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Plasmodium falciparum is the major human malaria agent responsible for 200 to 300 million infections and one to three million deaths annually , mainly among African infants . The origin and evolution of this pathogen within the human lineage is still unresolved . A single species , P . reichenowi , which infects chimpa...
In 2002 , the publication of the genome of Plasmodium falciparum , the most malignant agent of malaria , generated hopes in the fight against this deadly disease by the opportunities it offered to discover new drug targets . Since then results have not lived up to the expectations . The development of comparative genom...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases", "evolutionary", "biology/evolutionary", "and", "comparative", "genetics" ]
2009
A New Malaria Agent in African Hominids
Myosins are ATP-driven linear molecular motors that work as cellular force generators , transporters , and force sensors . These functions are driven by large-scale nucleotide-dependent conformational changes , termed “strokes”; the “power stroke” is the force-generating swinging of the myosin light chain–binding “neck...
Myosin Va is a “two-legged” ATP-dependent linear molecular motor that transports cellular organelles by “stepping” along actin filaments in a processive manner analogous to human walking , the two “feet” alternating between forward and backward positions . During stepping , the lifted leg undergoes rotational Brownian ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biomacromolecule-ligand", "interactions", "biochemistry", "enzyme", "structure", "cell", "motility", "actin", "filaments", "enzymes", "biology", "enzyme", "kinetics", "biophysics" ]
2011
Direct Observation of the Myosin Va Recovery Stroke That Contributes to Unidirectional Stepping along Actin
Apicomplexa tick-borne hemoparasites , including Babesia bovis , Babesia microti , and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis , respectively . These parasites of vast medical , epidemiological , and economic impact have complex life cycles in their vertebrate and tick hos...
The tick-borne apicomplexan parasites Babesia and Theileria are responsible for costly and devastating diseases globally . Improved control is needed , but the biology of these parasites remains poorly understood . Significant gaps include better understanding of the mechanisms involved in control of gene expression an...
[ "Abstract", "Introduction", "Concluding", "Remarks" ]
[ "sequencing", "techniques", "parasite", "groups", "plasmodium", "gene", "regulation", "regulatory", "proteins", "dna-binding", "proteins", "parasitic", "protozoans", "parasitology", "developmental", "biology", "apicomplexa", "review", "protozoans", "transcription", "factors",...
2016
Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi
Little is known about the genetic basis of ecologically important morphological variation such as the diverse color patterns of mammals . Here we identify genetic changes contributing to an adaptive difference in color pattern between two subspecies of oldfield mice ( Peromyscus polionotus ) . One mainland subspecies h...
The tremendous amount of variation in color patterns among organisms helps individuals survive and reproduce in the wild , yet we know surprisingly little about the genes that produce these adaptive patterns . Here we used a genomic analysis to uncover the molecular basis of a pale color pattern that camouflages beach ...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods", "Supporting", "Information" ]
[ "evolutionary", "biology", "mus", "(mouse)" ]
2007
Adaptive Variation in Beach Mice Produced by Two Interacting Pigmentation Genes
In the context of an ageing population , understanding the transmission of infectious diseases such as scabies through well-connected sub-units of the population , such as residential care homes , is particularly important for the design of efficient interventions to mitigate against the effects of those diseases . Her...
Our work makes five main contributions . ( 1 ) We study a previously under-modelled scenario—transmission of scabies in residential care homes—that is of significant and growing public health importance in the context of an ageing population . ( 2 ) We develop a Markov-chain-based modelling framework that accurately ca...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "death", "rates", "invertebrates", "medicine", "and", "health", "sciences", "markov", "models", "dose", "prediction", "methods", "applied", "mathematics", "tropical", "diseases", "social", "sciences", "parasitic", "diseases", "animals", "health", "care", "simulation", ...
2018
Scabies in residential care homes: Modelling, inference and interventions for well-connected population sub-units
In many sensory systems , transmembrane receptors are spatially organized in large clusters . Such arrangement may facilitate signal amplification and the integration of multiple stimuli . However , this organization likely also affects the kinetics of signaling since the cytoplasmic enzymes that modulate the activity ...
To navigate their environments , organisms must remain sensitive to small changes in their surroundings while adapting to persistent conditions . Bacteria travel by performing a random walk biased toward nutrients and away from toxins . The decision of a bacterium to continue in a given direction or to reorient is cont...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2013
Adaptation Dynamics in Densely Clustered Chemoreceptors
Repairing broken chromosomes via joint molecule ( JM ) intermediates is hazardous and therefore strictly controlled in most organisms . Also in budding yeast meiosis , where production of enough crossovers via JMs is imperative , only a subset of DNA breaks are repaired via JMs , closely regulated by the ZMM pathway . ...
Homologous recombination allows repair of DNA breaks from intact templates of identical sequence by a “copy-and-paste” like mechanism . However , the double Holliday Junction ( dHJ ) is a hazardous intermediate that can form during homologous recombination , if single stranded DNA from both ends of a lesion pair with t...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
Smc5/6-Mms21 Prevents and Eliminates Inappropriate Recombination Intermediates in Meiosis
An open problem in the field of computational neuroscience is how to link synaptic plasticity to system-level learning . A promising framework in this context is temporal-difference ( TD ) learning . Experimental evidence that supports the hypothesis that the mammalian brain performs temporal-difference learning includ...
What are the physiological changes that take place in the brain when we solve a problem or learn a new skill ? It is commonly assumed that behavior adaptations are realized on the microscopic level by changes in synaptic efficacies . However , this is hard to verify experimentally due to the difficulties of identifying...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "neuroscience/behavioral", "neuroscience", "neuroscience", "neuroscience/theoretical", "neuroscience" ]
2011
An Imperfect Dopaminergic Error Signal Can Drive Temporal-Difference Learning
Annual mass drug administration ( MDA ) over five years is the WHO's recommended strategy to eliminate lymphatic filariasis ( LF ) . Some experts , however , consider that longer periods of treatment might be necessary in certain high prevalence and transmission environments based upon past unsuccessful field experienc...
Large-scale intervention programmes to control filariasis are currently underway worldwide . However , a major unresolved question remains: what is the appropriate duration for these programmes ? Recent theoretical work and clinical field experience has highlighted how the ecological diversity between different endemic...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "infectious", "diseases", "neglected", "tropical", "diseases", "lymphatic", "filariasis" ]
2011
The Impact of a Filariasis Control Program on Lihir Island, Papua New Guinea
Photosynthesis is the final determinator for crop yield . To gain insight into genes controlling photosynthetic capacity , we selected from our large T-DNA mutant population a rice stunted growth mutant with decreased carbon assimilate and yield production named photoassimilate defective1 ( phd1 ) . Molecular and bioch...
Photosynthesis is carried out in chloroplast , a plant-specific organelle . Photosynthetic membranes in chloroplasts contain high levels of glycolipids , and UDP-galactose is a dominating donor for glycolipid biosynthesis . Although glycolipid assembly of photosynthetic membranes has been characterized at the genetic a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "agriculture", "biology" ]
2011
A Rice Plastidial Nucleotide Sugar Epimerase Is Involved in Galactolipid Biosynthesis and Improves Photosynthetic Efficiency
We investigated the relationship of treatment regimens for visceral leishmaniasis ( VL ) with post-kala-azar dermal leishmaniasis ( PKDL ) and visceral leishmaniasis relapse ( VLR ) development . Study subjects included cohorts of patients cured of VL since treatment with monotherapy by sodium stibogluconate ( SSG ) , ...
Post-kala-azar Dermal Leishmaniasis ( PKDL ) , a sequale of visceral leishmaniasis ( VL ) , and reappearance VL ( visceral leishmaniasis relapse , VLR ) are intra-epidemic reservoirs of VL and threats control of VL in long run . Currently there is no strategy for prevention of PKDL and VLR . If a relationship between t...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "kala-azar", "antimicrobials", "medicine", "and", "health", "sciences", "drugs", "tropical", "diseases", "microbiology", "geographical", "locations", "antifungals", "parasitic", "diseases", "data", "management", "pharmaceutics", "neglected", "tropical", "diseases", "pharmac...
2019
Relationship between treatment regimens for visceral leishmaniasis and development of post-kala-azar dermal leishmaniasis and visceral leishmaniasis relapse: A cohort study from Bangladesh
Broadly neutralizing antibodies ( bnAbs ) are thought to be a critical component of a protective HIV vaccine . However , designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date . Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natu...
Understanding how HIV-1-broadly neutralizing antibodies ( bnAbs ) develop during natural infection is essential to the design of an efficient HIV vaccine . We studied kinetics and correlates of neutralization breadth in a large sub-Saharan African longitudinal cohort of 439 participants with primary HIV-1 infection . B...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2016
Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort
Plasmodium vivax remains an important cause of malaria in South America and the Asia-Pacific . Naturally acquired antibody responses against multiple P . vivax proteins have been described in numerous countries , however , direct comparison of these responses has been difficult with different methodologies employed . W...
In the pursuit of eliminating all species of malaria , Plasmodium vivax presents one of the most substantial challenges , particularly in countries in Asia , the Western-Pacific and South America . This is primarily due to the ability of P . vivax to cause relapse infections months to years after the initial infectious...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "parasite", "groups", "medicine", "and", "health", "sciences", "immune", "physiology", "plasmodium", "immunology", "geographical", "locations", "tropical", "diseases", "parasitic", "diseases", "parasitology", "apicomplexa", "regional", "geography", "antibodies", "antibody",...
2017
Naturally acquired antibody responses to more than 300 Plasmodium vivax proteins in three geographic regions
CD1d-mediated presentation of glycolipid antigens to T cells is capable of initiating powerful immune responses that can have a beneficial impact on many diseases . Molecular analyses have recently detailed the lipid antigen recognition strategies utilized by the invariant Vα24-Jα18 TCR rearrangements of iNKT cells , w...
Certain lineages of T cells can recognize lipids as stimulatory antigens when presented in the context of CD1 molecules . We know how most Natural Killer T ( NKT ) cells react with this unusual ligand because they use a single invariant T cell receptor ( TCR ) alpha chain to do the job . NKT cells place particular emph...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "immunology", "biology" ]
2012
The Molecular Basis for Recognition of CD1d/α-Galactosylceramide by a Human Non-Vα24 T Cell Receptor
The metabolic symbiosis with photosynthetic algae allows corals to thrive in the oligotrophic environments of tropical seas . Different aspects of this relationship have been investigated using the emerging model organism Aiptasia . However , many fundamental questions , such as the nature of the symbiotic relationship...
The symbiotic relationship with photosynthetic algae is key to the success of reef building corals in the nutrient poor environment of tropical waters . Extensive insight has been obtained from both physiological and “omics” level studies , yet , there are still gaps in our knowledge with respect to the metabolic inter...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "invertebrates", "carbohydrate", "metabolism", "chemical", "compounds", "symbiosis", "statistics", "metaanalysis", "carbohydrates", "glucose", "metabolism", "animals", "organic", "compounds", "glucose", "organisms", "mathematics", "research", "and", "analysis", "methods", "...
2019
Host-dependent nitrogen recycling as a mechanism of symbiont control in Aiptasia
Characterising the spatio-temporal dynamics of pathogens in natura is key to ensuring their efficient prevention and control . However , it is notoriously difficult to estimate dispersal parameters at scales that are relevant to real epidemics . Epidemiological surveys can provide informative data , but parameter estim...
In spatial epidemiology , dispersal kernels quantify how the probability of pathogen dissemination varies with distance from an infection source . Spatial models of pathogen spread are sensitive to kernel parameters; yet these parameters have rarely been estimated using field data gathered at relevant scales . Robust e...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "orchards", "medicine", "and", "health", "sciences", "infectious", "disease", "epidemiology", "kernel", "functions", "plant", "science", "farms", "probability", "distribution", "mathematics", "plant", "pathology", "infectious", "disease", "control", "infectious", "disease...
2018
Estimation of the dispersal distances of an aphid-borne virus in a patchy landscape
Oxidative stress is a common etiological feature of neurological disorders , although the pathways that govern defence against reactive oxygen species ( ROS ) in neurodegeneration remain unclear . We have identified the role of oxidation resistance 1 ( Oxr1 ) as a vital protein that controls the sensitivity of neuronal...
Oxygen is vital for life , but it can also cause damage to cells . Consequently , protective proteins ( antioxidants ) are utilised to maintain the fine balance between oxygen metabolism and the production of potentially toxic reactive oxygen species ( ROS ) . If this balance is not maintained , oxidative stress occurs...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "animal", "models", "medicine", "neurobiology", "of", "disease", "and", "regeneration", "model", "organisms", "neurological", "disorders", "neurology", "neurodegenerative", "diseases", "biology", "neuroscience", "cerebellar", "disorders" ]
2011
Oxr1 Is Essential for Protection against Oxidative Stress-Induced Neurodegeneration
The dynamic nature of technological developments invites us to rethink the learning spaces . In this context , science education can be enriched by the contribution of new computational resources , making the educational process more up-to-date , challenging , and attractive . Bioinformatics is a key interdisciplinary ...
Bioinformatics is an interdisciplinary activity that complements and connects several fields with biology and can also be used as an educational tool for science . During 2017 , the Structural Bioinformatics Group at National University of Quilmes in Buenos Aires , Argentina , worked together with public and private sc...
[ "Abstract", "Background", "and", "motivation", "Discussion" ]
[ "learning", "education", "engineering", "and", "technology", "sociology", "social", "sciences", "teachers", "neuroscience", "learning", "and", "memory", "cell", "phones", "computers", "cognitive", "psychology", "research", "and", "analysis", "methods", "computer", "and"...
2019
Bioinformatics calls the school: Use of smartphones to introduce Python for bioinformatics in high schools
The Ebola virus disease epidemic between 2013 and 2016 in West Africa was unprecedented . It resulted in approximately 28 . 000 cases and 10 . 000 Ebola survivors . Many survivors face social , economic and health-related predicaments and media reporting is crucially important in infectious disease outbreaks . However ...
The largest Ebola epidemic occurred in West Africa between 2013 and 2016 . Liberia was one of the most affected countries with more than 1500 survivors registered . In the height of the Ebola outbreak survivors were increasingly included in the treatment and care of patients and in health sensitizing and social mobilis...
[ "Abstract", "Introduction", "Material", "and", "methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "body", "fluids", "pathology", "and", "laboratory", "medicine", "pathogens", "sociology", "tropical", "diseases", "microbiology", "geographical", "locations", "ebola", "hemorrhagic", "fever", "social", "sciences", "health", "care...
2017
"We are survivors and not a virus:" Content analysis of media reporting on Ebola survivors in Liberia
Self-renewing organs often experience a decline in function in the course of aging . It is unclear whether chronological age or external factors control this decline , or whether it is driven by stem cell self-renewal—for example , because cycling cells exhaust their replicative capacity and become senescent . Here we ...
Stem cell cycling is expected to be beneficial because it helps delay aging , by ensuring organ self-renewal . Yet stem cell cycling is best used sparingly: cycling likely causes mutation accumulation—increasing the likelihood of cancer—and may eventually cause stem cells to senesce and thus stop contributing to organ ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "physiology", "invertebrates", "medicine", "and", "health", "sciences", "reproductive", "system", "senescence", "gonads", "caenorhabditis", "cell", "cycle", "and", "cell", "division", "cell", "processes", "animals", "germ", "cells", "animal", "models", "physio...
2016
Intermittent Stem Cell Cycling Balances Self-Renewal and Senescence of the C. elegans Germ Line
The advent of two-photon microscopy now reveals unprecedented , detailed spatio-temporal data on cellular motility and interactions in vivo . Understanding cellular motility patterns is key to gaining insight into the development and possible manipulation of the immune response . Computational simulation has become an ...
Advances in imaging technology allow investigators to monitor the movements and interactions of immune cells in a live animal , processes essential to understanding and manipulating how an immune response is generated . T cells in the brains of Toxoplasma gondii-infected mice have previously been described as performin...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "blood", "cells", "cell", "motility", "medicine", "and", "health", "sciences", "immune", "cells", "classical", "mechanics", "fluid", "mechanics", "immunology", "mathematical", "models", "simulation", "and", "modeling", "mathematics", "brownian", "motion", "statistics", ...
2016
Leukocyte Motility Models Assessed through Simulation and Multi-objective Optimization-Based Model Selection
Subtelomeres are duplication-rich , structurally variable regions of the human genome situated just proximal of telomeres . We report here that the most terminally located human subtelomeric genes encode a previously unrecognized third subclass of the Wiskott-Aldrich Syndrome Protein family , whose known members reorga...
Human subtelomeres are rearrangement-prone regions near chromosome ends . They are concentrations of large , recent interchromosomal duplications . Over half of subtelomeric sequences changed copy number or location since humans and chimpanzee diverged , and subtelomeric content varies greatly among humans . Despite th...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion", "Supporting", "Information" ]
[ "primates", "developmental", "biology", "infectious", "diseases", "cell", "biology", "entamoeba", "caenorhabditis", "human", "computational", "biology", "evolutionary", "biology", "drosophila", "molecular", "biology", "genetics", "and", "genomics" ]
2007
Human Subtelomeric WASH Genes Encode a New Subclass of the WASP Family
Accurate diagnosis of Loa loa infection is essential to the success of mass drug administration efforts to eliminate onchocerciasis and lymphatic filariasis , due to the risk of fatal encephalopathic reactions to ivermectin occurring among highly microfilaremic Loa-infected individuals living in areas co-endemic for mu...
Loa loa is a filarial nematode that infects over 10 million people in Africa . Most infections cause no symptoms , but individuals with large numbers of blood-stage microfilariae are at risk for fatal reactions to ivermectin , an antiparasitic agent used to treat and prevent infections with Onchocerca volvulus , a rela...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "infectious", "diseases", "diagnostic", "medicine", "global", "health", "neglected", "tropical", "diseases", "loiasis" ]
2011
Rapid Molecular Assays for Specific Detection and Quantitation of Loa loa Microfilaremia
Persistent bacteremia caused by Staphylococcus aureus ( SA ) , especially methicillin-resistant SA ( MRSA ) , is a significant cause of morbidity and mortality . Despite susceptibility phenotypes in vitro , persistent MRSA strains fail to clear with appropriate anti-MRSA therapy during bacteremia in vivo . Thus , ident...
Staphylococcus aureus causes potentially lethal infections of the bloodstream and target organs when able to enter the body , often via skin trauma or catheterization . Methicillin-resistant Staphylococcus aureus ( MRSA ) resist common antibiotics , but are often successfully treated with vancomycin . However , in some...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "antimicrobials", "cell", "death", "medicine", "and", "health", "sciences", "body", "fluids", "pathology", "and", "laboratory", "medicine", "pathogens", "drugs", "immunology", "cell", "processes", "microbiology", "mathematical", "models", "vancomycin", "staphylococcus", ...
2019
Identifying determinants of persistent MRSA bacteremia using mathematical modeling
Mayaro virus ( MAYV ) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness , rash , headaches , and nausea that may turn into incapacitating , persistent arthralgias in some victims . Since its discovery in Trinidad in 1954 , cases of MAYV infection have lar...
Mayaro virus ( MAYV ) is a mosquito-transmitted virus that causes fever , headache , chills , nausea and joint pain that can last for months after infection . The rising number of cases , due to increased mosquito circulation , and the threat of an epidemic emphasize its importance as an emerging virus , but there are ...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "blood", "cells", "humoral", "immunity", "blood", "serum", "medicine", "and", "health", "sciences", "enzyme-linked", "immunoassays", "immune", "physiology", "body", "fluids", "immune", "cells", "immunology", "vaccines", "animal", "models", "model", "organisms", "exper...
2019
Protective immunity by an engineered DNA vaccine for Mayaro virus
Neuronal ceroid lipofuscinosis ( NCL ) is a progressive neurodegenerative disease characterized by brain and retinal atrophy and the intracellular accumulation of autofluorescent lysosomal storage bodies resembling lipofuscin in neurons and other cells . Tibetan terriers show a late-onset lethal form of NCL manifesting...
The neuronal ceroid lipofuscinosis ( NCL ) is a neurodegenerative storage diseases characterized by psychomotor retardation , blindness , and premature death . NCL has been reported in several dog breeds . NCL is characterized by progressive brain and retinal atrophy and the intracellular accumulation of autofluorescen...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "animal", "genetics", "veterinary", "neurology", "animal", "management", "animal", "breeding", "neuroscience", "genetics", "and", "genomics", "veterinary", "science", "veterinary", "medicine" ]
2011
A One Base Pair Deletion in the Canine ATP13A2 Gene Causes Exon Skipping and Late-Onset Neuronal Ceroid Lipofuscinosis in the Tibetan Terrier
Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection . Here we report a different impact of Foxp3+ regulatory T cells ( Treg ) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice . Infection with Strongyloides ratti ...
Parasitic worms are large multicellular organisms that manage completion of their life cycles despite exposure to their host's immune system . To avoid expulsion , parasitic worms actively suppress their host's immune response . Here we show that the pathogenic nematode Strongyloides ratti induces the expansion of a sp...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "immune", "cells", "immunity", "immunity", "to", "infections", "immunology", "immunoregulation", "biology", "zoology", "immunomodulation", "parasitology", "helminthology" ]
2014
Foxp3+ Regulatory T Cells Delay Expulsion of Intestinal Nematodes by Suppression of IL-9-Driven Mast Cell Activation in BALB/c but Not in C57BL/6 Mice
Muscle fatigue is a temporary decline in the force and power capacity of skeletal muscle resulting from muscle activity . Because control of muscle is realized at the level of the motor unit ( MU ) , it seems important to consider the physiological properties of motor units when attempting to understand and predict mus...
Skeletal muscle fatigue reduces strength during work and play and profoundly impairs motor function in many neuromuscular disorders . Muscle is composed of groupings of fibres called motor units and these have an extensive range of characteristics from small , weak , and fatigue-resistant to large , strong , and highly...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "material", "fatigue", "medicine", "and", "health", "sciences", "legs", "classical", "mechanics", "pathology", "and", "laboratory", "medicine", "fatigue", "skeletal", "muscles", "limbs", "(anatomy)", "neuroscience", "biomechanics", "muscle", "contraction", "motor", "neu...
2017
A motor unit-based model of muscle fatigue
DNA methylation is pervasive across all domains of life . In bacteria , the presence of N6-methyladenosine ( m6A ) has been detected among diverse species , yet the contribution of m6A to the regulation of gene expression is unclear in many organisms . Here we investigated the impact of DNA methylation on gene expressi...
DNA methylation is common among many bacterial species , yet the contribution of DNA methylation to the regulation of gene expression is unclear outside of a limited number of gram-negative species . We characterized sites of DNA methylation throughout the genome of the gram-positive pathogen Streptococcus pyogenes or ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "blood", "cells", "medicine", "and", "health", "sciences", "immune", "cells", "pathology", "and", "laboratory", "medicine", "gene", "regulation", "pathogens", "immunology", "microbiology", "streptococcus", "pyogenes", "signs", "and", "symptoms", "sequence", "motif", "...
2019
DNA methylation from a Type I restriction modification system influences gene expression and virulence in Streptococcus pyogenes
Memory-like CD8+ T cells expressing eomesodermin are a subset of innate T cells initially identified in a number of genetically modified mice , and also exist in wild mice and human . The acquisition of memory phenotype and function by these T cells is dependent on IL–4 produced by PLZF+ innate T cells; however , their...
Over the course of viral infection there may be a limited time period during which the host system can eliminate the virus . When viruses are not eliminated within this period of time , virus can establish persistent infection . Here , we show that IL-4-induced innate CD8+ T cells are able to effectively control chroni...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
IL-4 Induced Innate CD8+ T Cells Control Persistent Viral Infection
Viruses within a family often vary in their cellular tropism and pathogenicity . In many cases , these variations are due to viruses switching their specificity from one cell surface receptor to another . The structural requirements that underlie such receptor switching are not well understood especially for carbohydra...
Viruses need to bind to receptors on host cells for viral entry and infection , and the type of receptor bound determines the range of hosts and tissues the virus can infect . Viruses within a family often vary in their tissue distribution and pathogenicity because changes in receptor specificity can produce a virus wi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
A Structure-Guided Mutation in the Major Capsid Protein Retargets BK Polyomavirus
Evolutionary theory predicts that sexually antagonistic mutations accumulate differentially on the X chromosome and autosomes in species with an XY sex-determination system , with effects ( masculinization or feminization of the X ) depending on the dominance of mutations . Organisms with alternative modes of inheritan...
Males and females differ in their optimal values for most phenotypic traits , which makes intra-locus genetic conflicts among sexes common . Sex chromosomes have a sex-biased transmission , a pattern which might create favourable conditions for the spread of sexually antagonistic alleles ( i . e . alleles beneficial fo...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "genome", "expression", "analysis", "mutation", "sexual", "selection", "chromosomal", "inheritance", "chromosome", "biology", "natural", "selection", "sexual", "conflict", "heredity", "gene", "expression", "genetics", "genome", "evolution", "biology", "genomics", "evoluti...
2013
Masculinization of the X Chromosome in the Pea Aphid
While high-frequency deep brain stimulation is a well established treatment for Parkinson’s disease , its underlying mechanisms remain elusive . Here , we show that two competing hypotheses , desynchronization and entrainment in a population of model neurons , may not be mutually exclusive . We find that in a noisy gro...
While high-frequency deep brain stimulation ( DBS ) is a decades old treatment for alleviating the motor symptoms Parkinsons disease , the way in which it alleviates these symptoms is not well understood . Making matters more complicated , some experimental results suggest that DBS works by making neurons fire more reg...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2015
Clustered Desynchronization from High-Frequency Deep Brain Stimulation
Recent advances in single-cell time-lapse microscopy have revealed non-genetic heterogeneity and temporal fluctuations of cellular phenotypes . While different phenotypic traits such as abundance of growth-related proteins in single cells may have differential effects on the reproductive success of cells , rigorous exp...
Selection is a ubiquitous process in biological populations in which individuals are endowed with heterogeneous reproductive abilities , and it occurs even among genetically homogeneous cells due to the existence of phenotypic noise . Unlike genotypes , which can remain stable for many generations , phenotypic fluctuat...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "antimicrobials", "medicine", "and", "health", "sciences", "cell", "division", "analysis", "cell", "cycle", "and", "cell", "division", "drugs", "cell", "processes", "microbiology", "streptomycin", "protein", "expression", "probability", "distribution", "mathematics", "a...
2017
Inferring fitness landscapes and selection on phenotypic states from single-cell genealogical data
In order to maintain genome information accurately and relevantly , original genome annotations need to be updated and evaluated regularly . Manual reannotation of genomes is important as it can significantly reduce the propagation of errors and consequently diminishes the time spent on mistaken research . For this rea...
Entamoeba histolytica is an anaerobic parasitic protozoan that causes amoebic dysentery . The parasites colonize the large intestine , but under some circumstances may invade the intestinal mucosa , enter the bloodstream and lead to the formation of abscesses such amoebic liver abscesses . The draft genome of E . histo...
[ "Abstract", "Introduction", "Methods", "Results", "and", "Discussion" ]
[ "genetics", "and", "genomics/genome", "projects", "genetics", "and", "genomics/bioinformatics", "genetics", "and", "genomics/genomics" ]
2010
New Assembly, Reannotation and Analysis of the Entamoeba histolytica Genome Reveal New Genomic Features and Protein Content Information
Pattern classification of human brain activity provides unique insight into the neural underpinnings of diverse mental states . These multivariate tools have recently been used within the field of affective neuroscience to classify distributed patterns of brain activation evoked during emotion induction procedures . He...
Functional brain imaging techniques provide a window into neural activity underpinning diverse cognitive processes , including visual perception , decision-making , and memory , among many others . By treating functional imaging data as a pattern-recognition problem , similar to face- or character-recognition , researc...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "diagnostic", "radiology", "functional", "magnetic", "resonance", "imaging", "personality", "traits", "social", "sciences", "biomarkers", "neuroscience", "magnetic", "resonance", "imaging", "fear", "anxiety", "cognition", "brain", ...
2016
Decoding Spontaneous Emotional States in the Human Brain
Calorie restriction ( CR ) , the only non-genetic intervention known to slow aging and extend life span in organisms ranging from yeast to mice , has been linked to the down-regulation of Tor , Akt , and Ras signaling . In this study , we demonstrate that the serine/threonine kinase Rim15 is required for yeast chronolo...
Reduction in calorie intake is a well-established intervention that extends the life span of a variety of biological model organisms studied . Calorie restriction also delays and attenuates age-related changes in primates , although its longevity-promoting effect has not been demonstrated . Here , we utilized a single ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods", "Supporting", "Information" ]
[ "genetics", "and", "genomics", "cell", "biology", "developmental", "biology", "saccharomyces" ]
2008
Life Span Extension by Calorie Restriction Depends on Rim15 and Transcription Factors Downstream of Ras/PKA, Tor, and Sch9
In sub-Saharan Africa , systematic surveillance of young children with suspected invasive bacterial disease ( e . g . , septicemia , meningitis ) has revealed non-typhoidal Salmonella ( NTS ) to be a major pathogen exhibiting high case fatality ( ~20% ) . Where infant vaccination against Haemophilus influenzae type b (...
A surveillance program at Gabriel Touré Hospital in Mali observed a high burden of invasive disease caused by non-typhoidal Salmonella ( iNTS ) . This surveillance program was originally instituted to measure the amount of invasive disease ( e . g . , septicemia , meningitis ) caused by two bacteria that invade the res...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "mali", "pathology", "and", "laboratory", "medicine", "pathogens", "immunology", "geographical", "locations", "microbiology", "pediatrics", "vaccines", "preventive", "medicine", "bacterial", "diseases", "enterobacteriaceae", "vaccina...
2017
Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal Salmonella Disease in Young Children in Mali, West Africa
Variation in the branching of plant inflorescences determines flower number and , consequently , reproductive success and crop yield . Nightshade ( Solanaceae ) species are models for a widespread , yet poorly understood , program of eudicot growth , where short side branches are initiated upon floral termination . Thi...
Among the most distinguishing features of plants are the flower-bearing shoots , called inflorescences . Despite a solid understanding of flower development , the molecular mechanisms that control inflorescence architecture remain obscure . We have explored this question in tomato , where mutations in two genes , ANANT...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "plant", "biology" ]
2008
The Making of a Compound Inflorescence in Tomato and Related Nightshades
The differentiation of discrete and continuous movement is one of the pillars of motor behavior classification . Discrete movements have a definite beginning and end , whereas continuous movements do not have such discriminable end points . In the past decade there has been vigorous debate whether this classification i...
A fundamental question in motor control research is whether distinct movement classes exist . Candidate classes are discrete and continuous movement . Discrete movements have a definite beginning and end , whereas continuous movements do not have such discriminable end points . In the past decade there has been vigorou...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "neuroscience/behavioral", "neuroscience", "neuroscience/motor", "systems", "neuroscience/theoretical", "neuroscience", "computational", "biology/computational", "neuroscience" ]
2008
Distinct Timing Mechanisms Produce Discrete and Continuous Movements
Field-applicable tests detecting asymptomatic Mycobacterium leprae ( M . leprae ) infection or predicting progression to leprosy , are urgently required . Since the outcome of M . leprae infection is determined by cellular- and humoral immunity , we aim to develop diagnostic tests detecting pro-/anti-inflammatory and r...
Leprosy is one of the six diseases considered by WHO as a major threat in developing countries and often results in severe , life-long disabilities and deformities due to delayed diagnosis . Early detection of Mycobacterium leprae ( M . leprae ) infection , followed by effective interventions , is considered vital to i...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "humoral", "immunity", "infectious", "diseases", "medicine", "and", "health", "sciences", "clinical", "laboratory", "sciences", "immune", "cells", "diagnostic", "medicine", "cell", "biology", "animal", "cells", "immunity", "clinical", "immunology", "immunity", "to", "...
2014
Field-Evaluation of a New Lateral Flow Assay for Detection of Cellular and Humoral Immunity against Mycobacterium leprae
Vanillyl alcohol oxidase ( VAO ) is a homo-octameric flavoenzyme belonging to the VAO/PCMH family . Each VAO subunit consists of two domains , the FAD-binding and the cap domain . VAO catalyses , among other reactions , the two-step conversion of p-creosol ( 2-methoxy-4-methylphenol ) to vanillin ( 4-hydroxy-3-methoxyb...
Enzymes are bionanomachines , which speed up chemical reactions in organisms . To understand how they achieve that , we need to study their mechanisms . Computational enzymology can show us what happens in the enzyme’s active site during a reaction . But molecules need first to reach the active site before a reaction c...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "crystal", "structure", "chemical", "compounds", "oxides", "split-decomposition", "method", "condensed", "matter", "physics", "enzymology", "organic", "compounds", "multiple", "alignment", "calculation", "flavin", "crystallography", "hydrogen", "peroxide", "alcohols", "enzy...
2017
The ins and outs of vanillyl alcohol oxidase: Identification of ligand migration paths
Mutations causing replication stress can lead to genomic instability ( GIN ) . In vitro studies have shown that drastic depletion of the MCM2-7 DNA replication licensing factors , which form the replicative helicase , can cause GIN and cell proliferation defects that are exacerbated under conditions of replication stre...
Proper replication of the genome is essential for maintenance of the genetic material and normal cell proliferation . DNA replication can be compromised by exogenous factors and genetic disruptions . Such compromise can lead to disease such as cancer , which is characterized by genomic instability ( an elevated mutatio...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry/replication", "and", "repair", "genetics", "and", "genomics/cancer", "genetics", "genetics", "and", "genomics/animal", "genetics", "genetics", "and", "genomics/chromosome", "biology" ]
2010
Incremental Genetic Perturbations to MCM2-7 Expression and Subcellular Distribution Reveal Exquisite Sensitivity of Mice to DNA Replication Stress
Network motifs have been identified as building blocks of regulatory networks , including gene regulatory networks ( GRNs ) . The most basic motif , autoregulation , has been associated with bistability ( when positive ) and with homeostasis and robustness to noise ( when negative ) , but its general importance in netw...
Multicellular organisms show an incredible diversity of cell types in their different tissues . Functional classes of cells can be attributed to the activation and repression of genes , which enable each cell type to support different functions within the organism . These patterns of activity have been studied by means...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "developmental", "biology", "theoretical", "biology", "gene", "regulatory", "networks", "natural", "selection", "neutral", "theory", "biology", "and", "life", "sciences", "population", "genetics", "computational", "biology", "evolutionary", "biology", "evolutionary", "pro...
2014
Stability Depends on Positive Autoregulation in Boolean Gene Regulatory Networks
Seemingly minor details of mathematical and computational models of evolution are known to change the effect of population structure on the outcome of evolutionary processes . For example , birth-death dynamics often result in amplification of selection , while death-birth processes have been associated with suppressio...
Whether a mutation spreads in a population or not is one of the most important questions in biology . The evolution of cancer and antibiotic resistance , for example , are mediated by invading mutants . Recent work has shown that population structure can have important consequences for the outcome of evolution . For in...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "bacteriology", "infographics", "organismal", "evolution", "interaction", "networks", "population", "dynamics", "microbiology", "fungal", "evolution", "microbial", "evolution", "population", "biology", "computer", "and", "information", "sciences", "mycology", "molecular", "...
2019
Motion, fixation probability and the choice of an evolutionary process
Grade of membership models , also known as “admixture models” , “topic models” or “Latent Dirichlet Allocation” , are a generalization of cluster models that allow each sample to have membership in multiple clusters . These models are widely used in population genetics to model admixed individuals who have ancestry fro...
Gene expression profile of a biological sample ( either from single cells or pooled cells ) results from a complex interplay of multiple related biological processes . Consequently , for example , distal tissue samples may share a similar gene expression profile through some common underlying biological processes . Our...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "blastocysts", "sequencing", "techniques", "population", "genetics", "neuronal", "differentiation", "neuroscience", "cell", "differentiation", "developmental", "biology", "molecular", "biology", "techniques", "population", "biology", "embryos", "rna", "sequencing", "research"...
2017
Visualizing the structure of RNA-seq expression data using grade of membership models
The intestinal epithelium plays a critical role in host-microbe homeostasis by sensing gut microbes and subsequently initiating proper immune responses . During the neonatal stage , the intestinal epithelium is under immune repression , allowing the transition for newborns from a relatively sterile intra-uterine enviro...
Precisely controlled host-microbe interactions in the gastrointestinal tract are crucial for human overall health and well-being . Dysregulated host responses to gut microbiota are the major cause of autoimmune diseases , inflammatory disorders and cancers . The intestinal epithelium lines the gastrointestinal tract an...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "immunofluorescence", "staining", "immunology", "epithelial", "cells", "animal", "models", "developmental", "biology", "model", "organisms", "signs", "and", "symptoms", "experimental", ...
2017
hnRNP I regulates neonatal immune adaptation and prevents colitis and colorectal cancer
Many biological and clinical outcomes are based not on single proteins , but on modules of proteins embedded in protein networks . A fundamental question is how the proteins within each module contribute to the overall module activity . Here , we study the modules underlying three representative biological programs rel...
Biological outcomes are often determined by modules of proteins working in combination . In classic biological studies , these modules have been shown to encode a diverse repertoire of logic functions which provide the means to express complex regulatory programs using a limited number of proteins . Here , we integrate...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cancer", "detection", "and", "diagnosis", "medicine", "breast", "tumors", "cancers", "and", "neoplasms", "basic", "cancer", "research", "algorithms", "oncology", "neurological", "tumors", "developmental", "biology", "organism", "development", "regulatory", "networks", ...
2011
Protein Networks as Logic Functions in Development and Cancer
Praziquantel ( PZQ ) is the drug compound of choice in the control and treatment of schistosomiasis . PZQ is administered as a racemate , i . e . 1∶1 mixture of enantiomers . The schistosomicidal activity arises from one PZQ-enantiomer , whereas the other enantiomer does not contribute to the activity . The WHO's Speci...
Schistosomiasis , or Bilharzia , is a parasitic disease caused by flatworms , which affects about 200 million people worldwide . Praziquantel ( PZQ ) is the drug compound of choice in the control and treatment of this disease . Only half of the drug dose currently administered actually has activity against schistosomia...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases/helminth", "infections", "pediatrics", "and", "child", "health", "chemistry/organic", "chemistry", "infectious", "diseases/neglected", "tropical", "diseases" ]
2009
Taste, A New Incentive to Switch to (R)-Praziquantel in Schistosomiasis Treatment
Recent advances in experimental techniques have allowed the simultaneous recordings of populations of hundreds of neurons , fostering a debate about the nature of the collective structure of population neural activity . Much of this debate has focused on the empirical findings of a phase transition in the parameter spa...
Neurons encoding the natural world are correlated in their activities . The structure of this correlation fundamentally changes the population code , and these effects increase in larger neural populations . We experimentally recorded from populations of 100+ retinal ganglion cells and probed the structure of their joi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "action", "potentials", "membrane", "potential", "ocular", "anatomy", "electrophysiology", "neuroscience", "probability", "distribution", "mathematics", "ganglion", "cells", "systems", "science", "neuronal", "tuning", "computer", "...
2017
The structured ‘low temperature’ phase of the retinal population code
Klotho acts as a co-receptor for and dictates tissue specificity of circulating FGF23 . FGF23 inhibits PTH secretion , and reduced Klotho abundance is considered a pathogenic factor in renal secondary hyperparathyroidism . To dissect the role of parathyroid gland resident Klotho in health and disease , we generated mic...
Inorganic calcium is a critical element for a diverse range of cellular processes ranging from cell signaling to energy metabolism , and its extracellular concentration is controlled by parathyroid hormone ( PTH ) . Klotho is expressed in parathyroid chief cells and reported to facilitate PTH secretion during hypocalce...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
Parathyroid-Specific Deletion of Klotho Unravels a Novel Calcineurin-Dependent FGF23 Signaling Pathway That Regulates PTH Secretion
Osteoporotic fracture is a major cause of morbidity and mortality worldwide . Low bone mineral density ( BMD ) is a major predisposing factor to fracture and is known to be highly heritable . Site- , gender- , and age-specific genetic effects on BMD are thought to be significant , but have largely not been considered i...
Osteoporotic fracture is a major cause of early mortality and morbidity in the community . To identify genes associated with osteoporosis , we have performed a genome-wide association study . In order to improve study power and to address the demographic group of highest risk from osteoporotic fracture , we have used a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/genetics", "of", "disease", "diabetes", "and", "endocrinology/bone", "and", "mineral", "metabolism", "rheumatology/bone", "and", "mineral", "metabolism" ]
2011
Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk
Genome-wide association studies ( GWAS ) have recently identified KIF1B as susceptibility locus for hepatitis B virus ( HBV ) –related hepatocellular carcinoma ( HCC ) . To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association , we performed a large...
Previous studies strongly suggest the importance of genetic susceptibility for hepatocellular carcinoma ( HCC ) . However , the studies about genetic etiology on HBV–related HCC were limited . Our genome-wide association study included 523 , 663 autosomal SNPs in 1 , 538 HBV–positive HCC patients and 1 , 465 chronic HB...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "genome-wide", "association", "studies", "cancer", "genetics", "genetics", "biology", "genetics", "and", "genomics" ]
2012
GWAS Identifies Novel Susceptibility Loci on 6p21.32 and 21q21.3 for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers
Quantifying heterogeneity in gene expression among single cells can reveal information inaccessible to cell-population averaged measurements . However , the expression level of many genes in single cells fall below the detection limit of even the most sensitive technologies currently available . One proposed approach t...
Different cells can make different amounts of biomolecules such as RNA transcripts of genes . New technologies are emerging to measure the transcript level of many genes in single cells . However , accurate quantification of the biological variation from cell to cell can be challenging due to the low transcript level o...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "blood", "cells", "medicine", "and", "health", "sciences", "immune", "cells", "pathology", "and", "laboratory", "medicine", "engineering", "and", "technology", "signal", "processing", "immunology", "population", "genetics", "gene", "pool", "simulation", "and", "modeli...
2016
Robust Inference of Cell-to-Cell Expression Variations from Single- and K-Cell Profiling
The proper temporal and spatial expression of genes during plant development is governed , in part , by the regulatory activities of various types of small RNAs produced by the different RNAi pathways . Here we report that transgenic Arabidopsis plants constitutively expressing the rapeseed SB1 SINE retroposon exhibit ...
Short interspersed elements ( SINEs ) are transposable elements in eukaryotic genomes that mobilize through an RNA intermediate . Recently , mammalian SINE RNAs were shown to have roles as noncoding riboregulators in stress situations or in specific tissues . Mammalian SINE RNAs modulate the level of mRNAs and proteins...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/epigenetics", "genetics", "and", "genomics", "biochemistry/rna", "structure", "molecular", "biology/rna-protein", "interactions" ]
2008
SINE RNA Induces Severe Developmental Defects in Arabidopsis thaliana and Interacts with HYL1 (DRB1), a Key Member of the DCL1 Complex
Geophysical models of climate change are becoming increasingly sophisticated , yet less effort is devoted to modelling the human systems causing climate change and how the two systems are coupled . Here , we develop a simple socio-climate model by coupling an Earth system model to a social dynamics model . We treat soc...
The importance of anthropogenic CO2 emissions on climate change trajectories is widely acknowledged . However , geophysical climate models rarely account for dynamic human behaviour , which determines the emissions trajectory , and is itself affected by the climate system . Here , using a coupled socio-climate model , ...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "learning", "anthropogenic", "climate", "change", "ecology", "and", "environmental", "sciences", "chemical", "compounds", "atmospheric", "science", "social", "sciences", "neuroscience", "learning", "and", "memory", "physical", "geography", "simulation", "and", "modeling",...
2019
Charting pathways to climate change mitigation in a coupled socio-climate model
Lassa virus ( LASV ) , the causative agent of Lassa fever ( LF ) , is endemic in West Africa , accounting for substantial morbidity and mortality . In spite of ongoing research efforts , LF pathogenesis and mechanisms of LASV immune control remain poorly understood . While normal laboratory mice are resistant to LASV ,...
Lassa virus ( LASV ) is the causative agent of Lassa fever ( LF ) , accounting for substantial morbidity and mortality in West Africa . Yet the mechanisms leading to disease remain poorly understood . Here we propose a concept whereby the body's immune defense either defeats LASV rapidly or , if unsuccessful , becomes ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases/viral", "infections", "immunology/immunity", "to", "infections", "immunology/immune", "response", "immunology/innate", "immunity" ]
2010
T Cell-Dependence of Lassa Fever Pathogenesis
TLR2 is a cell surface receptor which elicits an immediate response to a wide repertoire of bacteria and viruses . Its response is usually thought to be proinflammatory rather than an antiviral . In monocytic cells TLR2 cooperates with coreceptors , e . g . CD14 , CD36 and αMβ2-integrin . In an earlier work we showed t...
In an earlier work we showed that a relevant contribution to the overall IFN-based antiviral response of the cell to herpes simplex virus is exerted by αvβ3-integrin which acts in concert with TLR2 in eliciting this response . Major characteristics of this branch of the innate response are the secretion of IFN-α and -β...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences" ]
2014
The Epithelial αvβ3-Integrin Boosts the MYD88-Dependent TLR2 Signaling in Response to Viral and Bacterial Components
Mucosal mononuclear ( MMC ) CCR5+CD4+ T cells of the gastrointestinal ( GI ) tract are selectively infected and depleted during acute HIV-1 infection . Despite early initiation of combination antiretroviral therapy ( cART ) , gut-associated lymphoid tissue ( GALT ) CD4+ T cell depletion and activation persist in the ma...
This study was undertaken to determine if the gastrointestinal tract is a site of ongoing viral replication during suppressive combination antiretroviral therapy ( cART ) ( defined by plasma HIV-1 RNA levels below 50 copies/ml ) . We found no evidence of substantial viral evolution in HIV-1 envelope sequences derived f...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "infectious", "diseases", "gastroenterology", "and", "hepatology", "hiv", "biology", "genomics", "viral", "diseases", "genetics", "and", "genomics" ]
2012
Absence of HIV-1 Evolution in the Gut-Associated Lymphoid Tissue from Patients on Combination Antiviral Therapy Initiated during Primary Infection
The single glycoprotein ( G ) of rabies virus ( RABV ) dictates all viral entry steps from receptor engagement to membrane fusion . To study the uptake of RABV into primary neuronal cells in culture , we generated a recombinant vesicular stomatitis virus in which the G protein was replaced with that of the neurotropic ...
Rabies virus is the causative agent of a generally fatal and incurable disease of the central nervous system ( CNS ) . Rabies lethality requires that the virus invade the brain , a feat accomplished by neuronal transmission from the site of infection to the CNS . Using cultures of peripheral neurons and chemicals that ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "physiology", "medicine", "and", "health", "sciences", "vesicles", "pathology", "and", "laboratory", "medicine", "pathogens", "cell", "processes", "microbiology", "viral", "structure", "neurites", "neuroscience", "motor", "neurons", "viruses", "rna", "viruses", ...
2016
Rabies Internalizes into Primary Peripheral Neurons via Clathrin Coated Pits and Requires Fusion at the Cell Body
HIV-1 can disseminate between susceptible cells by two mechanisms: cell-free infection following fluid-phase diffusion of virions and by highly-efficient direct cell-to-cell transmission at immune cell contacts . The contribution of this hybrid spreading mechanism , which is also a characteristic of some important comp...
The ability to spread using more than once mechanism , named hybrid spreading , is a ubiquitous feature of many real world epidemics including HIV and Hepatitis C virus infection in vivo , and computer worms spreading on the Internet . Hybrid spreading of HIV is well documented experimentally but its importance to HIV ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Hybrid Spreading Mechanisms and T Cell Activation Shape the Dynamics of HIV-1 Infection
The Toxin Complex ( TC ) is a large multi-subunit toxin first characterized in the insect pathogens Photorhabdus and Xenorhabdus , but now seen in a range of pathogens , including those of humans . These complexes comprise three protein subunits , A , B and C which in the Xenorhabdus toxin are found in a 4∶1∶1 stoichio...
Bacterial pathogens of insects deploy a range of toxins to combat the innate immune system and kill the host . There is significant interest in developing these toxins as candidates for crop protection strategies . To date , transgenic crops expressing Bacillus thuringiensis Cry toxins have been used to resist predatio...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "gram", "negative", "microbial", "pathogens", "biology", "microbiology", "host-pathogen", "interaction", "bacterial", "pathogens", "pathogenesis" ]
2012
Pdl1 Is a Putative Lipase that Enhances Photorhabdus Toxin Complex Secretion
Phylogenetically distinct Mycobacterium tuberculosis lineages differ in their phenotypes and pathogenicity . Consequently , understanding mycobacterial population structures phylogeographically is essential for design , interpretation and generalizability of clinical trials . Comprehensive efforts are lacking to date t...
Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex ( MTBc ) , which consists of seven major , phylogenetically distinct lineages and their families . West Africa is the only region in the world where , besides the common M . tuberculosis lineages , the two M . africanum lineages are ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "biogeography", "taxonomy", "ecology", "and", "environmental", "sciences", "medicine", "and", "health", "sciences", "population", "dynamics", "population", "genetics", "geographical", "locations", "tropical", "diseases", "bacterial", "diseases", "phylogenetics", "data", "...
2016
A Mycobacterial Perspective on Tuberculosis in West Africa: Significant Geographical Variation of M. africanum and Other M. tuberculosis Complex Lineages
Evolution is shaping the world around us . At the core of every evolutionary process is a population of reproducing individuals . The outcome of an evolutionary process depends on population structure . Here we provide a general formula for calculating evolutionary dynamics in a wide class of structured populations . T...
At the center of any evolutionary process is a population of reproducing individuals . The structure of this population can greatly affect the outcome of evolution . If the fitness of an individual is determined by its interactions with others , then we are in the world of evolutionary game theory . The population stru...
[ "Abstract", "Introduction", "Results", "Discussion" ]
[ "evolutionary", "biology/evolutionary", "ecology", "evolutionary", "biology/human", "evolution", "mathematics", "computational", "biology/evolutionary", "modeling", "evolutionary", "biology" ]
2009
Calculating Evolutionary Dynamics in Structured Populations
At the Drosophila NMJ , BMP signaling is critical for synapse growth and homeostasis . Signaling by the BMP7 homolog , Gbb , in motor neurons triggers a canonical pathway—which modulates transcription of BMP target genes , and a noncanonical pathway—which connects local BMP/BMP receptor complexes with the cytoskeleton ...
Synaptic activity and synapse development are intimately linked , but our understanding of the coupling mechanisms remains limited . Anterograde and retrograde signals together with trans-synaptic complexes enable intercellular communications . How synapse activity status is monitored and relayed across the synaptic cl...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "phosphorylation", "invertebrates", "medicine", "and", "health", "sciences", "nervous", "system", "electrophysiology", "neuroscience", "animals", "motor", "neurons", "animal", "models", "organisms", "developmental", "biology", "drosophila", "melanogaster", "model", "organis...
2016
A Novel, Noncanonical BMP Pathway Modulates Synapse Maturation at the Drosophila Neuromuscular Junction
Loops in proteins are flexible regions connecting regular secondary structures . They are often involved in protein functions through interacting with other molecules . The irregularity and flexibility of loops make their structures difficult to determine experimentally and challenging to model computationally . Confor...
Loops in proteins are flexible regions connecting regular secondary structures . They are often involved in protein functions through interacting with other molecules . The irregularity and flexibility of loops make their structures difficult to determine experimentally and challenging to model computationally . Despit...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry", "proteins", "protein", "folding", "protein", "structure", "biology", "and", "life", "sciences", "computational", "biology", "biophysics" ]
2014
Fast Protein Loop Sampling and Structure Prediction Using Distance-Guided Sequential Chain-Growth Monte Carlo Method
Viruses impose diverse and dynamic challenges on host defenses . Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts . The myxovirus resistance ( Mx ) genes encode interferon-inducible GTPases that constitute ...
Evolutionary analyses have the potential to reveal not only biochemical details about host-virus arms-races but also the nature of the pathogens that drove them . Primate MxB was recently shown to restrict the replication of primate lentiviruses , including HIV-1 . However , we find that positive selection in primate M...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Evolutionary Analyses Suggest a Function of MxB Immunity Proteins Beyond Lentivirus Restriction
Changes of synaptic connections between neurons are thought to be the physiological basis of learning . These changes can be gated by neuromodulators that encode the presence of reward . We study a family of reward-modulated synaptic learning rules for spiking neurons on a learning task in continuous space inspired by ...
Humans and animals learn if they receive reward . Such reward is likely to be communicated throughout the brain by neuromodulatory signals . In this paper we present a network of model neurons , which communicate by short electrical pulses ( spikes ) . Learning is achieved by modifying the input connections depending o...
[ "Abstract", "Results", "Discussion", "Methods" ]
[ "neuroscience/theoretical", "neuroscience" ]
2009
Spike-Based Reinforcement Learning in Continuous State and Action Space: When Policy Gradient Methods Fail
The upper respiratory tract mucosa is the location for commensal Streptococcus ( S . ) pneumoniae colonization and therefore represents a major site of contact between host and bacteria . The CD4+ T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invas...
The S . pneumoniae bacteria is a major cause of disease ( e . g . pneumonia and meningitis ) particularly affecting infants . In most cases bacteria can colonise the nose without causing harm , however colonisation is thought to be a prerequisite of disease . With increasing age colonization and disease , rates gradual...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "adaptive", "immunity", "immune", "cells", "aging", "and", "immunity", "streptococci", "immunity", "t", "cells", "immunology", "biology", "microbiology", "immunoregulation", "bacterial", "pathogens", "immune", "response" ]
2011
Acquisition of Pneumococci Specific Effector and Regulatory Cd4+ T Cells Localising within Human Upper Respiratory-Tract Mucosal Lymphoid Tissue
De novo creation of protein coding genes involves the formation of short ORFs from noncoding regions; some of these ORFs might then become fixed in the population . These orphan proteins need to , at the bare minimum , not cause serious harm to the organism , meaning that they should for instance not aggregate . Theref...
We show that the GC content of a genome is of great importance for the properties of an orphan protein . GC content affects the frequency of the codons and this affects the probability for each amino acid to be included in a de novo created protein . The codons encoding for Ala , Pro and Gly contain 80% GC , while codo...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "pathogens", "microbiology", "invertebrate", "genomics", "animals", "animal", "models", "age", "groups", "fungi", "drosophila", "melanogaster", "model", "organisms", ...
2017
High GC content causes orphan proteins to be intrinsically disordered
Plasmodium parasites , along with their Piroplasm relatives , have caused malaria-like illnesses in terrestrial mammals for millions of years . Several Plasmodium-protective alleles have recently evolved in human populations , but little is known about host adaptation to blood parasites over deeper evolutionary timesca...
Malaria caused by the parasite Plasmodium falciparum remains the third-most deadly infectious disease of humans . Over the last 75 , 000 years , partial genetic resistance to malaria has evolved several times , earning malaria the title of "one of the strongest selective forces on the human genome . " Yet , these human...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "parasite", "groups", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "plasmodium", "parasite", "evolution", "tropical", "diseases", "vertebrates", "parasitic", "diseases", "animals", "mammals", "parasitology", "parasitic", "protozoa...
2017
High rate of adaptation of mammalian proteins that interact with Plasmodium and related parasites
The molecular triggers for axon degeneration remain unknown . We identify endogenous Nmnat2 as a labile axon survival factor whose constant replenishment by anterograde axonal transport is a limiting factor for axon survival . Specific depletion of Nmnat2 is sufficient to induce Wallerian-like degeneration of uninjured...
In a normally functioning neuron , the cell body supplies the axon with materials needed to keep it healthy . This complex logistical activity breaks down completely after injury and often becomes compromised in neurodegenerative diseases , leading to degeneration of the isolated axon . Whilst there are probably many i...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "neurological", "disorders/peripheral", "neuropathies", "neuroscience/neuronal", "signaling", "mechanisms", "neuroscience/neurobiology", "of", "disease", "and", "regeneration", "neurological", "disorders/spinal", "disorders" ]
2010
Endogenous Nmnat2 Is an Essential Survival Factor for Maintenance of Healthy Axons
Arthropod vectors have multiple physical and immunological barriers that impede the development and transmission of parasites to new vertebrate hosts . These barriers include the peritrophic matrix ( PM ) , a chitinous barrier that separates the blood bolus from the midgut epithelia and modulates vector-pathogens inter...
Insects are responsible for transmission of parasites that cause deadly diseases in humans and animals . Understanding the key factors that enhance or interfere with parasite transmission processes can result in new control strategies . Here , we report that a proportion of tsetse flies with African trypanosome infecti...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Conclusion", "Methods" ]
[ "medicine", "and", "health", "sciences", "body", "fluids", "parasitic", "diseases", "parasitic", "protozoans", "protozoans", "mitochondria", "bioenergetics", "infectious", "disease", "control", "cellular", "structures", "and", "organelles", "cardia", "digestive", "system"...
2018
A fine-tuned vector-parasite dialogue in tsetse's cardia determines peritrophic matrix integrity and trypanosome transmission success
Immunotherapy using regulatory T cells ( Treg ) has been proposed , yet cellular and molecular mechanisms of human Tregs remain incompletely characterized . Here , we demonstrate that human Tregs promote the generation of myeloid dendritic cells ( DC ) with reduced capacity to stimulate effector T cell responses . In a...
Graft-versus-host disease ( GVHD ) is the most serious complication of bone marrow transplants between individuals ( so-called allogenic transplants ) . The class of suppressor immune cells called regulatory T cells ( Tregs ) inhibit GVHD by dampening the effects of donor immune cells in the grafted tissue . The cellul...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "immunology/immunomodulation", "hematology/bone", "marrow", "and", "stem", "cell", "transplantation", "immunology/immune", "response" ]
2010
Regulatory T Cells and Human Myeloid Dendritic Cells Promote Tolerance via Programmed Death Ligand-1
The earliest immune responses activated in acute human immunodeficiency virus type 1 infection ( AHI ) exert a critical influence on subsequent virus spread or containment . During this time frame , components of the innate immune system such as macrophages and DCs , NK cells , β-defensins , complement and other anti-m...
Acquired immune deficiency syndrome ( AIDS ) remains a major health problem worldwide , affecting predominantly the adult population in the western world and in developing countries in particular . Despite a tremendous effort to develop a cure or a vaccine that confers protection against human immunodeficiency virus ( ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry", "cell", "biology/cell", "signaling", "cell", "biology", "biochemistry/chemical", "biology", "of", "the", "cell", "chemical", "biology/protein", "chemistry", "and", "proteomics", "chemical", "biology/chemical", "biology", "of", "the", "cell" ]
2010
Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection
Thymus is crucial for generation of a diverse repertoire of T cells essential for adaptive immunity . Although thymic epithelial cells ( TECs ) are crucial for thymopoiesis and T cell generation , how TEC development and function are controlled is poorly understood . We report here that mTOR complex 1 ( mTORC1 ) in TEC...
The thymus is the primary organ for T cell generation . Abnormal thymus function profoundly affects host immunity and numerous diseases . Thymopoiesis and thymus function rely on orchestrated interaction between multiple cell types representing different origins . Among them , thymic epithelial cells ( TECs ) are cruci...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "blood", "cells", "medicine", "and", "health", "sciences", "immune", "cells", "pathology", "and", "laboratory", "medicine", "atrophy", "immunology", "cloning", "age", "groups", "adults", "signs", "and", "symptoms", "stem", "cells", "molecular", "biology", "technique...
2016
mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of γδT17 Development and TCRγ/δ Recombination
Establishing the sources of reinfestation after residual insecticide spraying is crucial for vector elimination programs . Triatoma infestans , traditionally considered to be limited to domestic or peridomestic ( abbreviated as D/PD ) habitats throughout most of its range , is the target of an elimination program that ...
Triatoma infestans , a highly domesticated species and historically the main vector of Trypanosoma cruzi , is the target of an insecticide-based elimination program in the southern cone countries of South America since 1991 . Only limited success has been achieved in the Gran Chaco region due to repeated reinfestations...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "spatial", "and", "landscape", "ecology", "medicine", "infectious", "diseases", "public", "health", "and", "epidemiology", "chagas", "disease", "ecology", "epidemiology", "genetics", "population", "genetics", "biology", "population", "ecology", "parasitic", "diseases", ...
2011
Hidden Sylvatic Foci of the Main Vector of Chagas Disease Triatoma infestans: Threats to the Vector Elimination Campaign?
Enteropathogenic Escherichia coli ( EPEC ) use a needle-like injection apparatus known as the type III secretion system ( T3SS ) to deliver protein effectors into host cells . Effector translocation is highly stratified in EPEC with the translocated intimin receptor ( Tir ) being the first effector delivered into the h...
Enteropathogenic Escherichia coli injects effector proteins into host cells using a type III secretion system ( T3SS ) . The translocated intimin receptor ( Tir ) is the first effector delivered into host cells and imparts efficient secretion of other effectors . However , the mechanism for Tir-dependent modulation of ...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "bacteriology", "dimers", "(chemical", "physics)", "complement", "system", "medicine", "and", "health", "sciences", "immune", "physiology", "pathology", "and", "laboratory", "medicine", "viral", "transmission", "and", "infection", "hela", "cells", "molecular", "probe", ...
2018
Molecular basis for CesT recognition of type III secretion effectors in enteropathogenic Escherichia coli
Treponema pallidum subsp . endemicum ( TEN ) is the causative agent of endemic syphilis ( bejel ) . An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan . The TEN 11q/j isolate was characterized using nested PCR followed by Sang...
Treponema pallidum subsp . endemicum ( TEN ) is an uncultivable pathogenic treponeme that causes bejel ( endemic syphilis ) , a chronic human infection mostly affecting children under 15 years of age , occurring mainly in several African and Middle East countries . In this work , we characterized a TEN 11q/j isolate fr...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "pathogens", "geographical", "locations", "microbiology", "sequence", "assembly", "tools", "genome", "analysis", "molecular", "biology", "techniques", "bacterial", "pathogens", "researc...
2017
Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively
Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis in many parts of the world , but there is limited knowledge of the pathogenesis of V . parahaemolyticus-induced diarrhea . The absence of an oral infection-based small animal model to study V . parahaemolyticus intestinal colonization and disea...
The marine bacterium Vibrio parahaemolyticus is a leading cause worldwide of gastroenteritis linked to the consumption of contaminated seafood . Despite the prevalence of V . parahaemolyticus-induced gastroenteritis , there is limited understanding of how this pathogen causes disease in the intestine . In part , the pa...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "infectious", "diseases", "gastroenterology", "and", "hepatology", "biology", "microbiology", "bacterial", "pathogens" ]
2012
Inflammation and Disintegration of Intestinal Villi in an Experimental Model for Vibrio parahaemolyticus-Induced Diarrhea
Riboswitches are non-coding RNA molecules that regulate gene expression by binding to specific ligands . They are primarily found in bacteria . However , one riboswitch type , the thiamin pyrophosphate ( TPP ) riboswitch , has also been described in some plants , marine protists and fungi . We find that riboswitches ar...
Thiamin , or Vitamin B1 , is an essential requirement in all living organisms because it is a co-factor for many enzymes in metabolism . Unlike animals , many yeasts can synthesize thiamin , or they can import it from the environment . Expression of thiamin biosynthesis genes and of thiamin transporters is strictly reg...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "fungal", "genetics", "gene", "regulation", "pathogens", "microbiology", "fungi", "model", "organisms", "experimental", "organism", "systems", "fungal", "pathogens", "saccharomyces", ...
2018
TPP riboswitch-dependent regulation of an ancient thiamin transporter in Candida
Temperature affects both the timing and outcome of animal development , but the detailed effects of temperature on the progress of early development have been poorly characterized . To determine the impact of temperature on the order and timing of events during Drosophila melanogaster embryogenesis , we used time-lapse...
Temperature profoundly impacts the rate of development of “cold-blooded” animals , which proceeds far faster when it is warm . There is , however , no universal relationship . Closely related species can develop at markedly different speeds at the same temperature . This creates a major challenge when comparing develop...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "invertebrates", "growth", "control", "evolutionary", "ecology", "ecology", "and", "environmental", "sciences", "animals", "animal", "models", "developmental", "biology", "drosophila", "melanogaster", "model", "organisms", "organism", "development", "evolutionary", "adaptat...
2014
Drosophila Embryogenesis Scales Uniformly across Temperature in Developmentally Diverse Species
Hemorrhagic fever viruses , including the filoviruses ( Ebola and Marburg ) and arenaviruses ( Lassa and Junín viruses ) , are serious human pathogens for which there are currently no FDA approved therapeutics or vaccines . Importantly , transmission of these viruses , and specifically late steps of budding , criticall...
Filoviruses ( Ebola and Marburg viruses ) and arenaviruses ( Lassa and Junín viruses ) are high-priority pathogens that hijack host proteins and pathways to complete their replication cycles and spread from cell to cell . Here we provide genetic and pharmacological evidence to demonstrate that the host calcium channel ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention
There has been much excitement about the possibility that exposure to specific environments can induce an ecological memory in the form of whole-sale , genome-wide epigenetic changes that are maintained over many generations . In the model plant Arabidopsis thaliana , numerous heritable DNA methylation differences have...
It continues to be hotly debated to what extent environmentally induced epigenetic change is stably inherited and thereby contributes to short-term adaptation . It has been shown before that natural Arabidopsis thaliana lines differ substantially in their methylation profiles . How much of this is independent of geneti...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biogeography", "ecology", "and", "environmental", "sciences", "plant", "science", "model", "organisms", "plant", "genomics", "epigenetics", "theoretical", "ecology", "plant", "ecology", "dna", "methylation", "arabidopsis", "thaliana", "research", "and", "analysis", "me...
2015
Century-scale Methylome Stability in a Recently Diverged Arabidopsis thaliana Lineage
Macrophages can be niches for bacterial pathogens or antibacterial effector cells depending on the pathogen and signals from the immune system . Here we show that type I and II IFNs are master regulators of gene expression during Legionella pneumophila infection , and activators of an alveolar macrophage-intrinsic immu...
Numerous intracellular bacterial pathogens replicate in specialized vacuoles within macrophages . We systematically study the molecular mechanism and the impact of macrophage-intrinsic antibacterial defense . Using L . pneumophila , an important cause of pneumonia and model organism for intracellular bacteria , we foun...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "blood", "cells", "medicine", "and", "health", "sciences", "immune", "cells", "pathology", "and", "laboratory", "medicine", "vacuoles", "intracellular", "pathogens", "pathogens", "immunology", "microbiology", "animal", "models", "model", "organisms", "mitochondria", "bi...
2016
IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid
Although enteroparasites are common causes of diarrheal illness , few studies have been performed among children in Tanzania . This study aimed to investigate the prevalence of Cryptosporidium parvum/hominis , Entamoeba histolytica and Giardia lamblia among young children in Dar es Salaam , Tanzania , and identify risk...
Diarrheal diseases are a leading cause of disease and deaths among young children . In Africa they contribute to more than one tenth of childhood deaths . Parasites like Cryptosporidium , Entamoeba histolytica and Giardia lamblia are all common causes of diarrheal illness , but there are few studies on these enteropara...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Prevalence of Cryptosporidium parvum/hominis, Entamoeba histolytica and Giardia lamblia among Young Children with and without Diarrhea in Dar es Salaam, Tanzania
Phosphoribosyl pyrophosphate synthetase ( PRPS ) is a rate-limiting enzyme whose function is important for the biosynthesis of purines , pyrimidines , and pyridines . Importantly , while missense mutations of PRPS1 have been identified in neurological disorders such as Arts syndrome , how they contribute to neuropathog...
Phosphoribosyl pyrophosphate synthetase ( PRPS ) is an important enzyme in nucleotide synthesis: the building blocks of DNA and RNA and other important metabolites . Importantly , while PRPS is mutated in neurological disorders such as Arts syndrome , Charcot-Marie-Tooth disease , and nonsyndromic sensorineural deafnes...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "death", "invertebrates", "lysosomes", "autophagic", "cell", "death", "medicine", "and", "health", "sciences", "oxidative", "stress", "cell", "processes", "animals", "animal", "models", "drosophila", "melanogaster", "model", "organisms", "experimental", "organis...
2019
Pleiotropic role of Drosophila phosphoribosyl pyrophosphate synthetase in autophagy and lysosome homeostasis
Poly ( A ) -binding proteins ( PABPs ) regulate mRNA fate by controlling stability and translation through interactions with both the poly ( A ) tail and eIF4F complex . Many organisms have several paralogs of PABPs and eIF4F complex components and it is likely that different eIF4F/PABP complex combinations regulate di...
Poly ( A ) -binding proteins ( PABPs ) bind to the poly ( A ) tails of eukaryotic mRNAs and function in regulating mRNA fate . Many eukaryotes have several PABP paralogs and the current view is that each PABP binds a specific subset of mRNAs . Trypanosoma brucei has two PABPs , and to understand the differential functi...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "cell", "physiology", "rna-binding", "proteins", "messenger", "rna", "parasitic", "protozoans", "organisms", "trypanosoma", "brucei", "fractional", "precipitation", "protozoans", "translation", "initiation", "research", "and", "analysis", "methods", "proteins", "gene", "e...
2018
Comparative proteomics of the two T. brucei PABPs suggests that PABP2 controls bulk mRNA
Severe fever with thrombocytopenia syndrome virus ( SFTSV ) , the causative agent for the fatal life-threatening infectious disease , severe fever with thrombocytopenia syndrome ( SFTS ) , was first identified in the central and eastern regions of China . Although the viral RNA was detected in free-living and parasitic...
Severe fever with thrombocytopenia syndrome virus ( SFTSV ) , a newly identified bunyavirus , has been found to circulate in mainland China , South Korea , and Japan since 2009 . This virus is the etiologic agent for an emerging fatal hemorrhagic fever , severe fever with thrombocytopenia syndrome ( SFTS ) with high fa...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
Experimental and Natural Infections of Goats with Severe Fever with Thrombocytopenia Syndrome Virus: Evidence for Ticks as Viral Vector
Hepatitis C virus ( HCV ) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers . Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population . Human monoclonal antibody...
The majority of individuals infected with hepatitis C virus ( HCV ) become chronically infected and many go on to develop liver failure requiring liver transplantation . Unfortunately , the transplanted liver becomes infected with HCV in nearly 100% of transplant patients . Current treatments for HCV are poorly tolerat...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biotechnology", "animal", "models", "of", "infection", "antivirals", "viral", "evolution", "mechanisms", "of", "resistance", "and", "susceptibility", "viral", "immune", "evasion", "virology", "immunology", "biology", "microbiology", "drug", "discovery", "immunoglobulins"...
2012
Human Monoclonal Antibody HCV1 Effectively Prevents and Treats HCV Infection in Chimpanzees
Schistosome eggs must traverse tissues of the intestine or bladder to escape the human host and further the life cycle . Escape from host tissues is facilitated by secretion of immuno-reactive molecules by eggs and the formation of an intense strong granulomatous response by the host which acts to exclude the egg into ...
Adult schistosomes live within portal veins of their human hosts . Their offspring , laid as eggs within the venous system , escape by traversing the tissues between the blood vessel and the gut or bladder lumen . Eggs voided into the external environment hatch spontaneously on contact with freshwater , and the hatched...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases/helminth", "infections", "developmental", "biology/embryology", "cell", "biology/developmental", "molecular", "mechanisms" ]
2008
Correlative and Dynamic Imaging of the Hatching Biology of Schistosoma japonicum from Eggs Prepared by High Pressure Freezing
The processing characteristics of neurons in the central auditory system are directly shaped by and reflect the statistics of natural acoustic environments , but the principles that govern the relationship between natural sound ensembles and observed responses in neurophysiological studies remain unclear . In particula...
We explore a fundamental question with regard to the representation of sound in the auditory system , namely: what are the coding strategies that underlie observed neurophysiological responses in central auditory areas ? There has been debate in recent years as to whether neural ensembles explicitly minimize their prop...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "computational", "neuroscience", "audio", "signal", "processing", "signal", "processing", "biology", "computational", "biology", "sensory", "systems", "neuroscience", "engineering", "coding", "mechanisms" ]
2013
Sustained Firing of Model Central Auditory Neurons Yields a Discriminative Spectro-temporal Representation for Natural Sounds
Several pathways control time to flowering in Arabidopsis thaliana through transcriptional and posttranscriptional gene regulation . In recent years , mRNA processing has gained interest as a critical regulator of flowering time control in plants . However , the molecular mechanisms linking RNA splicing to flowering ti...
Timing of flowering has a great effect on reproductive success and fitness . It is controlled by many external signals and internal states involving a large set of genes . Here we report that the Arabidopsis thaliana BRR2a gene is needed for normal flowering . BRR2 proteins are components of the spliceosome and highly ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "sequencing", "techniques", "rna", "extraction", "mutation", "epigenetics", "molecular", "biology", "techniques", "plants", "flowering", "plants", "extraction", "techniques", "chromatin", "research", "and", "analysis", "methods", "sequence", "analysis", "genome", "complex...
2016
BRR2a Affects Flowering Time via FLC Splicing
Multi-beam scanning electron microscopy ( mSEM ) enables high-throughput , nano-resolution imaging of macroscopic tissue samples , providing an unprecedented means for structure-function characterization of biological tissues and their cellular inhabitants , seamlessly across multiple length scales . Here we describe c...
Until recently , the assessment of organ and tissue health relied on site-sampling ( biopsy ) of micro-scale regions and was fraught with sampling errors . Overcoming these limitations requires a means for seamless imaging of organs , from their cellular inhabitants to whole organs , akin to charting a map of the organ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "stiffness", "mechanical", "properties", "medicine", "and", "health", "sciences", "diagnostic", "radiology", "engineering", "and", "technology", "cardiovascular", "anatomy", "signal", "processing", "osteoblasts", "microscopy", "pelvis", "connective", "tissue", "cells", "m...
2016
Creating High-Resolution Multiscale Maps of Human Tissue Using Multi-beam SEM
Covalent modification of DNA distinguishes cellular identities and is crucial for regulating the pluripotency and differentiation of embryonic stem ( ES ) cells . The recent demonstration that 5-methylcytosine ( 5-mC ) may be further modified to 5-hydroxymethylcytosine ( 5-hmC ) in ES cells has revealed a novel regulat...
Recent studies revealed the oxygenase-catalyzed production of 5-hydroxymethylcytosine ( 5-hmC ) as a modification to mammalian DNA . 5-hmC is known to play important roles in self-renewal and cell lineage specification in embryonic stem ( ES ) cells , suggesting a potential role for 5-hmC–mediated epigenetic regulation...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genome", "sequencing", "genomics", "chromosome", "biology", "genetics", "epigenetics", "biology", "human", "genetics", "genetics", "and", "genomics" ]
2011
Integrating 5-Hydroxymethylcytosine into the Epigenomic Landscape of Human Embryonic Stem Cells
To determine the sensitivity , specificity , and field utility of the Cepheid GeneXpert Chlamydia trachomatis ( CT ) Assay ( GeneXpert ) for ocular chlamydia infection compared to Roche Amplicor CT assay ( Amplicor ) . In a trachoma-endemic community in Kongwa Tanzania , 144 children ages 0 to 9 were surveyed to assess...
Trachoma , an eye infection caused by C . trachomatis , is the leading cause of infectious blindness worldwide , affecting the developing world . The current standard for trachoma treatment involves mass drug administration ( MDA ) of an antibiotic that is given to a community to reduce transmission . A field test for ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "neglected", "tropical", "diseases", "infectious", "diseases", "trachoma" ]
2013
Field Evaluation of the Cepheid GeneXpert Chlamydia trachomatis Assay for Detection of Infection in a Trachoma Endemic Community in Tanzania
Elg1 , the major subunit of a Replication Factor C-like complex , is critical to ensure genomic stability during DNA replication , and is implicated in controlling chromatin structure . We investigated the consequences of Elg1 loss for the dynamics of chromatin re-formation following DNA replication . Measurement of Ok...
DNA replication is the central process that duplicates the genetic information during cell multiplication . Many cellular factors play important roles in the efficient and accurate duplication of DNA , critical for faithful transmission of genetic information . One such factor is Elg1 . Elg1 acts to unload PCNA , the r...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "nucleases", "enzymes", "cell", "cycle", "and", "cell", "division", "cell", "processes", "dna-binding", "proteins", "enzymology", "fungi", "dna", "replication", "immunoprecipitation", "epigenetics", "dna", "synthesis", "phase", "co-immunoprecipitation", "chromatin", "rese...
2018
Identification of Elg1 interaction partners and effects on post-replication chromatin re-formation
Systemic lupus erythematosus ( SLE ) , a complex polygenic autoimmune disease , is associated with increased complement activation . Variants of genes encoding complement regulator factor H ( CFH ) and five CFH-related proteins ( CFHR1-CFHR5 ) within the chromosome 1q32 locus linked to SLE , have been associated with m...
Systemic lupus erythematosus ( SLE ) is a complex autoimmune disease , associated with increased complement activation . Previous studies have provided evidence for the presence of SLE susceptibility gene ( s ) in the chromosome 1q31-32 locus . Within 1q32 , genes encoding complement regulator factor H ( CFH ) and five...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "complement", "system", "clinical", "immunology", "genetic", "association", "studies", "lupus", "erythematosus", "genetics", "autoimmune", "diseases", "immunology", "biology", "human", "genetics", "genetics", "and", "genomics", "immune", "system" ]
2011
Association of Genetic Variants in Complement Factor H and Factor H-Related Genes with Systemic Lupus Erythematosus Susceptibility
Leprosy , caused by Mycobacterium leprae , can lead to scarring and deformities . Human immunodeficiency virus ( HIV ) , a lymphotropic virus with high rates of replication , leads to cell death in various stages of infection . These diseases have major social and quality of life costs , and although the relevance of t...
Leprosy and HIV infections , separately , are serious modern public health problems . Many studies have been conducted on these diseases , but knowledge gaps remain . This article provides the first account of important clinical information on a significant sample of patients with leprosy , as well as patients with bot...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Leprosy Reactions in Patients Coinfected with HIV: Clinical Aspects and Outcomes in Two Comparative Cohorts in the Amazon Region, Brazil
Chagas disease is one of the most important endemic parasitic diseases in Latin America . In its chronic phase , progression to cardiomyopathy has high morbidity and mortality . The persistence of a normal electrocardiogram ( ECG ) provides a similar prognosis to that of a non-diseased population . Benznidazole ( BNZ )...
Twenty years of follow-up of patients with Chagas disease treated with benznidazole is presented in this paper . The persistence of a normal electrocardiogram ( ECG ) provides a similar prognosis to that of a non-diseased population . Benznidazole ( BNZ ) is the only drug with trypanocidal action available in Brazil . ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "coronary", "artery", "disease", "medicine", "and", "health", "sciences", "parasite", "evolution", "tropical", "diseases", "parasitic", "diseases", "parasitology", "electrocardiography", "bioassays", "and", "physiological", "analysis", "neglected", "tropical", "diseases", ...
2016
Evaluation of Parasiticide Treatment with Benznidazol in the Electrocardiographic, Clinical, and Serological Evolution of Chagas Disease