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Elaboration of Bayesian phylogenetic inference methods has continued at pace in recent years with major new advances in nearly all aspects of the joint modelling of evolutionary data . It is increasingly appreciated that some evolutionary questions can only be adequately answered by combining evidence from multiple ind...
Bayesian phylogenetic inference methods have undergone considerable development in recent years , and joint modelling of rich evolutionary data , including genomes , phenotypes and fossil occurrences is increasingly common . Advanced computational software packages that allow robust development of compatible ( sub- ) m...
[ "Abstract", "Introduction", "New", "BEAST", "functionality", "Beyond", "time", "trees:", "Extended", "phylogenetic", "structures", "New", "models", "Model", "selection", "and", "model", "adequacy", "New", "simulation", "tools", "Validation,", "testing", "and", "qualit...
[]
2019
BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis
Discovery of efficient anti-cancer drug combinations is a major challenge , since experimental testing of all possible combinations is clearly impossible . Recent efforts to computationally predict drug combination responses retain this experimental search space , as model definitions typically rely on extensive drug p...
Fighting cancer with combinations of drugs increases success of treatment . However , due to the large number of drugs and tumor variants , it remains a tremendous challenge to identify efficient combinations . To illustrate this , a set of 150 drugs corresponds to more than 10 . 000 possible pairwise drug combinations...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Discovery of Drug Synergies in Gastric Cancer Cells Predicted by Logical Modeling
Dengue and chikungunya are global re-emerging mosquito-borne diseases . In Singapore , sustained vector control coupled with household improvements reduced domestic mosquito populations for the past 45 years , particularly the primary vector Aedes aegypti . However , while disease incidence was low for the first 30 yea...
Dengue and chikungunya are mosquito-borne diseases and re-emerging as a global burden of the 21st century . Because of the absence of cure and limitations of the current vaccine , vector control remains the sole efficient intervention to mitigate epidemics . The highly-populated city of Singapore represents an example ...
[ "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", "reproductive", "p...
2017
Peridomestic Aedes malayensis and Aedes albopictus are capable vectors of arboviruses in cities
Cell populations display heterogeneous and dynamic phenotypic states at multiple scales . Similar to molecular features commonly used to explore cell heterogeneity , cell behavior is a rich phenotypic space that may allow for identification of relevant cell states . Inference of cell state from cell behavior across a t...
Cells in a population are not all alike . The differences between cells impact how each cell responds to stimuli , with implications for development and disease . How do cells change between these functionally important states over time ? This question is difficult to answer using molecular biology , because these meth...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "motility", "classical", "mechanics", "mathematical", "models", "multivariate", "analysis", "developmental", "biology", "systems", "science", "mathematics", "stem", "cells", "statistics", "(mathematics)", "morphogenesis", "research", "and", "analysis", "methods", ...
2018
Inferring cell state by quantitative motility analysis reveals a dynamic state system and broken detailed balance
Interleukin-1 receptor-associated kinases ( IRAKs ) are crucial mediators of the IL-1R/TLR signaling pathways that regulate the immune and inflammation response in mammals . Recent studies also suggest a critical role of IRAKs in tumor development , though the underlying mechanism remains elusive . Pelle is the sole Dr...
In the present study we report a Toll pathway independent function of Pll in modulating apoptotic cell death . Our major findings include: 1 ) loss of pll generates Toll pathway-independent wing phenotypes , which are caused by a reduction in cell number but not cell size; 2 ) depletion of pll up-regulates the transcri...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Pelle Modulates dFoxO-Mediated Cell Death in Drosophila
Australian bat lyssavirus ( ABLV ) belongs to the genus Lyssavirus which also includes classic rabies virus and the European lyssaviruses . To date , the only three known human ABLV cases , all fatal , have been reported from Queensland , Australia . ABLV is widely distributed in Australian bats , and any bite or scrat...
Australian bat lyssavirus ( ABLV ) , closely related to classic rabies virus , is widely distributed in bats in Australia . So far , the only three known human ABLV cases , all fatal , have been reported in Queensland , Australia . Any Australian bat-related injury ( bite or scratch ) , or contact of bat saliva/neural ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "post-exposure", "prophylaxis", "membrane", "potential", "tropical", "diseases", "immunology", "vertebrates", "electrophysiology", "animals", "mammals", "vaccines", "preventive", "medicine", "rabies", "neglected", "tropical", "diseas...
2016
Potential Exposures to Australian Bat Lyssavirus Notified in Queensland, Australia, 2009−2014
Interactions of cell-autonomous circadian oscillators with diurnal cycles govern the temporal compartmentalization of cell physiology in mammals . To understand the transcriptional and epigenetic basis of diurnal rhythms in mouse liver genome-wide , we generated temporal DNA occupancy profiles by RNA polymerase II ( Po...
In mammalian organs such as the liver , many metabolic and physiological processes occur preferentially at specific times during the 24-hour daily cycle . The timing of these rhythmic functions depends on a complex interplay between the endogenous circadian clock and environmental timing cues relayed through the master...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "systems", "biology", "biochemistry", "biology", "computational", "biology", "molecular", "cell", "biology", "genetics", "and", "genomics" ]
2012
Genome-Wide RNA Polymerase II Profiles and RNA Accumulation Reveal Kinetics of Transcription and Associated Epigenetic Changes During Diurnal Cycles
Drosophila body pigmentation has emerged as a major Evo-Devo model . Using two Drosophila melanogaster lines , Dark and Pale , selected from a natural population , we analyse here the interaction between genetic variation and environmental factors to produce this complex trait . Indeed , pigmentation varies with genoty...
Complex traits such as size or disease susceptibility are typically modulated by both genetic variation and environmental conditions . Model organisms such as fruit flies ( Drosophila ) are particularly appropriate to analyse the interactions between genetic variation and environmental factors during the development of...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "skin", "invertebrates", "medicine", "and", "health", "sciences", "integumentary", "system", "gene", "regulation", "population", "genetics", "animals", "animal", "models", "developmental", "biology", "drosophila", "melanogaster", "model", "organisms", "pupae", "experiment...
2018
bric à brac (bab), a central player in the gene regulatory network that mediates thermal plasticity of pigmentation in Drosophila melanogaster
Dendritic morphology has been shown to have a dramatic impact on neuronal function . However , population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks . While detailed models for morp...
Computational models of neurons and neural networks provide a valuable avenue to test our understanding of brain regions and to make predictions to guide future experimentation . Each neuron has a unique dendritic tree , features of which can vary depending on the location of the neuron within the particular brain regi...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "neuroanatomy", "anatomy", "computational", "neuroscience", "nervous", "system", "single", "neuron", "function", "biology", "and", "life", "sciences", "computational", "biology", "neuroscience", "artificial", "neural", "networks" ]
2014
Linking Macroscopic with Microscopic Neuroanatomy Using Synthetic Neuronal Populations
We developed a new statistical framework to find genetic variants associated with extreme longevity . The method , informed GWAS ( iGWAS ) , takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity . To gain support for our approach , we fir...
Longevity is a complex phenotype , and few genetic variants that affect lifespan have been identified . However , aging and disease are closely related , and a great deal is known about the genetic basis of disease risk . Here , we show using genome-wide association studies ( GWAS ) of longevity and disease that there ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity
Proteins with long , pathogenic polyglutamine ( polyQ ) sequences have an enhanced propensity to spontaneously misfold and self-assemble into insoluble protein aggregates . Here , we have identified 21 human proteins that influence polyQ-induced ataxin-1 misfolding and proteotoxicity in cell model systems . By analyzin...
Spinocerebellar ataxias ( SCAs ) are a group of inherited neurodegenerative diseases with around 30 subtypes , which are characterized by a progressive loss of cerebellar neurons . Neuronal death has been linked to the aggregation of mutated disease-causing proteins , such as ataxin-1 ( ATXN1 ) . Pathogenic ATXN1 conta...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "protein", "interactions", "neurodegenerative", "diseases", "amyotrophic", "lateral", "sclerosis", "molecular", "genetics", "motor", "neuron", "diseases", "proteins", "gene", "expression", "biology", "proteomics", "systems", "biology", "biochemistry", "neurologi...
2012
Identification of Human Proteins That Modify Misfolding and Proteotoxicity of Pathogenic Ataxin-1
Overexpression of the histone methyltransferase MMSET in t ( 4;14 ) + multiple myeloma patients is believed to be the driving factor in the pathogenesis of this subtype of myeloma . MMSET catalyzes dimethylation of lysine 36 on histone H3 ( H3K36me2 ) , and its overexpression causes a global increase in H3K36me2 , redi...
Precise spatial and temporal gene expression is required for normal development , and aberrant regulation of gene expression is a common factor in many diseases , including cancer . Histone modifications contribute to the control of gene expression by altering chromatin structure and affecting the recruitment of transc...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "biology", "chromosome", "biology", "genetics", "biology", "and", "life", "sciences", "epigenetics", "chromatin", "histone", "modification" ]
2014
Histone Methyltransferase MMSET/NSD2 Alters EZH2 Binding and Reprograms the Myeloma Epigenome through Global and Focal Changes in H3K36 and H3K27 Methylation
Infection with Trypanosoma cruzi causes Chagas disease , a major public health problem throughout Latin America . There is no vaccine and the only drugs have severe side effects . Efforts to generate new therapies are hampered by limitations in our understanding of parasite biology and disease pathogenesis . Studies ar...
5–8 million people in Latin America are infected with the single-cell parasite Trypanosoma cruzi , the causative agent of Chagas disease . Of these , approximately one-third will develop chronic disease pathology , leading to disability and premature death . Only two drugs are available , both of which can have severe ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "transfection", "fluorescence", "imaging", "medicine", "and", "health", "sciences", "luciferase", "enzymes", "enzymology", "green", "fluorescent", "protein", "parasitic", "diseases", "parasitic", "protozoans", "luminescent", "proteins", "protozoans", "molecular", "biology",...
2018
Expanding the toolbox for Trypanosoma cruzi: A parasite line incorporating a bioluminescence-fluorescence dual reporter and streamlined CRISPR/Cas9 functionality for rapid in vivo localisation and phenotyping
Digestive organ expansion factor ( Def ) is a nucleolar protein that plays dual functions: it serves as a component of the ribosomal small subunit processome for the biogenesis of ribosomes and also mediates p53 degradation through the cysteine proteinase calpain-3 ( CAPN3 ) . However , nothing is known about the exact...
The nucleolus is primarily known as the subcellular organelle for the biogenesis of the ribosomal small and large subunits in eukaryotic cells . However , it is also increasingly evident that many nucleolar proteins also play essential roles in other biological processes . Here , we show that Digestive organ expansion ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "phosphorylation", "medicine", "and", "health", "sciences", "liver", "cell", "cycle", "and", "cell", "division", "cell", "processes", "vertebrates", "animals", "animal", "models", "osteichthyes", "developmental", "biology", "mutation", "substitution", "mutation", "model...
2016
Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3
Since the 1990s , paratyphoid fever caused by Salmonella Paratyphi A has emerged in Southeast Asia and China . In 2010 , a large-scale outbreak involving 601 cases of paratyphoid fever occurred in the whole of Yuanjiang county in China . Epidemiological and laboratory investigations were conducted to determine the etio...
Typhoid and paratyphoid fever remain public health concerns for developing countries . From May 2010 to June 2011 , a large-scale outbreak involving 601 cases of paratyphoid fever occurred in China . Epidemiological and laboratory investigations were conducted to determine the etiology , source and transmission factors...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
A Large-Scale Community-Based Outbreak of Paratyphoid Fever Caused by Hospital-Derived Transmission in Southern China
Dengue virus infection ( DVI ) among children is a leading cause of hospitalization in endemic areas . Hospitalized patients are at risk of receiving unnecessary antibiotics . A retrospective medical review analysis study was conducted to evaluate the prevalence , indication , and choice of antibiotics given to hospita...
DVI among children is a leading cause of hospitalization in endemic areas . In developing or underdeveloped countries , the antibiotics stewardship policy has not been well implemented yet . Thus , the risk of unnecessary antibiotics used in hospitalized patients becomes higher . Changing the way medical doctors use an...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "antimicrobials", "urology", "children", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "drugs", "tropical", "diseases", "microbiology", "pediatrics", "bacterial", "diseases", "age", "groups", "signs", "and", "symptoms", "antibiot...
2019
The inappropriate use of antibiotics in hospitalized dengue virus-infected children with presumed concurrent bacterial infection in teaching and private hospitals in Bandung, Indonesia
Sperm and egg proteins constitute a remarkable paradigm in evolutionary biology: despite their fundamental role in mediating fertilization ( suggesting stasis ) , some of these molecules are among the most rapidly evolving ones known , and their divergence can lead to reproductive isolation . Because of strong selectio...
Interacting sperm and egg proteins must co-evolve to maintain compatibility at fertilization , so their divergence among species should be correlated—lineages with rapidly evolving sperm proteins should have rapidly evolving egg proteins . We use this expectation to target biochemical studies of fertilization in a mode...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "biology", "evolutionary", "biology" ]
2013
Duplicate Abalone Egg Coat Proteins Bind Sperm Lysin Similarly, but Evolve Oppositely, Consistent with Molecular Mimicry at Fertilization
Ascaris spp . infection affects 800 million people worldwide , and half of the world population is currently at risk of infection . Recurrent reinfection in humans is mostly due to the simplicity of the parasite life cycle , but the impact of multiple exposures to the biology of the infection and the consequences to th...
Human ascariasis caused by the helminths Ascaris lumbricoides and Ascaris suum , is the most prevalent neglected tropical disease in the world , affecting more than 800 million people and mainly school-aged children . The parasite life cycle may be divided in two distinct phases after the initial infection: ( i ) migra...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "blood", "cells", "invertebrates", "medicine", "and", "health", "sciences", "immune", "cells", "pathology", "and", "laboratory", "medicine", "respiratory", "infections", "immunology", "tropical", "diseases", "parasitic", "diseases", "animals", "pulmonology", "developmenta...
2016
Multiple Exposures to Ascaris suum Induce Tissue Injury and Mixed Th2/Th17 Immune Response in Mice
What governs the concentrations of metabolites within living cells ? Beyond specific metabolic and enzymatic considerations , are there global trends that affect their values ? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations . The recently achieved exp...
What governs the identity and concentrations of metabolites within living cells ? The first part of this question has received much attention . Organisms were found to qualitatively prefer hydrophilic and charged metabolites , a phenomenon that was explained to be a result of constraints imposed by contemporary as well...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "systems", "biology", "microbial", "metabolism", "theoretical", "biology", "biology", "computational", "biology", "metabolic", "networks", "microbiology", "genetics", "and", "genomics" ]
2011
Hydrophobicity and Charge Shape Cellular Metabolite Concentrations
The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs , respectively . Although whipworms in human and non-human primates historically have been referred to as T . trichiura , recent reports suggest that several Trichuris spp . are found in primates . We sequenced and annot...
Trichuris trichiura and Trichuris suis are whipworms found in humans and pigs , respectively , causing morbidity in humans and being associated with production losses in pigs . Although Trichuris from non-human primates is attributed to T . trichiura , hence considered the same species as the one infecting humans , sev...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Mitochondrial Genome Analyses Suggest Multiple Trichuris Species in Humans, Baboons, and Pigs from Different Geographical Regions
The contact structure between hosts shapes disease spread . Most network-based models used in epidemiology tend to ignore heterogeneity in the weighting of contacts between two individuals . However , this assumption is known to be at odds with the data for many networks ( e . g . sexual contact networks ) and to have ...
Understanding how infectious diseases spread has public health and ecological implications . The contact structure between hosts strongly affects this spread . However , most studies assume that all types of contacts are identical , when in reality some individuals interact more strongly than others . This is particula...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "medicine", "network", "analysis", "(management)", "social", "and", "behavioral", "sciences", "theoretical", "biology", "management", "engineering", "epidemiology", "social", "networks", "sociology", "management", "planning", "and", "control", "biology", "spatial", "epide...
2013
Epidemic Spread on Weighted Networks
Small noncoding RNAs ( sRNAs ) are ubiquitous posttranscriptional regulators of gene expression . Using the model plant-pathogenic bacterium Xanthomonas campestris pv . vesicatoria ( Xcv ) , we investigated the highly expressed and conserved sRNA sX13 in detail . Deletion of sX13 impinged on Xcv virulence and the expre...
Since the discovery of the first regulatory RNA in 1981 , hundreds of small RNAs ( sRNAs ) have been identified in bacteria . Although sRNA-mediated control of virulence was demonstrated for numerous animal- and human-pathogenic bacteria , sRNAs and their functions in plant-pathogenic bacteria have been enigmatic . We ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genome", "expression", "analysis", "gene", "regulation", "host-pathogen", "interaction", "microbiology", "rna", "stability", "developmental", "biology", "genome", "analysis", "tools", "plant", "science", "molecular", "cell", "biology", "molecular", "development", "plant"...
2013
Small RNA sX13: A Multifaceted Regulator of Virulence in the Plant Pathogen Xanthomonas
Infectious prions propagate from peripheral entry sites into the central nervous system ( CNS ) , where they cause progressive neurodegeneration that ultimately leads to death . Yet the pathogenesis of prion disease can vary dramatically depending on the strain , or conformational variant of the aberrantly folded and a...
Prion diseases are fatal neurodegenerative disorders that are also infectious . Prions are composed of a misfolded , aggregated form of a normal cellular protein that is highly expressed in neurons . Prion- infected individuals show variability in the clinical signs and brain regions that selectively accumulate prions ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "infectious", "diseases", "neurological", "disorders", "neurology", "chemistry", "chemical", "biology" ]
2012
Biochemical Properties of Highly Neuroinvasive Prion Strains
Toxocarosis is a widespread zoonosis caused by the ascarid nematodes Toxocara canis and Toxocara cati , which primarily infect dogs and cats , respectively . Most human infections with Toxocara are asymptomatic; however , some infected individuals may develop a serious illness and even death . Nevertheless , epidemiolo...
Toxocarosis , a typical neglected and underestimated human health problem , is caused by the ascarid nematodes Toxocara canis and Toxocara cati , which primarily infect dogs and cats , respectively . Previous studies have reported an increased risk for Toxocara infection in humans worldwide , especially in children and...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases", "medicine", "and", "health", "sciences", "veterinary", "diseases", "zoonoses", "parasitic", "intestinal", "diseases", "biology", "and", "life", "sciences", "tropical", "diseases", "parasitic", "diseases", "veterinary", "science", "nematode", "i...
2014
Toxocara Seroprevalence among Clinically Healthy Individuals, Pregnant Women and Psychiatric Patients and Associated Risk Factors in Shandong Province, Eastern China
This article presents the first attempt to formalize the optimization of experimental design with the aim of comparing models of brain function based on neuroimaging data . We demonstrate our approach in the context of Dynamic Causal Modelling ( DCM ) , which relates experimental manipulations to observed network dynam...
During the past two decades , brain mapping research has undergone a paradigm switch . In addition to localizing brain regions that encode specific sensory , motor or cognitive processes , neuroimaging data is nowadays further exploited to ask questions about how information is transmitted through brain networks . The ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "experimental", "psychology", "psychology", "social", "and", "behavioral", "sciences", "mathematics", "statistics", "biology", "computational", "biology", "neuroscience", "probability", "theory" ]
2011
Optimizing Experimental Design for Comparing Models of Brain Function
Computational prediction of cancer associated SNPs from the large pool of SNP dataset is now being used as a tool for detecting the probable oncogenes , which are further examined in the wet lab experiments . The lack in prediction accuracy has been a major hurdle in relying on the computational results obtained by imp...
The genetic mutations in human were shown by single nucleotide polymorphisms ( SNPs ) , and several of them were supposed to cause deleterious and disease associated phenotypic effects . The ability to differentiate between pathogenic and neutral nsSNPs ( non-synonymous Single Nucleotide Polymorphisms ) using computati...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results/Discussion" ]
[ "biochemistry", "cancer", "genetics", "proteins", "protein", "folding", "protein", "structure", "genetics", "biology", "and", "life", "sciences", "biophysics" ]
2014
Use of Long Term Molecular Dynamics Simulation in Predicting Cancer Associated SNPs
Resection of DNA double-strand break ( DSB ) ends is generally considered a critical determinant in pathways of DSB repair and genome stability . Unlike for enzymatically induced site-specific DSBs , little is known about processing of random “dirty-ended” DSBs created by DNA damaging agents such as ionizing radiation ...
Double-strand breaks ( DSBs ) in chromosomal DNA are common sources of genomic change that may be beneficial or deleterious to an organism , from yeast to humans . While they can arise through programmed cellular events , DSBs are frequently associated with defective chromosomal replication , and they are induced by va...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "microbiology/environmental", "microbiology", "molecular", "biology/recombination", "genetics", "and", "genomics/chromosome", "biology", "molecular", "biology", "genetics", "and", "genomics", "molecular", "biology/dna", "repair" ]
2009
RAD50 Is Required for Efficient Initiation of Resection and Recombinational Repair at Random, γ-Induced Double-Strand Break Ends
We present a computational framework , called DISCERN ( DIfferential SparsE Regulatory Network ) , to identify informative topological changes in gene-regulator dependence networks inferred on the basis of mRNA expression datasets within distinct biological states . DISCERN takes two expression datasets as input: an ex...
Certain genes can regulate other genes’ expression and activity levels to perform key biological processes in a cell . Understanding how genes affect expression levels among one another is a fundamental goal in molecular biology . New statistical techniques that analyze genome-wide mRNA expression data obtained from di...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "acute", "myeloid", "leukemia", "leukemias", "medicine", "and", "health", "sciences", "genetic", "networks", "breast", "tumors", "myeloid", "leukemia", "gene", "regulation", "regulatory", "proteins", "cancers", "and", "neoplasms", "dna-binding", "proteins", "oncology", ...
2016
Identifying Network Perturbation in Cancer
Photoperiod dependent flowering is one of several mechanisms used by plants to initiate the developmental transition from vegetative growth to reproductive growth . The NUCLEAR FACTOR Y ( NF-Y ) transcription factors are heterotrimeric complexes composed of NF-YA and histone-fold domain ( HFD ) containing NF-YB/NF-YC ,...
For plants to have reproductive success , they must time their flowering with the most beneficial biotic and abiotic environmental conditions—after all , reproductive success would likely be low if flowers developed when pollinators were not present or freezing temperatures were on the horizon . Proper timing mechanism...
[ "Abstract", "Introduction", "Results" ]
[ "biotechnology", "plant", "anatomy", "gene", "regulation", "brassica", "dna-binding", "proteins", "regulator", "genes", "plant", "science", "model", "organisms", "genetically", "modified", "plants", "gene", "types", "molecular", "biology", "techniques", "plants", "flowe...
2016
NUCLEAR FACTOR Y, Subunit A (NF-YA) Proteins Positively Regulate Flowering and Act Through FLOWERING LOCUS T
The large size of metabolic networks entails an overwhelming multiplicity in the possible steady-state flux distributions that are compatible with stoichiometric constraints . This space of possibilities is largest in the frequent situation where the nutrients available to the cells are unknown . These two factors: net...
Metabolic fluxes are steady-state rates of metabolite interconversion within living cells . They determine the rates of growth and product formation , and are of biotechnological and medical importance . An important and pressing question is how to identify the actual distribution of fluxes in living cells among the ma...
[ "Abstract", "Introduction", "Results/Discussion", "Methods" ]
[ "biotechnology", "bioengineering", "biochemistry", "biological", "systems", "engineering", "biomedical", "engineering", "systems", "biology", "metabolic", "pathways", "biology", "computational", "biology", "metabolic", "networks", "metabolism", "genetics", "and", "genomics", ...
2013
Inferring Metabolic States in Uncharacterized Environments Using Gene-Expression Measurements
The innate immune system pattern recognition receptors ( PRR ) are the first line of host defenses recognizing the various pathogen- or danger-associated molecular patterns and eliciting defenses by regulating the production of pro-inflammatory cytokines such as IL-1β , IL-18 or interferon β ( IFN-β ) . NOD-like recept...
Invasion of a host cell by pathogens , including viruses , is sensed by pattern-recognition receptors resulting in the elicitation of the host innate defenses such as the formation of multi-protein inflammasome complexes , inflammatory IL-1β and IL-18 cytokine production and interferon-β production via the cytoplasmic ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-β Responses
In ecology , “disease tolerance” is defined as an evolutionary strategy of hosts against pathogens , characterized by reduced or absent pathogenesis despite high pathogen load . To our knowledge , tolerance has to date not been quantified and disentangled from host resistance to disease in any clinically relevant human...
When confronted with pathogens , hosts can either evolve to fight them or learn to live with them . The first of these two strategies is called “resistance” and the second “tolerance” . In the context of HIV , many genes conferring resistance have been identified , but no tolerance genes are known . Using statistical t...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases", "hiv", "infections", "evolutionary", "ecology", "medicine", "and", "health", "sciences", "major", "histocompatibility", "complex", "ecology", "clinical", "immunology", "population", "modeling", "aids", "biology", "and", "life", "sciences", "imm...
2014
Disentangling Human Tolerance and Resistance Against HIV
Point mutations in peripherin-2 ( PRPH2 ) are associated with severe retinal degenerative disorders affecting rod and/or cone photoreceptors . Various disease-causing mutations have been identified , but the exact contribution of a given mutation to the clinical phenotype remains unclear . Exonic point mutations are us...
Photoreceptors are the light sensing cells of the retina and consist of dim light and night vision mediating rods and daylight and color vision mediating cones . PRPH2 is crucial for the structural and functional integrity of photoreceptors . Some point mutations in PRPH2 lead to degeneration of rods , whereas others o...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2016
In Vivo Analysis of Disease-Associated Point Mutations Unveils Profound Differences in mRNA Splicing of Peripherin-2 in Rod and Cone Photoreceptors
Neurocysticercosis is a disease caused by the oral ingestion of eggs from the human parasitic worm Taenia solium . Although drugs are available they are controversial because of the side effects and poor efficiency . An expressed sequence tag ( EST ) library is a method used to describe the gene expression profile and ...
A method used to describe expressed genes at a specific stage in an organism is an EST library . In this method mRNA from a specific organism is isolated , transcribed into cDNA and sequenced . The sequence will derive from the 5′-end of the cDNA . The library will not have sequences from all genes , especially if they...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "molecular", "biology/bioinformatics", "infectious", "diseases/neglected", "tropical", "diseases", "microbiology/parasitology" ]
2010
Analyses of an Expressed Sequence Tag Library from Taenia solium, Cysticerca
To assess the efficacy of HIV vaccine candidates or preventive treatment , many research groups have started to challenge monkeys repeatedly with low doses of the virus . Such challenge data provide a unique opportunity to assess the importance of exposure history for the acquisition of the infection . I developed stoc...
Individuals are exposed to Human Immunodeficiency Virus ( HIV ) many times before they contract the virus . It is not known what an instance of exposure , which does not result in infection , does to the host . Frequent exposures to the virus are hypothesized to immunize an individual , and result in resistance to infe...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "infectious", "diseases", "immunology", "biology", "computational", "biology" ]
2012
The Role of Exposure History on HIV Acquisition: Insights from Repeated Low-dose Challenge Studies
An important challenge in the analysis of mechanochemical coupling in molecular motors is to identify residues that dictate the tight coupling between the chemical site and distant structural rearrangements . In this work , a systematic attempt is made to tackle this issue for the conventional myosin . By judiciously c...
Molecular motors are inherently allosteric in nature because the small structural changes associated with the chemistry in the active site are propagated over a long distance and amplified into much larger conformational transitions . A fundamental challenge for understanding such processes concerns the identification ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "in", "vitro", "none", "molecular", "biology", "computational", "biology" ]
2007
Mechanochemical Coupling in the Myosin Motor Domain. II. Analysis of Critical Residues
Active screening by mobile teams is considered the most effective method for detecting gambiense-type human African trypanosomiasis ( HAT ) but constrained funding in many post-conflict countries limits this approach . Non-specialist health care workers ( HCWs ) in peripheral health facilities could be trained to ident...
Human African trypanosomiasis ( HAT or sleeping sickness ) is a fatal but treatable disease affecting poor people in sub-Saharan Africa . Most HAT diagnostic equipment , infrastructure and expertise is located in hospitals . The expense of expanding testing services to remote areas using mobile teams severely restricts...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "conflict", "epidemiology", "public", "health", "medicine", "infectious", "diseases", "health", "screening", "social", "and", "behavioral", "sciences", "primary", "care", "mental", "health", "behavioral", "and", "social", "aspects", "of", "health", "epidemiology", "af...
2014
A Mixed Methods Study of a Health Worker Training Intervention to Increase Syndromic Referral for Gambiense Human African Trypanosomiasis in South Sudan
Phospoenolpyruvate carboxylase ( PEPC ) is absent from humans but encoded in the Plasmodium falciparum genome , suggesting that PEPC has a parasite-specific function . To investigate its importance in P . falciparum , we generated a pepc null mutant ( D10Δpepc ) , which was only achievable when malate , a reduction pro...
The genome of the human malaria parasite Plasmodium falciparum encodes a protein called phosphoenolpyruvate carboxylase ( PEPC ) absent from the human host . PEPC is known to fix CO2 to generate metabolites used for energy metabolism in plants and bacteria , but its function in malaria parasites remained an enigma . Ou...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "parastic", "protozoans", "systems", "biology", "biochemistry", "protozoology", "biology", "microbiology", "plasmodium", "falciparum", "parasitology", "parasite", "physiology", "pathogenesis" ]
2014
Phosphoenolpyruvate Carboxylase Identified as a Key Enzyme in Erythrocytic Plasmodium falciparum Carbon Metabolism
Estimation of division and death rates of lymphocytes in different conditions is vital for quantitative understanding of the immune system . Deuterium , in the form of deuterated glucose or heavy water , can be used to measure rates of proliferation and death of lymphocytes in vivo . Inferring these rates from labeling...
Understanding of cellular processes is impossible without quantitative estimates of how quickly cells in an organism divide and die . The most widely used approach to measure rates of cell turnover in humans is by labeling dividing cells with deuterium given in the form of deuterated glucose or heavy water . Surprising...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "mathematics/statistics", "immunology/immune", "response", "computational", "biology" ]
2010
Explicit Kinetic Heterogeneity: Mathematical Models for Interpretation of Deuterium Labeling of Heterogeneous Cell Populations
Mycobacterium tuberculosis ( Mtb ) remains a major public health problem , with an effective vaccine continuing to prove elusive . Progress in vaccination strategies has been hampered by a lack of appreciation of the bacterium's response to dynamic changes in the host immune environment . Here , we utilize reporter Mtb...
Mycobacterium tuberculosis ( Mtb ) remains a serious challenge to global health , a situation that is exacerbated by emerging drug resistance , the paucity of new antibiotics , and the absence of an effective vaccine . Whilst there is no doubt that an anti-tuberculosis vaccine would have an extraordinary impact on the ...
[ "Abstract", "Introduction", "Results", "and", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases", "medicine", "and", "health", "sciences", "biology", "and", "life", "sciences", "immunology", "microbiology" ]
2014
Exploitation of Mycobacterium tuberculosis Reporter Strains to Probe the Impact of Vaccination at Sites of Infection
Schistosomiasis is the most widespread water-based disease in sub-Saharan Africa . Transmission is governed by the spatial distribution of specific freshwater snails that act as intermediate hosts and human water contact patterns . Remote sensing data have been utilized for spatially explicit risk profiling of schistos...
Schistosomiasis is a parasitic worm infection that is widespread in sub-Saharan Africa where people get in contact with open freshwater bodies . For many years , the strategy to control schistosomiasis was to prevent morbidity through deworming of school-aged children . Recently , transmission control has gained intere...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Modeling and Validation of Environmental Suitability for Schistosomiasis Transmission Using Remote Sensing
Two different strategies for stabilizing proteins are ( i ) positive design in which the native state is stabilized and ( ii ) negative design in which competing non-native conformations are destabilized . Here , the circumstances under which one strategy might be favored over the other are explored in the case of latt...
Most proteins are functional only in their native states . The stability of the native state of proteins is , therefore , of paramount importance both in vivo and for many biotechnological applications in vitro . Protein stability is determined by the difference between the free energies of the native and non-native st...
[ "Abstract", "Introduction", "Results", "Discussion" ]
[ "computational", "biology/macromolecular", "sequence", "analysis", "biophysics/theory", "and", "simulation" ]
2009
Trade-off between Positive and Negative Design of Protein Stability: From Lattice Models to Real Proteins
The abundance and identity of functional variation segregating in natural populations is paramount to dissecting the molecular basis of quantitative traits as well as human genetic diseases . Genome sequencing of multiple organisms of the same species provides an efficient means of cataloging rearrangements , insertion...
DNA sequence variation makes an important contribution to most traits that vary in natural populations . However , mapping mutations that underlie a trait of interest is a significant challenge . Genome sequencing of multiple organisms provides a complete list of DNA sequence differences responsible for any trait that ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/genome", "projects", "genetics", "and", "genomics/population", "genetics" ]
2008
A Catalog of Neutral and Deleterious Polymorphism in Yeast
Herpes simplex virus type 1 ( HSV-1 ) infection results in lifelong chronic infection of trigeminal ganglion ( TG ) neurons , also referred to as neuronal HSV-1 latency , with periodic reactivation leading to recrudescent herpetic disease in some persons . HSV-1 proteins are expressed in a temporally coordinated fashio...
HSV-1 is an endemic human herpesvirus worldwide that establishes a lifelong latent infection of neurons in the trigeminal ganglion ( TG ) , allowing intermittent reactivation resulting in recurrent disease in some persons . Studies in HSV-1 models suggest a central role of TG-infiltrating virus-specific CD8 T-cells to ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "flow", "cytometry", "medicine", "immune", "cells", "cytokines", "herpes", "simplex", "immunologic", "subspecialties", "immunity", "to", "infections", "immunology", "host-pathogen", "interaction", "microbiology", "anatomy", "and", "physiology", "adaptive", "immunity", "im...
2013
Local CD4 and CD8 T-Cell Reactivity to HSV-1 Antigens Documents Broad Viral Protein Expression and Immune Competence in Latently Infected Human Trigeminal Ganglia
The highly pathogenic avian influenza ( HPAI ) H5N1 virus lineage has undergone extensive genetic reassortment with viruses from different sources to produce numerous H5N1 genotypes , and also developed into multiple genetically distinct sublineages in China . From there , the virus has spread to over 60 countries . Th...
H5N1 influenza virus has been responsible for poultry outbreaks over the last 12 years—the longest recorded example of highly pathogenic avian influenza ( HPAI ) circulation in poultry . The ecological success of this virus in diverse species of both poultry and wild birds with sporadic introduction to humans suggests ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "computational", "biology/population", "genetics", "virology/emerging", "viral", "diseases", "computational", "biology/evolutionary", "modeling", "evolutionary", "biology", "computational", "biology/molecular", "dynamics", "infectious", "diseases/epidemiology", "and", "control", ...
2008
Evolutionary Dynamics and Emergence of Panzootic H5N1 Influenza Viruses
Trichomonas vaginalis is an extracellular eukaryotic parasite that causes the most common , non-viral sexually transmitted infection worldwide . Although disease burden is high , molecular mechanisms underlying T . vaginalis pathogenesis are poorly understood . Here , we identify a family of putative T . vaginalis rhom...
Trichomonas vaginalis , a common pathogen with a worldwide distribution , causes a sexually transmitted infection and exacerbates other diseases . Estimated to infect over a million people annually in the United States alone , the Center for Disease Control and Prevention categorized trichomoniasis as one of five negle...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
A Trichomonas vaginalis Rhomboid Protease and Its Substrate Modulate Parasite Attachment and Cytolysis of Host Cells
Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites , the so-called dendritic spikes , results in independent spiking dendritic sub-units , which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions , such as the exclusive OR . O...
Classical views on single neuron computation treat dendrites as mere collectors of inputs , that is forwarded to the soma for linear summation and causes a spike output if it is sufficiently large . Such a single neuron model can only compute linearly separable input-output functions , representing a small fraction of ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "computational", "neuroscience", "single", "neuron", "function", "biology", "neuroscience" ]
2013
Passive Dendrites Enable Single Neurons to Compute Linearly Non-separable Functions
Primary visual cortex is often viewed as a “cyclopean retina” , performing the initial encoding of binocular disparities between left and right images . Because the eyes are set apart horizontally in the head , binocular disparities are predominantly horizontal . Yet , especially in the visual periphery , a range of no...
Because our eyes are set apart horizontally in our head , the images they see are mainly offset horizontally . However , small vertical disparities also occur , and can have a measurable effect on perception , showing that they must be detected by the visual system . The trouble is that encoding a two-dimensional quant...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "neuroscience/natural", "and", "synthetic", "vision", "neuroscience/theoretical", "neuroscience", "neuroscience/sensory", "systems" ]
2010
Vertical Binocular Disparity is Encoded Implicitly within a Model Neuronal Population Tuned to Horizontal Disparity and Orientation
Mosquitoes feed on plant-derived fluids such as nectar and sap and are exposed to bioactive molecules found in this dietary source . However , the role of such molecules on mosquito vectorial capacity is unknown . Weather has been recognized as a major determinant of the spread of dengue , and plants under abiotic stre...
The dramatic climate changes currently occurring on our planet may likely influence the biology and the distribution of mosquitoes . Aedes aegypti is a major vector of arboviruses . However , females feed on plants for a few days before feeding on blood for the first time . Plants are sessile and cannot move to search ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "invertebrates", "cell", "death", "fluorescence", "imaging", "medicine", "and", "health", "sciences", "autophagic", "cell", "death", "microbiome", "cell", "processes", "microbiology", "diet", "light", "microscopy", "animals", "nutrition", "microscopy", "insect", "vector...
2016
Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan
Bacteria are often attached to surfaces in natural ecosystems . A surface-associated lifestyle can have advantages , but shifts in the physiochemical state of the environment may result in conditions in which attachment has a negative fitness impact . Therefore , bacteria employ numerous mechanisms to control the trans...
Living on a surface within a community of cells confers a number of advantages to a bacterium . However , the transition from a free-living , planktonic state to a surface-attached lifestyle should be tightly regulated to ensure that cells avoid adhering to toxic or resource-limited niches . Many bacteria build adhesiv...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "antimicrobials", "medicine", "and", "health", "sciences", "chemical", "compounds", "caulobacter", "gene", "regulation", "drugs", "regulatory", "proteins", "microbiology", "dna-binding", "proteins", "organic", "compounds", "prokaryotic", "models", "regulator", "genes", "a...
2019
Regulation of bacterial surface attachment by a network of sensory transduction proteins
Necrosis and ethylene-inducing peptide 1 ( Nep1 ) -like proteins ( NLPs ) are secreted by several phytopathogenic microorganisms . They trigger necrosis in various eudicot plants upon binding to plant sphingolipid glycosylinositol phosphorylceramides ( GIPC ) . Interestingly , HaNLP3 from the obligate biotroph oomycete...
The rhizosphere and phyllosphere of terrestrial plants are home to a number of microorganisms , many of which are potentially pathogenic at certain stages during their associations with plants . The pathogens use diverse routes to penetrate physical barriers and colonize host plants with different lifestyles . Necrosis...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "plant", "anatomy", "medicine", "and", "health", "sciences", "vesicles", "crystal", "structure", "molecular", "dynamics", "pathology", "and", "laboratory", "medicine", "condensed", "matter", "physics", "toxicology", "membrane", "proteins", "toxicity", "plant", "science"...
2019
Molecular basis for functional diversity among microbial Nep1-like proteins
Wolbachia are intracellular bacterial symbionts that are able to protect various insect hosts from viral infections . This tripartite interaction was initially described in Drosophila melanogaster carrying wMel , its natural Wolbachia strain . wMel has been shown to be genetically polymorphic and there has been a recen...
Wolbachia are bacterial symbionts that infect many arthropods and can protect insects from viral infection . Here we show that different variants of Wolbachia from Drosophila melanogaster ( wMel ) are phenotypically heterogeneous: they differ in the level of protection they confer and the titres they reach in their hos...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
Wolbachia Variants Induce Differential Protection to Viruses in Drosophila melanogaster: A Phenotypic and Phylogenomic Analysis
In order to study the ability of coupled neural oscillators to synchronize in the presence of intrinsic as opposed to synaptic noise , we constructed hybrid circuits consisting of one biological and one computational model neuron with reciprocal synaptic inhibition using the dynamic clamp . Uncoupled , both neurons fir...
Many biological phenomena exhibit synchronized oscillations in the presence of noise and heterogeneity . These include brain rhythms that underlie cognition and spinal rhythms that underlie rhythmic motor activity like breathing and locomotion . A two oscillator system was constructed in which most of the circuit was i...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "biology", "and", "life", "sciences" ]
2014
Slow Noise in the Period of a Biological Oscillator Underlies Gradual Trends and Abrupt Transitions in Phasic Relationships in Hybrid Neural Networks
Circular DNA elements are involved in genome plasticity , particularly of tandem repeats . However , amplifications of DNA segments in Saccharomyces cerevisiae reported so far involve pre-existing repetitive sequences such as ribosomal DNA , Ty elements and Long Terminal Repeats ( LTRs ) . Here , we report the generati...
Xylose is an important component of lignocellulose hydrolysates used for the production of bioethanol , but the yeast Saccharomyces cerevisiae is unable to utilize xylose . Insertion of a bacterial xylose isomerase gene and improvement of growth on xylose by evolutionary adaptation resulted in amplification of this gen...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Rapid Evolution of Recombinant Saccharomyces cerevisiae for Xylose Fermentation through Formation of Extra-chromosomal Circular DNA
Computational biology is an interdisciplinary field , and many computational biology research projects involve distributed teams of scientists . To accomplish their work , these teams must overcome both disciplinary and geographic barriers . Introducing new training paradigms is one way to facilitate research progress ...
Computational biology research is frequently conducted by virtual teams: groups of scientists in different locations that use shared resources and online communication tools to collaborate on a problem . It is imperative that the next generation of computational biologists can easily work in these interdisciplinary , d...
[ "Abstract", "Introduction", "Student", "recruitment", "and", "selection", "Structure", "of", "the", "research", "experience", "Results", "Discussion" ]
[ "learning", "employment", "education", "social", "sciences", "neuroscience", "learning", "and", "memory", "careers", "research", "design", "scientists", "cognitive", "psychology", "undergraduates", "educational", "status", "science", "and", "technology", "workforce", "res...
2017
A cyber-linked undergraduate research experience in computational biomolecular structure prediction and design
The West African Ebola epidemic of 2013–2016 was by far the largest outbreak of the disease on record . Sierra Leone suffered nearly half of the 28 , 646 reported cases . This paper presents a set of culturally contextualized Ebola messages that are based on the findings of qualitative interviews and focus group discus...
The work on which the paper is based was conducted in two Ebola ‘hotspots’ in Sierra Leone ( urban Freetown and rural Bombali district ) between January and April 2015 . Numerous misperceptions about Ebola had developed in the community over the course of 2014 , and it was becoming increasingly clear that the largely t...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "learning", "medicine", "and", "health", "sciences", "engineering", "and", "technology", "transportation", "sociology", "geographical", "locations", "tropical", "diseases", "social", "sciences", "ebola", "hemorrhagic", "fever", "neuroscience", "learning", "and", "memory",...
2017
Development of a set of community-informed Ebola messages for Sierra Leone
Plague is still a public health problem in the world and is re-emerging , but no efficient vaccine is available . We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis , the recent ancestor of Yersinia pestis , provided protection against bubonic plague . However , the strain poo...
Plague , among the most deadly infections of mankind's history , is present in Africa , Asia and America , and is currently re-emerging , recently causing cases in areas from where it had disappeared for decades . Pneumonic plague , its most deadly and contagious form , is responsible for human-to-human spreading of th...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "medicine", "bacterial", "diseases", "infectious", "diseases", "immunity", "immunology", "biology", "microbiology", "bacterial", "pathogens" ]
2012
An Encapsulated Yersinia pseudotuberculosis Is a Highly Efficient Vaccine against Pneumonic Plague
Models of the hexagonally arrayed spatial activity pattern of grid cell firing in the literature generally fall into two main categories: continuous attractor models or oscillatory interference models . Burak and Fiete ( 2009 , PLoS Comput Biol ) recently examined noise in two continuous attractor models , but did not ...
For many animals , including rats , accurate spatial memory over relatively large areas is important in order to find food and shelter . Just as unique points in time can be efficiently represented by combinations of repeating elements like hours , days , and months , points in space can be represented as combinations ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "mathematics", "neuroscience", "neuroscience/theoretical", "neuroscience", "computational", "biology/computational", "neuroscience" ]
2009
Evaluation of the Oscillatory Interference Model of Grid Cell Firing through Analysis and Measured Period Variance of Some Biological Oscillators
Enteric bacterial pathogens such as enterohemorrhagic E . coli ( EHEC ) and Salmonella Typhimurium target the intestinal epithelial cells ( IEC ) lining the mammalian gastrointestinal tract . Despite expressing innate Toll-like receptors ( TLRs ) , IEC are innately hypo-responsive to most bacterial products . This is t...
Despite being in close contact with billions of commensal bacteria , the epithelial cells that line the intestine develop very weak innate inflammatory responses to bacterial products . The goal of this study was to explore why these cells respond so poorly , and how increasing their innate responsiveness would impact ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "bacterial", "and", "foodborne", "illness", "immunity", "gastroenterology", "and", "hepatology", "innate", "immunity", "immune", "defense", "immunology", "immune", "tolerance", "biology", "immunity", "to", "infections", "immunoregulation", "inflammatory", "bow...
2013
SIGIRR, a Negative Regulator of TLR/IL-1R Signalling Promotes Microbiota Dependent Resistance to Colonization by Enteric Bacterial Pathogens
Studies of evolutionary responses to novel environments typically consider single species or perhaps pairs of interacting species . However , all organisms co-occur with many other species , resulting in evolutionary dynamics that might not match those predicted using single species approaches . Recent theories predict...
Understanding how species adapt to new environments is important both for evolutionary theory and for predicting and managing ecosystem responses to changing environments . However , most research into adaptation to new environments has considered species in isolation . Whether results from these systems apply to more ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "community", "ecology", "evolutionary", "ecology", "adaptation", "coevolution", "ecology", "ecosystems", "evolutionary", "biology", "ecosystem", "functioning", "biology", "species", "interactions", "evolutionary", "processes" ]
2012
Species Interactions Alter Evolutionary Responses to a Novel Environment
To facilitate whole-genome association studies ( WGAS ) , several high-density SNP genotyping arrays have been developed . Genetic coverage and statistical power are the primary benchmark metrics in evaluating the performance of SNP arrays . Ideally , such evaluations would be done on a SNP set and a cohort of individu...
Advances in SNP genotyping array technologies have made whole-genome association studies ( WGAS ) a readily available approach . Genetic coverage and the statistical power are two key properties to evaluate on the arrays . In this study , 359 newly sampled individuals were genotyped using Affymetrix 500K and Illumina 6...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "genetics", "and", "genomics", "computational", "biology/genomics", "computational", "biology/transcriptional", "regulation" ]
2008
Calibrating the Performance of SNP Arrays for Whole-Genome Association Studies
The mechanism of intra-protein communication and allosteric coupling is key to understanding the structure-property relationship of protein function . For subtilisin Carlsberg , the Ca2+-binding loop is distal to substrate-binding and active sites , yet the serine protease function depends on Ca2+ binding . The atomic ...
A hallmark of protein molecules is their machine-like behaviors while carrying out biological functions . At the molecular level , molecular signals such as binding a metal ion at an action site can cause long-range effects and alter protein function . Such phenomena are often referred to as intra-protein communication...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "protein", "chemistry", "genomics", "computational", "chemistry", "molecular", "dynamics", "biophysic", "al", "simulations", "chemical", "physics", "gaussian", "fluctuations", "chemistry", "biology", "computational", "biology", "biophysics", "simulations", "biophysics", "ph...
2011
“Fluctuograms” Reveal the Intermittent Intra-Protein Communication in Subtilisin Carlsberg and Correlate Mechanical Coupling with Co-Evolution
The in vivo activity of CA1 pyramidal neurons alternates between regular spiking and bursting , but how these changes affect information processing remains unclear . Using a detailed CA1 pyramidal neuron model , we investigate how timing and spatial arrangement variations in synaptic inputs to the distal and proximal d...
Pyramidal neurons in the hippocampus are crucially involved in learning and memory functions , but the ways in which they contribute to the processing of sensory inputs and their internal representation remain mostly unclear . The principal neurons of the CA1 region of the hippocampus are surrounded by at least 21 diff...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "cell", "biology/neuronal", "and", "glial", "cell", "biology", "neuroscience", "neuroscience/sensory", "systems", "cell", "biology/cell", "signaling", "biophysics/experimental", "biophysical", "methods", "biophysics/theory", "and", "simulation", "cell", "biology", "cell", "...
2010
Encoding of Spatio-Temporal Input Characteristics by a CA1 Pyramidal Neuron Model
IbNAC1 is known to activate the defense system by reprogramming a genetic network against herbivory in sweet potato . This regulatory activity elevates plant defense potential but relatively weakens plants by IbNAC1-mediated JA response . The mechanism controlling IbNAC1 expression to balance plant vitality and surviva...
Plants develop sophisticated defense systems against insect attack . IbNAC1 is a transcriptional activator , which up-regulates sporamin expression against herbivory in sweet potato . However , it simultaneously injures the plant by IbNAC1-induced JA response . Thus , dynamic regulatory networks to coordinate the expre...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "plant", "anatomy", "ecology", "and", "environmental", "sciences", "gene", "regulation", "regulatory", "proteins", "brassica", "dna-binding", "proteins", "plant", "physiology", "sweet", "potato", "plant", "science", "model", "organisms", "herbivory", "transcription", "f...
2016
The Sweet Potato NAC-Domain Transcription Factor IbNAC1 Is Dynamically Coordinated by the Activator IbbHLH3 and the Repressor IbbHLH4 to Reprogram the Defense Mechanism against Wounding
In multicellular organisms , development , growth and reproduction require coordinated expression of numerous functional and regulatory genes . Insects , in addition to being the most speciose animal group with enormous biological and economical significance , represent outstanding model organisms for studying regulati...
In addition to being vectors of devastating human diseases , mosquitoes represent outstanding model organisms for studying regulatory mechanisms of differential gene expression due to their rapid reproductive cycles . About 7500 transcripts are differentially expressed in four sequential waves during the 72-h reproduct...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Regulation of Gene Expression Patterns in Mosquito Reproduction
Parental imprinting is a mammalian-specific form of epigenetic regulation in which one allele of a gene is silenced depending on its parental origin . Parentally imprinted genes have been shown to play a role in growth , metabolism , cancer , and behavior . Although the molecular mechanisms underlying parental imprinti...
Parental genomic imprinting is a mammalian-specific form of epigenetic control that regulates genes differently depending upon whether they are paternally or maternally inherited . The selective advantage of genomic imprinting is poorly understood and has been the subject of numerous theories . In the last several deca...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "neurochemistry", "milk", "body", "fluids", "vertebrates", "mice", "neuroscience", "animals", "mammals", "hormones", "animal", "models", "model", "organisms", "probability", "distribution", "animal", "behavior", "mathematics", "z...
2016
A Novel Mutant Allele of Pw1/Peg3 Does Not Affect Maternal Behavior or Nursing Behavior
In regenerative tissues , one of the strategies to protect stem cells from genetic aberrations , potentially caused by frequent cell division , is to transiently expand the stem cell daughters before further differentiation . However , failure to exit the transit amplification may lead to overgrowth , and the molecular...
In regenerative tissues , the successive differentiation of stem cell lineage is well controlled and coordinated with proper cell proliferation at each differentiation stage . Disruption of the control mechanism can lead to tumor growth or tissue degeneration . The germline stem cell lineage of Drosophila spermatogenes...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "gene", "function", "developmental", "biology", "stem", "cells", "animal", "cells", "cell", "biology", "genetics", "biology", "and", "life", "sciences", "cellular", "types", "cell", "differentiation", "adult", "stem", "cells" ]
2014
Three RNA Binding Proteins Form a Complex to Promote Differentiation of Germline Stem Cell Lineage in Drosophila
A challenge in structural genomics is prediction of the function of uncharacterized proteins . When proteins cannot be related to other proteins of known activity , identification of function based on sequence or structural homology is impossible and in such cases it would be useful to assess structurally conserved bin...
For a substantial proportion of proteins , their functions are not known since these proteins are not related in sequence to any other known proteins . Binding sites are evolutionarily conserved across very distant protein families , and finding similar binding sites between known and unknown proteins can provide clues...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2013
Structure-Based Function Prediction of Uncharacterized Protein Using Binding Sites Comparison
Downstream of gene expression , effectors such as the actomyosin contractile machinery drive embryo morphogenesis . During Drosophila embryonic axis extension , actomyosin has a specific planar-polarised organisation , which is responsible for oriented cell intercalation . In addition to these cell rearrangements , cel...
The morphogenesis of living organisms is a facinating process during which a genetic programme controls a sequence of molecular changes which will cause the original embryo to acquire a new shape . While we have a growing knowledge of the timing and spatial distribution of key molecules downstream of genetic programmes...
[ "Abstract", "Introduction", "Models", "Results", "Discussion" ]
[ "invertebrates", "classical", "mechanics", "fluid", "mechanics", "condensed", "matter", "physics", "anisotropy", "animals", "simulation", "and", "modeling", "animal", "models", "developmental", "biology", "viscosity", "drosophila", "melanogaster", "model", "organisms", "m...
2017
Geometry can provide long-range mechanical guidance for embryogenesis
Phagocytosis plays a key role in nutrient uptake and virulence of the protist parasite Entamoeba histolytica . Phagosomes have been characterized by proteomics , and their maturation in the cells has been studied . However , there is so far not much understanding about initiation of phagocytosis and formation of phagos...
Entamoeba histolytica is one of the major causes of morbidity and mortality in developing countries . Phagocytosis plays an important role in both survival and virulence , and has been used as one of the virulence markers . E . histolytica displays a high rate of phagocytosis and offers a unique system to understand th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry", "cell", "biology", "biology", "and", "life", "sciences", "microbiology", "molecular", "biology", "parasitology" ]
2014
A Novel Alpha Kinase EhAK1 Phosphorylates Actin and Regulates Phagocytosis in Entamoeba histolytica
It has recently been demonstrated that the nucleobase-density profiles of mRNA coding sequences are related in a complementary manner to the nucleobase-affinity profiles of their cognate protein sequences . Based on this , it has been proposed that cognate mRNA/protein pairs may bind in a co-aligned manner , especially...
Messenger RNAs and proteins , two essential types of biopolymers , have recently been shown to exhibit closely related , complementary physicochemical properties . Specifically , density profiles of certain groups in messenger RNA sequences directly match the affinity profiles for precisely those groups in protein sequ...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "protein", "interactions", "nucleobases", "messenger", "rna", "nucleotides", "amino", "acid", "sequence", "analysis", "mathematics", "statistics", "(mathematics)", "research", "and", "analysis", "methods", "sequence", "analysis", "rna", "structure", "bioinformatics", "pro...
2017
mRNA/protein sequence complementarity and its determinants: The impact of affinity scales
Venezuelan equine encephalitis virus ( VEEV ) is an arbovirus endemic to the Americas that is responsible for severe , sometimes fatal , disease in humans and horses . We previously described an IRES-based VEE vaccine candidate based up the IE serotype that offers complete protection against a lethal subtype IE VEEV ch...
Venezuelan equine encephalitis virus ( VEEV ) is a mosquito-borne arbovirus endemic to the Americas that affects a wide range of equids and humans . Vaccination has been one of the strategies to combat spread of disease in areas with high rates incidence of VEEV , although existing vaccines have proven less than effect...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
IRES-Containing VEEV Vaccine Protects Cynomolgus Macaques from IE Venezuelan Equine Encephalitis Virus Aerosol Challenge
Temperate phages are bacterial viruses that as part of their life cycle reside in the bacterial genome as prophages . They are found in many species including most clinical strains of the human pathogens , Staphylococcus aureus and Salmonella enterica serovar Typhimurium . Previously , temperate phages were considered ...
Viruses ( phages ) that only attack bacteria are highly common . Some of these phages naturally reside within the bacterial chromosome for extended periods of time . Upon release and propagation on phage susceptible cells , new phage particles are made but occasionally bacterial rather than phage DNA is packaged into p...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "bacteriology", "antimicrobials", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "bacteriophages", "pathogens", "drugs", "microbiology", "staphylococcus", "aureus", "viruses", "antibiotic", "resistance", "lysogeny", "antibiotics", "ba...
2019
Bacteriophages benefit from generalized transduction
Streptococcus equi subspecies equi ( S . equi ) is a clonal , equine host-adapted pathogen of global importance that causes a suppurative lymphodendopathy of the head and neck , more commonly known as Strangles . The disease is highly prevalent , can be severe and is highly contagious . Antibiotic treatment is usually ...
Numerous research groups have vaccinated , using recombinant antigens , against streptococcal infections in mouse model systems and shown protection . We have here demonstrated efficient protective vaccination of the natural host , the horse , using recombinant antigens . Streptococcus equi subspecies equi ( S . equi )...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "microbiology/immunity", "to", "infections", "immunology/immune", "response", "microbiology/innate", "immunity", "pathology/histopathology", "molecular", "biology/bioinformatics", "public", "health", "and", "epidemiology/infectious", "diseases", "infectious", "diseases/respiratory", ...
2009
Getting to Grips with Strangles: An Effective Multi-Component Recombinant Vaccine for the Protection of Horses from Streptococcus equi Infection
Misfolded proteins ( MP ) are a key component in aging and associated neurodegenerative disorders . For example , misfolded Amyloid-ß ( Aß ) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease . Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized . Here ,...
Misfolded proteins ( MP ) mechanisms are a characteristic pathogenic feature of most prevalent human neurodegenerative diseases , such as Alzheimer's disease ( AD ) . Characterizing the mechanisms underlying intra-brain MP propagation and deposition still constitutes a major challenge . Here , we hypothesize that these...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "connectomics", "medicine", "and", "health", "sciences", "dementia", "neuroanatomy", "anatomy", "mental", "health", "and", "psychiatry", "computational", "neuroscience", "nervous", "system", "neurology", "neurodegenerative", "diseases", "biology", "and", "life", "sciences...
2014
Epidemic Spreading Model to Characterize Misfolded Proteins Propagation in Aging and Associated Neurodegenerative Disorders
A high level of robustness against gene deletion is observed in many organisms . However , it is still not clear which biochemical features underline this robustness and how these are acquired during evolution . One hypothesis , specific to metabolic networks , is that robustness emerges as a byproduct of selection for...
One of the most surprising recent biological findings is the high level of tolerance organisms show towards loss of single genes . This observation suggests that there are certain features of biological systems that give them a high tolerance ( i . e . robustness ) towards gene loss . We still lack an exact understandi...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "cell", "biology/microbial", "physiology", "and", "metabolism", "biochemistry/molecular", "evolution", "genetics", "and", "genomics/microbial", "evolution", "and", "genomics", "evolutionary", "biology/microbial", "evolution", "and", "genomics", "mathematics", "computational", ...
2010
Evolution under Fluctuating Environments Explains Observed Robustness in Metabolic Networks
T cells orchestrate the adaptive immune response , making them targets for immunotherapy . Although immunosuppressive therapies prevent disease progression , they also leave patients susceptible to opportunistic infections . To identify novel drug targets , we established a logical model describing T-cell receptor ( TC...
The cells of the mammalian immune system do not exist in isolation , but rather form an integrated network that is constantly scanning the body for signs of ‘foreign’ invasion . Working together , these cells possess the ability to repel invaders and thereby establish protective immunity . One central population in thi...
[ "Abstract", "Introduction", "Methods", "Results/Discussion" ]
[ "biochemistry", "signal", "transduction", "molecular", "cell", "biology", "immune", "cells", "proteins", "t", "cells", "immunology", "biology", "computational", "biology", "signaling", "networks", "molecular", "biology", "t-cell", "receptors" ]
2011
Integrating Signals from the T-Cell Receptor and the Interleukin-2 Receptor
Latent toxoplasmosis , a lifelong infection with the protozoan Toxoplasma gondii , has cumulative effects on the behaviour of hosts , including humans . The most impressive effect of toxoplasmosis is the “fatal attraction phenomenon , ” the conversion of innate fear of cat odour into attraction to cat odour in infected...
Latent toxoplasmosis , a lifelong infection with the protozoan Toxoplasma gondii , has cumulative effects on the behaviour of hosts , including humans . The most impressive effect of toxoplasmosis is the so-called “fatal attraction phenomenon , ” the conversion of innate fear of odour of the definitive host , the cat ,...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "evolutionary", "ecology", "behavioral", "neuroscience", "animal", "behavior", "ecology", "parasitology", "biology", "sensory", "perception", "zoology", "neuroscience", "animal", "cognition", "behavioral", "ecology" ]
2011
Fatal Attraction Phenomenon in Humans – Cat Odour Attractiveness Increased for Toxoplasma-Infected Men While Decreased for Infected Women
Endogenous small molecule metabolites that regulate animal longevity are emerging as a novel means to influence health and life span . In C . elegans , bile acid-like steroids called the dafachronic acids ( DAs ) regulate developmental timing and longevity through the conserved nuclear hormone receptor DAF-12 , a homol...
Although well known for their role in the absorption of dietary fat , bile acids have emerged as important metabolic signaling molecules that regulate cholesterol , fat , and glucose metabolism . Bile acids work through nuclear receptors , a class of transcription factors that bind to fat soluble hormones to directly c...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "animal", "models", "biochemistry", "developmental", "biology", "lipids", "signal", "transduction", "model", "organisms", "molecular", "cell", "biology", "organism", "development", "molecular", "development", "biology", "metabolism", "molecular", "biology" ]
2012
A Novel 3-Hydroxysteroid Dehydrogenase That Regulates Reproductive Development and Longevity
The nucleolus is a multifunctional structure within the nucleus of eukaryotic cells and is the primary site of ribosome biogenesis . Almost all viruses target and disrupt the nucleolus—a feature exclusive to this pathogen group . Here , using a combination of bio-imaging , genetic and biochemical analyses , we demonstr...
Many of the world's most important diseases are caused by bacterial pathogens that deliver effector proteins into the cells of their host . Effector proteins are collectively responsible for causing disease and an important area of research is to define the functions of these proteins and identify how they are regulate...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases/bacterial", "infections", "virology/virulence", "factors", "and", "mechanisms", "microbiology/cellular", "microbiology", "and", "pathogenesis", "cell", "biology/nuclear", "structure", "and", "function" ]
2010
The Enteropathogenic E. coli Effector EspF Targets and Disrupts the Nucleolus by a Process Regulated by Mitochondrial Dysfunction
Genome-wide dynamic changes in DNA methylation are indispensable for germline development and genomic imprinting in mammals . Here , we report single-base resolution DNA methylome and transcriptome maps of mouse germ cells , generated using whole-genome shotgun bisulfite sequencing and cDNA sequencing ( mRNA-seq ) . Oo...
In mammals , germ-cell–specific methylation patterns and genomic imprints are established throughout large-scale de novo DNA methylation in oogenesis and spermatogenesis . These steps are required for normal germline differentiation and embryonic development; however , current DNA methylation analyses only provide us a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biotechnology", "developmental", "biology", "genetics", "biology", "genomics", "molecular", "cell", "biology", "genetics", "and", "genomics" ]
2012
Contribution of Intragenic DNA Methylation in Mouse Gametic DNA Methylomes to Establish Oocyte-Specific Heritable Marks
Polycomb Group ( PcG ) proteins are epigenetic repressors that control metazoan development and cell differentiation . In Drosophila , PcG proteins form five distinct complexes targeted to genes by Polycomb Response Elements ( PREs ) . Of all PcG complexes PhoRC is the only one that contains a sequence-specific DNA bin...
Polycomb Group ( PcG ) proteins are epigenetic repressors essential for development and cell differentiation . PcG proteins form five complexes targeted to specific genes by Polycomb Response Elements ( PREs ) . How PcG complexes are recruited to PREs is poorly understood . Here we investigate the recruitment of PhoRC ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "developmental", "biology", "model", "organisms", "genetics", "biology", "and", "life", "sciences", "genomics", "research", "and", "analysis", "methods" ]
2014
Combinatorial Interactions Are Required for the Efficient Recruitment of Pho Repressive Complex (PhoRC) to Polycomb Response Elements
The carbohydrate larval antigen , CarLA , is present on the exposed surface of all strongylid nematode infective L3 larvae tested , and antibodies against CarLA can promote rapid immune rejection of incoming Trichostrongylus colubriformis larvae in sheep . A library of ovine recombinant single chain Fv ( scFv ) antibod...
Strongylid nematode worm parasites currently infect hundreds of millions of people , and most farmed animals , causing enormous morbidity and economic loss . These parasites commonly produce chronic gastrointestinal infections that are highly refractory to immune clearance mechanisms . Mucosal antibodies against a carb...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases/helminth", "infections", "immunology/immunity", "to", "infections", "immunology/immune", "response", "infectious", "diseases/gastrointestinal", "infections" ]
2009
Intraspecific Epitopic Variation in a Carbohydrate Antigen Exposed on the Surface of Trichostrongylus colubriformis Infective L3 Larvae
Dengue virus ( DENV ) is an enveloped RNA virus that causes the most common arthropod-borne infection worldwide . The mechanism by which DENV infects the host cell remains unclear . In this work , we used live-cell imaging and single-virus tracking to investigate the cell entry , endocytic trafficking , and fusion beha...
Dengue virus ( DENV ) is the most common arthropod-borne infection worldwide with 50–100 million cases annually . Despite its high clinical impact , little is known about the infectious cell entry pathway of the virus . Previous studies have shown conflicting evidence about whether the virus fuses directly with the cel...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "virology/host", "invasion", "and", "cell", "entry" ]
2008
Dissecting the Cell Entry Pathway of Dengue Virus by Single-Particle Tracking in Living Cells
Many protein-protein interactions ( PPIs ) are compelling targets for drug discovery , and in a number of cases can be disrupted by small molecules . The main goal of this study is to examine the mechanism of binding site formation in the interface region of proteins that are PPI targets by comparing ligand-free and li...
Many protein-protein interfaces ( PPIs ) are biologically compelling drug targets . Disrupting the interaction between two large proteins by a small inhibitor requires forming a high affinity binding site in the interface that generally can bind both peptides and drug-like compounds . Here we investigate whether such s...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "biomacromolecule-ligand", "interactions", "biochemistry", "molecular", "complexes", "biophysics", "theory", "biology", "and", "life", "sciences", "computational", "biology", "biophysics", "molecular", "biology", "biophysical", "simulations" ]
2014
Evidence of Conformational Selection Driving the Formation of Ligand Binding Sites in Protein-Protein Interfaces
Several studies have shown Dengue Virus ( DENV ) nucleic acids and/or antibodies present in Neotropical wildlife including bats , suggesting that some bat species may be susceptible to DENV infection . Here we aim to elucidate the role of house-roosting bats in the DENV transmission cycle . Bats were sampled in househo...
Dengue is the most important human vector-borne disease . Several studies have shown DENV presence in mammalian wildlife such as bats , thus considering them putative reservoirs or hosts . We aimed to elucidate if bats that cohabit in houses in close proximity with humans may be involved in a dengue transmission cycle ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "taxonomy", "invertebrates", "dengue", "virus", "animal", "types", "medicine", "and", "health", "sciences", "body", "fluids", "immune", "physiology", "pathology", "and", "laboratory", "medicine", "pathogens", "immunology", "microbiology", "vertebrates", "animals", "mamm...
2017
Neotropical bats that co-habit with humans function as dead-end hosts for dengue virus
Interleukin-6 is a pleiotropic , pro-inflammatory cytokine that can promote both innate and adaptive immune responses . In humans with respiratory virus infections , such as Respiratory Syncytial Virus ( RSV ) , elevated concentrations of IL-6 are associated with more severe disease . In contrast the polymorphisms in t...
In clearing a respiratory virus , the host must strike a careful balance between the need to clear the infection and the potential of the immune response to damage the delicate structure of the lungs . Here we show that Interleukin-6 , a soluble mediator commonly associated with inflammation and seen in humans with sev...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "blood", "cells", "innate", "immune", "system", "medicine", "and", "health", "sciences", "immune", "cells", "immune", "physiology", "respiratory", "infections", "cytokines", "pathology", "and", "laboratory", "medicine", "pathogens", "immunology", "microbiology", "orthom...
2017
Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology
The recent emergence of a novel H7N9 influenza A virus ( IAV ) causing severe human infections in China raises concerns about a possible pandemic . The lack of pre-existing neutralizing antibodies in the broader population highlights the potential protective role of IAV-specific CD8+ cytotoxic T lymphocyte ( CTL ) memo...
The emergence of human infections with a novel strain of avian-origin H7N9 virus in China raises a pandemic concern . The introduction of a new subtype in humans makes people at all ages susceptible due to the lack of population-wide neutralizing antibodies . However , cross-subtype protection from existing host immuni...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Diverse Heterologous Primary Infections Radically Alter Immunodominance Hierarchies and Clinical Outcomes Following H7N9 Influenza Challenge in Mice
Viral invasion into a host is initially recognized by the innate immune system , mainly through activation of the intracellular cytosolic signaling pathway and coordinated activation of interferon regulatory factor 3 ( IRF3 ) and nuclear factor kappa B ( NF-κB ) transcription factors that promote type I interferon gene...
The innate immune system has evolved to detect and neutralize viral invasion . Triggering of this defense mechanism relies on the production and secretion of soluble factors that stimulate an intracellular antiviral defense mechanism . The protein Optineurin was shown to negatively regulate this process . Importantly ,...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Optineurin Regulates the Interferon Response in a Cell Cycle-Dependent Manner
Isolated influenza A virus nucleoprotein exists in an equilibrium between monomers and trimers . Samples containing only monomers or only trimers can be stabilized by respectively low and high salt . The trimers bind RNA with high affinity but remain trimmers , whereas the monomers polymerise onto RNA forming nucleopro...
The RNAs of negative strand RNA viruses are encapsidated by their specific viral nucleoproteins , forming helical nucleoprotein-RNA structures that are the template for transcription and replication . All these nucleoproteins have two activities in common: RNA binding and self-polymerisation , and it is likely that the...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry", "rna", "rna", "viruses", "nucleic", "acids", "virology", "viral", "classification", "biology", "microbiology" ]
2013
Monomeric Nucleoprotein of Influenza A Virus
The current unprecedented expansion of infrastructure promises to enhance human wellbeing but risks causing substantial harm to natural ecosystems and the benefits they provide for people . A framework for systematically and proactively identifying the likely benefits and costs of such developments is badly needed . He...
Proposals for new infrastructure in developing countries are typically muted on its environmental impacts , while environmentalists typically say little about its potential benefits for people . This study explores a more conciliatory approach by trying to identify where beneficial infrastructure might be expanded at l...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "ecology", "and", "environmental", "sciences", "engineering", "and", "technology", "transportation", "geographical", "locations", "vertebrates", "biodiversity", "animals", "transportation", "infrastructure", "roads", "habitats", "civil", "engineering", "birds", "ecosystems", ...
2016
Getting Road Expansion on the Right Track: A Framework for Smart Infrastructure Planning in the Mekong
Preventing germline stem cell proliferation extends lifespan in nematodes and flies . So far , studies on germline-longevity signaling have focused on daf-16/FOXO and daf-12/VDR . Here , we report on NHR-80/HNF4 , a nuclear receptor that specifically mediates longevity induced by depletion of the germ line through a me...
Reproduction and aging are two processes that seem to be closely intertwined . Experiments in Caenorhabditis elegans and Drosophila have shown that depletion of the germ line increases lifespan and that this process depends on insulin and lipophilic-hormone signaling . Recently , it was demonstrated that when germline ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology/aging" ]
2011
Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans
Abnormal accumulation of the microtubule-interacting protein tau is associated with neurodegenerative diseases including Alzheimer’s disease ( AD ) . β-amyloid ( Aβ ) lies upstream of abnormal tau behavior , including detachment from microtubules , phosphorylation at several disease-specific sites , and self-aggregatio...
Alzheimer’s disease ( AD ) is the most common cause of dementia resulting from progressive neuron loss . Two proteins , β-amyloid ( Aβ ) and tau , accumulate in AD brains and are involved in AD pathogenesis . In healthy neurons , tau binds to microtubules to regulate its stability; in AD brains , however , tau is detac...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "phosphorylation", "medicine", "and", "health", "sciences", "rna", "interference", "microtubules", "pathology", "and", "laboratory", "medicine", "neurodegenerative", "diseases", "toxicology", "toxicity", "epigenetics", "tubulins", "alzheimer", "disease", "cellular", "struct...
2016
Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity
Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature , viable gametes . In recent years there has been rapid growth in understanding fish reproductive biology , which has been motivated in part by recognition of the potentia...
Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature , viable gametes . Improving the ability to estimate reproductive performance in fish is important , due to the growth of the aquaculture industry and the need to maintain...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "reproductive", "system", "body", "fluids", "nervous", "system", "vertebrates", "neuroscience", "animals", "reproductive", "physiology", "endocrine", "physiology", "germ", "cells", "osteichthyes", "oocytes", "gnrh", "stimulation", ...
2016
A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis
Development and function of tissues and organs are powered by the activity of mitochondria . In humans , inherited genetic mutations that lead to progressive mitochondrial pathology often manifest during infancy and can lead to death , reflecting the indispensable nature of mitochondrial biogenesis and function . Here ...
Mitochondrial pathologies which result from mutations in the nuclear DNA remain incurable and often lead to death . As mitochondria play various roles in cellular and tissue-specific contexts , the symptoms of mitochondrial pathologies can differ between patients . Thus , diagnosis and treatment of mitochondrial disord...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "fish", "medicine", "and", "health", "sciences", "skeletal", "muscles", "computational", "biology", "vertebrates", "animals", "animal", "models", "osteichthyes", "developmental", "biology", "fungi", "model", "organisms", "experimental", "organism", "systems", "genome", ...
2018
Loss of the Mia40a oxidoreductase leads to hepato-pancreatic insufficiency in zebrafish
Severe leptospirosis features bleeding and multi-organ failure , leading to shock and death . Currently it is assumed that both exaggerated inflammation and immune suppression contribute to mortality in sepsis . Indeed , several proinflammatory cytokines are reported to be induced during leptospirosis . Toll-like recep...
Leptospirosis is a bacterial disease that is mainly spread by rodents and other small mammals . Transmission frequently occurs in ( sub- ) tropical countries , where environmental circumstances are most favourable . Severe leptospirosis can cause bleeding and vital organ dysfunction . An exaggerated immune response is ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases", "infectious", "diseases/neglected", "tropical", "diseases", "immunology/immune", "response", "immunology/innate", "immunity", "critical", "care", "and", "emergency", "medicine/sepsis", "and", "multiple", "organ", "failure", "immunology", "infectious"...
2009
Soluble ST2 Levels Are Associated with Bleeding in Patients with Severe Leptospirosis
T cells are known to contribute to immune protection against scrub typhus , a potentially fatal infection caused by the obligate intracellular bacterium Orientia ( O . ) tsutsugamushi . However , the contribution of CD8+ T cells to protection and pathogenesis during O . tsutsugamushi infection is still unknown . Using ...
Orientia ( O . ) tsutsugamushi is the causative agent of scrub typhus , a potentially fatal disease that is endemic in South East Asia . This bacterium replicates in the cytoplasm of its host cells . The obligate intracytoplasmic lifestyle resembles that of many viruses , but among pathogenic bacteria it is unique to O...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "blood", "cells", "medicine", "and", "health", "sciences", "immune", "cells", "immune", "physiology", "pathology", "and", "laboratory", "medicine", "spleen", "pathogens", "animal", "models", "of", "disease", "immunology", "microbiology", "animal", "models", "bacterial...
2016
Protective and Pathogenic Roles of CD8+ T Lymphocytes in Murine Orientia tsutsugamushi Infection
This paper presents a new agent-based model ( ABM ) for investigating T . b . rhodesiense human African trypanosomiasis ( rHAT ) disease dynamics , produced to aid a greater understanding of disease transmission , and essential for development of appropriate mitigation strategies . The ABM was developed to model rHAT i...
African trypanosomiasis is a parasitic disease which affects humans and other animals in 36 sub-Saharan African countries . The disease is transmitted by the tsetse fly , and the human form of the diseases is known as sleeping sickness . Infectious disease transmission has traditionally been modelled using techniques t...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion", "Conclusion" ]
[ "death", "rates", "invertebrates", "livestock", "animal", "types", "medicine", "and", "health", "sciences", "ruminants", "demography", "african", "trypanosomiasis", "tropical", "diseases", "vertebrates", "parasitic", "diseases", "animals", "mammals", "glossina", "simulati...
2016
A Multi-Host Agent-Based Model for a Zoonotic, Vector-Borne Disease. A Case Study on Trypanosomiasis in Eastern Province, Zambia
Associating genetic variation with quantitative measures of gene regulation offers a way to bridge the gap between genotype and complex phenotypes . In order to identify quantitative trait loci ( QTLs ) that influence the binding of a transcription factor in humans , we measured binding of the multifunctional transcrip...
We have systematically measured the effect of normal genetic variation present in a human population on the binding of a specific chromatin protein ( CTCF ) to DNA by measuring its binding in 51 human cell lines . We observed a large number of changes in protein binding that we can confidently attribute to genetic effe...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetic", "association", "studies", "genome", "analysis", "trait", "locus", "analysis", "genetics", "biology", "and", "life", "sciences", "epigenomics", "computational", "biology", "human", "genetics" ]
2014
Quantitative Genetics of CTCF Binding Reveal Local Sequence Effects and Different Modes of X-Chromosome Association
We present a study investigating the role of mitochondrial variability in generating noise in eukaryotic cells . Noise in cellular physiology plays an important role in many fundamental cellular processes , including transcription , translation , stem cell differentiation and response to medication , but the specific r...
Cellular variability has been found to play a major role in diverse and important phenomena , including stem cell differentiation and drug resistance , but the sources of this variability have yet to be satisfactorily explained . We propose a mechanism , supported by a substantial number of recent and new experiments ,...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "systems", "biology", "cellular", "structures", "theoretical", "biology", "cell", "biology", "biology", "computational", "biology", "molecular", "cell", "biology", "biophysics", "genetics", "and", "genomics" ]
2012
Mitochondrial Variability as a Source of Extrinsic Cellular Noise