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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", "Result/Discussion", "Materials and Methods", "Supporting Information" ]	[ "mus (mouse)", "genetics and genomics" ]	Unbiased Gene Expression Analysis Implicates the huntingtin Polyglutamine Tract in Extra-mitochondrial Energy Metabolism	journal.pgen.0030135	null	[ [ "The CAG trinucleotide repeat in the Huntington's disease gene ( HD ) is highly polymorphic in humans , with alleles ranging from ∼6 to >100 units encoding a variable polyglutamine tract in huntingtin , a large ( >350 kDa ) HEAT domain protein [1] .", "The gene was discovered because alleles over ∼35–37 u...	[ "The Huntington's disease ( HD ) CAG repeat , encoding a polymorphic glutamine tract in huntingtin , is inversely correlated with cellular energy level , with alleles over ∼37 repeats leading to the loss of striatal neurons .", "This early HD neuronal specificity can be modeled by respiratory chain inhibitor 3-ni...	[ "Huntington's disease ( HD ) is a tragic neurodegenerative disorder caused by a CAG repeat that specifies the size of a glutamine tract in the huntingtin protein , such that the longer the tract , the earlier the loss of striatal brain cells .", "A correlation of polyglutamine tract size has also implicated hunti...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "microbiology", "anatomy and physiology", "animal models", "physiological processes", "developmental biology", "model organisms", "nutrition", "gastroenterology and hepatology", "aquaculture", "molecular genetics", "gene expression", "marine and aquatic sciences", "biology", ...	Intronic Cis-Regulatory Modules Mediate Tissue-Specific and Microbial Control of angptl4/fiaf Transcription	journal.pgen.1002585	null	[ [ "The vertebrate intestine harbors a dense community of microorganisms ( gut microbiota ) that exerts a profound influence on distinct aspects of host physiology [1] , [2] .", "The gut microbiota has been identified as a potent environmental factor in a growing number of human diseases , including inflamma...	[ "The intestinal microbiota enhances dietary energy harvest leading to increased fat storage in adipose tissues .", "This effect is caused in part by the microbial suppression of intestinal epithelial expression of a circulating inhibitor of lipoprotein lipase called Angiopoietin-like 4 ( Angptl4/Fiaf ) .", "To ...	[ "Recent studies have revealed that the community of microorganisms residing in the intestine regulates fat storage .", "Microbes evoke this response in part by suppressing expression of the Angptl4 gene , which encodes a secreted inhibitor of fat storage .", "Although Angptl4 is expressed in multiple tissues , ...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biology", "computational biology" ]	In silico Experimentation of Glioma Microenvironment Development and Anti-tumor Therapy	journal.pcbi.1002355	null	[ [ "Tumor cells and stromal cells actively “talk” to each other via an array of soluble signaling molecules , leading to co-evolution of the tumor and its microenvironment [1] , [2] , [3] , [4] , [5] .", "This also implies that the tumor microenvironment itself is a critical aspect of disease mechanism and t...	[ "Tumor cells do not develop in isolation , but co-evolve with stromal cells and tumor-associated immune cells in a tumor microenvironment mediated by an array of soluble factors , forming a complex intercellular signaling network .", "Herein , we report an unbiased , generic model to integrate prior biochemical d...	[ "Tumor cells do not develop in isolation , but co-evolve with stromal cells via an array of soluble mediators .", "Here we report a model to integrate prior biochemical data and construct a glioma microenvironment in silico , which comprises 5 types of cells , 15 cytokines , and 69 signaling pathways .", "We ob...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "behavioral neuroscience", "model organisms", "genetics", "biology", "genetics of disease", "neuroscience", "genetics and genomics" ]	Hyperactive Neuroendocrine Secretion Causes Size, Feeding, and Metabolic Defects of C. elegans Bardet-Biedl Syndrome Mutants	journal.pbio.1001219	null	[ [ "Bardet-Biedl Syndrome is a rare , multigenic , pleiotropic disorder characterized by defects in many tissues including the eyes , kidneys , central nervous system , and reproductive organs [1] .", "The clinical presentations of BBS include broadly prevalent disease conditions such as obesity and retinopa...	[ "Bardet-Biedl syndrome , BBS , is a rare autosomal recessive disorder with clinical presentations including polydactyly , retinopathy , hyperphagia , obesity , short stature , cognitive impairment , and developmental delays .", "Disruptions of BBS proteins in a variety of organisms impair cilia formation and func...	[ "Bardet-Biedl syndrome , BBS , is a rare human genetic disease caused by mutations in many genes .", "The BBS phenotype is very complex; it is principally characterized by early-onset obesity , progressive blindness , extra digits on the hands and feet , and renal problems .", "BBS patients may also suffer from...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "physiology/sensory systems", "neuroscience/sensory systems" ]	synaptojanin1 Is Required for Temporal Fidelity of Synaptic Transmission in Hair Cells	journal.pgen.1000480	null	[ [ "Vertebrate hair cells generate graded receptor potentials in response to mechanical stimuli , resulting in neurotransmitter release with high temporal accuracy and fidelity .", "Precise timing of release supports the phase locking of post-synaptic activity to stimuli in the kilohertz range [1] .", "T...	[ "To faithfully encode mechanosensory information , auditory/vestibular hair cells utilize graded synaptic vesicle ( SV ) release at specialized ribbon synapses .", "The molecular basis of SV release and consequent recycling of membrane in hair cells has not been fully explored .", "Here , we report that comet ,...	[ "Ribbon synapses are found in the ear and eye and facilitate the transmission of sensory information to the brain .", "In hair cells of the ear , the molecules required for ribbon function have not been fully explored .", "Zebrafish are ideal for investigating molecular components of these specialized synapses ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Natural Genetic Variation of Integrin Alpha L (Itgal) Modulates Ischemic Brain Injury in Stroke	journal.pgen.1003807	null	[ [ "Stroke is the second leading cause of death and the most common cause of acquired adult disability worldwide [1] , [2] .", "Ischemic stroke is caused by disrupted blood flow within the territory of an occluded blood vessel that results in death of brain cells ( infarct ) .", "The severity of cerebral...	[ "During ischemic stroke , occlusion of the cerebrovasculature causes neuronal cell death ( infarction ) , but naturally occurring genetic factors modulating infarction have been difficult to identify in human populations .", "In a surgically induced mouse model of ischemic stroke , we have previously mapped Civq1...	[ "Stroke is the second leading cause of death and the most common cause of acquired adult disability worldwide .", "Ischemic stroke is caused by an interruption of blood flow in the cerebral arteries and results in neuronal damage ( infarct ) to the area of perfusion in the brain .", "Although significant progre...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "carbohydrate metabolism", "diabetes mellitus type 2", "diabetic endocrinology", "dna transcription", "animal models", "model organisms", "metabolic pathways", "gene expression", "endocrinology", "diabetes and endocrinology", "biology", "mouse", "molecular biology", "biochemi...	TCF7L2 Modulates Glucose Homeostasis by Regulating CREB- and FoxO1-Dependent Transcriptional Pathway in the Liver	journal.pgen.1002986	null	[ [ "Dysregulation of hepatic glucose metabolism is a major predicament for the development of type 2 diabetes .", "During insulin resistant conditions , physiological activation of Akt-dependent pathway under feeding is impaired , which results in the failure to suppress hepatic glucose production in part vi...	[ "Peripheral insulin resistance contributes to the development of type 2 diabetes .", "TCF7L2 has been tightly associated with this disease , although the exact mechanism was largely elusive .", "Here we propose a novel role of TCF7L2 in hepatic glucose metabolism in mammals .", "Expression of medium and short...	[ "Previous genome-wide association studies revealed that TCF7L2 is a strong candidate for a type 2 diabetes gene .", "However , the direct involvement of TCF7L2 on hepatic glucose metabolism has been elusive to date .", "Here we show that TCF7L2 is critical in mediating transcriptional control of hepatic glucose...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "oncology", "homo (human)", "hematology", "immunology" ]	Phenotype Frequencies of Autosomal Minor Histocompatibility Antigens Display Significant Differences among Populations	journal.pgen.0030103	null	[ [ "Minor histocompatibility ( H ) antigens are polymorphic peptides that are presented on the cell surface by major histocompatibility complex class I or II molecules [1] .", "These peptides are derived from allelic cellular proteins encoded by autosomal genes or by genes of the Y chromosome [2] .", "In...	[ "Minor histocompatibility ( H ) antigens are allogeneic target molecules having significant roles in alloimmune responses after human leukocyte antigen–matched solid organ and stem cell transplantation ( SCT ) .", "Minor H antigens are instrumental in the processes of transplant rejection , graft-versus-host dise...	[ "Peptides from cellular proteins evoking alloimmune responses in human leukocyte antigen–identical transplantation are called minor histocompatibility ( H ) antigens .", "Upon hematopoietic stem cell transplantation ( HSCT ) for hematological malignancies or for solid tumors , responses to minor H antigens may ha...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "tropical diseases", "parasitic diseases", "salmonellosis", "brucellosis", "bacterial diseases", "rabies", "neglected tropical diseases", "veterinary science", "campylobacteriosis", "echinococcosis", "public and occupational health", "infectious diseases", "...	The Burden of Zoonoses in Kyrgyzstan: A Systematic Review	journal.pntd.0004831	null	[ [ "Zoonoses are diseases in humans , which are naturally transmissible directly or indirectly from vertebrate animals .", "Of 1415 species of infectious organisms know to be human pathogens , 61% are zoonotic [1] .", "The Food and Agriculture Organization of the United Nations ( FAO ) , the World Health...	[ "Zoonotic disease ( ZD ) pose a serious threat to human health in low-income countries .", "In these countries the human burden of disease is often underestimated due to insufficient monitoring because of insufficient funding .", "Quantification of the impact of zoonoses helps in prioritizing healthcare needs ....	[ "Zoonoses are diseases transmitted from vertebrate animals to humans .", "They can cause a variety of symptoms ranging from mild gastrointestinal complaints to debilitating illness and even death .", "Especially in low-income countries where animals play an important role for many , the burden of these diseases...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Impact of Anti-Retroviral Treatment and Cotrimoxazole Prophylaxis on Helminth Infections in HIV-Infected Patients in Lambaréné, Gabon	journal.pntd.0003769	null	[ [ "Globally , more than 2 billion people are estimated to be infected with soil-transmitted helminths , and the geographical distribution of these infections overlaps considerably with regions of high HIV sero-prevalence [1 , 2] .", "Helminth infections have been hypothesized to be factors driving the HIV-e...	[ "Foci of the HIV epidemic and helminthic infections largely overlap geographically .", "Treatment options for helminth infections are limited , and there is a paucity of drug-development research in this area .", "Limited evidence suggests that antiretroviral therapy ( ART ) reduces prevalence of helminth infec...	[ "The geographical distribution of helminth infections , which are highly prevalent in many areas , overlaps considerably with regions of high HIV sero-prevalence .", "The highest burden of infection is found in resource-poor settings , making it unattractive for the pharmaceutical industry to invest .", "Limite...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "cell biology", "cell cycle and cell division", "genetics", "biology and life sciences", "cell processes", "molecular cell biology", "gene function" ]	Mouse Y-Linked Zfy1 and Zfy2 Are Expressed during the Male-Specific Interphase between Meiosis I and Meiosis II and Promote the 2nd Meiotic Division	journal.pgen.1004444	null	[ [ "Historically the realisation that there were spermatogenic factors on the human and mouse Y chromosomes distinct from the testis determinant came from the study of Y deletion variants [1] , [2] .", "However , it was not until the search for the testis determinant that Y-encoded genes began to be identifi...	[ "Mouse Zfy1 and Zfy2 encode zinc finger transcription factors that map to the short arm of the Y chromosome ( Yp ) .", "They have previously been shown to promote meiotic quality control during pachytene ( Zfy1 and Zfy2 ) and at the first meiotic metaphase ( Zfy2 ) .", "However , from these previous studies add...	[ "The mouse Y chromosome genes Zfy1 and Zfy2 were first identified in the late 1980s during the search for the gene on the Y that triggers male development; they encode proteins that regulate the expression of other genes to which they bind via a ‘zinc finger’ domain .", "We have now discovered that these genes pl...	2014
[ "Introduction", "Models and Methods", "Results", "Discussion" ]	[ "computational neuroscience", "biology", "neuroscience" ]	Modelling Trial-by-Trial Changes in the Mismatch Negativity	journal.pcbi.1002911	null	[ [ "A key theme of contemporary neuroscience is the notion that the brain embodies a generative model of the environment , enabling inference on the causes of sensory inputs and predicting future events .", "This is also known as the “Bayesian brain hypothesis” ( for reviews , see [1] and [2] ) .", "This...	[ "The mismatch negativity ( MMN ) is a differential brain response to violations of learned regularities .", "It has been used to demonstrate that the brain learns the statistical structure of its environment and predicts future sensory inputs .", "However , the algorithmic nature of these computations and the u...	[ "The ability to predict one's environment is crucial for adaptive and proactive behaviour .", "It requires learning a mental model that captures the environment's statistical regularities .", "A process of this sort is thought to be reflected by the mismatch negativity ( MMN ) potential , a non-invasive electro...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dermatology", "invertebrates", "medicine and health sciences", "respiratory infections", "urticaria", "helminths", "parasitic diseases", "animals", "pulmonology", "strongyloides stercoralis", "strongyloides", "parasitic intestinal diseases", "protozoan infections", "helminth infections", ...	Strongyloides stercoralis is associated with significant morbidity in rural Cambodia, including stunting in children	journal.pntd.0005685	null	[ [ "Strongyloides stercoralis , one of the most difficult to diagnose neglected tropical diseases , is an intestinal soil-transmitted parasitic nematode that occurs worldwide and is highly prevalent in warm regions with poor sanitation [1 , 2] .", "Its prevalence is largely underestimated due to the inabilit...	[ "Strongyloides stercoralis is a soil-transmitted nematode that can replicate within its host , leading to long-lasting and potentially fatal infections .", "It is ubiquitous and highly prevalent in Cambodia .", "The extent of morbidity associated with S . stercoralis infection is difficult to assess due to the ...	[ "Strongyloides stercoralis is an intestinal parasite that infects humans by penetrating intact skin .", "It thrives particularly in tropical countries with poor sanitation .", "Because it can replicate within its host , it causes long-lasting infections and is potentially fatal in patients with a disseminated i...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "pattern recognition receptors", "invertebrates", "medicine and health sciences", "immunology", "social sciences", "neuroscience", "animals", "artificial neural networks", "animal models", "drosophila melanogaster", "model organisms", "cognition", "artificial intelligence", "experimental o...	Neural coding in the visual system of Drosophila melanogaster: How do small neural populations support visually guided behaviours?	journal.pcbi.1005735	null	[ [ "As with many animals , vision plays a key role in a number of behaviours performed by the fruit fly Drosophila melanogaster , including mate-recognition [1] , place homing [2] , visual course control [3] , collision-avoidance [4] , landing [4] and escaping a looming object ( like a rolled newspaper , for exa...	[ "All organisms wishing to survive and reproduce must be able to respond adaptively to a complex , changing world .", "Yet the computational power available is constrained by biology and evolution , favouring mechanisms that are parsimonious yet robust .", "Here we investigate the information carried in small po...	[ "A general problem in neuroscience is understanding how sensory systems organise information to be at the service of behaviour .", "Computational approaches can be useful for such studies as they allow one to simulate the sensory experience of a behaving animal whilst considering how sensory information should be...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "systems ecology", "medicine and health sciences", "veterinary epidemiology", "ecology", "evolutionary biology", "population modeling", "epidemiology", "population dynamics", "biology and life sciences", "population biology", "computational biology", "population ecology", ...	Contact Heterogeneity, Rather Than Transmission Efficiency, Limits the Emergence and Spread of Canine Influenza Virus	journal.ppat.1004455	null	[ [ "Respiratory pathogens that emerge as the result of host-range shifts can cause serious epidemics in humans , livestock , and wild animals [1]–[4] .", "Two recent pandemics in humans – Severe Acute Respiratory Syndrome ( SARS ) in 2003 and H1N1 influenza in 2009 – involved host-range shifts in respiratory...	[ "Host-range shifts in influenza virus are a major risk factor for pandemics .", "A key question in the study of emerging zoonoses is how the evolution of transmission efficiency interacts with heterogeneity in contact patterns in the new host species , as this interplay influences disease dynamics and prospects f...	[ "Influenza virus infects a range of vertebrate hosts , including domesticated animals as well as humans .", "Some of the most serious influenza pandemics in humans have involved host range shifts , when an influenza virus jumps from one host species to another .", "Importantly , however , host range shifts do n...	2014
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "virology/host invasion and cell entry", "virology" ]	Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry Pathway	journal.ppat.1001329	null	[ [ "Influenza A virus ( IAV ) is an enveloped , segmented negative-strand RNA virus infecting a wide variety of birds and mammals .", "As its first step in infection IAV attaches to host cells by the binding of its major surface protein , the hemagglutinin ( HA ) , to sialic acids , which are omnipresent on ...	[ "Influenza A virus ( IAV ) enters host cells upon binding of its hemagglutinin glycoprotein to sialylated host cell receptors .", "Whereas dynamin-dependent , clathrin-mediated endocytosis ( CME ) is generally considered as the IAV infection pathway , some observations suggest the occurrence of an as yet uncharac...	[ "Attachment to and entry into a host cell are the first crucial steps in establishing a successful virus infection and critical factors in determining host cell and species tropism .", "Influenza A virus ( IAV ) attaches to host cells by binding of its major surface protein , hemagglutinin , to sialic acids that ...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology", "biology and life sciences", "population biology", "species interactions", "microbiology" ]	Vector Competence in West African Aedes aegypti Is Flavivirus Species and Genotype Dependent	journal.pntd.0003153	null	[ [ "Aedes aegypti is the primary vector of yellow fever virus ( YFV ) and all four serotypes of dengue viruses ( DENV1-4 ) , as well as being a known vector of chikungunya virus .", "Dengue remains an important public health problem with an expected 390 million cases per year [1] .", "Although there are ...	[ "Vector competence of Aedes aegypti mosquitoes is a quantitative genetic trait that varies among geographic locations and among different flavivirus species and genotypes within species .", "The subspecies Ae .", "aegypti formosus , found mostly in sub-Saharan Africa , is considered to be refractory to both den...	[ "Vector competence is defined as the intrinsic permissiveness of an arthropod vector for infection , dissemination , and transmission of a pathogen .", "The mosquito Aedes aegypti is the main vector for dengue and yellow fever viruses worldwide and is divided into two subspecies: Ae .", "aegypti aegypti and Ae ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology", "dna transcription", "genome sequencing", "epigenetics", "chromosome biology", "gene expression", "microbial pathogens", "comparative genomics", "biology", "dna modification", "systems biology", "genetics", "genomics", "genetics and genomics" ]	Comprehensive Methylome Characterization of Mycoplasma genitalium and Mycoplasma pneumoniae at Single-Base Resolution	journal.pgen.1003191	null	[ [ "Among a few documented mechanisms , methylation of specific DNA sequences by DNA methyltransferases provides one way by which epigenetic inheritance can be orchestrated [1] .", "For instance , in many eukaryotes , methylated cytosine residues at 5′-CG-3′ ( CpG ) sequences are recognized by methyl-CpG bin...	[ "In the bacterial world , methylation is most commonly associated with restriction-modification systems that provide a defense mechanism against invading foreign genomes .", "In addition , it is known that methylation plays functionally important roles , including timing of DNA replication , chromosome partitioni...	[ "DNA methylation in bacteria plays important roles in cell division , DNA repair , regulation of gene expression , and pathogenesis .", "Here , we use a novel sequencing technique , Single-Molecule Real-Time ( SMRT ) sequencing , to determine the methylomes of two related human pathogen species , Mycoplasma genit...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "bacteriology", "biofilms", "cell walls", "medicine and health sciences", "yeast infections", "pathology and laboratory medicine", "pathogens", "microbiology", "fungi", "model organisms", "tongue", "fungal diseases", "cellular structures and organelles", "fungal pathogens", "digestive sy...	Candida glabrata Binding to Candida albicans Hyphae Enables Its Development in Oropharyngeal Candidiasis	journal.ppat.1005522	null	[ [ "Oropharyngeal candidiasis ( OPC ) is an opportunistic mucosal infection caused by Candida species [1 , 2] .", "Candida albicans and Candida glabrata are the first and second major etiological agents of OPC , respectively [3] .", "Although other Candida species , including C . parapsilosis , C . tropi...	[ "Pathogenic mechanisms of Candida glabrata in oral candidiasis , especially because of its inability to form hyphae , are understudied .", "Since both Candida albicans and C . glabrata are frequently co-isolated in oropharyngeal candidiasis ( OPC ) , we examined their co-adhesion in vitro and observed adhesion of...	[ "Understanding how Candida glabrata is able to establish oral mucosal infections is particularly important since many C . glabrata strains are innately resistant to azole antifungal drugs used in treating mucosal and disseminated infections .", "The epidemiology of C . glabrata oral infections shows that C . glab...	2016
[ "Introduction", "1. Use learner personas to define your audience", "2. Design for effective learning strategies", "3. Write summative assessments to set concrete goals", "4. Write formative assessments for pacing, design, preparation, and reinforcement", "5. Integrate visual and linguistic information", ...	[ "learning", "neurolinguistics", "linguistics", "education", "social sciences", "neuroscience", "learning and memory", "cognitive psychology", "cognition", "memory", "vision", "cognitive linguistics", "instructors", "human learning", "memory recall", "people and places", "professions"...	Ten quick tips for creating an effective lesson	journal.pcbi.1006915	null	[ [ "There are many kinds of lessons , both formal and informal , from seconds long to lifelong .", "Most people have sat ( or suffered ) through hundreds of these but have never been shown how to design ones that are effective .", "These 10 simple tips for creating lessons are The key insight that underp...	[ "We present 10 tips for building effective lessons that are grounded in empirical research on pedagogy and cognitive psychology and that we have found to be practically useful in both classroom and free-range settings" ]	[ "As a species , we know as much about teaching and learning as we do about public health , but most people who teach at the postsecondary level are never introduced to even the basics of evidence-based pedagogy .", "Knowing just a few key facts will help you build more effective lessons in less time and with less...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "medicine", "genetic mutation", "gene regulation", "mutation types", "molecular genetics", "gene expression", "endocrinology", "diabetes and endocrinology", "biology", "autosomal dominant", "protein translation", "genetics", "human genetics", "genetics of disease", "genetics and genomics...	A Novel Mutation in the Upstream Open Reading Frame of the CDKN1B Gene Causes a MEN4 Phenotype	journal.pgen.1003350	null	[ [ "CDKN1B encodes the cyclin-dependent kinase ( CDK ) inhibitor , p27KIP1 , which negatively regulates the Cdk2/cyclin E and Cdk2/cyclin A protein complexes , thereby preventing the progression from the G1 to the S phase of the cell cycle [1] .", "In G0 and early G1 , p27KIP1 expression and stability are ma...	[ "The CDKN1B gene encodes the cyclin-dependent kinase inhibitor p27KIP1 , an atypical tumor suppressor playing a key role in cell cycle regulation , cell proliferation , and differentiation .", "Impaired p27KIP1 expression and/or localization are often observed in tumor cells , further confirming its central role ...	[ "Gene expression can be modulated at different steps on the way from DNA to protein including control of transcription , translation , and post-translational modifications .", "An abnormality in the regulation of mRNA and protein expression is a hallmark of many human diseases , including cancer .", "In some eu...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetic mutation", "cell differentiation", "gene function", "developmental biology", "organism development", "stem cells", "molecular development", "morphogenesis", "adult stem cells", "stem cell niche", "biology", "regeneration", "signaling", "cell migration", "genetics", "genetics a...	Post-Embryonic Nerve-Associated Precursors to Adult Pigment Cells: Genetic Requirements and Dynamics of Morphogenesis and Differentiation	journal.pgen.1002044	null	[ [ "A fundamental challenge for modern developmental biology is to determine how", "populations of stem and progenitor cells are established , maintained , and recruited", "to differentiate at particular times and places during post-embryonic development", "and in the adult organism .", "The sign...	[ "The pigment cells of vertebrates serve a variety of functions and generate a", "stunning variety of patterns .", "These cells are also implicated in human", "pathologies including melanoma .", "Whereas the events of pigment cell development", "have been studied extensively in the embryo , much less is kn...	[ "Understanding the biology of post-embryonic stem and progenitor cells is of both", "basic and translational importance .", "To identify mechanisms by which stem and", "progenitor cells are established , maintained , and recruited to particular fates ,", "we are using the zebrafish adult pigment pattern .",...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "learning", "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "engineering and technology", "signal processing", "social sciences", "random variables", "mathematical models", "neuroscience", "covariance", "learning and memory", "magnetic resonan...	Representational structure or task structure? Bias in neural representational similarity analysis and a Bayesian method for reducing bias	journal.pcbi.1006299	null	[ [ "Functional magnetic resonance imaging ( fMRI ) measures the blood-oxygen-level-dependent ( BOLD ) signals [1] , which rise to peak ∼6 seconds after neuronal activity increases in a local region [2] .", "Because of its non-invasiveness , full-brain coverage , and relatively favorable trade-off between spa...	[ "The activity of neural populations in the brains of humans and animals can exhibit vastly different spatial patterns when faced with different tasks or environmental stimuli .", "The degrees of similarity between these neural activity patterns in response to different events are used to characterize the represen...	[ "We show the severity of the bias introduced when performing representational similarity analysis ( RSA ) based on neural activity pattern estimated within imaging runs .", "Our Bayesian RSA method significantly reduces the bias and can learn a shared representational structure across multiple participants .", ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "genetics and genomics/chromosome biology", "molecular biology/transcription elongation", "genetics and genomics/epigenetics", "molecular biology/chromatin structure" ]	DSIF and RNA Polymerase II CTD Phosphorylation Coordinate the Recruitment of Rpd3S to Actively Transcribed Genes	journal.pgen.1001173	null	[ [ "Histone acetylation was the first covalent histone modification shown to be involved in transcription regulation .", "Indeed , histones at the promoter of active genes tend to be hyper-acetylated while repressed genes have promoters with hypo-acetylated nucleosomes .", "It is now well established tha...	[ "Histone deacetylase Rpd3 is part of two distinct complexes: the large ( Rpd3L ) and small ( Rpd3S ) complexes .", "While Rpd3L targets specific promoters for gene repression , Rpd3S is recruited to ORFs to deacetylate histones in the wake of RNA polymerase II , to prevent cryptic initiation within genes .", "M...	[ "Acetylation of histone N-terminal tails occurs on nucleosomes as a gene is being transcribed , therefore helping the RNA polymerase II traveling through nucleosomes .", "Histone acetylation , however , has to be reversed in the wake of the polymerase in order to prevent transcription from initiating at the wrong...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Spike-Timing Theory of Working Memory	journal.pcbi.1000879	null	[ [ "Various mechanisms have been proposed to model the main aspect of neural activity — elevated firing rates of a cue-specific population of neurons — observed during the delay period of a working memory ( WM ) task [1]–[4] .", "These include reentrant spiking activity [5] , intrinsic membrane currents [6] ...	[ "Working memory ( WM ) is the part of the brain's memory system that provides temporary storage and manipulation of information necessary for cognition .", "Although WM has limited capacity at any given time , it has vast memory content in the sense that it acts on the brain's nearly infinite repertoire of lifeti...	[ "Working memory ( WM ) is the part of the brain's vast memory system that provides temporary storage and manipulation of the information necessary for complex cognitive tasks , such as language comprehension , learning , and reasoning .", "Despite extensive neuroscience research , its mechanism is not clearly und...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "immune cells", "pathogens", "immunology", "microbiology", "opportunistic infections", "organisms", "developmental biology", "fu...	Langerin+ DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection	journal.ppat.1007069	null	[ [ "As part of the upper gastrointestinal tract , the oral cavity is colonized by microbes and constitutes an important entry point for hazardous pathogens .", "However , despite the relevance of the oral mucosa as a first site of interaction between microbes and the host , it remains little studied and its ...	[ "The opportunistic fungal pathogen Candida albicans frequently causes diseases such as oropharyngeal candidiasis ( OPC ) in immunocompromised individuals .", "Although it is well appreciated that the cytokine IL-17 is crucial for protective immunity against OPC , the cellular source and the regulation of this cyt...	[ "IL-17 is a key cytokine for immune homeostasis and host defense in barrier tissues , which can also drive inflammatory diseases and immunopathology under certain conditions .", "Most studies addressing IL-17-mediated processes focus on the lower gastrointestinal tract , while other barrier tissues such as the or...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/infectious diseases of the nervous system", "immunology/immunity to infections", "infectious diseases/viral infections", "immunology/leukocyte activation" ]	High Expression of CD244 and SAP Regulated CD8+ T Cell Responses of Patients with HTLV-I Associated Neurologic Disease	journal.ppat.1000682	null	[ [ "HTLV-I infects 20 million people worldwide [1] .", "While the majority of infected individuals are asymptomatic carriers ( ACs ) of the virus , 5–10% of infected people develop either adult T cell leukemia/lymphoma ( ATL ) [2] or a chronic , progressive neurological disease termed HTLV-I-associated myelo...	[ "HTLV-I-specific CD8+ T cells have been characterized with high frequencies in peripheral blood and cerebrospinal fluid and production of proinflammatory cytokines , which contribute to central nervous system inflammation in HTLV-I-associated myelopathy/tropical spastic paraparesis ( HAM/TSP ) .", "However , litt...	[ "Human T-lymphotropic virus type I ( HTLV-I ) is a retrovirus that persistently infects 20 million people worldwide .", "The majority of infected individuals are asymptomatic carriers of the virus , but 5–10% of infected people develop either adult T cell leukemia/lymphoma ( ATL ) or a chronic , progressive neuro...	2009
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "sphingolipids", "membrane proteins", "planar chromatography", "genetic interactions", "cellular structures and organelles", "thin-layer chromatography", "research and analysis methods", "lipids", "chromosome biology", "cell membranes", "chromatographic techniques", "biochemistry", "cell bio...	Chemogenetic E-MAP in Saccharomyces cerevisiae for Identification of Membrane Transporters Operating Lipid Flip Flop	journal.pgen.1006160	null	[ [ "All living cells define their boundaries by lipid-containing membranes , which in eukaryotes are mainly made of glycerophospholipids ( GPLs ) , sphingolipids and sterols .", "Phosphatidic acid ( PA ) is an obligatory intermediate in the biosynthesis of all GPLs [1 , 2] .", "In eukaryotes , PA is gene...	[ "While most yeast enzymes for the biosynthesis of glycerophospholipids , sphingolipids and ergosterol are known , genes for several postulated transporters allowing the flopping of biosynthetic intermediates and newly made lipids from the cytosolic to the lumenal side of the membrane are still not identified .", ...	[ "All living cells define their boundaries by lipid-containing membranes , which are impermeable to ions and water-soluble metabolic intermediates , and thus allow maintaining constant conditions inside the cells and stopping metabolic intermediates from diffusing away .", "Membranes are formed by amphiphilic lipi...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "geomorphology", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "landforms", "infectious disease epidemiology", "pathogens", "topography", "tropical diseases", "microbiology", "geographical locations", "alphaviruses", "viruses",...	Improving early epidemiological assessment of emerging Aedes-transmitted epidemics using historical data	journal.pntd.0006526	null	[ [ "Model-based assessments must be done in real time for emerging outbreaks: this was the case in recent years for MERS-CoV in the Middle East [1–3] , Ebola virus in West Africa [4–10] , chikungunya virus ( CHIKV ) [11] and Zika virus ( ZIKV ) [12–14] in the Americas .", "These analyses often focused on tra...	[ "Model-based epidemiological assessment is useful to support decision-making at the beginning of an emerging Aedes-transmitted outbreak .", "However , early forecasts are generally unreliable as little information is available in the first few incidence data points .", "Here , we show how past Aedes-transmitted...	[ "In December , 2015 , Aedes mosquito-transmitted Zika outbreaks started in the French West Indies , about two years after chikungunya epidemics , spread by the same mosquito , hit the same region .", "Building on the similarities between these epidemics—regarding the route of transmission , the surveillance syste...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Helminth Infection and Commensal Microbiota Drive Early IL-10 Production in the Skin by CD4+ T Cells That Are Functionally Suppressive	journal.ppat.1004841	null	[ [ "The skin provides an important first line of defence against infectious pathogens which can gain entry via open wounds/abrasions ( e . g . Staphylococcus aureus [1] ) , following injection via insect bites ( e . g . Leishmania sp . protozoa [2] or filarial nematodes [3] ) , or via direct percutaneous penetra...	[ "The skin provides an important first line of defence and immunological barrier to invasive pathogens , but immune responses must also be regulated to maintain barrier function and ensure tolerance of skin surface commensal organisms .", "In schistosomiasis-endemic regions , populations can experience repeated pe...	[ "The skin is a major barrier protecting the host from pathogen infection , but is also a site for immune regulation .", "Using a murine model of repeated percutaneous exposure to infectious Schistosoma mansoni cercariae , we show that , in the skin , CD4+ T cells that do not express markers of conventional regula...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "oxidative stress", "gene regulation", "regulatory proteins", "dna-binding proteins", "animals", "animal models", "drosophila melanogaster", "model organisms", "pharmaceutics", "transcription factors", "epigenetics", "d...	Keap1-Independent Regulation of Nrf2 Activity by Protein Acetylation and a BET Bromodomain Protein	journal.pgen.1006072	null	[ [ "Nrf2 transcription factors are critically important for the health , homeostasis and longevity of multicellular organisms [1–3] .", "When cells are confronted with oxidative or chemical stress , Nrf2 stimulates the expression of gene products that protect cell integrity including antioxidants , redox reg...	[ "Mammalian BET proteins comprise a family of bromodomain-containing epigenetic regulators with complex functions in chromatin organization and gene regulation .", "We identified the sole member of the BET protein family in Drosophila , Fs ( 1 ) h , as an inhibitor of the stress responsive transcription factor Cnc...	[ "Nrf2-related transcription factors regulate gene expression programs that protect organisms against chemical or oxidative stress .", "Nrf2-activating drugs hold promise for the treatment of diseases that are connected to oxidative stress or inflammation .", "We identified Fs ( 1 ) h , a bromodomain-containing ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "bovine tuberculosis in humans", "neglected tropical diseases" ]	Prevalence of Latent and Active Tuberculosis among Dairy Farm Workers Exposed to Cattle Infected by Mycobacterium bovis	journal.pntd.0002177	null	[ [ "The most frequent etiologic agent of tuberculosis ( TB ) in humans is Mycobacterium tuberculosis , followed by M . bovis , that causes bovine tuberculosis [1] .", "The zoonosis caused by M . bovis in developed countries is now considered a sporadic disease since control of the disease in cattle was achie...	[ "Human tuberculosis caused by M . bovis is a zoonosis presently considered sporadic in developed countries , but remains a poorly studied problem in low and middle resource countries .", "The disease in humans is mainly attributed to unpasteurized dairy products consumption .", "However , transmission due to ex...	[ "Mycobacterium tuberculosis complex causes tuberculosis in humans and other mammals .", "The complex includes M . bovis , which causes bovine tuberculosis .", "The main route of transmission of this zoonosis is the consumption of unpasteurized dairy products .", "Nevertheless , exposure to infected cattle whi...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational neuroscience", "neuroscience", "biology and life sciences", "computational biology" ]	Axonal Noise as a Source of Synaptic Variability	journal.pcbi.1003615	null	[ [ "The great majority of axons use action potentials ( APs ) to transmit information reliably to synapses .", "Once the AP arrives at the synapse the characteristics of its waveform are fundamental in determining the strength and reliability of information transmission , as was extensively shown in the cent...	[ "Post-synaptic potential ( PSP ) variability is typically attributed to mechanisms inside synapses , yet recent advances in experimental methods and biophysical understanding have led us to reconsider the role of axons as highly reliable transmission channels .", "We show that in many thin axons of our brain , th...	[ "The fundamental signal of the nervous system is the action potential: an electrical spike propagated along neurons and transmitted between them via synapses .", "Once triggered , action potentials are generally assumed to be robust to noise , and the variability observed at all levels of the nervous system is pr...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "animal types", "greece", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "geographical locations", "microbiology", "vertebrates", "sand flies", "pets and companion animals", "dogs", "animals", "mammals", "viruses", ...	Seroprevalence of Sandfly‐Borne Phleboviruses Belonging to Three Serocomplexes (Sandfly fever Naples, Sandfly fever Sicilian and Salehabad) in Dogs from Greece and Cyprus Using Neutralization Test	journal.pntd.0005063	null	[ [ "In the Old world , phleboviruses ( Bunyaviridae family , Phlebovirus genus ) transmitted by phlebotomines consist of three species or antigenic groups , namely Sandfly fever Naples , Salehabad , and Sandfly fever Sicilian serocomplexes .", "Each species contains several viruses among which Naples , Sicil...	[ "Phleboviruses transmitted by sandflies are endemic in the Mediterranean area .", "The last decade has witnessed the description of an accumulating number of novel viruses .", "Although , the risk of exposure of vertebrates is globally assessed , detailed geographic knowledge is poor even in Greece and Cyprus w...	[ "Phleboviruses transmitted by sandflies are endemic in the Mediterranean basin .", "An increased number of new viruses was described during the last decade .", "However , levels of exposure of human and animal populations are poorly known .", "A total of 1 , 250 dogs from Greece and 422 dogs from Cyprus were ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "post-exposure prophylaxis", "tropical diseases", "microbiology", "vertebrates", "dogs", "animals", "mammals", "health care", "viruses", "preventive medicine", "rabies", "health care providers", "rna viru...	An exploratory study on rabies exposure through contact tracing in a rural area near Bengaluru, Karnataka, India	journal.pntd.0006682	null	[ [ "Rabies is a 100% fatal viral zoonotic disease . [1]", "However , Rabies can be prevented if , health care providers are able to identify the type of exposure , categorize the wounds and provide post exposure prophylaxis ( PEP ) as early as possible . [2 , 3]", "South East Asia region accounts approxi...	[ "Rabies is a neglected zoonotic disease .", "Given the low incidence , apart from the existing reporting syst , there is a need to look for other means of case detection strategies for rabies .", "Contact tracing is one such method to efficiently capture information .", "To find out the rabid status of biting...	[ "In India , Rabies is a neglected zoonotic disease and the burden of rabies is usually not captured by the health system due to varied reasons .", "Hence , an exploratory study was attempted to find out the rabid status of the biting animal through contact tracing during the first quarter of 2017 in villages comi...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "diagnostic medicine", "clinical immunology", "biology and life sciences", "immunology" ]	Prevalence and Serological Diagnosis of Relapse in Paracoccidioidomycosis Patients	journal.pntd.0002834	null	[ [ "Paracoccidioidomycosis ( PCM ) is a systemic mycosis caused by thermo-dimorphic fungi from the Paracoccidioides brasiliensis complex and the Paracoccidioides lutzii complex [1] .", "Confined to Latin America , PCM is endemic to the area extending from Mexico to Argentina [2] .", "Although incomplete ...	[ "A review of 400 clinical records of paracoccidioidomycosis ( PCM ) patients , 93 with the acute/subacute ( AF ) and 307 with the chronic form ( CF ) , attended from 1977 to 2011 , selected as to the schedule of release for study by the Office of Medical Records at the University Hospital of the Faculdade de Medici...	[ "Paracoccidioidomycosis ( PCM ) is a systemic mycosis caused by fungi of the Paracoccidioides brasiliensis and Paracoccidioides lutzii complexes , which live in the soil and affect mainly rural workers in the most productive period of their lives .", "PCM can relapse after effective treatment because quiescent fu...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System	journal.ppat.1005293	null	[ [ "Human systemic fungal infections are typically opportunistic and primarily affect patients with acquired immunodeficiency ( i . e . commonly due to HIV infection or modern medical interventions such as cancer chemotherapy and transplantation ) or inborn errors of immunity [1 , 2] .", "Systemic candidiasi...	[ "Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense .", "Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system ( CNS ) .", "However , how CARD...	[ "CARD9 is a molecule expressed by mammalian immune cells and is centrally positioned downstream of several C-type lectin receptors , which sense fungi .", "The critical role of CARD9 in the activation of antifungal host defense has been highlighted by the demonstration that human mutations that disrupt the functi...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/molecular evolution", "molecular biology/translational regulation", "genetics and genomics/bioinformatics", "evolutionary biology/genomics" ]	A Universal Trend of Reduced mRNA Stability near the Translation-Initiation Site in Prokaryotes and Eukaryotes	journal.pcbi.1000664	null	[ [ "Synonymous mutations are frequently used as a neutral baseline to detect selection pressures at the amino-acid level [1] .", "Yet many mechanisms are now known that cause selection pressure on synonymous sites .", "Translationally preferred codons are selected for accurate and efficient translation i...	[ "Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli , and that translation is more efficient the less stable the secondary structure .", "We survey the complete genomes of 340 species for signals o...	[ "Synonymous mutations are mutations that change the nucleotide sequence of a gene without changing the amino-acid sequence .", "Because these mutations don't alter the expressed protein , they are frequently also called silent mutations .", "Yet increasing evidence demonstrates that synonymous mutations are not...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "developmental biology", "gene regulation", "gene expression", "regulatory networks", "molecular genetics", "biology", "computational biology", "genetics", "gene networks", "pattern formation", "genetics and genomics" ]	Modeling of Gap Gene Expression in Drosophila Kruppel Mutants	journal.pcbi.1002635	null	[ [ "The segmentation gene network in early Drosophila embryo provides a powerful model system to study the role of genes in pattern formation .", "This network solves the fundamental problem of embryonic patterning: how to establish a periodic pattern of gene expression , which determines both the positions ...	[ "The segmentation gene network in Drosophila embryo solves the fundamental problem of embryonic patterning: how to establish a periodic pattern of gene expression , which determines both the positions and the identities of body segments .", "The gap gene network constitutes the first zygotic regulatory tier in th...	[ "Systems biology is aimed to develop an understanding of biological function or process as a system of interacting components .", "Here we apply the systems-level approach to understand how the blueprints for segments in the fruit fly Drosophila embryo arise .", "We obtain gene expression data and use the gene ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "influenza", "applied mathematics", "geographical locations", "epidemiological methods and statistics", "simulation and modeling", "algorithms", "seasons", "mathematics", "infectious disease control", "research and analysis methods", "curve fitting", "infectio...	Early and Real-Time Detection of Seasonal Influenza Onset	journal.pcbi.1005330	null	[ [ "Seasonal influenza is a worldwide infectious disease estimated to be the cause of 3 to 5 million cases of severe illness and up to half a million deaths every year [1] , also placing a strong economic burden on health services [2] and [3] .", "To deal with these epidemics , the beginning of the flu seaso...	[ "Every year , influenza epidemics affect millions of people and place a strong burden on health care services .", "A timely knowledge of the onset of the epidemic could allow these services to prepare for the peak .", "We present a method that can reliably identify and signal the influenza outbreak .", "By co...	[ "Influenza , generally referred to as the flu , is a common infectious disease that affects millions of people .", "Every year , we expect this seasonal disease to occur during the Winter , but exactly when it will start and how severe it will be is not known .", "This places a strong burden on health services ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "medicine", "population genetics", "global health", "epigenetics", "biology", "evolutionary genetics", "adaptation", "natural selection", "genetics", "genomics", "evolutionary biology", "genomic evolution", "evolutionary processes", "genetics and genomi...	The Genetic Architecture of Adaptations to High Altitude in Ethiopia	journal.pgen.1003110	null	[ [ "Hypoxia is a major stress on human physiological processes and a powerful homeostasis system has evolved in animals to cope with fluctuations in oxygen concentration [1] .", "High altitude ( HA ) hypoxia , such as that experienced at 2500 m of altitude or greater , engages this system and elicits physiol...	[ "Although hypoxia is a major stress on physiological processes , several human populations have survived for millennia at high altitudes , suggesting that they have adapted to hypoxic conditions .", "This hypothesis was recently corroborated by studies of Tibetan highlanders , which showed that polymorphisms in c...	[ "Although hypoxia is a major stress on physiological processes , several human populations have survived for millennia at high altitudes , suggesting that they have adapted to hypoxic conditions .", "Consistent with this idea , previous studies have identified genetic variants in Tibetan highlanders associated wi...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "chemical compounds", "oxidative stress", "immunology", "tropical diseases", "microbiology", "parasitic diseases", "parasitic protozoans", "protozoan life cycles", "organic compounds", "developmental biology", "protozoans", "...	Increased miltefosine tolerance in clinical isolates of Leishmania donovani is associated with reduced drug accumulation, increased infectivity and resistance to oxidative stress	journal.pntd.0005641	null	[ [ "Visceral leishmaniasis ( VL ) is the most severe form of leishmaniasis , being fatal if left untreated .", "More than 90% of the global burden of VL occurs in just six countries: India , Bangladesh , Sudan , South Sudan , Brazil and Ethiopia [1] .", "India alone shares almost 50% of the world’s VL bu...	[ "Miltefosine ( MIL ) is an oral antileishmanial drug used for treatment of visceral leishmaniasis ( VL ) in the Indian subcontinent .", "Recent reports indicate a significant decline in its efficacy with a high rate of relapse in VL as well as post kala-azar dermal leishmaniasis ( PKDL ) .", "We investigated th...	[ "Increasing rate of relapse against miltefosine ( MIL ) and decline in its efficacy prompted us to study the parasitic factors associated with MIL unresponsiveness in clinical isolates of Leishmania donovani .", "Studies to explore the mechanism of MIL resistance in L . donovani are largely restricted to experime...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "physicians", "medical doctors", "pathology and laboratory medicine", "neurocysticercosis", "medical personnel", "tropical diseases", "parasitic diseases", "migraine", "health care", "headaches", "research design", "health care providers", "signs and symptom...	The impact of imperfect screening tools on measuring the prevalence of epilepsy and headaches in Burkina Faso	journal.pntd.0007109	null	[ [ "The Global Burden of Disease Study estimates epilepsy and migraines to be among the 30 leading causes of years of life lost due to disability [1] .", "The prevalence of epilepsy and headaches varies globally , likely due to different risk factors across populations or epidemiological biases [2 , 3] .", ...	[ "Epilepsy and progressively worsening severe chronic headaches ( WSCH ) are the two most common clinical manifestations of neurocysticercosis , a form of cysticercosis .", "Most community-based studies in sub-Saharan Africa ( SSA ) use a two-step approach ( questionnaire and confirmation ) to estimate the prevale...	[ "Epilepsy and progressively worsening severe chronic headaches are the two most common clinical manifestations of neurocysticercosis , a form of cysticercosis .", "To understand where the prevalence of these neurological disorders is highest for targeted infection control , valid prevalence estimates are needed ....	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene identification and analysis", "genetics", "molecular genetics", "biology" ]	Fragile DNA Motifs Trigger Mutagenesis at Distant Chromosomal Loci in Saccharomyces cerevisiae	journal.pgen.1003551	null	[ [ "Chromosomal instability and mutagenesis are two fundamental processes that alter prokaryotic and eukaryotic genomes .", "The deleterious consequences of excessive DNA perturbations are hereditary diseases and cancer in humans ( reviewed in [1] , [2] , [3] ) .", "At the same time , a fine balance betw...	[ "DNA sequences capable of adopting non-canonical secondary structures have been associated with gross-chromosomal rearrangements in humans and model organisms .", "Previously , we have shown that long inverted repeats that form hairpin and cruciform structures and triplex-forming GAA/TTC repeats induce the format...	[ "Eukaryotic chromosomes include regions that are susceptible for breakage and rearrangements .", "Repeats that can adopt non-B form DNA secondary structure are often found to be responsible for the induction of rearrangements .", "Here , we demonstrate that inverted repeats and GAA/TTC breakage sites are also s...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Macrophages Subvert Adaptive Immunity to Urinary Tract Infection	journal.ppat.1005044	null	[ [ "Urinary tract infection ( UTI ) is one of the most common bacterial infections , impacting more than 130 million people annually worldwide [1 , 2] .", "The principal causative agent is uropathogenic Escherichia coli ( UPEC ) , accounting for more than 75% of all community acquired infections , particular...	[ "Urinary tract infection ( UTI ) is one of the most common bacterial infections with frequent recurrence being a major medical challenge .", "Development of effective therapies has been impeded by the lack of knowledge of events leading to adaptive immunity .", "Here , we establish conclusive evidence that an a...	[ "Urinary tract infection is a common infection with a high propensity for recurrence .", "The majority of infections are caused by uropathogenic E . coli , a growing public health concern with increasing prevalence of antibiotic resistant strains .", "Finding therapeutic options that circumvent the need for ant...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome sequencing", "genome expression analysis", "neurobiology of disease and regeneration", "genome analysis tools", "functional genomics", "gene expression", "biology", "genomics", "molecular cell biology", "neuroscience", "transcriptomes" ]	Long Non-Coding RNA and Alternative Splicing Modulations in Parkinson's Leukocytes Identified by RNA Sequencing	journal.pcbi.1003517	null	[ [ "Recent studies have identified conspicuous diversity in large intergenic long non-coding RNAs ( lncRNAs ) found across many species [1] [2] .", "LncRNAs are currently defined as transcripts of over 200 nucleotides [3] .", "Nonetheless , the GENCODE non-coding RNA set , the largest currently lncRNA da...	[ "The continuously prolonged human lifespan is accompanied by increase in neurodegenerative diseases incidence , calling for the development of inexpensive blood-based diagnostics .", "Analyzing blood cell transcripts by RNA-Seq is a robust means to identify novel biomarkers that rapidly becomes a commonplace .", ...	[ "Long non-coding RNAs ( lncRNAs ) comprise a novel , fascinating class of RNAs with largely unknown biological functions .", "Parkinson's-disease ( PD ) is the most frequent motor disorder , and Deep-brain-stimulation ( DBS ) treatment alleviates the symptoms , but early disease biomarkers are still unknown and n...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "developmental biology", "cell biology", "neuroscience", "molecular biology" ]	A Mechanism Regulating the Onset of Sox2 Expression in the Embryonic Neural Plate	journal.pbio.0060002	The vertebrate nervous system develops from the neural plate, defined by the transcription factor Sox2. This paper uncovers a mechanism that regulates the timing of Sox2 expression, involving interactions between several proteins and chromatin remodeling.	[ [ "Sox2 is a transcription factor that plays multiple critical roles during embryonic development in vertebrates .", "In embryonic stem ( ES ) cells , as well as in adult central nervous system ( CNS ) stem cells , Sox2 expression is required for the maintenance of multipotency and for the ability of cells ...	[ "In vertebrate embryos , the earliest definitive marker for the neural plate , which will give rise to the entire central nervous system , is the transcription factor Sox2 .", "Although some of the extracellular signals that regulate neural plate fate have been identified , we know very little about the mechanism...	[ "During early development , when the embryo has three layers of cells ( ectoderm , mesoderm , and endoderm ) , a region of the ectoderm called the neural plate becomes specified to generate the entire nervous system .", "One of the earliest molecular markers for the neural plate is the transcription factor Sox2 ,...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "computational biology/transcriptional regulation", "genetics and genomics/gene expression", "evolutionary biology/genomics", "computational biology/evolutionary modeling", "developmental biology/cell differentiation", "computational biology/syste...	Evolution of Gene Regulatory Networks by Fluctuating Selection and Intrinsic Constraints	journal.pcbi.1000873	null	[ [ "The genetic basis of organismal evolution is one of the fundamental problems in biology [1]–[7] .", "The modes of selection for phenotypes would influence the fixation probabilities of the mutations that affect the phenotypes [8] , and the profile of the mutations fixed during the course of evolution wou...	[ "Various characteristics of complex gene regulatory networks ( GRNs ) have been discovered during the last decade , e . g . , redundancy , exponential indegree distributions , scale-free outdegree distributions , mutational robustness , and evolvability .", "Although progress has been made in this field , it is n...	[ "Various organismal traits , including the morphology of multicellular species and metabolism in unicellular species , are determined by the amount and combinations of proteins in the cell .", "The complex regulatory network plays an important role in controlling the protein profiles in a cell .", "Recent studi...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/nosocomial and healthcare-associated infections", "respiratory medicine/respiratory infections", "cell biology/membranes and sorting", "infectious diseases/bacterial infections", "cell biology/cytoskeleton" ]	Long-Distance Delivery of Bacterial Virulence Factors by Pseudomonas aeruginosa Outer Membrane Vesicles	journal.ppat.1000382	null	[ [ "Nosocomial infections contribute $4 . 5 billion to annual healthcare costs in this country alone , with an estimated 2 million nosocomial infections occurring in the US annually , resulting in 99 , 000 deaths [1] .", "Many of these nosocomial infections are caused by Gram-negative pathogens , and interac...	[ "Bacteria use a variety of secreted virulence factors to manipulate host cells , thereby causing significant morbidity and mortality .", "We report a mechanism for the long-distance delivery of multiple bacterial virulence factors , simultaneously and directly into the host cell cytoplasm , thus obviating the nee...	[ "Gram-negative pathogens are responsible for 2 million annual hospital-acquired infections , adding tremendously to U . S . healthcare costs .", "Pseudomonas aeruginosa , an opportunistic human pathogen , is commonly associated with nosocomial infections , particularly ventilator-associated infections and pseudom...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology and life sciences", "population biology", "microbiology" ]	Comprehensive Identification of Single Nucleotide Polymorphisms Associated with Beta-lactam Resistance within Pneumococcal Mosaic Genes	journal.pgen.1004547	null	[ [ "Recent research aimed at finding the genetic causes of beta-lactam resistance in Streptococcus pneumoniae has been focused on laboratory mutagenesis [1]–[4] , sequence comparison [1] , [5] , [6] , and identification of interspecies sequence transfer that promotes penicillin non-susceptibility [7]–[10] .", ...	[ "Traditional genetic association studies are very difficult in bacteria , as the generally limited recombination leads to large linked haplotype blocks , confounding the identification of causative variants .", "Beta-lactam antibiotic resistance in Streptococcus pneumoniae arises readily as the bacteria can quick...	[ "Streptococcus pneumoniae is carried asymptomatically in the nasopharyngeal tract .", "However , it is capable of causing multiple diseases , including pneumonia , bacteraemia and meningitis , which are common causes of morbidity and mortality in young children .", "Antibiotic treatment has become more difficul...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/recombination", "molecular biology/chromosome structure", "molecular biology/dna repair" ]	Competitive Repair by Naturally Dispersed Repetitive DNA during Non-Allelic Homologous Recombination	journal.pgen.1001228	null	[ [ "Human structural variation contributes to phenotypic differences and susceptibility to disease [1] .", "Recent studies suggest that many structural variants are mediated by non-allelic homologous recombination ( NAHR ) between dispersed repetitive DNA elements [2]–[5] .", "While the importance of NAH...	[ "Genome rearrangements often result from non-allelic homologous recombination ( NAHR ) between repetitive DNA elements dispersed throughout the genome .", "Here we systematically analyze NAHR between Ty retrotransposons using a genome-wide approach that exploits unique features of Saccharomyces cerevisiae purebre...	[ "The human genome is structurally dynamic , frequently undergoing loss , duplication , and rearrangement of large chromosome segments .", "These structural changes occur both in normal and in cancerous cells and are thought to cause both benign and deleterious changes in cell function .", "Many of these structu...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Membrane-Derived Phospholipids Control Synaptic Neurotransmission and Plasticity	journal.pbio.1002153	Lysophospholipids derived from membranes are important regulators of neurotransmission, acting as local messengers that couple synaptic strength to recent neuronal activity.	[ [ "Activity-dependent plasticity of neuronal networks refers to the adaptive changes in their properties in response to external and internal stimuli .", "In a prominent form of central nervous system ( CNS ) plasticity , synaptic strength results in an increase ( potentiation ) or decrease ( depression ) o...	[ "Synaptic communication is a dynamic process that is key to the regulation of neuronal excitability and information processing in the brain .", "To date , however , the molecular signals controlling synaptic dynamics have been poorly understood .", "Membrane-derived bioactive phospholipids are potential candida...	[ "Neuronal networks are modules of synaptic connectivity that underlie all brain functions , from simple reflexes to complex cognitive processes .", "Synaptic plasticity allows these networks to adapt to changing external and internal environments .", "Membrane-derived bioactive phospholipids are potential candi...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods", "" ]	[ "developmental biology", "computational biology", "evolutionary biology", "genetics and genomics" ]	Evolutionary Plasticity of Polycomb/Trithorax Response Elements in Drosophila Species	journal.pbio.0060261	A combination of computational and experimental approaches reveals surprisingly dynamic evolution of regulatory DNA elements, involving changes not only in motif composition, but also in genomic position and number of elements.	[ [ "cis-Regulatory DNA elements are essential for the correct activation , repression , and maintenance of gene expression .", "These elements typically contain multiple short DNA motifs , which are recognised by sequence-specific DNA binding proteins , that either themselves act as activators and repressors...	[ "cis-Regulatory DNA elements contain multiple binding sites for activators and repressors of transcription .", "Among these elements are enhancers , which establish gene expression states , and Polycomb/Trithorax response elements ( PREs ) , which take over from enhancers and maintain transcription states of seve...	[ "The evolution of regulatory DNA plays a crucial role in making species different from one another .", "One way to study the evolution of regulatory DNA is by genome alignment , which assumes that elements with conserved function will be found in conserved pieces of DNA .", "Although conservation does imply fun...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "transfection", "viral transmission and infection", "microbiology", "parasitic protozoans", "protozoan life cycles", "developmental biology", "trypomastigotes", "protozoans", "molecular biology techniques", "epimastigotes", "research and analysis methods", "specimen preparation and treatment",...	Utilization of proliferable extracellular amastigotes for transient gene expression, drug sensitivity assay, and CRISPR/Cas9-mediated gene knockout in Trypanosoma cruzi	journal.pntd.0007088	null	[ [ "Trypanosoma cruzi is the causative agent of Chagas’ disease , which affects 6–7 million people mainly in Latin America[1] .", "The parasite is transmitted by a reduviid bug through its contaminated feces , and enters into the mammalian host when the bite site is rubbed or scratched .", "Chagas’ disea...	[ "Trypanosoma cruzi has three distinct life cycle stages; epimastigote , trypomastigote , and amastigote .", "Amastigote is the replication stage in host mammalian cells , hence this stage of parasite has clinical significance in drug development research .", "Presence of extracellular amastigotes ( EA ) and the...	[ "We developed an experimental system to study amastigote stage of Trypanosoma cruzi as a proliferable axenic culture .", "Use of axenic amastigotes allows us to directly introduce exogenous gene into T . cruzi amastigote and select for drug resistant parasite to enrich the transfectants .", "Our strategy bypass...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dermatology/pediatric skin diseases, including genetic diseases", "infectious diseases/neglected tropical diseases", "dermatology/skin infections", "public health and epidemiology/infectious diseases", "infectious diseases/skin infections", "public health and epidemiology/screening", "infectious diseas...	A Regional Initiative to Reduce Skin Infections amongst Aboriginal Children Living in Remote Communities of the Northern Territory, Australia	journal.pntd.0000554	null	[ [ "Pyoderma is a generic term used to describe a clinical diagnosis of superficial bacterial skin infection [1] .", "Also known as skin sores or impetigo , it has been estimated that there are in excess of 111 million children with pyoderma worldwide and that many of these children will also have scabies [1...	[ "Linked to extreme rates of chronic heart and kidney disease , pyoderma is endemic amongst Aboriginal children in Australia's Northern Territory ( NT ) .", "Many of those with pyoderma will also have scabies .", "We report the results of a community-based collaboration within the East Arnhem Region , which aime...	[ "Skin infections are endemic in many in remote Australian Aboriginal communities and have been linked to very high rates of chronic heart and kidney disease in this population .", "We report the results of a regional collaboration that aimed to reduce skin infections amongst children aged less than 15 years in fi...	2009
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "molecular biology/chromatin structure", "microbiology/parasitology" ]	Toxoplasma gondii Lysine Acetyltransferase GCN5-A Functions in the Cellular Response to Alkaline Stress and Expression of Cyst Genes	journal.ppat.1001232	null	[ [ "Stress responses are critical to cell survival , allowing cells to adapt to changing environmental conditions .", "In certain pathogenic eukaryotes , such as the protozoan Toxoplasma gondii ( phylum Apicomplexa ) , the stress response takes on added significance as it triggers a developmental change into...	[ "Parasitic protozoa such as the apicomplexan Toxoplasma gondii progress through their life cycle in response to stimuli in the environment or host organism .", "Very little is known about how proliferating tachyzoites reprogram their expressed genome in response to stresses that prompt development into latent bra...	[ "Protozoan parasites cause significant disease in humans and livestock , and many of our current therapies have serious side effects or are being rendered useless due to the development of drug resistance .", "These parasites typically have complex life cycles involving multiple hosts and some , like Toxoplasma g...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "infectious diseases/gastrointestinal infections", "infectious diseases/antimicrobials and drug resistance", "microbiology" ]	Key Role of Mfd in the Development of Fluoroquinolone Resistance in Campylobacter jejuni	journal.ppat.1000083	null	[ [ "Campylobacter jejuni , a Gram-negative microaerobic bacterium , is one of the most prevalent bacterial foodborne pathogens in humans , causing more than 2 million cases of diarrhea each year in the U . S . alone [1] , [2] , [3] .", "As an enteric pathogen , this organism causes watery diarrhea and/or hem...	[ "Campylobacter jejuni is a major food-borne pathogen and a common causative agent of human enterocolitis .", "Fluoroquinolones are a key class of antibiotics prescribed for clinical treatment of enteric infections including campylobacteriosis , but fluoroquinolone-resistant Campylobacter readily emerges under the...	[ "As a food-borne bacterial pathogen , Campylobacter jejuni is a common causative agent of gastrointestinal illnesses in humans .", "Development of antibiotic resistance in Campylobacter , especially to fluoroquinolone ( a broad-spectrum antimicrobial ) , compromises clinical treatments and presents a major public...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Risk Factors for Visceral Leishmaniasis Relapse in Immunocompetent Patients following Treatment with 20 mg/kg Liposomal Amphotericin B (Ambisome) in Bihar, India	journal.pntd.0002536	null	[ [ "Visceral leishmaniasis ( VL ) is a neglected tropical disease that results in the loss of an estimated 1 million disability-adjusted life years annually in South East Asia [1]; it is typically fatal if untreated .", "VL predominantly affects the poorest strata of society and those with limited access to ...	[ "A proportion of all immunocompetent patients treated for visceral leishmaniasis ( VL ) are known to relapse; however , the risk factors for relapse are not well understood .", "With the support of the Rajendra Memorial Research Institute ( RMRI ) , Médecins Sans Frontières ( MSF ) implemented a program in Bihar ...	[ "Visceral leishmaniasis ( VL ) , also known as Kala azar , accounts for the second-highest burden of parasitic disease worldwide .", "Fifty percent of VL cases worldwide occur in India , and up to 90% of these in the state of Bihar .", "Up to 10% of VL patients relapse within 6 months of treatment , particularl...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "medicine", "gene expression", "genetics", "cancer treatment", "biology", "genetics and genomics" ]	Gene Reactivation by 5-Aza-2′-Deoxycytidine–Induced Demethylation Requires SRCAP–Mediated H2A.Z Insertion to Establish Nucleosome Depleted Regions	journal.pgen.1002604	null	[ [ "The eukaryotic genome is compacted into chromatin and associated proteins .", "The fundamental repeating unit of chromatin is the nucleosome , which contains ∼147 bp of DNA wrapped around a histone protein octamer [1] .", "However , chromatin conformations change during various cellular processes , s...	[ "5-Aza-2′-deoxycytidine , approved by the FDA for the treatment of myelodysplastic syndrome ( MDS ) , is incorporated into the DNA of dividing cells where it specifically inhibits DNA methylation by forming covalent complexes with the DNA methyltransferases ( DNMTs ) .", "In an effort to study the correlations be...	[ "Epigenetic changes , which include chemical modifications to the DNA and changes in the proteins that package DNA to fit into a cell , play an important role in gene expression regulation .", "The fact that a number of abnormal epigenetic changes that lead to the silencing of genes occur during tumorigenesis has...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "drugs and devices", "neglected tropical diseases", "veterinary science", "veterinary medicine" ]	Efficacy and Safety of Artemether in the Treatment of Chronic Fascioliasis in Egypt: Exploratory Phase-2 Trials	journal.pntd.0001285	null	[ [ "Fascioliasis , a zoonotic disease caused by a liver fluke infection of the species Fasciola hepatica and F . gigantica , is of considerable veterinary and public health importance [1] , [2] .", "Owing to global changes , infections with Fasciola spp .", "appear to be emerging or re-emerging in severa...	[ "Fascioliasis is an emerging zoonotic disease of considerable veterinary and public health importance .", "Triclabendazole is the only available drug for treatment .", "Laboratory studies have documented promising fasciocidal properties of the artemisinins ( e . g . , artemether ) .", "We carried out two expl...	[ "Fasciola hepatica and F . gigantica are two liver flukes that parasitize herbivorous large size mammals ( e . g . , sheep and cattle ) , as well as humans .", "A single drug is available to treat infections with Fasciola flukes , namely , triclabendazole .", "Recently , laboratory studies and clinical trials i...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "chromosome biology", "biology", "genomics", "genetics and genomics" ]	A Novel Mouse Synaptonemal Complex Protein Is Essential for Loading of Central Element Proteins, Recombination, and Fertility	journal.pgen.1002088	null	[ [ "Meiosis is a special type of cell division which gives rise to haploid , genetically diverse gametes .", "For organisms that reproduce sexually the correct haploidization of paternal and maternal genomes is of utmost importance .", "To ensure the correct separation of homologous chromosomes during an...	[ "The synaptonemal complex ( SC ) is a proteinaceous , meiosis-specific structure that is highly conserved in evolution .", "During meiosis , the SC mediates synapsis of homologous chromosomes .", "It is essential for proper recombination and segregation of homologous chromosomes , and therefore for genome haplo...	[ "Meiosis is a special type of cell division that takes place in the germ line of sexually reproducing diploid organisms .", "Major events during meiosis are the pairing , recombination , and segregation of homologous chromosomes .", "As a consequence , daughter cells are haploid and genetically diverse .", "T...	2011
[ "Introduction", "Results", "Discussion" ]	[ "simulation languages", "community structure", "computerized simulations", "marine biology", "corals", "coral reefs", "marine and aquatic sciences", "biology", "community ecology", "computer science", "programming languages", "ecology", "marine ecology", "species interactions" ]	Simulations of Long-Term Community Dynamics in Coral Reefs - How Perturbations Shape Trajectories	journal.pcbi.1002791	null	[ [ "Tropical coral reefs are highly productive but also fragile ecosystems that provide habitats for the coastal fauna and multiple services to local human communities [1] .", "Due to their high biodiversity , they exhibit a complex pattern of interactions between organisms and their environment with feedbac...	[ "Tropical coral reefs feature extraordinary biodiversity and high productivity rates in oligotrophic waters .", "Due to increasing frequencies of perturbations – anthropogenic and natural – many reefs are under threat .", "Such perturbations often have devastating effects on these unique ecosystems and especial...	[ "The degradation of coral reefs is a major threat for tropical coastal environments , worldwide .", "For this reason we developed a spatially explicit model which simulates competition in a benthic reef community under the influence of various environmental factors .", "Here we highlight the impact of two major...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/disease models", "genetics and genomics/complex traits", "genetics and genomics/bioinformatics", "genetics and genomics/population genetics" ]	Designing Genome-Wide Association Studies: Sample Size, Power, Imputation, and the Choice of Genotyping Chip	journal.pgen.1000477	null	[ [ "The International HapMap project [1] , [2] documented the strong correlations between alleles at polymorphic loci in close physical proximity along human chromosomes .", "As a consequence it is necessary to genotype only a subset of loci to capture much of the common variation in the genome .", "Comb...	[ "Genome-wide association studies are revolutionizing the search for the genes underlying human complex diseases .", "The main decisions to be made at the design stage of these studies are the choice of the commercial genotyping chip to be used and the numbers of case and control samples to be genotyped .", "The...	[ "Genome-wide association studies are a powerful and now widely-used method for finding genetic variants that increase the risk of developing particular diseases .", "These studies are complex and must be planned carefully in order to maximize the probability of finding novel associations .", "The main design ch...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "gene expression", "genetics", "biology", "genetics and genomics" ]	Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis	journal.pgen.1003394	null	[ [ "Rheumatoid arthritis ( RA ) is an autoimmune disease characterized by chronic inflammation of the synovial lining of the joint [1] .", "If left untreated , outcome varies from self-limited disease in a small proportion of RA patients to severe disease resulting in profound structural damage , excess morb...	[ "Anti-tumor necrosis factor alpha ( anti-TNF ) biologic therapy is a widely used treatment for rheumatoid arthritis ( RA ) .", "It is unknown why some RA patients fail to respond adequately to anti-TNF therapy , which limits the development of clinical biomarkers to predict response or new drugs to target refract...	[ "There are no genetic predictors of response to one of the most widely used classes of drugs in the treatment of rheumatoid arthritis—biological modifiers of the inflammatory cytokine tumor necrosis factor-alpha ( or anti-TNF therapy ) .", "To identify genetic predictors , we performed the largest genome-wide ass...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/animal genetics", "computational biology/systems biology", "computational biology/transcriptional regulation", "genetics and genomics/gene expression", "molecular biology/bioinformatics", "computational biology/genomics", "genetics and genomics/...	Directed Mammalian Gene Regulatory Networks Using Expression and Comparative Genomic Hybridization Microarray Data from Radiation Hybrids	journal.pcbi.1000407	null	[ [ "Interrogating genome-scale datasets is a necessary step to a systems biology of the mammalian cell [1] , [2] .", "Networks have been constructed using various approaches .", "In the transcriptome , coexpression networks have been constructed by linking genes whose correlations exceed a selected p-val...	[ "Meiotic mapping of quantitative trait loci regulating expression ( eQTLs ) has allowed the construction of gene networks .", "However , the limited mapping resolution of these studies has meant that genotype data are largely ignored , leading to undirected networks that fail to capture regulatory hierarchies .",...	[ "An important problem in systems biology is to map gene networks , which help identify gene functions and discover critical disease pathways .", "Current methods for constructing gene networks have identified a number of biologically significant functional modules .", "However , these networks do not reveal dir...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "hepacivirus", "pathogens", "microbiology", "viral structure", "liver diseases", "viruses", "rna viruses", "pharmaceutics", "gastroenterology and hepatology", "pharmacology", "viral loa...	Modelling how responsiveness to interferon improves interferon-free treatment of hepatitis C virus infection	journal.pcbi.1006335	null	[ [ "Direct-acting antiviral agents ( DAAs ) are revolutionizing the treatment of chronic hepatitis C virus ( HCV ) infection .", "Sustained virological response ( SVR ) rates of over 90% have been achieved in recent clinical trials with all-oral DAA treatments lasting as short as 12 weeks , in striking contr...	[ "Direct-acting antiviral agents ( DAAs ) for hepatitis C treatment tend to fare better in individuals who are also likely to respond well to interferon-alpha ( IFN ) , a surprising correlation given that DAAs target specific viral proteins whereas IFN triggers a generic antiviral immune response .", "Here , we po...	[ "Treatment of hepatitis C virus ( HCV ) infection is seeing a paradigm shift with powerful drugs called direct-acting antiviral agents ( DAAs ) replacing earlier treatments involving interferon ( IFN ) .", "DAAs target specific HCV proteins .", "IFN stimulates our immune response against HCV .", "The two shou...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "immune cells", "immunity", "immunology", "biology", "microbiology", "bacterial pathogens", "immune system" ]	Depletion of Dendritic Cells Enhances Innate Anti-Bacterial Host Defense through Modulation of Phagocyte Homeostasis	journal.ppat.1002552	null	[ [ "Innate immunity as well as adaptive immunity is involved in the response of the host towards pathogens [1]–[3] .", "Dendritic cells ( DCs ) are professional antigen presenting cells playing a central role in immune response by linking the innate and adaptive immunity [4]–[6] .", "The activation of in...	[ "Dendritic cells ( DCs ) as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response .", "However , their role in the innate immune response against bacterial infections is not completely defined .", "Here we have analyzed the role of DCs and ...	[ "Dendritic cells ( DCs ) are professional antigen-presenting cells playing a crucial role in the initiation of T-cell responses to combat infection .", "DCs adapt their immune response according to the type of pathogen .", "For example , in response to intracellular bacteria , DCs produce IL-12 , thereby initia...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "infectious diseases", "molecular cell biology", "immunology", "biology", "microbiology", "evolutionary biology", "proteomics" ]	HIV-1 Capsid-Cyclophilin Interactions Determine Nuclear Import Pathway, Integration Targeting and Replication Efficiency	journal.ppat.1002439	null	[ [ "The ability to infect terminally differentiated cells of the monocyte-macrophage lineage is a conserved property of lentiviruses , including HIV-1 [1] .", "This process requires pre-integration complexes ( PICs ) to traverse the nuclear pore , though the molecular mechanism remains unclear .", "The H...	[ "Lentiviruses such as HIV-1 traverse nuclear pore complexes ( NPC ) and infect terminally differentiated non-dividing cells , but how they do this is unclear .", "The cytoplasmic NPC protein Nup358/RanBP2 was identified as an HIV-1 co-factor in previous studies .", "Here we report that HIV-1 capsid ( CA ) binds...	[ "During infection HIV-1 enters the nucleus by crossing the nuclear membrane and incorporating itself into the host DNA by a process called integration .", "Here we show that the viral capsid protein gets tethered to a cyclophilin protein called Nup358 , a component of the nuclear membrane gateways that allow tran...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "hiv infections", "medicine and health sciences", "immune physiology", "immune cells", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "immunology", "cell processes", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses",...	HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies	journal.ppat.1006987	null	[ [ "Antibodies form a link between the adaptive and innate immune systems and serve as a correlate of protection for many viral vaccines .", "They mediate diverse functions through the use of the Fab portion to bind specific antigens and the Fc portion that interacts with cellular receptors to effect a varie...	[ "While the induction of broadly neutralizing antibodies ( bNAbs ) is a major goal of HIV vaccination strategies , there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection .", "Here we investigated Fc effector functionality of HIV-specific ...	[ "Some HIV-infected individuals develop antibodies that are capable of neutralizing the majority of HIV strains , a highly desirable function mediated by the antibody Fab portion .", "While antibodies elicited by current vaccines have failed to recreate this activity , the partial protection seen in the RV144 vacc...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/macromolecular structure analysis", "computer science", "molecular biology/bioinformatics", "computational biology/macromolecular sequence analysis", "computational biology" ]	Predicting Protein Ligand Binding Sites by Combining Evolutionary Sequence Conservation and 3D Structure	journal.pcbi.1000585	null	[ [ "Sequence-based functional site prediction has been dominated by the search for residue positions that show evidence of evolutionary constraint .", "Amino acid conservation in the columns of a multiple sequence alignment of homologs is the most common source of such estimates ( see [22] for a review ) .",...	[ "Identifying a protein's functional sites is an important step towards characterizing its molecular function .", "Numerous structure- and sequence-based methods have been developed for this problem .", "Here we introduce ConCavity , a small molecule binding site prediction algorithm that integrates evolutionary...	[ "Protein molecules are ubiquitous in the cell; they perform thousands of functions crucial for life .", "Proteins accomplish nearly all of these functions by interacting with other molecules .", "These interactions are mediated by specific amino acid positions in the proteins .", "Knowledge of these “function...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "infectious disease epidemiology", "leishmaniasis", "neglected tropical diseases", "infectious disease control" ]	Epidemiologic Aspects of an Emerging Focus of Visceral Leishmaniasis in Tbilisi, Georgia	journal.pntd.0001415	null	[ [ "Visceral leishmaniasis ( VL ) caused by parasites of the Leishmania donovani complex ( L . donovani , L . infantum/L . chagasi ) is a severe disease with a fatal outcome if left untreated .", "It is clinically characterized by low-grade fever , enlarged spleen and liver , and weight loss .", "Anthrop...	[ "Over the last 15 years , visceral leishmaniasis ( VL ) has emerged as a public health concern in Tbilisi , the capital of Georgia .", "Seroepidemiological surveys were conducted to determine the prevalence and incidence of infection in children and dogs within the main focus of VL , and to identify risk factors ...	[ "Visceral leishmaniasis ( VL ) has emerged as a public health problem in Tbilisi , the capital of Georgia .", "Dogs are the main infection reservoirs for transmission by sand flies of Leishmania infantum to humans , many of whom may become infected without developing disease .", "Since majority of cases are in ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	EBV BART MicroRNAs Target Multiple Pro-apoptotic Cellular Genes to Promote Epithelial Cell Survival	journal.ppat.1004979	null	[ [ "MicroRNAs ( miRNAs ) are 22 ± 2 nucleotide ( nt ) non-coding RNAs that are expressed by all multicellular eukaryotes as well as by several viruses [1–3] .", "MiRNAs are generally initially transcribed by RNA polymerase II in the form of a long primary miRNA ( pri-miRNA ) precursor that is sequentially pr...	[ "Epstein-Barr virus ( EBV ) is a ubiquitous human γ-herpesvirus that can give rise to cancers of both B-cell and epithelial cell origin .", "In EBV-induced cancers of epithelial origin , including nasopharyngeal carcinomas ( NPCs ) and gastric carcinomas , the latent EBV genome expresses very high levels of a clu...	[ "One important innate immune response to viral infection is apoptosis , also called programmed cell death , whereby the infected cells commit suicide rather than serve as factories for virus production .", "As a result , many viruses have developed strategies to inhibit apoptosis .", "Here , we demonstrate that...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immunology", "messenger rna", "cancers and neoplasms", "cell processes", "rna extraction", "dna-binding proteins", "oncology", "hematologic cancers and related disorders", "immunoprecipitation", "lymphomas", "co-immunoprecipit...	An essential EBV latent antigen 3C binds Bcl6 for targeted degradation and cell proliferation	journal.ppat.1006500	null	[ [ "B-cell development through the germinal center ( GC ) is controlled strictly by sequential activation or repression of crucial transcription factors , executing the pre- and post-GC B-cell differentiation [1] .", "The deregulation of induced GC reactions during B-cell development is associated with malig...	[ "The latent EBV nuclear antigen 3C ( EBNA3C ) is required for transformation of primary human B lymphocytes .", "Most mature B-cell malignancies originate from malignant transformation of germinal center ( GC ) B-cells .", "The GC reaction appears to have a role in malignant transformation , in which a major pl...	[ "Epstein-Barr virus ( EBV ) is the first characterized human tumor virus , which is associated with a broad range of human cancers .", "One of the latent proteins , EBV encoded nuclear antigen 3C ( EBNA3C ) plays a critical role in EBV-mediated B-cell transformation .", "Bcl6 is a master regulator required in m...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacterial genomics", "organismal evolution", "microbial mutation", "microbial evolution", "genetics", "biology and life sciences", "microbiology", "genomics", "evolutionary biology", "bacterial evolution", "microbial genomics" ]	Coexistence and Within-Host Evolution of Diversified Lineages of Hypermutable Pseudomonas aeruginosa in Long-term Cystic Fibrosis Infections	journal.pgen.1004651	null	[ [ "The opportunistic pathogen Pseudomonas aeruginosa is found in many environments and can cause acute or chronic infections in a range of hosts from protozoans to plants to humans [1] , [2] .", "In particular , patients with cystic fibrosis ( CF ) are highly susceptible to chronic colonization by P . aerug...	[ "The advent of high-throughput sequencing techniques has made it possible to follow the genomic evolution of pathogenic bacteria by comparing longitudinally collected bacteria sampled from human hosts .", "Such studies in the context of chronic airway infections by Pseudomonas aeruginosa in cystic fibrosis ( CF )...	[ "Patients with cystic fibrosis ( CF ) are often colonized by a single clone of the common , widespread bacterium Pseudomonas aeruginosa , resulting in chronic airway infections .", "Long-term persistence of the bacteria involves the emergence and selection of multiple phenotypic variants .", "Among these are “m...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "immunology/innate immunity", "infectious diseases/viral infections", "infectious diseases/respiratory infections", "immunology/immunity to infections" ]	Co-ordinated Role of TLR3, RIG-I and MDA5 in the Innate Response to Rhinovirus in Bronchial Epithelium	journal.ppat.1001178	null	[ [ "Human rhinovirus ( RV ) belongs to the Picornaviridae family and are implicated in an extensive range of human respiratory disorders including the common cold , viral bronchiolitis , and exacerbations of asthma and chronic obstructive pulmonary disease [1]–[5] .", "RV are classified as major or minor gro...	[ "The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA helicases RIG-I and MDA5 in viral infection is much debated .", "We investigated the roles of each pattern recognition receptor in rhinovirus infection using primary bronchial epithelial cells .", "TLR3 was constitutively expressed; howe...	[ "Host-pathogen interactions are mediated by pattern recognition receptors that identify conserved structures of micro-organisms that are distinct from self .", "During a viral infection , important pattern recognition receptors include the endosomal Toll-like receptors ( TLRs ) , and a second set of cytoplasmic p...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "infectious diseases of the nervous system", "herpes simplex", "neurology", "neurological disorders", "viral diseases", "encephalitis" ]	The Calcitonin Receptor Gene Is a Candidate for Regulation of Susceptibility to Herpes simplex Type 1 Neuronal Infection Leading to Encephalitis in Rat	journal.ppat.1002753	null	[ [ "Herpes simplex type 1 virus ( HSV-1 ) is a member of the Herpesviridae family ( Alphaherpesvirinae subfamily ) that infects a large fraction of humans resulting in transient cold sores or non-symptomatic infection that persists lifelong in the sensory ganglia .", "Recurrent herpetic disease results from ...	[ "Herpes simplex encephalitis ( HSE ) is a fatal infection of the central nervous system ( CNS ) predominantly caused by Herpes simplex virus type 1 .", "Factors regulating the susceptibility to HSE are still largely unknown .", "To identify host gene ( s ) regulating HSE susceptibility we performed a genome-wid...	[ "Herpes simplex encephalitis ( HSE ) is a rare , but severe infection of the central nervous system ( CNS ) caused by Herpes simplex virus type 1 .", "We have previously characterized a model for HSE in the inbred DA rat which resembles human HSE .", "Interestingly the inbred PVG rat is completely resistant to ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "plant evolution", "virology", "plant pathogens", "plant biology", "plant pathology", "biology", "microbiology", "viral evolution" ]	Widespread Endogenization of Genome Sequences of Non-Retroviral RNA Viruses into Plant Genomes	journal.ppat.1002146	null	[ [ "Events of horizontal gene transfer ( HGT ) have been identified between various combinations of viruses and their eukaryotic hosts .", "HGT can occur during evolution in 2 inverse directions: “from host to virus” or “from virus to host . ”", "In the host to virus direction , viral acquisition of host...	[ "Non-retroviral RNA virus sequences ( NRVSs ) have been found in the chromosomes of vertebrates and fungi , but not plants .", "Here we report similarly endogenized NRVSs derived from plus- , negative- , and double-stranded RNA viruses in plant chromosomes .", "These sequences were found by searching public gen...	[ "Eukaryotic genomes contain sequences that have originated from DNA viruses and reverse-transcribing viruses , i . e . , retroviruses , pararetroviruses ( DNA viruses ) , and transposons .", "However , the sequences of non-retroviral RNA viruses , which are unable to convert their genomes to DNA , were until rece...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "crystal structure", "monomers", "condensed matter physics", "geometry", "mathematics", "materials science", "protein structure", "crystallography", "oligomers", "polymer chemistry", "contractile proteins", "actins", "solid state physics", "proteins", "dimers", "chemistry", "biophysi...	Conservation of conformational dynamics across prokaryotic actins	journal.pcbi.1006683	null	[ [ "The eukaryotic cytoskeleton , which is critical for many cellular functions such as cargo transport and morphogenesis , is comprised of three major elements: actin , tubulin , and intermediate filaments .", "These proteins bind nucleotides and form highly dynamic polymers [1] .", "Each of these prote...	[ "The actin family of cytoskeletal proteins is essential to the physiology of virtually all archaea , bacteria , and eukaryotes .", "While X-ray crystallography and electron microscopy have revealed structural homologies among actin-family proteins , these techniques cannot probe molecular-scale conformational dyn...	[ "Simulations are a critical tool for uncovering the molecular mechanisms underlying biological form and function .", "Here , we use molecular-dynamics simulations to identify common and specific dynamical behaviors in four prokaryotic homologs of actin , a cytoskeletal protein that plays important roles in cellul...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "dermatology", "medicine and health sciences", "clinical research design", "synthetic biology", "immunology", "microbiology", "pediatrics", "research design", "developmental biology", "clinical medicine", "global health", "veterinary science", "veterinary medicine", "research and analysis ...	Easy Identification of Leishmania Species by Mass Spectrometry	journal.pntd.0002841	null	[ [ "Cutaneous leishmaniasis ( CL ) affects 1 . 5 million patients each year and displays a wide spectrum of clinical forms from small self-resolving papules to severe destructive mucosal lesions .", "The infecting Leishmania species influence the clinical presentation of CL [1] but lesion characteristics are...	[ "Cutaneous leishmaniasis is caused by several Leishmania species that are associated with variable outcomes before and after therapy .", "Optimal treatment decision is based on an accurate identification of the infecting species but current methods to type Leishmania isolates are relatively complex and/or slow ."...	[ "Cutaneous leishmaniasis is a disease due to a small parasite called Leishmania .", "This parasite causes disfiguring skin lesions that last for months or years .", "There are many different subtypes of Leishmania , each giving rise to lesions of different severity and responding to therapies in its own way .",...	2014
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "taxonomy", "database searching", "phylogenetics", "data management", "protein structure", "sequence motif analysis", "protein structure databases", "sequence similarity searching", "research and analysis methods", "sequence analysis", "computer and information sciences", "bioinformatics", "...	An Atlas of Peroxiredoxins Created Using an Active Site Profile-Based Approach to Functionally Relevant Clustering of Proteins	journal.pcbi.1005284	null	[ [ "Peroxiredoxins ( Prxs ) are a large and ubiquitous superfamily of thiol dependent peroxidases , which have long been known to be involved in the reduction of aliphatic and aromatic hydroperoxides and peroxynitrite in biological systems [1–3] .", "Historically , these proteins have also been called TSA ( ...	[ "Peroxiredoxins ( Prxs or Prdxs ) are a large protein superfamily of antioxidant enzymes that rapidly detoxify damaging peroxides and/or affect signal transduction and , thus , have roles in proliferation , differentiation , and apoptosis .", "Prx superfamily members are widespread across phylogeny and multiple m...	[ "Peroxiredoxins ( Prxs ) are a large , ubiquitous superfamily of proteins that are arguably the most important reductants of peroxide in biological systems .", "These proteins are involved in a diverse array of essential cellular functions , including peroxide reduction , signal transduction , circadian rhythms ,...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Auxin-Mediated Transcriptional System with a Minimal Set of Components Is Critical for Morphogenesis through the Life Cycle in Marchantia polymorpha	journal.pgen.1005084	The liverwort Marchantia polymorpha has a minimal but required repertoire of components for auxin-mediated transcriptional regulation, which is sufficient for achieving the simple yet multi-dimensional body plan.	[ [ "In angiosperms , the plant hormone auxin regulates many aspects of growth and development such as axis formation during embryogenesis [1] , initiation of leaf primordia at the shoot apical meristem [2] , root development [3] , and tropic responses to light or gravity [4 , 5] .", "A major auxin-signaling ...	[ "The plant hormone auxin regulates many aspects of plant growth and development .", "Recent progress in Arabidopsis provided a scheme that auxin receptors , TIR1/AFBs , target transcriptional co-repressors , AUX/IAAs , for degradation , allowing ARFs to regulate transcription of auxin responsive genes .", "The ...	[ "Auxin is an important plant hormone which regulates many aspects of plant growth and development , such as embryogenesis and directional growth in response to light or gravity .", "Recent molecular genetics advances in angiosperms revealed that transcriptional regulation is critical for auxin response .", "Alt...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology/animal genetics", "evolutionary biology/evolutionary and comparative genetics", "evolutionary biology/sexual behavior", "genetics and genomics/disease models", "genetics and genomics/population genetics", "genetics and genomics", "evolutionary biology/developmental evolution" ]	Widespread Presence of Human BOULE Homologs among Animals and Conservation of Their Ancient Reproductive Function	journal.pgen.1001022	null	[ [ "Evolution of sexual reproduction , consisting of the origin and maintenance of sex , has been a central focus of evolutionary biology since the time of Darwin .", "The origin of sex has generally been simplified to the question of the origin of meiosis , which is known to have a single origin among all e...	[ "Sex-specific traits that lead to the production of dimorphic gametes , sperm in males and eggs in females , are fundamental for sexual reproduction and accordingly widespread among animals .", "Yet the sex-biased genes that underlie these sex-specific traits are under strong selective pressure , and as a result ...	[ "While sexual reproduction is widespread among animals , it remains enigmatic to what extent sexual reproduction is conserved and when sex-specific gametogenesis ( spermatogenesis and oogenesis ) originated in animals .", "Here we demonstrate the presence of the reproductive-specific protein Boule throughout bila...	2010
[ "Introduction", "Results", "Discussion", "Methods and Materials" ]	[ "genome analysis tools", "functional genomics", "genetic screens", "microbial pathogens", "biology", "genomics", "microbiology", "microbial growth and development", "genetics and genomics" ]	Global Assessment of Genomic Regions Required for Growth in Mycobacterium tuberculosis	journal.ppat.1002946	null	[ [ "Mutagenesis has long been a powerful tool for understanding the roles of genes and other chromosomal elements .", "Recently , high-density transposon insertion mutagenesis coupled with deep sequencing has enabled comprehensive identification of the required genes in many important bacterial pathogens [1]...	[ "Identifying genomic elements required for viability is central to our understanding of the basic physiology of bacterial pathogens .", "Recently , the combination of high-density mutagenesis and deep sequencing has allowed for the identification of required and conditionally required genes in many bacteria .", ...	[ "The significant rise in drug resistant strains of Mycobacterium tuberculosis has highlighted the need for new drug targets .", "Here , we present a novel method of defining genetic elements required for optimal growth , a key first step for identifying potential drug targets .", "Similar strategies in other ba...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Functional Brachyury Binding Sites Establish a Temporal Read-out of Gene Expression in the Ciona Notochord	journal.pbio.1001697	During notochord formation in chordate embryos, the transcription factor Brachyury employs different regulatory strategies to ensure the sequential activation of downstream genes and thereby the deployment of a specific developmental program at the right time and place.	[ [ "The transcription factor Brachyury plays a paramount role in mesoderm formation in animals with widely diverse body plans [1] , [2] .", "In chordate embryos ranging from sea squirts to mice , Brachyury is required for the formation of the notochord from axial mesoderm [3] , [4] .", "In addition to it...	[ "The appearance of the notochord represented a milestone in Deuterostome evolution .", "The notochord is necessary for the development of the chordate body plan and for the formation of the vertebral column and numerous organs .", "It is known that the transcription factor Brachyury is required for notochord fo...	[ "Transcription factors control where and when gene expression is switched on by binding to specific stretches of DNA known as cis-regulatory modules ( CRMs ) .", "In this study , we investigated the architecture and composition of CRMs that direct gene expression in the notochord—a transient rod-like structure fo...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "nervous system", "population genetics", "neuroscience", "gene pool", "developmental biology", "nerve fibers", "population biology", "embryos", "immunologic techniques", "morphogenesis", "research and analysis methods", "embryology", "spinal cord", "muscul...	Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis	journal.pbio.2004734	null	[ [ "Neuromuscular morphogenesis involves complex tissue interactions simultaneously governing the generation of skeletal muscles and the production of the somatic motor neurons ( MNs ) that innervate them .", "Both processes independently rely on the execution of a generic regulatory program sequentially lea...	[ "Muscle morphogenesis is tightly coupled with that of motor neurons ( MNs ) .", "Both MNs and muscle progenitors simultaneously explore the surrounding tissues while exchanging reciprocal signals to tune their behaviors .", "We previously identified the Fat1 cadherin as a regulator of muscle morphogenesis and s...	[ "Fat cadherins are evolutionarily conserved cell adhesion molecules , which play key roles in modulating tissue morphogenesis through the control of collective cell behavior and polarity .", "We previously identified the mouse Fat1 gene as a regulator of muscle morphogenesis and reported a role for this gene in m...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "immunology", "tropical diseases", "cloning", "bacterial diseases", "developmental biology", "molecular development", "molecular biology techniques", "infectious disease...	Patients with Tuberculosis Have a Dysfunctional Circulating B-Cell Compartment, Which Normalizes following Successful Treatment	journal.ppat.1005687	null	[ [ "Human B-cells not only mediate humoral immunity but are also key players in the initiation and regulation of T-cell responses .", "B-cells can act as professional antigen presenting cells , provide co-stimulatory signals , produce cytokines and can exert immunoregulatory properties .", "Antigen uptak...	[ "B-cells not only produce immunoglobulins and present antigens to T-cells , but also additional key roles in the immune system .", "Current knowledge on the role of B-cells in infections caused by intracellular bacteria is fragmentary and contradictory .", "We therefore analysed the phenotypical and functional ...	[ "In infections with intracellular pathogens like Mycobacterium tuberculosis ( Mtb ) , B-cells have long been ignored as their primary product , immunoglobulins , are unlikely to recognize intracellular bacteria .", "However , we have analysed here the frequency , phenotype and function of B-cells in tuberculosis ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetic networks", "quantitative trait loci", "variant genotypes", "quantitative traits", "genetic mapping", "epistasis", "mathematics", "statistics (mathematics)", "test statistics", "genome analysis", "network analysis", "research and analysis methods", "computer and information sciences"...	Functional Regression Models for Epistasis Analysis of Multiple Quantitative Traits	journal.pgen.1005965	null	[ [ "In the past several years , we have witnessed remarkable progresses in the development of methodologies for identification of epistasis that detect deviation from summation of genetic additive effects for a quantitative trait [1] .", "The classical approach to epistasis analysis is a single variant test ...	[ "To date , most genetic analyses of phenotypes have focused on analyzing single traits or analyzing each phenotype independently .", "However , joint epistasis analysis of multiple complementary traits will increase statistical power and improve our understanding of the complicated genetic structure of the comple...	[ "The widely used statistical methods test interaction for single phenotype .", "However , we often observe pleotropic genetic interaction effects .", "The simultaneous gene-gene ( GxG ) interaction analysis of multiple complementary traits will increase statistical power to detect GxG interactions .", "Althou...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/morphogenesis and cell biology", "cell biology/cell signaling", "cell biology/morphogenesis and cell biology", "cell biology/developmental molecular mechanisms", "developmental biology/molecular development", "developmental biology/organogenesis", "developmental biology/developmen...	A RAC/CDC-42–Independent GIT/PIX/PAK Signaling Pathway Mediates Cell Migration in C. elegans	journal.pgen.1000269	null	[ [ "The GIT/PIX/PAK signaling pathway is a highly conserved signaling module which controls cytoskeletal dynamics across metazoans .", "The functions of this signaling complex are diverse .", "In humans it controls the migrations of fibroblasts through modulation of adhesion complexes , and participates ...	[ "P21 activated kinase ( PAK ) , PAK interacting exchange factor ( PIX ) , and G protein coupled receptor kinase interactor ( GIT ) compose a highly conserved signaling module controlling cell migrations , immune system signaling , and the formation of the mammalian nervous system .", "Traditionally , this signali...	[ "Cell migration is essential for the development and maintenance of metazoan tissue .", "A migrating cell must navigate through complex environments and properly interpret the signals present in its path .", "This cellular movement is accomplished through transduction of the signals into directed reorganization...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "in vitro", "homo (human)", "genetics and genomics" ]	Allele-Specific Chromatin Immunoprecipitation Studies Show Genetic Influence on Chromatin State in Human Genome	journal.pgen.0030081	null	[ [ "Polymorphisms and quantitative differences in gene expression provide the genetic basis for human variation .", "Studies in humans and other organisms suggest that variation at the transcript level accounts for the majority of the phenotypic variation among species and across individuals within species [...	[ "Several recent studies have shown a genetic influence on gene expression variation , including variation between the two chromosomes within an individual and variation between individuals at the population level .", "We hypothesized that genetic inheritance may also affect variation in chromatin states .", "To...	[ "Human health and disease are determined by an interaction between genetic background and environmental exposures .", "Both normal development and disease are mediated by epigenetic regulation of gene expression .", "The epigenetic regulation causes heritable changes in gene expression , which is not associated...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "saccharomyces", "computational biology" ]	A Nucleosome-Guided Map of Transcription Factor Binding Sites in Yeast	journal.pcbi.0030215	null	[ [ "Finding functional DNA binding sites of transcription factors ( TFs ) throughout the genome is a necessary step in understanding transcriptional regulation .", "However , despite an explosion of TF binding data from high-throughput technologies like ChIP-chip ( [1 , 2] , and many more ) , DIP-chip [3] , ...	[ "Finding functional DNA binding sites of transcription factors ( TFs ) throughout the genome is a crucial step in understanding transcriptional regulation .", "Unfortunately , these binding sites are typically short and degenerate , posing a significant statistical challenge: many more matches to known TF motifs ...	[ "Identifying transcription factor ( TF ) binding sites across the genome is an important problem in molecular biology .", "Large-scale discovery of TF binding sites is usually carried out by searching for short DNA patterns that appear often within promoter regions of genes that are known to be co-bound by a TF ....	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "metabolomics", "medicine and health sciences", "pathology and laboratory medicine", "host-pathogen interactions", "biology and life sciences", "pathogenesis", "metabolism" ]	Metabolic Responses to Orientia tsutsugamushi Infection in a Mouse Model	journal.pntd.0003427	null	[ [ "Orientia tsutsugamushi , a mite-borne disease , is the causative agent of scrub typhus ( tsutsugamushi disease ) , the most prevalent febrile illness in the Asia-Pacific region [1] , [2] .", "This disease is characterized by fever , exanthematous rash , eschar , pneumonitis , meningitis , myalgia , and d...	[ "Tsutsugamushi disease is an infectious disease transmitted to humans through the bite of the Orientia tsutsugamushi-infected chigger mite; however , host-pathogen interactions and the precise mechanisms of damage in O . tsutsugamushi infections have not been fully elucidated .", "Here , we analyzed the global me...	[ "Scrub typhus is an acute febrile illness caused by attacks of Orientia tsutsugamushi-carrying mites , and is the most prevalent febrile illness in the Asia-Pacific region .", "If not properly treated with antibiotics , patients often develop severe vasculitis that affects multiple organs , and the mortality rate...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels	journal.pgen.1005014	null	[ [ "Interphase genome organization in eukaryotic cells is non-random [1 , 2 , 3] .", "Indeed , organization of the genome is crucial because it influences nuclear shape and processes such as DNA repair and replication , as well as gene expression [4 , 5 , 6] .", "While chromosomes are highly organized wi...	[ "The spatial organization of chromosomes within interphase nuclei", "is important for gene expression and epigenetic inheritance .", "Although", "the extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types , it is unclear how...	[ "The Cap-H2 condensin II subunit is required for interphase condensin II activity .", "Previous work has shown that low levels of Cap-H2 protein in interphase is achieved by SCFSlimb mediated protein turnover and limits chromatin-bound protein levels .", "Here we show that Casein Kinase I alpha ( CK1α ) is also...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "ecology and environmental sciences", "surface water", "microbiome", "rivers", "community structure", "microbiology", "data management", "metagenomics", "aquatic environments", "bodies of water", "microbial genomics", "research and analysis methods", "hydrology", "sequence an...	Latent environment allocation of microbial community data	journal.pcbi.1006143	null	[ [ "Microbial communities are present worldwide in almost all possible environments .", "Because the composition ( structure ) of a microbial community and its surrounding environment are closely related to each other , it is important to understand what kinds of structural patterns are possible and how envi...	[ "As data for microbial community structures found in various environments has increased , studies have examined the relationship between environmental labels given to retrieved microbial samples and their community structures .", "However , because environments continuously change over time and space , mixed stat...	[ "In the past decade , microbiomes from various natural and human symbiotic environments have been thoroughly studied .", "However , our knowledge is limited as to what types of environments affect the structure of a microbial community .", "In the first place , how can we define “environments” , in particular ,...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "protein transport", "medicine and health sciences", "crystal structure", "pathology and laboratory medicine", "chemical compounds", "pathogens", "cell processes", "condensed matter physics", "microbiology", "organic compounds", "physiological processes", "bacterial diseases"...	Structural and functional dissection reveals distinct roles of Ca2+-binding sites in the giant adhesin SiiE of Salmonella enterica	journal.ppat.1006418	null	[ [ "Salmonella enterica is a food-borne Gram-negative pathogen which causes self-limiting gastroenteritis .", "To survive inside the host , Salmonella possesses sophisticated virulence factors and protein secretion systems [1] .", "A Salmonella pathogenicity island ( SPI ) 1-encoded type 3 secretion syst...	[ "The giant non-fimbrial adhesin SiiE of Salmonella enterica mediates the first contact to the apical site of epithelial cells and enables subsequent invasion .", "SiiE is a 595 kDa protein composed of 53 repetitive bacterial immunoglobulin ( BIg ) domains and the only known substrate of the SPI4-encoded type 1 se...	[ "The interaction of Salmonella enterica with polarized epithelial cells depends on the function of SiiE , a 595 kDa adhesin containing 53 repeats of a bacterial immunoglobulin ( BIg ) domain .", "SiiE is secreted and surface-expressed by a cognate type I secretion system ( T1SS ) .", "We found that BIg domains ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cellular stress responses", "monomers", "cell processes", "fungi", "sumoylation", "mapk signaling cascades", "polymer chemistry", "stress signaling cascade", "proteins", "chemistry", "yeast", "biochemistry", "signal transduction", "eukaryota", "cell biology", "post-translational modif...	Osmolyte accumulation regulates the SUMOylation and inclusion dynamics of the prionogenic Cyc8-Tup1 transcription corepressor	journal.pgen.1008115	null	[ [ "Cellular stresses are abiotic perturbations that can severely and irreversibly damage biomolecules and essential cell structures .", "All organisms experience cellular stress and subsequently must adjust a variety of cellular programs to reestablish homeostasis .", "Many of these include signal trans...	[ "Environmental stressors can severely perturb cellular homeostasis and compromise viability .", "To cope with environmental stressors , eukaryotes have developed distinct signaling programs that allow for adaptation during different stress conditions .", "These programs often require a host of post-translationa...	[ "The ability to sense and react to diverse environmental cues is a central aspect in the maintenance of cellular homeostasis .", "In response to harsh conditions , cells must rapidly deploy specific stress responses in order to adapt , survive , and proliferate .", "To ensure optimal spatial and temporal contro...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "plant science", "emerging infectious diseases", "infectious disease epidemiology", "epidemiology", "vector biology", "disease dynamics", "screening guidelines", "plant pathology", "biology and life sciences", "vector-borne diseases", "i...	Quantifying the Contribution of Hosts with Different Parasite Concentrations to the Transmission of Visceral Leishmaniasis in Ethiopia	journal.pntd.0003288	null	[ [ "An important factor influencing the transmission dynamics of Vector-Borne Diseases ( VBDs ) is the contribution of hosts with different parasitemia ( no . of parasites per ml of blood ) to the infected vector population ( the Host Infectiousness Profile , HIP ) [1] , [2] .", "Identifying the hosts that c...	[ "An important factor influencing the transmission dynamics of vector-borne diseases is the contribution of hosts with different parasitemia ( no . of parasites per ml of blood ) to the infected vector population .", "Today , estimation of this contribution is often impractical since it relies exclusively on limit...	[ "An important factor influencing the transmission dynamics of vector-borne diseases is the contribution of hosts with different parasitemia ( no . of parasites per ml of blood ) to the infected vector population .", "In this study we developed a novel mechanistic model that facilitates the quantification of this ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome expression analysis", "genome evolution", "animal models", "drosophila melanogaster", "model organisms", "molecular cell biology", "chromatin", "chromosome biology", "gene expression", "comparative genomics", "biology", "evolutionary genetics", "microarrays", "cell biology", "gen...	Faster-X Evolution of Gene Expression in Drosophila	journal.pgen.1003013	null	[ [ "Comparing the evolutionary rates of X-linked ( or Z-linked ) and autosomal genes can be informative of the nature of allelic dominance [1] , the type of variation acted upon by natural selection [2] , [3] , the mutational process [4]–[8] , and the effect of differences in population size on the efficacy of n...	[ "DNA sequences on X chromosomes often have a faster rate of evolution when compared to similar loci on the autosomes , and well articulated models provide reasons why the X-linked mode of inheritance may be responsible for the faster evolution of X-linked genes .", "We analyzed microarray and RNA–seq data collect...	[ "As species diverge over evolutionary time , they accumulate differences in the sequences of their genes and how those genes are expressed .", "We show that gene expression changes accumulate faster for genes on the X chromosome than for genes on the other chromosomes ( autosomes ) in Drosophila ( the “faster-X” ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Identifying Loci Contributing to Natural Variation in Xenobiotic Resistance in Drosophila	journal.pgen.1005663	null	[ [ "Living organisms are subjected to a barrage of toxic compounds , or xenobiotics , in their environment and their diet .", "Animals are frequently exposed to toxins produced by potential prey and/or plant hosts as chemical defenses [1 , 2] , and are increasingly subject to pressures from human activity , ...	[ "Natural populations exhibit a great deal of interindividual genetic variation in the response to toxins , exemplified by the variable clinical efficacy of pharmaceutical drugs in humans , and the evolution of pesticide resistant insects .", "Such variation can result from several phenomena , including variable m...	[ "A striking feature of biology is that within populations there is substantial interindividual phenotypic variation for traits of biomedical significance .", "Some fraction of this variation is due to environmental factors , but for many traits segregating genetic differences contribute significantly to phenotypi...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell physiology", "cell motility", "dictyosteliomycota", "cell polarity", "model organisms", "cellular structures and organelles", "cytoskeleton", "research and analysis methods", "contractile proteins", "actins", "slime molds", "proteins", "protozoan models", "ras signaling", "cell mem...	Gβ Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration	journal.pbio.1002381	Coupling of individual oscillators regulates biological functions ranging from crickets chirping in unison to the coordination of pacemaker cells of the heart. This study finds that a similar concept—coupling between actin oscillators—is at work within single slime mold cells to establish polarity and guide their direc...	[ [ "For cells to move , their cytoskeletal structures become spatially organized by internal polarity signals [1–3] as well as external chemoattractant [4–6] .", "How such signaling cues tame actin dynamics to produce a pseudopod and guide cellular motility remains a key question in eukaryotic chemotaxis .",...	[ "For directional movement , eukaryotic cells depend on the proper organization of their actin cytoskeleton .", "This engine of motility is made up of highly dynamic nonequilibrium actin structures such as flashes , oscillations , and traveling waves .", "In Dictyostelium , oscillatory actin foci interact with s...	[ "The actin cytoskeleton of motile cells is comprised of highly dynamic structures .", "Recently , small oscillating actin foci have been discovered around the periphery of Dictyostelium cells .", "These oscillators are thought to enable pseudopod formation , but how their dynamics are regulated for this is unkn...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biophysic al simulations", "marine and aquatic sciences", "biology", "computational biology", "marine biology" ]	Modelling Growth and Form of the Scleractinian Coral Pocillopora verrucosa and the Influence of Hydrodynamics	journal.pcbi.1002849	null	[ [ "Some corals are known to have a high degree of morphological plasticity along different environmental conditions [1]–[3] .", "Light and water motion are the main environmental factors related to morphological variations of a coral colony [2] .", "The water movement over a reef is responsible to trans...	[ "The growth of scleractinian corals is strongly influenced by the effect of water motion .", "Corals are known to have a high level of phenotypic variation and exhibit a diverse range of growth forms , which often contain a high level of geometric complexity .", "Due to their complex shape , simulation models r...	[ "A long-standing question in marine biology and coral biology is the morphological plasticity of corals , sponges and other marine sessile organisms and the influence of water movement .", "Usually branching species tend to develop symmetrical colonies where branches are being formed in all directions .", "Ther...	2013

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