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Modeling the transport , activation , and adhesion of platelets is crucial in predicting thrombus formation and growth following a thrombotic event in normal or pathological conditions . We propose a shear-dependent platelet adhesive model based on the Morse potential that is calibrated by existing in vivo and in vitro...
Hemostasis ( thrombus formation ) is the normal physiological response that prevents significant blood loss after vascular injury . The resulting clots can form under different flow conditions in the veins as well as the arteries . The excessive and undesirable formation of clots ( i . e . , thrombosis ) in our circula...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "blood", "cells", "medicine", "and", "health", "sciences", "body", "fluids", "classical", "mechanics", "pathology", "and", "laboratory", "medicine", "fluid", "mechanics", "platelet", "aggregation", "platelet", "activation", "signs", "and", "symptoms", "materials", "sc...
2017
A General Shear-Dependent Model for Thrombus Formation
Plant NLR ( Nucleotide-binding domain and Leucine-rich Repeat ) immune receptor proteins are encoded by Resistance ( R ) genes and confer specific resistance to pathogen races that carry the corresponding recognized effectors . Some NLR proteins function in pairs , forming receptor complexes for the perception of speci...
Paired NLR immune receptors have evolved in both plants and animals to enable host cells to detect intracellular pathogen effectors or ligands . Generally , one of the two NLR proteins in the two-component immune complex acts as a sensor that enables effector detection , while the helper ( or executor ) NLR activates a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biotechnology", "immune", "complex", "plant", "anatomy", "medicine", "and", "health", "sciences", "molecular", "probe", "techniques", "immunology", "brassica", "microbiology", "immunoblotting", "plant", "science", "model", "organisms", "luminescent", "proteins", "immunop...
2017
Protein-protein interactions in the RPS4/RRS1 immune receptor complex
The high-risk pedigree ( HRP ) design is an established strategy to discover rare , highly-penetrant , Mendelian-like causal variants . Its success , however , in complex traits has been modest , largely due to challenges of genetic heterogeneity and complex inheritance models . We describe a HRP strategy that addresse...
Although family-based studies demonstrate inherited variants play a role in many common and complex diseases , finding the genes responsible remains a challenge . High-risk pedigrees , or families with more disease than expected by chance , have aided discovery of genes responsible for less complex diseases , but high-...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "united", "states", "medicine", "and", "health", "sciences", "myelomas", "gene", "regulation", "geographical", "locations", "cancers", "and", "neoplasms", "north", "america", "oncology", "hematologic", "cancers", "and", "related", "disorders", "plasma", "cell", "disor...
2018
Novel pedigree analysis implicates DNA repair and chromatin remodeling in multiple myeloma risk
Overexpression of SPARC , a collagen-binding glycoprotein , is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers . SPARC regulates numerous cellular processes including integrin-mediated cell adhesion , cell signaling pathways , and extracellular matrix assembly; however , ...
SPARC is an extracellular matrix protein that is present at high levels in many metastatic cancers where it promotes tumor invasion into neighboring tissues . The mechanism linking a surplus of SPARC to cell invasion , however , is not clear due to the challenge of examining SPARCs function in complex tumor environment...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "rna", "interference", "fluorescence", "caenorhabditis", "basic", "cancer", "research", "animals", "electromagnetic", "radiation", "collagens", "animal", "models", "oncology", "caenorhabditis", "elegans", "model", ...
2016
SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane
Transcriptional enhancers integrate the contributions of multiple classes of transcription factors ( TFs ) to orchestrate the myriad spatio-temporal gene expression programs that occur during development . A molecular understanding of enhancers with similar activities requires the identification of both their unique an...
The development of multicellular organisms requires the formation of a diversity of cell types . Each cell has a unique genetic program that is orchestrated by regulatory sequences called enhancers , comprising multiple short DNA sequences that bind distinct transcription factors . Understanding developmental regulator...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "systems", "biology", "developmental", "biology", "genomics", "genetics", "biology", "computational", "biology", "genetics", "and", "genomics" ]
2012
A Machine Learning Approach for Identifying Novel Cell Type–Specific Transcriptional Regulators of Myogenesis
Klebsiella pneumoniae has emerged as an important cause of two distinct public health threats: multi-drug resistant ( MDR ) healthcare-associated infections and drug susceptible community-acquired invasive infections . These pathotypes are generally associated with two distinct subsets of K . pneumoniae lineages or ‘cl...
Klebsiellla pneumoniae is classified by the World Health Organization as a priority drug-resistant organism because it causes a significant burden of hospital infections that are extremely difficult to treat . However , outside of the hospital setting this bacterium is also an important cause of severe drug-susceptible...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[]
2019
Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae
Oxygen depletion of Mycobacterium tuberculosis engages the DosR regulon that coordinates an overall down-regulation of metabolism while up-regulating specific genes involved in respiration and central metabolism . We have developed a chemostat model of M . tuberculosis where growth rate was a function of dissolved oxyg...
Tuberculosis in its latent form infects one-third of the total human population , hiding in structures called granulomas in the lung . The dense tissue formed by the granuloma severely limits the amount of oxygen available and yet somehow the bacteria manage to survive for many years . In this study we have examined TB...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "bacteriology", "bacterial", "physiology", "microbial", "metabolism", "medical", "microbiology", "biology", "microbiology", "bacterial", "pathogens", "gram", "positive" ]
2011
Fumarate Reductase Activity Maintains an Energized Membrane in Anaerobic Mycobacterium tuberculosis
Inverse Stochastic Resonance ( ISR ) is a phenomenon in which the average spiking rate of a neuron exhibits a minimum with respect to noise . ISR has been studied in individual neurons , but here , we investigate ISR in scale-free networks , where the average spiking rate is calculated over the neuronal population . We...
The rhythmic activity of spiking neurons is known to be sensitive to noise . In such neurons , inverse stochastic resonance ( ISR ) , in which the average spiking activity of a neuron exhibits a pronounced minimum as the noise intensity increases , can occur . But macroscopic phenomena such as information processing , ...
[ "Abstract", "Introduction", "Models", "and", "methods", "Results", "Discussion" ]
[ "cell", "physiology", "action", "potentials", "medicine", "and", "health", "sciences", "neural", "networks", "nervous", "system", "membrane", "potential", "junctional", "complexes", "electrophysiology", "neuroscience", "gap", "junctions", "ion", "channels", "scale-free", ...
2017
Inverse stochastic resonance in networks of spiking neurons
The Locus Control Region ( LCR ) requires intronic elements within β-globin transgenes to direct high level expression at all ectopic integration sites . However , these essential intronic elements cannot be transmitted through retrovirus vectors and their deletion may compromise the therapeutic potential for gene ther...
Expression of the β-globin gene is regulated by interactions between a distant Locus Control Region ( LCR ) and regulatory elements in or near the gene . We previously showed that LCR activity requires specific β-globin intron elements to consistently activate transgene expression in mice . These important intronic ele...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "hematology/hemoglobinopathies", "genetics", "and", "genomics/gene", "expression", "genetics", "and", "genomics/nuclear", "structure", "and", "function", "genetics", "and", "genomics/gene", "therapy", "genetics", "and", "genomics/epigenetics" ]
2008
β-Globin LCR and Intron Elements Cooperate and Direct Spatial Reorganization for Gene Therapy
Polylysogeny is frequently considered to be the result of an adaptive evolutionary process in which prophages confer fitness and/or virulence factors , thus making them important for evolution of both bacterial populations and infectious diseases . The Enterococcus faecalis V583 isolate belongs to the high-risk clonal ...
Enterococcus faecalis is a member of the core-microbiome of the human gastrointestinal tract . In the last decades however , this bacterial species has emerged as a major cause of hospital-acquired infections worldwide . Some isolates are particularly adapted to the hospital environment , and this adaptation was recent...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "gram", "positive", "bacterial", "pathogens", "biology", "microbiology" ]
2013
Enterococcus faecalis Prophage Dynamics and Contributions to Pathogenic Traits
Herpes simplex encephalitis ( HSE ) is a lethal neurological disease resulting from infection with Herpes Simplex Virus 1 ( HSV-1 ) . Loss-of-function mutations in the UNC93B1 , TLR3 , TRIF , TRAF3 , and TBK1 genes have been associated with a human genetic predisposition to HSE , demonstrating the UNC93B-TLR3-type I IF...
Herpes simplex encephalitis ( HSE ) is a lethal neurological disease resulting from infection with Herpes Simplex Virus 1 ( HSV-1 ) . Previous studies have demonstrated a human genetic predisposition to HSE . However , the gene mutations that have been suggested as critical in protective immunity to HSV-1 , exhibit inc...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "immunopathology", "animal", "models", "of", "infection", "mechanisms", "of", "resistance", "and", "susceptibility", "genetics", "of", "the", "immune", "system", "genetic", "screens", "virology", "genetics", "immunology", "host-pathogen", "interaction", "biology", "micr...
2013
Genome-Wide Mouse Mutagenesis Reveals CD45-Mediated T Cell Function as Critical in Protective Immunity to HSV-1
Computational models in biomedicine rely on biological and clinical assumptions . The selection of these assumptions contributes substantially to modeling success or failure . Assumptions used by experts at the cutting edge of research , however , are rarely explicitly described in scientific publications . One can dir...
Mathematical models and scientific theories fail not only from internal inconsistency , but also from the poor selection of basic assumptions . Assumptions in computational models of biomedicine are typically provided by scientists who interact directly with empirical data . If we seek to model the dynamics of cancer m...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "oncology", "medicine", "basic", "cancer", "research", "biology", "computational", "biology" ]
2011
Conflicting Biomedical Assumptions for Mathematical Modeling: The Case of Cancer Metastasis
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis ( GCTA ) has provided a means to quantify heritability attributable to all interrogated variants . We have quantified the variance in liability to disease explained by all SNPs for...
Family and twin studies have shown that genetic risk factors are important in the development of Tourette Syndrome ( TS ) and obsessive compulsive disorder ( OCD ) . However , efforts to identify the individual genetic risk factors involved in these two neuropsychiatric disorders have been largely unsuccessful . One po...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2013
Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
Epistasis , commonly defined as the interaction between multiple genes , is an important genetic component underlying phenotypic variation . Many statistical methods have been developed to model and identify epistatic interactions between genetic variants . However , because of the large combinatorial search space of i...
Epistasis is an important genetic component that underlies phenotypic variation and is also a key mechanism that accounts for missing heritability . Identifying epistatic interactions in genetic association studies can help us better understand the genetic architecture of complex traits and diseases . However , the abi...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "epistasis", "gene", "mapping", "simulation", "and", "modeling", "cell", "biology", "chromosome", "biology", "heredity", "phenotypes", "gene", "expression", "genetics", "biology", "and", "life", "sciences", "molecular", "biology", "techniques", "variant", "genotypes", ...
2017
Detecting epistasis with the marginal epistasis test in genetic mapping studies of quantitative traits
Heme-containing peroxidases are important components of innate immunity . Many of them functionally associate with NADPH oxidase ( NOX ) /dual oxidase ( DUOX ) enzymes by using the hydrogen peroxide they generate in downstream reactions . Caenorhabditis elegans encodes for several heme peroxidases , and in a previous s...
Reactive oxygen species ( ROS ) production by the host tissues is one of the first lines of defense when microbial infection occurs . ROS has been shown to be involved in multiple protective pathways in innate immunity . However , given the complexity of mammalian systems , the exact manner in which ROS are used for ho...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "skin", "invertebrates", "medicine", "and", "health", "sciences", "peroxidases", "rna", "interference", "integumentary", "system", "pathology", "and", "laboratory", "medicine", "caenorhabditis", "enzymes", "pathogens", "microbiology", "enzymology", "animals", "animal", "m...
2019
Heme peroxidase HPX-2 protects Caenorhabditis elegans from pathogens
Streptococcus agalactiae is a major neonatal pathogen whose infectious route involves septicemia . This pathogen does not synthesize heme , but scavenges it from blood to activate a respiration metabolism , which increases bacterial cell density and is required for full virulence . Factors that regulate heme pools in S...
The infectious route of numerous bacterial pathogens includes septicemia , where bacteria are exposed to heme-rich blood . Heme ( iron protoporphyrin IX ) is generally considered a bacterial iron source . However , while some pathogens do not biosynthesize heme , they use environmental heme to activate key functions . ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "microbiology/microbial", "physiology", "and", "metabolism", "microbiology", "microbiology/applied", "microbiology", "microbiology/microbial", "growth", "and", "development", "molecular", "biology", "microbiology/medical", "microbiology" ]
2010
Two Coregulated Efflux Transporters Modulate Intracellular Heme and Protoporphyrin IX Availability in Streptococcus agalactiae
Association mapping is a powerful approach for dissecting the genetic architecture of complex quantitative traits using high-density SNP markers in maize . Here , we expanded our association panel size from 368 to 513 inbred lines with 0 . 5 million high quality SNPs using a two-step data-imputation method which combin...
Genotype imputation has been used widely in the analysis of genome-wide association studies ( GWAS ) to boost power and fine-map associations . We developed a two-step data imputation method to meet the challenge of large proportion missing genotypes . GWAS have uncovered an extensive genetic architecture of complex qu...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genome-wide", "association", "studies", "cereal", "crops", "crop", "science", "population", "modeling", "genome", "analysis", "crops", "maize", "genetics", "biology", "and", "life", "sciences", "population", "biology", "computational", "biology", "agriculture" ]
2014
Genome Wide Association Studies Using a New Nonparametric Model Reveal the Genetic Architecture of 17 Agronomic Traits in an Enlarged Maize Association Panel
The type IX secretion system ( T9SS ) has been recently discovered and is specific to Bacteroidetes species . Porphyromonas gingivalis , a keystone pathogen for periodontitis , utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell su...
Chronic periodontitis is a major public health problem and Porphyromonas gingivalis is considered a keystone pathogen of the disease . The major virulence factors of P . gingivalis are the extracellular proteases called the gingipains . These gingipains and 30 other proteins that have a conserved C-terminal domain are ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "bacteriology", "protein", "transport", "periplasm", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "enzymes", "pathogens", "cell", "processes", "microbiology", "diet", "enzymology", "animal", "products", "membrane", "proteins", "...
2016
Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System
Single-trial analyses have the potential to uncover meaningful brain dynamics that are obscured when averaging across trials . However , low signal-to-noise ratio ( SNR ) can impede the use of single-trial analyses and decoding methods . In this study , we investigate the applicability of a single-trial approach to dec...
Averaging brain activity across trials is a powerful way to increase signal-to-noise ratio in MEG data . This approach , however , potentially obscures meaningful brain dynamics that unfold on the single-trial level . Single-trial analyses have been successfully applied to time domain or low frequency oscillatory activ...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "syllables", "auditory", "cortex", "medicine", "and", "health", "sciences", "linguistics", "applied", "mathematics", "brain", "social", "sciences", "neuroscience", "simulation", "and", "modeling", "algorithms", "mathematics", "artificial", "intelligence", "brain", "mappin...
2018
Across-subjects classification of stimulus modality from human MEG high frequency activity
Aggregation of amyloidogenic proteins is associated with several neurodegenerative diseases . Sequestration of misfolded and aggregated proteins into specialized deposition sites may reduce their potentially detrimental properties . Yeast exhibits a distinct deposition site for amyloid aggregates termed “Insoluble PrOt...
The occurrence of large inclusions of aggregated amyloidogenic proteins is a hallmark of several neurodegenerative diseases . The most toxic species are believed to represent smaller units such as oligomers , whereas larger amyloid depositions are viewed rather cell protective . Therefore , it is important to understan...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "death", "autophagic", "cell", "death", "vesicles", "chemical", "compounds", "cell", "processes", "light", "microscopy", "galactose", "carbohydrates", "organic", "compounds", "glucose", "hormones", "plant", "science", "plant", "hormones", "microscopy", "cellular...
2016
Prion Aggregates Are Recruited to the Insoluble Protein Deposit (IPOD) via Myosin 2-Based Vesicular Transport
In Gram-negative bacterial pathogens , specialized chaperones bind to secreted effector proteins and maintain them in a partially unfolded form competent for translocation by type III secretion systems/injectisomes . How diverse sets of effector-chaperone complexes are recognized by injectisomes is unclear . Here we de...
The obligate intracellular bacteria Chlamydia trachomatis is a common sexually transmitted pathogen and the leading cause of preventable blindness worldwide . Chlamydia co-opts host cells by secreting virulence factors directly into target cells through a multi-protein complex termed a type III secretion system or “inj...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "microbiology/cellular", "microbiology", "and", "pathogenesis", "genetics", "and", "genomics/functional", "genomics" ]
2009
The Chlamydia Type III Secretion System C-ring Engages a Chaperone-Effector Protein Complex
Reduced bacterial genomes and most genomes of cell organelles ( chloroplasts and mitochondria ) do not encode the full set of 32 tRNA species required to read all triplets of the genetic code according to the conventional wobble rules . Superwobbling , in which a single tRNA species that contains a uridine in the wobbl...
Reduced genomes of parasitic bacteria , chloroplasts , and mitochondria do not encode the full set of 32 tRNAs required to read all triplets of the genetic code according to Francis Crick's wobble rules . tRNAs with U in the wobble position of their anticodon might be able to make up for the deficit by pairing with any...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "functional", "genomics", "genome", "evolution", "plant", "biology", "gene", "function", "plant", "science", "plant", "genomics", "gene", "expression", "plant", "genetics", "biology", "evolutionary", "genetics", "plant", "biochemistry", "plant", "evolution", "protein", ...
2012
The Contributions of Wobbling and Superwobbling to the Reading of the Genetic Code
A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality . A subset of HIV-infected adults receiving effective antiretroviral therapy ( ART ) fails to normalize this ratio , even after they achieve normal CD4+ T cell counts . The immunologic and clinical characteristics ...
The CD4/CD8 ratio , a hallmark of the collection of T cell defects related to aging –“immunosenescence”- and a predictor of mortality in the general population , often fails to normalize in an important proportion of HIV-infected individuals with adequate CD4+ T cell recovery after ART initiation . However , the immuno...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "blood", "cells", "innate", "immune", "system", "medicine", "and", "health", "sciences", "immune", "cells", "hiv", "immunopathogenesis", "immune", "activation", "immunology", "microbiology", "lymphoid", "organs", "immunodeficiency", "viruses", "lymphatic", "system", "in...
2014
HIV-Infected Individuals with Low CD4/CD8 Ratio despite Effective Antiretroviral Therapy Exhibit Altered T Cell Subsets, Heightened CD8+ T Cell Activation, and Increased Risk of Non-AIDS Morbidity and Mortality
Retinoblastoma ( pRb ) is a multifunctional regulator , which was likely present in the last common ancestor of all eukaryotes . The Arabidopsis pRb homolog RETINOBLASTOMA RELATED 1 ( RBR1 ) , similar to its animal counterparts , controls not only cell proliferation but is also implicated in developmental decisions , s...
The Retinoblastoma ( pRb ) tumor suppressor is a master regulator of the cell cycle and its inactivation is associated with many types of cancer . Since pRb’s first description as a transcriptional repressor of genes important for cell cycle progression , many more functions have been elucidated , e . g . in developmen...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "biotechnology", "engineering", "and", "technology", "gene", "regulation", "cell", "cycle", "and", "cell", "division", "cell", "processes", "brassica", "dna", "damage", "plant", "science", "model", "organisms", "experimental", "organism", "systems", "plant", "genomics...
2018
Genome-wide identification of RETINOBLASTOMA RELATED 1 binding sites in Arabidopsis reveals novel DNA damage regulators
Adenovirus E4orf4 protein induces the death of human cancer cells and Saccharomyces cerevisiae . Binding of E4orf4 to the B/B55/Cdc55 regulatory subunit of protein phosphatase 2A ( PP2A ) is required , and such binding inhibits PP2AB55 activity leading to dose-dependent cell death . We found that E4orf4 binds across th...
The adenovirus E4orf4 protein when expressed alone at high levels induces the death of human cancer cells but not normal primary cells . It also is toxic in the yeast Saccharomyces cerevisiae , which we have used as a model system in some studies . Toxicity induced by the E4orf4 protein is largely dependent on its abil...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
Identification of the Adenovirus E4orf4 Protein Binding Site on the B55α and Cdc55 Regulatory Subunits of PP2A: Implications for PP2A Function, Tumor Cell Killing and Viral Replication
During vertebrate embryogenesis , the rhythmic and sequential segmentation of the body axis is regulated by an oscillating genetic network termed the segmentation clock . We describe a new dynamic model for the core pace-making circuit of the zebrafish segmentation clock based on a systematic biochemical investigation ...
The segmented pattern of the vertebral column , one of the defining features of the vertebrate body , is established during embryogenesis . The embryo's segments , called somites , form sequentially and rhythmically from head to tail . The periodicity of somite formation is regulated by the segmentation clock , a genet...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biomacromolecule-ligand", "interactions", "protein", "interactions", "dna-binding", "proteins", "developmental", "biology", "model", "organisms", "organism", "development", "mathematics", "molecular", "development", "pattern", "formation", "embryology", "theoretical", "biology...
2012
Topology and Dynamics of the Zebrafish Segmentation Clock Core Circuit
Dengue virus infection causes major public health problems in tropical and subtropical areas . In many endemic areas , including the Lao PDR , inadequate access to laboratory facilities is a major obstacle to surveillance and study of dengue epidemiology . Filter paper is widely used for blood collection for subsequent...
Dengue fever , caused by a virus transmitted by mosquitoes , is a public health problem in tropical and subtropical regions . Dengue Rapid Diagnostic Tests , in which a drop of blood is loaded onto a paper strip in a plastic cassette , are simple to use and have good diagnostic accuracy . They are becoming the test of ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "reverse", "transcriptase-polymerase", "chain", "reaction", "dengue", "virus", "medicine", "and", "health", "sciences", "body", "fluids", "pathology", "and", "laboratory", "medicine", "laboratory", "equipment", "engineering", "and", "technology", "pathogens", "rna", "ex...
2016
Using Rapid Diagnostic Tests as a Source of Viral RNA for Dengue Serotyping by RT-PCR - A Novel Epidemiological Tool
Clonorchis sinensis is a group I bio-carcinogen responsible for cholangiocarcinoma ( CHCA ) in humans . However , the mechanism by which C . sinensis promotes carcinogenesis is unclear . Using the human cholangiocyte line H69 , we investigated cell proliferation and gap junction protein expression after stimulation wit...
Clonorchis sinensis , a human fluke , resides in the liver of humans and is commonly found in the common bile duct and gall bladder . This parasite is the main cause of cholangiocarcinoma , also called bile duct cancer , in humans . Of note , the excretory-secretory products ( ESP ) of C . sinensis are known to cause i...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "cell", "physiology", "invertebrates", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "helminths", "nervous", "system", "gene", "regulation", "cell", "cycle", "and", "cell", "division", "cell", "processes", "immunology", "juncti...
2019
Connexin 43 plays an important role in the transformation of cholangiocytes with Clonochis sinensis excretory-secretory protein and N-nitrosodimethylamine
Visuomotor rotation tasks have proven to be a powerful tool to study adaptation of the motor system . While adaptation in such tasks is seemingly automatic and incremental , participants may gain knowledge of the perturbation and invoke a compensatory strategy . When provided with an explicit strategy to counteract a r...
Motor learning has been modeled as an implicit process in which an error , signaling the difference between the predicted and actual outcome is used to modify a model of the actor-environment interaction . This process is assumed to operate automatically and implicitly . However , people can employ cognitive strategies...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "neuroscience/behavioral", "neuroscience", "neuroscience/cognitive", "neuroscience", "neuroscience/motor", "systems", "computational", "biology/computational", "neuroscience", "neuroscience/experimental", "psychology" ]
2011
Flexible Cognitive Strategies during Motor Learning
Binding of odorants to olfactory receptors ( ORs ) elicits downstream chemical and neural signals , which are further processed to odor perception in the brain . Recently , Mainland and colleagues have measured more than 500 pairs of odorant-OR interaction by a high-throughput screening assay method , opening a new ave...
Despite the decades of research , quantitative details of human olfaction have remained largely unexplored . However , a high-throughput measurement has recently been carried out to produce dose-response data between a set of odorants and a repertoire of human olfactory receptors . We characterized each pair of odorant...
[ "Abstract", "Introduction", "Model", "Results", "Discussion" ]
[ "smell", "medicine", "and", "health", "sciences", "olfactory", "receptors", "social", "sciences", "neuroscience", "g-protein", "signaling", "odorants", "materials", "science", "g", "protein", "coupled", "receptors", "sensory", "physiology", "animal", "cells", "proteins"...
2018
Implications for human odor sensing revealed from the statistics of odorant-receptor interactions
Pollen presents a powerful model for studying mechanisms of precise formation and deposition of extracellular structures . Deposition of the pollen wall exine leads to the generation of species-specific patterns on pollen surface . In most species , exine does not develop uniformly across the pollen surface , resulting...
Deposition of extracellular materials next to a cell can protect the cell , change its morphology , or help it to move and communicate . To be able to perform such functions , extracellular materials must be deposited very precisely , but how cells achieve such precision is mostly unknown . A beautiful example of a ver...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "meiosis", "plant", "anatomy", "nuclear", "staining", "cell", "cycle", "and", "cell", "division", "population", "genetics", "ploidy", "cell", "processes", "membrane", "staining", "departures", "from", "diploidy", "pollen", "plant", "science", "tetraploidy", "cytokines...
2016
A Ploidy-Sensitive Mechanism Regulates Aperture Formation on the Arabidopsis Pollen Surface and Guides Localization of the Aperture Factor INP1
Spectro-temporal receptive fields ( STRFs ) have been widely used as linear approximations to the signal transform from sound spectrograms to neural responses along the auditory pathway . Their dependence on statistical attributes of the stimuli , such as sound intensity , is usually explained by nonlinear mechanisms a...
Spectro-temporal receptive fields ( STRFs ) have been widely used as linear approximations of the signal transform from sound spectrograms to neural responses along the auditory pathway . Their dependence on the ensemble of input stimuli has usually been examined mechanistically as a possibly complex nonlinear process ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "auditory", "system", "computational", "neuroscience", "biology", "sensory", "systems", "neuroscience" ]
2011
Understanding Auditory Spectro-Temporal Receptive Fields and Their Changes with Input Statistics by Efficient Coding Principles
Several lines of evidence suggest that genome-wide association studies ( GWAS ) have the potential to explain more of the “missing heritability” of common complex phenotypes . However , reliable methods to identify a larger proportion of single nucleotide polymorphisms ( SNPs ) that impact disease risk are currently la...
Genome-wide association studies ( GWAS ) have thus far identified only a small fraction of the heritability of common complex disorders , such as severe mental disorders . We used a conditional false discovery rate approach for analysis of GWAS data , exploiting “genetic pleiotropy” to increase discovery of common gene...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "psychoses", "mathematics", "mental", "health", "clinical", "research", "design", "heredity", "statistics", "genetics", "schizophrenia", "biology", "biostatistics", "statistical", "methods", "mood", "disorders", "complex", "traits", "psychiatry" ]
2013
Improved Detection of Common Variants Associated with Schizophrenia and Bipolar Disorder Using Pleiotropy-Informed Conditional False Discovery Rate
We recently described our most potently neutralizing monoclonal antibody , E106 , which protected against lethal Dengue virus type 1 ( DENV-1 ) infection in mice . To further understand its functional properties , we determined the crystal structure of E106 Fab in complex with domain III ( DIII ) of DENV-1 envelope ( E...
Dengue virus ( DENV ) is a globally important mosquito-transmitted human pathogen for which there is no approved vaccine or antiviral therapy . In recent years , the number and severity of DENV human infections have increased due to the expanded geographic range of the virus . Neutralizing antibodies are a key componen...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry", "infectious", "diseases", "medicine", "and", "health", "sciences", "biology", "and", "life", "sciences", "immunology", "microbiology", "biophysics" ]
2014
Potent Dengue Virus Neutralization by a Therapeutic Antibody with Low Monovalent Affinity Requires Bivalent Engagement
We aimed to establish the prevalence of amphotericin B deoxycholate ( AmBd ) -related toxicities among South African patients with cryptococcosis and determine adherence to international recommendations to prevent , monitor and manage AmBd-related toxicities . Clinical data were collected from cases of laboratory-confi...
Amphotericin B deoxycholate ( AmBd ) -based induction therapy is recommended for treatment of HIV-associated cryptococcosis in South Africa . We reviewed 846 patient records to determine adherence to World Health Organization ( WHO ) recommendations to prevent , monitor and manage AmBd-related toxicities and determine ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "cryptococcosis", "antimicrobials", "medicine", "and", "health", "sciences", "physicians", "medical", "doctors", "cryptococcus", "pathology", "and", "laboratory", "medicine", "drugs", "microbiology", "antifungals", "biomarkers", "anemia", "toxicology", "health", "care", "...
2016
Prevalence and Hospital Management of Amphotericin B Deoxycholate-Related Toxicities during Treatment of HIV-Associated Cryptococcal Meningitis in South Africa
Salmonella enterica serotype Paratyphi A is a human-restricted cause of paratyphoid fever , accounting for up to a fifth of all cases of enteric fever in Asia . In this work , we applied an RNA analysis method , Selective Capture of Transcribed Sequences ( SCOTS ) , and cDNA hybridization-microarray technology to ident...
Salmonella enterica serotype Paratyphi A is a significant and emerging global public health problem and accounts for one fifth of all cases of enteric fever in many areas of Asia . S . Paratyphi A only infects humans , and the lack of an appropriate animal model has limited the study of S . Paratyphi A infection . In t...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "microbiology", "genetics", "and", "genomics/gene", "expression" ]
2010
Analysis of Salmonella enterica Serotype Paratyphi A Gene Expression in the Blood of Bacteremic Patients in Bangladesh
Synaptic plasticity is widely believed to constitute a key mechanism for modifying functional properties of neuronal networks . This belief implicitly implies , however , that synapses , when not driven to change their characteristics by physiologically relevant stimuli , will maintain these characteristics over time ....
Neurons communicate via synapses , and it is believed that activity-dependent modifications to synaptic connections—synaptic plasticity—is a fundamental mechanism for stably altering the function of neuronal networks . This belief implies that synapses , when not driven to change their properties by physiologically rel...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "neuroscience/neural", "homeostasis", "neuroscience/neurodevelopment", "neuroscience/neuronal", "signaling", "mechanisms", "neuroscience/neuronal", "and", "glial", "cell", "biology", "neuroscience" ]
2009
Long-Term Relationships between Synaptic Tenacity, Synaptic Remodeling, and Network Activity
Recurrent submicroscopic deletions in genes affecting key cellular pathways are a hallmark of pediatric acute lymphoblastic leukemia ( ALL ) . To gain more insight into the mechanism underlying these deletions , we have studied the occurrence and nature of abnormalities in one of these genes , the B-cell translocation ...
Recent studies have alluded to the existence of a complex clonal cellular architecture in acute lymphoblastic leukemia ( ALL ) , where multiple subclones contribute to leukemogenesis . Here , we show that in pediatric B-cell precursor ALL ( BCP-ALL ) monoallelic deletions in the tumor suppressor BTG1 locus , which were...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "hematologic", "cancers", "and", "related", "disorders", "oncology", "medicine", "pediatrics", "and", "child", "health", "genetics", "genetics", "and", "genomics", "biology", "hematology", "pediatrics" ]
2012
The Origin and Nature of Tightly Clustered BTG1 Deletions in Precursor B-Cell Acute Lymphoblastic Leukemia Support a Model of Multiclonal Evolution
Staphylococcus aureus infection is a frequent cause of sepsis in humans , a disease associated with high mortality and without specific intervention . When suspended in human or animal plasma , staphylococci are known to agglutinate , however the bacterial factors responsible for agglutination and their possible contri...
Staphylococcus aureus secretes factors that perturb blood coagulation in infected hosts . We report here that three bacterial products – coagulase ( Coa ) , von Willebrand factor binding protein ( vWbp ) and clumping factor ( ClfA ) - act together and promote agglutination , the association of staphylococci with polyme...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "biochemistry", "infectious", "diseases", "public", "health", "and", "epidemiology", "drugs", "and", "devices", "global", "health", "genetics", "genetics", "and", "genomics", "biology", "microbiology", "public", "health", "critical", "care", "and", "emerge...
2011
Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood
The multitude of functions performed in the cell are largely controlled by a set of carefully orchestrated protein interactions often facilitated by specific binding of conserved domains in the interacting proteins . Interacting domains commonly exhibit distinct binding specificity to short and conserved recognition pe...
Many functions performed within a living cell are mediated by specific interactions between proteins . Precise geometric and chemical matches between segments of the protein structures facilitate those interactions . Such binding surfaces are often evolutionarily conserved elements of protein structures known as conser...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "saccharomyces", "computational", "biology" ]
2007
Structure-Templated Predictions of Novel Protein Interactions from Sequence Information
To infer the subclonality of rhabdomyosarcoma ( RMS ) and predict the temporal order of genetic events for the tumorigenic process , and to identify novel drivers , we applied a systematic method that takes into account germline and somatic alterations in 44 tumor-normal RMS pairs using deep whole-genome sequencing . I...
To decipher the dynamic mutational process and identify the causative genomic events in rhabdomyosarcoma ( RMS ) , we developed a systematic method that incorporates multiple types of genomic information to estimate normal cell contamination , tumor clonality , and a timeline of somatic events that occurred prior to th...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2015
Clonality and Evolutionary History of Rhabdomyosarcoma
The bacterial core genome is of intense interest and the volume of whole genome sequence data in the public domain available to investigate it has increased dramatically . The aim of our study was to develop a model to estimate the bacterial core genome from next-generation whole genome sequencing data and use this mod...
Whole genome sequencing has revolutionised the study of pathogenic microorganisms . It has also become so affordable that hundreds of samples can reasonably be sequenced in an individual project , creating a wealth of data . Estimating the bacterial core genome – traditionally defined as those genes present in all geno...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "bacteriology", "bacterial", "diseases", "infectious", "diseases", "medicine", "and", "health", "sciences", "genetics", "biology", "and", "life", "sciences", "microbiology", "genomics", "microbial", "genomics" ]
2014
Defining the Estimated Core Genome of Bacterial Populations Using a Bayesian Decision Model
Ducks and seabirds are natural hosts for influenza A viruses ( IAV ) . On oceanic islands , the ecology of IAV could be affected by the relative diversity , abundance and density of seabirds and ducks . Seabirds are the most abundant and widespread avifauna in the Western Indian Ocean and , in this region , oceanic isl...
Avian influenza viruses circulate in wild birds , worldwide , in particular in ducks and seabirds from which a large diversity of viruses have been described . The continued emergence of influenza viruses in poultry and humans has stimulated both research activities and surveillance programs; however , there are still ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
Influenza A Virus on Oceanic Islands: Host and Viral Diversity in Seabirds in the Western Indian Ocean
Identifying master regulators of biological processes and mapping their downstream gene networks are key challenges in systems biology . We developed a computational method , called iRegulon , to reverse-engineer the transcriptional regulatory network underlying a co-expressed gene set using cis-regulatory sequence ana...
Gene regulatory networks control developmental , homeostatic , and disease processes by governing precise levels and spatio-temporal patterns of gene expression . Determining their topology can provide mechanistic insight into these processes . Gene regulatory networks consist of interactions between transcription fact...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "computer", "and", "information", "sciences", "genomics", "network", "analysis", "genome", "analysis", "transcriptome", "analysis", "genetics", "biology", "and", "life", "sciences", "regulatory", "networks", "computational", "biology" ]
2014
iRegulon: From a Gene List to a Gene Regulatory Network Using Large Motif and Track Collections
Despite the progress achieved in scaling-up mass drug administration ( MDA ) for lymphatic filariasis ( LF ) in Ghana , communities with persistent LF still exist even after 10 years of community treatment . To understand the reasons for persistence , we conducted a study to assess the status of disease elimination and...
Lymphatic filariasis ( LF ) is a mosquito-borne disease and a leading cause of disability and chronic morbidity worldwide . Despite the progress achieved so far in stopping LF transmission by treating the affected communities with specific drugs over several years , areas where lymphatic filariasis persists still exist...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "immune", "physiology", "body", "fluids", "immunology", "geographical", "locations", "tropical", "diseases", "antigenic", "variation", "parasitic", "diseases", "animals", "filariasis", "pharmaceutics", "neglected", ...
2019
Elimination within reach: A cross-sectional study highlighting the factors that contribute to persistent lymphatic filariasis in eight communities in rural Ghana
Translation initiation has been described as a key step for the control of growth and differentiation of several protozoan parasites in response to environmental changes . This occurs by the activation of protein kinases that phosphorylate the alpha subunit of the translation initiation factor 2 ( eIF2α ) , which decre...
Trypanosoma cruzi proliferates as epimastigotes in the midgut of the insect vector filled with blood meal . There , it accumulates nutrients in specific endosomal organelles . The parasite moves towards the hindgut and when the blood is completely digested , these organelles are consumed . At this moment , the insect i...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
A Membrane-bound eIF2 Alpha Kinase Located in Endosomes Is Regulated by Heme and Controls Differentiation and ROS Levels in Trypanosoma cruzi
Integrating information across sensory domains to construct a unified representation of multi-sensory signals is a fundamental characteristic of perception in ecological contexts . One provocative hypothesis deriving from neurophysiology suggests that there exists early and direct cross-modal phase modulation . We prov...
When faced with ecologically relevant stimuli in natural scenes , our brains need to coordinate information from multiple sensory systems in order to create accurate internal representations of the outside world . Unfortunately , we currently have little information about the neuronal mechanisms for this cross-modal pr...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "neuroscience/cognitive", "neuroscience", "neuroscience/sensory", "systems" ]
2010
Auditory Cortex Tracks Both Auditory and Visual Stimulus Dynamics Using Low-Frequency Neuronal Phase Modulation
The prospect of using whole genome sequence data to investigate bacterial disease outbreaks has been keenly anticipated in many quarters , and the large-scale collection and sequencing of isolates from cases is becoming increasingly feasible . While sequence data can provide many important insights into disease spread ...
With the advent of affordable large-scale genome sequencing for bacterial pathogens , there is much interest in using such data to identify who infected whom in a disease outbreak . Many methods exist to reconstruct the phylogeny of sampled bacteria , but the resulting tree does not necessarily share the same structure...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "ecological", "metrics", "mutation", "population", "size", "ecology", "effective", "population", "size", "population", "modeling", "evolutionary", "modeling", "genetics", "biology", "and", "life", "sciences", "population", "genetics", "infectious", "disease", "modeling", ...
2014
Within-Host Bacterial Diversity Hinders Accurate Reconstruction of Transmission Networks from Genomic Distance Data
Proteins from thermophiles are generally more thermostable than their mesophilic homologs , but little is known about the evolutionary process driving these differences . Here we attempt to understand how the diverse thermostabilities of bacterial ribonuclease H1 ( RNH ) proteins evolved . RNH proteins from Thermus the...
The biophysical properties of proteins must adjust to accommodate environmental temperatures because of the narrow range over which any given protein sequence can remain folded and functional . We compared the evolution of homologous bacterial enzymes ( ribonucleases H1 ) from two lineages: one from Escherichia coli , ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry", "protein", "chemistry", "proteins", "biology", "and", "life", "sciences", "molecular", "evolution", "evolutionary", "biology", "biophysics" ]
2014
Thermodynamic System Drift in Protein Evolution
The cellular and molecular mechanisms underpinning the unusually high virulence of highly pathogenic avian influenza H5N1 viruses in mammalian species remains unknown . Here , we investigated if the cell tropism of H5N1 virus is a determinant of enhanced virulence in mammalian species . We engineered H5N1 viruses with ...
In healthy individuals , the symptoms of seasonal influenza virus infection are mild and the infection is cleared within 4–7 days . However , infection with highly pathogenic avian influenza virus ( H5N1 ) can be severe and often results in fatal pneumonia even in healthy adults . While it is known that both viral and ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "innate", "immune", "system", "medicine", "and", "health", "sciences", "immune", "physiology", "cytokines", "pathology", "and", "laboratory", "medicine", "gene", "regulation", "pathogens", "endothelial", "cells", "immunology", "microbiology", "vertebrates", "orthomyxoviru...
2017
Endothelial cell tropism is a determinant of H5N1 pathogenesis in mammalian species
A molecular device that records time-varying signals would enable new approaches in neuroscience . We have recently proposed such a device , termed a “molecular ticker tape” , in which an engineered DNA polymerase ( DNAP ) writes time-varying signals into DNA in the form of nucleotide misincorporation patterns . Here ,...
Recording of physiological signals from inaccessible microenvironments is often hampered by the macroscopic sizes of current recording devices . A signal-recording device constructed on a molecular scale could advance biology by enabling the simultaneous recording from millions or billions of cells . We recently propos...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "physics", "mathematics", "statistics", "genetics", "applied", "mathematics", "biology", "biophysics", "neuroscience" ]
2013
Statistical Analysis of Molecular Signal Recording
The human filarial parasites cause diseases that are among the most important causes of morbidity in the developing world . The elimination programs targeting these infections rely on a limited number of drugs , making the identification of new chemotherapeutic agents a high priority . The study of these parasites has ...
The human filarial parasites are the causative agents of lymphatic filariasis ( elephantiasis ) and onchocerciasis ( river blindness ) that are some of the most important causes of morbidity worldwide . Both of these diseases have been targeted for elimination by the international community . However , the elimination ...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "transfection", "invertebrates", "medicine", "and", "health", "sciences", "marker", "genes", "parasitic", "diseases", "animals", "parasitology", "plasmid", "construction", "developmental", "biology", "luminescent", "proteins", "brugia", "yellow", "fluorescent", "protein", ...
2018
Development of a toolkit for piggyBac-mediated integrative transfection of the human filarial parasite Brugia malayi
The herpesvirus life cycle has two distinct phases: latency and lytic replication . The balance between these two phases is critical for viral pathogenesis . It is believed that cellular signals regulate the switch from latency to lytic replication . To systematically evaluate the cellular signals regulating this react...
Kaposi sarcoma is a cancer that commonly occurs in AIDS patients . The tumor-associated virus , Kaposi sarcoma–associated herpesvirus , has two distinct phases in its life cycle: inactive latency and active lytic replication . The balance between these two phases is critical for viral pathogenesis . Cellular signals pl...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "oncology", "viruses", "infectious", "diseases", "cell", "biology", "virology", "computational", "biology", "molecular", "biology" ]
2007
Systematic Identification of Cellular Signals Reactivating Kaposi Sarcoma–Associated Herpesvirus
Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A . albopictus and increasing urbanization . With no effective treatment and limited success of vector control , dengue vaccines constitute the best control measure for the f...
An estimated 40% of the world's population is at risk of infection with dengue , a mosquito-borne disease that can lead to hospitalization or death . Dengue vaccines are currently being tested in clinical trials and at least one product will likely be available within a couple of years . Before widespread deployment , ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "public", "health", "and", "epidemiology", "viral", "vaccines", "infectious", "disease", "epidemiology", "applied", "mathematics", "immunology", "microbiology", "computerized", "simulations", "vaccines", "mathematics", "population", "biology", "vaccination", "ep...
2012
Controlling Dengue with Vaccines in Thailand
DNA methylation patterns are reprogrammed in primordial germ cells and in preimplantation embryos by demethylation and subsequent de novo methylation . It has been suggested that epigenetic reprogramming may be necessary for the embryonic genome to return to a pluripotent state . We have carried out a genome-wide promo...
Large scale epigenetic reprogramming occurs in mammalian germ cells and the early embryo . The biological purpose of this reprogramming is largely unknown , although it has been suggested that it may be required for the embryonic genome to return to a pluripotent state . We carried out a genome-wide screen of promoter ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology/germ", "cells", "developmental", "biology/stem", "cells", "cell", "biology/developmental", "molecular", "mechanisms", "developmental", "biology/cell", "differentiation", "molecular", "biology/dna", "methylation", "genetics", "and", "genomics/epigenetics"...
2008
Global Mapping of DNA Methylation in Mouse Promoters Reveals Epigenetic Reprogramming of Pluripotency Genes
Predicting protein structure from primary sequence is one of the ultimate challenges in computational biology . Given the large amount of available sequence data , the analysis of co-evolution , i . e . , statistical dependency , between columns in multiple alignments of protein domain sequences remains one of the most...
Whenever two residues are in close contact in the structure of a protein , their interaction will often constrain which amino acid substitutions can occur without perturbing the functionality of the protein , leading to “co-evolution” of the residues . With the large amount of data currently available , deep multiple a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "computational", "biology/macromolecular", "structure", "analysis", "computational", "biology/protein", "structure", "prediction", "computational", "biology/macromolecular", "sequence", "analysis", "biochemistry/structural", "genomics", "mathematics/statistics", "genetics", "and", ...
2010
Disentangling Direct from Indirect Co-Evolution of Residues in Protein Alignments
Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance , colonisation and/or disease . Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective ag...
Exposure to respiratory pathogens such as Streptococcus pneumoniae ( pneumococcus ) is a frequent event that can result in immediate clearance , nasal colonisation or disease for the host . Human and mouse studies have shown that natural colonisation is an immunising event . Colonisation is prevalent in children but ra...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "medicine", "bacterial", "diseases", "infectious", "diseases", "respiratory", "infections", "immunology", "biology", "respiratory", "medicine", "pulmonology" ]
2012
Human Nasal Challenge with Streptococcus pneumoniae Is Immunising in the Absence of Carriage
In 2009 , three years after stopping mass treatment with azithromycin , a trachoma impact survey in four health districts in the Kayes region of Mali found a prevalence of trachomatous inflammation—follicular ( TF ) among children aged 1 to 9 years of >5% and a trachomatous trichiasis ( TT ) prevalence within the gener...
Trachoma is a leading infectious cause of preventable blindness worldwide . The World Health Organization ( WHO ) recommends that endemic states implement the SAFE strategy ( surgery for trichiasis , antibiotic treatment , facial cleanliness and environmental improvement ) to achieve trachoma elimination by the year 20...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "antimicrobials", "medicine", "and", "health", "sciences", "mali", "face", "drugs", "tropical", "diseases", "geographical", "locations", "microbiology", "surgical", "and", "invasive", "medical", "procedures", "health", "care", "bacterial", "diseases", "antibiotics", "ey...
2018
Prevalence of trachoma in the Kayes region of Mali eight years after stopping mass drug administration
In eukaryotes , DNA replication is coupled to the cell cycle through the actions of cyclin-dependent kinases and associated factors . In bacteria , the prevailing view , based primarily from work in Escherichia coli , is that growth-dependent accumulation of the highly conserved initiator , DnaA , triggers initiation ....
DNA replication must be coordinated with growth and division to ensure the viability of cells and organisms . In bacteria , it is believed that cell growth–dependent accumulation of the initiator of DNA replication , DnaA , to critical levels determines the timing of initiation . This view is based primarily on data fr...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biology", "microbiology" ]
2012
Cell Size and the Initiation of DNA Replication in Bacteria
Standard diagnosis of human soil-transmitted helminth ( STH ) infections is based on the microscopic detection of helminth eggs in stool and supports programmatic decision making in control programs . However , the current standard diagnostic techniques still show a number of limitations . Recently , the FECPAKG2 metho...
Today , infections with soil-transmitted helminths are diagnosed by looking for the eggs of these helminths in stool samples using different microscopic techniques . However , these standard diagnostic techniques still show a number of limitations . The FECPAKG2 method was recently developed for diagnosing worm infecti...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "helminths", "tropical", "diseases", "hookworms", "parasitic", "diseases", "animals", "ascaris", "slurries", "materials", "science", "materials", "physics", "sedimentation", "neglected", "tropical", "diseases", "tr...
2018
Modification and optimization of the FECPAKG2 protocol for the detection and quantification of soil-transmitted helminth eggs in human stool
Voltage-dependent K+ ( Kv ) channels gate open in response to the membrane voltage . To further our understanding of how cell membrane voltage regulates the opening of a Kv channel , we have studied the protein interfaces that attach the voltage-sensor domains to the pore . In the crystal structure , three physical int...
Voltage-dependent ion channels open with a voltage dependence that is remarkably steep . This steep voltage dependence , which is essential to the propagation of nerve impulses , originates in the interaction between voltage-sensor domains of the ion channel and its pore . The voltage-sensor domains transmit voltage-dr...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry" ]
2009
Two Separate Interfaces between the Voltage Sensor and Pore Are Required for the Function of Voltage-Dependent K+ Channels
Epigenetic information , such as parental imprints , can be transmitted with genetic information from parent to offspring through the germ line . Recent reports show that histone modifications can be transmitted through sperm as a component of this information transfer . How the information that is transferred is estab...
Epigenetic information such as parental imprints can be transmitted along with genetic information through the germ line from parent to offspring . Recent reports show that histone modifications marking developmentally regulated loci can be transmitted through sperm as a component of this information transfer . How the...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "developmental", "biology/germ", "cells", "developmental", "biology/embryology", "molecular", "biology/histone", "modification", "developmental", "biology/stem", "cells", "genetics", "and", "genomics/chromosome", "biology", "genetics", "and", "genomics/epigenetics", "molecular", ...
2011
Epigenetic Patterns Maintained in Early Caenorhabditis elegans Embryos Can Be Established by Gene Activity in the Parental Germ Cells
Cytomegalovirus ( CMV ) is a β-herpesvirus that establishes a lifelong latent or persistent infection . A hallmark of chronic CMV infection is the lifelong persistence of large numbers of virus-specific CD8+ effector/effector memory T cells , a phenomenon called “memory inflation” . How the virus continuously stimulate...
Cytomegalovirus ( CMV ) establishes life-long , asymptomatic infections in healthy people . Ongoing immune surveillance prevents viral disease but also results in the accumulation of large numbers of virus-specific T cells . The mechanisms by which the virus persists while stimulating such strong immune responses are u...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "immune", "cells", "viral", "persistence", "and", "latency", "virology", "t", "cells", "immunology", "biology", "microbiology", "immune", "response" ]
2011
Sustained CD8+ T Cell Memory Inflation after Infection with a Single-Cycle Cytomegalovirus
Lymphatic filariasis is caused by filarial nematode parasites , including Brugia malayi . Adult worms live in the lymphatic system and cause a strong immune reaction that leads to the obstruction of lymph vessels and swelling of the extremities . Chronic disease leads to the painful and disfiguring condition known as e...
The World Health Organization estimates that there are approximately 37 million people who are afflicted by Onchocerca volvulus ( the parasitic worm that causes river blindness ) and over 120 million people afflicted by the filarial worms Wuchereria and Brugia spp . ( causative agents of lymphatic filariasis or elephan...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "biotechnology", "algorithms", "medicine", "biochemistry", "infectious", "diseases", "computer", "science", "biology" ]
2012
WormAssay: A Novel Computer Application for Whole-Plate Motion-based Screening of Macroscopic Parasites
Rice tungro disease is caused by synergistic interaction of an RNA picorna-like virus Rice tungro spherical virus ( RTSV ) and a DNA pararetrovirus Rice tungro bacilliform virus ( RTBV ) . It is spread by insects owing to an RTSV-encoded transmission factor . RTBV has evolved a ribosome shunt mechanism to initiate tran...
Ribosome shunting , first discovered in plant pararetroviruses , is a translation initiation mechanism that combines 5′ end-dependent scanning and internal initiation and allows a bypass of highly-structured leaders of certain viral and cellular mRNAs . Here we demonstrate that a similar shunt mechanism has been develo...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "plant", "science", "plant", "biology", "plant", "pathology", "biology" ]
2012
Short ORF-Dependent Ribosome Shunting Operates in an RNA Picorna-Like Virus and a DNA Pararetrovirus that Cause Rice Tungro Disease
Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis by production of the Rho GTPase-glucosylating toxins A and B . Recently emerging hypervirulent Clostridium difficile strains additionally produce the binary ADP-ribosyltransferase toxin CDT ( Clostridium difficile transferase ) , w...
Clostridium difficile is responsible for ∼20 percent of antibiotic-related cases of diarrhea and nearly all cases of pseudomembranous colitis . The pathogens produce two protein toxins ( toxins A and B ) , which inactivate Rho-GTPases of host cells by glucosylation . Recently emerging hypervirulent strains of C . diffi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "gastroenterology", "and", "hepatology/gastrointestinal", "infections", "microbiology/cellular", "microbiology", "and", "pathogenesis", "cell", "biology/cytoskeleton" ]
2009
Clostridium difficile Toxin CDT Induces Formation of Microtubule-Based Protrusions and Increases Adherence of Bacteria
Meiotic crossover frequency varies extensively along chromosomes and is typically concentrated in hotspots . As recombination increases genetic diversity , hotspots are predicted to occur at immunity genes , where variation may be beneficial . A major component of plant immunity is recognition of pathogen Avirulence ( ...
The majority of plants , animals and fungi reproduce sexually , which has a profound effect on patterns of genetic diversity . For sexual reproduction to occur a specialized cell division called meiosis generates gametes ( sex cells ) with recombined DNA . During meiosis homologous chromosomes undergo reciprocal exchan...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biotechnology", "sequencing", "techniques", "plant", "anatomy", "brassica", "pollen", "plant", "science", "model", "organisms", "plant", "genomics", "sequence", "motif", "analysis", "molecular", "biology", "techniques", "dna", "plants", "genotyping", "research", "and",...
2016
Recombination Rate Heterogeneity within Arabidopsis Disease Resistance Genes
The multidrug exporter AcrB is the inner membrane component of the AcrAB-TolC drug efflux system in Escherichia coli and is responsible for the resistance of this organism to a wide range of drugs . Here we describe the crystal structure of the trimeric AcrB in complex with a designed ankyrin-repeat protein ( DARPin ) ...
Bacterial resistance to antibiotics is a major challenge for the current treatment of infectious diseases . One way bacteria can escape destruction is by pumping out administered drugs through specific transporter proteins that span the cell membrane . We used designer proteins that bind to and stabilize proteins of in...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods", "Supporting", "Information" ]
[ "biochemistry", "molecular", "biology", "e.", "coli" ]
2007
Drug Export Pathway of Multidrug Exporter AcrB Revealed by DARPin Inhibitors
Inadequate understanding of the transmission of Mycobacterium leprae makes it difficult to predict the impact of leprosy control interventions . Genotypic tests that allow tracking of individual bacterial strains would strengthen epidemiological studies and contribute to our understanding of the disease . Genotyping as...
Molecular typing has provided an important tool for studies of many pathogens . Such methods could be particularly useful in studies of leprosy , given the many outstanding questions about the pathogenesis and epidemiology of this disease . The approach is particularly difficult with leprosy , however , because of the ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases/epidemiology", "and", "control", "of", "infectious", "diseases" ]
2008
Use of Short Tandem Repeat Sequences to Study Mycobacterium leprae in Leprosy Patients in Malawi and India
Trypanosoma brucei variant surface glycoproteins ( VSG ) are glycosylated by both paucimannose and oligomannose structures which are involved in the formation of a protective barrier against the immune system . Here , we report that the stinging nettle lectin ( UDA ) , with predominant N-acetylglucosamine-binding speci...
Trypanosoma brucei , the causative agent of African trypanosomiasis , is covered by glycosylphosphatidylinositol-anchored glycoproteins , which shield parasites from effectors of the host immune system . The most abundant protein is the variant surface glycoprotein ( VSG ) , which plays an essential role in antigenic v...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
Exposure of Trypanosoma brucei to an N-acetylglucosamine-Binding Lectin Induces VSG Switching and Glycosylation Defects Resulting in Reduced Infectivity
Many of the type 2 diabetes loci identified through genome-wide association studies localize to non-protein-coding intronic and intergenic regions and likely contain variants that regulate gene transcription . The CDC123/CAMK1D type 2 diabetes association signal on chromosome 10 spans an intergenic region between CDC12...
GWAS have identified more than 1200 loci contributing to risk of disease , including more than 70 loci associated with type 2 diabetes . With a majority of associated variants localized to non-coding regions of the genome , focus has moved to identifying the functional variants explaining the association signals . One ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "genetic", "disorders", "gene", "regulation", "dna-binding", "proteins", "alleles", "diabetes", "mellitus", "transcription", "factors", "molecular", "genetics", "type", "2", "diabetes", "proteins", "gene", "expression", "metaboli...
2014
Identification of a Regulatory Variant That Binds FOXA1 and FOXA2 at the CDC123/CAMK1D Type 2 Diabetes GWAS Locus
Burkholderia pseudomallei , the causative agent of melioidosis poses a serious threat to humankind . B . pseudomallei secretes numerous virulence proteins that alter host cell functions to escape from intracellular immune sensors . However , the events underlying disease pathogenesis are poorly understood . We determin...
Burkholderia pseudomallei , the causative agent of the fatal infectious disease melioidosis , is endemic across parts of South East Asia and Northern Australia . Melioidosis poses a serious worldwide emerging infectious disease problem and bioterrorism threat . Of the key features of B . pseudomallei , is its ability t...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "protein", "transport", "cell", "physiology", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "intracellular", "pathogens", "gene", "regulation", "pathogens", "cell", "processes", "cell", "metabolism", "cell", "signaling", "bioassa...
2016
Burkholderia pseudomallei Differentially Regulates Host Innate Immune Response Genes for Intracellular Survival in Lung Epithelial Cells
Neuroblastoma is characterized by a relative paucity of recurrent somatic mutations at diagnosis . However , recent studies have shown that the mutational burden increases at relapse , likely as a result of clonal evolution of mutation-carrying cells during primary treatment . To inform the development of personalized ...
Neuroblastoma is a pediatric cancer that usually affects children within the first five years of life . The survival rate for the high-risk form of the disease is 40–50% , and patients suffering metastatic recurrences have no known curative therapeutic options . Drugs targeted to specific genetic alterations in neurobl...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cancer", "detection", "and", "diagnosis", "cancer", "genomics", "medicine", "and", "health", "sciences", "biopsy", "cancer", "treatment", "clinical", "oncology", "blastomas", "cancers", "and", "neoplasms", "basic", "cancer", "research", "surgical", "and", "invasive",...
2016
Enrichment of Targetable Mutations in the Relapsed Neuroblastoma Genome
The localization of mRNAs encoding secreted/membrane proteins ( mSMPs ) to the endoplasmic reticulum ( ER ) likely facilitates the co-translational translocation of secreted proteins . However , studies have shown that mSMP recruitment to the ER in eukaryotes can occur in a manner that is independent of the ribosome , ...
Proteins destined for secretion from the cell , including soluble secreted and membrane proteins ( SMPs ) , are translocated into the endoplasmic reticulum ( ER ) either directly upon translation on the ER surface or post-translationally , as in the case of type II membrane proteins . Interestingly , several studies ha...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "protein", "transport", "cell", "walls", "medicine", "and", "health", "sciences", "messenger", "rna", "cell", "processes", "physiological", "processes", "fungi", "model", "organisms", "experimental", "organism", "systems", "sequence", "motif", "analysis", "cellular", ...
2019
A secretion-enhancing cis regulatory targeting element (SECReTE) involved in mRNA localization and protein synthesis
Onchocerciasis a neglected tropical disease that historically has been a major cause of morbidity and an obstacle to economic development in the developing world . It is caused by infection with Onchocerca volvulus , which is transmitted by black flies of the genus Simulium . The discovery of the potent effect of Mecti...
River blindness is one of the most important causes of morbidity in the developing world . The discovery of ivermectin and the decision by its manufacturer to donate the drug for river blindness spawned the development of programs to eliminate river blindness through mass treatment of afflicted populations . But iverme...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "ecology", "and", "environmental", "sciences", "onchocerca", "volvulus", "rivers", "helminths", "tropical", "diseases", "geographical", "locations", "uganda", "parasitic", "diseases", "animals", "onchocerca", "deve...
2018
Community-directed vector control to supplement mass drug distribution for onchocerciasis elimination in the Madi mid-North focus of Northern Uganda
Characteristic skin lesions play a key role in clinical diagnosis of spotted fever group rickettsioses and this study describes these cutaneous manifestations along with basic histological features . Study was conducted at Medical Unit , Teaching Hospital , Peradeniya , from November 2009 to October 2011 , where a pros...
Rickettsial organisms infect humans causing a wider array of clinical features and have re-emerged in Sri Lanka where three known disease entities; spotted fever group , murine typhus and scrub typhus do exist . These diseases cause clinical illnesses varying from mild febrile illness to severe multiple organ involveme...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "bacterial", "diseases", "infectious", "diseases", "medicine", "and", "health", "sciences", "medical", "microbiology", "microbial", "pathogens", "biology", "and", "life", "sciences", "microbiology", "rickettsia", "bacterial", "pathogens" ]
2014
Cutaneous Manifestations of Spotted Fever Rickettsial Infections in the Central Province of Sri Lanka: A Descriptive Study
The TGF-β homolog Decapentaplegic ( Dpp ) acts as a secreted morphogen in the Drosophila wing disc , and spreads through the target tissue in order to form a long range concentration gradient . Despite extensive studies , the mechanism by which the Dpp gradient is formed remains controversial . Two opposing mechanisms ...
Morphogens are signaling molecules that trigger specific responses in cells in a concentration-dependent manner . The formation of morphogen gradients is essential for the patterning of tissues and organs . Decapentaplegic ( Dpp ) is the Drosophila homolog of the bone morphogenic proteins in vertebrates and forms a mor...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "genetics", "biology", "computational", "biology", "molecular", "cell", "biology", "genetics", "and", "genomics" ]
2011
Formation of the Long Range Dpp Morphogen Gradient
The Tier 1 select agent Burkholderia pseudomallei is an environmental bacterium that causes melioidosis , a high mortality disease . Variably present genetic markers used to elucidate strain origin , relatedness and virulence in B . pseudomallei include the Burkholderia intracellular motility factor A ( bimA ) and fila...
Burkholderia pseudomallei is a pathogenic soil bacterium that causes the disease melioidosis , which occurs in many tropical regions globally and in recent years has emerged in non-tropical regions . Melioidosis has been predicted to affect 165 , 000 people every year resulting in an estimated 89 , 000 deaths . Person ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "biogeography", "medicine", "and", "health", "sciences", "ecology", "and", "environmental", "sciences", "burkholderia", "pseudomallei", "pathology", "and", "laboratory", "medicine", "melioidosis", "pathogens", "population", "genetics", "geographical", "locations", "microbio...
2019
Tracing the environmental footprint of the Burkholderia pseudomallei lipopolysaccharide genotypes in the tropical “Top End” of the Northern Territory, Australia
Strongyloidiasis is a persistent human parasitic infection caused by the intestinal nematode , Strongyloides stercoralis . The parasite has a world-wide distribution , particularly in tropical and subtropical regions with poor sanitary conditions . Since individuals with strongyloidiasis are typically asymptomatic , th...
A rapid and sensitive serodiagnostic assay for strongyloidiasis based on a 31-kDa recombinant antigen from Strongyloides stercoralis ( NIE ) was developed using a novel diffraction-based optical biosensor technology . Assay performance was tested using retrospectively collected sera from patients with parasitologically...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "biology", "and", "life", "sciences", "parasitology", "microbiology" ]
2014
Development of a Rapid Serological Assay for the Diagnosis of Strongyloidiasis Using a Novel Diffraction-Based Biosensor Technology
To mate , MTL-homozygous strains of the yeast pathogen Candida albicans must switch from the white to opaque phase . Mating-competent opaque cells then release pheromone that induces polarization , a G1 block and conjugation tube formation in opaque cells of opposite mating type . Pheromone also induces mating-incompet...
Candida albicans , like other microbial pathogens , form protective biofilms on host tissue , prosthetics and catheters . But C . albicans forms two types of biofilm , one by cells of majority strains that are heterozygous at the mating type locus , and another by white cells of minority strains that are homozygous at ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "biology", "pathology", "microbiology" ]
2009
Genes Selectively Up-Regulated by Pheromone in White Cells Are Involved in Biofilm Formation in Candida albicans
Understanding the mechanisms involved in long-term persistence of humoral immunity after natural infection or vaccination is challenging and crucial for further research in immunology , vaccine development as well as health policy . Long-lived plasma cells , which have recently been shown to reside in survival niches i...
Recent studies evidenced the existence of long-lived plasma-cells which could play a major role in the long-term persistence of antibodies after infection or vaccination . A mathematical model , accounting for two plasma-cells populations ( short and long-lived ) , was developed to analyze data from two long-term follo...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "medicine", "infectious", "diseases", "immune", "cells", "immunity", "immunology", "biology" ]
2012
Living on Three Time Scales: The Dynamics of Plasma Cell and Antibody Populations Illustrated for Hepatitis A Virus
The effectiveness of the annual influenza vaccine has declined in recent years , especially for the H3N2 component , and is a concern for global public health . A major cause for this lack in effectiveness has been attributed to the egg-based vaccine production process . Substitutions on the hemagglutinin glycoprotein ...
Seasonal influenza vaccine does not always confer protection in vaccinated individuals . Vaccine candidates are selected from clinical isolates based on their antigenic properties . It is common to use chicken eggs for culturing clinical isolates and for large-scale production of vaccines . However , influenza virus of...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "viral", "vaccines", "medicine", "and", "health", "sciences", "immune", "physiology", "enzyme-linked", "immunoassays", "pathology", "and", "laboratory", "medicine", "influenza", "pathogens", "immunology", "condensed", "matter", "physics", "microbiology", "orthomyxoviruses",...
2017
A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine
Antibody-detecting rapid diagnostic tests ( RDTs ) against rK39 are available to aid in the diagnosis of visceral leishmaniasis ( VL ) . Although these rK39 RDTs have been developed , validated and approved for use with serum , they are universally performed using whole blood . It was therefore necessary to determine w...
Visceral leishmaniasis ( VL ) , is a neglected tropical disease that is highly endemic in the Indian subcontinent and in East Africa and is the second most fatal parasitic disease after malaria . There currently exists several effective treatments for VL and it is therefore essential that the diagnosis be as accessible...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "science", "policy" ]
2013
Diagnosis of Visceral Leishmaniasis in Bihar India: Comparison of the rK39 Rapid Diagnostic Test on Whole Blood Versus Serum
Insects exposed to pesticides undergo strong natural selection and have developed various adaptive mechanisms to survive . Resistance to pyrethroid insecticides in the malaria vector Anopheles gambiae is receiving increasing attention because it threatens the sustainability of malaria vector control programs in sub-Sah...
Malaria , a disease spread by anopheline mosquitoes , is a global health problem with an enormous economic and social impact . Pyrethroid insecticides are critical in reducing malaria transmission , and resistance to these insecticides threatens current control efforts . With a limited number of public health insectici...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "biochemistry", "infectious", "diseases/neglected", "tropical", "diseases", "public", "health", "and", "epidemiology/infectious", "diseases", "public", "health", "and", "epidemiology/screening", "molecular", "biology", "genetics", "and", "genomics" ]
2008
Field-Caught Permethrin-Resistant Anopheles gambiae Overexpress CYP6P3, a P450 That Metabolises Pyrethroids
Dengue virus ( DENV ) was reintroduced into Brazil in 1986 and by 1995 it had spread throughout the country . In 2007 the number of dengue hemorrhagic fever ( DHF ) cases more than doubled and a shift in the age distribution was reported . While previously the majority of DHF cases occurred among adults , in 2007 53% o...
The spread of dengue virus is a major public health problem . Though the burden of dengue has historically been concentrated in Southeast Asian countries , Brazil has become the country that reports the largest number of cases in the world . While prior to 2007 the disease affected mostly adults , during the 2007 epide...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases/viral", "infections", "infectious", "diseases/epidemiology", "and", "control", "of", "infectious", "diseases" ]
2011
From Re-Emergence to Hyperendemicity: The Natural History of the Dengue Epidemic in Brazil
Bacterial etiologies of non-malaria febrile illnesses have significantly become important due to high mortality and morbidity , particularly in children . Despite their importance , there are few reports on the epidemiology of these diseases in Tanzania , and the true burden of such illnesses remains unknown . This stu...
Understanding the bacterial causes of fever , particularly in the era of reported decline of malaria , is very important . In Tanzania , data on the prevalence of these diseases in several regions is limited . These infections cannot be recognized clinically , and thus the lack of diagnostic tools in most health facili...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
Prevalence of Bacterial Febrile Illnesses in Children in Kilosa District, Tanzania
Gene assembly , which recovers gene segments from short reads , is an important step in functional analysis of next-generation sequencing data . Lacking quality reference genomes , de novo assembly is commonly used for RNA-Seq data of non-model organisms and metagenomic data . However , heterogeneous sequence coverage ...
Next-generation sequencing ( NGS ) provides an efficient and affordable way to sequence the genomes or transcriptomes of a large amount of organisms . With fast accumulation of the sequencing data from various NGS projects , the bottleneck is to efficiently mine useful knowledge from the data . As NGS platforms usually...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "biology", "and", "life", "sciences", "computational", "biology" ]
2014
A Scalable and Accurate Targeted Gene Assembly Tool (SAT-Assembler) for Next-Generation Sequencing Data
Clinical diagnosis of Buruli ulcer ( BU ) due to Mycobacterium ulcerans can be challenging . We aimed to specify the differential diagnosis of skin lesions in a BU endemic area . We conducted a prospective diagnostic study in Akonolinga , Cameroon . Patients presenting with a skin ulcer suspect of BU were included . M ...
In some areas of Africa , Australia or Japan , a specific skin infection presents as a wound which progressively increases in size in children and people of any age . The agent which causes this infection is named Mycobacterium ulcerans , close to the tuberculosis agent . This wound , also named Buruli ulcer ( BU ) , m...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "cancer", "detection", "and", "diagnosis", "rheumatology", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "tropical", "diseases", "osteomyelitis", "oncology", "bacterial", "diseases", "signs", "and", "symptoms", "ulcers", "neglect...
2016
Differential Diagnosis of Skin Ulcers in a Mycobacterium ulcerans Endemic Area: Data from a Prospective Study in Cameroon
Analysis methods based on simulations and optimization have been previously developed to estimate relative translation rates from next-generation sequencing data . Translation involves molecules and chemical reactions , hence bioinformatics methods consistent with the laws of chemistry and physics are more likely to pr...
The process of translating the genetic information encoded in an mRNA molecule to a protein is crucial to cellular life and plays a role in regulating gene expression . The translation initiation rate of a transcript is a direct measure of the rate of protein synthesis and is the key kinetic parameter defining translat...
[ "Abstract", "Introduction", "Discussion", "Methods" ]
[ "transfer", "rna", "messenger", "rna", "fungi", "protein", "synthesis", "model", "organisms", "experimental", "organism", "systems", "genome", "analysis", "cellular", "structures", "and", "organelles", "chemical", "synthesis", "research", "and", "analysis", "methods", ...
2019
A chemical kinetic basis for measuring translation initiation and elongation rates from ribosome profiling data
The World Health Organization ( WHO ) now requires a second surveillance survey for trachoma after an impact assessment has found follicular trachoma ( TF ) <5% to determine if re-emergence has occurred . Using new WHO guidelines , we undertook surveillance surveys , and determined the prevalence of infection and antib...
Once districts have shown that the prevalence of follicular trachoma ( TF ) in children ages 1–9 years is below 5% , they must monitor for re-emergence . The World Health Organization ( WHO ) recommends a second surveillance or “pre-validation” survey to determine if re-emergence has occurred . Using new WHO guidelines...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "immune", "physiology", "enzyme-linked", "immunoassays", "pathology", "and", "laboratory", "medicine", "body", "fluids", "chlamydia", "trachomatis", "pathogens", "immunology", "tropical", "diseases", "microbiology", "geographical", ...
2016
The World Health Organization Recommendations for Trachoma Surveillance, Experience in Nepal and Added Benefit of Testing for Antibodies to Chlamydia trachomatis pgp3 Protein: NESTS Study
A genetic absence of the common IFN- α/β signaling receptor ( IFNAR ) in mice is associated with enhanced viral replication and altered adaptive immune responses . However , analysis of IFNAR-/- mice is limited for studying the functions of type I IFN at discrete stages of viral infection . To define the temporal funct...
Although it is well established that type I IFN responses protect against viral infections by inducing expression of antiviral genes and modulators of adaptive immune responses , its function at different stages of viral infections has remained poorly studied . In this paper , we administered a monoclonal antibody that...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "immune", "activation", "emerging", "viral", "diseases", "immunity", "to", "infections", "immunology", "microbiology", "host-pathogen", "interaction", "adaptive", "immunity", "emerging", "infectious", "diseases", "immune", "defense", "animal", "models", "of", "infection",...
2011
A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection
Chagas disease is caused by Trypanosoma cruzi infection , being cardiomyopathy the more frequent manifestation . New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy . There is growing evidence linking immune response and metabolism in inflammatory processes and speci...
Chagas disease , caused by Trypanosoma cruzi , is the most common cause of cardiomyopathy in Latin America . After the acute phase myocarditis , the disease becomes asymptomatic , and many years later some patients may develop Chagas cardiomyopathy . Treatment is available , but causes side effects . Thus , new drugs a...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "biochemistry", "infectious", "diseases", "medicine", "and", "health", "sciences", "biology", "and", "life", "sciences", "tropical", "diseases", "parasitic", "diseases", "parasitology", "cardiology" ]
2014
Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection
The inherent capacity of somatic cells to switch their phenotypic status in response to damage stimuli in vivo might have a pivotal role in ageing and cancer . However , how the entry-exit mechanisms of phenotype reprogramming are established remains poorly understood . In an attempt to elucidate such mechanisms , we h...
Certain modifications of the structure and functioning of the protein/DNA complex called chromatin can allow adult , fully differentiated , cells to adopt a stem cell-like pluripotent state in a purely epigenetic manner , not involving changes in the underlying DNA sequence . Such reprogramming-like phenomena may const...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "gene", "regulation", "cancer", "risk", "factors", "cell", "differentiation", "simulation", "and", "modeling", "oncology", "developmental", "biology", "stem", "cells", "epigenetics", "medical", "risk", "factors", "dna", "promot...
2019
A multiscale model of epigenetic heterogeneity-driven cell fate decision-making
The correspondence between protein sequences and structures , or sequence-structure map , relates to fundamental aspects of structural , evolutionary and synthetic biology . The specifics of the mapping , such as the fraction of accessible sequences and structures , or the sequences' ability to fold fast , are dictated...
If we were to design a proteome , what types and what proportion of amino acids would we use in order to optimize properties such as the diversity of sequences and structures , their robustness to mutations , or their ability to fold efficiently ? Here , I use simple models to study the sequence-structure map of protei...
[ "Abstract", "Introduction", "Models", "Results", "Discussion" ]
[ "biochemistry", "theoretical", "biology", "synthetic", "biology", "biology", "and", "life", "sciences", "computational", "biology", "evolutionary", "biology", "molecular", "biology" ]
2014
The Amino Acid Alphabet and the Architecture of the Protein Sequence-Structure Map. I. Binary Alphabets
Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload . A key role in this process plays ferroportin , the only known mammalian transmembrane iron exporter , which releases iron from duodenal enterocytes , hepatocytes , or iron-recyc...
The importance of iron in many physiological processes relies on its ability to participate in reduction-oxidation reactions . This property also leads to potential toxicity if concentrations of free iron are not properly managed by cells and tissues . Multicellular organisms therefore evolved intricate regulatory mech...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "liver", "immune", "physiology", "pathology", "and", "laboratory", "medicine", "spleen", "immunology", "messenger", "rna", "diet", "simulation", "and", "modeling", "physiological", "processes", "nutrition", "signs", "and", "sym...
2017
Modelling Systemic Iron Regulation during Dietary Iron Overload and Acute Inflammation: Role of Hepcidin-Independent Mechanisms
Sensory ataxic neuropathy ( SAN ) is a recently identified neurological disorder in golden retrievers . Pedigree analysis revealed that all affected dogs belong to one maternal lineage , and a statistical analysis showed that the disorder has a mitochondrial origin . A one base pair deletion in the mitochondrial tRNATy...
Mitochondrial disorders are a group of heterogeneous diseases . It has been estimated that the prevalence of mitochondrial diseases in humans , due to mutations of the mitochondrial genome ( mtDNA ) , is approximately 1 in 8000 in a Caucasian population . Since the late 1980s , when the first disease-causing mutation i...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "neurological", "disorders/neuromuscular", "diseases", "genetics", "and", "genomics/animal", "genetics", "genetics", "and", "genomics/disease", "models", "genetics", "and", "genomics/genetics", "of", "disease", "neurological", "disorders/peripheral", "neuropathies" ]
2009
Sensory Ataxic Neuropathy in Golden Retriever Dogs Is Caused by a Deletion in the Mitochondrial tRNATyr Gene
A large fraction of genome variation between individuals is comprised of submicroscopic copy number variation of genomic DNA segments . We assessed the relative contribution of structural changes and gene dosage alterations on phenotypic outcomes with mouse models of Smith-Magenis and Potocki-Lupski syndromes . We phen...
Mammalian genomes contain many forms of genetic variation . For example , some genome segments were shown to vary in their number of copies between individuals of the same species , i . e . there is a range of number of copies in the normal population instead of the usual two copies ( one per chromosome ) . These genet...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/genomics", "genetics", "and", "genomics/animal", "genetics", "genetics", "and", "genomics/gene", "expression", "genetics", "and", "genomics/functional", "genomics", "genetics", "and", "genomics/chromosome", "biology", "genetics", "and", "genomic...
2010
Phenotypic Consequences of Copy Number Variation: Insights from Smith-Magenis and Potocki-Lupski Syndrome Mouse Models
Two theories address the origin of repeating patterns , such as hair follicles , limb digits , and intestinal villi , during development . The Turing reaction–diffusion system posits that interacting diffusible signals produced by static cells first define a prepattern that then induces cell rearrangements to produce a...
Repeating anatomical units , forming a pattern , are present in different parts of the body . This is particularly obvious in the skin , where the many hair follicles become regularly arranged and fixed in place in the embryo as a pattern of evenly spaced spots . The basis for the formation of such repeating patterns h...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "skin", "medicine", "and", "health", "sciences", "integumentary", "system", "endocrine", "physiology", "developmental", "biology", "signal", "inhibition", "growth", "factors", "epidermis", "morphogenesis", "fibroblast", "growth", "factor", "pattern", "formation", "hair", ...
2017
Hierarchical patterning modes orchestrate hair follicle morphogenesis
Gene duplication followed by neo- or sub-functionalization deeply impacts the evolution of protein families and is regarded as the main source of adaptive functional novelty in eukaryotes . While there is ample evidence of adaptive gene duplication in prokaryotes , it is not clear whether duplication outweighs the cont...
Prokaryotes can be found in the most diverse and severe ecological niches of the planet . Their rapid adaptation is , in part , the result of the ability to acquire genetic information horizontally . This means that prokaryotes utilize two major paths to expand their repertoire of protein families: they can duplicate a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "computational", "biology/population", "genetics", "genetics", "and", "genomics/genomics", "genetics", "and", "genomics/microbial", "evolution", "and", "genomics", "evolutionary", "biology/evolutionary", "and", "comparative", "genetics", "computational", "biology/comparative", ...
2011
Horizontal Transfer, Not Duplication, Drives the Expansion of Protein Families in Prokaryotes
Skeletal muscle remodelling and contractile dysfunction occur through both acute and chronic disease processes . These include the accumulation of insoluble aggregates of misfolded amyloid proteins that is a pathological feature of Huntington’s disease ( HD ) . While HD has been described primarily as a neurological di...
Huntington’s disease ( HD ) is a neurodegenerative disorder in which the mutation results in an extra-long tract of glutamines that causes the huntingtin protein to aggregate . It is characterized by neurological symptoms and brain pathology , which is associated with nuclear and cytoplasmic protein aggregates and with...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
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2015
HDAC4-Myogenin Axis As an Important Marker of HD-Related Skeletal Muscle Atrophy