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Diagnostic guidelines for Visceral Leishmaniasis ( VL ) in the East African region are complex . Patients meeting the VL clinical case definition should be tested by rK39 rapid diagnostic test ( RDT ) followed by the Direct Agglutination Test ( DAT ) or tissue aspiration if RDT-negative . Otherwise , RDT-positive patie...
The introduction of RDTs is one of the major advancements in leishmaniasis control programs . While the variability in performance from one endemic region to the other is well recognized , the utilization of these RDTs in the routine clinical setting has not been evaluated to date . In this study , we showed that the R...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Impact of the Use of a Rapid Diagnostic Test for Visceral Leishmaniasis on Clinical Practice in Ethiopia: A Retrospective Study
Visceral leishmaniasis is an important parasitic disease of the developing world with a limited arsenal of drugs available for treatment . The existing drugs have significant deficiencies so there is an urgent need for new and improved drugs . In the human host , Leishmania are obligate intracellular parasites which po...
New drugs for visceral leishmaniasis , are urgently required as existing drugs have serious shortcomings including toxicity and drug resistance . This disease is caused by parasites from the Leishmania family which live inside human cells . Screening large collections of chemicals ( >100 , 000 ) to identify compounds t...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Development and Validation of a Novel Leishmania donovani Screening Cascade for High-Throughput Screening Using a Novel Axenic Assay with High Predictivity of Leishmanicidal Intracellular Activity
Inverted repeats capable of forming hairpin and cruciform structures present a threat to chromosomal integrity . They induce double strand breaks , which lead to gross chromosomal rearrangements , the hallmarks of cancers and hereditary diseases . Secondary structure formation at this motif has been proposed to be the ...
Inverted repeats are found in many eukaryotic genomes including humans . They have a potential to cause chromosomal breakage and rearrangements that contribute to genome polymorphism and the development of diseases . Instability of inverted repeats is accounted for by their propensity to adopt DNA secondary structures ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
Genome-Wide Screen Reveals Replication Pathway for Quasi-Palindrome Fragility Dependent on Homologous Recombination
Auxin is a major developmental regulator in plants and the acquisition of a transcriptional response to auxin likely contributed to developmental innovations at the time of water-to-land transition . Auxin Response Factors ( ARFs ) Transcription Factors ( TFs ) that mediate auxin-dependent transcriptional changes are d...
Plants transition from water to land was determining for the history of our planet , since it led to atmospheric and soil condition changes that promoted the appearance of other life forms . This transition initiated around 1 billion years ago from a Charophyte algae lineage that acquired features allowing it to adapt ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "&", "methods" ]
[ "organismal", "evolution", "brassica", "dna-binding", "proteins", "hormones", "plant", "science", "model", "organisms", "plant", "hormones", "experimental", "organism", "systems", "sequence", "motif", "analysis", "plants", "research", "and", "analysis", "methods", "arab...
2019
Evolution of the Auxin Response Factors from charophyte ancestors
The computation represented by a sensory neuron's response to stimuli is constructed from an array of physiological processes both belonging to that neuron and inherited from its inputs . Although many of these physiological processes are known to be nonlinear , linear approximations are commonly used to describe the s...
Sensory neurons are capable of representing a wide array of computations on sensory stimuli . Such complex computations are thought to arise in large part from the accumulation of relatively simple nonlinear operations across the sensory processing hierarchies . However , models of sensory processing typically rely on ...
[ "Abstract", "Introduction", "Results", "Methods" ]
[ "auditory", "system", "visual", "system", "mathematics", "computational", "neuroscience", "single", "neuron", "function", "statistics", "sensory", "systems", "biology", "neuroscience", "statistical", "methods" ]
2013
Inferring Nonlinear Neuronal Computation Based on Physiologically Plausible Inputs
Polymerase mu ( Polμ ) is an error-prone , DNA-directed DNA polymerase that participates in non-homologous end-joining ( NHEJ ) repair . In vivo , Polμ deficiency results in impaired Vκ-Jκ recombination and altered somatic hypermutation and centroblast development . In Polμ−/− mice , hematopoietic development was defec...
Double-strand breaks ( DSB ) in DNA are a highly deleterious type of genetic damage , potentially causing genomic rearrangements or cell death if unrepaired . DSB can be triggered by environmental factors ( such as electromagnetic radiation or clastogenic chemicals ) or normal cell metabolism . The main mechanism of DS...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "molecular", "biology/dna", "repair" ]
2009
Altered Hematopoiesis in Mice Lacking DNA Polymerase μ Is Due to Inefficient Double-Strand Break Repair
The spleen is one of the main affected organs in canine visceral leishmaniasis ( CVL ) . Disorganization of the splenic white pulp ( SWP ) has been associated with immunosuppression and disease progression . This study aims to assess structural and cellular changes in the splenic extracellular matrix of dogs with CVL ,...
Infected dogs play important roles in the transmission of visceral leishmaniasis . These dogs are considered reservoirs of parasites in urban areas and fail to mount an efficient anti-Leishmania immune response . However , the specific immunosuppression profile is not completely understood . In our report , we evaluate...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "immune", "physiology", "immune", "cells", "spleen", "granulomas", "immunology", "vertebrates", "parasitic", "diseases", "dogs", "animals", "collagens", "mammals", "parasitic", "protozoans", "protozoans", "leishmania", "cellular", ...
2018
Morphophysiological changes in the splenic extracellular matrix of Leishmania infantum-naturally infected dogs is associated with alterations in lymphoid niches and the CD4+ T cell frequency in spleens
Mice lacking the type I interferon receptor ( IFNAR−/− mice ) reproduce relevant aspects of Crimean-Congo hemorrhagic fever ( CCHF ) in humans , including liver damage . We aimed at characterizing the liver pathology in CCHF virus-infected IFNAR−/− mice by immunohistochemistry and employed the model to evaluate the ant...
Crimean-Congo hemorrhagic fever ( CCHF ) is endemic in Africa , Asia , southeast Europe , and the Middle East . The case fatality rate is 30–50% . Studies on pathophysiology and treatment of CCHF have been hampered by the lack of an appropriate animal model . We have employed CCHF virus-infected transgenic mice , which...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "antimicrobials", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "emerging", "viral", "diseases", "crimean-congo", "hemorrhagic", "fever", "tropical", "diseases", "microbiology", "animal", "models", "model", "organisms", "emerging",...
2014
Evaluation of Antiviral Efficacy of Ribavirin, Arbidol, and T-705 (Favipiravir) in a Mouse Model for Crimean-Congo Hemorrhagic Fever
The mechanism by which a complex auditory scene is parsed into coherent objects depends on poorly understood interactions between task-driven and stimulus-driven attentional processes . We illuminate these interactions in a simultaneous behavioral–neurophysiological study in which we manipulate participants' attention ...
Attention is the cognitive process underlying our ability to focus on specific aspects of our environment while ignoring others . By its very definition , attention plays a key role in differentiating foreground ( the object of attention ) from unattended clutter , or background . We investigate the neural basis of thi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "neuroscience/cognitive", "neuroscience", "neuroscience/sensory", "systems" ]
2009
Interaction between Attention and Bottom-Up Saliency Mediates the Representation of Foreground and Background in an Auditory Scene
Simultaneous analysis of genetic associations with multiple phenotypes may reveal shared genetic susceptibility across traits ( pleiotropy ) . For a locus exhibiting overall pleiotropy , it is important to identify which specific traits underlie this association . We propose a Bayesian meta-analysis approach ( termed C...
Genome-wide association studies ( GWAS ) have detected shared genetic susceptibility to various human diseases ( pleiotropy ) . We propose a Bayesian meta-analysis method CPBayes that simultaneously evaluates the evidence of overall pleiotropy while determining which traits are pleiotropic . This approach investigates ...
[ "Abstract", "Introduction", "Discussion", "Materials", "and", "methods" ]
[ "genome-wide", "association", "studies", "medicine", "and", "health", "sciences", "simulation", "and", "modeling", "diabetes", "mellitus", "research", "design", "dyslipidemia", "endocrine", "disorders", "genome", "analysis", "type", "2", "diabetes", "research", "and", ...
2018
An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations
Major human pathologies are caused by nuclear replicative viruses establishing life-long latent infection in their host . During latency the genomes of these viruses are intimately interacting with the cell nucleus environment . A hallmark of herpes simplex virus type 1 ( HSV-1 ) latency establishment is the shutdown o...
After an initial lytic infection , many viruses establish a lifelong latent infection that hides them from the host immune system activity until reactivation . To understand the resurgence of the associated diseases , it is indispensable to acquire a better knowledge of the different mechanisms involved in the antivira...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cellular", "structures", "cellular", "stress", "responses", "viral", "classification", "microbiology", "host-pathogen", "interaction", "animal", "models", "model", "organisms", "dna", "viruses", "cell", "nucleus", "animal", "models", "of", "infection", "biology", "mous...
2012
HSV-1 Genome Subnuclear Positioning and Associations with Host-Cell PML-NBs and Centromeres Regulate LAT Locus Transcription during Latency in Neurons
CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma . Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally , a phenomenon called “synaptic democracy” . How this is established is unclear . The backpropagating action...
Neurons receive information from other neurons via hundreds of contacts ( synapses ) spread across their dendritic branches . Input signals from synapses propagate along a dendrite to the cell body ( soma ) , where the neuron decides whether or not to produce an action potential . Signals that travel further decay more...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "cellular", "neuroscience", "computational", "neuroscience", "biology", "neuroscience" ]
2012
Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy
After loading with live Leishmania ( L ) amazonensis amastigotes , mouse myeloid dendritic leucocytes/DLs are known to undergo reprogramming of their immune functions . In the study reported here , we investigated whether the presence of live L . amazonensis amastigotes in mouse bone marrow-derived DLs is able to trigg...
Once they have gained entry to mammals , live Leishmania ( L ) amazonensis amastigotes are known to subvert both macrophages and dendritic leucocytes ( DLs ) as host cells . These L . amazonensis amastigotes then may or may not proliferate in these two phagocytic leucocyte lineages , but in both cases the otherwise ver...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "and", "Discussion" ]
[ "eukaryotic", "cells", "molecular", "cell", "biology", "immune", "cells", "antigen", "processing", "and", "recognition", "immunity", "gene", "expression", "parasitology", "immunology", "host-pathogen", "interaction", "biology", "genomics", "microbiology", "cellular", "typ...
2013
Reprogramming Neutral Lipid Metabolism in Mouse Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes
The waggle dance of honey bee ( Apis mellifera L . ) foragers communicates to nest mates the location of a profitable food source . We used solid-phase microextraction and gas chromatography coupled with mass spectrometry to show that waggle-dancing bees produce and release two alkanes , tricosane and pentacosane , and...
A honey bee colony consists of many thousands of individuals , all of which help to perform the work that allows their colony to thrive . To coordinate their efforts , honey bees have evolved a complex communication system , no part of which is more sophisticated than the waggle dance . The waggle dance is unique , bec...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "evolutionary", "biology", "ecology", "chemical", "biology", "insects" ]
2007
The Scent of the Waggle Dance
A working knowledge of the proximate factors intrinsic to sterile caste differentiation is necessary to understand the evolution of eusocial insects . Genomic and transcriptomic analyses in social hymenopteran insects have resulted in the hypothesis that sterile castes are generated by the novel function of co-opted or...
The acquisition of a sterile caste is a key step in animal eusocial evolution . The soldier is the first acquired permanently sterile caste in termites , which are distantly related to hymenopteran eusocial insects ( bees , ants and wasps ) . However , the evolutionary background to acquiring the soldier caste is still...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "rna", "interference", "gene", "regulation", "regulatory", "proteins", "dna-binding", "proteins", "animals", "organisms", "physiological", "processes", "transcription", "factors", "epigenetics", "zoology", "molting",...
2018
TGFβ signaling related genes are involved in hormonal mediation during termite soldier differentiation
As well as their importance to nutrition , fatty acids ( FA ) represent a unique group of quorum sensing chemicals that modulate the behavior of bacterial population in virulence . However , the way in which full-length , membrane-bound receptors biochemically detect FA remains unclear . Here , we provide genetic , enz...
Besides roles in nutrition , lipids also function as important signals in the regulation of prokaryotic and eukaryotic cells . In bacteria , fatty acids are part of the language of cell-cell communication known as quorum sensing for a decade . However , how bacteria detect these signals and regulate virulence remains e...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "bacteriology", "biofilms", "exopolysaccharides", "vesicles", "chemical", "compounds", "xanthomonas", "campestris", "microbiology", "organic", "compounds", "mutation", "plant", "science", "amino", "acid", "substitution", "amino", "acids", "plant", "pathology", "cellular", ...
2017
Fatty acid DSF binds and allosterically activates histidine kinase RpfC of phytopathogenic bacterium Xanthomonas campestris pv. campestris to regulate quorum-sensing and virulence
Patterned expression of many developmental genes is specified by transcription factor gene expression , but is thought to be refined by chromatin-mediated repression . Regulatory DNA sequences called Polycomb Response Elements ( PREs ) are required to repress some developmental target genes , and are widespread in geno...
Eukaryotic genes are packaged in chromatin , and their transcription relies on activators that recruit RNA polymerases and on repressive factors . In multicellular organisms , cell types have distinct patterns of gene expression , and these patterns are controlled by by the expression of cell-type-specific transcriptio...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "invertebrates", "gene", "regulation", "dna-binding", "proteins", "invertebrate", "genomics", "animals", "animal", "models", "developmental", "biology", "drosophila", "melanogaster", "model", "organisms", "methylation", "experimental", "organism", "systems", "epigenetics", ...
2019
Separate Polycomb Response Elements control chromatin state and activation of the vestigial gene
Hepatitis B virus ( HBV ) replicates its DNA genome through reverse transcription of a viral RNA pregenome . We report herein that the interferon ( IFN ) stimulated exoribonuclease gene of 20 KD ( ISG20 ) inhibits HBV replication through degradation of HBV RNA . ISG20 expression was observed at basal level and was high...
HBV is a DNA virus but replicates its DNA via retrotranscription of a viral RNA pregenome . ISG20 , an antiviral RNase induced by interferons , inhibits the replication of many RNA viruses but the underlying molecular antiviral mechanism remains elusive . Since all the known viruses , except for prions , have RNA produ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "electrophoretic", "mobility", "shift", "assay", "gene", "regulation", "pathogens", "microbiology", "hepatitis", "b", "virus", "plasmid", "construction", "viruses", "dna", "replicatio...
2017
Interferon-inducible ribonuclease ISG20 inhibits hepatitis B virus replication through directly binding to the epsilon stem-loop structure of viral RNA
Since the outbreak of severe acute respiratory syndrome ( SARS ) in 2003 , the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus ( SARS-CoV ) , the non-structural proteins ( Nsps ) , have been determined . However , within the large Nsp3 ( 1922 amino-acid residues ) ,...
The genome of the SARS coronavirus codes for 16 non-structural proteins that are involved in replicating this huge RNA ( approximately 29 kilobases ) . The roles of many of these in replication ( and/or transcription ) are unknown . We attempt to derive conclusions concerning the possible functions of these proteins fr...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry", "biochemistry/rna", "structure", "virology/viral", "replication", "and", "gene", "regulation", "biophysics/structural", "genomics", "biophysics/protein", "folding", "virology/virulence", "factors", "and", "mechanisms", "virology/emerging", "viral", "diseases", "...
2009
The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes
The acquisition of the external genitalia allowed mammals to cope with terrestrial-specific reproductive needs for internal fertilization , and thus it represents one of the most fundamental steps in evolution towards a life on land . How genitalia evolved remains obscure , and the key to understanding this process may...
Mammalian limbs and external genitalia are body appendages specialized for locomotion and internal fertilization , respectively . Despite their marked anatomical and functional differences , development of the limb and external genitalia appears to involve similar genetic controls , and some have suggested that regulat...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "embryology", "molecular", "development", "biology" ]
2013
Delineating a Conserved Genetic Cassette Promoting Outgrowth of Body Appendages
M . tuberculosis ( MTB ) species-specific antigenic determinants of the human T cell response are important for immunodiagnosis and vaccination . As hypoxia is a stimulus in chronic tuberculosis infection , we analyzed transcriptional profiles of MTB subject to 168 hours of hypoxia to test the hypothesis that upregulat...
Mycobacterium tuberculosis ( the cause of tuberculosis ) can persist for many years in humans without causing disease but has the potential to reactivate . One of the conditions the bacterium must survive in these circumstances is hypoxia . In order to do so , the bacterium uses a characteristic set of genes that help ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "immunology/antigen", "processing", "and", "recognition", "microbiology/immunity", "to", "infections", "immunology/immune", "response", "infectious", "diseases/bacterial", "infections", "immunology/immunity", "to", "infections" ]
2010
Hypoxia Induces an Immunodominant Target of Tuberculosis Specific T Cells Absent from Common BCG Vaccines
Hepadnavirus covalently closed circular ( ccc ) DNA is the bona fide viral transcription template , which plays a pivotal role in viral infection and persistence . Upon infection , the non-replicative cccDNA is converted from the incoming and de novo synthesized viral genomic relaxed circular ( rc ) DNA , presumably th...
Hepadnavirus cccDNA is the persistent form of viral genome , and in terms of human hepatitis B virus ( HBV ) , cccDNA is the basis for viral rebound after the cessation of therapy , as well as the elusiveness of a cure with current medications . Therefore , the elucidation of molecular mechanism of cccDNA formation wil...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "molecular", "probe", "techniques", "enzymes", "enzymology", "plasmid", "construction", "dna", "replication", "dna", "construction", "dna", "molecular", "biology", "techniques", "gel", "electrophoresis", "ligases", "extraction", "techniques", "research", "and", "analysis"...
2017
The role of host DNA ligases in hepadnavirus covalently closed circular DNA formation
TGF-β involvement in Chagas disease cardiomyopathy has been clearly demonstrated . The TGF-β signaling pathway is activated in the cardiac tissue of chronic phase patients and is associated with an increase in extracellular matrix protein expression . The aim of this study was to investigate the effect of GW788388 , a ...
TGF-β is a key molecule in many physiological processes as well as pathologies . We have previously described the role of TGF-β in Chagas disease , caused by the eukaryotic protozoan parasite Trypanosoma cruzi . Besides the high disease burden in many countries , one of the severe aspects of Chagas disease is the chron...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "cardiovascular", "anatomy", "tropical", "diseases", "fibrosis", "parasitic", "diseases", "parasitic", "protozoans", "animal", "models", "organisms", "developmental", "biology", "electrocardiography", "model", "organisms", "protozoan...
2019
TGF-β inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a pre-clinical study of chronic Chagas’ heart disease
The metacercariae of the Clonorchis sinensis liver fluke excyst in the duodenum of mammalian hosts , and the newly excysted juveniles ( CsNEJs ) migrate along the bile duct via bile chemotaxis . Cholic acid is a major component of bile that induces this migration . We investigated the neuronal control of chemotactic be...
The liver fluke Clonorchis sinensis is a flatworm parasite dwelling in the bile duct , which can induce serious pathological inflammatory changes , and chronic infection is associated with bile duct cancer . In order to gain access to its habitat , C . sinensis larva follows chemical cues from the liver , a phenomenon ...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "cell", "motility", "neurochemistry", "chemical", "compounds", "dopaminergics", "neuroscience", "organic", "compounds", "hormones", "serotonin", "muscarinic", "acetylcholine", "receptors", "amines", "neurotransmitters", "neuropeptides", "catecholamines", "dopamine", "nicotinic"...
2019
Chemotactic migration of newly excysted juvenile Clonorchis sinensis is suppressed by neuro-antagonists
Herbivores can gain indirect access to recalcitrant carbon present in plant cell walls through symbiotic associations with lignocellulolytic microbes . A paradigmatic example is the leaf-cutter ant ( Tribe: Attini ) , which uses fresh leaves to cultivate a fungus for food in specialized gardens . Using a combination of...
Leaf-cutter ants form massive subterranean colonies containing millions of workers that harvest hundreds of kilograms of leaves each year . They use these leaves to grow a mutualistic fungus that serves as the colony's primary food source . By farming fungus in specialized garden chambers , these dominant Neotropical h...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/genomics", "genetics", "and", "genomics/microbial", "evolution", "and", "genomics", "evolutionary", "biology/microbial", "evolution", "and", "genomics", "genetics", "and", "genomics/comparative", "genomics", "evolutionary", "biology/evolutionary", ...
2010
An Insect Herbivore Microbiome with High Plant Biomass-Degrading Capacity
The cohesin complex , which is essential for sister chromatid cohesion and chromosome segregation , also inhibits resolution of sister chromatid intertwinings ( SCIs ) by the topoisomerase Top2 . The cohesin-related Smc5/6 complex ( Smc5/6 ) instead accumulates on chromosomes after Top2 inactivation , known to lead to ...
When cells divide , sister chromatids have to be segregated away from each other for the daughter cells to obtain a correct set of chromosomes . Using yeast as model organism , we have analyzed the function of the cohesin and the Smc5/6 complexes , which are essential for chromosome segregation . Cohesin is known to ho...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "mitosis", "biochemistry", "dna", "replication", "cell", "biology", "chromosome", "biology", "chromosome", "structure", "and", "function", "centromeres", "cell", "cycle", "and", "cell", "division", "genetics", "biology", "and", "life", "sciences", "dna", "cell", "pr...
2014
The Chromosomal Association of the Smc5/6 Complex Depends on Cohesion and Predicts the Level of Sister Chromatid Entanglement
Trypanosoma brucei's mitochondrial genome , kinetoplast DNA ( kDNA ) , is a giant network of catenated DNA rings . The network consists of a few thousand 1 kb minicircles and several dozen 23 kb maxicircles . Here we report that TbPIF5 , one of T . brucei's six mitochondrial proteins related to Saccharomyces cerevisiae...
Trypanosoma brucei is a protozoan parasite that causes human sleeping sickness in sub-Saharan Africa . Trypanosomes are primitive eukaryotes and they have many unusual biological features . One prominent example is their mitochondrial genome , known as kinetoplast DNA or kDNA . kDNA , with a structure unique in nature ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "molecular", "biology/dna", "replication", "microbiology/parasitology" ]
2009
TbPIF5 Is a Trypanosoma brucei Mitochondrial DNA Helicase Involved in Processing of Minicircle Okazaki Fragments
Although evolution is a multifactorial process , theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear . To what extent these two biochemical and population-scale processes are related in nature , however , is largely unknown . Viruses are an...
Viruses are an excellent system for addressing the evolutionary implications of mutation because their mutation rates vary by orders of magnitude , and their evolution takes place within the time frame of human observation . Theory posits a direct relationship between these two processes , but this has rarely been test...
[ "Abstract", "Introduction", "Results/Discussion", "Methods" ]
[ "microbial", "mutation", "virology", "population", "genetics", "biology", "evolutionary", "biology", "microbiology", "evolutionary", "genetics" ]
2012
From Molecular Genetics to Phylodynamics: Evolutionary Relevance of Mutation Rates Across Viruses
To gain insights into complex biological processes , genome-scale data ( e . g . , RNA-Seq ) are often overlaid on biochemical networks . However , many networks do not have a one-to-one relationship between genes and network edges , due to the existence of isozymes and protein complexes . Therefore , decisions must be...
Over the past two decades , systems biology approaches have permeated all fields of biology . Indeed , biological networks are commonly used for the analysis of omics datasets and to test hypotheses through computational simulations . Many of these types of studies require one to overlay omics data to a biological netw...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "genetic", "networks", "protein", "metabolism", "engineering", "and", "technology", "enzymes", "metabolic", "networks", "enzymology", "network", "analysis", "genome", "analysis", "molecular", "biology", "techniques", "research", "and", "analysis", "methods", "computer", ...
2019
Assessing key decisions for transcriptomic data integration in biochemical networks
Measureable rates of genome evolution are well documented in human pathogens but are less well understood in bacterial pathogens in the wild , particularly during and after host switches . Mycoplasma gallisepticum ( MG ) is a pathogenic bacterium that has evolved predominantly in poultry and recently jumped to wild hou...
Documenting the evolutionary changes occurring in pathogens when they switch hosts is important for understanding mechanisms of adaptation and rates of evolution . We took advantage of a novel host–pathogen system involving a bacterial pathogen ( Mycoplasma gallisepticum , or MG ) and a songbird host , the House Finch ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "zoology", "biology", "microbiology", "evolutionary", "biology", "population", "biology" ]
2012
Ultrafast Evolution and Loss of CRISPRs Following a Host Shift in a Novel Wildlife Pathogen, Mycoplasma gallisepticum
The gene regulation mechanism along the life cycle of the genus Schistosoma is complex . Small non-coding RNAs ( sncRNAs ) are essential post transcriptional gene regulation elements that affect gene expression and mRNA stability . Preliminary studies indicated that sncRNAs in schistosomal parasites are generated throu...
Schistosomiasis , a debilitating disease , caused by agents of the genus Schistosoma afflicts more than 200 million people worldwide . Schistosomes could serve as an interesting model to explore gene regulation due to its evolutional position , complex life cycle and sexual dimorphism . We previously indicated that snc...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "and", "Discussion" ]
[ "medicine", "infectious", "diseases", "schistosomiasis", "parasitic", "diseases", "helminth", "infection" ]
2011
Profiles of Small Non-Coding RNAs in Schistosoma japonicum during Development
The spiking activity of principal cells in mammalian hippocampus encodes an internalized neuronal representation of the ambient space—a cognitive map . Once learned , such a map enables the animal to navigate a given environment for a long period . However , the neuronal substrate that produces this map is transient: t...
The reliability of our memories is nothing short of remarkable . Synaptic connections between neurons appear and disappear at a rapid rate , and the resulting networks constantly change their architecture due to various forms of neural plasticity . How can the brain develop a reliable representation of the world , lear...
[ "Abstract", "Results", "Discussion", "Methods" ]
[ "learning", "cell", "physiology", "action", "potentials", "medicine", "and", "health", "sciences", "neural", "networks", "membrane", "potential", "social", "sciences", "electrophysiology", "neuroscience", "learning", "and", "memory", "cognitive", "psychology", "mathematic...
2018
Robust spatial memory maps encoded by networks with transient connections
Noninvasive imaging and tractography methods have yielded information on broad communication networks but lack resolution to delineate intralaminar cortical and subcortical pathways in humans . An important unanswered question is whether we can use the wealth of precise information on pathways from monkeys to understan...
Can the wealth of information from animal studies on the structure and connections of the cerebral cortex—the brain’s outer rim—be translated to understand neural communication in humans and disruption in brain diseases ? To address this question , we examined the prefrontal cortex , which is associated with attention ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "nervous", "system", "prefrontal", "cortex", "pervasive", "developmental", "disorders", "brain", "vertebrates", "social", "sciences", "neuroscience", "animals", "mammals", "developmental", "psychology", "animal", "models", "primate...
2018
Parallel trends in cortical gray and white matter architecture and connections in primates allow fine study of pathways in humans and reveal network disruptions in autism
All vertebrate brains develop following a common Bauplan defined by anteroposterior ( AP ) and dorsoventral ( DV ) subdivisions , characterized by largely conserved differential expression of gene markers . However , it is still unclear how this Bauplan originated during evolution . We studied the relative expression o...
According to textbooks , vertebrate brains develop from a neural tube that rapidly becomes regionalized into the forebrain ( which includes the secondary prosencephalon and diencephalon ) , midbrain , and hindbrain . These regions are then further subdivided; in particular , the diencephalon gives rise to the prethalam...
[ "Abstract", "Introduction", "Results", "Discussion", "Concluding", "remarks", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "in", "situ", "hybridization", "molecular", "probe", "techniques", "nervous", "system", "brain", "vertebrates", "animals", "developmental", "biology", "molecular", "biology", "techniques", "amphioxus", "research", "and", "analysi...
2017
Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain
Spike timing dependent plasticity ( STDP ) is believed to play an important role in shaping the structure of neural circuits . Here we show that STDP generates effective interactions between synapses of different neurons , which were neglected in previous theoretical treatments , and can be described as a sum over cont...
Plasticity between neural connections plays a key role in our ability to process and store information . One of the fundamental questions on plasticity , is the extent to which local processes , affecting individual synapses , are responsible for large scale structures of neural connectivity . Here we focus on two type...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "and", "health", "sciences", "action", "potentials", "neural", "networks", "nervous", "system", "membrane", "potential", "electrophysiology", "neuroscience", "synaptic", "plasticity", "network", "analysis", "neuronal", "plasticity", "computer", "and", "informa...
2016
Shaping Neural Circuits by High Order Synaptic Interactions
Transcription factor ( TF ) regulation is often post-translational . TF modifications such as reversible phosphorylation and missense mutations , which can act independent of TF expression level , are overlooked by differential expression analysis . Using bovine Piedmontese myostatin mutants as proof-of-concept , we pr...
Evolution , development , and cancer are governed by regulatory circuits where the central nodes are transcription factors . Consequently , there is great interest in methods that can identify the causal mutation/perturbation responsible for any circuit rewiring . The most widely available high-throughput technology , ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "physiology/muscle", "and", "connective", "tissue", "developmental", "biology/developmental", "molecular", "mechanisms", "computational", "biology/systems", "biology" ]
2009
A Differential Wiring Analysis of Expression Data Correctly Identifies the Gene Containing the Causal Mutation
Neurons display a wide range of intrinsic firing patterns . A particularly relevant pattern for neuronal signaling and synaptic plasticity is burst firing , the generation of clusters of action potentials with short interspike intervals . Besides ion-channel composition , dendritic morphology appears to be an important...
Neurons possess highly branched extensions , called dendrites , which form characteristic tree-like structures . The morphology of these dendritic arborizations can undergo significant changes in many pathological conditions . It is still poorly known , however , how alterations in dendritic morphology affect neuronal ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "neuroscience/theoretical", "neuroscience", "computational", "biology/computational", "neuroscience" ]
2010
Impact of Dendritic Size and Dendritic Topology on Burst Firing in Pyramidal Cells
The goal of influenza-like illness ( ILI ) surveillance is to determine the timing , location and magnitude of outbreaks by monitoring the frequency and progression of clinical case incidence . Advances in computational and information technology have allowed for automated collection of higher volumes of electronic dat...
In November 2008 , Google Flu Trends was launched as an open tool for influenza surveillance in the United States . Engineered as a system for early detection and daily monitoring of the intensity of seasonal influenza epidemics , Google Flu Trends uses internet search data and a proprietary algorithm to provide a surr...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2013
Reassessing Google Flu Trends Data for Detection of Seasonal and Pandemic Influenza: A Comparative Epidemiological Study at Three Geographic Scales
The HIV-specific cytotoxic T lymphocyte ( CTL ) response is a critical component in controlling viral replication in vivo , but ultimately fails in its ability to eradicate the virus . Our intent in these studies is to develop ways to enhance and restore the HIV-specific CTL response to allow long-term viral suppressio...
There is a desperate need for the development of new therapeutic strategies to eradicate HIV infection . HIV actively subverts the potent natural immune responses against it , particularly cellular cytotoxic T lymphocyte ( CTL ) responses . The development of a therapy that allows long-lived immune self-containment of ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "immune", "cells", "viral", "transmission", "and", "infection", "immunology", "microbiology", "immunodeficiency", "viruses", "adaptive", "immunity", "immunotherapy", "animal", "models", "of", "infection", "viral", "clearance", "t", "cells", "biology", "immunity", "virol...
2012
In Vivo Suppression of HIV by Antigen Specific T Cells Derived from Engineered Hematopoietic Stem Cells
Patients with Chagas disease have migrated to cities , where obesity , hypertension and other cardiac risk factors are common . The study included adult patients evaluated by the cardiology service in a public hospital in Santa Cruz , Bolivia . Data included risk factors for T . cruzi infection , medical history , phys...
Latin America is undergoing a transition from disease patterns characteristic of developing countries with high rates of infectious disease and premature deaths to a pattern more like industrialized countries , in which chronic conditions such as obesity , hypertension and diabetes are more common . Many rural resident...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "cardiovascular", "disorders" ]
2010
Chagas Cardiomyopathy in the Context of the Chronic Disease Transition
Pathogenic bacteria may modify their surface to evade the host innate immune response . Yersinia enterocolitica modulates its lipopolysaccharide ( LPS ) lipid A structure , and the key regulatory signal is temperature . At 21°C , lipid A is hexa-acylated and may be modified with aminoarabinose or palmitate . At 37°C , ...
Lipopolysaccharide ( LPS ) is one of the major surface components of Gram-negative bacteria . The LPS contains a molecular pattern recognized by the innate immune system . Not surprisingly , the modification of the LPS pattern is a virulence strategy of several pathogens to evade the innate immune system . Yersinia ent...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "bacteriology", "gram", "negative", "biology", "microbiology", "host-pathogen", "interaction", "bacterial", "biochemistry", "bacterial", "pathogens" ]
2012
Deciphering the Acylation Pattern of Yersinia enterocolitica Lipid A
Little is known about the origin and long-term evolutionary mode of retroviruses . Retroviruses can integrate into their hosts' genomes , providing a molecular fossil record for studying their deep history . Here we report the discovery of an endogenous foamy virus-like element , which we designate ‘coelacanth endogeno...
The deep history of retroviruses is still obscure . Retroviruses can leave integrated copies within their hosts' genomes , providing a fossil record for studying their long-term evolution . Endogenous forms of foamy viruses , complex retroviruses known to infect only mammalian species , appear to be extremely rare , so...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "genome", "evolution", "biology", "genomics", "evolutionary", "biology", "genetics", "and", "genomics" ]
2012
An Endogenous Foamy-like Viral Element in the Coelacanth Genome
In evolution strategies aimed at isolating molecules with new functions , screening for the desired phenotype is generally performed in vitro or in bacteria . When the final goal of the strategy is the modification of the human cell , the mutants selected with these preliminary screenings may fail to confer the desired...
We exploited the error-prone replication machinery of HIV-1 and its ability to stably introduce transgenes in human cells to develop a novel system , Retrovolution , to generate libraries of mutants of cellular genes . When libraries are screened to isolate variants that modify the phenotype of the human cell for biome...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biotechnology", "mutagenesis", "biochemistry", "genetic", "mutation", "molecular", "cell", "biology", "mutation", "types", "nucleic", "acids", "proteins", "genetics", "biology", "genetics", "and", "genomics", "genetic", "engineering", "gene", "function" ]
2012
Retrovolution: HIV–Driven Evolution of Cellular Genes and Improvement of Anticancer Drug Activation
Much of the research on cannabinoids ( CBs ) has focused on their effects at the molecular and synaptic level . However , the effects of CBs on the dynamics of neural circuits remains poorly understood . This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral ...
Research into cannabinoids ( CBs ) over the last several decades has found that they induce a large variety of oftentimes opposing effects on various neuronal receptors and processes . Due to this plethora of effects , disentangling how CBs influence neuronal circuits has proven challenging . This paper contributes to ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "and", "health", "sciences", "action", "potentials", "nervous", "system", "drugs", "membrane", "potential", "electrophysiology", "neuroscience", "ganglion", "cells", "interneurons", "pharmacology", "animal", "management", "animal", "performance", "cannabinoids",...
2017
Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3
Surface recognition and penetration are critical steps in the infection cycle of many plant pathogenic fungi . In Magnaporthe oryzae , cAMP signaling is involved in surface recognition and pathogenesis . Deletion of the MAC1 adenylate cyclase gene affected appressorium formation and plant infection . In this study , we...
In Magnaporthe oryzae , cAMP signaling is known to play an important role in surface recognition and plant penetration . The Mac1 adenylate cyclase is essential for plant infection . To better understand Mac1 activation mechanisms , in this study we used the affinity purification approach to identify proteins that are ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "mycology", "plant", "microbiology", "biology", "microbiology" ]
2012
The Cyclase-Associated Protein Cap1 Is Important for Proper Regulation of Infection-Related Morphogenesis in Magnaporthe oryzae
The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years . The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protei...
The prevalence of natural selection at the DNA level remains a controversial issue in evolutionary biology . In particular , estimates of the proportion of adaptive amino acid changes ( α ) vary greatly between taxa , being 50% or more in bacteria and fruit flies , but at most 13% in hominids . Here , we infer the freq...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "evolutionary", "biology", "genetics", "and", "genomics" ]
2010
Evidence for Pervasive Adaptive Protein Evolution in Wild Mice
Mucosal transmission of HIV is inefficient . The virus must breach physical barriers before it infects mucosal CD4+ T cells . Low-level viral replication occurs initially in mucosal CD4+ T cells , but within days high-level replication occurs in Peyer's patches , the gut lamina propria and mesenteric lymph nodes . Unde...
In the first days following sexual transmission , HIV replication occurs initially at relatively low levels in mucosal tissues because of a paucity of CD4+ T cell targets for the virus to infect . After a period of days , virus accesses specific gut tissues that are enriched in activated CD4+ T cells , where near-expon...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "virology/virus", "evolution", "and", "symbiosis", "virology/vaccines", "virology/immunodeficiency", "viruses", "virology", "infectious", "diseases/viral", "infections", "infectious", "diseases/sexually", "transmitted", "diseases", "virology/host", "invasion", "and", "cell", "e...
2011
The Genotype of Early-Transmitting HIV gp120s Promotes α4β7 –Reactivity, Revealing α4β7+/CD4+ T cells As Key Targets in Mucosal Transmission
Breaks at common fragile sites ( CFS ) are a recognized source of genome instability in pre-neoplastic lesions , but how such checkpoint-proficient cells escape surveillance and continue cycling is unknown . Here we show , in lymphocytes and fibroblasts , that moderate replication stresses like those inducing breaks at...
Accurate genome duplication is crucial at each cell generation to maintain genetic information . However , replication forks routinely face lesions on the DNA template and/or travel through sequences intrinsically difficult to replicate , such as common fragile sites ( CFS ) . To help the fork to proceed , the cells ha...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "mutagenesis", "cellular", "stress", "responses", "cancer", "genetics", "genetic", "mutation", "dna", "replication", "nucleic", "acids", "genetics", "dna", "dna", "repair", "biology", "dna", "recombination", "molecular", "cell", "biology" ]
2013
Stepwise Activation of the ATR Signaling Pathway upon Increasing Replication Stress Impacts Fragile Site Integrity
Unlike for other retroviruses , only a few host cell factors that aid the replication of foamy viruses ( FVs ) via interaction with viral structural components are known . Using a yeast-two-hybrid ( Y2H ) screen with prototype FV ( PFV ) Gag protein as bait we identified human polo-like kinase 2 ( hPLK2 ) , a member of...
Viruses are masters at exploiting host cell machineries for their replication . For human immunodeficiency virus type 1 ( HIV-1 ) , the best-studied representative of the Orthoretrovirinae subfamily from the genus lentiviruses , numerous important virus-host interactions have been described . In contrast , only a few c...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "phosphorylation", "protein", "interactions", "viral", "transmission", "and", "infection", "293t", "cells", "cell", "cycle", "and", "cell", "division", "biological", "cultures", "cell", "processes", "microbiology", "viral", "structure", "research", "and", "analysis", ...
2016
Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration
Transcription factors are a main component of gene regulation as they activate or repress gene expression by binding to specific binding sites in promoters . The de-novo discovery of transcription factor binding sites in target regions obtained by wet-lab experiments is a challenging problem in computational biology , ...
Binding of transcription factors to promoters of genes , and subsequent enhancement or repression of transcription , is one of the main steps of transcriptional gene regulation . Direct or indirect wet-lab experiments allow the identification of approximate regions potentially bound or regulated by a transcription fact...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results/Discussion" ]
[ "developmental", "biology", "computational", "biology/sequence", "motif", "analysis", "computational", "biology/transcriptional", "regulation", "cell", "biology/cell", "signaling", "genetics", "and", "genomics/plant", "genetics", "and", "gene", "expression", "molecular", "bio...
2011
De-Novo Discovery of Differentially Abundant Transcription Factor Binding Sites Including Their Positional Preference
The Notch signaling pathway controls a large number of processes during animal development and adult homeostasis . One of the conserved post-translational modifications of the Notch receptors is the addition of an O-linked glucose to epidermal growth factor-like ( EGF ) repeats with a C-X-S-X- ( P/A ) -C motif by Prote...
In multi-cellular organisms , neighboring cells need to communicate with each other to ensure proper cell fate decisions and differentiation . Signaling through the Notch receptors is the primary means by which local cell-cell communication is accomplished in animals . Given the broad usage of Notch signaling in animal...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "animal", "models", "biochemistry", "developmental", "biology", "pattern", "formation", "cell", "fate", "determination", "animal", "genetics", "model", "organisms", "organism", "development", "drosophila", "melanogaster", "signaling", "molecular", "development", "gene", "...
2013
Negative Regulation of Notch Signaling by Xylose
This study systematically reviews the literature on the occurrence , incidence and case fatality rate ( CFR ) of invasive nontyphoidal Salmonella ( iNTS ) disease in Africa from 1966 to 2014 . Data on the burden of iNTS disease in Africa are sparse and generally have not been aggregated , making it difficult to describ...
Although Salmonella are a common global cause of mild gastro-intestinal illness that usually presents with self-limiting diarrhoea , the invasive nontyphoidal form of Salmonella disease manifests as bacteraemia which often presents only with fever . If left untreated , iNTS disease often results in death . iNTS disease...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "body", "fluids", "pathology", "and", "laboratory", "medicine", "pathogens", "geographical", "locations", "tropical", "diseases", "database", "searching", "microbiology", "parasitic", "diseases", "health", "care", "retroviruses", ...
2017
A Systematic Review of the Incidence, Risk Factors and Case Fatality Rates of Invasive Nontyphoidal Salmonella (iNTS) Disease in Africa (1966 to 2014)
Seeing the direction of motion is essential for survival of all sighted animals . Consequently , nerve cells that respond to visual stimuli moving in one but not in the opposite direction , so-called ‘direction-selective’ neurons , are found abundantly . In general , direction selectivity can arise by either signal amp...
Seeing the direction of motion is essential for survival of all sighted animals . Consequently , nerve cells that respond preferentially to visual stimuli moving in a certain direction are found abundantly . However , directional information is not represented at the level of single photoreceptors but rather has to be ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "and", "health", "sciences", "engineering", "and", "technology", "motion", "detectors", "signal", "processing", "membrane", "potential", "electrophysiology", "light", "neuroscience", "signal", "filtering", "electromagnetic", "radiation", "luminance", "visible", ...
2018
A biophysical mechanism for preferred direction enhancement in fly motion vision
Many signaling proteins and transcription factors that induce and pattern organs have been identified , but relatively few of the downstream effectors that execute morphogenesis programs . Because such morphogenesis genes may function in many organs and developmental processes , mutations in them are expected to be ple...
Elucidating the genetic programs that control formation and maintenance of body organs is a central goal of developmental biology , and understanding how these programs go awry in disease has important implications for medicine . Many such organogenesis genes have been identified , but most are early-acting “patterning...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "organism", "development", "genetic", "screens", "genetics", "organogenesis", "biology", "morphogenesis", "genetics", "and", "genomics" ]
2011
A Systematic Screen for Tube Morphogenesis and Branching Genes in the Drosophila Tracheal System
To characterize the consequences of eliminating essential functions needed for peptidoglycan synthesis , we generated deletion mutations of Acinetobacter baylyi by natural transformation and visualized the resulting microcolonies of dead cells . We found that loss of genes required for peptidoglycan precursor synthesis...
Although essential genes control the most basic functions of bacterial life , they are difficult to study genetically because mutants lacking the functions die . We have developed a simple procedure for creating bacteria in which different essential genes have been completely deleted , making it possible to analyze the...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "antimicrobials", "deletion", "mutation", "medicine", "and", "health", "sciences", "evolutionary", "biology", "cell", "cycle", "and", "cell", "division", "drugs", "cell", "processes", "population", "genetics", "microbiology", "precursor", "cells", "gene", "pool", "phy...
2019
Essential gene deletions producing gigantic bacteria
Homologous recombination is a universal mechanism that allows repair of DNA and provides support for DNA replication . Homologous recombination is therefore a major pathway that suppresses non-homology-mediated genome instability . Here , we report that recovery of impeded replication forks by homologous recombination ...
The appropriate transmission of genetic material during successive cell divisions requires the accurate duplication and segregation of parental DNA . The semi-conservative replication of chromosomes during S-phase is highly accurate and prevents accumulation of deleterious mutations . However , during each round of dup...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cellular", "stress", "responses", "microbiology", "mitosis", "model", "organisms", "dna", "replication", "dna", "dna", "synthesis", "mycology", "chromosome", "biology", "schizosaccharomyces", "pombe", "biology", "molecular", "biology", "yeast", "cell", "biology", "nucl...
2012
Recovery of Arrested Replication Forks by Homologous Recombination Is Error-Prone
In the present study , we assessed the annual screening coverage ( i . e . , the percentage of dogs that are screened for anti-Leishmania antibodies annually ) in the municipality of Sobral , Ceará state , Brazil . Data on the number of dogs screened during 2008−2017 ( except 2010 ) were obtained from the Centre for Zo...
The euthanasia of Leishmania-seropositive dogs has been recommended for controlling human visceral leishmaniasis ( VL ) in some countries where this zoonosis is endemic . We assessed the annual screening coverage ( i . e . , the percentage of dogs living in a given area that are screened for anti-Leishmania antibodies ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "kala-azar", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "tropical", "diseases", "geographical", "locations", "vertebrates", "parasitic", "diseases", "dogs", "animals", "mammals", "parasitic", "protozoans", "protozoans", "leishma...
2019
Failure of the dog culling strategy in controlling human visceral leishmaniasis in Brazil: A screening coverage issue?
Type 2 immune responses are essential in protection against intestinal helminth infections . In this study we show that IL-22 , a cytokine important in defence against bacterial infections in the intestinal tract , is also a critical mediator of anti-helminth immunity . After infection with Nippostrongylus brasiliensis...
Intestinal helminth ( worm ) infections are some of the most common parasite infections in the world . Immunity to worm infection is dependent on the production of Type 2 cytokines , such as IL-4 and IL-13 , and the induction of mucosal defence mechanisms including production of mucus by intestinal goblet cells . Here ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "and", "Discussion" ]
[]
2013
IL-22 Mediates Goblet Cell Hyperplasia and Worm Expulsion in Intestinal Helminth Infection
Interspecific and intervarietal hybridization may contribute to the biological diversity of fungal populations . Cryptococcus neoformans is a pathogenic yeast and the most common fungal cause of meningitis in patients with AIDS . Most patients are infected with either of the two varieties of C . neoformans , designated...
Hybridization between individuals of different species or varieties is common among fungi . However , the impact of hybridization on the evolution of pathogenic fungi is unresolved . Several hybrids of phytopathogenic fungi exhibit expanded host ranges . To our knowledge , this report is the first description of increa...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods", "Supporting", "Information" ]
[ "yeast", "and", "fungi", "microbiology", "evolutionary", "biology", "molecular", "biology" ]
2007
Many Globally Isolated AD Hybrid Strains of Cryptococcus neoformans Originated in Africa
Netrin is a key axon guidance cue that orients axon growth during neural circuit formation . However , the mechanisms regulating netrin and its receptors in the extracellular milieu are largely unknown . Here we demonstrate that in Caenorhabditis elegans , LON-2/glypican , a heparan sulfate proteoglycan , modulates UNC...
During the development of the nervous system , migrating axons are guided as they navigate through complex environments to reach their target destinations . These directed migrations are essential to ensure the proper wiring and function of the nervous system and are instructed by guidance cues and receptors . There is...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Glypican Is a Modulator of Netrin-Mediated Axon Guidance
The elongation phase of transcription by RNA Polymerase II ( Pol II ) involves numerous events that are tightly coordinated , including RNA processing , histone modification , and chromatin remodeling . RNA splicing factors are associated with elongating Pol II , and the interdependent coupling of splicing and elongati...
mRNA splicing can occur co-transcriptionally; i . e . , splicing occurs as the RNA emerges from the RNA Polymerase II holoenzyme during transcription elongation . Recent studies suggest that defective splicing can cause defective transcription elongation , suggesting an interdependency of the two mechanisms . The C . e...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "phosphorylation", "invertebrates", "rna", "interference", "caenorhabditis", "animals", "dna", "transcription", "animal", "models", "developmental", "biology", "caenorhabditis", "elegans", "model", "organisms", "epigenetics", "embryos", "research", "and", "analysis", "metho...
2016
A Conserved Nuclear Cyclophilin Is Required for Both RNA Polymerase II Elongation and Co-transcriptional Splicing in Caenorhabditis elegans
The pathways that trigger exacerbated immune reactions in leprosy could be determined by genetic variations . Here , in a prospective approach , both genetic and non-genetic variables influencing the amount of time before the development of reactional episodes were studied using Kaplan–Meier survival curves , and the g...
Leprosy reactions are abrupt inflammatory episodes that can occur before , during or after treatment . Although reactional episodes are the main cause of physical disabilities in patients , there are few genetic studies evaluating this outcome . We studied the influence of both risk factors and genetic markers in lepro...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "innate", "immune", "system", "medicine", "and", "health", "sciences", "immune", "physiology", "cytokines", "pathology", "and", "laboratory", "medicine", "enzyme-linked", "immunoassays", "immunology", "tropical", "diseases", "variant", "genotypes", "genetic", "mapping", ...
2017
Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy
Rift Valley fever ( RVF ) is a viral mosquito-borne disease with the potential for global expansion , causes hemorrhagic fever , and has a high case fatality rate in young animals and in humans . Using a cross-sectional community-based study design , we investigated the knowledge , attitudes and practices of people liv...
Rift Valley fever ( RVF ) , is a neglected , emerging , mosquito-borne disease that has caused outbreaks in Africa and the Arabian Peninsula . RVF outbreaks have a severe negative impact on livestock , human health and economy , placing further demands on communities already experiencing high levels of poverty . We bel...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]
[ "livestock", "medicine", "and", "health", "sciences", "tropical", "diseases", "geographical", "locations", "sudan", "rift", "valley", "fever", "neglected", "tropical", "diseases", "infectious", "disease", "control", "veterinarians", "africa", "veterinary", "science", "v...
2017
The One Health approach to identify knowledge, attitudes and practices that affect community involvement in the control of Rift Valley fever outbreaks
A role for variant histone H2A . Z in gene expression is now well established but little is known about the mechanisms by which it operates . Using a combination of ChIP–chip , knockdown and expression profiling experiments , we show that upon gene induction , human H2A . Z associates with gene promoters and helps in r...
DNA in living cells is packaged into chromatin by histones and non-histone proteins . This packaging is very dynamic , allowing the controlled access of regulatory proteins such as transcription factors to DNA . Most chromatin is packaged with so-called canonical histones; namely H2A , H2B , H3 , and H4 . In some regio...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "molecular", "biology/histone", "modification", "cell", "biology/gene", "expression", "molecular", "biology/transcription", "initiation", "and", "activation", "genetics", "and", "genomics/gene", "expression", "genetics", "and", "genomics/functional", "genomics", "molecular", ...
2009
The Euchromatic and Heterochromatic Landscapes Are Shaped by Antagonizing Effects of Transcription on H2A.Z Deposition
Systematic analysis of synthetic lethality ( SL ) constitutes a critical tool for systems biology to decipher molecular pathways . The most accepted mechanistic explanation of SL is that the two genes function in parallel , mutually compensatory pathways , known as between-pathway SL . However , recent genome-wide anal...
Organizing gene functions into molecular pathways is a major challenge in biology . The observation that two viable gene mutations become lethal when combined as a double mutant has been developed into a major genetic tool called synthetic lethality . The classic interpretation of synthetic lethality stipulates that th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "biology" ]
2013
Synthetic Lethality between Gene Defects Affecting a Single Non-essential Molecular Pathway with Reversible Steps
In areas where health resources are limited , community participation in the recognition and reporting of disease hazards is critical for the identification of outbreaks . This is particularly true for zoonotic diseases such as monkeypox that principally affect people living in remote areas with few health services . H...
Human monkeypox is a potentially severe illness that begins with a high fever soon followed by the development of a smallpox-like rash . Both monkeypox and smallpox are caused by infection with viruses in the genus Orthopoxvirus . But smallpox , which only affected humans , has been eradicated , whereas monkeypox conti...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "infectious", "diseases", "public", "health", "and", "epidemiology", "zoonoses", "skin", "infections", "smallpox", "global", "health", "neglected", "tropical", "diseases", "viral", "diseases", "public", "health" ]
2011
Assessing the Effectiveness of a Community Intervention for Monkeypox Prevention in the Congo Basin
Onchocerca volvulus is the causative agent of onchocerciasis , or “river blindness” . Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years , and recently there have been reports of poor parasitological responses to the drug . Should ivermectin resistance be developing , it would have a genet...
Onchocerca volvulus is the causative agent of onchocerciasis , or “river blindness” . Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years , and recently there have been reports of poor parasitological responses to the drug and evidence of drug resistance . Drug resistance has a genetic basi...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "pharmacology/drug", "resistance", "genetics", "and", "genomics/population", "genetics" ]
2007
Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin Treatment
Although bubonic plague is an endemic zoonosis in many countries around the world , the factors responsible for the persistence of this highly virulent disease remain poorly known . Classically , the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible roden...
Bubonic plague , known to have marked human history by three deadly pandemics , is an infectious disease which mainly circulates in wild rodent populations and is transmitted by fleas . Although this disease can be quickly lethal to its host , it has persisted on long-term in many rodent populations around the world . ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "computer", "science", "evolutionary", "ecology", "computer", "modeling", "theoretical", "biology", "ecology", "population", "modeling", "epidemiology", "infectious", "disease", "epidemiology", "theoretical", "ecology", "population", "biology", "infectious", "disease", "mod...
2013
Host Resistance, Population Structure and the Long-Term Persistence of Bubonic Plague: Contributions of a Modelling Approach in the Malagasy Focus
Identifying the forces that drive proteins to misfold and aggregate , rather than to fold into their functional states , is fundamental to our understanding of living systems and to our ability to combat protein deposition disorders such as Alzheimer's disease and the spongiform encephalopathies . We report here the fi...
In order to carry out their biological functions , most proteins fold into well-defined conformations known as native states . Failure to fold , or to remain folded correctly , may result in misfolding and aggregation , which are processes associated with a wide range of highly debilitating , and so far incurable , hum...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "biophysic", "al", "simulations", "biology", "computational", "biology" ]
2011
Inversion of the Balance between Hydrophobic and Hydrogen Bonding Interactions in Protein Folding and Aggregation
Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions . Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signalin...
The diversity of allosteric mechanisms in the Hsp70 proteins could range from modulation of the inter-domain interactions and conformational dynamics to fine-tuning of the Hsp70 interactions with co-chaperones . The goal of this study is to present a systematic computational analysis of the dynamic and evolutionary fac...
[ "Abstract", "Introduction", "Results", "and", "Discussion", "Conclusions", "Materials", "and", "Methods" ]
[ "allosteric", "regulation", "crystal", "structure", "protein", "interaction", "networks", "condensed", "matter", "physics", "enzymology", "network", "analysis", "chaperone", "proteins", "protein", "structure", "dna", "dna", "structure", "crystallography", "enzyme", "chemi...
2017
Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication
A major challenge to developing a successful HIV vaccine is the vast diversity of viral sequences , yet it is generally assumed that an epitope conserved between different strains will be recognised by responding T-cells . We examined whether an invariant HLA-B8 restricted Nef90–97 epitope FL8 shared between five high ...
One of the greatest challenges to developing an effective HIV vaccine is the ability of HIV to rapidly alter its viral sequence . Such variation in viral sequence enables the virus to frequently evade recognition by the host immune system . To counteract this problem , there has been increasing interest in developing H...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "immunology/antigen", "processing", "and", "recognition", "infectious", "diseases/hiv", "infection", "and", "aids", "virology/immune", "evasion", "immunology/immunity", "to", "infections", "virology/host", "antiviral", "responses" ]
2011
The Antiviral Efficacy of HIV-Specific CD8+ T-Cells to a Conserved Epitope Is Heavily Dependent on the Infecting HIV-1 Isolate
Understanding the principles underlying the plasticity of signal transduction networks is fundamental to decipher the functioning of living cells . In Myxococcus xanthus , a particular chemosensory system ( Frz ) coordinates the activity of two separate motility systems ( the A- and S-motility systems ) , promoting mul...
Deciphering the circuit design of signal transduction networks is a fundamental question in cell biology . This task is challenging because many pathways are branched and control multiple cellular processes in response to one or several environmental signals . Studying pathway diversification in bacteria could be a pow...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Evolution and Design Governing Signal Precision and Amplification in a Bacterial Chemosensory Pathway
Tsetse flies serve as biological vectors for several species of African trypanosomes . In order to survive , proliferate and establish a midgut infection , trypanosomes must cross the tsetse fly peritrophic matrix ( PM ) , which is an acellular gut lining surrounding the blood meal . Crossing of this multi-layered stru...
African trypanosomes are transmitted by the haematophagous tsetse vector . For transmission to occur , bloodmeal ingested trypanosomes must overcome numerous barriers imposed by the fly . The first obstacle is the crossing of peritrophic matrix ( PM ) , a cell-free structure that protects the midgut epithelial cells fr...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "and", "Discussion" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "microbiology", "parasitic", "protozoans", "animals", "parasitology", "glossina", "protozoans", "tsetse", "fly", "epidemiology", "pathogenesis", "disease", "vectors", "...
2014
An Investigation into the Protein Composition of the Teneral Glossina morsitans morsitans Peritrophic Matrix
Dengue virus ( DENV ) is the leading cause of mosquito-borne viral illness and death in humans . Like many viruses , DENV has evolved potent mechanisms that abolish the antiviral response within infected cells . Nevertheless , several in vivo studies have demonstrated a key role of the innate immune response in control...
Viral recognition by the host often triggers an antiviral state , which suppresses viral spread and imparts adaptive immunity . Like many viruses , dengue virus ( DENV ) defeats the host-sensing pathway within infected cells . However , in vivo studies have demonstrated a key role of innate immunity in controlling DENV...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "innate", "immune", "system", "immunity", "virology", "emerging", "viral", "diseases", "biology", "and", "life", "sciences", "immunology", "microbiology", "immune", "system" ]
2014
Sensing of Immature Particles Produced by Dengue Virus Infected Cells Induces an Antiviral Response by Plasmacytoid Dendritic Cells
Pathogens that traffic in blood , lymphatics , or interstitial fluids must adopt strategies to evade innate immune defenses , notably the complement system . Through recruitment of host regulators of complement to their surface , many pathogens are able to escape complement-mediated attack . The Lyme disease spirochete...
The human complement system is a connected network of blood proteins capable of recognizing and eliminating microbial intruders . To avoid the destructive force of complement activation , many microorganisms that enter the bloodstream express molecules that disrupt key steps of the complement cascade by interacting wit...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "complement", "system", "medicine", "and", "health", "sciences", "immune", "physiology", "pathology", "and", "laboratory", "medicine", "zymogens", "enzymes", "pathogens", "immunology", "microbiology", "enzymology", "enzyme", "inhibitors", "bacteria", "bacterial", "pathoge...
2016
Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex
Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems . Such responses emerge in higher brain areas , thereby suggesting that they occur by integrating afferent input . However , the mechanisms by which such integration occurs are...
We provide the first experimental evidence showing that midbrain electrosensory neurons in the weakly electric fish species Apteronotus leptorhynchus can respond in an invariant manner to the heterogeneous stimulus waveforms associated with natural electrocommunication stimuli . Interestingly , hindbrain neuron populat...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2015
Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli
Translational errors occur at high rates , and they influence organism viability and the onset of genetic diseases . To investigate how organisms mitigate the deleterious effects of protein synthesis errors during evolution , a mutant yeast strain was engineered to translate a codon ambiguously ( mistranslation ) . It ...
Although fidelity of information transfer has a substantial impact on cellular survival , many steps in protein production are strikingly error-prone . Such errors during protein synthesis can have a substantial influence on viability and the onset of genetic diseases . These considerations raise the question as to how...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Evolution of Robustness to Protein Mistranslation by Accelerated Protein Turnover
Arthropod-borne flaviviruses cause life-threatening diseases associated with endothelial hyperpermeability and vascular leak . We recently found that vascular leak can be triggered by dengue virus ( DENV ) non-structural protein 1 ( NS1 ) via the disruption of the endothelial glycocalyx-like layer ( EGL ) . However , t...
Vascular leak is a hallmark of severe dengue disease . Recently , our group revealed a critical role for NS1 in induction of endothelial hyperpermeability and vascular leakage in an endothelial cell-intrinsic manner . However , the upstream pathway triggered by NS1 , as well as the molecular determinants of NS1 require...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "binding", "cell", "physiology", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "chemical", "compounds", "gene", "regulation", "endothelial", "cells", "pathogens", "cell", "processes", "salts", "microbiology", "epithelial"...
2019
Endocytosis of flavivirus NS1 is required for NS1-mediated endothelial hyperpermeability and is abolished by a single N-glycosylation site mutation
Blood flukes of the genus Schistosoma are platyhelminth parasites that infect 200 million people worldwide . Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction . A network of proteolytic enzymes ( proteases ) facilitates hydrolysis of host hemoglobin and serum protei...
Parasitic infection caused by blood flukes of the genus Schistosoma is a major global health problem . More than 200 million people are infected . Identifying and characterizing the constituent enzymes of the parasite's biochemical pathways should reveal opportunities for developing new therapies ( i . e . , vaccines ,...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "biochemistry", "infectious", "diseases", "infectious", "diseases/neglected", "tropical", "diseases", "computational", "biology/comparative", "sequence", "analysis", "biochemistry/protein", "chemistry", "infectious", "diseases/helminth", "infections", "biochemistry/bioinformatics", ...
2009
SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni
The establishment of precise neuronal connectivity during development is critical for sensing the external environment and informing appropriate behavioral responses . In the visual system , many connections are organized topographically , which preserves the spatial order of the visual scene . The superior colliculus ...
In order to process sensory stimuli , precise connections must be established between sensory neurons during development . In the visual system , many connections are organized topographically , such that neighboring neurons monitor adjacent regions of space . In the superior colliculus ( SC ) , converging topographic ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "and", "health", "sciences", "topographic", "maps", "ocular", "anatomy", "social", "sciences", "neuroscience", "simulation", "and", "modeling", "ganglion", "cells", "nerve", "fibers", "vision", "neuronal", "dendrites", "research", "and", "analysis", "metho...
2016
Novel Models of Visual Topographic Map Alignment in the Superior Colliculus
Germ line specification is a crucial step in the life cycle of all organisms . For sexual plant reproduction , the megaspore mother cell ( MMC ) is of crucial importance: it marks the first cell of the plant “germline” lineage that gets committed to undergo meiosis . One of the meiotic products , the functional megaspo...
Germline specification is a key step in sexual reproduction . In plants , the reproductive lineage or “germline” doesn't arise early in development , as it does in animals; rather , the germline is specified during flower development . In the female reproductive organs of the flower , a single sporophytic cell in each ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "plant", "science", "model", "organisms", "plant", "biology", "genetics", "biology", "genomics", "molecular", "cell", "biology", "genetics", "and", "genomics" ]
2011
Transcriptome Analysis of the Arabidopsis Megaspore Mother Cell Uncovers the Importance of RNA Helicases for Plant Germline Development
LRRK2 plays an important role in Parkinson's disease ( PD ) , but its biological functions are largely unknown . Here , we cloned the homolog of human LRRK2 , characterized its expression , and investigated its biological functions in zebrafish . The blockage of zebrafish LRRK2 ( zLRRK2 ) protein by morpholinos caused ...
Parkinson's disease ( PD ) is a degenerative disease of the brain ( central nervous system ) that often impairs motor skills , speech , and other functions . PD was long thought to be caused by environmental factors , but the discovery of several gene mutations in the patients ( mostly with familial form of PD ) clearl...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/disease", "models", "developmental", "biology/neurodevelopment", "neurological", "disorders/movement", "disorders" ]
2010
Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect
Cell autonomous cancer dependencies are now routinely identified using CRISPR loss-of-function viability screens . However , a bias exists that makes it difficult to assess the true essentiality of genes located in amplicons , since the entire amplified region can exhibit lethal scores . These false-positive hits can e...
Cancer vulnerabilities have been identified by systematically disrupting individual genes in cancer cells and observing the resulting effect on cell proliferation . In recent years , a new gene editing technique called CRISPR has made it easier and cheaper to disrupt genes by precisely and completely suppressing the fu...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "biotechnology", "genome", "engineering", "cancer", "detection", "and", "diagnosis", "medicine", "and", "health", "sciences", "engineering", "and", "technology", "synthetic", "biology", "genomic", "library", "screening", "health", "care", "crispr", "synthetic", "bioengi...
2018
Correction of copy number induced false positives in CRISPR screens
Birds have a unique bone physiology , due to the demands placed on them through egg production . In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling . We take advantage of the fact that bone traits have diverged massively dur...
In this work we seek to further the understanding of bone genetics by mapping bone traits and gene expression in the chicken . Bone in female birds is special due to egg production . In this study , we combine the genetic mapping of bone traits with bone gene expression to find candidate quantitative trait genes that e...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Genetic Regulation of Bone Metabolism in the Chicken: Similarities and Differences to Mammalian Systems
Genome-wide association studies ( GWAS ) have discovered thousands loci associated with disease risk and quantitative traits , yet most of the variants responsible for risk remain uncharacterized . The majority of GWAS-identified loci are enriched for non-coding single-nucleotide polymorphisms ( SNPs ) and defining the...
The promise of effective personalized medicine is dependent upon the ability to identify genetic variants in the population that influence disease risk and then use this information to accurately predict the likelihood of disease incidence for individual patients . High-risk individuals may be entered into clinical tra...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "binding", "genome-wide", "association", "studies", "cell", "physiology", "medicine", "and", "health", "sciences", "breast", "tumors", "chemical", "characterization", "cancers", "and", "neoplasms", "oncology", "genome", "analysis", "sequence", "motif", "analysis...
2017
Identification of breast cancer associated variants that modulate transcription factor binding
Curation and interpretation of copy number variants identified by genome-wide testing is challenged by the large number of events harbored in each personal genome . Conventional determination of phenotypic relevance relies on patterns of higher frequency in affected individuals versus controls; however , an increasing ...
Improvements in sequencing and microarray technologies have increased the resolution and scope of genetic testing . As a result , millions of variations are identified in each personal genome of unrelated individuals . In the context of testing for genetic diseases , identifying the variant or variants contributing to ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
Fusion of Large-Scale Genomic Knowledge and Frequency Data Computationally Prioritizes Variants in Epilepsy
The Sec1/munc18 protein family is essential for vesicle fusion in eukaryotic cells via binding to SNARE proteins . Protein kinase C modulates these interactions by phosphorylating munc18a thereby reducing its affinity to one of the central SNARE members , syntaxin-1a . The established hypothesis is that the reduced aff...
Protein phosphorylation plays a significant regulatory role in multi-component systems engaged in signal transduction or coordination of cellular processes , by activating or deactivating proteins . The potential of phosphorylation to induce substantial conformational changes in proteins , thereby changing their affini...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "neuroscience/neuronal", "signaling", "mechanisms", "neuroscience/theoretical", "neuroscience", "biophysics/theory", "and", "simulation", "biochemistry/theory", "and", "simulation" ]
2011
Dynamic Conformational Changes in MUNC18 Prevent Syntaxin Binding
Type III secretion systems ( T3SSs ) are specialized macromolecular machines critical for bacterial virulence , and allowing the injection of bacterial effectors into host cells . The T3SS-dependent injection process requires the prior insertion of a protein complex , the translocon , into host cell membranes consistin...
Enteropathogenic Escherichia coli ( EPEC ) is an important diarrheal pathogen responsible for infant diarrhoea associated with significant morbidity and mortality rates in developing countries . Upon ingestion EPEC colonizes the intestinal mucosa , causing characteristic lesions on enterocytes . Using a type III secret...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
The Serine Protease EspC from Enteropathogenic Escherichia coli Regulates Pore Formation and Cytotoxicity Mediated by the Type III Secretion System
In the United States , the introduction of the heptavalent pneumococcal conjugate vaccine ( PCV ) largely eliminated vaccine serotypes ( VT ) ; non-vaccine serotypes ( NVT ) subsequently increased in carriage and disease . Vaccination also disrupts the composition of the pneumococcal pangenome , which includes mobile g...
Pneumococcal disease caused by the bacteria Streptococcus pneumoniae remains a significant cause of morbidity and mortality despite the existence of an effective vaccine . This is because the vaccines only target a small proportion of the total pneumococcal population . Introduction of vaccine in the United States remo...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "taxonomy", "medicine", "and", "health", "sciences", "ecology", "and", "environmental", "sciences", "immune", "physiology", "immunology", "population", "genetics", "antigenic", "variation", "vaccines", "phylogenetics", "data", "management", "population", "biology", "infec...
2018
The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome
A long-standing goal in artificial intelligence is creating agents that can learn a variety of different skills for different problems . In the artificial intelligence subfield of neural networks , a barrier to that goal is that when agents learn a new skill they typically do so by losing previously acquired skills , a...
A long-standing goal in artificial intelligence ( AI ) is creating computational brain models ( neural networks ) that learn what to do in new situations . An obstacle is that agents typically learn new skills only by losing previously acquired skills . Here we test whether such forgetting is reduced by evolving modula...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2015
Neural Modularity Helps Organisms Evolve to Learn New Skills without Forgetting Old Skills
Interactions between commensal fungi and gut immune system are critical for establishing colonic homeostasis . Here we found that mice deficient in Dectin-3 ( Clec4d-/- ) , a C-type lectin receptor that senses fungal infection , were more susceptible to dextran sodium sulfate ( DSS ) -induced colitis compared with wild...
C-type lectin receptors ( CLRs ) comprise a diverse family of soluble and trans-membrane proteins that function as pattern recognition receptors ( PRRs ) . Dectin-3 ( also known as MCL/CLECSF8/Clec4d ) , a myeloid cell-specific CLR family member , could recognize bacterial and fungal components and induce intracellular...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "blood", "cells", "innate", "immune", "system", "medicine", "and", "health", "sciences", "immune", "physiology", "cytokines", "immune", "cells", "pathology", "and", "laboratory", "medicine", "immunology", "colitis", "developmental", "biology", "fungi", "signs", "and",...
2016
Dectin-3 Deficiency Promotes Colitis Development due to Impaired Antifungal Innate Immune Responses in the Gut
Visceral leishmaniasis belongs to the list of neglected tropical diseases and is considered a public health problem worldwide . Spatial correlation between the occurrence of the disease in humans and high rates of canine infection suggests that in the presence of the vector , canine visceral leishmaniasis is the key fa...
Visceral leishmaniasis is listed as a neglected tropical disease and is considered a public health problem worldwide . The disease has been documented since 1885 , the first case being reported in India . After over 120 years , the incidence of the disease remains high despite control strategies implemented . In areas ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "population", "modeling", "epidemiology", "infectious", "disease", "epidemiology", "disease", "dynamics", "population", "dynamics", "population", "biology", "infectious", "disease", "modeling", "biology", "computational", "biology" ]
2013
Culling Dogs in Scenarios of Imperfect Control: Realistic Impact on the Prevalence of Canine Visceral Leishmaniasis
Sensory neuron diversity is required for organisms to decipher complex environmental cues . In Drosophila , the olfactory environment is detected by 50 different olfactory receptor neuron ( ORN ) classes that are clustered in combinations within distinct sensilla subtypes . Each sensilla subtype houses stereotypically ...
Drosophila uses 50 different olfactory receptor neuron ( ORN ) classes that are clustered in combinations within distinct sensilla subtypes to decipher a complex chemical environment . Each sensilla subtype houses 1–4 ORN identities that arise through asymmetric divisions from a single multipotent sensory organ precurs...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2016
A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity
Talin serves an essential function during integrin-mediated adhesion in linking integrins to actin via the intracellular adhesion complex . In addition , the N-terminal head domain of talin regulates the affinity of integrins for their ECM-ligands , a process known as inside-out activation . We previously showed that i...
Cells are the building blocks of our bodies . How do cells rearrange to form three-dimensional body plans and maintain specific tissue structures ? Specialized adhesion molecules on the cell surface mediate attachment between cells and their surrounding environment to hold tissues together . Our work uses the developin...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "missense", "mutation", "developmental", "biology", "mutation", "point", "mutation", "integrins", "animal", "genetics", "organism", "development", "invertebrate", "genetics", "cell", "biology", "cell", "adhesion", "embryogenesis", "genetics", "muscle", "development", "bio...
2014
The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering
Short-term synaptic plasticity ( STP ) critically affects the processing of information in neuronal circuits by reversibly changing the effective strength of connections between neurons on time scales from milliseconds to a few seconds . STP is traditionally studied using intracellular recordings of postsynaptic potent...
Information processing in the nervous system critically depends on dynamic changes in the strength of connections between neurons . Short-term synaptic plasticity ( STP ) , changes that occur on timescales from milliseconds to a few seconds , is thought to play a role in tasks such as speech recognition , motion detect...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods", "and", "models" ]
[ "action", "potentials", "medicine", "and", "health", "sciences", "vesicles", "nervous", "system", "membrane", "potential", "electrophysiology", "neuroscience", "synaptic", "plasticity", "cellular", "structures", "and", "organelles", "neuronal", "plasticity", "mood", "diso...
2017
Estimating short-term synaptic plasticity from pre- and postsynaptic spiking
Cytomegalovirus ( CMV ) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people . Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-pepti...
Cytomegalovirus ( CMV ) is a member of the herpesvirus family and most humans carry chronic CMV infection . This drives the development of large expansions of CD8+ CMV-specific T cells , which increase further during ageing . CMV infection is associated with vascular disease and increased risk of mortality in older peo...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "blood", "cells", "innate", "immune", "system", "medicine", "and", "health", "sciences", "immune", "cells", "immune", "physiology", "cytokines", "immunology", "cell", "differentiation", "developmental", "biology", "molecular", "development", "bioassays", "and", "physiol...
2016
Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium
Revealing QTLs with a minor effect in complex traits remains difficult . Initial strategies had limited success because of interference by major QTLs and epistasis . New strategies focused on eliminating major QTLs in subsequent mapping experiments . Since genetic analysis of superior segregants from natural diploid st...
Most traits of organisms are determined by an interplay of different genes interacting in a complex way . For instance , nearly all industrially-important traits of the yeast Saccharomyces cerevisiae are complex traits . We have analyzed high thermotolerance , which is important for industrial fermentations , reducing ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetic", "networks", "quantitative", "traits", "genetic", "maps", "gene", "function", "genome", "sequencing", "genome", "analysis", "tools", "model", "organisms", "linkage", "maps", "trait", "locus", "analysis", "molecular", "genetics", "linkage", "(genetics)", "gen...
2013
QTL Analysis of High Thermotolerance with Superior and Downgraded Parental Yeast Strains Reveals New Minor QTLs and Converges on Novel Causative Alleles Involved in RNA Processing
Many strategies to control opisthorchiasis have been employed in Thailand , but not in the other neighbouring countries . Specific control methods include mass drug administration ( MDA ) and health education to reduce raw fish consumption . These control efforts have greatly shifted the epidemiology of Opisthorchis vi...
Improved diagnostic methods for the detection of Opisthorchis viverrini ( OV ) infection in humans is required for effective surveillance and control of this food borne parasite and the prevention of OV-induced bile duct cancer ( cholangiocarcinoma or CCA ) . In this study , a novel urinary antigen detection method was...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
Advances in the Diagnosis of Human Opisthorchiasis: Development of Opisthorchis viverrini Antigen Detection in Urine
The pathogenesis of rabies is associated with the inability to deliver immune effectors across the blood-brain barrier and to clear virulent rabies virus from CNS tissues . However , the mechanisms that facilitate immune effector entry into CNS tissues are induced by infection with attenuated rabies virus . Infection o...
Every year over 50 , 000 people die from rabies worldwide , primarily due to the poor availability of rabies vaccine in developing countries . However , even when vaccines are available , human deaths from rabies occur if exposure to the causative virus is not recognized and vaccination is not sought in time . This is ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "virology/vaccines", "neurological", "disorders/infectious", "diseases", "of", "the", "nervous", "system", "immunology/immune", "response", "virology", "immunology", "virology/immune", "evasion", "immunology/immunity", "to", "infections", "virology/host", "antiviral", "response...
2009
The Production of Antibody by Invading B Cells Is Required for the Clearance of Rabies Virus from the Central Nervous System
Imputation-based association methods provide a powerful framework for testing untyped variants for association with phenotypes and for combining results from multiple studies that use different genotyping platforms . Here , we consider several issues that arise when applying these methods in practice , including: ( i )...
Genotype imputation is becoming a popular approach to comparing and combining results of multiple association studies that used different SNP genotyping platforms . The basic idea is to exploit the fact that , due to correlation among untyped and typed SNPs , genotypes of untyped SNPs in each study can be inferred ( “i...
[ "Abstract", "Introduction", "Results", "Discussion" ]
[ "mathematics/statistics", "genetics", "and", "genomics" ]
2008
Practical Issues in Imputation-Based Association Mapping