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Nasal colonization by both gram-positive and gram-negative pathogens induces expression of the innate immune protein lipocalin 2 ( Lcn2 ) . Lcn2 binds and sequesters the iron-scavenging siderophore enterobactin ( Ent ) , preventing bacterial iron acquisition . In addition , Lcn2 bound to Ent induces release of IL-8 fro...
Bacterial pathogens such as Klebsiella pneumoniae require iron and use secreted molecules called siderophores to strip iron from mammalian proteins . When bacteria colonize the upper respiratory tract , the mucosa secretes the protein lipocalin 2 ( Lcn2 ) that binds to the siderophore enterobactin ( Ent ) and disrupts ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "microbiology/innate", "immunity", "microbiology/immunity", "to", "infections", "microbiology" ]
2009
Mucosal Lipocalin 2 Has Pro-Inflammatory and Iron-Sequestering Effects in Response to Bacterial Enterobactin
The pilus 2a backbone protein ( BP-2a ) is one of the most structurally and functionally characterized components of a potential vaccine formulation against Group B Streptococcus . It is characterized by six main immunologically distinct allelic variants , each inducing variant-specific protection . To investigate the ...
Group B Streptococcus ( GBS ) is the leading cause of neonatal invasive diseases and pili , as long filamentous fibers protruding from the bacterial surface , have been discovered as important virulence factors and potential vaccine candidates . The bacterial surface is the main interface between host and pathogen , an...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "sequence", "analysis", "computer", "science", "computer", "modeling", "antigen", "processing", "and", "recognition", "streptococci", "protein", "structure", "immunology", "host-pathogen", "interaction", "biology", "computational", "biology", "microbiology", "computerized", ...
2013
Understanding the Molecular Determinants Driving the Immunological Specificity of the Protective Pilus 2a Backbone Protein of Group B Streptococcus
Genetic transformation , in which cells internalize exogenous DNA and integrate it into their chromosome , is widespread in the bacterial kingdom . It involves a specialized membrane-associated machinery for binding double-stranded ( ds ) DNA and uptake of single-stranded ( ss ) fragments . In the human pathogen Strept...
Natural genetic transformation , a programmed mechanism for horizontal gene transfer , permits the passage of environmental double-stranded ( ds ) DNA through the bacterial membrane and its subsequent integration into the recipient chromosome by homology . In the human pathogen Streptococcus pneumoniae , it requires de...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "streptococci", "genetics", "microbial", "pathogens", "molecular", "genetics", "biology", "microbiology", "molecular", "cell", "biology", "bacterial", "pathogens", "gram", "positive" ]
2013
Midcell Recruitment of the DNA Uptake and Virulence Nuclease, EndA, for Pneumococcal Transformation
Aedes aegypti is the major vector of yellow and dengue fevers . After 10 generations of adult selection , an A . aegypti strain ( SP ) developed 1650-fold resistance to permethrin , which is one of the most widely used pyrethroid insecticides for mosquito control . SP larvae also developed 8790-fold resistance followin...
Aedes aegypti inhabits tropical and subtropical regions worldwide and is the major vector of dengue and yellow fevers , and a secondary vector of chikungunya fever . Dengue fever is epidemic in more than 110 countries and causes up to 100 million infections annually . As there is no efficient vaccine or medicine curren...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "biochemistry", "entomology", "enzyme", "metabolism", "enzymes", "biology", "and", "life", "sciences", "enzymology", "zoology", "enzyme", "chemistry", "genetic", "toxicology", "toxicology", "neurotoxicology" ]
2014
Mechanisms of Pyrethroid Resistance in the Dengue Mosquito Vector, Aedes aegypti: Target Site Insensitivity, Penetration, and Metabolism
Wing pattern evolution in Heliconius butterflies provides some of the most striking examples of adaptation by natural selection . The genes controlling pattern variation are classic examples of Mendelian loci of large effect , where allelic variation causes large and discrete phenotypic changes and is responsible for b...
Identifying the genetic changes responsible for beneficial variation is essential for understanding how organisms adapt . Here , we use a combination of mapping , population genetic analysis , and gene expression studies to identify the genomic regions responsible for phenotypic evolution in the Neotropical butterfly H...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "evolutionary", "biology/evolutionary", "and", "comparative", "genetics", "evolutionary", "biology/genomics", "evolutionary", "biology/pattern", "formation", "evolutionary", "biology", "genetics", "and", "genomics/population", "genetics" ]
2010
Genomic Hotspots for Adaptation: The Population Genetics of Müllerian Mimicry in Heliconius erato
orb is a founding member of the CPEB family of translational regulators and is required at multiple steps during Drosophila oogenesis . Previous studies showed that orb is required during mid-oogenesis for the translation of the posterior/germline determinant oskar mRNA and the dorsal-ventral determinant gurken mRNA . ...
The specification of polarity axes in the Drosophila egg and embryo depends on the proper organization of the microtubule ( MT ) and actin cytoskeleton during mid-oogenesis . During this period , the MT organizing center at the posterior of the oocyte is disassembled and a MT network is established at the anterior and ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "physiology", "medicine", "and", "health", "sciences", "reproductive", "system", "rna", "interference", "messenger", "rna", "reproductive", "physiology", "cell", "polarity", "germ", "cells", "oocytes", "epigenetics", "cellular", "structures", "and", "organelles"...
2019
The CPEB translational regulator, Orb, functions together with Par proteins to polarize the Drosophila oocyte
Predators of all kinds , be they lions hunting in the Serengeti or fishermen searching for their catch , display various collective strategies . A common strategy is to share information about the location of prey . However , depending on the spatial characteristics and mobility of predators and prey , information shar...
When should we work together and when should we work alone ? This question is central to our efforts to understand social and ecological systems alike , from lions hunting in the Serengeti to fishermen searching for their catch . Here , we develop a mathematical modeling framework to identify the essential spatial fact...
[ "Abstract", "Introduction", "Behavioral", "Modeling", "of", "Predators", "Agent-Based", "Model", "Simulation", "Experiments", "Results", "Discussion" ]
[ "ecology", "and", "environmental", "sciences", "predator-prey", "dynamics", "population", "dynamics", "mathematical", "models", "animal", "signaling", "and", "communication", "simulation", "and", "modeling", "systems", "science", "mathematics", "animal", "behavior", "popu...
2016
The Spatial Dynamics of Predators and the Benefits and Costs of Sharing Information
As a major component of ideal plant architecture , leaf angle especially flag leaf angle ( FLA ) makes a large contribution to grain yield in rice . We utilized a worldwide germplasm collection to elucidate the genetic basis of FLA that would be helpful for molecular design breeding in rice . Genome-wide association st...
Rice leaf angle is a major component of ideal plant architecture that determines plant density . Many leaf angle-related genes have been characterized based on mutants , but natural variations of these genes and potential values in genetic improvement have not been evaluated . Here we explore the genetic basis of rice ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biotechnology", "genome-wide", "association", "studies", "plant", "anatomy", "ecology", "and", "environmental", "sciences", "quantitative", "trait", "loci", "conservation", "genetics", "genetic", "mapping", "plant", "science", "rice", "genetically", "modified", "plants",...
2018
Genome-wide association studies reveal that members of bHLH subfamily 16 share a conserved function in regulating flag leaf angle in rice (Oryza sativa)
Inside individual cells , expression of genes is inherently stochastic and manifests as cell-to-cell variability or noise in protein copy numbers . Since proteins half-lives can be comparable to the cell-cycle length , randomness in cell-division times generates additional intercellular variability in protein levels . ...
Inside individual cells , gene products often occur at low molecular counts and are subject to considerable stochastic fluctuations ( noise ) in copy numbers over time . An important consequence of noisy expression is that the level of a protein can vary considerably even among genetically identical cells exposed to th...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "engineering", "and", "technology", "cell", "cycle", "and", "cell", "division", "signal", "processing", "cell", "processes", "binomials", "random", "variables", "noise", "reduction", "dna", "transcription", "probability", "distribution", "mathematics", "algebra", "polyn...
2016
Intercellular Variability in Protein Levels from Stochastic Expression and Noisy Cell Cycle Processes
Kinetochores are multi-protein complexes that mediate the physical coupling of sister chromatids to spindle microtubule bundles ( called kinetochore ( K ) -fibres ) from respective poles . These kinetochore-attached K-fibres generate pushing and pulling forces , which combine with polar ejection forces ( PEF ) and elas...
To achieve proper cell division , newly duplicated chromosomes must be segregated into daughter cells with high fidelity . This occurs in mitosis where during the crucial metaphase stage chromosomes are aligned on an imaginary plate , called the metaphase plate . Chromosomes are attached to a structural scaffold—the mi...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
Inferring the Forces Controlling Metaphase Kinetochore Oscillations by Reverse Engineering System Dynamics
The potential of broadly neutralizing antibodies targeting the HIV-1 envelope trimer to prevent HIV-1 transmission has opened new avenues for therapies and vaccines . However , their implementation remains challenging and would profit from a deepened mechanistic understanding of HIV-antibody interactions and the mucosa...
Successful solicitation of the potential of neutralizing antibodies for HIV-1 prevention will require a deepened understanding of HIV-1 transmission and antibody neutralization . In this study , we experimentally determined molecular parameters of the HIV-1-antibody interaction , and subsequently used this knowledge to...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "immune", "physiology", "body", "fluids", "pathology", "and", "laboratory", "medicine", "viral", "transmission", "and", "infection", "pathogens", "immunology", "microbiology", "vertebrates", "viral", "structure", "animals", "mamm...
2017
Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters
Interaction between the hepatitis C virus ( HCV ) envelope protein E2 and the host receptor CD81 is essential for HCV entry into target cells . The number of E2-CD81 complexes necessary for HCV entry has remained difficult to estimate experimentally . Using the recently developed cell culture systems that allow persist...
The interaction between the hepatitis C virus ( HCV ) envelope protein E2 and the host cell surface receptor CD81 is critical for HCV entry into hepatocytes and presents a promising drug and vaccine target . Yet , the number of E2-CD81 complexes that must be formed between a virus and a target cell to enable viral entr...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "infectious", "diseases", "theoretical", "biology", "gastroenterology", "and", "hepatology", "biology", "computational", "biology" ]
2011
Mathematical Model of Viral Kinetics In Vitro Estimates the Number of E2-CD81 Complexes Necessary for Hepatitis C Virus Entry
Asymmetric cell division and apoptosis ( programmed cell death ) are two fundamental processes that are important for the development and function of multicellular organisms . We have found that the processes of asymmetric cell division and apoptosis can be functionally linked . Specifically , we show that asymmetric c...
Asymmetric cell division and apoptosis ( programmed cell death ) are two fundamental processes that are important for the development and function of multicellular organisms . Asymmetric cell division creates daughter cells of different fates , and this is critical for the generation of cellular diversity . Apoptosis e...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods", "Supporting", "Information" ]
[ "developmental", "biology", "cell", "biology", "genetics", "and", "genomics" ]
2008
Control of Apoptosis by Asymmetric Cell Division
Cytokines such as TNF and FASL can trigger death or survival depending on cell lines and cellular conditions . The mechanistic details of how a cell chooses among these cell fates are still unclear . The understanding of these processes is important since they are altered in many diseases , including cancer and AIDS . ...
Activation of death receptors ( TNFR and Fas ) can trigger either survival or cell death according to the cell type and the cellular conditions . In other words , the same signal can have antagonist responses . On one hand , the cell can survive by activating the NFκB signalling pathway . On the other hand , it can die...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "cell", "biology/cellular", "death", "and", "stress", "responses", "computational", "biology/signaling", "networks", "computational", "biology/systems", "biology", "cell", "biology/cell", "signaling" ]
2010
Mathematical Modelling of Cell-Fate Decision in Response to Death Receptor Engagement
Cellular toxicity introduced by protein misfolding threatens cell fitness and viability . Failure to eliminate these polypeptides is associated with various aggregation diseases . In eukaryotes , the ubiquitin proteasome system ( UPS ) plays a vital role in protein quality control ( PQC ) , by selectively targeting mis...
The accumulation of misfolded proteins threatens cell fitness and viability and their aggregation is commonly associated with numerous neurodegenerative disorders . Cells therefore rely on a number of protein quality control ( PQC ) pathways to prevent protein aggregation . In eukaryotes , the ubiquitin proteasome syst...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[]
2015
The Protein Quality Control Machinery Regulates Its Misassembled Proteasome Subunits
Iron sequestration by host iron-binding proteins is an important mechanism of resistance to microbial infections . Inside oral epithelial cells , iron is stored within ferritin , and is therefore not usually accessible to pathogenic microbes . We observed that the ferritin concentration within oral epithelial cells was...
Iron is an essential nutrient for all microbes . Many human pathogenic microbes have developed sophisticated strategies to acquire iron from the host as most compartments in the body contain little free iron . For example , in oral epithelial cells intracellular iron is bound to ferritin , a protein that is highly resi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases/fungal", "infections", "genetics", "and", "genomics/gene", "function", "microbiology/cellular", "microbiology", "and", "pathogenesis", "genetics", "and", "genomics/gene", "expression" ]
2008
The Hyphal-Associated Adhesin and Invasin Als3 of Candida albicans Mediates Iron Acquisition from Host Ferritin
Glycosyltransferases are a class of enzymes that catalyse the posttranslational modification of proteins to produce a large number of glycoconjugate acceptors from a limited number of nucleotide-sugar donors . The products of one glycosyltransferase can be the substrates of several other enzymes , causing a combinatori...
While enzymes tend to have a narrow substrate specificity , there are a number of enzymes that are promiscuous , acting on a wide range of substrates . In this article we derive expressions for general multi-substrate competitive inhibition for the class of transferases , with particular emphasis on glycosylation . By ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "biochemistry", "competitive", "inhibitors", "post-translational", "modification", "proteins", "enzyme", "metabolism", "enzymes", "transferases", "biology", "and", "life", "sciences", "glycosylation", "enzymology", "enzyme", "kinetics", "enzyme", "inhibitors", "enzyme", "ch...
2018
A mechanism for bistability in glycosylation
Human T lymphotropic virus type I ( HTLV-I ) infection is largely latent in infected persons . How HTLV-1 establishes latency and reactivates is unclear . Here we show that most HTLV-1-infected HeLa cells become senescent . By contrast , when NF-κB activity is blocked , senescence is averted , and infected cells contin...
Most HTLV-1-infected individuals are asymptomatic . It is thought that the proviral DNA is transcriptionally inert and HTLV-1 replicates through mitotic expansion of host cells . The evolving provirus integration patterns in HTLV-1 carriers , however , suggest new infection occurs continuously . Whether or how HTLV-1 e...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases", "medicine", "and", "health", "sciences", "hiv", "immunopathogenesis", "clinical", "immunology", "virology", "biology", "and", "life", "sciences", "immunology", "microbiology", "viral", "diseases" ]
2014
Regulation of Human T-Lymphotropic Virus Type I Latency and Reactivation by HBZ and Rex
Nipah virus ( NiV ) is an emerging disease that causes severe encephalitis and respiratory illness in humans . Pigs were identified as an intermediate host for NiV transmission in Malaysia . In Bangladesh , NiV has caused recognized human outbreaks since 2001 and three outbreak investigations identified an epidemiologi...
Nipah virus ( NiV ) , is an emerging disease that causes severe encephalitis and respiratory illness in humans . Pigs were identified as an intermediate host for NiV transmission in Malaysia , and in Bangladesh three NiV outbreak investigations since 2001 identified an epidemiological association between close contact ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "public", "and", "occupational", "health", "research", "design", "infectious", "diseases", "medicine", "and", "health", "sciences", "animal", "studies", "epidemiology", "tropical", "diseases", "research", "and", "analysis", "methods" ]
2014
Serological Evidence of Henipavirus Exposure in Cattle, Goats and Pigs in Bangladesh
Echinococcosis is a neglected zoonotic disease affecting over 1 million people worldwide at any given time . It is the leading cause of hospital admissions for parasitic diseases in Chile . We conducted a retrospective investigation of hospitalized cases to describe the epidemiological trends of echinococcosis in Chile...
Humans are infected by many types of parasites that originate from animals . Cystic echinococcosis ( CE ) is a tapeworm infection that affects over 1 million people over the world at any given time , with symptoms such as abdominal pain , chest pain , vomiting , and allergic reactions . The lifecycle of this parasite i...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "hospitalizations", "livestock", "medicine", "and", "health", "sciences", "chile", "(country)", "ruminants", "tropical", "diseases", "geographical", "locations", "vertebrates", "parasitic", "diseases", "animals", "mammals", "health", "care", "neglected", "tropical", "dise...
2017
Trends and correlates of cystic echinococcosis in Chile: 2001–2012
Lytic herpes simplex virus 1 ( HSV-1 ) infection triggers disruption of transcription termination ( DoTT ) of most cellular genes , resulting in extensive intergenic transcription . Similarly , cellular stress responses lead to gene-specific transcription downstream of genes ( DoG ) . In this study , we performed a det...
Recently , we reported that productive herpes simplex virus 1 ( HSV-1 ) infection leads to disruption of transcription termination ( DoTT ) of most but not all cellular genes . This results in extensive transcription beyond poly ( A ) sites and into downstream genes . Subsequently , cellular stress responses were found...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cellular", "stress", "responses", "classical", "mechanics", "gene", "regulation", "cell", "processes", "dna-binding", "proteins", "vertebrates", "mechanical", "stress", "dogs", "animals", "mammals", "dna", "transcription", "epigenetics", "chromatin", "chromosome", "biolo...
2018
HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes
In the current study , we used a mouse model and human blood samples to determine the effects of chronic alcohol consumption on immune responses during Mycobacterium tuberculosis ( Mtb ) infection . Alcohol increased the mortality of young mice but not old mice with Mtb infection . CD11b+Ly6G+ cells are the major sourc...
Chronic alcohol consumption modulates the host immune defense mechanism ( s ) and makes the host susceptible to various fungal , viral and bacterial infections , including Mycobacterium tuberculosis ( Mtb ) . However , limited information is available about the mechanisms involved in alcohol-mediated host susceptibilit...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "death", "rates", "blood", "cells", "medicine", "and", "health", "sciences", "immune", "cells", "chemical", "compounds", "immunology", "social", "sciences", "diet", "light", "microscopy", "organic", "compounds", "nutrition", "microscopy", "confocal", "microscopy", "po...
2018
Alcohol enhances type 1 interferon-α production and mortality in young mice infected with Mycobacterium tuberculosis
In a living cell , the antiparallel double-stranded helix of DNA is a dynamically changing structure . The structure relates to interactions between and within the DNA strands , and the array of other macromolecules that constitutes functional chromatin . It is only through its changing conformations that DNA can organ...
In a living cell , DNA both is an information carrier and carries out important structural tasks , such as organizing its replication and distributing the chromosomes to the daughter cells . DNA is frequently depicted as an antiparallel double-stranded helix , but DNA may rather be viewed as having a dynamically changi...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "molecular", "biology", "genetics", "and", "genomics", "homo", "(human)", "computational", "biology" ]
2007
The Human Genomic Melting Map
Neural population equations such as neural mass or field models are widely used to study brain activity on a large scale . However , the relation of these models to the properties of single neurons is unclear . Here we derive an equation for several interacting populations at the mesoscopic scale starting from a micros...
Understanding the brain requires mathematical models on different spatial scales . On the “microscopic” level of nerve cells , neural spike trains can be well predicted by phenomenological spiking neuron models . On a coarse scale , neural activity can be modeled by phenomenological equations that summarize the total a...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "action", "potentials", "medicine", "and", "health", "sciences", "neural", "networks", "population", "dynamics", "membrane", "potential", "condensed", "matter", "physics", "computational", "biology", "electrophysiology", "neuroscience", "computational", "neuroscience", "pop...
2017
Towards a theory of cortical columns: From spiking neurons to interacting neural populations of finite size
Dengue is the most important mosquito-borne viral disease affecting humans . The only prevention measure currently available is the control of its vectors , primarily Aedes aegypti . Recent advances in genetic engineering have opened the possibility for a new range of control strategies based on genetically modified mo...
Dengue is a viral disease that affects approximately 50 million people annually , and is estimated to result in 12 , 500 fatalities . Dengue viruses are vectored by mosquitoes , predominantly by the species Aedes aegypti . Because there is currently no vaccine or specific treatment , the only available strategy to redu...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "ecology/population", "ecology", "infectious", "diseases/epidemiology", "and", "control", "of", "infectious", "diseases", "genetics", "and", "genomics/population", "genetics" ]
2009
Skeeter Buster: A Stochastic, Spatially Explicit Modeling Tool for Studying Aedes aegypti Population Replacement and Population Suppression Strategies
The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein ( NP ) . Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA , and prior work has compared human and avian viral strains to identify amino-acid differences in NP that af...
During viral infection , human cells express proteins that can restrict virus replication . However , in many cases it remains unclear what determines the sensitivity of a given viral strain to a particular restriction factor . Here we use a high-throughput approach to measure how all amino-acid mutations to the nucleo...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbial", "mutation", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "influenza", "pathogens", "microbiology", "dna-binding", "proteins", "vertebrates", "orthomyxoviruses", "animals", "viruses", "polymerases", "rna", "viruses", "...
2017
Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA
The European & Developing Countries Clinical Trials Partnership ( EDCTP ) is a partnership of European and sub-Saharan African countries that aims to accelerate the development of medical interventions against poverty-related diseases ( PRDs ) . A bibliometric analysis was conducted to 1 ) measure research output from ...
The European & Developing Countries Clinical Trials Partnership ( EDCTP ) was created in 2003 as a European response to the global health crisis caused by the three main poverty-related diseases ( PRDs ) of HIV/AIDS , tuberculosis and malaria . EDCTP funds research focusing on clinical trials for diagnosing , preventin...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Bibliometric Assessment of European and Sub-Saharan African Research Output on Poverty-Related and Neglected Infectious Diseases from 2003 to 2011
Calorie restriction ( CR ) robustly extends the lifespan of numerous species . In the yeast Saccharomyces cerevisiae , CR has been proposed to extend lifespan by boosting the activity of sirtuin deacetylases , thereby suppressing the formation of toxic repetitive ribosomal DNA ( rDNA ) circles . An alternative theory i...
There are only a few techniques that reliably promote longevity in multiple , distantly related species . Perhaps the best known , caloric restriction ( CR ) , was first shown to promote lifespan in rodents in the 1930s and has since been shown to work in most species it has been tested on . We and others have previous...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "biology", "microbiology", "molecular", "biology", "genetics", "and", "genomics", "saccharomyces" ]
2007
MSN2 and MSN4 Link Calorie Restriction and TOR to Sirtuin-Mediated Lifespan Extension in Saccharomyces cerevisiae
AGGF1 is an angiogenic factor with therapeutic potential to treat coronary artery disease ( CAD ) and myocardial infarction ( MI ) . However , the underlying mechanism for AGGF1-mediated therapeutic angiogenesis is unknown . Here , we show for the first time that AGGF1 activates autophagy , a housekeeping catabolic cel...
Coronary artery disease is the number one killer disease worldwide . Recently , therapeutic angiogenesis has been proposed as an attractive new strategy for treating this and other ischemic diseases . This study establishes the angiogenic factor AGGF1 as a novel target and agent that can successfully treat coronary art...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "death", "autophagic", "cell", "death", "medicine", "and", "health", "sciences", "diagnostic", "radiology", "ultrasound", "imaging", "cardiovascular", "physiology", "cardiovascular", "anatomy", "gene", "regulation", "cell", "processes", "echocardiography", "angiog...
2016
Angiogenic Factor AGGF1 Activates Autophagy with an Essential Role in Therapeutic Angiogenesis for Heart Disease
The mechanisms by which RNA-binding proteins control the translation of subsets of mRNAs are not yet clear . Slf1p and Sro9p are atypical-La motif containing proteins which are members of a superfamily of RNA-binding proteins conserved in eukaryotes . RIP-Seq analysis of these two yeast proteins identified overlapping ...
All organisms must respond to changes in their external environment such as exposure to different stresses . The availability of genome sequences and post-genomic technologies has enabled the analysis of these adaptive responses at the molecular level in terms of altered gene expression profiles . However , relatively ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry", "rna", "cell", "biology", "oxidative", "stress", "gene", "expression", "genetics", "biology", "and", "life", "sciences", "proteomics", "molecular", "cell", "biology", "oxidative", "damage", "antioxidants", "ribosomes" ]
2015
The Yeast La Related Protein Slf1p Is a Key Activator of Translation during the Oxidative Stress Response
Arf4 is proposed to be a critical regulator of membrane protein trafficking in early secretory pathway . More recently , Arf4 was also implicated in regulating ciliary trafficking , however , this has not been comprehensively tested in vivo . To directly address Arf4’s role in ciliary transport , we deleted Arf4 specif...
Primary cilia are sensory organelles found on most cells and contain specific receptors that detect extracellular stimuli . Defects in trafficking receptors to cilia cause a diverse set of diseases called ciliopathies , which include polycystic kidney disease , obesity , cerebral anomalies and retinal degeneration . Ba...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "zymogens", "enzymology", "social", "sciences", "neuroscience", "animal", "models", "model", "organisms", "experimental", "organism", "systems", "sequence", "motif", "analysis", "kidneys", "cellular", "structures", "and", "organe...
2017
Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration
The interaction between an antibiotic and bacterium is not merely restricted to the drug and its direct target , rather antibiotic induced stress seems to resonate through the bacterium , creating selective pressures that drive the emergence of adaptive mutations not only in the direct target , but in genes involved in...
While antibiotic resistant bacterial pathogens cause millions of deaths each year it remains largely unclear how a bacterium deals with antibiotic-induced stress and how this leads to the emergence of resistance . Moreover , many bacterial species are composed of strains whose genomes vary considerably , and while this...
[ "Abstract", "Introduction", "Results", "and", "Discussion", "Methods" ]
[ "bacteriology", "antimicrobials", "medicine", "and", "health", "sciences", "genetic", "networks", "pathology", "and", "laboratory", "medicine", "pneumococcus", "gene", "regulation", "pathogens", "drugs", "microbiology", "antibiotic", "resistance", "regulator", "genes", "a...
2016
Strain Dependent Genetic Networks for Antibiotic-Sensitivity in a Bacterial Pathogen with a Large Pan-Genome
A major bottleneck in understanding zoonotic pathogens has been the analysis of pathogen co-infection dynamics . We have addressed this challenge using a novel direct sequencing approach for pathogen quantification in mixed infections . The major zoonotic food-borne pathogen Campylobacter jejuni , with an important res...
Pathogenic bacteria that can be transferred from animals to humans represent a highly potent human health hazard . Understanding the ecology of these pathogens in the animal host is of fundamental importance . A major analytical challenge , however , is the fact that individual animal hosts can be colonised by multiple...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods", "Supporting", "Information" ]
[ "chicken", "ecology", "public", "health", "and", "epidemiology" ]
2007
Co-Infection Dynamics of a Major Food-Borne Zoonotic Pathogen in Chicken
Autocrine priming of cells by small quantities of constitutively produced type I interferon ( IFN ) is a well-known phenomenon . In the absence of type I IFN priming , cells display attenuated responses to other cytokines , such as anti-viral protection in response to IFNγ . This phenomenon was proposed to be because I...
Cells of the immune system release interferons ( IFNs ) in response to pathogens or tumor cells; these proteins signal to other immune cells to initiate the body's defense mechanisms . The two classes of IFNs—types I and II—have different receptors and distinct effects on the cells; however , there is “crosstalk” betwe...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "biology/cell", "signaling", "biochemistry/chemical", "biology", "of", "the", "cell", "immunology/immune", "response", "infectious", "diseases/viral", "infections", "immunology/immunity", "to", "infections", "cell", "biology/gene", "expression" ]
2010
Functional Crosstalk between Type I and II Interferon through the Regulated Expression of STAT1
Clonorchiasis , caused by the infection of Clonorchis sinensis ( C . sinensis ) , is a kind of neglected tropical disease , but it is highly related to cholangiocarcinoma and hepatocellular carcinoma ( HCC ) . It has been well known that the excretory/secretory products of C . sinensis ( CsESPs ) play key roles in clon...
Clonorchis sinensis ( C . sinensis ) has afflicted more than 35 million people in world and approximately 15 million in China , creating a socio-economic burden in epidemic regions . The infection of C . sinensis is highly related to cholangiocarcinoma and hepatocellular carcinoma ( HCC ) . It has been documented that ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2013
Molecular Characterization of Severin from Clonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells
Despite the wealth of knowledge regarding the mechanisms of action and the mechanisms of resistance to azole antifungals , very little is known about how the azoles are imported into pathogenic fungal cells . Here the in-vitro accumulation and import of Fluconazole ( FLC ) was examined in the pathogenic fungus , Candid...
Azole antifungals are used to treat a wide variety of fungal infections of humans , animals and plants . A great deal is known about how the azoles interact with their target enzyme within fungal cells and how the azoles are exported from the fungal cell through various efflux pumps . Altered interactions with the targ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases/fungal", "infections", "microbiology/medical", "microbiology", "infectious", "diseases/antimicrobials", "and", "drug", "resistance" ]
2010
Azole Drugs Are Imported By Facilitated Diffusion in Candida albicans and Other Pathogenic Fungi
Fluoroquinolones are antibacterial drugs that inhibit DNA Gyrase and Topoisomerase IV . These essential enzymes facilitate chromosome replication and RNA transcription by regulating chromosome supercoiling . High-level resistance to fluoroquinolones in E . coli requires the accumulation of multiple mutations , includin...
The increasing frequency of human pathogens resistant to important classes of antibiotics poses a serious and growing challenge for medicine and society . We need improved strategies to reduce the rate of resistance development , for established and novel drugs , based on knowledge of the factors that drive the increas...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases/antimicrobials", "and", "drug", "resistance", "microbiology" ]
2009
Interplay in the Selection of Fluoroquinolone Resistance and Bacterial Fitness
Understanding how genetic variation interacts with the environment is essential for understanding adaptation . In particular , the life cycle of plants is tightly coordinated with local environmental signals through complex interactions with the genetic variation ( G x E ) . The mechanistic basis for G x E is almost co...
Many traits are influenced by genetic variation in interaction with the environment , so called G x E variation . In agriculture , for example , different varieties are optimal in different environments . In evolution , G x E is also crucial for local adaptation . Identifying the genes underlying G x E has proven extre...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
"Missing" G x E Variation Controls Flowering Time in Arabidopsis thaliana
Between October 2013 and April 2014 , more than 30 , 000 cases of Zika virus ( ZIKV ) disease were estimated to have attended healthcare facilities in French Polynesia . ZIKV has also been reported in Africa and Asia , and in 2015 the virus spread to South America and the Caribbean . Infection with ZIKV has been associ...
Since the first reported major outbreak of Zika virus disease in Micronesia in 2007 , the virus has caused outbreaks throughout the Pacific and South America . Transmitted by the Aedes genus of mosquitoes , the virus has been linked to possible neurological complications including Guillain-Barré Syndrome and microcepha...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "invertebrates", "dengue", "virus", "medicine", "and", "health", "sciences", "microcephaly", "pathology", "and", "laboratory", "medicine", "demography", "pathogens", "geographical", "locations", "microbiology", "vector-borne", "diseases", "mathematical", "models", "animals"...
2016
Transmission Dynamics of Zika Virus in Island Populations: A Modelling Analysis of the 2013–14 French Polynesia Outbreak
Fish-borne zoonotic trematodes ( FZT ) infections including liver- and minute intestinal flukes are common in Southeast Asia in both humans and domestic animals eating raw fish and since 2010 , the liver flukes are recognised as neglected tropical diseases by WHO . Mass drug treatment with praziquantel is advised for h...
Fish-borne zoonotic trematodes ( FZT ) including liver and small intestinal flukes in humans and domestic animals are a growing problem in Southeast Asia . WHO has recently recognized the problem , listed the liver flukes as neglected tropical diseases and recommends mass drug treatment of humans to overcome the diseas...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2014
Reinfection of Dogs with Fish-Borne Zoonotic Trematodes in Northern Vietnam following a Single Treatment with Praziquantel
Proteins perform their function or interact with partners by exchanging between conformational substates on a wide range of spatiotemporal scales . Structurally characterizing these exchanges is challenging , both experimentally and computationally . Large , diffusional motions are often on timescales that are difficul...
Multi-cellular physiology is an emergent property , which depends critically on inter-cellular signaling pathways . Transmembrane G protein-coupled receptors ( GPCRs ) mediate a large variety of physiological events throughout the body , such as vision or cardiovascular regulation . It is thus no surprise that GPCRs ar...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Nullspace Sampling with Holonomic Constraints Reveals Molecular Mechanisms of Protein Gαs
Quantitative imaging has become a vital technique in biological discovery and clinical diagnostics; a plethora of tools have recently been developed to enable new and accelerated forms of biological investigation . Increasingly , the capacity for high-throughput experimentation provided by new imaging modalities , cont...
New technologies have increased the size and content-richness of biological imaging datasets . As a result , automated image processing is increasingly necessary to extract relevant data in an objective , consistent and time-efficient manner . While image processing tools have been developed for general problems that a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Automated Processing of Imaging Data through Multi-tiered Classification of Biological Structures Illustrated Using Caenorhabditis elegans
Large-scale protein interaction networks ( PINs ) have typically been discerned using affinity purification followed by mass spectrometry ( AP/MS ) and yeast two-hybrid ( Y2H ) techniques . It is generally recognized that Y2H screens detect direct binary interactions while the AP/MS method captures co-complex associati...
To understand and model cellular processes , we require accurate descriptions of the interactions occurring between constituent proteins . Large-scale protein interaction maps have typically been measured in two distinct ways . The first detects direct pair-wise associations by testing only two proteins at a time for a...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "genetics", "and", "genomics/bioinformatics", "computational", "biology/systems", "biology" ]
2009
A Novel Scoring Approach for Protein Co-Purification Data Reveals High Interaction Specificity
A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle . We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from t...
Molecular motors are perhaps the most important proteins present in the cell . The importance specifically lies with the fact that these proteins use the chemical energy source ( such as ATP ) of the cell to generate mechanical work and perform a wide range of functionalities . In this article , we generalize the idea ...
[ "Abstract", "Introduction", "Results", "and", "Discussion", "Methods" ]
[ "cell", "motility", "kinesins", "crystal", "structure", "actin", "filaments", "engineering", "and", "technology", "condensed", "matter", "physics", "engines", "molecular", "motors", "actin", "motors", "crystallography", "motor", "proteins", "contractile", "proteins", "s...
2016
Strain Mediated Adaptation Is Key for Myosin Mechanochemistry: Discovering General Rules for Motor Activity
The aim of this study was to determine , through a genome-wide association study ( GWAS ) , the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis ( SSc ) . We considered limited ( lcSSc ) and diffuse ( dcSSc ) cutaneous involvement , and the relationships with presence of the SS...
Scleroderma or systemic sclerosis is a complex autoimmune disease affecting one individual of every 100 , 000 in Caucasian populations . Even though current genetic studies have led to better understanding of the pathogenesis of the disease , much remains unknown . Scleroderma is a heterogeneous disease , which can be ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "clinical", "immunology", "genetics", "immunology", "biology", "genetics", "and", "genomics" ]
2011
Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy
Tripartite Motif ( TRIM ) ubiquitin ligases act in the innate immune response against viruses . One of the best characterized members of this family , TRIM5α , serves as a potent retroviral restriction factor with activity against HIV . Here , we characterize what are likely to be the youngest TRIM genes in the human g...
A fundamental question in biology is how the immune system is able to inactivate the enormous number of pathogens that it faces . The vast majority of pathogens are quickly neutralized by the innate immune system , a large network of defenses to which approximately 1/30 of the human genome is devoted . Because pathogen...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "biology", "genomics", "evolutionary", "biology", "genetics", "and", "genomics" ]
2011
Identification of a Genomic Reservoir for New TRIM Genes in Primate Genomes
Plasmodium falciparum employs antigenic variation to evade the human immune response by switching the expression of different variant surface antigens encoded by the var gene family . Epigenetic mechanisms including histone modifications and sub-nuclear compartmentalization contribute to transcriptional regulation in t...
Plasmodium falciparum is a protist parasite that causes malaria and kills more than 800 , 000 people per year . The parasite escapes from the human immune response by antigenic variation through switching between expression of different var genes . These encode different variant antigens that are expressed on the surfa...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases/protozoal", "infections", "genetics", "and", "genomics/epigenetics", "cell", "biology/gene", "expression" ]
2011
Expression of P. falciparum var Genes Involves Exchange of the Histone Variant H2A.Z at the Promoter
Middle East respiratory syndrome coronavirus ( MERS-CoV ) remains a threat to public health worldwide; however , effective vaccine or drug against CoVs remains unavailable . CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses , thus making it an important target for drug development . W...
Severe acute respiratory syndrome coronavirus ( SARS-CoV ) and Middle East respiratory syndrome coronavirus ( MERS-CoV ) caused global pandemics in 2003 and 2012 with the fatality rates of 10–35% . Outbreak of MERS-CoV in the Republic of Korea in 2015 highlighted that the newly emerged CoVs remain a concern for the pub...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "coronaviruses", "crystal", "structure", "pathology", "and", "laboratory", "medicine", "enzymes", "pathogens", "split-decomposition", "method", "condensed", "matter", "physics", "microbiology", "enzymology", "phosphatases", "viruses"...
2017
Crystal structure of Middle East respiratory syndrome coronavirus helicase
Learning in biologically relevant neural-network models usually relies on Hebb learning rules . The typical implementations of these rules change the synaptic strength on the basis of the co-occurrence of the neural events taking place at a certain time in the pre- and post-synaptic neurons . Differential Hebbian learn...
Which learning rules can be used to capture the temporal relations between activation events involving pairs of neurons in artificial neural networks ? Previous computational research proposed various differential Hebbian learning ( DHL ) rules that rely on the activation of neurons and time derivatives of their activa...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "learning", "medicine", "and", "health", "sciences", "action", "potentials", "engineering", "and", "technology", "nervous", "system", "signal", "processing", "membrane", "potential", "social", "sciences", "electrophysiology", "neuroscience", "learning", "and", "memory", ...
2018
General differential Hebbian learning: Capturing temporal relations between events in neural networks and the brain
Filamentous fungi produce a diverse array of secondary metabolites ( SMs ) critical for defense , virulence , and communication . The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes , an atypical arrangement for metabolic pathways in other eukaryotes . Comparative studies of ...
All organisms produce metabolites , which are small molecules important for growth , reproduction , and other essential functions . Some organisms , including fungi , plants , and bacteria , make specialized forms of metabolites known as “secondary” metabolites that are ecologically important and improve their producer...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "taxonomy", "aspergillus", "fumigatus", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "aspergillus", "fungal", "genetics", "pathogens", "microbiology", "fungi", "phylogenetics", "data", "management", "metabolites", "fungal", "patho...
2017
Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species
As a result of evolution , the biology of triatomines must have been significantly adapted to accommodate trypanosome infection in a complex network of vector-vertebrate-parasite interactions . Arthropod-borne parasites have probably developed mechanisms , largely still unknown , to exploit the vector-vertebrate host i...
The control of Chagas disease , an infection that affects ca . 8 million people in Latin America , is mostly based on vector control activities . Understanding vector biology and how these insects interact with their environment , hosts and pathogens is crucial to improve vector control strategies . The behavior of tri...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
Trypanosomes Modify the Behavior of Their Insect Hosts: Effects on Locomotion and on the Expression of a Related Gene
Retroviruses and Long Terminal Repeat ( LTR ) -retrotransposons have distinct patterns of integration sites . The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters . The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe i...
Retroviruses and retrotransposons are genetic elements that propagate by integrating into chromosomes of eukaryotic cells . Genetic disorders are being treated with retrovirus-based vectors that integrate corrective genes into the chromosomes of patients . Unfortunately , the vectors can alter expression of adjacent ge...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "recombination-based", "assay", "dna-binding", "proteins", "fungi", "model", "organisms", "experimental", "organism", "systems", "dna", "epigenetics", "molecular", "biology", "techniques", "chromatin", "schizosaccharomyces", "homologous", "recombination", "research", "and", ...
2017
Host factors that promote retrotransposon integration are similar in distantly related eukaryotes
CD8+ T cells have been shown to play a crucial role in Trypanosoma cruzi infection . Memory CD8+ T cells can be categorised based on their distinct differentiation stages and functional activities as follows: stem cell memory ( TSCM ) , central memory ( TCM ) , transitional memory ( TTM ) , effector memory ( TEM ) and ...
Chagas disease is caused by the intracellular parasite Trypanosoma cruzi . After the onset of acute infection , all individuals enter the chronic phase and approximately 70% of them never have symptoms . However , nearly 30% of infected individuals develop symptoms , mainly of heart disease , even decades after the ini...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "chagas", "disease", "neglected", "tropical", "diseases", "biology", "and", "life", "sciences", "immunology", "tropical", "diseases", "protozoan", "infections", "parasitic", "diseases", "immune", "response" ]
2015
Low Frequency of Circulating CD8+ T Stem Cell Memory Cells in Chronic Chagasic Patients with Severe Forms of the Disease
Trypanosomes show an intriguing organization of their mitochondrial DNA into a catenated network , the kinetoplast DNA ( kDNA ) . While more than 30 proteins involved in kDNA replication have been described , only few components of kDNA segregation machinery are currently known . Electron microscopy studies identified ...
Proper segregation of the mitochondrial genome during cell division is a prerequisite of healthy eukaryotic cells . However , the mechanism underlying the segregation process is only poorly understood . We use the single celled parasite Trypanosoma brucei , which , unlike most model organisms , harbors a single large m...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "rna", "interference", "nuclear", "staining", "pathology", "and", "laboratory", "medicine", "pathogens", "mitochondria", "epigenetics", "bioenergetics", "cellular", "structures", "and", "organelles", "research", "and", "analysis", ...
2016
TAC102 Is a Novel Component of the Mitochondrial Genome Segregation Machinery in Trypanosomes
Cell fate choices are tightly controlled by the interplay between intrinsic and extrinsic signals , and gene regulatory networks . In Saccharomyces cerevisiae , the decision to enter into gametogenesis or sporulation is dictated by mating type and nutrient availability . These signals regulate the expression of the mas...
The cell-fate controlling gametogenesis is essential for all sexual reproducing organisms . In Saccharomyces cerevisiae , entry into gametogenesis or sporulation is dictated by mating type and nutrient availability . These signals regulate the expression of the master regulator of entry into sporulation , IME1 . In thi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "meiosis", "medicine", "and", "health", "sciences", "chemical", "compounds", "cell", "cycle", "and", "cell", "division", "cell", "processes", "messenger", "rna", "carbohydrates", "organic", "compounds", "glucose", "reproductive", "physiology", "glucose", "signaling", ...
2016
Nutrient Control of Yeast Gametogenesis Is Mediated by TORC1, PKA and Energy Availability
The Adenovirus ( Ad ) genome within the capsid is tightly associated with a virus-encoded , histone-like core protein—protein VII . Two other Ad core proteins , V and X/μ , also are located within the virion and are loosely associated with viral DNA . Core protein VII remains associated with the Ad genome during the ea...
The Ad major core protein VII protects the viral genome from recognition by a cellular DNA damage response during the early stages of infection and alters cellular chromatin to block innate signaling mechanisms . The packaging of the Ad genome into the capsid is thought to follow the paradigm of dsDNA bacteriophage whe...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "hek", "293", "cells", "biological", "cultures", "microbiology", "viral", "structure", "dna", "replication", "dna", "molecular", "biology", "techniques", "microbial", "genomics", "research", "and", "analysis", "methods", "viral", "genomics", "viral", "core", "proteins...
2017
The adenovirus major core protein VII is dispensable for virion assembly but is essential for lytic infection
Trypanosoma brucei , the causative agent of Human African Trypanosomiasis ( HAT ) , expresses two proteins with homology to human glycogen synthase kinase 3β ( HsGSK-3 ) designated TbruGSK-3 short and TbruGSK-3 long . TbruGSK-3 short has previously been validated as a potential drug target and since this enzyme has als...
Over 60 million people in sub-Saharan Africa are at risk of infection with the parasite Trypanosoma brucei which causes Human African Trypanosomiasis ( HAT ) , also known as sleeping sickness . The disease results in systemic and neurological disability to its victims . At present , only four drugs are available for tr...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "infectious", "diseases", "medical", "microbiology", "global", "health", "african", "trypanosomiasis", "neglected", "tropical", "diseases", "biology", "microbiology", "parasitic", "diseases", "parasitology" ]
2011
Trypanosoma brucei Glycogen Synthase Kinase-3, A Target for Anti-Trypanosomal Drug Development: A Public-Private Partnership to Identify Novel Leads
Src tyrosine kinases are deregulated in numerous cancers and may favor tumorigenesis and tumor progression . We previously described that Src activation in NIH-3T3 mouse fibroblasts promoted cell resistance to apoptosis . Indeed , Src was found to accelerate the degradation of the pro-apoptotic BH3-only protein Bik and...
Personalizing medicine on a molecular basis has proven its clinical benefits . The molecular study of the patient's tumor and healthy tissues allowed the identification of determinant mutations and the subsequent optimization of healthy and cancer cells specific response to treatments . Here , we propose a combined mat...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "oncology", "systems", "biology", "cell", "death", "medicine", "mathematics", "theoretical", "biology", "applied", "mathematics", "cancer", "treatment", "chemotherapy", "and", "drug", "treatment", "signaling", "networks", "biology", "molecular", "cell", "biology", "comp...
2013
Data-Driven Modeling of Src Control on the Mitochondrial Pathway of Apoptosis: Implication for Anticancer Therapy Optimization
Short non-coding transcripts can be transcribed from distant-acting transcriptional enhancer loci , but the prevalence of such enhancer RNAs ( eRNAs ) within the transcriptome , and the association of eRNA expression with tissue-specific enhancer activity in vivo remain poorly understood . Here , we investigated the ex...
Up to 80% of mammalian genomes are actively transcribed , producing large numbers of non-coding RNAs without known functions . One particularly exciting category of such non-coding transcripts are the recently discovered enhancer RNAs ( eRNAs ) transcribed from distant-acting enhancer elements . Studies in cell-based p...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "genetics", "biology", "and", "life", "sciences", "developmental", "biology" ]
2014
Tissue-Specific RNA Expression Marks Distant-Acting Developmental Enhancers
Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments . This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life . Bacteria have evolved enormous bio...
Adaptive radiation is the rapid origination of an array of species by the divergent colonization of disparate ecological niches . In the case of pathogenic bacteria , radiations can lead to the emergence of novel human pathogens . Being divergently adapted to a range of different mammalian hosts , including humans as r...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/genomics", "genetics", "and", "genomics/microbial", "evolution", "and", "genomics", "evolutionary", "biology/microbial", "evolution", "and", "genomics", "infectious", "diseases", "genetics", "and", "genomics/comparative", "genomics", "evolutionary...
2011
Parallel Evolution of a Type IV Secretion System in Radiating Lineages of the Host-Restricted Bacterial Pathogen Bartonella
Recent genome-wide ( GW ) scans have identified several independent loci affecting human stature , but their contribution through the different skeletal components of height is still poorly understood . We carried out a genome-wide scan in 12 , 611 participants , followed by replication in an additional 7 , 187 individ...
The first genetic association studies of adult height have confirmed a role of many common variants in influencing human height , but to date , the genetic basis of differences between different skeletal components of height have not been addressed . Here , we take advantage of recent technical and methodological advan...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/complex", "traits", "rheumatology/bone", "and", "mineral", "metabolism", "genetics", "and", "genomics", "rheumatology/cartilage", "biology", "and", "osteoarthritis" ]
2009
Meta-Analysis of Genome-Wide Scans for Human Adult Stature Identifies Novel Loci and Associations with Measures of Skeletal Frame Size
Ecological niche models are useful tools to infer potential spatial and temporal distributions in vector species and to measure epidemiological risk for infectious diseases such as the Leishmaniases . The ecological niche of 28 North and Central American sand fly species , including those with epidemiological relevance...
The present study models the niche of the most abundant sand fly species in North and Central America , including all proven and incriminated vectors of Leishmaniases , an important neglected tropical disease of the region . The expansion and elevation or centroid shifts of the species' niche are modeled for extreme ( ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2013
Current and Future Niche of North and Central American Sand Flies (Diptera: Psychodidae) in Climate Change Scenarios
Animal heterotrimeric G proteins are activated by guanine nucleotide exchange factors ( GEF ) , typically seven transmembrane receptors that trigger GDP release and subsequent GTP binding . In contrast , the Arabidopsis thaliana G protein ( AtGPA1 ) rapidly activates itself without a GEF and is instead regulated by a s...
Extracellular signals activate intracellular changes that lead to cell behaviors . This spatial coupling is mediated by cell-surface receptor activation of the heterotrimeric G protein complex located on the cytoplasmic side of the plasma membrane . Unlike the case for metazoans , plant G proteins are constitutively ac...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "signal", "transduction", "molecular", "cell", "biology", "biology", "evolutionary", "biology", "molecular", "biology" ]
2012
G Protein Activation without a GEF in the Plant Kingdom
Many algorithms that compare protein structures can reveal similarities that suggest related biological functions , even at great evolutionary distances . Proteins with related function often exhibit differences in binding specificity , but few algorithms identify structural variations that effect specificity . To addr...
Proteins carry out vital and specific functions by physically binding other molecules . Understanding specificity , the preferential binding of certain molecules to one another , is essential for numerous medical and industrial applications . Given the structure of a protein with unknown function , algorithms are avail...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "computational", "biology/macromolecular", "structure", "analysis", "biochemistry/bioinformatics" ]
2010
VASP: A Volumetric Analysis of Surface Properties Yields Insights into Protein-Ligand Binding Specificity
The 22q11 . 2 deletion syndrome ( 22q11 . 2DS; velo-cardio-facial syndrome; DiGeorge syndrome ) is a congenital anomaly disorder in which haploinsufficiency of TBX1 , encoding a T-box transcription factor , is the major candidate for cardiac outflow tract ( OFT ) malformations . Inactivation of Tbx1 in the anterior hea...
To understand the genetic relationship between Tbx1 and canonical Wnt/β-catenin , we performed gene expression profiling and genetic rescue experiments . We found that Tbx1 and β-catenin may provide a negative feedback loop to restrict premature differentiation in the anterior heart field . This is relevant to understa...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "and", "health", "sciences", "cardiovascular", "anatomy", "cardiac", "ventricles", "ventricular", "septal", "defects", "animal", "models", "developmental", "biology", "model", "organisms", "experimental", "organism", "systems", "embryos", "morphogenesis", "car...
2017
Reduced dosage of β-catenin provides significant rescue of cardiac outflow tract anomalies in a Tbx1 conditional null mouse model of 22q11.2 deletion syndrome
Mutations in Pten-induced kinase 1 ( PINK1 ) are linked to early-onset familial Parkinson's disease ( FPD ) . PINK1 has previously been implicated in mitochondrial fission/fusion dynamics , quality control , and electron transport chain function . However , it is not clear how these processes are interconnected and whe...
Parkinson's disease ( PD ) is the second most common neurodegenerative disease . It mainly affects movement in elderly people and was traditionally considered a sporadic disease with no known cause . Discoveries of genes associated with familial PD ( FPD ) have demonstrated that PD pathogenesis can be significantly inf...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "animal", "models", "medicine", "cellular", "structures", "model", "organisms", "molecular", "cell", "biology", "cell", "biology", "neurological", "disorders", "neurology", "biology", "neuroscience" ]
2012
Parkinson's Disease–Associated Kinase PINK1 Regulates Miro Protein Level and Axonal Transport of Mitochondria
Comprising nearly half of the human and mouse genomes , transposable elements ( TEs ) are found within most genes . Although the vast majority of TEs in introns are fixed in the species and presumably exert no significant effects on the enclosing gene , some markedly perturb transcription and result in disease or a mut...
Sequences derived from transposable elements ( TEs ) are major constituents of mammalian genomes and are found within introns of most genes . While nearly all TEs within introns appear harmless , some de novo intronic TE insertions do disrupt gene transcription and splicing and cause disease . It is unclear why some in...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "genomics", "genome", "evolution", "evolutionary", "biology", "gene", "regulation", "molecular", "genetics", "biology", "computational", "biology", "genomic", "evolution" ]
2011
Distributions of Transposable Elements Reveal Hazardous Zones in Mammalian Introns
Localization of specific mRNAs is an important mechanism through which cells achieve polarity and direct asymmetric growth . Based on a framework established in Saccharomyces cerevisiae , we describe a She3-dependent RNA transport system in Candida albicans , a fungal pathogen of humans that grows as both budding ( yea...
Generation of cellular polarity – asymmetry in shape , protein distribution , and/or sub-cellular function – is an essential feature of most eukaryotic cells and underlies such diverse processes as differentiation , mating , nutrient acquisition , and growth . Localization of specific mRNAs is one mechanism through whi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "biology/microbial", "physiology", "and", "metabolism", "infectious", "diseases/fungal", "infections", "cell", "biology/developmental", "molecular", "mechanisms", "molecular", "biology/mrna", "transport", "and", "localization", "evolutionary", "biology", "genetics", "...
2009
An RNA Transport System in Candida albicans Regulates Hyphal Morphology and Invasive Growth
Phototrophic organisms such as cyanobacteria utilize the sun’s energy to convert atmospheric carbon dioxide into organic carbon , resulting in diurnal variations in the cell’s metabolism . Flux balance analysis is a widely accepted constraint-based optimization tool for analyzing growth and metabolism , but it is gener...
Phototrophic organisms such as cyanobacteria harvest the sun’s energy to convert atmospheric CO2 into organic carbon , due to which their metabolism is heavily influenced by light availability . The strongly diurnal nature of their metabolism is reflected in the presence of two distinct metabolic phases–a light-depende...
[ "Abstract", "Introduction", "Results/Discussion", "Methods" ]
[ "light", "plant", "physiology", "electromagnetic", "radiation", "plant", "science", "metabolites", "genome", "analysis", "photosynthesis", "bacteria", "genomics", "metabolic", "pathways", "cyanobacteria", "physics", "biochemistry", "plant", "biochemistry", "nitrogen", "fixa...
2019
A diurnal flux balance model of Synechocystis sp. PCC 6803 metabolism
CD8 T cells are necessary for the elimination of intracellular pathogens , but during chronic viral infections , CD8 T cells become exhausted and unable to control the persistent infection . Programmed cell death-1 ( PD-1 ) blockade therapies have been shown to improve CD8 T cell responses during chronic viral infectio...
Although PD-1 therapies have revolutionized cancer treatment , these therapies have not yet been licensed to treat chronic viral infections . This is because limited benefit is seen in pre-clinical models of chronic viral infection . Interestingly , recent reports in cancer models have suggested that certain microbes c...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "blood", "cells", "medicine", "and", "health", "sciences", "immune", "cells", "immune", "physiology", "viral", "transmission", "and", "infection", "spleen", "cancer", "treatment", "immunology", "microbiology", "cancer", "immunotherapy", "oncology", "clinical", "medicine...
2019
TLR4 signaling improves PD-1 blockade therapy during chronic viral infection
Biological systems often detect species-specific signals in the environment . In humans , speech and language are species-specific signals of fundamental biological importance . To detect the linguistic signal , human brains must form hierarchical representations from a sequence of perceptual inputs distributed in time...
Human language is a fundamental biological signal with computational properties that differ from other perception-action systems: hierarchical relationships between sounds , words , phrases , and sentences and the unbounded ability to combine smaller units into larger ones , resulting in a "discrete infinity" of expres...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "learning", "neurolinguistics", "linguistics", "neural", "networks", "engineering", "and", "technology", "signal", "processing", "social", "sciences", "neuroscience", "learning", "and", "memory", "sentence", "processing", "cognitive", "psychology", "cognition", "memory", ...
2017
A mechanism for the cortical computation of hierarchical linguistic structure
Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression . For example , cytidine deaminase ( CDA ) deficiency leads to an excess of dCTP , slowing the replication fork . We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the...
The maintenance of genome stability is essential for the accurate transmission of genetic information , to ensure the successful duplication of chromosomes and their even segregation during mitosis . Errors occurring during DNA replication may affect both the accuracy of chromosome duplication and the balance of chromo...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA
Mutations in the glucosylceramidase beta ( GBA ) gene are strongly associated with neurodegenerative diseases marked by protein aggregation . GBA encodes the lysosomal enzyme glucocerebrosidase , which breaks down glucosylceramide . A common explanation for the link between GBA mutations and protein aggregation is that...
Mutations in the GBA gene , which encodes the enzyme glucocerebrosidase , are common and increase the risk of Parkinson disease . A widely accepted explanation for the increased risk is that the fatty substance normally broken down by glucocerebrosidase builds up in the lysosome , which is the cell’s recycling center ,...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "death", "invertebrates", "autophagic", "cell", "death", "lysosomes", "vesicles", "protein", "aggregation", "cell", "processes", "animals", "animal", "models", "membrane", "proteins", "drosophila", "melanogaster", "model", "organisms", "experimental", "organism", ...
2018
Glucocerebrosidase deficiency promotes protein aggregation through dysregulation of extracellular vesicles
What does it take to convert a heap of sequencing data into a publishable result ? First , common tools are employed to reduce primary data ( sequencing reads ) to a form suitable for further analyses ( i . e . , the list of variable sites ) . The subsequent exploratory stage is much more ad hoc and requires the develo...
Galaxy users can utilize a large number of tools and workflows . What they could not previously do is run ad hoc scripts and arbitrary tools within their Galaxy instance . This was very limiting , as initial analyses of data often involve interactive exploration with tools like Jupyter or RStudio—powerful platforms tha...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results/Discussion" ]
[ "sequencing", "techniques", "education", "mitochondrial", "dna", "astronomical", "sciences", "invertebrate", "genomics", "next-generation", "sequencing", "genome", "analysis", "forms", "of", "dna", "energy-producing", "organelles", "molecular", "biology", "techniques", "bio...
2017
Jupyter and Galaxy: Easing entry barriers into complex data analyses for biomedical researchers
In order to propagate a solid tumor , cancer cells must adapt to and survive under various tumor microenvironment ( TME ) stresses , such as hypoxia or lactic acidosis . To systematically identify genes that modulate cancer cell survival under stresses , we performed genome-wide shRNA screens under hypoxia or lactic ac...
During the development of most solid tumors , there are characteristic physiological differences in the tumor that result from tumor cells outgrowing their local blood supply . Two of these physiological differences , or “stresses , ” that occur in the tumor are low oxygen levels ( hypoxia ) and an accumulation of lact...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
ACLY and ACC1 Regulate Hypoxia-Induced Apoptosis by Modulating ETV4 via α-ketoglutarate
Heterozygous Twirler ( Tw ) mice develop obesity and circling behavior associated with malformations of the inner ear , whereas homozygous Tw mice have cleft palate and die shortly after birth . Zeb1 is a zinc finger protein that contributes to mesenchymal cell fate by repression of genes whose expression defines epith...
Twirler ( Tw ) mice have a combination of abnormalities that includes cleft palate , malformations of the inner ear , hearing loss , vestibular dysfunction , obesity , and lymphoid hypoplasia . In this study , we show that the underlying mutation affects the Zeb1 gene . Zeb1 was already known to encode a protein normal...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "biology", "veterinary", "science" ]
2011
A Noncoding Point Mutation of Zeb1 Causes Multiple Developmental Malformations and Obesity in Twirler Mice
Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is a human oncogenic virus associated with Kaposi’s sarcoma and two B-cell malignancies . The rhesus monkey rhadinovirus ( RRV ) is a virus of nonhuman primates that is closely related to KSHV . Eph family receptor tyrosine kinases ( Ephs ) are cellular receptors for the...
In immunocompromised individuals in general and in the context of HIV infection in particular , KSHV is a major cause of cancer and B-cell proliferative malignancies . We identified and mutated conserved residues in the N-terminal domain of the gH/gL glycoprotein complex of KSHV and the related monkey virus RRV that ar...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "crystal", "structure", "pathology", "and", "laboratory", "medicine", "pathogens", "endothelial", "cells", "condensed", "matter", "physics", "microbiology", "fibroblasts", "epithelial", "cells", "viruses", "mutation", "dna", "vir...
2018
A conserved Eph family receptor-binding motif on the gH/gL complex of Kaposi’s sarcoma-associated herpesvirus and rhesus monkey rhadinovirus
Proteins interact in complex protein–protein interaction ( PPI ) networks whose topological properties—such as scale-free topology , hierarchical modularity , and dissortativity—have suggested models of network evolution . Currently preferred models invoke preferential attachment or gene duplication and divergence to p...
Proteins function together forming stable protein complexes or transient interactions in various cellular processes , such as gene regulation and signaling . Here , we address the basic question of how these networks of interacting proteins evolve . This is an important problem , as the structures of such networks unde...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "biochemistry/molecular", "evolution", "biophysics/macromolecular", "assemblies", "and", "machines", "biophysics/theory", "and", "simulation", "computational", "biology/evolutionary", "modeling", "biochemistry/bioinformatics", "biochemistry/theory", "and", "simulation", "biochemistry...
2008
Age-Dependent Evolution of the Yeast Protein Interaction Network Suggests a Limited Role of Gene Duplication and Divergence
Fusion peptides from influenza hemagglutinin act on membranes to promote membrane fusion , but the mechanism by which they do so remains unknown . Recent theoretical work has suggested that contact of protruding lipid tails may be an important feature of the transition state for membrane fusion . If this is so , then i...
Membrane fusion is a common process critical to both cellular function and infection by enveloped viruses . Influenza is a particularly useful model system for studying fusion because the fusion reaction is accomplished by a single protein , hemagglutinin . Furthermore , mutations to the membrane-inserted portion of he...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "biology", "computational", "biology" ]
2013
Lipid Tail Protrusion in Simulations Predicts Fusogenic Activity of Influenza Fusion Peptide Mutants and Conformational Models
The extent by which different cellular components generate phenotypic diversity is an ongoing debate in evolutionary biology that is yet to be addressed by quantitative comparative studies . We conducted an in vivo mass-spectrometry study of the phosphoproteomes of three yeast species ( Saccharomyces cerevisiae , Candi...
Natural selection at a population level requires phenotypic diversity , which at the molecular level arises by mutation of the genome of each individual . What kinds of changes at the level of the DNA are most important for the generation of phenotypic differences remains a fundamental question in evolutionary biology ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "computational", "biology/signaling", "networks", "genetics", "and", "genomics/comparative", "genomics", "evolutionary", "biology/evolutionary", "and", "comparative", "genetics", "cell", "biology/cell", "signaling" ]
2009
Evolution of Phosphoregulation: Comparison of Phosphorylation Patterns across Yeast Species
The analysis of double-strand break ( DSB ) repair is complicated by the existence of several pathways utilizing a large number of genes . Moreover , many of these genes have been shown to have multiple roles in DSB repair . To address this complexity we used a repair reporter construct designed to measure multiple rep...
DNA is a fragile thread that often breaks . When it does , the cell must find a way to splice the broken ends back together in order to continue its cycle of replication . Cells possess an array of ways to rejoin broken DNA ends , each with advantages and disadvantages . Some are “quick and dirty , ” sacrificing accura...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "molecular", "biology", "genetics", "and", "genomics", "drosophila", "melanogaster" ]
2007
Multiple-Pathway Analysis of Double-Strand Break Repair Mutations in Drosophila
The control of virulence regulator/sensor kinase ( CovRS ) two-component system is critical to the infectivity of group A streptococcus ( GAS ) , and CovRS inactivating mutations are frequently observed in GAS strains causing severe human infections . CovS modulates the phosphorylation status and with it the regulatory...
Group A streptococcus ( GAS ) , also known as Streptococcus pyogenes , causes a broad array of human infections of varying severity . Tight control of production of virulence factors is critical to GAS pathogenesis , and the control of virulence two-component signaling system ( CovRS ) is central to this process . The ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "phosphorylation", "medicine", "and", "health", "sciences", "body", "fluids", "pathology", "and", "laboratory", "medicine", "enzymes", "pathogens", "gene", "regulation", "enzymology", "phosphatases", "animal", "models", "model", "organisms", "experimental", "organism", ...
2018
Phosphatase activity of the control of virulence sensor kinase CovS is critical for the pathogenesis of group A streptococcus
The anthelmintic emodepside paralyses adult filarial worms , via a mode of action distinct from previous anthelmintics and has recently garnered interest as a new treatment for onchocerciasis . Whole organism data suggest its anthelmintic action is underpinned by a selective activation of the nematode isoform of an evo...
Filarial diseases affect an estimated 200 million people and the Drugs for Neglected Diseases initiative ( DNDi ) has identified development of macrofilaricidal drugs as a priority . Emodepside , currently used in companion animals , paralyses adult filarial worms and may address this unmet need for human medicine . It...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
The Cyclooctadepsipeptide Anthelmintic Emodepside Differentially Modulates Nematode, Insect and Human Calcium-Activated Potassium (SLO) Channel Alpha Subunits
Insect molting and metamorphosis are intricately governed by two hormones , ecdysteroids and juvenile hormones ( JHs ) . JHs prevent precocious metamorphosis and allow the larva to undergo multiple rounds of molting until it attains the proper size for metamorphosis . In the silkworm , Bombyx mori , several “moltinism”...
The number of larval instars in insects varies greatly across insect taxa and can even vary at the intraspecific level . However , little is known about how the number of larval instars is fixed in each species or modified by the environment . The silkworm , Bombyx mori , provides a unique bioresource for investigating...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry", "developmental", "biology", "genetics", "biology", "zoology", "genetics", "and", "genomics" ]
2012
Precocious Metamorphosis in the Juvenile Hormone–Deficient Mutant of the Silkworm, Bombyx mori
In mammalian auditory cortex , sound source position is represented by a population of broadly tuned neurons whose firing is modulated by sounds located at all positions surrounding the animal . Peaks of their tuning curves are concentrated at lateral position , while their slopes are steepest at the interaural midline...
Ability to localize the position of a sound source is vital to many organisms , since audition provides information about areas which are not accessible visually . While its importance is undisputed , its neuronal mechanisms are not well understood . It has been observed in experimental studies that despite the crucial...
[ "Abstract", "Introduction", "Results", "Properties", "of", "the", "second", "layer", "representation", "Discussion", "Methods" ]
[]
2015
The Opponent Channel Population Code of Sound Location Is an Efficient Representation of Natural Binaural Sounds
To assess if a probabilistic model could be used to estimate the combined prevalence of infection with any species of intestinal nematode worm when only the separate prevalence of each species is reported , and to estimate the extent to which simply taking the highest individual species prevalence underestimates the co...
Mixed infections with roundworm , whipworm and hookworm are common , but survey reports often give only the separate prevalence of each type . However , the combined prevalence is important to estimate accurately the number of individuals who would benefit from control programmes and to make decisions about the frequen...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "public", "health", "and", "epidemiology/infectious", "diseases" ]
2010
Using the Prevalence of Individual Species of Intestinal Nematode Worms to Estimate the Combined Prevalence of Any Species
Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in-patient care for people afflicted by Buruli ulcer ( BU ) and chronic ulcers . Research on hospitals as therapeutic communities is virtually non-existent in Africa and is curr...
Little is known about communication patterns and social relations between health staff and long -term patients in African hospitals . An ethnography of a reference hospital treating patients afflicted with Buruli Ulcer ( BU ) and other chronic ulcers in Benin was conducted . Sources of psychosocial distress and communi...
[ "Abstract", "Introduction", "Methods", "Discussion" ]
[ "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "health", "services", "research", "sociology", "tropical", "diseases", "social", "sciences", "health", "care", "bacterial", "diseases", "research", "design", "scientists", "signs", ...
2016
Steps Toward Creating A Therapeutic Community for Inpatients Suffering from Chronic Ulcers: Lessons from Allada Buruli Ulcer Treatment Hospital in Benin
Recently , a molecular pathway linking inflammation to cell transformation has been discovered . This molecular pathway rests on a positive inflammatory feedback loop between NF-κB , Lin28 , Let-7 microRNA and IL6 , which leads to an epigenetic switch allowing cell transformation . A transient activation of an inflamma...
An increasing amount of evidence demonstrates a close relation between inflammation and cancer development , which reveals the importance of the tumor microenvironment for the development of cancers . Recently , a molecular pathway linking inflammation to cell transformation , which is a prerequisite to cancer developm...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "complex", "systems", "systems", "biology", "nonlinear", "dynamics", "signal", "transduction", "stat", "signaling", "family", "signaling", "in", "cellular", "processes", "mathematics", "theoretical", "biology", "oncogenic", "signaling", "applied", "mathematics", "ras", ...
2014
A Model for the Epigenetic Switch Linking Inflammation to Cell Transformation: Deterministic and Stochastic Approaches
Since leprosy is both treated and controlled by multidrug therapy ( MDT ) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy . All three objectives can be reached with single nucleotide resolution using next gene...
Leprosy , one of the most ancient human infectious diseases , affects skin and nerves and is caused by Mycobacterium leprae infection . Despite the effective use of multidrug therapy/MDT since the 80´s , over 200 , 000 new cases are reported yearly , indicating active transmission , especially in India and Brazil . Alt...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "sequencing", "techniques", "mycobacterium", "leprae", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "biopsy", "tropical", "diseases", "surgical", "and", "invasive", "medical", "procedures", "genome", "sequencing", "bacterial", "...
2017
Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases
Polycomb group ( PcG ) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state . PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3 , catalyzed by the Polycomb repressive complex 2 . Here , we present ...
In Parkinson's disease ( PD ) the motor impairment produced by the progressive death of midbrain dopaminergic neurons is commonly treated with the dopamine precursor , L-DOPA . Utilizing a mouse model of PD , we show that L-DOPA , via activation of dopamine D1 receptors , promotes the expression of genes normally repre...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biology", "and", "life", "sciences", "medicine", "and", "health", "sciences" ]
2014
Dopamine Signaling Leads to Loss of Polycomb Repression and Aberrant Gene Activation in Experimental Parkinsonism
We performed a genome-level computational study of sequence and structure similarity , the latter using crystal structures and models , of the proteases of Homo sapiens and the human parasite Trypanosoma brucei . Using sequence and structure similarity networks to summarize the results , we constructed global views tha...
Human African trypanosomiasis ( HAT ) is caused by the protozoan parasite Trypanosoma brucei . HAT is fatal unless treated , yet the current treatment itself can cause death . New treatments are urgently needed . Our study focuses on proteases , which are enzymes that break down proteins . Because of their roles in man...
[ "Abstract", "Introduction", "Methods", "Results", "and", "Discussion", "Conclusions" ]
[ "genomics", "biology", "computational", "biology", "structural", "genomics", "genetics", "and", "genomics" ]
2012
A Global Comparison of the Human and T. brucei Degradomes Gives Insights about Possible Parasite Drug Targets
The burden of leptospirosis in humans and animals in Africa is higher than that reported from other parts of the world . However , the disease is not routinely diagnosed in the continent . One of major factors limiting diagnosis is the poor availability of live isolates of locally circulating Leptospira serovars for in...
Leptospirosis disease is widespread in humans and broad range of animal species in Africa . However , leptospirosis is highly neglected and not extensively taught in both medical and veterinary schools almost across Africa . Availability of live leptospires isolated from Africa for use in its diagnosis by the gold stan...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
Leptospira Serovars for Diagnosis of Leptospirosis in Humans and Animals in Africa: Common Leptospira Isolates and Reservoir Hosts
Prominent immune alterations associated with aging include the loss of naïve T-cell numbers , diversity and function . While genetic contributors and mechanistic details in the aging process have been addressed in multiple studies , the role of environmental agents in immune aging remains incompletely understood . From...
The cytomegalovirus ( CMV ) is a widespread virus of the herpesvirus family , which latently infects the majority of the adult human population worldwide . While CMV causes severe disease in AIDS patients , in recipients of organ transplants , or when infection occurs during pregnancy , this virus is considered apathog...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "infectious", "diseases", "immune", "cells", "west", "nile", "fever", "influenza", "immunology", "biology", "viral", "diseases", "cytomegalovirus", "infection", "immunomodulation" ]
2012
Cytomegalovirus Infection Impairs Immune Responses and Accentuates T-cell Pool Changes Observed in Mice with Aging
Cyclin-dependent kinase 9 ( Cdk9 ) promotes elongation by RNA polymerase II ( RNAPII ) , mRNA processing , and co-transcriptional histone modification . Cdk9 phosphorylates multiple targets , including the conserved RNAPII elongation factor Spt5 and RNAPII itself , but how these different modifications mediate Cdk9 fun...
The expression of many eukaryotic genes is regulated during the elongation phase of transcription . Cyclin-dependent kinase 9 ( CDK9 ) enzymes are key positive regulators of RNA polymerase II ( RNAPII ) elongation , and are required for co-transcriptional events such as mRNA processing and chromatin modification . Cdk9...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
The PAF Complex and Prf1/Rtf1 Delineate Distinct Cdk9-Dependent Pathways Regulating Transcription Elongation in Fission Yeast
The developmental time of vector insects is important in population dynamics , evolutionary biology , epidemiology and in their responses to global climatic change . In the triatomines ( Triatominae , Reduviidae ) , vectors of Chagas disease , evolutionary ecology concepts , which may allow for a better understanding o...
The developmental time of vector insects is important to their population dynamics , evolutionary biology , epidemiology of the diseases they transmit , and to their responses to global climatic change . In various triatomine species vectors of Chagas disease ( Triatominae , Reduviidae ) , a delay in the molt of a smal...
[ "Abstract", "Introduction", "Results", "Discussion" ]
[ "ecology/evolutionary", "ecology", "public", "health", "and", "epidemiology", "evolutionary", "biology/evolutionary", "ecology" ]
2010
Adaptive Developmental Delay in Chagas Disease Vectors: An Evolutionary Ecology Approach
The insulin/IGF-1 signaling ( IIS ) pathway is a conserved regulator of longevity , development , and metabolism . In Caenorhabditis elegans IIS involves activation of DAF-2 ( insulin/IGF-1 receptor tyrosine kinase ) , AGE-1 ( PI 3-kinase ) , and additional downstream serine/threonine kinases that ultimately phosphoryl...
Cells in the body respond to a variety of on/off signals that are relayed in a defined spatial and temporal manner . These signals influence several processes such as growth , fat storage , and the repair of damaged molecules . As humans age , the onset of diseases such as Type 2 Diabetes , obesity , and cancer often r...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/animal", "genetics", "genetics", "and", "genomics/gene", "discovery", "developmental", "biology/aging", "diabetes", "and", "endocrinology", "molecular", "biology", "developmental", "biology/developmental", "molecular", "mechanisms" ]
2011
PDP-1 Links the TGF-β and IIS Pathways to Regulate Longevity, Development, and Metabolism
For decades La Réunion has experienced a number of epidemics that have resulted in efforts to control the density of Aedes species on this Island . This study was conducted to assess household-level expenditure on protective measures against mosquito nuisance on the Island of La Réunion in 2012 . Data was collected dur...
The French Ministry of Health has , for decades , dedicated numerous resources to control mosquito density on the Island of La Réunion . These efforts were strengthened following an outbreak of chikungunya , a virus transmitted by Aedes mosquitoes , in 2005–2006 . In order to understand how public perception and behavi...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "social", "and", "behavioral", "sciences", "economics" ]
2014
Household-Level Expenditure on Protective Measures Against Mosquitoes on the Island of La Réunion, France
For most of the world , human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts , factors that are captured by the concepts of biogeographic ancestry and admixture , respectively . The ancestry of non-admixed individuals can often be tr...
Admixed individuals , such as African Americans and Latinos , arise from mating between individuals from different continents . Detailed knowledge about the ancestral origin of an admixed population not only provides insight regarding the history of the population itself , but also affords opportunities to study the ev...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genome-wide", "association", "studies", "genomics", "mathematics", "evolutionary", "biology", "statistics", "genetics", "population", "genetics", "biology", "computational", "biology", "statistical", "methods", "genetics", "and", "genomics" ]
2011
Ancestral Components of Admixed Genomes in a Mexican Cohort
Mutator phenotypes accelerate the evolutionary process of neoplastic transformation . Historically , the measurement of mutation rates has relied on scoring the occurrence of rare mutations in target genes in large populations of cells . Averaging mutation rates over large cell populations assumes that new mutations ar...
Mutations fuel microbial evolution and cancer . Cells with an increased rate of mutation are said to have a “mutator phenotype” and adapt more rapidly than non-mutator cells . Our study utilizes a novel way of measuring mutation rates of individual cell divisions to show that mutator cells can adopt one of two mutation...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Volatility of Mutator Phenotypes at Single Cell Resolution
Identifying driver mutations in cancer is notoriously difficult . To date , recurrence of a mutation in patients remains one of the most reliable markers of mutation driver status . However , some mutations are more likely to occur than others due to differences in background mutation rates arising from various forms o...
Cancer development and progression is associated with accumulation of mutations . However , only a small fraction of mutations identified in a patient is responsible for cellular transformations leading to cancer . These so-called drivers characterize molecular profiles of tumors and could be helpful in predicting clin...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "mutation", "substitution", "mutation", "point", "mutation", "cancer", "genetics", "nonsense", "mutation", "database", "and", "informatics", "methods", "silent", "mutation", "genetics", "biological", "databases", "biology", "and", "life", "sciences", "mutation", "databa...
2019
Finding driver mutations in cancer: Elucidating the role of background mutational processes