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The MYC genes encode nuclear sequence specific–binding DNA-binding proteins that are pleiotropic regulators of cellular function , and the c-MYC proto-oncogene is deregulated and/or mutated in most human cancers . Experimental studies of MYC binding to the genome are not fully consistent . While many c-MYC recognition ...
c-MYC is an important proto-oncogene that controls the expression of many other genes , and MYC regulation is deranged in many cancers . Identifying c-MYC target genes is one of the key steps to understand both the biological role and molecular mechanism of c-MYC action . Defining the complete list of c-MYC target gene...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "primates", "oncology", "mammals", "computational", "biology", "homo", "(human)", "genetics", "and", "genomics" ]
2007
Integration of Genome and Chromatin Structure with Gene Expression Profiles To Predict c-MYC Recognition Site Binding and Function
Scaffolding proteins that direct the assembly of multiple kinases into a spatially localized signaling complex are often essential for the maintenance of an appropriate biological response . Although scaffolds are widely believed to have dramatic effects on the dynamics of signal propagation , the mechanisms that under...
Signal transduction is the science of cellular communication . Cells detect signals from their environment and use them to make decisions such as whether or when to proliferate . Tight regulation of signal transduction is required for all healthy cells , and aberrant signaling leads to countless diseases such as cancer...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "physics/interdisciplinary", "physics", "cell", "biology/cell", "signaling", "cell", "biology/cell", "growth", "and", "division", "biophysics/theory", "and", "simulation", "computational", "biology/molecular", "dynamics", "computer", "science/numerical", "analysis", "and", "t...
2008
Regulation of Signal Duration and the Statistical Dynamics of Kinase Activation by Scaffold Proteins
Ligand virtual screening is a widely used tool to assist in new pharmaceutical discovery . In practice , virtual screening approaches have a number of limitations , and the development of new methodologies is required . Previously , we showed that remotely related proteins identified by threading often share a common b...
As an integral part of drug development , high-throughput virtual screening is a widely used tool that could in principle significantly reduce the cost and time to discovery of new pharmaceuticals . In practice , virtual screening algorithms suffer from a number of limitations . The high sensitivity of all-atom ligand ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "biophysics/biomacromolecule-ligand", "interactions", "biochemistry/biomacromolecule-ligand", "interactions", "biochemistry/drug", "discovery" ]
2009
FINDSITELHM: A Threading-Based Approach to Ligand Homology Modeling
The sparse coding hypothesis has enjoyed much success in predicting response properties of simple cells in primary visual cortex ( V1 ) based solely on the statistics of natural scenes . In typical sparse coding models , model neuron activities and receptive fields are optimized to accurately represent input stimuli us...
The popular sparse coding theory posits that the receptive fields of visual cortical neurons maximize the efficiency of the neural representation of natural images . Models implementing this idea typically minimize a combination of the error in reconstructing natural images from neural activities , and the average leve...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "systems", "biology", "developmental", "neuroscience", "theoretical", "biology", "neural", "homeostasis", "computational", "neuroscience", "sensory", "systems", "biology", "neuroscience" ]
2013
Sparse Coding Models Can Exhibit Decreasing Sparseness while Learning Sparse Codes for Natural Images
It is well established that RNA viruses exhibit higher rates of spontaneous mutation than DNA viruses and microorganisms . However , their mutation rates vary amply , from 10−6 to 10−4 substitutions per nucleotide per round of copying ( s/n/r ) and the causes of this variability remain poorly understood . In addition t...
RNA viruses show high rates of spontaneous mutation , a feature that profoundly influences viral evolution , disease emergence , the appearance of drug resistances , and vaccine efficacy . However , RNA virus mutation rates vary substantially and the factors determining this variability remain poorly understood . Here ...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "microbial", "evolution", "virology", "population", "genetics", "biology", "microbiology", "evolutionary", "biology" ]
2014
Variation in RNA Virus Mutation Rates across Host Cells
The mean age of dengue has been increasing in some but not all countries . We sought to determine the incidence of dengue virus ( DENV ) infection in adults and children in a prospective cohort study in the Philippines where dengue is hyperendemic . A prospective cohort of subjects ≥6 months old in Cebu City , Philippi...
The average age of dengue has been increasing in some but not all dengue endemic countries . To investigate the age pattern of dengue in people of all ages ≥6 months old , a prospective community-based cohort study was undertaken in Cebu City , Philippines where dengue virus has been circulating for many decades . Acti...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "dengue", "virus", "children", "medicine", "and", "health", "sciences", "body", "fluids", "pathology", "and", "laboratory", "medicine", "pathogens", "microbiology", "pediatrics", "viruses", "age", "groups", "research", "design", "adults", "rna", "viruses", "signs", ...
2016
Incidence of Dengue Virus Infection in Adults and Children in a Prospective Longitudinal Cohort in the Philippines
Hemorrhagic fever with renal syndrome ( HFRS ) and hantavirus pulmonary syndrome ( HPS ) are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier . Hantavirus-infected endothelial cells ( EC ) display no overt cytopathology; consequently , path...
Primary manifestations of disease due to hantavirus infections include systemic vascular leakage and hypotension for which the underlying mechanism is not known . A particularly perplexing finding is that the vascular endothelium remains intact during hantavirus infection and with no apparent cytopathic effects to expl...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "biochemistry", "infectious", "diseases", "zoonoses", "hantavirus", "coagulation", "factors", "proteins", "virology", "biology", "microbiology", "viral", "diseases" ]
2013
Endothelial Cell Permeability during Hantavirus Infection Involves Factor XII-Dependent Increased Activation of the Kallikrein-Kinin System
Due to worldwide increased human mobility , air-transportation data and mathematical models have been widely used to measure risks of global dispersal of pathogens . However , the seasonal and interannual risks of pathogens importation and onward transmission from endemic countries have rarely been quantified and valid...
Given the global expanding distribution of Aedes mosquitoes , dengue has established itself throughout the world’s tropical and subtropical regions in both endemic and epidemic transmission cycles , causing significant morbidity and mortality . Moreover , the rise of air travel over the past century has resulted in a h...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "dengue", "virus", "invertebrates", "medicine", "and", "health", "sciences", "air", "travel", "pathology", "and", "laboratory", "medicine", "china", "pathogens", "geographical", "locations", "microbiology", "social", "sciences", "human", "mobility", "animals", "viruses"...
2018
Seasonal and interannual risks of dengue introduction from South-East Asia into China, 2005-2015
In rhesus macaques ( RMs ) , experimental depletion of CD4+ T-cells prior to SIV infection results in higher viremia and emergence of CD4-independent SIV-envelopes . In this study we used the rhesus recombinant anti-CD4 antibody CD4R1 to deplete RM CD4+ T-cells prior to SIVmac251 infection and investigate the sources o...
CD4+ T-cells are both mediators of antiviral immune response and critical targets for HIV replication . We have previously shown that experimental depletion of CD4+ T-cells prior to SIV infection in rhesus macaques results in higher viremia and the emergence of CD4-independent SIV-envelopes . The findings reported in t...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases", "hiv", "infections", "medicine", "and", "health", "sciences", "clinical", "immunology", "aids", "immune", "deficiency", "biology", "and", "life", "sciences", "immunology", "viral", "diseases" ]
2014
CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells
A growing body of evidence highlights the importance of the cellular microenvironment as a regulator of phenotypic and functional cellular responses to perturbations . We have previously developed cell patterning techniques to control population context parameters , and here we demonstrate context-explorer ( CE ) , a s...
Cell behavior is influenced by cues that cells receive from their surrounding environment such as signals secreted from other cells and cell-to-cell contact . These factors are spatially heterogeneous and cells at different positions within a colony will experience varying degrees of influence from such environmental c...
[ "Abstract", "Introduction", "Design", "and", "implementation", "Results", "Availability", "and", "future", "directions" ]
[ "graphical", "user", "interfaces", "engineering", "and", "technology", "protein", "expression", "human", "factors", "engineering", "stem", "cells", "molecular", "biology", "techniques", "research", "and", "analysis", "methods", "computer", "and", "information", "science...
2019
Context-explorer: Analysis of spatially organized protein expression in high-throughput screens
Arboviruses are viruses transmitted to humans and other animals by the bite of hematophagous arthropods . Infections caused by chikungunya virus ( CHIKV ) , dengue virus ( DENV ) , Zika virus ( ZIKV ) , and the deadlier yellow fever virus ( YFV ) are current public health problems in several countries , mainly those lo...
The control of the vast majority of arbovirus infections relies on entomological measures to reduce mosquito infestation . Therefore , this study analyzed the use of ovitraps for arboviral surveillance in a mid-size city of the Amazonas state , Brazil . We found one larva pool infected with chikungunya virus , before t...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "togaviruses", "chikungunya", "infection", "pathogens", "tropical", "diseases", "microbiology", "geographical", "locations", "animals", "alphaviruses", "viruses", "develo...
2018
Evidence of vertical transmission of Zika virus in field-collected eggs of Aedes aegypti in the Brazilian Amazon
Despite several leprosy control measures in Nigeria , child proportion and disability grade 2 cases remain high while new cases have not significantly reduced , suggesting continuous spread of the disease . Hence , there is the need to review detection methods to enhance identification of early cases for effective cont...
Reported increases in child proportions and disability grade 2 cases in Nigeria suggest that leprosy disease is still spreading in the country . This indicates the need to review case finding strategies to improve case detection for effective control of the disease . It was necessary that available methods be assessed ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "clinical", "research", "design" ]
2012
Cost-Effectiveness Analysis of Three Leprosy Case Detection Methods in Northern Nigeria
Precise temporal and spatial control of cell division is essential for progeny survival . The current general view is that precise positioning of the division site at midcell in rod-shaped bacteria is a result of the combined action of the Min system and nucleoid ( chromosome ) occlusion . Both systems prevent assembly...
How organisms regulate biological processes so that they occur at the correct place within the cell is a fundamental question in research . Spatial regulation of cell division is vital to ensure equal partitioning of DNA into newborn cells . Correct positioning of the division site at the cell centre in rod-shaped bact...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "biology", "microbiology", "molecular", "cell", "biology", "genetics", "and", "genomics" ]
2012
The Min System and Nucleoid Occlusion Are Not Required for Identifying the Division Site in Bacillus subtilis but Ensure Its Efficient Utilization
In all sensory modalities , the data acquired by the nervous system is shaped by the biomechanics , material properties , and the morphology of the peripheral sensory organs . The rat vibrissal ( whisker ) system is one of the premier models in neuroscience to study the relationship between physical embodiment of the s...
Animals move in order to sense the world . Sensing is thus an active process , constrained by muscle biomechanics and by the material , shape , and structure of the sensing organs . The rat vibrissal system provides an ideal model to examine how the physical embodiment of a sensory array shapes the sensing process . Ra...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "neuroscience/behavioral", "neuroscience", "neuroscience/sensory", "systems", "computational", "biology/computational", "neuroscience", "evolutionary", "biology/animal", "behavior", "computational", "biology/systems", "biology" ]
2011
The Morphology of the Rat Vibrissal Array: A Model for Quantifying Spatiotemporal Patterns of Whisker-Object Contact
Genome-scale metabolic models provide a valuable context for analyzing data from diverse high-throughput experimental techniques . Models can quantify the activities of diverse pathways and cellular functions . Since some metabolic reactions are only catalyzed in specific environments , several algorithms exist that bu...
Genome-scale models of human metabolism have facilitated numerous exciting discoveries regarding human physiology and therapeutics . The accuracy of results from such studies requires that models capture the tissue or cell-type specific metabolism . In hopes to obtain accurate models , several algorithms have been deve...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "cell", "physiology", "carbohydrate", "metabolism", "medicine", "and", "health", "sciences", "applied", "mathematics", "enzymology", "cell", "metabolism", "simulation", "and", "modeling", "algorithms", "mathematics", "genome", "analysis", "enzyme", "metabolism", "pharmaco...
2019
Increasing consensus of context-specific metabolic models by integrating data-inferred cell functions
Tight control over gene expression is essential for precision in embryonic development and acquisition of the regulatory elements responsible is the predominant driver for evolution of new structures . Tbx5 and Tbx4 , two genes expressed in forelimb and hindlimb-forming regions respectively , play crucial roles in the ...
The acquisition of limbs during vertebrate evolution was a very successful innovation that enabled this group of species to diversify and colonise land . It has become clear recently that the primary driver behind the evolution of new structures , such as limbs , is the acquisition of novel regulatory elements that con...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "embryology", "organism", "development", "gene", "expression", "genetics", "organogenesis", "biology", "anatomy", "and", "physiology", "evolutionary", "biology", "pattern", "formation", "evolutionary", "developmental", "biology" ]
2014
A Combination of Activation and Repression by a Colinear Hox Code Controls Forelimb-Restricted Expression of Tbx5 and Reveals Hox Protein Specificity
The evolution of drug resistance in fungal pathogens compromises the efficacy of the limited number of antifungal drugs . Drug combinations have emerged as a powerful strategy to enhance antifungal efficacy and abrogate drug resistance , but the impact on the evolution of drug resistance remains largely unexplored . Ta...
Fungal infections are a leading cause of mortality worldwide and are difficult to treat due to the limited number of antifungal drugs , whose effectiveness is compromised by the emergence of drug resistance . A powerful strategy to combat drug resistance is combination therapy . Inhibiting the molecular chaperone Hsp90...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "mycology", "model", "organisms", "fungal", "evolution", "microbial", "evolution", "microbial", "pathogens", "yeast", "and", "fungal", "models", "biology", "microbiology", "yeast" ]
2013
Genetic and Genomic Architecture of the Evolution of Resistance to Antifungal Drug Combinations
During meiotic prophase , chromosomes display rapid movement , and their telomeres attach to the nuclear envelope and cluster to form a “chromosomal bouquet . ” Little is known about the roles of the chromosome movement and telomere clustering in this phase . In budding yeast , telomere clustering is promoted by a meio...
Meiosis is a specialized cell division that produces haploid gametes . Homologous recombination plays a pivotal role in the segregation of homologous chromosomes during meiosis I by creating physical linkages between the chromosomes . Drastic reorganization of chromosomes in the nucleus is a prominent feature of meioti...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "genetics", "and", "genomics/chromosome", "biology" ]
2008
Csm4-Dependent Telomere Movement on Nuclear Envelope Promotes Meiotic Recombination
Human mobility , presence and passive transportation of Aedes aegypti mosquito , and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment . To understand this process , we assess data from dengue national and municipal basins regarding population and de...
The present ecological study is aimed at characterizing introduction and spread of dengue in the state of Acre , located in Brazil’s north region . We use sociodemographic and entomological data from the year 2000 , when the first case was registered in Acre , up to 2015 , when it was already endemic in most of the sta...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "invertebrates", "dengue", "virus", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "engineering", "and", "technology", "transportation", "pathogens", "geographical", "locations", "microbiology", "social", "sciences", "human", "mobil...
2017
The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil: A network-based analysis
The amount of genetic variance underlying a phenotypic trait and the strength of selection acting on that trait are two key parameters that determine any evolutionary response to selection . Despite substantial evidence that , in natural populations , both parameters may vary across environmental conditions , very litt...
The speed of evolutionary change in a phenotypic trait is determined by two key components: the amount of genetic variance underlying the trait and the strength of selection acting on it . Many studies have shown that both selection and expression of genetic variance may depend on the environmental conditions the popul...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "evolutionary", "biology/evolutionary", "ecology", "evolutionary", "biology/evolutionary", "and", "comparative", "genetics", "genetics", "and", "genomics/complex", "traits" ]
2011
Speeding Up Microevolution: The Effects of Increasing Temperature on Selection and Genetic Variance in a Wild Bird Population
Hepatitis C virus ( HCV ) induces interferon ( IFN ) stimulated genes in the liver despite of distinct innate immune evasion mechanisms , suggesting that beyond HCV infected cells other cell types contribute to innate immune activation . Upon coculture with HCV replicating cells , human CD141+ myeloid dendritic cells (...
HCV is an RNA virus that , following exposure , in most cases establishes chronic infection . The virus has evolved numerous immune evasion strategies , including direct interference with interferon production . Nevertheless , HCV infection activates interferon-stimulated genes in the liver , implying that non-infected...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "immune", "cells", "vesicles", "pathology", "and", "laboratory", "medicine", "enzyme-linked", "immunoassays", "hepacivirus", "antigen-presenting", "cells", "pathogens", "immunology", "biological", "cultures", "microbiology", "hepatom...
2016
Hepatitis C Virus Stimulates Murine CD8α-Like Dendritic Cells to Produce Type I Interferon in a TRIF-Dependent Manner
The responses of neurons in sensory cortex depend on the summation of excitatory and inhibitory synaptic inputs . How the excitatory and inhibitory inputs scale with stimulus depends on the network architecture , which ranges from the lateral inhibitory configuration where excitatory inputs are more narrowly tuned than...
The cerebral cortex contains a network of electrically active cells ( neurons ) interconnected by synapses , which may be excitatory ( tending to increase activity ) or inhibitory . Network activity , i . e . , the ensemble of activity patterns of the individual cells , is driven by input from the sense organs , and cr...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "circuit", "models", "auditory", "system", "central", "nervous", "system", "synapses", "computational", "neuroscience", "biology", "sensory", "systems", "neuroscience", "neurophysiology" ]
2011
Coexistence of Lateral and Co-Tuned Inhibitory Configurations in Cortical Networks
Neurons communicate primarily with spikes , but most theories of neural computation are based on firing rates . Yet , many experimental observations suggest that the temporal coordination of spikes plays a role in sensory processing . Among potential spike-based codes , synchrony appears as a good candidate because neu...
How does the brain compute ? Traditional theories of neural computation describe the operating function of neurons in terms of average firing rates , with the timing of spikes bearing little information . However , numerous studies have shown that spike timing can convey information and that neurons are highly sensitiv...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "computational", "neuroscience", "biology", "sensory", "systems", "neuroscience" ]
2012
Computing with Neural Synchrony
Entamoeba histolytica is responsible for causing amoebiasis . Polyamine biosynthesis pathway enzymes are potential drug targets in parasitic protozoan diseases . The first and rate-limiting step of this pathway is catalyzed by ornithine decarboxylase ( ODC ) . ODC enzyme functions as an obligate dimer . However , parti...
E . histolytica genome sequence divulged the existence of ornithine decarboxylase enzyme that performs the first-rate limiting catalytic step of polyamine biosynthetic pathway . ODC enzyme is a potent therapeutic target in many eukaryotic disease causing pathogens . DFMO , a potent substrate analogue inhibitor , is wid...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "and", "Discussion" ]
[ "biology", "computational", "biology", "microbiology", "biophysics", "macromolecular", "structure", "analysis" ]
2012
Biochemical, Mutational and In Silico Structural Evidence for a Functional Dimeric Form of the Ornithine Decarboxylase from Entamoeba histolytica
Increasing volumes of data and computational capacity afford unprecedented opportunities to scale up infectious disease ( ID ) mapping for public health uses . Whilst a large number of IDs show global spatial variation , comprehensive knowledge of these geographic patterns is poor . Here we use an objective method to p...
Maps have long been used to not only visualise , but also to inform infectious disease control efforts , identify and predict areas of greatest risk of specific diseases , and better understand the epidemiology of disease over various spatial scales . In spite of the utilities of such outputs , globally comprehensive m...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Prioritising Infectious Disease Mapping
Chromosome replication in Escherichia coli is in part controlled by three non-coding genomic sequences , DARS1 , DARS2 , and datA that modulate the activity of the initiator protein DnaA . The relative distance from oriC to the non-coding regions are conserved among E . coli species , despite large variations in genome...
Replication of the E . coli chromosome is the central event in the cell cycle , with the control of replication enforced at the level of initiation . DnaA is the key protein responsible for initiation at the origin of replication ( oriC ) , and is active in this when bound to ATP and inactive when bound to ADP . The ac...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "bacteriology", "sequencing", "techniques", "cell", "cycle", "and", "cell", "division", "cell", "processes", "microbiology", "cloning", "genome", "sequencing", "genetic", "elements", "bacterial", "genetics", "molecular", "biology", "techniques", "microbial", "genetics", ...
2016
DNA Replication Control Is Linked to Genomic Positioning of Control Regions in Escherichia coli
Mlh1-Mlh3 ( MutLγ ) is a mismatch repair factor with a central role in formation of meiotic crossovers , presumably through resolution of double Holliday junctions . MutLγ has DNA-binding , nuclease , and ATPase activities , but how these relate to one another and to in vivo functions are unclear . Here , we combine bi...
Sexual reproduction involves the fusion of two gametes that each contain half of the DNA from each parent . These gametes are generated through a specialized cellular division called meiosis . During meiosis , the cell faces the challenge of identifying the appropriate pairs of chromosomes that need to be separated . T...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[]
2017
Distinct DNA-binding surfaces in the ATPase and linker domains of MutLγ determine its substrate specificities and exert separable functions in meiotic recombination and mismatch repair
Increasing evidence of a role of chronic inflammation in type 2 diabetes progression has led to the development of therapies targeting the immune system . We develop a model of interleukin-1β dynamics in order to explain principles of disease onset . The parameters in the model are derived from in vitro experiments and...
Insulin resistance and relative insulin deficiency are two hallmarks of type 2 diabetes . While insulin resistance is always present in the early phase , it is β-cell failure that determines the pace of the disease onset . Increasing evidence that the immune system is activated and plays an important role in type 2 dia...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "diabetes", "mellitus", "type", "2", "diabetes", "metabolic", "disorders", "medicine", "and", "health", "sciences" ]
2014
Possible Role of Interleukin-1β in Type 2 Diabetes Onset and Implications for Anti-inflammatory Therapy Strategies
Lignin is a polymer in secondary cell walls of plants that is known to have negative impacts on forage digestibility , pulping efficiency , and sugar release from cellulosic biomass . While targeted modifications of different lignin biosynthetic enzymes have permitted the generation of transgenic plants with desirable ...
The organization of cooperating enzymes into complexes is a pervasive feature of metabolism . In particular , this phenomenon has been shown to participate in the regulation of flux through the networks of both primary and secondary metabolism in plants . It remains a challenging task to unravel the organizing principl...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "systems", "biology", "biochemistry", "plant", "science", "mathematics", "plant", "biology", "applied", "mathematics", "biology", "computational", "biology", "genetics", "and", "genomics" ]
2012
Functional Analysis of Metabolic Channeling and Regulation in Lignin Biosynthesis: A Computational Approach
Even across genomes of the same species , prokaryotes exhibit remarkable flexibility in gene content . We do not know whether this flexible or “accessory” content is mostly neutral or adaptive , largely due to the lack of explicit analyses of accessory gene function . Here , across 96 diverse prokaryotic species , I sh...
Recent and rapid advancements in genome sequencing technologies have revealed key insights into the world of bacteria and archaea . One puzzling aspect uncovered by these studies is the following: genomes of the same species can often look very different . Specifically , some “core” genes are maintained across all intr...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Methods" ]
[ "functional", "genomics", "genome", "evolution", "statistics", "metabolic", "networks", "operons", "regression", "analysis", "genomic", "databases", "mathematics", "metabolites", "network", "analysis", "genome", "analysis", "dna", "research", "and", "analysis", "methods",...
2018
Metabolic adaptations underlying genome flexibility in prokaryotes
Ectotherms rely for their body heat on surrounding temperatures . A key question in biology is why most ectotherms mature at a larger size at lower temperatures , a phenomenon known as the temperature–size rule . Since temperature affects virtually all processes in a living organism , current theories to explain this p...
Biologists are fascinated by variation in body size , which is hardly surprising , considering that the range of body sizes spans orders of magnitude from bacteria to blue whales . Even within species , body sizes can vary dramatically . This intraspecies variation is intriguing because it suggests strong associations ...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "ecology", "caenorhabditis", "evolutionary", "biology", "genetics", "and", "genomics" ]
2007
A Caenorhabditis elegans Wild Type Defies the Temperature–Size Rule Owing to a Single Nucleotide Polymorphism in tra-3
The dual specificity protein/lipid kinase , phosphoinositide 3-kinase ( PI3K ) , promotes growth factor-mediated cell survival and is frequently deregulated in cancer . However , in contrast to canonical lipid-kinase functions , the role of PI3K protein kinase activity in regulating cell survival is unknown . We have e...
The ability of cells to survive in the absence of proliferation ( cell division ) , differentiation ( cell maturation ) or activation allows tissues to maintain cell populations that are poised for rapid responses to damage , infections , or other physiological demands . While this “survival-only” response is fundament...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "protein", "kinase", "signaling", "cascade", "signal", "transduction", "molecular", "cell", "biology", "immune", "physiology", "cytokines", "physiology", "biology", "anatomy", "and", "physiology", "signaling", "cascades" ]
2013
Protein Kinase Activity of Phosphoinositide 3-Kinase Regulates Cytokine-Dependent Cell Survival
Translation of mRNA into a polypeptide chain is a highly accurate process . Many prokaryotic and eukaryotic viruses , however , use leaky termination of translation to optimize their coding capacity . Although growing evidence indicates the occurrence of ribosomal readthrough also in higher organisms , a biological fun...
Eukaryotic organisms use various strategies to generate protein isoforms with different function or intracellular localization from a single gene . While differential splicing of mRNA is the most common mechanism to expand the number of encoded proteins , translational readthrough of stop codons is an alternative strat...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "cell", "biology", "protein", "translation", "fungal", "genetics", "gene", "expression", "genetics", "translation", "termination", "biology", "and", "life", "sciences", "peroxisomes", "cellular", "structures", "and", "organelles" ]
2014
Ribosomal Readthrough at a Short UGA Stop Codon Context Triggers Dual Localization of Metabolic Enzymes in Fungi and Animals
In Hedgehog ( Hh ) signaling , binding of Hh to the Patched-Interference Hh ( Ptc-Ihog ) receptor complex relieves Ptc inhibition on Smoothened ( Smo ) . A longstanding question is how Ptc inhibits Smo and how such inhibition is relieved by Hh stimulation . In this study , we found that Hh elevates production of phosph...
The Hedgehog ( Hh ) signaling pathway plays important roles in both embryonic development and adult tissue homeostasis . A critical step in Hh signal transduction is the inhibition of Smoothened ( Smo ) , an atypical G protein-coupled receptor ( GPCR ) , by the Hh receptor Patched ( Ptc ) . It is a longstanding questio...
[ "Abstract", "Introduction", "Results", "Discussion", "Experimental", "Procedures" ]
[ "phosphorylation", "rna", "interference", "enzyme-linked", "immunoassays", "chemical", "compounds", "organic", "compounds", "immunoprecipitation", "basic", "amino", "acids", "amino", "acids", "epigenetics", "immunologic", "techniques", "cellular", "structures", "and", "orga...
2016
PI(4)P Promotes Phosphorylation and Conformational Change of Smoothened through Interaction with Its C-terminal Tail
The HER/ErbB family of receptor tyrosine kinases drives critical responses in normal physiology and cancer , and the expression levels of the various HER receptors are critical determinants of clinical outcomes . HER activation is driven by the formation of various dimer complexes between members of this receptor famil...
A family of cell surface molecules called the HER receptor family plays important roles in normal physiology and cancer . This family has four members , HER1-4 . These receptors convert signals received from the extracellular environment into cell decisions such as growth and survival – a process termed signal transduc...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "mechanisms", "of", "signal", "transduction", "signaling", "networks", "membrane", "receptor", "signaling", "growth", "factors", "signaling", "pathways", "biophysics", "simulations", "biochemistry", "simulations", "proteins", "biology", "biophysics", "systems", "biology", ...
2013
Model-Based Analysis of HER Activation in Cells Co-Expressing EGFR, HER2 and HER3
Little is known about immediate phases after viral infection and how an incoming viral genome complex counteracts host cell defenses , before the start of viral gene expression . Adenovirus ( Ad ) serves as an ideal model , since entry and onset of gene expression are rapid and highly efficient , and mechanisms used 24...
Viruses have acquired functions that target and modulate host cell signaling and diverse regulatory cascades , leading to efficient viral propagation . During the course of productive infection , Ad gene products manipulate destruction pathways to prevent viral clearance or cell death prior to viral genome amplificatio...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
SPOC1-Mediated Antiviral Host Cell Response Is Antagonized Early in Human Adenovirus Type 5 Infection
Cell type specification is a fundamental process that all cells must carry out to ensure appropriate behaviors in response to environmental stimuli . In fungi , cell identity is critical for defining “sexes” known as mating types and is controlled by components of mating type ( MAT ) loci . MAT–encoded genes function t...
All organisms that undergo sexual reproduction carry out specific mechanisms to establish different sexes . In fungi , sexual identity is typically determined by components housed within specialized regions of chromosomes known as mating-type ( MAT ) loci . MAT–encoded genes function to define sexes via two distinct pa...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/microbial", "evolution", "and", "genomics", "cell", "biology", "microbiology", "evolutionary", "biology", "molecular", "biology" ]
2010
Allelic Exchange of Pheromones and Their Receptors Reprograms Sexual Identity in Cryptococcus neoformans
Human genome-wide association studies ( GWAS ) have shown that genetic variation at >130 gene loci is associated with type 2 diabetes ( T2D ) . We asked if the expression of the candidate T2D-associated genes within these loci is regulated by a common locus in pancreatic islets . Using an obese F2 mouse intercross segr...
Genome-wide association studies ( GWAS ) and linkage studies provide a powerful way to establish a causal connection between a gene locus and a physiological or pathophysiological phenotype . We wondered if candidate genes associated with type 2 diabetes in human populations , in addition to being causal for the diseas...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "genome-wide", "association", "studies", "medicine", "and", "health", "sciences", "diabetic", "endocrinology", "gene", "regulation", "cell", "cycle", "and", "cell", "division", "cell", "processes", "hormones", "endocrine", "physiology", "genome", "analysis", "mammalian"...
2016
The Transcription Factor Nfatc2 Regulates β-Cell Proliferation and Genes Associated with Type 2 Diabetes in Mouse and Human Islets
Laiwu District is recognized as a hyper-endemic region for scrub typhus in Shandong Province , but the seriousness of this problem has been neglected in public health circles . A disability-adjusted life years ( DALYs ) approach was adopted to measure the burden of scrub typhus in Laiwu , China during the period 2006 t...
Scrub typhus , also known as tsutsugamushi disease , is a zoonosis transmitted by chigger bites ( larval trombiculid mites ) and the pathogen Orientia tsutsugamushi ( O . tsutsugamushi ) , a Gram-negative obligate intracellular bacterium . It is distributed widely in the Pacific regions of Asia , and the islands of the...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "plant", "science", "infectious", "disease", "epidemiology", "epidemiology", "plant", "pathology", "biology", "and", "life", "sciences" ]
2015
Burden of Disease Measured by Disability-Adjusted Life Years and a Disease Forecasting Time Series Model of Scrub Typhus in Laiwu, China
Cutaneous infection by Mycobacterium ulcerans , also known as Buruli ulcer ( BU ) , represents the third most common mycobacterial disease in the world after tuberculosis and leprosy . Data on the burden of BU disease in the Democratic Republic of Congo are scanty . This study aimed to estimate the prevalence rate and ...
Buruli ulcer ( BU ) is a necrotizing bacterial infection of skin , subcutaneous tissue and bone , caused by an environmental pathogen , Mycobacterium ulcerans . BU is considered as one of the Neglected Tropical Diseases with a poorly known global prevalence , and mainly affects remote rural African communities . Data o...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2013
Burden of Mycobacterium ulcerans Disease (Buruli Ulcer) and the Underreporting Ratio in the Territory of Songololo, Democratic Republic of Congo
Hepatitis delta virus ( HDV ) increases morbidity in Hepatitis B virus ( HBV ) -infected patients . In the mid-eighties , an outbreak of HDV fulminant hepatitis ( FH ) in the Central African Republic ( CAR ) killed 88% of patients hospitalized in Bangui . We evaluated infections with HBV and HDV among students and preg...
In the Central African Republic ( CAR ) , due to 20 years of conflict , the health system has been disorganized . This could contribute to maintenance of high transmission levels of Hepatitis B Virus ( HBV ) and its satellite Hepatitis Delta Virus ( HDV ) . This work studies the evolution of both infections 25 years af...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "taxonomy", "medicine", "and", "health", "sciences", "body", "fluids", "pathology", "and", "laboratory", "medicine", "pathogens", "immunology", "microbiology", "hepatitis", "b", "virus", "liver", "diseases", "viruses", "preventive", "medicine", "phylogenetics", "data", ...
2018
Hepatitis B and hepatitis D virus infections in the Central African Republic, twenty-five years after a fulminant hepatitis outbreak, indicate continuing spread in asymptomatic young adults
The global incidence of snakebite is estimated at more than 2 . 5 million cases annually , with greater than 100 , 000 deaths . Historically , Myanmar has one of the highest incidences of venomous snakebites . In order to improve the health outcomes of snakebite patients in Myanmar , access to accurate snakebite incide...
Snakebite is a major health issue affecting large numbers of people , particularly in tropical developing countries . Myanmar has one of the highest incidences of venomous snakebite in the world . Considering changes in demography , development , agricultural practices , knowledge about prevention and preventive practi...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "health", "education", "and", "awareness", "health", "services", "research", "tropical", "diseases", "geographical", "locations", "vertebrates", "animals", "health", "care", "reptiles", "myanmar", "rural", "areas", "neglected", ...
2018
Snakebite incidence in two townships in Mandalay Division, Myanmar
Cancer drivers are genomic alterations that provide cells containing them with a selective advantage over their local competitors , whereas neutral passengers do not change the somatic fitness of cells . Cancer-driving mutations are usually discriminated from passenger mutations by their higher degree of recurrence in ...
Cancer genome sequencing projects result in vast amounts of cancer mutation data . However , our understanding of which mutations are driving tumor growth and which are selectively neutral is lagging behind . Functional interactions among mutations can result in mutational dependencies , and these mutations then displa...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "oncology", "statistical", "models", "medicine", "and", "health", "sciences", "mathematics", "statistics", "(mathematics)", "basic", "cancer", "research", "biology", "and", "life", "sciences", "physical", "sciences", "computational", "biology", "evolutionary", "biology", ...
2015
Identification of Constrained Cancer Driver Genes Based on Mutation Timing
In the Indian subcontinent , Visceral leishmaniasis is endemic in a geographical area coinciding with the Lower Gangetic Plain , at low altitude . VL occurring in residents of hill districts is therefore often considered the result of Leishmania donovani infection during travel . Early 2014 we conducted an outbreak inv...
Visceral leishmaniasis is a neglected but deadly disease occurring in north-eastern India , the south-eastern lowland of Nepal , and the Ganges delta in Bangladesh; all part of the Lower Gangetic plains . Districts at higher altitude , such as those situated in the foothills of the Himalaya in Nepal , are considered no...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Transmission of Leishmania donovani in the Hills of Eastern Nepal, an Outbreak Investigation in Okhaldhunga and Bhojpur Districts
Fossil records indicate that life appeared in marine environments ∼3 . 5 billion years ago ( Gyr ) and transitioned to terrestrial ecosystems nearly 2 . 5 Gyr . Sequence analysis suggests that “hydrobacteria” and “terrabacteria” might have diverged as early as 3 Gyr . Bacteria of the genus Azospirillum are associated w...
Genome sequencing and analysis of plant-associated beneficial soil bacteria Azospirillum spp . reveals that these organisms transitioned from aquatic to terrestrial environments significantly later than the suggested major Precambrian divergence of aquatic and terrestrial bacteria . Separation of Azospirillum from thei...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "genome", "sequencing", "genome", "complexity", "genome", "evolution", "microbial", "evolution", "biology", "genomics", "comparative", "genomics", "microbiology", "genetics", "and", "genomics" ]
2011
Azospirillum Genomes Reveal Transition of Bacteria from Aquatic to Terrestrial Environments
Many questions about the genetic basis of complex traits remain unanswered . This is in part due to the low statistical power of traditional genetic mapping studies . We used a statistically powerful approach , extreme QTL mapping ( X-QTL ) , to identify the genetic basis of resistance to 13 chemicals in all 6 pairwise...
Most heritable traits of agricultural , evolutionary , and medical significance are specified by multiple genetic loci . Despite decades of research , we have only a limited understanding of the genetic basis of such complex traits . Studies in model organisms have the potential to provide fundamental insights into thi...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "genetics", "biology", "genomics", "evolutionary", "biology", "genetics", "and", "genomics" ]
2012
Genetic Architecture of Highly Complex Chemical Resistance Traits across Four Yeast Strains
The improved capacity to acquire quantitative data in a clinical setting has generally failed to improve outcomes in acutely ill patients , suggesting a need for advances in computer-supported data interpretation and decision making . In particular , the application of mathematical models of experimentally elucidated p...
Although quantitative physiology has developed numerous mathematical descriptions of components of the human body , their application in clinical medicine has been limited to a few mostly primitive and physiologically inaccurate models . One reason for this is that the inverse problem of identifying unknown model param...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "mathematics", "physiology", "dog", "computational", "biology", "homo", "(human)", "cardiovascular", "disorders" ]
2007
From Inverse Problems in Mathematical Physiology to Quantitative Differential Diagnoses
The cellular immune system screens peptides presented by host cells on MHC molecules to assess if the cells are infected . In this study we examined whether the presented peptides contain enough information for a proper self/nonself assessment by comparing the presented human ( self ) and bacterial or viral ( nonself )...
Human cells sample short peptides from endogenous proteins , and present them to the immune system via HLA class I molecules on the cell surface . T-cells scan the presented peptides and need to discriminate foreign ( nonself ) peptides from human ( self ) peptides . We show that this is a difficult task , despite the ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "vaccination", "infectious", "diseases", "immune", "cells", "clinical", "immunology", "immunity", "immunology", "biology", "computational", "biology", "microbiology" ]
2012
Degenerate T-cell Recognition of Peptides on MHC Molecules Creates Large Holes in the T-cell Repertoire
Cereal endosperm represents 60% of the calories consumed by human beings worldwide . In addition , cereals also serve as the primary feedstock for livestock . However , the regulatory mechanism of cereal endosperm and seed development is largely unknown . Polycomb complex has been shown to play a key role in the regula...
Rice is the staple food for over half of the world's population and an important feedstock for livestock . The rice grain is mainly endosperm tissue . The regulatory mechanism of rice endosperm development is still largely unknown thus far . Understanding the underlying mechanism will lead to crop yield and quality imp...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "agriculture", "biology" ]
2013
Polycomb Group Gene OsFIE2 Regulates Rice (Oryza sativa) Seed Development and Grain Filling via a Mechanism Distinct from Arabidopsis
The genetic impact associated to the Neolithic spread in Europe has been widely debated over the last 20 years . Within this context , ancient DNA studies have provided a more reliable picture by directly analyzing the protagonist populations at different regions in Europe . However , the lack of available data from th...
Since the original human expansions out of Africa 200 , 000 years ago , different prehistoric and historic migration events have taken place in Europe . Considering that the movement of the people implies a consequent movement of their genes , it is possible to estimate the impact of these migrations through the geneti...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "haplotypes", "social", "sciences", "archaeology", "gene", "pool", "genetic", "polymorphism", "physical", "anthropology", "paleontology", "genetics", "biology", "and", "life", "sciences", "population", "genetics", "gene", "flow", "population", "biology", "evolutionary", ...
2014
Ancient DNA Analysis of 8000 B.C. Near Eastern Farmers Supports an Early Neolithic Pioneer Maritime Colonization of Mainland Europe through Cyprus and the Aegean Islands
Until recently , NADPH oxidase ( NOX ) enzymes were thought to be a property of multicellularity , where the reactive oxygen species ( ROS ) produced by NOX acts in signaling processes or in attacking invading microbes through oxidative damage . We demonstrate here that the unicellular yeast and opportunistic fungal pa...
We demonstrate here that the opportunistic human fungal pathogen Candida albicans uses a NADPH oxidase enzyme ( NOX ) and reactive oxygen species ( ROS ) to control morphogenesis in an animal host . C . albicans was not previously known to express NOX enzymes as these were thought to be a property of multicellular orga...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biofilms", "blood", "cells", "medicine", "and", "health", "sciences", "immune", "cells", "pathology", "and", "laboratory", "medicine", "chemical", "compounds", "oxides", "pathogens", "immunology", "microbiology", "animal", "models", "developmental", "biology", "fungi",...
2017
Candida albicans FRE8 encodes a member of the NADPH oxidase family that produces a burst of ROS during fungal morphogenesis
The Vibrio cholerae type VI secretion system ( T6SS ) assembles as a molecular syringe that injects toxic protein effectors into both eukaryotic and prokaryotic cells . We previously reported that the V . cholerae O37 serogroup strain V52 maintains a constitutively active T6SS to kill other Gram-negative bacteria while...
Vibrio cholerae is the causative agent of the diarrheal disease cholera . This bacterium uses the type VI secretion system ( T6SS ) to kill other bacteria and host cells . The T6SS is a molecular syringe that Gram-negative bacteria use to inject toxic effectors into target cells in a contact-dependent manner . The V . ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2013
Dual Expression Profile of Type VI Secretion System Immunity Genes Protects Pandemic Vibrio cholerae
Interactions among microbial community members can lead to emergent properties , such as enhanced productivity , stability , and robustness . Iron-oxide mats in acidic ( pH 2–4 ) , high-temperature ( > 65 °C ) springs of Yellowstone National Park contain relatively simple microbial communities and are well-characterize...
Microbial communities often display emergent properties , such as enhanced productivity , stability , and robustness , compared to their component populations in isolation . However , determining the governing principles of these emergent properties can be elusive due to the complexities of interpreting and integrating...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "physiology", "ecology", "and", "environmental", "sciences", "chemical", "compounds", "electron", "donors", "oxygen", "cell", "metabolism", "sulfur", "oxygen", "metabolism", "sulfides", "ecological", "metrics", "chemistry", "oxidation", "biochemistry", "biomass", ...
2018
Multiscale analysis of autotroph-heterotroph interactions in a high-temperature microbial community
Gene duplication is the predominant mechanism for the evolution of new genes . Major existing models of this process assume that duplicate genes are redundant; degenerative mutations in one copy can therefore accumulate close to neutrally , usually leading to loss from the genome . When gene products dimerize or intera...
Most genes evolved by duplication of more ancient genes . Under existing models of this process , mutations that compromise one copy have no effect on the other; as long as one copy remains intact , such “degenerative” mutations are shielded from selection . Because degenerative mutations are common , most duplicates a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "evolutionary", "biology", "genetics", "and", "genomics" ]
2008
Evolution of a New Function by Degenerative Mutation in Cephalochordate Steroid Receptors
Clinical examination of trachoma is used to justify intervention in trachoma-endemic regions . Currently , field graders are certified by determining their concordance with experienced graders using the kappa statistic . Unfortunately , trachoma grading can be highly variable and there are cases where even expert grade...
Trachoma is the leading infectious cause of blindness and the World Health Organization plans to eliminate it as a public health concern worldwide by the year 2020 . This effort in large part involves mass oral antibiotic distributions to communities . A simplified trachoma grading scale is used to assess presence of a...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "eye", "infections", "public", "and", "occupational", "health", "bacterial", "diseases", "infectious", "diseases", "medicine", "and", "health", "sciences", "global", "health", "ophthalmology", "neglected", "tropical", "diseases", "tropical", "diseases", "trachoma" ]
2014
Reliability of Trachoma Clinical Grading—Assessing Grading of Marginal Cases
Amyloidogenic neurodegenerative diseases are incurable conditions with high social impact that are typically caused by specific , largely disordered proteins . However , the underlying molecular mechanism remains elusive to established techniques . A favored hypothesis postulates that a critical conformational change i...
Neurodegenerative diseases like Alzheimer's or Parkinson's are currently incurable . They are caused by different proteins that , under certain circumstances , aggregate and become toxic as we grow older , but the molecular events underlying this process remain unclear . The lack of a well-defined structure , and the t...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "protein", "interactions", "drugs", "and", "devices", "chemical", "biology", "biomechanics", "protein", "folding", "protein", "structure", "proteins", "chemistry", "biology", "recombinant", "proteins", "biophysics", "physics", "biochemistry", "protein", "chemi...
2012
Common Features at the Start of the Neurodegeneration Cascade
An outstanding question in human genetics has been the degree to which adaptation occurs from standing genetic variation or from de novo mutations . Here , we combine several common statistics used to detect selection in an Approximate Bayesian Computation ( ABC ) framework , with the goal of discriminating between mod...
Considerable effort has been devoted to detecting genes that are under natural selection , and hundreds of such genes have been identified in previous studies . Here , we present a method for extending these studies by inferring parameters , such as selection coefficients and the time when a selected variant arose . Of...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "natural", "selection", "human", "genetics", "genetics", "population", "genetics", "biology", "evolutionary", "biology", "evolutionary", "processes", "genetics", "and", "genomics", "evolutionary", "genetics", "evolutionary", "theory" ]
2012
Distinguishing between Selective Sweeps from Standing Variation and from a De Novo Mutation
CMT4J is a severe form of Charcot-Marie-Tooth neuropathy caused by mutation of the phosphoinositide phosphatase FIG4/SAC3 . Affected individuals are compound heterozygotes carrying the missense allele FIG4-I41T in combination with a null allele . Analysis using the yeast two-hybrid system demonstrated that the I41T mut...
Charcot-Marie-Tooth disease type 4J is a severe neurological disorder with childhood or adult onset and progression to loss of mobility and death . Patients inherit a mutation that changes amino acid residue 41 of the FIG4 protein from isoleucine to threonine . We report that this mutation destabilizes the FIG4 protein...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "model", "organisms", "neurological", "disorders", "neurology", "genetics", "biology", "neuroscience", "genetics", "and", "genomics" ]
2011
Pathogenic Mechanism of the FIG4 Mutation Responsible for Charcot-Marie-Tooth Disease CMT4J
It has long been thought that iminosugar antiviral activity is a function of inhibition of endoplasmic reticulum-resident α-glucosidases , and on this basis , many iminosugars have been investigated as therapeutic agents for treatment of infection by a diverse spectrum of viruses , including dengue virus ( DENV ) . How...
Current treatment of dengue virus infection is supportive; however , iminosugars have been widely investigated as an antiviral strategy . The means by which these molecules are thought to exert their antiviral effects is through inhibition of host-resident glycoprotein processing enzymes , the endoplasmic reticulum-res...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "glycolipids", "animal", "models", "of", "disease", "endoplasmic", "reticulum", "cell", "processes", "enzymology", "biological", "cultures", "microbiology", "animal", "models", "model", "organisms", "cell", "cultures", "glycoproteins", "enzyme", "inhibitors", "cellular", ...
2016
Iminosugars Inhibit Dengue Virus Production via Inhibition of ER Alpha-Glucosidases—Not Glycolipid Processing Enzymes
Recent studies have revealed an important role for hormones in plant immunity . We are now beginning to understand the contribution of crosstalk among different hormone signaling networks to the outcome of plant–pathogen interactions . Cytokinins are plant hormones that regulate development and responses to the environ...
Plant hormones play an important role in many aspects of a plant's life cycle , from the regulation of development to responses to constantly changing environmental conditions . In the past decade , the importance of hormones in plant immunity against a variety of pathogens has been uncovered . In this manuscript , we ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "plant", "science", "plant", "biology", "biology" ]
2012
Two-Component Elements Mediate Interactions between Cytokinin and Salicylic Acid in Plant Immunity
Activated protein kinase R ( PKR ) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses . Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR . The NSs ( Non-structural s ) protein which is encoded by Rift Valle...
Rift Valley fever ( RVF ) is a severe disease caused by infection with the Rift Valley fever virus ( RVFV ) that affects humans and livestock and occurs in large epidemics . Currently there are no FDA-approved drugs or vaccines to treat RVF . Many viruses have evolved unique strategies to overcome host immune responses...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "rift", "valley", "fever", "virus", "pathology", "and", "laboratory", "medicine", "hela", "cells", "gene", "regulation", "pathogens", "enzymes", "biological", "cultures", "vector-borne", "diseases", "microbiology", "enzymology", ...
2016
Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase
Transcription factor binding to DNA in vivo causes the recruitment of chromatin modifiers that can cause changes in chromatin structure , including the modification of histone tails . We previously showed that estrogen receptor ( ER ) target gene activation is facilitated by peptidylarginine deiminase 2 ( PAD2 ) -catal...
Transcription factors bind to DNA to activate and repress gene transcription . Many transcription factors , particularly nuclear receptors , associate with their cognate DNA element in a highly dynamic manner in vivo . Highly acetylated histone tails and DNase sensitive chromatin are amenable to the initial binding of ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "chromatin", "immunoprecipitation", "biochemistry", "genomics", "proteins", "genome", "analysis", "transcription", "factors", "gene", "expression", "genetics", "gene", "regulation", "biology", "and", "life", "sciences", "dna-binding", "proteins", "computational", "biology" ...
2014
Targeted H3R26 Deimination Specifically Facilitates Estrogen Receptor Binding by Modifying Nucleosome Structure
Bacterial microcompartments are large , roughly icosahedral shells that assemble around enzymes and reactants involved in certain metabolic pathways in bacteria . Motivated by microcompartment assembly , we use coarse-grained computational and theoretical modeling to study the factors that control the size and morpholo...
Bacterial microcompartments are protein shells that encase enzymes and reactants to enable bacteria to perform vital reactions , such as breaking down chemicals for energy or converting the products of photosynthesis into sugars . Microcompartments are essential for many bacteria , including human pathogens . Thus , th...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "and", "discussion" ]
[ "protein", "interactions", "condensed", "matter", "physics", "geometry", "cargo", "proteins", "plant", "science", "mathematics", "photosynthesis", "ribulose-1,5-bisphosphate", "carboxylase", "oxygenase", "thermodynamics", "proteins", "chemistry", "physics", "biochemistry", "s...
2018
The role of the encapsulated cargo in microcompartment assembly
West Nile virus ( WNV ) —a mosquito-borne arbovirus—entered the USA through New York City in 1999 and spread to the contiguous USA within three years while transitioning from epidemic outbreaks to endemic transmission . The virus is transmitted by vector competent mosquitoes and maintained in the avian populations . WN...
The underlying pattern of West Nile virus ( WNV ) geographic spread across the United States is not completely clear , which is a necessary step for continental or state level mitigation strategies to reduce WNV transmission . We report a network model that explains the geographic spread of WNV in the United States . W...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "statistics", "pathogens", "microbiology", "vertebrates", "social", "sciences", "animals", "simulation", "and", "modeling", "viruses", "animal", "behavior", "rna", "v...
2019
A spatio-temporal individual-based network framework for West Nile virus in the USA: Spreading pattern of West Nile virus
Immunity to the murine cytomegalovirus ( MCMV ) is critically dependent on the innate response for initial containment of viral replication , resolution of active infection , and proper induction of the adaptive phase of the anti-viral response . In contrast to NK cells , the Vα14 invariant natural killer T cell respon...
An efficient immune response to viral infection requires both innate and adaptive immune cells . Natural killer ( NK ) cells are a critical innate cellular component of the immune response to murine cytomegalovirus ( MCMV ) . Natural killer T ( NK T ) cells are non-classical T cells that have the potential to bridge th...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases", "immunology/immune", "response", "immunology/innate", "immunity", "infectious", "diseases/viral", "infections", "immunology/immunity", "to", "infections" ]
2008
NK Cell–Like Behavior of Vα14i NK T Cells during MCMV Infection
The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system and is of critical importance for vaccine design . We used an O1-specific lytic bacteriophage as a tool to probe the capacity of V . cholerae to alter its O1 antigen and identified a novel mechanism by whic...
The O1 serogroup of Vibrio cholerae is the most common cause of the potentially fatal diarrheal disease cholera , which remains a significant global health burden worldwide . The O1 antigen is a constituent of the lipopolysaccharide portion of the outer membrane , and its location on the bacterial surface makes it a ma...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "biology", "microbiology" ]
2012
Phase Variable O Antigen Biosynthetic Genes Control Expression of the Major Protective Antigen and Bacteriophage Receptor in Vibrio cholerae O1
Microsaccades aid vision by helping to strategically sample visual scenes . Despite the importance of these small eye movements , no cortical area has ever been implicated in their generation . Here , we used unilateral and bilateral reversible inactivation of the frontal eye fields ( FEF ) to identify a cortical drive...
Microsaccades are small , fixational eye movements that precisely relocate the visual axis . Despite evidence that microsaccades can be strategically controlled in high-acuity visual tasks , impacting visual processing , and considerable knowledge about how microsaccades are generated by the oculomotor brainstem , litt...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "velocity", "cognitive", "science", "medicine", "and", "health", "sciences", "classical", "mechanics", "reaction", "time", "vertebrates", "social", "sciences", "neuroscience", "animals", "mammals", "primates", "cognitive", "neuroscience", "vision", "eyes", "neuronal", "...
2016
A Causal Role for the Cortical Frontal Eye Fields in Microsaccade Deployment
Schistosomiasis remains a global public health challenge , with 93% of the ∼237 million infections occurring in sub-Saharan Africa . Though rarely fatal , its recurring nature makes it a lifetime disorder with significant chronic health burdens . Much of its negative health impact is due to non-specific conditions such...
Because urogenital schistosomiasis is a multi-decadal chronic disease that begins in early childhood , and because it is a disease that may affect nearly everyone in endemic communities , its impact on personal health-related quality of life ( HrQoL ) has been difficult to gauge accurately . In order to provide a more ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "public", "health", "and", "epidemiology", "growth", "retardation", "social", "and", "behavioral", "sciences", "infectious", "disease", "epidemiology", "sociology", "pediatrics", "social", "epidemiology", "nutrition", "clinical", "epidemiology", "global", "hea...
2013
Evaluation of the Health-related Quality of Life of Children in Schistosoma haematobium-endemic Communities in Kenya: A Cross-sectional Study
Rabies , resulting from infection by Rabies virus ( RABV ) and related lyssaviruses , is one of the most deadly zoonotic diseases and is responsible for up to 70 , 000 estimated human deaths worldwide each year . Rapid and accurate laboratory diagnosis of rabies is essential for timely administration of post-exposure p...
Rabies is a preventable disease–but is still responsible for approximately 70 , 000 human deaths worldwide each year . The majority of human deaths occur in Asia and Africa where there is a lack of diagnostic resources and expertise , making it difficult to develop effective prevention and control strategies . In recen...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "reverse", "transcriptase-polymerase", "chain", "reaction", "sequencing", "techniques", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "pathogens", "split-decomposition", "method", "tropical", "diseases", "microbiology", "vertebrates", ...
2017
A Pan-Lyssavirus Taqman Real-Time RT-PCR Assay for the Detection of Highly Variable Rabies virus and Other Lyssaviruses
The origin of syphilis is still controversial . Different research avenues explore its fascinating history . Here we employed a new integrative approach , where paleopathology and molecular analyses are combined . As an exercise to test the validity of this approach we examined different hypotheses on the origin of syp...
Syphilis is a reemerging disease burden . Although it has been studied for five centuries , its origin and spread is still controversial . Did it accompany the evolution of the genus Homo and does it date back to more than a million years or did it emerge only after Columbus's return to Europe ? Initially , to test the...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results/Discussion" ]
[ "evolutionary", "biology/human", "evolution", "infectious", "diseases/neglected", "tropical", "diseases", "microbiology/microbial", "evolution", "and", "genomics", "non-clinical", "medicine/history", "of", "medicine", "infectious", "diseases/sexually", "transmitted", "diseases", ...
2010
Syphilis at the Crossroad of Phylogenetics and Paleopathology
Babesiosis is considered an emerging disease because its incidence has significantly increased in the last 30 years , providing evidence of the expanding range of this rare but potentially life-threatening zoonotic disease . Babesia divergens is a causative agent of babesiosis in humans and cattle in Europe . The recen...
Babesiosis has long been recognized as an economically important disease of cattle , but only in the last 40 years has Babesia been recognized as an important pathogen in humans . Babesiosis in humans is caused by one of several species ( B . microti , B . divergens , B . duncani and B . venatorum ) . The complete Babe...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Methods" ]
[ "sequencing", "techniques", "parasite", "groups", "parasitic", "protozoans", "parasitology", "membrane", "proteins", "developmental", "biology", "apicomplexa", "molecular", "motors", "protozoans", "molecular", "biology", "techniques", "rna", "sequencing", "cellular", "struc...
2019
Comparative and functional genomics of the protozoan parasite Babesia divergens highlighting the invasion and egress processes
Accumulation of filamentous actin ( F-actin ) at the immunological synapse ( IS ) is a prerequisite for the cytotoxic function of natural killer ( NK ) cells . Subsequent to reorganization of the actin network , lytic granules polarize to the IS where their contents are secreted directly toward a target cell , providin...
The immune system's natural killer cells eliminate diseased cells in the body . They do so by secreting toxic molecules directly towards the diseased cells , so causing their death . This process is essential for the host organism to defend itself against infectious diseases . The interface between the natural killer c...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cellular", "structures", "subcellular", "organelles", "molecular", "cell", "biology", "immune", "cells", "cell", "biology", "nk", "cells", "immunology", "biology", "cytoskeleton" ]
2011
Natural Killer Cell Lytic Granule Secretion Occurs through a Pervasive Actin Network at the Immune Synapse
Current drugs to treat African sleeping sickness are inadequate and new therapies are urgently required . As part of a medicinal chemistry programme based upon the simplification of acetogenin-type ether scaffolds , we previously reported the promising trypanocidal activity of compound 1 , a bis-tetrahydropyran 1 , 4-t...
Millions of people are at risk of developing African sleeping sickness through infection with the parasite Trypanosoma brucei , which is fatal if untreated . Current therapies are antiquated and inadequate , requiring hospitalization to deliver them through complex regimens , thus new effective , cheap and easy to admi...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "b", "vitamins", "medicine", "and", "health", "sciences", "chemical", "compounds", "biotin", "metabolic", "processes", "parasitic", "protozoans", "organic", "compounds", "oxidative", "phosphorylation", "protozoans", "alkynes", "amino", "acids", "mitochondria", "energy-pro...
2017
Photo-affinity labelling and biochemical analyses identify the target of trypanocidal simplified natural product analogues
APOBEC3s ( A3s ) are potent restriction factors of human immunodeficiency virus type 1/simian immunodeficiency viruses ( HIV-1/SIV ) , and can repress cross-species transmissions of lentiviruses . HIV-1 originated from a zoonotic infection of SIV of chimpanzee ( SIVcpz ) to humans . However , the impact of human A3s on...
Cellular cytidine deaminases of the APOBEC3 ( A3 ) family are potent restriction factors that are able to inhibit retroviruses , this A3 restriction is counteracted by lentivirus Vif proteins . Human APOBEC3H ( A3H ) represents the most evolutionarily divergent A3 gene; it includes seven haplotypes and several splice v...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "293t", "cells", "pathogens", "biological", "cultures", "microbiology", "vertebrates", "animals", "mammals", "genetic", "mapping", "plasmid", "construction", "retroviruses", "primates",...
2017
Stably expressed APOBEC3H forms a barrier for cross-species transmission of simian immunodeficiency virus of chimpanzee to humans
Lung cancer , with its most prevalent form non-small-cell lung carcinoma ( NSCLC ) , is one of the leading causes of cancer-related deaths worldwide , and is commonly treated with chemotherapeutic drugs such as cisplatin . Lung cancer patients frequently suffer from chemotherapy-induced anemia , which can be treated wi...
A major challenge in the development of therapeutic interventions is the selective inhibition of a signal transduction pathway in one cell type such as a cancer cell leaving the other cell type such as a healthy cell as unaffected as possible . Here , we propose a new approach that combines mathematical modeling based ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "phosphorylation", "medicine", "and", "health", "sciences", "molecular", "probe", "techniques", "messenger", "rna", "cancers", "and", "neoplasms", "immunoblotting", "simulation", "and", "modeling", "oncology", "immunoprecipitation", "molecular", "biology", "techniques", "...
2016
Identification of Cell Type-Specific Differences in Erythropoietin Receptor Signaling in Primary Erythroid and Lung Cancer Cells
Selenocysteine ( Sec ) is cotranslationally inserted into protein in response to UGA codons and is the 21st amino acid in the genetic code . However , the means by which Sec is synthesized in eukaryotes is not known . Herein , comparative genomics and experimental analyses revealed that the mammalian Sec synthase ( Sec...
Biosynthesis of the 20 canonical amino acids is well established in eukaryotes . However , many eukaryotes also have a rare selenium-containing amino acid , selenocysteine , which is the 21st amino acid in the genetic code . Selenium is essential for human health , and its health benefits , including preventing cancer ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods", "Supporting", "Information" ]
[ "biochemistry", "eukaryotes", "molecular", "biology", "genetics", "and", "genomics" ]
2007
Biosynthesis of Selenocysteine on Its tRNA in Eukaryotes
Critical aspects of HIV-1 infection occur in mucosal tissues , particularly in the gut , which contains large numbers of HIV-1 target cells that are depleted early in infection . We used electron tomography ( ET ) to image HIV-1 in gut-associated lymphoid tissue ( GALT ) of HIV-1–infected humanized mice , the first thr...
HIV/AIDS remains a global public health problem with over 33 million people infected worldwide . High-resolution imaging of infected tissues by three-dimensional electron microscopy can reveal details of the structure of HIV-1 , the virus that causes AIDS , how it infects cells , and how and where the virus accumulates...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "immune", "cells", "viral", "classification", "immunology", "host-pathogen", "interaction", "microbiology", "lymphoid", "organs", "retroviruses", "animal", "models", "immunodeficiency", "viruses", "model", "organisms", "animal", "models", "of", "infection", "i...
2014
Electron Tomography of HIV-1 Infection in Gut-Associated Lymphoid Tissue
Chromatoid bodies ( CBs ) are spermiogenesis-specific organelles of largely unknown function . CBs harbor various RNA species , RNA-associated proteins and proteins of the tudor domain family like TDRD6 , which is required for a proper CB architecture . Proteome analysis of purified CBs revealed components of the nonse...
Tudor-domain containing protein 6 ( TDRD6 ) is a central component of the chromatoid body ( CB ) in male germ cells . Chromatoid bodies , which are present in spermatids , contain RNA and protein , are not enclosed by membranes , and typically reside close to the nucleus . Without TDRD6 , a much distorted CB structure ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "rna-binding", "proteins", "3'", "utr", "messenger", "rna", "rna", "extraction", "germ", "cells", "untranslated", "regions", "extraction", "techniques", "sperm", "research", "and", "analysis", "methods", "spermatids", "animal", "cells", "proteins", "gene", "expression...
2016
Chromatoid Body Protein TDRD6 Supports Long 3’ UTR Triggered Nonsense Mediated mRNA Decay
Cell membranes are complex multicomponent systems , which are highly heterogeneous in the lipid distribution and composition . To date , most molecular simulations have focussed on relatively simple lipid compositions , helping to inform our understanding of in vitro experimental studies . Here we describe on simulatio...
Cell membranes play important roles in vivo both in shielding the cell interior from the surrounding environment and in cell function through lipid components of the membrane having roles in controlling protein function , cell signaling etc . We employ molecular dynamics simulations to explore the behavior of biologica...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods", "Cluster", "distribution", "Correlation", "between", "bilayer", "surface", "curvature", "and", "the", "clustering", "of", "lipid", "molecules" ]
[ "cell", "physiology", "biochemistry", "lipids", "cell", "biology", "biology", "and", "life", "sciences", "computational", "biology", "molecular", "cell", "biology", "biophysics", "membrane", "trafficking", "biophysical", "simulations" ]
2014
Lipid Clustering Correlates with Membrane Curvature as Revealed by Molecular Simulations of Complex Lipid Bilayers
Drosophila melanogaster , like other invertebrates , relies solely on its innate immune response to fight invading microbes; by definition , innate immunity lacks adaptive characteristics . However , we show here that priming Drosophila with a sublethal dose of Streptococcus pneumoniae protects against an otherwise-let...
Due to the common practice of vaccination and prominence of AIDS , people are already aware of the distinction between adaptive and innate immunity without realizing it . All organisms have an innate immune response , but only vertebrates possess T cells and the ability to produce antibodies . It has been a long-standi...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "drosophila", "melanogaster", "beauveria", "bassiana", "streptococcus", "pneumoniae", "immunology", "microbiology" ]
2007
A Specific Primed Immune Response in Drosophila Is Dependent on Phagocytes
Cutaneous leishmaniasis ( CL ) represents a range of skin diseases caused by infection with Leishmania parasites and associated with tissue inflammation and skin ulceration . CL is clinically widespread in both the Old and New World but lacks treatments that are well tolerated , effective and inexpensive . Oleylphospho...
Cutaneous leishmaniasis ( CL ) is a vector-borne parasitic disease transmitted to humans by sandflies and characterized by local ulcerative skin lesions . The disease is linked to poverty in the Middle-East , North and East Africa , South-Central Asia and South America , with 0 . 7 to 1 . 2 million new annual cases est...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "dermatology", "infectious", "diseases", "drug", "therapy", "veterinary", "diseases", "zoonoses", "medicine", "and", "health", "sciences", "skin", "infections", "pharmaceutics", "population", "modeling", "leishmaniasis", "protozoan", "infections", "biology", "and", "life"...
2014
Direct Comparison of the Efficacy and Safety of Oral Treatments with Oleylphosphocholine (OlPC) and Miltefosine in a Mouse Model of L. major Cutaneous Leishmaniasis
We developed new methods for parameter estimation-in-context and , with the help of 125 authors , built the AmP ( Add-my-Pet ) database of Dynamic Energy Budget ( DEB ) models , parameters and referenced underlying data for animals , where each species constitutes one database entry . The combination of DEB parameters ...
We discovered that parameters of Dynamic Energy Budget ( DEB ) models can be estimated from a set of simple data on animal life history aspects , growth and reproduction , if treated in combination . Apart from goodness-of-fit as an estimation criterion , relations with parameter values of other species are important ,...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "taxonomy", "invertebrates", "organismal", "evolution", "medicine", "and", "health", "sciences", "ecology", "and", "environmental", "sciences", "evolutionary", "biology", "biodiversity", "animals", "endocrine", "physiology", "developmental", "biology", "data", "management",...
2018
The AmP project: Comparing species on the basis of dynamic energy budget parameters
Dengue dynamics are driven by complex interactions between human-hosts , mosquito-vectors and viruses that are influenced by environmental and climatic factors . The objectives of this study were to analyze and model the relationships between climate , Aedes aegypti vectors and dengue outbreaks in Noumea ( New Caledoni...
Dengue fever is a major public health problem in the tropics and subtropics . Since no vaccine exists , understanding and predicting outbreaks remain of crucial interest . Climate influences the mosquito-vector biology and the viral transmission cycle . Its impact on dengue dynamics is of growing interest . We analyzed...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine" ]
2012
Climate-Based Models for Understanding and Forecasting Dengue Epidemics
Malaria parasites ( Plasmodium spp . ) and related apicomplexan pathogens contain a nonphotosynthetic plastid called the apicoplast . Derived from an unusual secondary eukaryote–eukaryote endosymbiosis , the apicoplast is a fascinating organelle whose function and biogenesis rely on a complex amalgamation of bacterial ...
Plasmodium parasites , which cause malaria , and related pathogens belonging to the phylum Apicomplexa contain a relict chloroplast called the apicoplast . During evolution , the apicoplast lost photosynthetic functions but retained critical metabolic pathways that are required for host cell infection . Because of its ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "b", "vitamins", "parasite", "groups", "methods", "and", "resources", "chemical", "compounds", "biotin", "plasmodium", "endoplasmic", "reticulum", "cell", "processes", "green", "fluorescent", "protein", "organic", "compounds", "parasitic", "protozoans", "parasitology", ...
2018
Integrative proteomics and bioinformatic prediction enable a high-confidence apicoplast proteome in malaria parasites
Efforts are underway to scale-up the facial cleanliness and environmental improvement ( F&E ) components of the World Health Organization’s SAFE strategy for elimination of trachoma as a public health problem . Improving understanding of the F&E intervention landscape could inform advancements prior to scale-up , and l...
Trachoma is the world’s leading infectious cause of blindness . In light of a 2020 global target , the international trachoma community is intensifying its efforts to scale-up facial cleanliness and environmental improvement ( F&E ) components of the WHO-endorsed SAFE strategy for the elimination of trachoma as a publi...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "face", "tropical", "diseases", "health", "care", "preventive", "medicine", "bacterial", "diseases", "health", "services", "administration", "and", "management", "eye", "diseases", "global", "health", "neglected", "tropical", "...
2018
Interventions to maximize facial cleanliness and achieve environmental improvement for trachoma elimination: A review of the grey literature
OVATE gene was first identified as a key regulator of fruit shape in tomato . OVATE family proteins ( OFPs ) are characterized as plant-specific transcription factors and conserved in Arabidopsis , tomato , and rice . Roles of OFPs involved in plant development and growth are largely unknown . Brassinosteroids ( BRs ) ...
OVATE family proteins ( OFPs ) are characterized as plant-specific transcription factors and mainly function in affecting fruit shape , but the molecular mechanisms by which they function are largely unknown . Rice genome contains 31 OFPs , the roles of these OsOFPs involved in plant development and growth are not unde...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "phosphorylation", "plant", "anatomy", "rna", "interference", "gene", "regulation", "regulatory", "proteins", "brassica", "dna-binding", "proteins", "cereal", "crops", "plant", "science", "model", "organisms", "rice", "transcription", "factors", "crops", "epigenetics", ...
2016
OVATE Family Protein 8 Positively Mediates Brassinosteroid Signaling through Interacting with the GSK3-like Kinase in Rice
Lassa fever is caused by a viral haemorrhagic arenavirus that affects two to three million people in West Africa , causing a mortality of between 5 , 000 and 10 , 000 each year . The natural reservoir of Lassa virus is the multi-mammate rat Mastomys natalensis , which lives in houses and surrounding fields . With the a...
Previous studies on the eco-epidemiology of Lassa fever in Guinea , West Africa , have shown that the reservoir is two to three times more infected by Lassa virus in the rainy season than in the dry season . None of the intrinsic variables of the murine population , such as abundance or reproduction , was able to expla...
[ "Abstract", "Introduction", "Results", "Discussion" ]
[ "infectious", "diseases/neglected", "tropical", "diseases", "computational", "biology/ecosystem", "modeling", "infectious", "diseases/viral", "infections", "virology/emerging", "viral", "diseases" ]
2009
Risk Maps of Lassa Fever in West Africa
Cells generate diverse microtubule populations by polymerization of a common α/β-tubulin building block . How microtubule associated proteins translate microtubule heterogeneity into specific cellular functions is not clear . We evaluated the ability of kinesin motors involved in vesicle transport to read microtubule h...
Eukaryotic cells assemble a variety of cytoskeletal structures from a set of highly conserved building blocks . For example , all microtubules are generated by the polymerization of a common α/β-tubulin subunit , yet cells can contain diverse , discrete populations of microtubule structures such as axonemes , spindles ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biophysics/macromolecular", "assemblies", "and", "machines", "cell", "biology/morphogenesis", "and", "cell", "biology", "biophysics/experimental", "biophysical", "methods", "cell", "biology/membranes", "and", "sorting", "cell", "biology/cytoskeleton" ]
2009
Single Molecule Imaging Reveals Differences in Microtubule Track Selection Between Kinesin Motors
Burkholderia pseudomallei is an environmental bacterium that causes melioidosis , a major community-acquired infection in tropical regions . Melioidosis presents with a range of clinical symptoms , is often characterized by a robust inflammatory response , may relapse after treatment , and results in high mortality rat...
Melioidosis is a tropical infection caused by Burkholderia pseudomallei . Disease ranges from mild to lethal , and patients who die from melioidosis have greater inflammatory responses than survivors . Identifying variation in bacterial structures that alter the immune response is therefore important . B . pseudomallei...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "chemical", "compounds", "phosphates", "melioidosis", "immunology", "bacterial", "diseases", "lipid", "structure", "lipid", "analysis", "research", "and", "analysis", "methods", "infectious", "diseases", "lipids", "chemistry", "m...
2018
Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation
The cohesion of sister chromatids is mediated by cohesin , a protein complex containing members of the structural maintenance of chromosome ( Smc ) family . How cohesins tether sister chromatids is not yet understood . Here , we mutate SMC1 , the gene encoding a cohesin subunit of budding yeast , by random insertion do...
Complexes containing members of the structural maintenance of chromosomes ( Smc ) family regulate higher order chromosome architecture in diverse aspects of DNA metabolism including chromosome condensation , sister chromatid cohesion , DNA repair , and global control of transcription . Smc complexes are thought to regu...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "yeast", "and", "fungi", "genetics", "and", "genomics", "saccharomyces" ]
2007
A Multi-Step Pathway for the Establishment of Sister Chromatid Cohesion
It has long been known that loss of the retinoblastoma protein ( Rb ) perturbs neural differentiation , but the underlying mechanism has never been solved . Rb absence impairs cell cycle exit and triggers death of some neurons , so differentiation defects may well be indirect . Indeed , we show that abnormalities in bo...
The retinoblastoma protein ( Rb ) , an important tumor suppressor , blocks division and death by inhibiting the E2f transcription factor family . In contrast , Rb is thought to promote differentiation by potentiating tissue-specific transcription factors , although differentiation defects in Rb null cells could be an i...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods", "Supporting", "Information" ]
[ "developmental", "biology", "cell", "biology", "mus", "(mouse)", "neuroscience" ]
2007
Rb-Mediated Neuronal Differentiation through Cell-Cycle–Independent Regulation of E2f3a
Accumulating evidence supports the role of an aberrant transcriptome as a driver of metastatic potential . Deadenylation is a general regulatory node for post-transcriptional control by microRNAs and other determinants of RNA stability . Previously , we demonstrated that the CCR4-NOT scaffold component Cnot2 is an inhe...
The majority of human cancer related death is due to the effects of metastasis , the process of cancer dissemination to and growth in distant organs . Primarily due to its complexity , the metastatic process remains incompletely understood . This complexity stems from the tumor cell’s dependence on multiple cellular an...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "rna-binding", "proteins", "medicine", "and", "health", "sciences", "breast", "tumors", "protein", "interactions", "cancers", "and", "neoplasms", "basic", "cancer", "research", "oncology", "immunoprecipitation", "secondary", "lung", "tumors", "research", "and", "analysi...
2016
Post-transcriptional Control of Tumor Cell Autonomous Metastatic Potential by CCR4-NOT Deadenylase CNOT7
Human metapneumovirus ( hMPV ) is a paramyxovirus that is a common cause of bronchiolitis and pneumonia in children less than five years of age . The hMPV fusion ( F ) glycoprotein is the primary target of neutralizing antibodies and is thus a critical vaccine antigen . To facilitate structure-based vaccine design , we...
Human metapneumovirus ( hMPV ) is a frequent cause of severe lower respiratory tract infections in very young children and a vaccine is not yet available . Protection against hMPV infection is afforded mainly by neutralizing antibodies directed against the fusion ( F ) glycoprotein . After iterative rounds of protein e...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "flow", "cytometry", "medicine", "and", "health", "sciences", "immune", "physiology", "crystal", "structure", "enzyme-linked", "immunoassays", "immunology", "condensed", "matter", "physics", "membrane", "fusion", "protein", "structure", "crystallography", "antibodies", "i...
2016
Engineering, Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformation
Gene expression analysis has become a ubiquitous tool for studying a wide range of human diseases . In a typical analysis we compare distinct phenotypic groups and attempt to identify genes that are , on average , significantly different between them . Here we describe an innovative approach to the analysis of gene exp...
Genes are a repository of information that provides the framework for cellular processes , with the flow of information from gene ( DNA ) to phenotype via an intermediate molecule—the messenger RNA . We understand that sequence variations in a gene may lead to phenotypic variations , but less well understood is how var...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genome", "expression", "analysis", "mathematics", "statistics", "genetics", "biology", "genomics", "biostatistics", "gene", "networks", "genetics", "and", "genomics" ]
2011
Variance of Gene Expression Identifies Altered Network Constraints in Neurological Disease
Melioidosis is caused by the facultative intracellular bacterium Burkholderia pseudomallei and is potentially fatal . Despite a growing global burden and high fatality rate , little is known about the disease . Recent studies demonstrate that cyclooxygenase-2 ( COX-2 ) inhibition is an effective post-exposure therapeut...
Burkholderia pseudomallei is the causative agent of melioidosis , a fatal tropical disease endemic in parts of Southwest Asia and Northern Australia . While it was once believed to be isolated to these areas , recent research indicates the global burden on melioidosis is growing . Furthermore , treatment of melioidosis...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "antimicrobials", "medicine", "and", "health", "sciences", "immune", "physiology", "pathology", "and", "laboratory", "medicine", "spleen", "melioidosis", "drugs", "immunology", "microbiology", "animal", "models", "bacterial", "diseases", "model", "organisms", "signs", "...
2016
Immune Modulation as an Effective Adjunct Post-exposure Therapeutic for B. pseudomallei
Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation . In contrast to other common post-translational modifications , such as phosphorylation , little is known about how non-degradative ubiquitination modulates protein structure , dynami...
Attachment of ubiquitin to another protein is typically used to mark the protein for degradation by the proteasome . However , recent studies show that many proteins are tagged with ubiquitin and not degraded . We hypothesized that ubiquitin can regulate the protein it is attached to by changing its structure and dynam...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "phosphorylation", "crystal", "structure", "chemical", "compounds", "enzymes", "condensed", "matter", "physics", "enzymology", "organic", "compounds", "basic", "amino", "acids", "protein", "structure", "amino", "acids", "crystallography", "solid", "state", "physics", "p...
2016
Non-degradative Ubiquitination of Protein Kinases
West Nile virus ( WNV ) , a mosquito-borne single-stranded RNA flavivirus , can cause significant human morbidity and mortality . Our data show that interleukin-10 ( IL-10 ) is dramatically elevated both in vitro and in vivo following WNV infection . Consistent with an etiologic role of IL-10 in WNV pathogenesis , we f...
West Nile virus ( WNV ) , a mosquito-transmitted RNA virus , is a worldwide cause of severe human and animal infection . Mammalian host immune responses to WNV infection are not completely understood and a vaccine or specific therapy is unavailable for use in humans . In the present study , we investigated the putative...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "virology/effects", "of", "virus", "infection", "on", "host", "gene", "expression", "immunology/immunity", "to", "infections", "virology/new", "therapies,", "including", "antivirals", "and", "immunotherapy", "virology/host", "antiviral", "responses" ]
2009
IL-10 Signaling Blockade Controls Murine West Nile Virus Infection
The collective dynamics of multicellular systems arise from the interplay of a few fundamental elements: growth , division and apoptosis of single cells; their mechanical and adhesive interactions with neighboring cells and the extracellular matrix; and the tendency of polarized cells to move . Micropatterned substrate...
The collective dynamics of many cells is more than the sum of its parts . For example , large cell collectives often form streams , swirls or bridges that cannot be achieved by single cells . Yet the dynamic processes of single cells , especially their response to adhesive and mechanical cues , stays an essential eleme...
[ "Abstract", "Introduction", "Results", "Discussion", "Models" ]
[ "cell", "physiology", "cell", "motility", "ellipses", "classical", "mechanics", "fluid", "mechanics", "cell", "cycle", "and", "cell", "division", "cell", "processes", "cadherins", "surface", "tension", "geometry", "cell", "polarity", "developmental", "biology", "mathe...
2016
Dynamics of Cell Ensembles on Adhesive Micropatterns: Bridging the Gap between Single Cell Spreading and Collective Cell Migration
Progeny capsids of herpesviruses leave the nucleus by budding through the nuclear envelope . Two viral proteins , the membrane protein pUL34 and the nucleo-phosphoprotein pUL31 form the nuclear egress complex that is required for capsid egress out of the nucleus . All pUL31 orthologs are composed of a diverse N-termina...
Herpesviral capsid assembly is initiated in the host nucleus . Due to size constraints , newly formed nucleocapsids are unable to leave the nucleus through the nuclear pore complex . Instead herpesviruses apply an evolutionarily conserved mechanism for nuclear export of capsids called nuclear egress . This process is i...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
The Herpes Simplex Virus Protein pUL31 Escorts Nucleocapsids to Sites of Nuclear Egress, a Process Coordinated by Its N-Terminal Domain
Hospital-acquired infections ( HAIs ) , including emerging multi-drug resistant organisms , threaten healthcare systems worldwide . Efficient containment measures of HAIs must mobilize the entire healthcare network . Thus , to best understand how to reduce the potential scale of HAI epidemic spread , we explore patient...
Hospital-acquired infections ( HAIs ) , including emerging multi-drug resistant organisms , threaten healthcare systems worldwide . Efficient containment measures of HAIs must mobilize the entire healthcare network . Thus , to best understand how to reduce the scale of potential HAI epidemic spread , we explore patient...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "and", "health", "sciences", "sociology", "geographical", "locations", "social", "sciences", "health", "care", "ethnicities", "scale-free", "networks", "network", "analysis", "social", "networks", "nosocomial", "infections", "patients", "infectious", "diseases...
2017
Spread of hospital-acquired infections: A comparison of healthcare networks