuclear receptor that counteracts the neuropeptide signaling pathway responsible for activating hormone pulses in Drosophila melanogaster.	[ [ "The development of higher organisms is fundamentally dependent on the precise progression of specific gene programs , and even minor differences in the timing of these events can be fatal [1] , [2] .", "The regulation of simultaneous developmental programs generally relies on systemic signals—typically h...	[ "In insects , precisely timed periodic pulses of the molting hormone ecdysone control major developmental transitions such as molts and metamorphosis .", "The synthesis and release of ecdysone , a steroid hormone , is itself controlled by PTTH ( prothoracicotopic hormone ) .", "PTTH transcript levels oscillate ...	[ "Steroid hormones play fundamental roles in development and disease .", "They are often released as pulses , thereby orchestrating multiple physiological and developmental changes throughout the body .", "Hormone pulses must be regulated in a way so that they have a defined beginning , peak , and end .", "In ...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cell binding", "cell physiology", "cell death", "tumor stem cells", "medicine and health sciences", "endothelial cells", "cancer treatment", "cell processes", "cancer stem cells", "cell differentiation", "epithelial cells", "oncology", "developmental biology", "stem cells", "animal cell...	A mathematical model for IL-6-mediated, stem cell driven tumor growth and targeted treatment	journal.pcbi.1005920	null	[ [ "It is widely believed , based on increasing evidence , that a small population of tumorigenic cells , which are in many ways similar to normal adult stem cells , is responsible for the initiation and maintenance of malignant tumors [1–5] .", "This concept , termed the cancer stem cell ( CSC ) hypothesis ...	[ "Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment .", "Here we present a modeling framework that operates at both the cellular and molecular levels , for investigating IL-6 mediated , cancer stem cell d...	[ "A small population of cancer stem cells that share many of the biological characteristics of normal adult stem cells are believed to initiate and sustain tumor growth for a wide variety of malignancies .", "Growth and survival of these cancer stem cells is highly influenced by tumor micro-environmental factors a...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics	journal.pgen.1005435	null	[ [ "Normal development requires precise temporal control of differential gene expression , yet development must be robust to natural genetic variation and environmental changes .", "[1–3] .", "This resilience of developmental systems is important for keeping a wide genotypic pool adaptable in changing en...	[ "Accurate temporal control of gene expression is essential for normal development and must be robust to natural genetic and environmental variation .", "Studying gene expression variation within and between related species can delineate the level of expression variability that development can tolerate .", "Here...	[ "Embryonic development necessitates a delicate balancing act .", "On one hand , precise regulation of the expression of developmental genes is crucial for the maintenance of morphology and function .", "On the other hand , these same regulatory networks must allow normal development to proceed through genetic v...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Use of Recombinant Virus Replicon Particles for Vaccination against Mycobacterium ulcerans Disease	journal.pntd.0004011	null	[ [ "Mycobacterium ulcerans causes Buruli ulcer ( BU ) , a disease of the skin and underlying subcutaneous tissue , which is reported from over 30 countries worldwide [1] .", "BU is most prevalent in West African countries and mainly affects children less than 15 years of age , living in remote , rural areas ...	[ "Buruli ulcer , caused by infection with Mycobacterium ulcerans , is a necrotizing disease of the skin and subcutaneous tissue , which is most prevalent in rural regions of West African countries .", "The majority of clinical presentations seen in patients are ulcers on limbs that can be treated by eight weeks of...	[ "Infection with Mycobacterium ulcerans can lead to a slow progressing , ulcerative disease of the skin and underlying soft tissue called Buruli ulcer .", "The disease is most prevalent in rural African communities with limited access to health care facilities .", "The most efficient means to prevent the disease...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "infectious disease epidemiology", "theoretical ecology", "population biology", "infectious disease control", "infectious diseases", "environmental epidemiology", "epidemiology", "biology", "vectors and hosts", "infectious disease modeling", "mos...	Modeling Dynamic Introduction of Chikungunya Virus in the United States	journal.pntd.0001918	null	[ [ "Chikungunya fever ( CHIKF ) is a mosquito-borne viral infection first isolated in Tanzania in 1953 [1] , [2] .", "CHIKF is caused by Chikungunya virus ( CHIKV ) , an alphavirus with different variants endemic to countries in Africa and Southeast Asia [3] , [4] .", "Illness caused by CHIKV is usually ...	[ "Chikungunya is a mosquito-borne viral infection of humans that previously was confined to regions in central Africa .", "However , during this century , the virus has shown surprising potential for geographic expansion as it invaded other countries including more temperate regions .", "With no vaccine and no s...	[ "Chikungunya fever is a mosquito-borne viral infection showing a surprising potential for geographic expansion .", "Similar to other tropical infectious diseases having no vaccine and no specific treatment , the main control strategy for Chikungunya remains reduction of mosquito population size .", "We develope...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "t helper cells", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "immune cells", "pathogens", "antigen-presenting cells", "immunology", "microbiology", "surgical and invasive medical procedures", ...	Chemokine Levels in the Penile Coronal Sulcus Correlate with HIV-1 Acquisition and Are Reduced by Male Circumcision in Rakai, Uganda	journal.ppat.1006025	null	[ [ "Two million individuals acquired HIV-1 ( HIV ) in 2014 , contributing to the nearly 37 million living with this still incurable infection [1] .", "While most individuals acquired the virus through heterosexual sex [2] , the per act risk of female-to-male transmission is generally low ( less than 1/250 pe...	[ "Individual susceptibility to HIV is heterogeneous , but the biological mechanisms explaining differences are incompletely understood .", "We hypothesized that penile inflammation may increase HIV susceptibility in men by recruiting permissive CD4 T cells , and that male circumcision may decrease HIV susceptibili...	[ "The per-contact risk of infection with HIV through sexual exposure is low and highly variable .", "Understanding the biological basis for this variability could help in the development of new methods to prevent infection .", "There is some evidence that penile inflammation , even in the absence of any clinical...	2016
[ "Introduction", "Results", "Methods", "Discussion" ]	[ "sequencing techniques", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "markov models", "evolutionary biology", "split-decomposition method", "pathogens", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "multi...	Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity	journal.pcbi.1004870	null	[ [ "The prediction of antibody ( Abs , or immunoglobulins , Igs ) affinity for antigens is among the most interesting open challenges across bioinformatics and structural immunology .", "Most of the current methods rely on the structures ( either experimentally resolved or modeled ) of both antibodies and th...	[ "The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire .", "One of these mechanisms , the affinity maturation process , works in an evolutionary-like fashion: after binding to a foreign molecule , the antibody-producing B-cells exhibit a high-frequenc...	[ "Affinity maturation is a very complex biological process which enables activated B-cells to produce antibodies with increased affinity for a given antigen .", "Once B-cells begin to proliferate , each of the progeny cells introduces mutations in the antigen binding region in order to explore different affinities...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/new therapies, including antivirals and immunotherapy", "virology/animal models of infection", "virology/emerging viral diseases" ]	A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease in a New Ferret Model of Acute Nipah Virus Infection	journal.ppat.1000642	null	[ [ "Nipah virus ( NiV ) together with Hendra virus ( HeV ) are closely related highly pathogenic zoonoses and are the type species within the paramyxovirus genus Henipavirus .", "Both viruses can cause significant morbidity and mortality in a variety of vertebrate species including humans .", "The henipa...	[ "Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats .", "Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals ."...	[ "Nipah virus and Hendra virus are closely related and highly pathogenic zoonoses whose primary natural reservoirs are several species of Pteropus fruit bats .", "Both Nipah and Hendra viruses can cause severe and often fatal disease in a variety of mammalian hosts , including humans .", "The henipaviruses are c...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Epstein-Barr Virus Encoded BART miRNAs Potentiate Tumor Growth In Vivo	journal.ppat.1004561	null	[ [ "Epstein-Barr virus ( EBV ) is a ubiquitous human herpes virus .", "It infects virtually every human being for life and in the overwhelming number of people this persistent infection is benign [1] .", "The virus achieves this by entering into a quiescent latent state within circulating , resting , mem...	[ "The human herpes virus Epstein-Barr virus ( EBV ) latently infects and drives the proliferation of B lymphocytes in vitro and is associated with several forms of lymphoma and carcinoma in vivo .", "The virus encodes ~30 miRNAs in the BART region , the function of most of which remains elusive .", "Here we have...	[ "Epstein-Barr virus is a herpes virus that persistently infects essentially every human being for life .", "It also has the ability to latently infect B lymphocytes and cause them to proliferate indefinitely in culture , and is associated with several forms of carcinoma and lymphoma .", "The virus contains gene...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/molecular dynamics", "computational biology/comparative sequence analysis", "biophysics/protein chemistry and proteomics" ]	Mechanical Network in Titin Immunoglobulin from Force Distribution Analysis	journal.pcbi.1000306	null	[ [ "Cellular functions such as growth , motility , and signaling are tightly coupled with mechanical forces [1]–[3] .", "Proteins play a pivotal role in such mechanically guided processes , as robust elements bearing cellular stress , and as mechanosensors transducing the mechanical signal into a biochemical...	[ "The role of mechanical force in cellular processes is increasingly revealed by single molecule experiments and simulations of force-induced transitions in proteins .", "How the applied force propagates within proteins determines their mechanical behavior yet remains largely unknown .", "We present a new method...	[ "Many biological processes such as cell proliferation and signaling are guided by mechanical stress .", "Proteins as the molecular machinery behind these processes are reacting to or withstanding mechanical forces in specific ways .", "How mechanical stress propagates through proteins to induce a certain mechan...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Competence of Cimex lectularius Bed Bugs for the Transmission of Bartonella quintana, the Agent of Trench Fever	journal.pntd.0003789	null	[ [ "Bartonella quintana is a fastidious gram-negative bacterium that is regarded as a re-emerging human pathogen [1] .", "B . quintana DNA has been detected in the dental pulp of a 4000-year-old man [2] and in lice found in a mass grave of Napoleon’s soldiers in Lithuania , which suggests that many of the so...	[ "Bartonella quintana , the etiologic agent of trench fever and other human diseases , is transmitted by the feces of body lice .", "Recently , this bacterium has been detected in other arthropod families such as bed bugs , which begs the question of their involvement in B . quintana transmission .", "Although s...	[ "Bartonella quintana , the etiologic agent of trench fever and other human diseases , is known to be transmitted by the feces of body lice .", "Recently , the DNA of this bacterium has been detected in bed bugs .", "Several pathogens have been associated and suggested to be transmitted by bed bugs , despite the...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "ecosystem modeling", "ecology", "biology", "computational biology", "microbiology", "microbial ecology" ]	Social Interaction, Noise and Antibiotic-Mediated Switches in the Intestinal Microbiota	journal.pcbi.1002497	null	[ [ "Recent advances in metagenomics provide an unprecedented opportunity to investigate the intestinal microbiota and its role in human health and disease [1] , [2] .", "The analysis of microflora composition has a great potential in diagnostics [3] and may lead to the rational design of new therapeutics tha...	[ "The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens .", "As with other ecosystems , its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically .", "Antibiotic cessation does...	[ "Recent applications of metagenomics have led to a flood of novel studies and a renewed interest in the role of the gut microbiota in human health .", "We can now envision a time in the near future where analysis of microbiota composition can be used for diagnostics and the rational design of new therapeutics .",...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "invertebrates", "medicine and health sciences", "immune cells", "molecular probe techniques", "antigen-presenting cells", "immunology", "immunoblotting", "vertebrates", "animals", "mammals", "animal models", "developmental biology", "signal inhibition", "drosophila me...	Supramolecular assembly of the beta-catenin destruction complex and the effect of Wnt signaling on its localization, molecular size, and activity in vivo	journal.pgen.1007339	null	[ [ "Cell-cell signaling is critical for cell fate decisions during embryonic development and cell fate maintenance during adult homeostasis .", "Altered signaling by these same pathways underlies most solid tumors .", "The Wnt signaling pathway provides a paradigm—it regulates cell fate choice in tissues...	[ "Wnt signaling provides a paradigm for cell-cell signals that regulate embryonic development and stem cell homeostasis and are inappropriately activated in cancers .", "The tumor suppressors APC and Axin form the core of the multiprotein destruction complex , which targets the Wnt-effector beta-catenin for phosph...	[ "Cell-cell communication is critical for cells to choose fates during embryonic development and often goes wrong in diseases like cancer .", "The Wnt cell signaling pathway provides a superb example .", "Loss of negative regulatory proteins like APC and Axin takes the brakes off cell proliferation and thus cont...	2018
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "medicine and health sciences", "luciferase", "molecular probe techniques", "natural antisense transcripts", "gene regulation", "enzymes", "enzymology", "hormones", "developmental biology", "regulator genes", "micrornas", "animal anatomy", "nymphs", "gene types", "molecular biology techn...	miR-34 modulates wing polyphenism in planthopper	journal.pgen.1008235	null	[ [ "The phenomenon of polyphenism is that two or more distinct phenotypes are displayed by an organism with the same genotype .", "This phenomenon is triggered by environmental cues such as population density , host nutrition , and temperature [1] .", "For example , locusts show density-dependent phenoty...	[ "Polyphenism is a successful strategy adopted by organisms to adapt to environmental changes .", "Brown planthoppers ( BPH , Nilaparvata lugens ) develop two wing phenotypes , including long-winged ( LW ) and short-winged ( SW ) morphs .", "Though insulin receptor ( InR ) and juvenile hormone ( JH ) have been k...	[ "Polyphenism is a fascinating phenomenon which significantly improves the ability of a species to explore various environmental resources .", "Brown planthopper ( Nilaparvata lugens , BPH ) is a notorious insect pest which causes huge damages to rice .", "BPH has two wing phenotypes , long-winged ( LW ) and sho...	2019
[ "Introduction", "Model", "Results", "Discussion" ]	[ "developmental biology/morphogenesis and cell biology", "mathematics", "developmental biology/developmental evolution", "developmental biology/pattern formation", "neuroscience/neurodevelopment", "developmental biology/neurodevelopment", "evolutionary biology/pattern formation", "evolutionary biology/...	Chemically Based Mathematical Model for Development of Cerebral Cortical Folding Patterns	journal.pcbi.1000524	null	[ [ "Cerebral cortical patterns have fascinated scientists for centuries with their beauty and complexity .", "Numerous groups relate malformations in sulcal patterns to different diseases in humans , such as autism [1] and attention deficit/hyperactivity disorder ( ADHD ) [2] .", "Though many advances ha...	[ "The mechanism for cortical folding pattern formation is not fully understood .", "Current models represent scenarios that describe pattern formation through local interactions , and one recent model is the intermediate progenitor model .", "The intermediate progenitor ( IP ) model describes a local chemically ...	[ "The size and shape of the cerebral cortex varies across species .", "The cortical folding pattern also varies from a smooth surface where no pattern is visible , as observed in the common treeshrew ( Tupaia glis ) and Eastern mole ( Scalopus aquaticus ) , to an intricate labyrinthine pattern , as observed in hum...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "sequencing techniques", "nucleic acid synthesis", "experimental design", "rna extraction", "nucleotides", "research design", "molecular biology techniques", "rna synthesis", "rna sequencing", "extraction techniques", "rna transcription labeling", "chemical synthesis", "research and analysis...	On the optimal design of metabolic RNA labeling experiments	journal.pcbi.1007252	null	[ [ "Changes in gene expression are frequently observed in pathological conditions .", "In the simplest model [1] , steady state RNA levels are governed by synthesis ( transcription ) and degradation rates ( RNA stability ) .", "A paradigm is the generation of the hypoxic response in pathological conditio...	[ "Massively parallel RNA sequencing ( RNA-seq ) in combination with metabolic labeling has become the de facto standard approach to study alterations in RNA transcription , processing or decay .", "Regardless of advances in the experimental protocols and techniques , every experimentalist needs to specify the key ...	[ "Massively parallel RNA sequencing ( RNA-seq ) in combination with metabolic labeling has become the de facto standard approach to study alterations in RNA transcription , processing or decay .", "In our manuscript , we address several key aspects of experimental design:", "1 ) The optimal labeling time ,", "...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Transcription Profiling of Malaria-Naïve and Semi-immune Colombian Volunteers in a Plasmodium vivax Sporozoite Challenge	journal.pntd.0003978	null	[ [ "One of the features of Plasmodium species that make them such pernicious parasites is their ability to avoid the host immune system [1 , 2] .", "While this is achieved in part by virtue of their complex life cycle that includes intra-erythrocyte cycling and periodic sequestration in various tissue compar...	[ "Continued exposure to malaria-causing parasites in endemic regions of malaria induces significant levels of acquired immunity in adult individuals .", "A better understanding of the transcriptional basis for this acquired immunological response may provide insight into how the immune system can be boosted during...	[ "Plasmodium vivax malaria is a debilitating , occasionally life-threatening , and economically burdensome disease in Central Latin America , where 70%- 80% of the population lives with the risk of infection .", "We performed a gene expression profiling experiment taking advantage of a previously described sporozo...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/systems biology", "cell biology/gene expression", "computational biology/transcriptional regulation" ]	Dynamic Analysis of Stochastic Transcription Cycles	journal.pbio.1000607	Cycling of gene expression in individual cells is controlled by dynamic chromatin remodeling.	[ [ "Gene expression in living cells is dynamic and unstable , and fluctuations in transcription may be subject to stochastic regulation of processes including transcription factor and polymerase recruitment , and chromatin remodeling [1]–[5] .", "Cell-to-cell variation in the amount of protein a gene encodes...	[ "In individual mammalian cells the expression of some genes such as prolactin is highly variable over time and has been suggested to occur in stochastic pulses .", "To investigate the origins of this behavior and to understand its functional relevance , we quantitatively analyzed this variability using new mathem...	[ "Timing of biological processes such as gene transcription is crucial to ensure that cells and tissues respond appropriately to their environment .", "Until recently it was assumed that most cells in a tissue responded in a similar way , and that changes in cellular activity were relatively stable .", "However ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "muscle tissue", "skeletal muscles", "cell differentiation", "muscle regeneration", "developmental biology", "organism development", "epigenetics", "dna", "morphogenesis", "dna methylation", "chromatin", "musculoskeletal system", "chromosome biology", "mus...	Dnmt3a Regulates Proliferation of Muscle Satellite Cells via p57Kip2	journal.pgen.1006167	null	[ [ "Myogenic differentiation program has been extensively studied as a model of tissue differentiation since the discovery of MyoD [1] .", "Although much is known about the gene cascade of myogenesis [2 , 3] , the epigenetic mechanisms that regulate the physiological and pathological condition of skeletal mu...	[ "Cell differentiation status is defined by the gene expression profile , which is coordinately controlled by epigenetic mechanisms .", "Cell type-specific DNA methylation patterns are established by chromatin modifiers including de novo DNA methyltransferases , such as Dnmt3a and Dnmt3b .", "Since the discovery...	[ "How muscle homeostasis is maintained is not completely elucidated yet .", "Epigenetic disorders such as Beckwith-Wiedemann syndrome , which causes hypergrowth of skeletal muscles and rhabdomyosarcoma , indicate that epigenetic regulations such as DNA methylation , contribute to this homeostasis control .", "DN...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/immunity to infections", "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "infectious diseases/neglected tropical diseases", "immunology/innate immunity", "cell biology/microbial growth and development", "microbiology/parasitology" ]	Mosquito Infection Responses to Developing Filarial Worms	journal.pntd.0000529	null	[ [ "It is estimated that 120 million people are infected with Wuchereria bancrofti , Brugia malayi , or B . timori , the mosquito-transmitted , parasitic nematodes that cause human lymphatic filariasis ( LF ) .", "In approximately 40% of cases , the disease is manifested by lymphedema of the extremities or h...	[ "Human lymphatic filariasis is a mosquito-vectored disease caused by the nematode parasites Wuchereria bancrofti , Brugia malayi and Brugia timori .", "These are relatively large roundworms that can cause considerable damage in compatible mosquito vectors .", "In order to assess how mosquitoes respond to infect...	[ "Filarial worms that cause human lymphatic filariasis ( LF ) are transmitted by many species of mosquitoes .", "Within susceptible mosquitoes , Brugia malayi develop from microfilariae ( mf ) to infective-stage larvae ( L3s ) , in approximately eight days .", "These nematodes develop as intracellular parasites ...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Unraveling the Transmission Ecology of Polio	journal.pbio.1002172	Using models to reveal the epidemiology of historic poliovirus transmission in the US, this study reconstructs the millions of silent infections and identifies why polio epidemics are explosive, seasonal, and vary geographically.	[ [ "Poliovirus , like other members of Picornaviridae , usually generates mildly symptomatic infection .", "However , the clinical manifestation of polio , Acute Flaccid Paralysis ( AFP ) , can result when the virus invades the central nervous system [1] .", "Wild poliovirus ( WPV ) is transmitted fecal–...	[ "Sustained and coordinated vaccination efforts have brought polio eradication within reach .", "Anticipating the eradication of wild poliovirus ( WPV ) and the subsequent challenges in preventing its re-emergence , we look to the past to identify why polio rose to epidemic levels in the mid-20th century , and how...	[ "Thanks to global vaccination efforts , poliovirus is on the brink of worldwide eradication .", "However , achieving eradication and preventing re-emergence requires intimate knowledge of how the virus persists .", "In order to understand a system that is complicated by heavy human intervention , such as vaccin...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "chemical compounds", "helminths", "salts", "parasitic diseases", "animals", "animal models", "model organisms", "experimental organism systems", "glycosylation", "digestive system", "research and analysis methods", "mucus",...	Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion	journal.ppat.1006218	null	[ [ "The intestinal epithelium is lined by a continuous mucus barrier which provides physical protection and chemically protects the epithelial cell layer by sequestering important host defence factors within its complex matrix [1] .", "Gel-forming mucins ( Muc2 in the intestine ) produced by goblet cells , g...	[ "Mucins are heavily glycosylated proteins that give mucus its gel-like properties .", "Moreover , the glycans decorating the mucin protein core can alter the protective properties of the mucus barrier .", "To investigate whether these alterations could be parasite-induced we utilized the Trichuris muris ( T . m...	[ "Approximately 2 billion people are infected with worms every year , causing physical , nutritional and cognitive impairment particularly in children .", "Mucins are large sugar-coated ( glycosylated ) proteins that form the intestinal mucus layer .", "This mucus layer protects our ‘insides’ from external insul...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Mismatch Repair Genes Mlh1 and Mlh3 Modify CAG Instability in Huntington's Disease Mice: Genome-Wide and Candidate Approaches	journal.pgen.1003930	null	[ [ "Huntington's disease ( HD ) is a fatal , dominantly inherited neurodegenerative disease , which is caused by the expansion of a CAG repeat within exon 1 of the HTT gene , resulting in an extended glutamine tract in the huntingtin protein ( HTT ) [1] .", "The length of the longer CAG repeat tract is the p...	[ "The Huntington's disease gene ( HTT ) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis .", "Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation , an approach that is likely applicable to other trinucleotide repeat diseases ....	[ "The expansion of a CAG repeat underlies Huntington's disease ( HD ) , with longer CAG tracts giving rise to earlier onset and more severe disease .", "In individuals harboring a CAG expansion the repeat undergoes further somatic expansion over time , particularly in brain cells most susceptible to disease pathog...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell signaling", "virology/virion structure, assembly, and egress", "cell biology/membranes and sorting", "biochemistry/cell signaling and trafficking structures", "virology/viruses and cancer", "cell biology/cytoskeleton" ]	Vesicular Egress of Non-Enveloped Lytic Parvoviruses Depends on Gelsolin Functioning	journal.ppat.1000126	null	[ [ "The genus parvovirus ( PV ) consists of small icosahedral non-enveloped particles with a 5 . 1-kb linear single-stranded DNA genome .", "During productive infection , PVs induce dramatic morphological and physiological changes in their host cells , culminating in cell death and lysis .", "PV cytotoxi...	[ "The autonomous parvovirus Minute Virus of Mice ( MVM ) induces specific changes in the cytoskeleton filaments of infected permissive cells , causing in particular the degradation of actin fibers and the generation of “actin patches . ”", "This is attributed to a virus-induced imbalance between the polymerization...	[ "Rodent parvoviruses are non-enveloped lytic viruses that are thought excellent tools for a virotherapy of cancer because of their strong natural oncolytic potential and low pathogenicity in humans .", "Egress of non-enveloped lytic viruses is commonly thought to occur as a virus burst after cell disintegration ....	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "diagnostic medicine", "women's health", "clinical immunology", "global health", "immunology", "public health", "veterinary science" ]	Transplacental Transmission of Leishmania infantum as a Means for Continued Disease Incidence in North America	journal.pntd.0001019	null	[ [ "Zoonotic visceral leishmaniasis ( ZVL ) is a vector-borne disease caused by obligate intracellular protozoan parasites of the genus Leishmania .", "In South America , dogs are the primary domestic reservoir host for ZVL [1] .", "Control measures for this disease are focused on vector-control and euth...	[ "Dogs are the predominant domestic reservoir for human L . infantum infection .", "Zoonotic visceral leishmaniasis ( ZVL ) is an emerging problem in some U . S . dog breeds , with an annual quantitative PCR prevalence of greater than 20% within an at-risk Foxhound population .", "Although classically Leishmania...	[ "Dogs are a favored feeding source for sand flies that transmit human L . infantum infection .", "Zoonotic visceral leishmaniasis ( ZVL ) is an emerging problem in some U . S . dog breeds , with over 20% of at-risk Foxhounds infected .", "Although classically Leishmania is transmitted by infected sand flies whi...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/metabolic networks" ]	Graph-Based Analysis of the Metabolic Exchanges between Two Co-Resident Intracellular Symbionts, Baumannia cicadellinicola and Sulcia muelleri, with Their Insect Host, Homalodisca coagulata	journal.pcbi.1000904	null	[ [ "Intracellular symbiosis involves a unicellular organism ( the endocytobiont ) which durably lives inside the cells of the other partner ( the host ) .", "In the last century , the crucial role of intracellular symbiosis in the ecology and evolution of many eukaryotes was many times demonstrated [1] , [2]...	[ "Endosymbiotic bacteria from different species can live inside cells of the same eukaryotic organism .", "Metabolic exchanges occur between host and bacteria but also between different endocytobionts .", "Since a complete genome annotation is available for both , we built the metabolic network of two endosymbio...	[ "Some bacteria , called endocytobionts , permanently live inside the cells of a pluricellular organism and often bring an adaptative advantage to their host by providing compounds that the latter cannot produce or find in its diet .", "The association may involve several species of bacteria within the same host ....	2010
[ "Introduction", "Models", "Results", "Discussion" ]	[ "mathematics", "theoretical biology", "applied mathematics", "biology", "evolutionary biology" ]	Effect of Dedifferentiation on Time to Mutation Acquisition in Stem Cell-Driven Cancers	journal.pcbi.1003481	null	[ [ "Certain aspects of the cancer stem cell hypothesis have previously been addressed by mathematical models .", "It has been shown that having a hierarchical tissue design , where a small population of stem cells maintains a transient population of differentiating cells , may slow the accumulation of mutati...	[ "Accumulating evidence suggests that many tumors have a hierarchical organization , with the bulk of the tumor composed of relatively differentiated short-lived progenitor cells that are maintained by a small population of undifferentiated long-lived cancer stem cells .", "It is unclear , however , whether cancer...	[ "Recent evidence suggests that , like many normal tissues , many cancers are maintained by a small population of immortal stem cells that divide indefinitely to produce many differentiated cells .", "Cancer stem cells may come directly from mutation of normal stem cells , but this route demands high mutation rate...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "genome expression analysis", "developmental biology", "genomics", "functional genomics", "biology", "computational biology", "genetics and genomics", "cell fate determination" ]	Predicting Spatial and Temporal Gene Expression Using an Integrative Model of Transcription Factor Occupancy and Chromatin State	journal.pcbi.1002798	null	[ [ "Gene expression is regulated through the interplay of transcription factors binding to cis-regulatory modules ( CRMs ) , chromatin modifications and the basal transcriptional machinery recruited to promoter elements .", "CRMs function as discrete regulatory elements [1] , [2] , that can act at varying ge...	[ "Precise patterns of spatial and temporal gene expression are central to metazoan complexity and act as a driving force for embryonic development .", "While there has been substantial progress in dissecting and predicting cis-regulatory activity , our understanding of how information from multiple enhancer elemen...	[ "Development is a complex process in which a single cell gives rise to a multi-cellular organism comprised of diverse cell types and well-organized tissues .", "This transformation requires tightly coordinated expression , both spatially and temporally , of hundreds to thousands of genes specific to any given tis...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	The Availability and Consistency of Dengue Surveillance Data Provided Online by the World Health Organization	journal.pntd.0003511	null	[ [ "Threats to public health around the world have become increasingly complex and the importance of high quality disease surveillance for preparedness and disease control will continue to grow [1] .", "Scientific progress and global cooperation against emerging threats will depend on the availability and sh...	[ "The use of high quality disease surveillance data has become increasingly important for public health action against new threats .", "In response , countries have developed a wide range of disease surveillance systems enabled by technological advancements .", "The heterogeneity and complexity of country data s...	[ "The use of high quality data and information has become essential for public health agencies to monitor and protect population health .", "Technological advancement has enabled the development of sophisticated disease surveillance systems by many countries .", "Increasingly , countries are making surveillance ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "flow cytometry", "immune cells", "viral transmission and infection", "antigen-presenting cells", "immunity to infections", "immunology", "microbiology", "host-pathogen interaction", "immunodeficiency viruses", "viruslike particles", "immune defense", "cytometry", "viral immune evasion", "...	Sialyllactose in Viral Membrane Gangliosides Is a Novel Molecular Recognition Pattern for Mature Dendritic Cell Capture of HIV-1	journal.pbio.1001315	An accessible sialyllactose moiety on viral membrane gangliosides is shown to be essential for HIV-1 uptake into mature dendritic cells, thereby promoting viral transfer and infection of bystander CD4+ T lymphocytes.	[ [ "Dendritic cells ( DCs ) are the most potent antigen-presenting cells found in the organism and play a paramount role in initiating immune responses to assaulting pathogens [1] , [2] .", "DCs that patrol the mucosal tissue display an immature phenotype and are able to capture incoming pathogens , which le...	[ "HIV-1 is internalized into mature dendritic cells ( mDCs ) via an as yet undefined mechanism with subsequent transfer of stored , infectious virus to CD4+ T lymphocytes .", "Thus , HIV-1 subverts a DC antigen capture mechanism to promote viral spread .", "Here , we show that gangliosides in the HIV-1 membrane ...	[ "Antigen-presenting cells such as dendritic cells ( DCs ) are required to combat infections , but viruses including HIV have evolved strategies to evade their anti-viral activity .", "HIV can enter DCs via a non-infectious endocytic mechanism and trick them into passing infectious virus on to bystander CD4+ T cel...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Multiscale Estimation of Binding Kinetics Using Brownian Dynamics, Molecular Dynamics and Milestoning	journal.pcbi.1004381	null	[ [ "Molecular dynamics is a simulation technique that uses Newton’s or Langevin’s equations of motion in combination with a specified molecular bond structure , parametrized force fields , and a starting conformation of atomic positions and velocities in order to propagate the dynamics of atoms within a molecula...	[ "The kinetic rate constants of binding were estimated for four biochemically relevant molecular systems by a method that uses milestoning theory to combine Brownian dynamics simulations with more detailed molecular dynamics simulations .", "The rate constants found using this method agreed well with experimentall...	[ "We estimated the kon rate constant of four biochemically relevant ligand-receptor systems using milestoning theory .", "All results closely resemble experimentally and theoretically determined results , indicating that this technique may be applied toward accurate estimation of binding rate constants for additio...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Lack of GDAP1 Induces Neuronal Calcium and Mitochondrial Defects in a Knockout Mouse Model of Charcot-Marie-Tooth Neuropathy	journal.pgen.1005115	null	[ [ "Charcot-Marie-Tooth ( CMT ) disease is one of the most frequent inherited neurological disorders and is characterized by either demyelinating or axonal neuropathy of motor and sensory peripheral nerves [1–3] .", "More than eighty genes are related to the pathogenesis of CMT and other peripheral neuropath...	[ "Mutations in GDAP1 , which encodes protein located in the mitochondrial outer membrane , cause axonal recessive ( AR-CMT2 ) , axonal dominant ( CMT2K ) and demyelinating recessive ( CMT4A ) forms of Charcot-Marie-Tooth ( CMT ) neuropathy .", "Loss of function recessive mutations in GDAP1 are associated with decr...	[ "Charcot-Marie-Tooth ( CMT ) disease is an inherited motor and sensory peripheral neuropathy .", "Mutations in the GDAP1 gene cause either an axonapathy or an myelinopathy that can be transmitted recessively or dominantly to offspring .", "GDAP1 is located in the mitochondrial outer membrane and seems to partic...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Sequential Vesicle Pool Model with a Single Release Sensor and a Ca2+-Dependent Priming Catalyst Effectively Explains Ca2+-Dependent Properties of Neurosecretion	journal.pcbi.1003362	null	[ [ "Neurotransmitter release and synaptic transmission depend on the fusion of secretory vesicles with the plasma membrane by exocytosis , and the ensuing release of the contained neurotransmitter molecules .", "Exocytosis itself is the conclusion of a number of steps , which starts by the generation of the ...	[ "Neurotransmitter release depends on the fusion of secretory vesicles with the plasma membrane and the release of their contents .", "The final fusion step displays higher-order Ca2+ dependence , but also upstream steps depend on Ca2+ .", "After deletion of the Ca2+ sensor for fast release – synaptotagmin-1 – s...	[ "The release of neurotransmitter involves the rapid Ca2+-dependent fusion of vesicles with the plasma membrane .", "Kinetic heterogeneity is ubiquitous in secretory systems , with fast phases of release on the millisecond time scale being followed by slower phases .", "In the absence of synaptotagmin-1 – the Ca...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine and health sciences", "pathology and laboratory medicine", "cell cycle and cell division", "plasmids", "cell processes", "pathogens", "microbiology", "vibrio", "plasmid construction", "vibrio cholerae", "dna replication", "genetic elements", "bacterial genetics", ...	Orderly Replication and Segregation of the Four Replicons of Burkholderia cenocepacia J2315	journal.pgen.1006172	null	[ [ "The long-held view that bacteria carry the essential part of their genomes on a single chromosome blurred about 25 years ago , when the species Rhodobacter sphaeroides was found to carry certain essential genes on a large replicon distinct from the main chromosome [1] .", "The size and essentiality of th...	[ "Bacterial genomes typically consist of a single chromosome and , optionally , one or more plasmids .", "But whole-genome sequencing reveals about ten per-cent of them to be multipartite , with additional replicons which by size and indispensability are considered secondary chromosomes .", "This raises the ques...	[ "Unlike higher organisms , bacteria typically carry their genetic information on a single chromosome .", "But in a few bacterial families the genome includes one to three additional chromosome-like DNA molecules .", "Because these families are rich in pathogenic and environmentally versatile species , it is imp...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell motility", "luciferase", "gene regulation", "natural antisense transcripts", "enzymes", "enzymology", "long non-coding rnas", "developmental biology", "micrornas", "epigenetics", "dna", "molecular biology techniques", "dna methylation", "chromatin", "research and analysis methods",...	Oncogenic KSHV-encoded interferon regulatory factor upregulates HMGB2 and CMPK1 expression to promote cell invasion by disrupting a complex lncRNA-OIP5-AS1/miR-218-5p network	journal.ppat.1007578	null	[ [ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) , also known as human herpesvirus 8 ( HHV-8 ) , is a double-stranded DNA virus , which belongs to γ-herpesvirus .", "KSHV was initially identified in an AIDS-associated Kaposi’s sarcoma ( AIDS-KS ) lesion , and has since been strongly linked to Kaposi’s sa...	[ "Kaposi’s sarcoma ( KS ) , a highly disseminated tumor of hyperproliferative spindle endothelial cells , is the most common AIDS-associated malignancy caused by infection of Kaposi’s sarcoma-associated herpesvirus ( KSHV ) .", "KSHV-encoded viral interferon regulatory factor 1 ( vIRF1 ) is a viral oncogene but it...	[ "Kaposi's sarcoma-associated herpesvirus ( KSHV ) infection caused Kaposi’s sarcoma ( KS ) , a highly disseminated tumor that frequently occurs in patients with AIDS .", "KSHV-encoded viral interferon regulatory factor 1 ( vIRF1 ) is an oncogenic protein , which has been shown to be vital in KSHV evasion of innat...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "lysosomes", "pathology and laboratory medicine", "chemical compounds", "intracellular pathogens", "hela cells", "gene regulation", "pathogens", "biological cultures", "microbiology", "organic compounds", "electromagnetic radiation", "cell cultures", "amino ...	Host cell depletion of tryptophan by IFNγ-induced Indoleamine 2,3-dioxygenase 1 (IDO1) inhibits lysosomal replication of Coxiella burnetii	journal.ppat.1007955	null	[ [ "Coxiella burnetii is a gram-negative , obligate intracellular pathogen that causes an infectious disease called Q-fever .", "Humans are occasionally infected through inhalation of aerosols or through close contact with infected livestock , and the symptoms range from mild flu-like illness to vascular com...	[ "Most intracellular pathogens that reside in a vacuole prevent transit of their compartment to lysosomal organelles .", "Effector mechanisms induced by the pro-inflammatory cytokine Interferon-gamma ( IFNγ ) can promote the delivery of pathogen-occupied vacuoles to lysosomes for proteolytic degradation and are th...	[ "Coxiella burnetii is a mammalian pathogen that can cause a predominantly zoonotic disease called Q-fever .", "In humans , Q-fever manifests as an acute or chronic illness especially in immunocompromised individuals .", "C . burnetii is uniquely adapted to live in a lysosome-derived vacuole that degrades protei...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "medicine and health sciences", "applied mathematics", "algorithms", "mathematics", "statistics (mathematics)", "genome analysis", "trait locus analysis", "population biology", "biostatistics", "genetic epidemiology", "cardiology", "epidemiology", "statis...	Canonical Correlation Analysis for Gene-Based Pleiotropy Discovery	journal.pcbi.1003876	null	[ [ "Pleiotropy refers to a phenomenon in which a single locus affects two or more apparently unrelated phenotypic traits .", "It is often identified as a single mutation that affects these two or more wild-type traits [1] .", "The study of pleiotropic genes usually involves the mapping of phenotypic trai...	[ "Genome-wide association studies have identified a wealth of genetic variants involved in complex traits and multifactorial diseases .", "There is now considerable interest in testing variants for association with multiple phenotypes ( pleiotropy ) and for testing multiple variants for association with a single p...	[ "Pleiotropy appears when a variation in one gene affects to several non-related phenotypes .", "The study of this phenomenon can be useful in gene function discovery , but also in the study of the evolution of a gene .", "In this paper , we present a methodology , based on Canonical Correlation Analysis , which...	2014
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "rna interference", "social sciences", "cloning", "neuroscience", "pigments", "materials science", "molecular biology techniques", "epigenetics", "eyes", "research and analysis methods", "animal cells", "proteins", "genetic interference"...	Prickle is phosphorylated by Nemo and targeted for degradation to maintain Prickle/Spiny-legs isoform balance during planar cell polarity establishment	journal.pgen.1007391	null	[ [ "Planar cell polarity ( PCP ) instructs tissue patterning in a wide range of organisms from Drosophila to humans , through input into cellular orientation across tissues , individual cell fate decisions , and the coordinated movement of groups of cells [1–8] .", "In the Drosophila eye , Frizzled core PCP ...	[ "Planar cell polarity ( PCP ) instructs tissue patterning in a wide range of organisms from fruit flies to humans .", "PCP signaling coordinates cell behavior across tissues and is integrated by cells to couple cell fate identity with position in a developing tissue .", "In the fly eye , PCP signaling is requir...	[ "For functional tissues to form , individual cells must correctly orient themselves and function appropriately for their particular location in the body .", "The Planar Cell Polarity ( PCP ) complexes transmit one set of spatial cues by acting as signposts to mark direction across an epithelial layer .", "PCP s...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "ecology and environmental sciences", "computational biology", "cloning", "fluorescence-activated cell sorting", "fungal evolution", "copy number variation", "molecular biology techniques", "evolutionary adaptation", "research and analysis methods", "sequence analysis", "ecological metrics", "...	Single-cell copy number variant detection reveals the dynamics and diversity of adaptation	journal.pbio.3000069	A fluorescent reporter system reveals that copy number variants (CNVs) are repeatedly generated and selected during the early stages of adaptive evolution, resulting in initially predictable dynamics with thousands of independent CNV-containing lineages competing within populations.	[ [ "Copy number variants ( CNVs ) drive rapid adaptive evolution in diverse scenarios ranging from niche specialization to speciation and tumor evolution [1–4] .", "CNVs , which include duplications and deletions of genomic segments , underlie phenotypic diversity in natural populations [5–10] and provide a ...	[ "Copy number variants ( CNVs ) are a pervasive source of genetic variation and evolutionary potential , but the dynamics and diversity of CNVs within evolving populations remain unclear .", "Long-term evolution experiments in chemostats provide an ideal system for studying the molecular processes underlying CNV f...	[ "Duplications and deletions of genomic sequence , known as copy number variants , are a common source of genetic diversity across all domains of life .", "Copy number variants play a crucial role in driving evolutionary processes but can also cause genetic disease and cancer .", "Although copy number variants a...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections" ]	Crystal Structure of Legionella DotD: Insights into the Relationship between Type IVB and Type II/III Secretion Systems	journal.ppat.1001129	null	[ [ "Pathogenic bacteria transport functional proteins , such as effector proteins and exotoxins , across bacterial membranes .", "These bacterial proteins interact with host proteins to manipulate host cellular functions .", "Therefore , the secretion process plays a central role in bacterial pathogenesi...	[ "The Dot/Icm type IVB secretion system ( T4BSS ) is a pivotal determinant of Legionella pneumophila pathogenesis .", "L . pneumophila translocate more than 100 effector proteins into host cytoplasm using Dot/Icm T4BSS , modulating host cellular functions to establish a replicative niche within host cells .", "T...	[ "Bacterial pathogens deliver virulence factors such as exotoxins and effector proteins to host cells .", "To accomplish this bacteria utilize specialized secretion systems such as type III and type IV secretion systems .", "The type IV secretion systems ( T4SS ) play a central role in pathogenesis by many impor...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "genetic fingerprinting", "cultured fibroblasts", "biological cultures", "human genomics", "dna transcription", "genetic elements", "molecular biology techniques", "rna sequencing", "research and analysis methods", "genomic signal processing", "artificial gene amplific...	TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements	journal.pcbi.1007293	null	[ [ "Long interspersed nuclear element 1 ( LINE-1 ) has attracted much attention in the last decade due to its capacity to promote genetic plasticity of the human genome .", "LINE-1 is a DNA sequence capable of duplicating itself and other DNA sequences by mobilizing messenger RNAs ( mRNAs ) to new genomic lo...	[ "The Long interspersed nuclear element 1 ( LINE-1 ) is a primary source of genetic variation in humans and other mammals .", "Despite its importance , LINE-1 activity remains difficult to study because of its highly repetitive nature .", "Here , we developed and validated a method called TeXP to gauge LINE-1 ac...	[ "Repetitive sequences , such as LINEs , comprise more than half of the human genome .", "Due to their repetitive nature , LINEs are hard to grasp .", "In particular , we find that pervasive transcription is a major confounding factor in transcriptome data .", "We observe that , on average , more than 90% of L...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunopathology", "medicine", "infectious diseases", "inflammation", "cytokines", "immunity", "hiv", "innate immunity", "retrovirology and hiv immunopathogenesis", "immunology", "biology", "viral diseases", "immune system" ]	Intact Type I Interferon Production and IRF7 Function in Sooty Mangabeys	journal.ppat.1003597	null	[ [ "In contrast to human immunodeficiency virus ( HIV ) infection of humans and experimental simian immunodeficiency virus ( SIV ) infection of Asian macaques , SIV infection of African monkeys that are natural hosts , such as sooty mangabeys ( SM ) , is typically non-pathogenic despite high virus replication [1...	[ "In contrast to pathogenic HIV/SIV infections of humans and rhesus macaques ( RMs ) , natural SIV infection of sooty mangabeys ( SMs ) is typically non-pathogenic despite high viremia .", "Several studies suggested that low immune activation and relative resistance of CD4+ central memory T-cells from virus infect...	[ "Sooty mangabey ( SM ) monkeys are an important model for studying HIV disease processes because they do not develop AIDS when infected with SIV , a primate version of HIV .", "The reasons why SIV-infected SMs remain healthy are not completely understood , but are related to reduced activation of the immune syste...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "viral vaccines", "clinical immunology", "immunity", "virology", "immunology", "biology", "microbiology" ]	Partially Neutralizing Potency against Emerging Genotype I Virus among Children Received Formalin-Inactivated Japanese Encephalitis Virus Vaccine	journal.pntd.0001834	null	[ [ "South and Southeast Asia are Japanese encephalitis ( JE ) endemic areas in which approximately 10% of the susceptible populations are infected with JE virus ( JEV ) each year , based on the ratio of asymptomatic to symptomatic infections of 200 to 1 [1] , [2] , [3] .", "The most cost-effective control st...	[ "Genotype I ( GI ) Japanese encephalitis virus ( JEV ) that replaced GIII virus has become the dominant circulating virus in Asia .", "Currently , all registered live and inactivated JEV vaccines are derived from genotype III viruses .", "In Taiwan , the compulsory JEV vaccination policy recommends that childre...	[ "Genotype I ( GI ) Japanese encephalitis virus ( JEV ) that replaced GIII virus has become the dominant circulating virus in Asia; however , all available JEV vaccines are derived from genotype III viruses , and no study has been conducted on the cross-neutralization and protection elicited by GIII JEV vaccines aga...	2012
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "oryza", "caenorhabditis", "arabidopsis", "computational biology", "homo (human)", "genetics and genomics" ]	Characterization and Identification of MicroRNA Core Promoters in Four Model Species	journal.pcbi.0030037	null	[ [ "MicroRNAs are endogenous single-stranded RNAs ranging from 19–25 nt in length .", "They are generated from long precursors , which fold into hairpin structures , and are known to repress post-transcriptional gene expression in both animals and plants [1 , 2] .", "The two well-understood microRNAs , l...	[ "MicroRNAs are short , noncoding RNAs that play important roles in post-transcriptional gene regulation .", "Although many functions of microRNAs in plants and animals have been revealed in recent years , the transcriptional mechanism of microRNA genes is not well-understood .", "To elucidate the transcriptiona...	[ "MicroRNAs are a class of short RNA sequences that have many regulatory functions in complex organisms such as plants and animals .", "However , our knowledge of the transcriptional mechanisms of microRNA genes is limited .", "Here , we analyze the upstream sequences of known microRNA genes in four model specie...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "physiology" ]	A Point Mutation in the Hair Cell Nicotinic Cholinergic Receptor Prolongs Cochlear Inhibition and Enhances Noise Protection	journal.pbio.1000018	A point mutation in the cochlear hair cell nicotinic cholinergic receptor leads to strengthened central nervous system feedback to the cochlea and enhances protection from noise-induced hearing loss.	[ [ "In bringing information about the world to an individual , sensory systems perform a series of common functions .", "Each system responds with some specificity to a stimulus , and each one employs some specialized receptor cells at the periphery to translate specific stimuli into electrical signals that ...	[ "The transduction of sound in the auditory periphery , the cochlea , is inhibited by efferent cholinergic neurons projecting from the brainstem and synapsing directly on mechanosensory hair cells .", "One fundamental question in auditory neuroscience is what role ( s ) this feedback plays in our ability to hear ....	[ "Nicotinic cholinergic receptors are essential to higher order brain function .", "Structurally , these operate through a myriad of ligand-gated pentameric arrangements of different homologous subunits .", "Here , we report progress in understanding the structural properties of a neuronal nicotinic receptor at ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell biology/cell signaling", "physiology/cell signaling", "biochemistry/cell signaling and trafficking structures", "pharmacology", "biotechnology/bioengineering", "computational biology", "computational biology/signaling networks", "biophysics/cell signaling and trafficking structures", "computat...	Dose-to-Duration Encoding and Signaling beyond Saturation in Intracellular Signaling Networks	journal.pcbi.1000197	null	[ [ "Many substances , such as hormones , neurotransmitters and a variety of pharmaceuticals , affect cellular behavior by binding to membrane receptors and activating intracellular signaling pathways .", "These pathways transmit information from the plasma membrane to selected cellular components to generate...	[ "The cellular response elicited by an environmental cue typically varies with the strength of the stimulus .", "For example , in the yeast Saccharomyces cerevisiae , the concentration of mating pheromone determines whether cells undergo vegetative growth , chemotropic growth , or mating .", "This implies that t...	[ "Cells must be able to detect and respond to changes in their surroundings .", "Often environmental cues , such as hormones or growth factors , are received by membrane receptors that in turn activate intracellular signaling pathways .", "These pathways then transmit information about the stimulus to the cellul...	2008
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ruminants", "trypanosoma congolense", "rna extraction", "vertebrates", "parasitic diseases", "parasitic protozoans", "mammals", "animals", "parasitology", "trypanosoma brucei", "protozoans", "extraction techniques", "veterinary science", "research and ana...	Parasite specific 7SL-derived small RNA is an effective target for diagnosis of active trypanosomiasis infection	journal.pntd.0007189	null	[ [ "African trypanosomes , vector borne protozoa transmitted by tsetse flies ( Glossina species ) , cause Human African Trypanosomiasis ( HAT ) and Animal African Trypanosomiasis ( AAT ) across sub-Saharan Africa .", "AAT , caused by Trypanosoma congolense , Trypanosoma vivax and Trypanosoma brucei , infects...	[ "Human and animal African trypanosomiasis ( HAT & AAT , respectively ) remain a significant health and economic issue across much of sub-Saharan Africa .", "Effective control of AAT and potential eradication of HAT requires affordable , sensitive and specific diagnostic tests that can be used in the field .", "...	[ "African trypanosomes cause significant disease in humans and animals across sub-Saharan Africa .", "For both human and animal infections diagnostics that can accurately identify an active infection are lacking–this is particularly the case in animal disease where most diagnosis is based upon clinical signs , whi...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/neuronal signaling mechanisms" ]	Biphasic Synaptic Ca Influx Arising from Compartmentalized Electrical Signals in Dendritic Spines	journal.pbio.1000190	Dendritic spines compartmentalize synaptically-evoked biochemical signals. The authors show that electrical compartmentalization provided by a spine endows the associated synapse with additional modes of calcium signaling by shaping the kinetics of synaptic calcium currents.	[ [ "Various theories have been proposed to explain why excitatory synapses of principal neurons are formed onto the heads of dendritic spines .", "These include proposals that spines increase the maximal density of contacts onto a linear dendrite [1] , [2] , that the long spine increases the repertoire of po...	[ "Excitatory synapses on mammalian principal neurons are typically formed onto dendritic spines , which consist of a bulbous head separated from the parent dendrite by a thin neck .", "Although activation of voltage-gated channels in the spine and stimulus-evoked constriction of the spine neck can influence synapt...	[ "The vast majority of excitatory synapses in the mammalian central nervous system are made onto dendritic spines , small ( < 1 fL ) membranous structures stippled along the dendrite .", "The head of each spine is separated from its parent dendrite by a thin neck – a morphological feature that intuitively suggests...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Latent Membrane Protein LMP2A Impairs Recognition of EBV-Infected Cells by CD8+ T Cells	journal.ppat.1004906	null	[ [ "Epstein-Barr virus ( EBV ) , which belongs to the human herpesvirus family , is a persistent virus carried by more than 90% of the adult population worldwide .", "EBV has a preferential B cell tropism , and latently infected B cells constitute the viral reservoir in healthy carriers [1] .", "Acute in...	[ "The common pathogen Epstein-Barr virus ( EBV ) transforms normal human B cells and can cause cancer .", "Latent membrane protein 2A ( LMP2A ) of EBV supports activation and proliferation of infected B cells and is expressed in many types of EBV-associated cancer .", "It is not clear how latent EBV infection an...	[ "Epstein-Barr virus ( EBV ) is carried by most humans .", "It can cause several types of cancer .", "In healthy infected people , EBV persists for life in a \"latent\" state in white blood cells called B cells .", "For infected persons to remain healthy , it is crucial that they harbor CD8-positive \"killer\"...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Analysis of Behavior and Trafficking of Dendritic Cells within the Brain during Toxoplasmic Encephalitis	journal.ppat.1002246	null	[ [ "Resistance to the parasite Toxoplasma gondii is characterized by an acute phase of infection associated with activation of innate immune cells such as neutrophils , dendritic cells ( DCs ) , and macrophages that produce IL-12 , which promotes NK and T cell production of IFN-γ [1] , [2] These events lead to t...	[ "Under normal conditions the immune system has limited access to the brain; however , during toxoplasmic encephalitis ( TE ) , large numbers of T cells and APCs accumulate within this site .", "A combination of real time imaging , transgenic reporter mice , and recombinant parasites allowed a comprehensive analys...	[ "Toxoplasmic encephalitis ( TE ) , caused by the protozoan parasite Toxoplasma gondii , can be potentially life threatening especially in immuno-compromised individuals .", "Immune cells including dendritic cells have been shown to accumulate in the brain during chronic toxoplasmosis; however , little is known ab...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "plant biology/plant genetics and gene expression", "genetics and genomics/complex traits", "plant biology/agricultural biotechnology", "evolutionary biology/genomics", "plant biology", "molecular biology/dna methylation", "genetics and genomics/epigenetics", "molec...	Assessing the Impact of Transgenerational Epigenetic Variation on Complex Traits	journal.pgen.1000530	null	[ [ "Continuous trait variation in natural and experimental populations is usually attributed to the actions and interactions of numerous DNA sequence polymorphisms and environmental factors [1] .", "These so-called complex traits encompass many of the prevalent diseases in humans ( e . g . diabetes , cancer ...	[ "Loss or gain of DNA methylation can affect gene expression and is sometimes transmitted across generations .", "Such epigenetic alterations are thus a possible source of heritable phenotypic variation in the absence of DNA sequence change .", "However , attempts to assess the prevalence of stable epigenetic va...	[ "DNA methylation is defined as an epigenetic modification because it can be inherited across cell division .", "Since variations in DNA methylation can affect gene expression and be inherited across generations , they can provide a source of heritable phenotypic variation that is not caused by changes in the DNA ...	2009
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Phenotypic and Genetic Consequences of Protein Damage	journal.pgen.1003810	null	[ [ "Proteome activity sustains life , whereas genome assures perpetuation of life by ongoing renewal of the proteome , granted the capacity of the proteome to repair , replicate and express the genome .", "Dedicated proteins determine mutation rates via the precision of the DNA replication machinery and the ...	[ "Although the genome contains all the information necessary for maintenance and perpetuation of life , it is the proteome that repairs , duplicates and expresses the genome and actually performs most cellular functions .", "Here we reveal strong phenotypes of physiological oxidative proteome damage at the functio...	[ "Cellular life is maintained by the activities of proteins that , together , prevent molecular damage from occurring in the first place and repair damaged DNA , proteins and other damaged cellular components .", "Cellular fitness decreases due to the fact that these proteins are themselves subject to damage , lea...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "neurochemistry", "optogenetics", "chemical compounds", "neural networks", "engineering and technology", "aliphatic amino acids", "lasers", "brain", "light", "neuroscience", "organic compounds", "electromagnetic radiation", "brain mapping", "amino acids", ...	Organization of the core respiratory network: Insights from optogenetic and modeling studies	journal.pcbi.1006148	null	[ [ "Rhythmic movements such as breathing and locomotion are produced in the nervous system by central pattern generator ( CPG ) networks consisting of interacting inhibitory and excitatory circuits that constitute the basic neural machinery generating motor behavior .", "Defining the structural-functional ar...	[ "The circuit organization within the mammalian brainstem respiratory network , specifically within and between the pre-Bötzinger ( pre-BötC ) and Bötzinger ( BötC ) complexes , and the roles of these circuits in respiratory pattern generation are continuously debated .", "We address these issues with a combinatio...	[ "We investigated the organization of key circuits within the brainstem respiratory central pattern generator ( CPG ) responsible for generating the basic breathing pattern in mammals .", "Our study focused on the organization and interactions of two core components of this CPG: the pre-Bötzinger ( pre-BötC ) and ...	2018
[ "Introduction", "Results", "Discussion", "Methods and Materials" ]	[ "immunology/antigen processing and recognition", "immunology/autoimmunity", "immunology/innate immunity" ]	Innate-Like Control of Human iNKT Cell Autoreactivity via the Hypervariable CDR3β Loop	journal.pbio.1000402	T-cell receptor variability gives rise to a functional hierarchy of human invariant Natural Killer T-cells through a powerful effect on CD1d binding affinity, which is independent of CD1d ligands.	[ [ "Invariant Natural Killer T ( iNKT ) cells are a conserved subset of highly potent and versatile T-cells which specifically recognize the non-polymorphic lipid-presenting molecule CD1d [UniprotKB P15813] [1] .", "iNKT cells co-express a unique T-Cell Receptor ( iNKT TCR ) , which mediates recognition of C...	[ "Invariant Natural Killer T cells ( iNKT ) are a versatile lymphocyte subset with important roles in both host defense and immunological tolerance .", "They express a highly conserved TCR which mediates recognition of the non-polymorphic , lipid-binding molecule CD1d .", "The structure of human iNKT TCRs is uni...	[ "Our immune system uses randomly modified T-cell receptors ( TCRs ) to adapt its discriminative capacity to rapidly changing pathogens .", "The T-cell receptor ( TCR ) has six flexible , variable peptide loops that make contact with antigens presented to them on the surface of other cells .", "Invariant Natural...	2010
[ "Introduction", "Results", "Discussion" ]	[ "homo (human)", "genetics and genomics" ]	Analysis and Application of European Genetic Substructure Using 300 K SNP Information	journal.pgen.0040004	null	[ [ "Differences in population genetic structure and substructure between cases and controls can lead to false positive association tests [1–5] .", "Interest in this issue has accelerated with the application of whole genome association ( WGA ) screens for deciphering the genetics of complex diseases .", ...	[ "European population genetic substructure was examined in a diverse set of >1 , 000 individuals of European descent , each genotyped with >300 K SNPs .", "Both STRUCTURE and principal component analyses ( PCA ) showed the largest division/principal component ( PC ) differentiated northern from southern European a...	[ "Ancestry differences corresponding to ethnic groups may be important in determining disease risk factors and optimizing treatment .", "Our study further defines ancestry relationship among different European ethnic groups by examining over 300 thousand variations in DNA , in over 2 , 000 individuals .", "This ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signal transduction", "signaling in cellular processes", "biology", "molecular cell biology", "molecular biology" ]	Phosphorylation-Dependent Interactions between Crb2 and Chk1 Are Essential for DNA Damage Checkpoint	journal.pgen.1002817	null	[ [ "Maintaining genome integrity requires the DNA damage checkpoint signaling pathways , which typically involve a protein kinase cascade .", "In vertebrates , residing at the top of the signaling pathways are two members of the phosphatidylinositol 3-kinase-like protein kinase ( PIKK ) family , ATM ( ataxia...	[ "In response to DNA damage , the eukaryotic genome surveillance system activates a checkpoint kinase cascade .", "In the fission yeast Schizosaccharomyces pombe , checkpoint protein Crb2 is essential for DNA damage-induced activation of downstream effector kinase Chk1 .", "The mechanism by which Crb2 mediates C...	[ "To preserve the integrity of genomic DNA , eukaryotic cells use a genome surveillance system to detect DNA damage and send a signal to prevent cell division before DNA repair has been completed .", "This signal transduction mechanism is called checkpoint signaling and is conserved from yeasts to humans .", "A ...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics", "molecular genetics", "biology", "human genetics", "genetics and genomics" ]	Microhomology-Mediated Mechanisms Underlie Non-Recurrent Disease-Causing Microdeletions of the FOXL2 Gene or Its Regulatory Domain	journal.pgen.1003358	null	[ [ "Copy number variations ( CNVs ) are defined as DNA segments that are present at a variable copy number in comparison with a reference genome such as a deletions , duplications or insertions [1] , [2] .", "In recent years it has become clear that CNVs are a major source of genetic diversity , competing wi...	[ "Genomic disorders are often caused by recurrent copy number variations ( CNVs ) , with nonallelic homologous recombination ( NAHR ) as the underlying mechanism .", "Recently , several microhomology-mediated repair mechanisms—such as microhomology-mediated end-joining ( MMEJ ) , fork stalling and template switchi...	[ "Genomic disorder is a general term describing conditions caused by genomic aberrations leading to a copy number change of one or more genes .", "Copy number changes with the same length and clustered breakpoints for a group of patients with the same disorder are named recurrent rearrangements .", "These origin...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular neuroscience", "protein interactions", "mechanisms of signal transduction", "signaling in selected disciplines", "neuroscience", "gtpase signaling", "developmental signaling", "cell movement signaling", "protein structure", "signaling pathways", "signaling in cellular processes", "p...	A Dual Binding Mode for RhoGTPases in Plexin Signalling	journal.pbio.1001134	A novel binding site for RhoGTPases on the intracellular region of plexins induces a trimeric ligand—receptor arrangement that appears crucial for plexin function.	[ [ "Plexins constitute a large family of semaphorin receptors that mediate the repulsive chemotactic response necessary for axon guidance in the developing nervous system .", "They also play an important role in regulating cell migration , angiogenesis , and immune responses [1] , [2] .", "Mutations in p...	[ "Plexins are cell surface receptors for the semaphorin family of cell guidance cues .", "The cytoplasmic region comprises a Ras GTPase-activating protein ( GAP ) domain and a RhoGTPase binding domain .", "Concomitant binding of extracellular semaphorin and intracellular RhoGTPase triggers GAP activity and signa...	[ "Axon guidance is fundamental to the development of the central nervous system .", "The growing axon is guided to its correct location by a plethora of extracellular signals .", "One of the most important extracellular signals is semaphorin , which binds to plexin receptors on the axon .", "Usually , this kin...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "innate immune system", "medicine and health sciences", "rna interference", "pathology and laboratory medicine", "gene regulation", "pathogens", "immunology", "microbiology", "parasitic diseases", "pseudomonas aeruginosa", "nematode infections", "epigenetics", "bacteria", "bacterial pathog...	Molecular Control of Innate Immune Response to Pseudomonas aeruginosa Infection by Intestinal let-7 in Caenorhabditis elegans	journal.ppat.1006152	null	[ [ "The free-living nematode Caenorhabditis elegans lives in soil , and potentially composts rich in the microorganisms , including those that are human microbial pathogens [1–2] .", "In the laboratory , once pathogenic bacteria can be deposited in the gut , they will invade the host cells , and even kill th...	[ "The microRNA ( miRNA ) let-7 is an important miRNA identified in Caenorhabditis elegans and has been shown to be involved in the control of innate immunity .", "The underlying molecular mechanisms for let-7 regulation of innate immunity remain largely unclear .", "In this study , we investigated the molecular ...	[ "Some microRNAs ( miRNAs ) have been identified recently to play important roles in the regulation of innate immunity in Caenorhabditis elegans .", "let-7 is one of important miRNAs identified to be involved in the control of innate immune response .", "However , the underlying molecular mechanism for let-7 in ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "chemical compounds", "sodium chloride", "salts", "diet", "developmental biology", "nutrition", "evolutionary adaptation", "cadmium", "gene expression", "life cycles", "chemistry", "evolutionary genetics", "genetic screens", "evolutionary processes", "ge...	Experimental Evolution of Gene Expression and Plasticity in Alternative Selective Regimes	journal.pgen.1006336	null	[ [ "Phenotypic plasticity is the phenomenon of one genotype producing different phenotypes ( e . g . , physical or behavioral ) when exposed to different environments .", "To produce different phenotypes from a single genotype , one of the essential intermediate steps is the induction of gene expression chan...	[ "Little is known of how gene expression and its plasticity evolves as populations adapt to different environmental regimes .", "Expression is expected to evolve adaptively in all populations but only those populations experiencing environmental heterogeneity are expected to show adaptive evolution of plasticity ....	[ "Different developmental environments change how genes are expressed and what phenotypes are produced .", "Here we examine how the responsiveness of gene expression to different environments ( “expression plasticity” ) evolves in populations adapted to constant environments or heterogeneous ones ( temporal or spa...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "skin", "blood cells", "langerhans cells", "dermatology", "flow cytometry", "medicine and health sciences", "immune cells", "integumentary system", "antigen-presenting cells", "immunology", "animal models", "dendritic cells", "infectious disease immunology", "model organisms", "skin infe...	Monocyte Recruitment to the Dermis and Differentiation to Dendritic Cells Increases the Targets for Dengue Virus Replication	journal.ppat.1004541	null	[ [ "The skin is the barrier to the environment and provides a first line of defense against invasion of microbial pathogens .", "Dendritic cells ( DCs ) and macrophages ( MΦs ) serve as immune sentinels in the skin [1] .", "DCs take up antigen , sense the presence of invading pathogens , and migrate to d...	[ "Dengue virus ( DENV ) causes the most prevalent arthropod-borne viral disease in humans .", "Although Aedes mosquitoes transmit DENV when probing for blood in the skin , no information exists on DENV infection and immune response in the dermis , where the blood vessels are found .", "DENV suppresses the interf...	[ "The skin and its immune cells are an important barrier against invading pathogens .", "Dengue is a major public health problem worldwide , with no specific therapeutic or vaccine available .", "Aedes mosquitoes transmit dengue virus ( DENV ) to humans via the skin when taking a blood meal .", "Previous studi...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "cellular structures", "gene function", "animal models", "mitosis", "developmental biology", "drosophila melanogaster", "model organisms", "cell division", "molecular development", "molecular genetics", "cell nucleus", "cytoskeleton", "biology", "cell biology", "genetic scre...	PP2A-Twins Is Antagonized by Greatwall and Collaborates with Polo for Cell Cycle Progression and Centrosome Attachment to Nuclei in Drosophila Embryos	journal.pgen.1002227	null	[ [ "The cell cycle is largely driven by networks of kinases and phosphatases that coordinate the sequential events of cell division in addition to regulating each other [1] .", "Kinases of the Polo , Aurora and cyclin-dependent families play particularly important roles in this process [2]–[4] .", "Phosp...	[ "Cell division and development are regulated by networks of kinases and phosphatases .", "In early Drosophila embryogenesis , 13 rapid nuclear divisions take place in a syncytium , requiring fine coordination between cell cycle regulators .", "The Polo kinase is a conserved , crucial regulator of M-phase .", ...	[ "The development and survival of all living organisms relies on the fine regulation of cell division at the molecular level .", "This coordination depends on kinases and phosphatases , enzymes that catalyze the addition and removal of phosphate groups on specific target proteins .", "The genes encoding these en...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "urology", "cell motility", "medicine and health sciences", "pathology and laboratory medicine", "cancer cell migration", "293t cells", "pathogens", "biological cultures", "cancers and neoplasms", "genitourinary tract tumors", "microbiology", "retroviruses", "oncology", "viruses", "devel...	Dysregulation of INF2-mediated mitochondrial fission in SPOP-mutated prostate cancer	journal.pgen.1006748	null	[ [ "Large-scale exome/genome sequencing studies have recently revealed that recurrent mutations in the SPOP gene occur in up to 15% of prostate cancers [1–4] .", "Interestingly , the SPOP mutant subset of prostate cancers had some notable molecular features , including mutual exclusivity with ERG gene rearra...	[ "Next-generation sequencing of the exome and genome of prostate cancers has identified numerous genetic alternations .", "SPOP ( Speckle-type POZ Protein ) was one of the most frequently mutated genes in primary prostate cancer , suggesting SPOP is a potential driver of prostate cancer development and progression...	[ "Prostate cancer is the leading cause of global cancer-related death .", "The development of improved diagnoses and novel therapies has been confounded by significant patient heterogeneity .", "During recent years , significant progress has been made in identifying the molecular alterations in prostate cancer u...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "infectious diseases/urological infections", "infectious diseases", "microbiology/immunity to infections", "immunology/immune response", "microbiology/innate immunity", "immunology/innate immunity", "microbiology/cellular microbiology and pathogenes...	Early Severe Inflammatory Responses to Uropathogenic E. coli Predispose to Chronic and Recurrent Urinary Tract Infection	journal.ppat.1001042	null	[ [ "Persistent microbial infections are a rapidly expanding problem because of increased antimicrobial resistance [1] .", "This trend is particularly concerning because of the increasingly appreciated role that chronic infections may play in cancer and chronic inflammatory diseases [2] , [3] , [4] .", "O...	[ "Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms .", "Therefore , understanding the host-pathogen interactions that result in chronic infection is of great importance .", "Here , we investigate the molecular basis of chronic bacterial c...	[ "The natural history of urinary tract infection ( UTI ) with uropathogenic E . coli in humans frequently includes persistent bacterial shedding in the urine for weeks after the initial infection , despite varying degrees of improvement of symptoms .", "Although antibiotic treatment has been very successful in tre...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/effects of virus infection on host gene expression", "virology" ]	Enterovirus 71 3C Protease Cleaves a Novel Target CstF-64 and Inhibits Cellular Polyadenylation	journal.ppat.1000593	null	[ [ "Enterovirus 71 ( EV71 ) belongs to the family of Picornaviridae , to which poliovirus also belongs .", "EV71 infection usually causes childhood herpagina or exanthema , which is also called hand , foot , and mouth disease ( HFMD ) .", "Acute EV71 infection may also cause a severe polio-like neurologi...	[ "Identification of novel cellular proteins as substrates to viral proteases would provide a new insight into the mechanism of cell–virus interplay .", "Eight nuclear proteins as potential targets for enterovirus 71 ( EV71 ) 3C protease ( 3Cpro ) cleavages were identified by 2D electrophoresis and MALDI-TOF analys...	[ "Many viruses contain specific proteases that are essential for processing their own viral proteins .", "For an efficient replication within their hosts , on the other hand , viruses also utilize these proteases to cleave a number of key host proteins and hijack cellular machineries .", "In this study , host pr...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Release of Lungworm Larvae from Snails in the Environment: Potential for Alternative Transmission Pathways	journal.pntd.0003722	null	[ [ "Gastropod-borne agents infect approximately 300 million people worldwide , causing major debilitating conditions , as well as adversely affecting quality of life and healthcare .", "For example , some ailments may contribute to the development of neoplastic tumours , such as cholangiocarcinoma during opi...	[ "Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts .", "However , the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some z...	[ "Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans .", "The infection occurs by consumption of intermediate hosts ( i . e . , snails ) .", "However , the ingestion of fresh vegetables contaminated by water and/or snail mucus has been proposed as a transmission source for...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "trypanosoma)", "microbiology", "computational biology", "evolutionary biology", "molecular biology", "kinetoplastid (leishmania" ]	Members of a Large Retroposon Family Are Determinants of Post-Transcriptional Gene Expression in Leishmania	journal.ppat.0030136	null	[ [ "Trypanosomatids are members of the kinetoplastid family of unicellular protists , which includes human pathogens responsible for Chagas disease ( Trypanosoma cruzi ) , African sleeping sickness ( Trypanosoma brucei ) , and leishmaniasis ( Leishmania spp . ) .", "T . brucei and T . cruzi belong to the mon...	[ "Trypanosomatids are unicellular protists that include the human pathogens Leishmania spp .", "( leishmaniasis ) , Trypanosoma brucei ( sleeping sickness ) , and Trypanosoma cruzi ( Chagas disease ) .", "Analysis of their recently completed genomes confirmed the presence of non–long-terminal repeat retrotranspo...	[ "Transposable elements ( TEs ) are DNA sequences capable of moving from one chromosomal region to another .", "A considerable fraction of higher eukaryote genomes is comprised of TEs , as exemplified in human ( over 40% of the genome ) and maize ( over 50% of the genome ) .", "There is now a growing body of evi...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "viral transmission and infection", "spleen", "immunology", "microbiology", "animal models", "model organisms", "experimental organism systems", "cytotoxic t cells", "antibodies", "viral load", "antibody ...	Immunization with a murine cytomegalovirus based vector encoding retrovirus envelope confers strong protection from Friend retrovirus challenge infection	journal.ppat.1008043	null	[ [ "In the last two decades , vector-based immunization approaches for the development of an HIV vaccine have been pursued intensively , and recently vectors based on cytomegalovirus ( CMV ) have drawn a lot of interest .", "At first glance , CMV is not an obvious choice as basis for a vaccine vector: as a β...	[ "Immunization vectors based on cytomegalovirus ( CMV ) have attracted a lot of interest in recent years because of their high efficacy in the simian immunodeficiency virus ( SIV ) macaque model , which has been attributed to their ability to induce strong , unusually broad , and unconventionally restricted CD8+ T c...	[ "CMV-based vectors have attracted a lot of attention in the vaccine development field , since they were shown to induce unconventionally restricted CD8+ T cell responses and strong protection in the SIV rhesus macaque model .", "In a mouse retrovirus model , we show now that immunization with a mouse CMV-based ve...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "biology and life sciences", "microbiology" ]	A Novel Signal Transduction Pathway that Modulates rhl Quorum Sensing and Bacterial Virulence in Pseudomonas aeruginosa	journal.ppat.1004340	null	[ [ "Pseudomonas aeruginosa is an important opportunistic pathogen that accounts for 10% of all hospital-acquired infections [1] , [2] .", "Most notably , P . aeruginosa is the leading cause of chronic pulmonary infections and mortality in cystic fibrosis ( CF ) patients [3] .", "The success of P . aerugi...	[ "The rhl quorum-sensing ( QS ) system plays critical roles in the pathogenesis of P . aeruginosa .", "However , the regulatory effects that occur directly upstream of the rhl QS system are poorly understood .", "Here , we show that deletion of gene encoding for the two-component sensor BfmS leads to the activat...	[ "The rhl quorum-sensing ( QS ) system allows P . aeruginosa to regulate diverse metabolic adaptations and virulence .", "However , how rhl QS system is regulated remains largely unknown .", "Here , we report that two-component sensor BfmS controls rhl QS system by repressing its cognate response regulator BfmR ...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "neurochemistry", "diabetic endocrinology", "neuroscience", "animals", "hormones", "animal models", "fluorophotometry", "physiological processes", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism ...	Peptidergic signaling from clock neurons regulates reproductive dormancy in Drosophila melanogaster	journal.pgen.1008158	null	[ [ "To synchronize with the Earth’s rhythmic environment , most higher organisms have evolved endogenous time-keeping systems [1 , 2] .", "While the highly conserved circadian clock is well-characterized [3 , 4] , our knowledge of the seasonal clock that governs the overwintering response ( diapause ) in ins...	[ "With the approach of winter , many insects switch to an alternative protective developmental program called diapause .", "Drosophila melanogaster females overwinter as adults by inducing a reproductive arrest that is characterized by inhibition of ovarian development at previtellogenic stages .", "The insulin ...	[ "Diapause is a hormonally mediated process that allows insects to predict and respond to unfavourable conditions by altering their metabolism and behavior to resist the oncoming environmental challenges .", "In Drosophila melanogaster females a protective state of reproductive dormancy is induced by lower tempera...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular neuroscience", "genetic mutation", "gene regulation", "immunology", "neuroscience", "gene function", "molecular genetics", "neurotransmitters", "gene expression", "biology", "genetics of the immune system", "genetic screens", "genetics", "genetics and genomics" ]	RFX Transcription Factor DAF-19 Regulates 5-HT and Innate Immune Responses to Pathogenic Bacteria in Caenorhabditis elegans	journal.pgen.1003324	null	[ [ "Innate immunity is an integral part of the stress response program in which the host activates a range of defense genes to enhance the chance of survival against internal and environmental threats .", "In mammals , signals associated with pathogenic microbes trigger Toll-like receptors to recruit Toll-in...	[ "In Caenorhabditis elegans the Toll-interleukin receptor domain adaptor protein TIR-1 via a conserved mitogen-activated protein kinase ( MAPK ) signaling cascade induces innate immunity and upregulates serotonin ( 5-HT ) biosynthesis gene tph-1 in a pair of ADF chemosensory neurons in response to infection .", "H...	[ "Toll-interleukin receptor ( TIR ) –domain adaptor proteins are keys to activate signaling cascades inducing transcriptional responses to internal and external pathogenic signals in evolutionary disparate organisms .", "Despite lacking a homolog of the mammalian innate immunity transcriptional regulator nuclear f...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "viral hemorrhagic fevers", "infectious diseases", "hemorrhagic fever with renal syndrome", "adaptive immunity", "immunity", "virology", "neglected tropical diseases", "biology", "microbiology", "host-pathogen interaction", "viral diseases" ]	HLA-A2 and B35 Restricted Hantaan Virus Nucleoprotein CD8+ T-Cell Epitope-Specific Immune Response Correlates with Milder Disease in Hemorrhagic Fever with Renal Syndrome	journal.pntd.0002076	null	[ [ "Hantaan virus ( HTNV ) , the prototype member of the genus Hantavirus of the family Bunyaviridae , was first isolated in Korea in 1978 and can cause a severe disease of hemorrhagic fever with renal syndrome ( HFRS ) in humans [1] .", "The genus Hantavirus is naturally maintained in persistently infected ...	[ "Hantaan virus ( HTNV ) infection in humans is a serious public health concern in Asia .", "A potent T cell activation peptide vaccine from HTNV structure protein represents a promising immunotherapy for disease control .", "However , the T cell epitopes of the HTNV restricted by the HLA alleles and the role of...	[ "Hantaan virus ( HTNV ) , the prototype of the Hantavirus genus , is a rodent-borne pathogen that causes human hemorrhagic fever with renal syndrome ( HFRS ) with a mortality rate of approximately 15% in Asia .", "Since effective prevention is not available currently and the non-specific symptoms at the early sta...	2013
[ "Introduction", "Model", "Results", "Discussion", "Methods and Materials" ]	[]	Testing Foundations of Biological Scaling Theory Using Automated Measurements of Vascular Networks	journal.pcbi.1004455	null	[ [ "Networks that supply resources are essential to the maintenance and growth of many natural and engineered systems .", "These resource-distribution networks are pervasive throughout biology .", "Examples include the tracheal system in insects , xylem networks in plants [1] , foraging trails of ant col...	[ "Scientists have long sought to understand how vascular networks supply blood and oxygen to cells throughout the body .", "Recent work focuses on principles that constrain how vessel size changes through branching generations from the aorta to capillaries and uses scaling exponents to quantify these changes .", ...	[ "Vascular networks distribute resources and constrain metabolic rate .", "Founded on a few key principles , biological scaling theories predict characteristic patterns for vascular networks as they branch from large to small vessels .", "These theories also predict seemingly unrelated phenomena , such as size l...	2015
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "medicine", "cell motility", "biological data management", "parasitic diseases", "parasitology", "zoology", "infectious diseases", "cell adhesion", "biology", "vectors and hosts", "biophysics", "physics", "cell biology", "malaria", "computational biology", "molecular cell biology" ]	Environmental Constraints Guide Migration of Malaria Parasites during Transmission	journal.ppat.1002080	null	[ [ "Optical analysis of cell migration can be performed in simple cell culture assays , in reconstituted 3D-environments , tissue explants or in living animals [1] , [2] .", "Clearly , the migratory patterns of cells have evolved in the context of the environment they maneuver in .", "Many cells , such a...	[ "Migrating cells are guided in complex environments mainly by chemotaxis or structural cues presented by the surrounding tissue .", "During transmission of malaria , parasite motility in the skin is important for Plasmodium sporozoites to reach the blood circulation .", "Here we show that sporozoite migration v...	[ "Guidance of motile cells plays an important role during the life of a multi-cellular organism from early embryogenesis to the intricate interactions of immune cells during an infection .", "These migrations , like those of pathogens , can be directed by both chemical and physical cues .", "The malaria parasite...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "chemical characterization", "vesicles", "protein interactions", "protein interaction networks", "cell processes", "membrane proteins", "network analysis", "cellular structures and organelles", "research and analysis methods", "cell binding assay", "computer and information sciences", "network...	Stoichiometric balance of protein copy numbers is measurable and functionally significant in a protein-protein interaction network for yeast endocytosis	journal.pcbi.1006022	null	[ [ "Protein copy numbers in yeast vary from a few to well over a million[1 , 2] .", "Expression levels , along with a protein’s binding partners and corresponding affinities , are critical determinants of a protein’s function within the cell .", "In the context of multiprotein complexes–especially obliga...	[ "Stoichiometric balance , or dosage balance , implies that proteins that are subunits of obligate complexes ( e . g . the ribosome ) should have copy numbers expressed to match their stoichiometry in that complex .", "Establishing balance ( or imbalance ) is an important tool for inferring subunit function and as...	[ "Protein copy numbers are often found to be stoichiometrically balanced for subunits of multi-protein complexes .", "Imbalance is believed to be deleterious because it lowers complex yield ( the dosage balance hypothesis ) and increases the risk of misinteractions , but imbalance may also provide unexplored funct...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Variable Suites of Non-effector Genes Are Co-regulated in the Type III Secretion Virulence Regulon across the Pseudomonas syringae Phylogeny	journal.ppat.1003807	null	[ [ "Many Gram-negative bacteria attach to host cells and translocate effector proteins into them via type III secretion systems ( T3SS ) .", "Such systems are necessary for pathogenesis , are horizontally transferred across species , and are accompanied by dynamically evolving repertoires of type III effecto...	[ "Pseudomonas syringae is a phylogenetically diverse species of Gram-negative bacterial plant pathogens responsible for crop diseases around the world .", "The HrpL sigma factor drives expression of the major P . syringae virulence regulon .", "HrpL controls expression of the genes encoding the structural and fu...	[ "Pseudomonas syringae are environmentally ubiquitous bacteria of wide phylogenetic distribution , which can cause disease on a broad range of plant species .", "Pathogenicity requires the master regulator HrpL .", "HrpL controls the activation of virulence factor genes , including those encoding the type III se...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion", "Conclusions" ]	[ "parasite groups", "medicine and health sciences", "plasmodium", "tropical diseases", "geographical locations", "vertebrates", "parasitic diseases", "parasitic protozoans", "animals", "parasitology", "mammals", "indonesia", "primates", "apicomplexa", "protozoans", "molecular biology te...	Laboratory challenges of Plasmodium species identification in Aceh Province, Indonesia, a malaria elimination setting with newly discovered P. knowlesi	journal.pntd.0006924	null	[ [ "Plasmodium knowlesi is a newly emergent zoonotic human malaria species previously thought to only infect macaques .", "Since the first report of a human case from Peninsular Malaysia in 1965 [1] and the large cluster of human knowlesi malaria in Sarawak in 2004 [2] , endemic cases have been reported from...	[ "The discovery of the life-threatening zoonotic infection Plasmodium knowlesi has added to the challenges of prompt and accurate malaria diagnosis and surveillance .", "In this study from Aceh Province , Indonesia , a malaria elimination setting where P . knowlesi endemicity was not previously known , we report t...	[ "In Southeast Asia , Plasmodium knowlesi , a malaria parasite of macaques , was recently discovered to infect humans .", "This emerging disease is important because it has potential for causing severe disease and death , and it is a threat to malaria elimination efforts in the region .", "In this report from Ac...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuropsychiatric disorders", "medicine and health sciences", "pathology and laboratory medicine", "adhd", "prader-willi syndrome", "angelman syndrome", "social sciences", "developmental psychology", "neuroscience", "disorders of imprinting", "autism spectrum disorder", "developmental neurosci...	Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders	journal.pgen.1005993	null	[ [ "Recurrent duplications of ~4Mb at 15q11 . 2-q13 . 3 , overlapping the Prader-Willi syndrome /Angelman syndrome ( PWS/AS ) region between breakpoints 2 and 3 or 1 and 3 ( BP2-BP3 or BP1-BP3 ) are recognised risk factors for developmental delay ( DD ) and autism spectrum disorders ( ASD ) [1–4] .", "More r...	[ "Duplications at 15q11 . 2-q13 . 3 overlapping the Prader-Willi/Angelman syndrome ( PWS/AS ) region have been associated with developmental delay ( DD ) , autism spectrum disorder ( ASD ) and schizophrenia ( SZ ) .", "Due to presence of imprinted genes within the region , the parental origin of these duplications...	[ "The genetic interval 15q11 . 2-q13 . 3 on human chromosome 15 contains several so-called “imprinted genes” which are subject to epigenetic marking leading to activity from only one parental copy .", "This is in contrast to non-imprinted genes , whose activity is independent of their parent-of-origin .", "Delet...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immunology", "surgical and invasive medical procedures", "sequence motif analysis", "dna", "mammalian genomics", "research and analysis methods", "sequence analysis", "white blood cells", "genomics", "sequence alignment", "ani...	DSB structure impacts DNA recombination leading to class switching and chromosomal translocations in human B cells	journal.pgen.1008101	null	[ [ "DNA recombination at the immunoglobulin heavy chain ( IGH ) locus is required for class switch recombination ( CSR ) , the process that changes the class of immunoglobulin expressed by B cells , e . g . , from IgM to IgG or IgA , etc .", "CSR increases diversity of immunoglobulin isotypes , which is nece...	[ "Class switch recombination ( CSR ) requires activation-induced cytidine deaminase ( AID ) to trigger DNA double strand breaks ( DSBs ) at the immunoglobulin heavy chain ( IGH ) in B cells .", "Joining of AID-dependent DSBs within IGH facilitate CSR and effective humoral immunity , but ligation to DSBs in non-IGH...	[ "The production of different classes of antibodies/immunoglobulins ( IgM , IgG , etc . ) is essential for protection against diverse pathogens and effective immunity .", "This cellular process is triggered by the enzyme activation-induced cytidine deaminase ( AID ) .", "AID mutates DNA predominantly in antibody...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "mali", "onchocerca volvulus", "immune physiology", "helminths", "immunology", "tropical diseases", "geographical locations", "parasitic diseases", "animals", "onchocerca", "filariasis", "pharmaceutics", "drug administration", "neglected...	Integrated seroprevalence-based assessment of Wuchereria bancrofti and Onchocerca volvulus in two lymphatic filariasis evaluation units of Mali with the SD Bioline Onchocerciasis/LF IgG4 Rapid Test	journal.pntd.0007064	null	[ [ "Approaches to onchocerciasis control and lymphatic filariasis ( LF ) elimination have proceeded along parallel but independent courses in Mali .", "For LF , annual mass drug administration ( MDA ) with albendazole and ivermectin began in 2004 and continued for 5 to 9 consecutive MDA campaigns .", "On...	[ "Mali has become increasingly interested in the evaluation of transmission of both Wuchereria bancrofti and Onchocerca volvulus as prevalences of both infections move toward their respective elimination targets .", "The SD Bioline Onchocerciasis/LF IgG4 Rapid Test was used in 2 evaluation units ( EU ) to assess i...	[ "After years of mass drug administration for lymphatic filariasis and onchocerciasis , many co-endemic countries need to demonstrate the interruption of transmission of these parasitic infections .", "This interruption of transmission is the key to stopping mass drug administration .", "One of the major challen...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	DNA Is an Antimicrobial Component of Neutrophil Extracellular Traps	journal.ppat.1004593	null	[ [ "Neutrophils are central mediators of the innate immune defense system and perform their role by killing invading microbes through phagocytosis , degranulation , and the release of neutrophil extracellular traps ( NETs ) [1 , 2] .", "The scaffold of NETs is composed of genomic DNA , which is enmeshed with...	[ "Neutrophil extracellular traps ( NETs ) comprise an ejected lattice of chromatin enmeshed with granular and nuclear proteins that are capable of capturing and killing microbial invaders .", "Although widely employed to combat infection , the antimicrobial mechanism of NETs remains enigmatic .", "Efforts to elu...	[ "Comprising the first line of the innate immune response , neutrophils combat infectious microorganisms through the release of toxic molecules , phagocytosis of invaders and the production of the recently characterized neutrophil extracellular traps ( NETs ) .", "The antimicrobial activity of NETs has been attrib...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "protein interactions", "molecular probe techniques", "enzymes", "enzymology", "immunoblotting", "plasmid construction", "sequence motif analysis", "molecular biology techniques", "dna construction", "research and analysis methods", "protein kinase signaling cascade", "seq...	Comprehensive profiling of the STE20 kinase family defines features essential for selective substrate targeting and signaling output	journal.pbio.2006540	null	[ [ "Protein kinases are key enzymes in signal transduction networks critical to essentially all aspects of cellular regulation .", "The human genome encodes over 500 protein kinases that function in distinct processes yet share a structurally conserved catalytic domain [1] .", "The unique functions of ea...	[ "Specificity within protein kinase signaling cascades is determined by direct and indirect interactions between kinases and their substrates .", "While the impact of localization and recruitment on kinase–substrate targeting can be readily assessed , evaluating the relative importance of direct phosphorylation si...	[ "Protein kinases , which catalyze the transfer of phosphate from ATP to substrate proteins , are important enzymes in cellular signal transduction pathways mediating responses to extracellular cues .", "In order to function properly in signal transmission , each kinase must phosphorylate only a limited number of ...	2019
[ "Introduction", "Patients and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "c-reactive proteins", "clinical laboratory sciences", "ixodes", "pathology and laboratory medicine", "china", "geographical locations", "animals", "signs and symptoms", "nosocomial infections", "ticks", "infectious diseases", "thrombocytope...	Severe Fever with Thrombocytopenia Syndrome in South Korea, 2013-2015	journal.pntd.0005264	null	[ [ "Severe fever with thrombocytopenia syndrome ( SFTS ) is an emerging infectious disease that is caused by a novel SFTS virus ( SFTSV ) which was first reported in China in 2011 [1] .", "China’s neighboring two countries , South Korea and Japan , have also reported the infection [2 , 3] .", "The virus ...	[ "Severe fever with thrombocytopenia syndrome ( SFTS ) is an emerging infectious disease that was recently identified in China , South Korea and Japan .", "The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea .", "SFTS is a reportable disease in South K...	[ "Severe fever with thrombocytopenia ( SFTS ) is an emerging infectious disease that was first discovered in China in 2009 .", "Subsequently , SFTS has also been found in South Korea and Japan .", "Here , we report the epidemiologic and clinical characteristics of 172 confirmed SFTS cases in South Korea that occ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "physiological processes", "medicine and health sciences", "mathematics", "statistics (mathematics)", "computational neuroscience", "physiology", "sleep", "mathematical and statistical techniques", "biology and life sciences", "physical sciences", "computational biology", "neuroscience", "st...	Tracking the Sleep Onset Process: An Empirical Model of Behavioral and Physiological Dynamics	journal.pcbi.1003866	null	[ [ "There have been numerous ways in which scientists have attempted to measure behavioral and physiological dynamics during the SOP .", "For an in-depth look at the methods employed in the past , see Ogilvie's review paper [1] , which comprehensively details the many multimodal correlates of sleep onset and...	[ "The sleep onset process ( SOP ) is a dynamic process correlated with a multitude of behavioral and physiological markers .", "A principled analysis of the SOP can serve as a foundation for answering questions of fundamental importance in basic neuroscience and sleep medicine .", "Unfortunately , current method...	[ "How can we tell when someone has fallen asleep ?", "Understanding the way we fall asleep is an important problem in sleep medicine , since sleep disorders can disrupt the process of falling asleep .", "In the case of insomnia , subjects may fall asleep too slowly , whereas during sleep deprivation or narcoleps...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "mosquitoes", "health screening", "disease ecology", "public health and epidemiology", "global health", "dengue fever", "neglected tropical diseases", "vectors and hosts", "public health" ]	The Value of Educational Messages Embedded in a Community-Based Approach to Combat Dengue Fever: A Systematic Review and Meta Regression Analysis	journal.pntd.0001278	null	[ [ "Dengue fever ( DF ) is an acute viral disease affecting all age groups .", "It occurs mainly in tropical and subtropical areas , the predominant vectors being the mosquitoes Aedes aegypti and albopictus , which become infected with any of the four dengue viruses and transmit the disease via a bite to hum...	[ "The effects of various dengue control measures have been investigated in previous studies .", "The aim of this review was to investigate the relative effectiveness ( RE ) of different educational messages embedded in a community-based approach on the incidence of Aedes aegypti larvae using entomological measures...	[ "Dengue fever is a mosquito-borne viral infection that is widespread in the tropics .", "Each year there are an estimated 50 million infections worldwide .", "Preventing infection relies on controlling the mosquitoes that spread disease .", "Unfortunately it is still not clear what does and does not work in t...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Power of Gene-Based Rare Variant Methods to Detect Disease-Associated Variation and Test Hypotheses About Complex Disease	journal.pgen.1005165	null	[ [ "To assess whether a single variant at a locus contributes to disease risk , the statistical analysis framework is relatively straightforward: compare the frequencies of alleles or genotypes at the site in relation to phenotype .", "To assess whether multiple variants in the same gene contribute to diseas...	[ "Genome and exome sequencing in large cohorts enables characterization of the role of rare variation in complex diseases .", "Success in this endeavor , however , requires investigators to test a diverse array of genetic hypotheses which differ in the number , frequency and effect sizes of underlying causal varia...	[ "Re-sequencing technologies allow for a more complete interrogation of the role of human variation in complex disease .", "The inadequate power of single variant methods to assess the role of less common variation has led to the development of numerous statistical methods for testing aggregate groups of variants ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "pharmacologic analysis", "mycobacterium leprae", "medicine and health sciences", "demography", "tropical diseases", "geographical locations", "factor analysis", "bacterial diseases", "compartment models", "mathematics", "statistics (mathematics)", "neglected tropical diseases...	Proposing a Compartmental Model for Leprosy and Parameterizing Using Regional Incidence in Brazil	journal.pntd.0004925	null	[ [ "Hansen’s disease ( HD , or leprosy ) is a chronic progressive disease caused in Brazil by infection with Mycobacterium leprae .", "Transmission is most likely through nasal droplets [1] , and is associated with socioeconomic status [2] .", "While leprosy is curable through chemotherapy [3] , detectio...	[ "Hansen’s disease ( HD ) , or leprosy , is still considered a public health risk in much of Brazil .", "Understanding the dynamics of the infection at a regional level can aid in identification of targets to improve control .", "A compartmental continuous-time model for leprosy dynamics was designed based on un...	[ "Control of Hansen’s disease , or leprosy , requires understanding how quickly the infection moves through the population and how long it takes to detect the disease .", "These rates vary regionally , resulting in differences in the number of people detected with disease each year .", "We have estimated the ris...	2016
[ "Introduction", "Results", "Discussion", "Material and Methods", "Acknowledgments" ]	[ "computational biology/evolutionary modeling", "evolutionary biology/bioinformatics", "computational biology/genomics" ]	A Methodological Framework for the Reconstruction of Contiguous Regions of Ancestral Genomes and Its Application to Mammalian Genomes	journal.pcbi.1000234	null	[ [ "The reconstruction of ancestral karyotypes and gene orders from homologies between extant species is a long-standing problem [1] .", "In the case of mammalian genomes , it has first been approached using cytogenetics methods [2]–[7] .", "The recent availability of sequenced and assembled genomes has ...	[ "The reconstruction of ancestral genome architectures and gene orders from homologies between extant species is a long-standing problem , considered by both cytogeneticists and bioinformaticians .", "A comparison of the two approaches was recently investigated and discussed in a series of papers , sometimes with ...	[ "No DNA molecule is preserved after a few hundred thousand years , so inferring the DNA sequence organization of ancient living organisms beyond several million years can only be achieved by computational estimations , using the similarities and differences between chromosomes of extant species .", "This is the s...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "social sciences" ]	Factors Affecting Perceived Stigma in Leprosy Affected Persons in Western Nepal	journal.pntd.0002940	null	[ [ "Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae .", "Besides clinical sequel followed usually after infection , the consequences of stigma associated with leprosy outweigh the burden of physical afflictions [1] .", "Three kinds of stigma associated with leprosy affected pers...	[ "There are various factors which construct the perception of stigma in both leprosy affected persons and unaffected persons .", "The main purpose of this study was to determine the level of perceived stigma and the risk factors contributing to it among leprosy affected person attending the Green Pastures Hospital...	[ "A total of 135 leprosy affected persons were interviewed with a questionnaire containing EMIC questions designed to assess the level of perceived stigma and the questionnaire containing variables for socio-demographic characteristics , knowledge about leprosy and the clinical presentations of the participants .", ...	2014

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