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The classical Hodgkin-Huxley ( HH ) model neglects the time-dependence of ion concentrations in spiking dynamics . The dynamics is therefore limited to a time scale of milliseconds , which is determined by the membrane capacitance multiplied by the resistance of the ion channels , and by the gating time constants . We ...
The classical theory by Hodgkin and Huxley ( HH ) describes nerve impulses ( spikes ) that manifest communication between nerve cells . The underlying mechanism of a single spike is excitability , i . e . , a small disturbance triggers a large excursion that reverts without further input to the original state . A spike...
[ "Abstract", "Introduction", "Model", "Results", "Discussion" ]
[ "nonlinear", "dynamics", "computer", "and", "information", "sciences", "systems", "science", "mathematics", "neural", "homeostasis", "computational", "neuroscience", "single", "neuron", "function", "physiology", "biology", "and", "life", "sciences", "brain", "electrophysi...
2014
Dynamics from Seconds to Hours in Hodgkin-Huxley Model with Time-Dependent Ion Concentrations and Buffer Reservoirs
Plasmodium parasites , the causal agents of malaria , result in more than 1 million deaths annually . Plasmodium are unicellular eukaryotes with small ∼23 Mb genomes encoding ∼5200 protein-coding genes . The protein-coding genes comprise about half of these genomes . Although evolutionary processes have a significant i...
Malaria causes debilitating ill-health in millions of people and kills about one million people annually , mostly young children . It is caused by a single-cell Plasmodium parasite transmitted to humans via mosquito bites . It is difficult to control this parasite because variable genetic make-up enables it to evade de...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/population", "genetics", "infectious", "diseases", "genetics", "and", "genomics/comparative", "genomics", "evolutionary", "biology/genomics" ]
2010
Long- and Short-Term Selective Forces on Malaria Parasite Genomes
The importance of the large number of thin-diameter and unmyelinated axons that connect different cortical areas is unknown . The pronounced propagation delays in these axons may prevent synchronization of cortical networks and therefore hinder efficient information integration and processing . Yet , such global inform...
The brain mediates behavior by orchestrating the activity of billions of neurons that communicate with each other through electric impulses . The transmission of these action potentials is surprisingly slow for a large fraction of these connections . Given the importance of precise timing of neuronal activity , the fun...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2013
Emergence of Metastable State Dynamics in Interconnected Cortical Networks with Propagation Delays
Normal mode analysis ( NMA ) methods are widely used to study dynamic aspects of protein structures . Two critical components of NMA methods are coarse-graining in the level of simplification used to represent protein structures and the choice of potential energy functional form . There is a trade-off between speed and...
Normal mode analysis ( NMA ) methods can be used to explore potential movements around an equilibrium conformation by mean of calculating the eigenvectors and eigenvalues associated to different normal modes . Each normal mode represents a global collective , correlated and complex , form of motion of the entire protei...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "biochemistry", "proteins", "protein", "structure", "biology", "and", "life", "sciences", "computational", "biology", "biophysics", "molecular", "biology", "macromolecular", "structure", "analysis", "biophysical", "simulations" ]
2014
A Coarse-Grained Elastic Network Atom Contact Model and Its Use in the Simulation of Protein Dynamics and the Prediction of the Effect of Mutations
Despite the ∼1018 αβ T cell receptor ( TCR ) structures that can be randomly manufactured by the human thymus , some surface more frequently than others . The pinnacles of this distortion are public TCRs , which exhibit amino acid-identical structures across different individuals . Public TCRs are thought to result fro...
The human immune recombination machinery can generate approximately 1018 unique αβ T cell receptor structures . The recombination event , once thought to be random , has now been shown to involve enzymatic biases during chromosomal rearrangement; additional biases occur during thymic selection and antigen-driven expans...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "immunology/antigen", "processing", "and", "recognition", "immunology/immune", "response", "infectious", "diseases/viral", "infections", "immunology/immunity", "to", "infections" ]
2010
Genetic and Structural Basis for Selection of a Ubiquitous T Cell Receptor Deployed in Epstein-Barr Virus Infection
Mitotic kinesins are essential for faithful chromosome segregation and cell proliferation . Therefore , in humans , kinesin motor proteins have been identified as anti-cancer drug targets and small molecule inhibitors are now tested in clinical studies . Phylogenetic analyses have assigned five of the approximately fif...
Kinesins represent a class of mechanochemical enzymes that are able to move along microtubule filaments and transport cargo in a directional manner within the cell . Of particular importance are mitotic kinesins , as they ensure the accurate segregation of chromosomes and therefore cell survival . Such kinesins are inv...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "biology/cell", "growth", "and", "division", "microbiology/parasitology", "cell", "biology/cytoskeleton" ]
2010
Functional Characterisation and Drug Target Validation of a Mitotic Kinesin-13 in Trypanosoma brucei
Syncytins are envelope genes from endogenous retroviruses , “captured” for a role in placentation . They mediate cell-cell fusion , resulting in the formation of a syncytium ( the syncytiotrophoblast ) at the fetomaternal interface . These genes have been found in all placental mammals in which they have been searched ...
Syncytins are “captured” genes of retroviral origin , corresponding to the fusogenic envelope gene of endogenized retroviruses . They are present in all placental mammals in which they have been searched for , where they play an essential role in placentation via their cell-cell fusion activity . Here we show that they...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "cell", "physiology", "gene", "regulation", "vertebrates", "animals", "mammals", "cell", "differentiation", "muscle", "regeneration", "animal", "models", "developmental", "biology", "model", "organisms", "organism", "development", "stem", "cells", "bioassays", "and", "p...
2016
Genetic Evidence That Captured Retroviral Envelope syncytins Contribute to Myoblast Fusion and Muscle Sexual Dimorphism in Mice
Due to relatively high costs and labor required for experimental profiling of the full target space of chemical compounds , various machine learning models have been proposed as cost-effective means to advance this process in terms of predicting the most potent compound-target interactions for subsequent verification ....
Significant efforts have been devoted in recent years to the development of machine learning models to support different stages of drug development process . Given the enormous size of the chemical universe , such models could offer a complementary and cost-effective means to experimental determination of drug-target i...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "sequencing", "techniques", "medicine", "and", "health", "sciences", "protein", "interactions", "applied", "mathematics", "enzymology", "simulation", "and", "modeling", "algorithms", "mathematics", "forecasting", "statistics", "(mathematics)", "artificial", "intelligence", ...
2017
Computational-experimental approach to drug-target interaction mapping: A case study on kinase inhibitors
We present a model for flicker phosphenes , the spontaneous appearance of geometric patterns in the visual field when a subject is exposed to diffuse flickering light . We suggest that the phenomenon results from interaction of cortical lateral inhibition with resonant periodic stimuli . We find that the best temporal ...
When the human visual system is subjected to diffuse flickering light in the range of 5-25 Hz , many subjects report beautiful swirling colorful geometric patterns . In the years since Jan Purkinje first described them , there have been many qualitative and quantitative analyses of the conditions in which they occur . ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "visual", "system", "mathematics", "computational", "neuroscience", "biology", "computational", "biology", "sensory", "systems", "neuroscience", "nonlinear", "dynamics" ]
2011
A Model for the Origin and Properties of Flicker-Induced Geometric Phosphenes
KDM2A is a histone demethylase associated with transcriptional silencing , however very little is known about its in vivo role in development and disease . Here we demonstrate that loss of the orthologue kdm2aa in zebrafish causes widespread transcriptional disruption and leads to spontaneous melanomas at a high freque...
Epigenetic modifications of DNA and histones , the major components of chromatin , play a central role in transcriptional regulation . KDM2A is a histone demethylase that integrates DNA and histone modification signatures and is involved in transcriptional silencing through heterochromatin maintenance . Here we show th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "cancers", "and", "neoplasms", "vertebrates", "animals", "oncology", "animal", "models", "osteichthyes", "developmental", "biology", "negative", "staining", "model", "organisms", "experimental", "organism", "systems", "epigenetics"...
2017
Loss of the chromatin modifier Kdm2aa causes BrafV600E-independent spontaneous melanoma in zebrafish
RAS-induced MAPK signaling is a central driver of the cell proliferation apparatus . Disruption of this pathway is widely observed in cancer and other pathologies . Consequently , considerable effort has been devoted to understanding the mechanistic aspects of RAS-MAPK signal transmission and regulation . While much in...
The RAS-MAPK pathway plays a central role in the development of multicellular organisms , predominantly by regulating cell proliferation and differentiation . At its core , the pathway includes the RAS GTPase and three kinases ( RAF , MEK , and MAPK ) that transmit RAS signals through a phosphorylation cascade . Severa...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "invertebrates", "rna", "interference", "chemical", "compounds", "enzymes", "enzymology", "animals", "organic", "compounds", "animal", "models", "drosophila", "melanogaster", "model", "organisms", "basic", "amino", "acids", "amino", "acids", "epigenetics", "genetic", "i...
2016
The Deubiquitinase USP47 Stabilizes MAPK by Counteracting the Function of the N-end Rule ligase POE/UBR4 in Drosophila
The communities in fishing villages in the Great Lakes Region of Africa and particularly in Uganda experience recurrent cholera outbreaks that lead to considerable mortality and morbidity . We evaluated cholera epidemiology and population characteristics in the fishing villages of Uganda to better target prevention and...
Cholera , though a preventable and treatable disease , remains a major cause of morbidity and mortality in the Great Lakes Region of Africa , including Uganda . The communities in the fishing villages constitute 5–10% of the total Ugandan population . Most fishing villages are located along Lakes Victoria , Albert and ...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion", "Conclusions" ]
[ "medicine", "and", "health", "sciences", "ecology", "and", "environmental", "sciences", "surface", "water", "tropical", "diseases", "geographical", "locations", "uganda", "health", "care", "bacterial", "diseases", "aquatic", "environments", "bodies", "of", "water", "n...
2017
Epidemiology of cholera outbreaks and socio-economic characteristics of the communities in the fishing villages of Uganda: 2011-2015
Rift Valley fever ( RVF ) , a mosquito-borne zoonosis , is a major public health and veterinary problem in sub-Saharan Africa . Surveillance to monitor mosquito populations during the inter-epidemic period ( IEP ) and viral activity in these vectors is critical to informing public health decisions for early warning and...
Enzootic transmission of arboviral diseases such as Rift Valley Fever ( RVF ) continues to occur at a low intensity among mosquito vectors in Kenya , which may remain undetected by most monitoring programs unless very sensitive tools are employed to detect virus activity before an outbreak occurs . Here , we report a m...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "chemistry", "biology" ]
2013
Common Host-Derived Chemicals Increase Catches of Disease-Transmitting Mosquitoes and Can Improve Early Warning Systems for Rift Valley Fever Virus
It has been suggested that Schistosoma infection may be associated with Plasmodium falciparum infection or related reduction in haemoglobin level , but the nature of this interaction remains unclear . This systematic review synthesized evidence on the relationship of S . haematobium or S . mansoni infection with the oc...
A clear understanding of the epidemiology of malaria during Schistosoma co-infection is essential to inform decisions on appropriate control strategies for schistosomiasis and malaria in SSA . In this systematic review and meta-analysis , we synthesized evidence on the nature of relationship of S . haematobium and S . ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]
[ "schistosoma", "invertebrates", "schistosoma", "mansoni", "parasite", "groups", "medicine", "and", "health", "sciences", "plasmodium", "helminths", "tropical", "diseases", "microbiology", "plasmodium", "falciparum", "parasitic", "diseases", "animals", "parasitic", "protozoa...
2016
Plasmodium falciparum Infection Status among Children with Schistosoma in Sub-Saharan Africa: A Systematic Review and Meta-analysis
In this study , we investigate if phase-locking of fast oscillatory activity relies on the anatomical skeleton and if simple computational models informed by structural connectivity can help further to explain missing links in the structure-function relationship . We use diffusion tensor imaging data and alpha band-lim...
Brain imaging techniques are broadly divided into the two categories of structural and functional imaging . Structural imaging provides information about the static physical connectivity within the brain , while functional imaging provides data about the dynamic ongoing activation of brain areas . Computational models ...
[ "Abstract", "Introduction", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "neural", "networks", "engineering", "and", "technology", "nervous", "system", "applied", "mathematics", "brain", "electrophysiology", "electrophysiology", "neuroscience", "simulation", "and", "modeling", "algorithms", "mathematics",...
2016
Modeling of Large-Scale Functional Brain Networks Based on Structural Connectivity from DTI: Comparison with EEG Derived Phase Coupling Networks and Evaluation of Alternative Methods along the Modeling Path
The mammalian neocortex has a repetitious , laminar structure and performs functions integral to higher cognitive processes , including sensory perception , memory , and coordinated motor output . What computations does this circuitry subserve that link these unique structural elements to their function ? Potjans and D...
What computations do existing biophysically-plausible models of cortex perform on their inputs , and how do these computations relate to theories of cortical processing ? We begin with a computational model of cortical tissue and seek to understand its input/output transformations . Our approach limits confirmation bia...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "engineering", "and", "technology", "nervous", "system", "signal", "processing", "electrical", "circuits", "membrane", "potential", "electrophysiology", "neuroscience", "signal", "filtering", "simulation", "and", "modeling", "proba...
2016
The Computational Properties of a Simplified Cortical Column Model
Mycobacterium ulcerans disease ( Buruli ulcer ) is a neglected tropical disease common amongst children in rural West Africa . Animal experiments have shown that tissue destruction is caused by a toxin called mycolactone . A molecule was identified among acetone-soluble lipid extracts from M . ulcerans ( Mu ) -infected...
Skin infection with bacteria called Mycobacterium ulcerans causes Buruli ulcer , a disease common in West Africa and mainly affecting children . M . ulcerans is the only mycobacterium to cause disease by production of a toxin . This lipid molecule called mycolactone diffuses from the site of infection , killing surroun...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases/bacterial", "infections" ]
2010
Detection of Mycolactone A/B in Mycobacterium ulcerans–Infected Human Tissue
Parasite egress from infected erythrocytes and invasion of new red blood cells are essential processes for the exponential asexual replication of the malaria parasite . These two tightly coordinated events take place in less than a minute and are in part regulated and mediated by proteases . Dipeptidyl aminopeptidases ...
Malaria remains one of the most devastating infectious diseases and its clinical manifestation is caused by the exponential multiplication of parasites in patients . This asexual replication cycle consists of red blood cell invasion , intracellular parasite multiplication , and release ( also known as egress ) of daugh...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "parasite", "groups", "nuclear", "staining", "parasite", "replication", "plasmodium", "parasitic", "protozoans", "parasitology", "plasmid", "construction", "apicomplexa", "protozoans", "dna", "construction", "molecular", "biology", "techniques", "research", "and", "analysis...
2018
Plasmodium falciparum dipeptidyl aminopeptidase 3 activity is important for efficient erythrocyte invasion by the malaria parasite
Among animal species , cell types vary greatly in terms of number and kind . The number of cell types found within an organism differs considerably between species , and cell type diversity is a significant contributor to differences in organismal structure and function . These observations suggest that cell type origi...
Animals consist of a wide variety of cells that serve different functions depending on their location in the body . Cells with similar functions , or cell types , in different animal species are related both by an evolutionary line of descent—similar to the relatedness of species themselves—and by a developmental line ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "death", "cellular", "stress", "responses", "forkhead", "box", "evolutionary", "biology", "gene", "regulation", "cell", "processes", "hormones", "developmental", "biology", "small", "interfering", "rnas", "proteins", "gene", "expression", "biochemistry", "rna", ...
2018
The mammalian decidual cell evolved from a cellular stress response
Translesion DNA synthesis ( TLS ) by specialized DNA polymerases ( Pols ) is a conserved mechanism for tolerating replication blocking DNA lesions . The actions of TLS Pols are managed in part by ring-shaped sliding clamp proteins . In addition to catalyzing TLS , altered expression of TLS Pols impedes cellular growth ...
Bacterial DNA polymerase IV ( Pol IV ) is capable of replicating damaged DNA via a process termed translesion DNA synthesis ( TLS ) . Pol IV-mediated TLS can be accurate or error-prone , depending on the type of DNA damage . Errors made by Pol IV contribute to antibiotic resistance and adaptation of bacterial pathogens...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
A Genetic Selection for dinB Mutants Reveals an Interaction between DNA Polymerase IV and the Replicative Polymerase That Is Required for Translesion Synthesis
Convergent phenotypic evolution is often caused by recurrent changes at particular nodes in the underlying gene regulatory networks ( GRNs ) . The genes at such evolutionary ‘hotspots’ are thought to maximally affect the phenotype with minimal pleiotropic consequences . This has led to the suggestion that if a GRN is u...
A major goal of biology is to identify the genetic causes of organismal diversity . Convergent evolution of traits is often caused by changes in the same genes–evolutionary ‘hotspots’ . shavenbaby is a ‘hotspot’ for larval trichome loss in Drosophila , but microRNA-92a underlies the gain of leg trichomes . To understan...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "invertebrates", "plant", "anatomy", "trichomes", "medicine", "and", "health", "sciences", "legs", "limbs", "(anatomy)", "animals", "animal", "models", "developmental", "biology", "plant", "science", "model", "organisms", "drosophila", "melanogaster", "experimental", "o...
2018
Gene regulatory network architecture in different developmental contexts influences the genetic basis of morphological evolution
The inhibitor of apoptosis protein ( IAP ) family has been implicated in immune regulation , but the mechanisms by which IAP proteins contribute to immunity are incompletely understood . We show here that X-linked IAP ( XIAP ) is required for innate immune control of Listeria monocytogenes infection . Mice deficient in...
During a bacterial infection , the innate immune response plays two critical roles: controlling early bacterial replication and stimulating the adaptive immune response to clear infection . Host recognition of bacterial components occurs through pathogen sensors at the cell surface or within the host cell cytosol . Inh...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "microbiology/immunity", "to", "infections", "microbiology/innate", "immunity", "immunology/innate", "immunity", "infectious", "diseases/bacterial", "infections", "immunology/immunity", "to", "infections" ]
2008
XIAP Regulates Cytosol-Specific Innate Immunity to Listeria Infection
We introduce a flexible and robust simulation-based framework to infer demographic parameters from the site frequency spectrum ( SFS ) computed on large genomic datasets . We show that our composite-likelihood approach allows one to study evolutionary models of arbitrary complexity , which cannot be tackled by other cu...
We present a new likelihood-based method to infer the past demography of a set of populations from large genomic datasets . Our method can be applied to arbitrarily complex models as the likelihood is estimated by coalescent simulations . Under simple scenarios , our method behaves similarly to a widely used diffusion-...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2013
Robust Demographic Inference from Genomic and SNP Data
The cuticular exoskeleton of insects and other arthropods is a remarkably versatile material with a complex multilayer structure . We made use of the ability to isolate cuticle synthesizing cells in relatively pure form by dissecting pupal wings and we used RNAseq to identify genes expressed during the formation of the...
Insects and other arthropods are an extremely successful group of animals . A unique and key feature of their lifestyle is their chitin containing cuticular exoskeleton , a complex layered material , which remains rather poorly understood for so prominent of a biological material . We have characterized the gene expres...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "chitin", "invertebrates", "animals", "animal", "models", "drosophila", "melanogaster", "animal", "anatomy", "model", "organisms", "microscopy", "materials", "science", "zoology", "macromolecules", "drosophila", "materials", "by", "structure", "research", "and", "analysis...
2016
The Gene Expression Program for the Formation of Wing Cuticle in Drosophila
Trypanosoma brucei gambiense is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness , a disease endemic across often poor and rural areas of Western and Central Africa . We have previously published the genome sequence of a T . b . brucei isolate , and have now employed a comparative genom...
Sleeping sickness , or Human African Trypanosomiasis , is a disease affecting the health and productivity of poor people in many rural areas of sub-Saharan Africa . The disease is caused by a single-celled flagellate , Trypanosoma brucei , which evades the immune system by periodically switching the proteins on its sur...
[ "Abstract", "Introduction", "Methods", "Results/Discussion" ]
[ "genetics", "and", "genomics/gene", "discovery", "genetics", "and", "genomics/comparative", "genomics", "evolutionary", "biology/evolutionary", "and", "comparative", "genetics", "infectious", "diseases/neglected", "tropical", "diseases", "evolutionary", "biology/genomics", "gen...
2010
The Genome Sequence of Trypanosoma brucei gambiense, Causative Agent of Chronic Human African Trypanosomiasis
Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle rather than its entry into host cells . However , little is known about the stimuli elicited upon such pathogen host-cell interactions . Here , we report that type IV pili ( Tfp ) -producing Neisseria gonorrhoeae ( P+GC ) induces an immed...
Like many bacterial pathogens , successful attachment of Neisseria gonorrhoeae—the causative agent of the sexually transmitted disease gonorrhoea—to its host cells depends on specialized structures on the bacterial surface called type IV pili ( Tfp ) . Pathogen attachment induces changes within host cells that may faci...
[ "Abstract", "Introduction", "Results/Discussion", "Methods" ]
[ "infectious", "diseases/bacterial", "infections", "cell", "biology/cytoskeleton", "molecular", "biology", "cell", "biology/cell", "signaling" ]
2010
Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements
Following the widespread use of genome-wide association studies ( GWAS ) , focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits . As a step towards a high-throughput method to identify genome-wide , non-coding , functional regulatory variants , we describe...
The identification of genetic variants associated with complex diseases has rapidly grown through lowering costs of genome sequencing and the use of large-scale genotyping chips based on this sequencing data . There have not been corresponding advances in the identification of causal genetic variants compared to varian...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genome-wide", "association", "studies", "genome", "expression", "analysis", "genomics", "functional", "genomics", "gene", "expression", "genetics", "molecular", "genetics", "biology", "human", "genetics", "population", "genetics", "genetics", "of", "disease", "genetics",...
2012
Use of Allele-Specific FAIRE to Determine Functional Regulatory Polymorphism Using Large-Scale Genotyping Arrays
Cyclic AMP-activated intestinal Cl− secretion plays an important role in pathogenesis of cholera . This study aimed to investigate the effect of diclofenac on cAMP-activated Cl− secretion , its underlying mechanisms , and possible application in the treatment of cholera . Diclofenac inhibited cAMP-activated Cl− secreti...
Diarrhea in cholera results from stimulation of cAMP-mediated intestinal Cl− secretion by cholera toxin ( CT ) . This study demonstrates that diclofenac , a widely used non-steroidal anti-inflammatory drug ( NSAID ) , inhibited cAMP-activated Cl− secretion in human intestinal epithelial ( T84 ) cells by inhibiting both...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "gastroenterology", "and", "hepatology", "medicine", "and", "health", "sciences" ]
2014
Inhibition of cAMP-Activated Intestinal Chloride Secretion by Diclofenac: Cellular Mechanism and Potential Application in Cholera
Challenges in maintaining high effectiveness of classic vector control in urban areas has renewed the interest in indoor residual spraying ( IRS ) as a promising approach for Aedes-borne disease prevention . While IRS has many benefits , application time and intrusive indoor applications make its scalability in urban a...
Vector control is the primary strategy for managing Aedes aegypti and reducing transmission of Aedes-borne diseases; however , the indoor resting behavior of Ae . aegypti and the evolution of insecticide resistance reduces the effectiveness of many vector control tactics . Indoor residual spraying ( IRS ) is effective ...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "chemical", "compounds", "carbamates", "tropical", "diseases", "parasitic", "diseases", "animals", "organic", "compounds", "infectious", "disease", "control", "insect", "vectors", "zoology", "public", "and", "occ...
2019
Efficacy of novel indoor residual spraying methods targeting pyrethroid-resistant Aedes aegypti within experimental houses
Extensive cell-to-cell variation exists even among putatively identical cells , and there is great interest in understanding how the properties of transcription relate to this heterogeneity . Differential expression from the two gene copies in diploid cells could potentially contribute , yet our ability to measure from...
In mammals , most cells of the body contain two genetic datasets: one from the mother and one from the father , and—in theory—these two sets of information could contribute equally to produce the molecules in a given cell . In practice , however , this is not always the case , which can have dramatic implications for m...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "sequencing", "techniques", "medicine", "and", "health", "sciences", "x", "chromosome", "inactivation", "gene", "regulation", "messenger", "rna", "dna", "transcription", "simulation", "and", "modeling", "molecular", "biology", "techniques", "epigenetics", "rna", "sequen...
2019
Allele-specific RNA imaging shows that allelic imbalances can arise in tissues through transcriptional bursting
Long non-coding ( lnc ) RNAs are numerous and found throughout the mammalian genome , and many are thought to be involved in the regulation of gene expression . However , the majority remain relatively uncharacterised and of uncertain function making the use of model systems to uncover their mode of action valuable . I...
Long non-coding ( lnc ) RNAs are numerous in the mammalian genome and many have been implicated in gene regulation . However , the vast majority are uncharacterised and of uncertain function making known functional lncRNAs valuable models for understanding their mechanism of action . One mode of lncRNA action is to rec...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "prader-willi", "syndrome", "long", "non-coding", "rnas", "disorders", "of", "imprinting", "developmental", "biology", "epigenetics", "chromatin", "embryology", "genetic", "interference", "chromosome", "biology", "genomic", "imprin...
2019
The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes
Chagas disease ( CD ) , caused by the protozoan Trypanosoma cruzi , is a prototypical neglected tropical disease . Specific immunity promotes acute phase survival . Nevertheless , one-third of CD patients develop chronic chagasic cardiomyopathy ( CCC ) associated with parasite persistence and immunological unbalance . ...
The idea that Chagas disease ( CD ) has an important autoimmune involvement contributed to delay the development of therapies and vaccines . CD is a parasitic neglected disease which afflicts millions of people mostly in Latin America . The cardiac form is the main clinical manifestation of CD . Currently , patients wi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy
Cortical oscillations are likely candidates for segmentation and coding of continuous speech . Here , we monitored continuous speech processing with magnetoencephalography ( MEG ) to unravel the principles of speech segmentation and coding . We demonstrate that speech entrains the phase of low-frequency ( delta , theta...
Continuous speech is organized into a nested hierarchy of quasi-rhythmic components ( prosody , syllables , phonemes ) with different time scales . Interestingly , neural activity in the human auditory cortex shows rhythmic modulations with frequencies that match these speech rhythms . Here , we use magnetoencephalogra...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "auditory", "system", "natural", "language", "processing", "cognitive", "neuroscience", "computational", "neuroscience", "sensory", "systems", "biology", "computational", "biology", "neuroscience", "neuroimaging" ]
2013
Speech Rhythms and Multiplexed Oscillatory Sensory Coding in the Human Brain
The objectives of this study were to 1 ) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal , placental , and cord blood , 2 ) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes , and 3 ) evaluate the impact of other helmint...
Schistosomiasis is one of the most prevalent parasitic tropical diseases , and it is primarily treated with the drug praziquantel . This study examined the effects of praziquantel treatment for schistosomiasis and the presence of geohelminth infections during pregnancy on cytokines in maternal , placental , and cord bl...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "invertebrates", "innate", "immune", "system", "medicine", "and", "health", "sciences", "reproductive", "system", "immune", "physiology", "cytokines", "body", "fluids", "maternal", "health", "obstetrics", "and", "gynecology", "helminths", "immunology", "tropical", "dise...
2019
Maternal, placental and cord blood cytokines and the risk of adverse birth outcomes among pregnant women infected with Schistosoma japonicum in the Philippines
In HPV–related cancers , the “high-risk” human papillomaviruses ( HPVs ) are frequently found integrated into the cellular genome . The integrated subgenomic HPV fragments express viral oncoproteins and carry an origin of DNA replication that is capable of initiating bidirectional DNA re-replication in the presence of ...
High-risk human papillomavirus infection can cause several types of cancers . During the normal virus life cycle , these viruses maintain their genomes as multicopy nuclear plasmids in infected cells . However , in cancer cells , the viral plasmids are lost , which leaves one of the HPV genomes to be integrated into th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "virology/viral", "replication", "and", "gene", "regulation", "virology/viruses", "and", "cancer", "virology/host", "antiviral", "responses" ]
2009
Mechanism of Genomic Instability in Cells Infected with the High-Risk Human Papillomaviruses
An algorithm is presented that returns the optimal pairwise gapped alignment of two sets of signed numerical sequence values . One distinguishing feature of this algorithm is a flexible comparison engine ( based on both relative shape and absolute similarity measures ) that does not rely on explicit gap penalties . Add...
Trend discovery is an important way to generate understanding from large amounts of data . We have developed a novel tool that discovers significantly similar trends shared between two numerical data sets . Since the tool's algorithmic method compares both the relative shapes of the “peaks” and “valleys” in the data , ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2013
A Horizontal Alignment Tool for Numerical Trend Discovery in Sequence Data: Application to Protein Hydropathy
Despite many prior studies demonstrating offline behavioral gains in motor skills after sleep , the underlying neural mechanisms remain poorly understood . To investigate the neurophysiological basis for offline gains , we performed single-unit recordings in motor cortex as rats learned a skilled upper-limb task . We f...
Sleep has been shown to help in consolidating learned motor tasks . In other words , sleep can induce “offline” gains in a new motor skill even in the absence of further training . However , how sleep induces this change has not been clearly identified . One hypothesis is that consolidation of memories during sleep occ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation
During infection the host imposes manganese and zinc starvation on invading pathogens . Despite this , Staphylococcus aureus and other successful pathogens remain capable of causing devastating disease . However , how these invaders adapt to host-imposed metal starvation and overcome nutritional immunity remains unknow...
The ubiquitous pathogen Staphylococcus aureus is a serious threat to human health due to the continued spread of antibiotic resistance . This spread has made it challenging to treat staphylococcal infections and led to the call for new approaches to treat this devastating pathogen . One approach is to disrupt the abili...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "chemical", "compounds", "manganese", "engineering", "and", "technology", "pathogens", "microbiology", "carbohydrates", "staphylococcus", "aureus", "organic", "compounds", "glucose", "o...
2016
The Two-Component System ArlRS and Alterations in Metabolism Enable Staphylococcus aureus to Resist Calprotectin-Induced Manganese Starvation
The mechanisms by which human immunodeficiency virus type 1 ( HIV-1 ) crosses mucosal surfaces to establish infection are unknown . Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody . We found that the combination of acidic pH and Env-specific IgG , including that from cervicovag...
HIV-1 causes a sexually transmitted disease . However , the mechanisms employed by the virus to cross genital tract tissue and establish infection are uncertain . Since cervicovaginal fluid is acidic and HIV-1 in cervicovaginal fluid is likely coated with antibodies , we explored the effect of low pH and HIV-1-specific...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2013
The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells
The mutation rate is known to vary between adjacent sites within the human genome as a consequence of context , the most well-studied example being the influence of CpG dinucelotides . We investigated whether there is additional variation by testing whether there is an excess of sites at which both humans and chimpanze...
Understanding the process of mutation is important , not only mechanistically , but also because it has implications for the analysis of sequence evolution and population genetic inference . The mutation rate is known to differ between sites within the human genome . The most dramatic example of this is when a C is fol...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics", "evolutionary", "biology" ]
2009
Cryptic Variation in the Human Mutation Rate
The positioning of the DNA replication machinery ( replisome ) has been the subject of several studies . Two conflicting models for replisome localization have been proposed: In the Factory Model , sister replisomes remain spatially co-localized as the replicating DNA is translocated through a stationary replication fa...
Cell proliferation depends on efficient replication of the genome . Bacteria typically have a single origin of replication on a circular chromosome . After replication initiation , two replisomes assemble at the origin and each copy one of the two arms of the chromosome until they reach the terminus . There have been c...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "fluorescence", "imaging", "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "cell", "division", "analysis", "cell", "cycle", "and", "cell", "division", "pathogens", "cell", "processes", "bacillus", "microbiology", "light", "micros...
2017
The Replisomes Remain Spatially Proximal throughout the Cell Cycle in Bacteria
The gamma-herpesvirus Epstein-Barr virus ( EBV ) persists for life in infected individuals despite the presence of a strong immune response . During the lytic cycle of EBV many viral proteins are expressed , potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells . We have recently i...
Epstein-Barr virus ( EBV ) is carried by approximately 90% of the world's population , where it persists and is chronically shed despite a vigorous specific immune response , a key component of which are CD8+ T cells that recognize and kill infected cells . The mechanisms the virus uses to evade these responses are not...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "immunology/antigen", "processing", "and", "recognition", "virology/viral", "replication", "and", "gene", "regulation", "immunology/immune", "response", "virology/immune", "evasion", "immunology/immunity", "to", "infections" ]
2009
Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle
Chromatin insulators/boundary elements share the ability to insulate a transgene from its chromosomal context by blocking promiscuous enhancer–promoter interactions and heterochromatin spreading . Several insulating factors target different DNA consensus sequences , defining distinct subfamilies of insulators . Whether...
The genome of eukaryotes is packaged in chromatin , which consists of DNA , histones , and accessory proteins . This leads to a general repression of genes , particularly for those exposed to mostly condensed , heterochromatin regions . DNA sequences called chromatin insulators/boundary elements are able to insulate a ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "biology", "computational", "biology", "molecular", "biology" ]
2008
BEAF Regulates Cell-Cycle Genes through the Controlled Deposition of H3K9 Methylation Marks into Its Conserved Dual-Core Binding Sites
Behavioral and neuroimaging evidence shows that human decisions are sensitive to the statistical regularities ( mean , variance , skewness , etc . ) of reward distributions . However , it is unclear what representations human observers form to approximate reward distributions , or probability distributions in general ....
Life is full of uncertainties: An action may yield multiple possible consequences and a percept may imply multiple possible causes . To survive , humans and animals must compensate for the uncertainty in the environment and in their own perceptual and motor systems . However , how humans represent probability distribut...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "statistical", "noise", "decision", "making", "statistics", "social", "sciences", "vertebrates", "neuroscience", "animals", "mammals", "primates", "probability", "distribution", "mathematics", "cognitive", "psychology", "cognition", "skewness", "gaussian", "noise", "statist...
2019
Human representation of multimodal distributions as clusters of samples
Of the membrane proteins of known structure , we found that a remarkable 67% of the water soluble domains are structurally similar to water soluble proteins of known structure . Moreover , 41% of known water soluble protein structures share a domain with an already known membrane protein structure . We also found that ...
Membrane proteins play important roles in cellular communication and molecular transport . However , experimental difficulties and lack of structural information have limited the functional characterization of membrane proteins . In this study , we find that over 60% of the extramembrane domains were structurally relat...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biology", "computational", "biology" ]
2013
Rampant Exchange of the Structure and Function of Extramembrane Domains between Membrane and Water Soluble Proteins
The emergence of variant Creutzfeldt Jakob Disease ( vCJD ) is considered a likely consequence of human dietary exposure to Bovine Spongiform Encephalopathy ( BSE ) agent . More recently , secondary vCJD cases were identified in patients transfused with blood products prepared from apparently healthy donors who later w...
Variant Creutzfeldt Jakob Disease ( vCJD ) cases were identified in patients who received blood products that had been prepared from donors who later developed the disease . The blood borne transmission of vCJD is a major concern for blood transfusion banks , plasma derived products manufacturers and public health auth...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "biotechnology", "public", "and", "occupational", "health", "infectious", "diseases", "medicine", "and", "health", "sciences", "biology", "and", "life", "sciences" ]
2014
Preclinical Detection of Variant CJD and BSE Prions in Blood
The scarcity of information on the immature stages of sand flies and their preferred breeding sites has resulted in the focus of vectorial control on the adult stage using residual insecticide house-spraying . This strategy , along with the treatment of human cases and the euthanasia of infected dogs , has proven ineff...
Sand flies are the vectors of a number of pathogens that infect man , especially cutaneous and visceral leishmaniasis . The control of sand flies through residual house-spraying insecticide has proven inefficient in preventing the spread of these diseases in several areas of the globe . Sand flies have a life cycle inc...
[ "Abstract", "Introduction", "Methods", "Results" ]
[]
2013
Larval Breeding Sites of Lutzomyia longipalpis (Diptera: Psychodidae) in Visceral Leishmaniasis Endemic Urban Areas in Southeastern Brazil
Bacterial biofilms account for a significant number of hospital-acquired infections and complicate treatment options , because bacteria within biofilms are generally more tolerant to antibiotic treatment . This resilience is attributed to transient bacterial subpopulations that arise in response to variations in the mi...
Bacteria are commonly found in multicellular communities known as biofilms . Biofilms can form on a variety of surfaces , both outside and within living things , and can have detrimental effects on human health . The characteristics of bacteria occupying different areas within biofilms are not well understood , and suc...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Adhesive Fiber Stratification in Uropathogenic Escherichia coli Biofilms Unveils Oxygen-Mediated Control of Type 1 Pili
Most cellular processes are conducted by multi-protein complexes . However , little is known about how these complexes are assembled . In particular , it is not known if they are formed while one or more members of the complexes are being translated ( cotranslational assembly ) . We took a genomic approach to address t...
Most proteins do not function in isolation . Instead , they associate with other proteins to form complexes . Little is known about the assembly of protein complexes within cells . One possibility is that proteins are completely synthesised before they bind to each other . An alternative is that proteins attach to each...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry", "functional", "genomics", "protein", "interactions", "proteins", "genetics", "biology", "genomics", "gene", "networks", "genetics", "and", "genomics" ]
2011
Widespread Cotranslational Formation of Protein Complexes
Schlafen11 ( encoded by the SLFN11 gene ) has been shown to inhibit the accumulation of HIV-1 proteins . We show that the SLFN11 gene is under positive selection in simian primates and is species-specific in its activity against HIV-1 . The activity of human Schlafen11 is relatively weak compared to that of some other ...
Schlafen11 was recently identified as a human antiviral protein with activity against HIV-1 . Here we show that some nonhuman primate versions of Schlafen11 are much stronger at blocking the accumulation of viral proteins than is human Schlafen11 . These relatively larger phenotypes of nonhuman primate Schlafen11 allow...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "molecular", "probe", "techniques", "293t", "cells", "pathogens", "biological", "cultures", "microbiology", "vertebrates", "marmosets", "immunoblotting", "animals", "mammals", "retrovir...
2016
Non-human Primate Schlafen11 Inhibits Production of Both Host and Viral Proteins
The fungal cell wall not only plays a critical role in maintaining cellular integrity , but also forms the interface between fungi and their environment . The composition of the cell wall can therefore influence the interactions of fungi with their physical and biological environments . Chitin , one of the main polysac...
Magnaporthe oryzae is a filamentous fungal pathogen which causes devastating crop losses in rice . Successful invasion of the host is dependent upon the ability of the fungus to remain undetected by the innate immune system of the plant , which recognizes conserved components of the fungal cell wall , such as chitin . ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "chitin", "cell", "walls", "plant", "anatomy", "plant", "cell", "biology", "fungal", "structure", "plant", "cell", "walls", "cereal", "crops", "fungi", "plant", "science", "rice", "model", "organisms", "developmental", "biology", "materials", "science", "crops", "...
2016
Chitosan Mediates Germling Adhesion in Magnaporthe oryzae and Is Required for Surface Sensing and Germling Morphogenesis
The reports on the origin of human CD8+ Vα24+ T-cell receptor ( TCR ) natural killer T ( NKT ) cells are controversial . The underlying mechanism that controls human CD4 versus CD8 NKT cell development is not well-characterized . In the present study , we have studied total 177 eligible patients and subjects including ...
We show that the average frequency of total and CD8+ NKT cells in PBMCs from 128 healthy latent EBV-infected subjects is significantly higher than in 17 patients with acute lytic EBV infection , 16 EBV-associated HL patients , and 16 EBV-negative normal subjects . The frequency of total and CD8+ NKT cells is remarkably...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology/cell", "differentiation", "immunology/leukocyte", "development", "immunology/immunity", "to", "infections", "immunology/innate", "immunity" ]
2010
EBV Promotes Human CD8+ NKT Cell Development
African trypanosomes are extracellular parasitic protozoa , predominantly transmitted by the bite of the haematophagic tsetse fly . The main mechanism considered to mediate parasitemia control in a mammalian host is the continuous interaction between antibodies and the parasite surface , covered by variant-specific sur...
African trypanosomiasis is a disease caused by different species of extracellular flagellated protozoan trypanosome parasites . Trypanosomes have developed a mechanism of regular antigenic variation of their variant-specific surface glycoprotein ( VSG ) coat which allows chronic infection . Replacement of this coat occ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases/protozoal", "infections", "immunology/immunity", "to", "infections" ]
2008
The Role of B-cells and IgM Antibodies in Parasitemia, Anemia, and VSG Switching in Trypanosoma brucei–Infected Mice
Single-molecule tweezers measurements of double-stranded nucleic acids ( dsDNA and dsRNA ) provide unprecedented opportunities to dissect how these fundamental molecules respond to forces and torques analogous to those applied by topoisomerases , viral capsids , and other biological partners . However , tweezers data a...
DNA and RNA are fundamental molecules in the central dogma of molecular biology . Many biological behaviors of double-stranded DNA and RNA – including transcription/translation by proteins and packaging into compact structures – depend on their ability to flex and twist . Single-molecule tweezers now provide accurate m...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "biochemistry", "rna", "nucleic", "acids", "biology", "and", "life", "sciences", "dna", "biophysics", "biophysical", "simulations" ]
2014
Blind Predictions of DNA and RNA Tweezers Experiments with Force and Torque
α-defensins are abundant antimicrobial peptides with broad , potent antibacterial , antifungal , and antiviral activities in vitro . Although their contribution to host defense against bacteria in vivo has been demonstrated , comparable studies of their antiviral activity in vivo are lacking . Using a mouse model defic...
Mammals express abundant antimicrobial peptides , including α-defensins , to protect their epithelial surfaces from microbes . α-defensins are potently antibacterial and antiviral ex vivo; however , their contribution to host defense from viral infection in vivo has not been demonstrated . We show that mice lacking fun...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "paneth", "cells", "antimicrobials", "medicine", "and", "health", "sciences", "immune", "physiology", "viral", "transmission", "and", "infection", "drugs", "immunology", "microbiology", "vertebrates", "mice", "animals", "mammals", "epithelial", "cells", "animal", "model...
2016
Defensins Potentiate a Neutralizing Antibody Response to Enteric Viral Infection
Synchronized neuronal activity is vital for complex processes like behavior . Circadian pacemaker neurons offer an unusual opportunity to study synchrony as their molecular clocks oscillate in phase over an extended timeframe ( 24 h ) . To identify where , when , and how synchronizing signals are perceived , we first s...
Circadian molecular clocks are essential for daily cycles in animal behavior and we have a good understanding of how these clocks work in individual pacemaker neurons . However , the accuracy of these individual clocks is meaningless unless they are synchronized with one another . In this study we show that synchronizi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "circadian", "rhythms", "biochemistry", "molecular", "neuroscience", "behavioral", "neuroscience", "animal", "genetics", "cellular", "neuroscience", "genetics", "chronobiology", "biology", "and", "life", "sciences", "neuroscience", "circadian", "oscillators" ]
2014
Differentially Timed Extracellular Signals Synchronize Pacemaker Neuron Clocks
Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni ( blood fluke ) and Fasciola hepatica ( liver fluke ) . These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis , respectively . As no vaccine is currently available for ant...
Schistosomiasis and fascioliasis are caused by two related trematodes found within the phylum Platyhelminthes ( flatworms ) , and are classified as neglected diseases of poverty due to their effects on people living in the most underprivileged areas of the world . With no vaccine currently near development , and the ex...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
The Diterpenoid 7-Keto-Sempervirol, Derived from Lycium chinense, Displays Anthelmintic Activity against both Schistosoma mansoni and Fasciola hepatica
We assess how presymptomatic infection affects predictability of infectious disease epidemics . We focus on whether or not a major outbreak ( i . e . an epidemic that will go on to infect a large number of individuals ) can be predicted reliably soon after initial cases of disease have appeared within a population . Fo...
Emerging epidemics pose a significant challenge to human health worldwide . Accurate real-time forecasts of whether or not initial reports will be followed by a major outbreak are necessary for efficient deployment of control . For all infectious diseases , there is a delay between infection and the appearance of sympt...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "infectious", "disease", "epidemiology", "pathogens", "tropical", "diseases", "ebola", "hemorrhagic", "fever", "probability", "distribution", "mathematics", "forecasting", "statistics", ...
2016
Detecting Presymptomatic Infection Is Necessary to Forecast Major Epidemics in the Earliest Stages of Infectious Disease Outbreaks
The invasive forms of apicomplexan parasites share a conserved form of gliding motility that powers parasite migration across biological barriers , host cell invasion and egress from infected cells . Previous studies have established that the duration and direction of gliding motility are determined by actin polymeriza...
Gliding motility is a unique property of the Apicomplexa . Members of this phylum include important human and animal pathogens . An actomyosin-based machine powers parasite motility and is crucial for parasite migration across biological barriers , host cell invasion and egress from infected cells . The timing , durati...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases/protozoal", "infections", "microbiology/cellular", "microbiology", "and", "pathogenesis", "cell", "biology/cytoskeleton" ]
2010
Concerted Action of Two Formins in Gliding Motility and Host Cell Invasion by Toxoplasma gondii
Fundamental aspects of embryonic and post-natal development , including maintenance of the mammalian female germline , are largely unknown . Here we employ a retrospective , phylogenetic-based method for reconstructing cell lineage trees utilizing somatic mutations accumulated in microsatellites , to study female germl...
Many aspects of mammalian female germline development during embryogenesis and throughout adulthood are either unknown or under debate . In this study we applied a novel method for the reconstruction of cell lineage trees utilizing microsatellite mutations , accumulated during mouse life , in oocytes and other cells , ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "algorithms", "systems", "biology", "developmental", "biology", "computer", "science", "genomics", "mathematics", "physiology", "genetics", "biology", "anatomy", "and", "physiology", "evolutionary", "biology", "population", "biology", "computational", "biology", "genetics",...
2012
Cell Lineage Analysis of the Mammalian Female Germline
Cellular receptors usually contain a designated sensory domain that recognizes the signal . Per/Arnt/Sim ( PAS ) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans . Although PAS domains were described as intracellular sensors , recent structural studies revealed PAS-like domains in ...
Cell-surface receptors control multiple cellular functions and are attractive targets for drug design . These receptors often have dedicated extracellular domains that bind signaling molecules , such as hormones and nutrients . Computational identification of these ligand-binding domains in genomic sequences is a pre-r...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "sequencing", "techniques", "database", "searching", "social", "sciences", "neuroscience", "molecular", "biology", "techniques", "sequence", "similarity", "searching", "research", "and", "analysis", "methods", "sequence", "analysis", "sequence", "alignment", "proteins", "...
2016
Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes
It is widely documented that hybridisation occurs between many closely related species , but the importance of introgression in adaptive evolution remains unclear , especially in animals . Here , we have examined the role of introgressive hybridisation in transferring adaptations between mimetic Heliconius butterflies ...
Hybridisation occurs between many animal species , however its evolutionary relevance is still a matter of great debate . While some argue that hybridisation leads to maladaptive gene combinations , and therefore to an evolutionary dead end , others consider interspecific hybridisation as a process with great potential...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "introgression", "biology", "evolutionary", "biology", "hybridization", "evolutionary", "processes" ]
2012
Adaptive Introgression across Species Boundaries in Heliconius Butterflies
Hepatitis C virus ( HCV ) is a blood-borne pathogen and a major cause of liver disease worldwide . Gene expression profiling was used to characterize the transcriptional response to HCV H77c infection . Evidence is presented for activation of innate antiviral signaling pathways as well as induction of lipid metabolism ...
Hepatitis C virus is a common cause of liver disease worldwide . The details of how HCV causes liver disease are not well understood . It has been thought that HCV infection does not kill liver cells directly , but indirectly by stimulating the immune system to kill HCV-infected liver cells . In this study we have used...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "virology/viral", "replication", "and", "gene", "regulation", "virology/animal", "models", "of", "infection", "infectious", "diseases/viral", "infections", "virology/effects", "of", "virus", "infection", "on", "host", "gene", "expression", "virology/host", "antiviral", "r...
2009
HCV Induces Oxidative and ER Stress, and Sensitizes Infected Cells to Apoptosis in SCID/Alb-uPA Mice
Controlled human malaria infection ( CHMI ) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development . However , power calculations are essential to obtain meaningful estimates of protective efficacy , while minimizing the risk of adverse events . To optimize power calculati...
Controlled human malaria infection ( CHMI ) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development . However , to obtain meaningful estimates of protective efficacy , it is important to include an appropriate minimum number of participants , while minimizing the risks and ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "body", "fluids", "parasite", "replication", "immunology", "tropical", "diseases", "parasitic", "diseases", "parasitic", "protozoans", "parasitology", "vaccines", "preventive", "medicine", "protozoans", "mathematics", "statistics", ...
2017
The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection
Ductal carcinoma is one of the most common cancers among women , and the main cause of death is the formation of metastases . The development of metastases is caused by cancer cells that migrate from the primary tumour site ( the mammary duct ) through the blood vessels and extravasating they initiate metastasis . Here...
Breast cancer is caused by genetic mutations leading to uncontrollable cell reproduction . During successive proliferations , the progenies of tumour cells acquire further mutations increasing their heterogeneity . Among the tumoural mutated cells , there are some which present specific markers of increased aggressiven...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2015
Modelling Circulating Tumour Cells for Personalised Survival Prediction in Metastatic Breast Cancer
ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases , usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs . While several PARPs have known antiviral activities , these activities are mostly indep...
ADP-ribosylation , an understudied post-translational modification , facilitates the host response to virus infection . Several viruses , including all members of the coronavirus family , encode a macrodomain to reverse ADP-ribosylation and combat this immune response . As such , viruses with mutations in the macrodoma...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "medicine", "and", "health", "sciences", "vesicular", "stomatitis", "virus", "pathology", "and", "laboratory", "medicine", "gene", "regulation", "pathogens", "microbiology", "light", "microscopy", "viruses", "rna", "viruses", "microscopy", "adp-ribosylation", "research", ...
2019
The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression
The sexual Fus3 MAP kinase module of yeast is highly conserved in eukaryotes and transmits external signals from the plasma membrane to the nucleus . We show here that the module of the filamentous fungus Aspergillus nidulans ( An ) consists of the AnFus3 MAP kinase , the upstream kinases AnSte7 and AnSte11 , and the A...
Mitogen activated protein ( MAP ) kinase cascades are conserved from yeast to man to transmit an external signal to the nucleus and induce an appropriate cellular response . The yeast Fus3 MAP kinase module represents a textbook paradigm for signal transduction . The pathway is activated by external sexual hormones tri...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "protein", "interactions", "microbiology", "gene", "function", "developmental", "biology", "model", "organisms", "molecular", "development", "molecular", "genetics", "microbial", "growth", "and", "development", "gene", "expression", "biology", "proteomics", "molecular", "...
2012
The Aspergillus nidulans MAPK Module AnSte11-Ste50-Ste7-Fus3 Controls Development and Secondary Metabolism
The healing of a fracture depends largely on the development of a new blood vessel network ( angiogenesis ) in the callus . During angiogenesis tip cells lead the developing sprout in response to extracellular signals , amongst which vascular endothelial growth factor ( VEGF ) is critical . In order to ensure a correct...
The healing of a fracture largely depends on the development of a new blood vessel network ( angiogenesis ) , which can be investigated and simulated with mathematical models . The current mathematical models of angiogenesis during fracture healing do not , however , implement all relevant biological scales ( e . g . a...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "biotechnology", "medicine", "anatomy", "and", "physiology", "cardiovascular", "biomedical", "engineering", "biological", "systems", "engineering", "bone", "bioengineering", "musculoskeletal", "system", "theoretical", "biology", "biology", "cardiovascular", "system", "systems...
2012
MOSAIC: A Multiscale Model of Osteogenesis and Sprouting Angiogenesis with Lateral Inhibition of Endothelial Cells
Recommended treatment for severe rabies exposure in unvaccinated individuals includes wound cleaning , administration of rabies immunoglobulins ( RIG ) , and rabies vaccination . We conducted a survey of rabies treatment outcomes in the Philippines . This was a case series involving 7 , 660 patients ( 4 months to 98 ye...
Infection from a bite by a rabid animal is fatal unless rapid treatment ( thorough cleaning of the wound , administration of rabies immunoglobulins ( RIG ) , and a full anti-rabies vaccination course ) is provided . Ideally human RIG should be used , but cheaper , more readily available purified horse RIG ( pERIG ) are...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases/infectious", "diseases", "of", "the", "nervous", "system", "infectious", "diseases/viral", "infections", "pathology/neuropathology", "virology/emerging", "viral", "diseases" ]
2008
Rabies Post-Exposure Prophylaxis in the Philippines: Health Status of Patients Having Received Purified Equine F(ab')2 Fragment Rabies Immunoglobulin (Favirab)
A meta-analysis of the effects of vector saliva on the immune response and progression of vector-transmitted disease , specifically with regard to pathology , infection level , and host cytokine levels was conducted . Infection in the absence or presence of saliva in naïve mice was compared . In addition , infection in...
Arthropod vectors transmit a wide variety of diseases resulting in substantial human morbidity and economic costs worldwide . When hematophagous arthropods blood feed , they release saliva into the host . This saliva elicits a strong immune response and has recently been a focus for vaccine research . There is evidence...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "infectious", "diseases", "infectious", "disease", "immunology", "veterinary", "diseases", "zoonoses", "medicine", "and", "health", "sciences", "clinical", "immunology", "leishmaniasis", "biology", "and", "life", "sciences", "immunology", "vector-borne", "diseases", "vete...
2014
Meta-analysis of the Effects of Insect Vector Saliva on Host Immune Responses and Infection of Vector-Transmitted Pathogens: A Focus on Leishmaniasis
The Notch pathway controls proliferation during development and in adulthood , and is frequently affected in many disorders . However , the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging . Here , we address the complexity of Notch signal...
Communication between cells is critical for controlling proliferation , and the Notch signal transduction pathway plays a well-established and evolutionary conserved role during these processes . However , in spite of numerous studies of this pathway over the years , the genetic sensitivity of the pathway , combined wi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "abdomen", "gene", "regulation", "cell", "cycle", "and", "cell", "division", "cell", "processes", "neuroscience", "animals", "notch", "signaling", "animal", "models", "drosophila", "melanogaster", "model", "org...
2016
Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling
Cryptosporidium epidemiology is poorly understood , but infection is suspected of contributing to childhood malnutrition and diarrhea-related mortality worldwide . A prospective cohort of 108 women and their infants in rural/semi-rural Tanzania were followed from delivery through six months . Cryptosporidium infection ...
Early infancy and childhood Cryptosporidium infection is associated with poor nutritional status , stunted growth , and cognitive deficits , yet minimal research is available regarding the burden and risk factors worldwide . Since there is no vaccine available , and because diagnostic challenges exist and treatment for...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "neonatology", "hiv", "infections", "medicine", "and", "health", "sciences", "maternal", "health", "geographical", "locations", "parasitic", "diseases", "parasitology", "pediatrics", "health", "care", "age", "groups", "nutrition", "women's", "health", "tanzania", "infan...
2014
Cryptosporidium Prevalence and Risk Factors among Mothers and Infants 0 to 6 Months in Rural and Semi-Rural Northwest Tanzania: A Prospective Cohort Study
Capillaries are the prime location for oxygen and nutrient exchange in all tissues . Despite their fundamental role , our knowledge of perfusion and flow regulation in cortical capillary beds is still limited . Here , we use in vivo measurements and blood flow simulations in anatomically accurate microvascular network ...
Glucose and oxygen are key energy sources of the brain . As energy storage capabilities are limited in the brain , a continuous supply of oxygen and glucose via the bloodstream is crucial for the brain’s functioning . The bulk of discharge occurs at the level of capillaries , which are the smallest and most frequent ve...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "blood", "cells", "medicine", "and", "health", "sciences", "body", "fluids", "classical", "mechanics", "fluid", "mechanics", "cardiovascular", "anatomy", "oxygen", "blood", "counts", "capillaries", "red", "blood", "cells", "arterioles", "blood", "vessels", "animal", ...
2019
Red blood cells stabilize flow in brain microvascular networks
Organisms cope with physiological stressors through acclimatizing mechanisms in the short-term and adaptive mechanisms over evolutionary timescales . During adaptation to an environmental or genetic perturbation , beneficial mutations can generate numerous physiological changes: some will be novel with respect to prior...
Acclimatizing and adaptive ( evolutionary ) processes allow organisms to thrive despite cellular and environmental perturbations . Our work examined whether adaptation restores stress responses towards wild-type ( pre-stressed ) versus novel physiological states during adaptation by studying a bacterium ( Methylobacter...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genome", "expression", "analysis", "microbial", "metabolism", "gene", "regulation", "population", "genetics", "microbiology", "parallel", "evolution", "microbial", "evolution", "molecular", "genetics", "forms", "of", "evolution", "microbial", "physiology", "metabolic", "...
2013
Evolution after Introduction of a Novel Metabolic Pathway Consistently Leads to Restoration of Wild-Type Physiology
Human embryonic stem cells ( hESCs ) and neural progenitor ( NP ) cells are excellent models for recapitulating early neuronal development in vitro , and are key to establishing strategies for the treatment of degenerative disorders . While much effort had been undertaken to analyze transcriptional and epigenetic diffe...
Deriving neural progenitors ( NP ) from human embryonic stem cells ( hESC ) is the first step in creating homogeneous populations of cells that will differentiate into myriad neuronal subtypes necessary to form a human brain . During alternative RNA splicing ( AS ) , noncoding sequences ( introns ) in a pre-mRNA are di...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "homo", "(human)", "computational", "biology", "neuroscience" ]
2007
Alternative Splicing Events Identified in Human Embryonic Stem Cells and Neural Progenitors
Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis ( PCM ) , whose drug therapy is usually prolonged and associated with toxic side effects and relapses . The current study was undertaken to determine if the injection of a T helper (...
P . brasiliensis is a thermally dimorphic human pathogenic fungus that causes paracoccidioidomycosis ( PCM ) , the most prevalent human systemic mycosis in Latin America , whose drug therapy is usually prolonged and associated with toxic side effects and relapses . Although immunostimulatory therapy is a promising appr...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results/Discussion" ]
[ "infectious", "diseases", "immunology/immunomodulation", "infectious", "diseases/fungal", "infections", "immunology", "immunology/immunity", "to", "infections" ]
2008
T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis
We study the elongation stage of mRNA translation in eukaryotes and find that , in contrast to the assumptions of previous models , both the supply and the demand for tRNA resources are important for determining elongation rates . We find that increasing the initiation rate of translation can lead to the depletion of s...
In this paper we show that the rate at which proteins are produced can be controlled at the elongation stage of mRNA translation . Regulation of translation initiation has been a focus of much study , but the subsequent effect of changes in the initiation rate on the overall translation rate , and the role of slow and ...
[ "Abstract", "Introduction", "Methods", "Results", "What", "is", "the", "Nature", "of", "the", "Queueing?", "Mixtures", "of", "Multiple", "mRNA", "Species", "Discussion" ]
[ "physics", "rna", "rna", "processing", "statistical", "mechanics", "nucleic", "acids", "biophysic", "al", "simulations", "biology", "computational", "biology", "biophysics", "simulations", "biophysics" ]
2011
The Dynamics of Supply and Demand in mRNA Translation
An accurate diagnosis is essential for the control of infectious diseases . In the search for effective and efficient tests , biosensors have increasingly been exploited for the development of new and highly sensitive diagnostic methods . Here , we describe a new fluorescent based immunosensor comprising magnetic polym...
Dogs are the most important domestic reservoirs of the parasite Leishmania infantum . Some infected animals develop a subclinical infection , without the classical symptoms characteristics of this disease . One of the major challenges in the serodiagnosis of canine leishmaniasis is the detection of actively infected an...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "infectious", "diseases", "veterinary", "diseases", "immunology", "biology", "microbiology", "veterinary", "science" ]
2013
Development of a Fluorescent Based Immunosensor for the Serodiagnosis of Canine Leishmaniasis Combining Immunomagnetic Separation and Flow Cytometry
Infection with HIV-1 perturbs homeostasis of human T cell subsets , leading to accelerated immunologic deterioration . While studying changes in CD4+ memory and naïve T cells during HIV-1 infection , we found that a subset of CD4+ effector memory T cells that are CCR7−CD45RO−CD45RA+ ( referred to as TEMRA cells ) , was...
HIV-1 infection profoundly perturbs the immune system and is characterized by depletion of CD4+ T cells and chronic immune activation , which lead to AIDS . Although HIV-1 targets CD4+ T cells , it also requires a second receptor in order to infect the target cells . The majority of HIV-1 strains that are transmitted u...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "viruses", "infectious", "diseases", "immunology", "homo", "(human)" ]
2007
Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection
Clustered Regularly Interspaced Short Palindromic Repeats ( CRISPR ) , together with associated genes ( cas ) , form the CRISPR–cas adaptive immune system , which can provide resistance to viruses and plasmids in bacteria and archaea . Here , we use mathematical models , population dynamic experiments , and DNA sequenc...
The evidence that the CRISPR regions of the genomes of archaea and bacteria play a role in the ecology and ( co ) evolution of these microbes and their viruses is overwhelming: ( i ) the spacers ( variable sequences of 26–72 bp of DNA between the repeats of this region ) of these prokaryotes are homologous to the DNA o...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "model", "organisms", "theoretical", "biology", "ecology", "genetics", "biology", "microbiology", "evolutionary", "biology", "population", "biology", "genetics", "and", "genomics" ]
2013
The Population and Evolutionary Dynamics of Phage and Bacteria with CRISPR–Mediated Immunity
ZEBRA is a site-specific DNA binding protein that functions as a transcriptional activator and as an origin binding protein . Both activities require that ZEBRA recognizes DNA motifs that are scattered along the viral genome . The mechanism by which ZEBRA discriminates between the origin of lytic replication and promot...
Epstein-Barr virus encodes a protein , ZEBRA , which plays an essential role in the switch between viral latency and the viral lytic cycle . ZEBRA activates transcription of early viral genes and also promotes lytic viral DNA replication . It is not understood how these two functions are discriminated . We studied five...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "molecular", "biology/dna", "replication", "virology/viral", "replication", "and", "gene", "regulation", "virology/viruses", "and", "cancer", "virology" ]
2010
A Subset of Replication Proteins Enhances Origin Recognition and Lytic Replication by the Epstein-Barr Virus ZEBRA Protein
Phenotypic mutations are errors that occur during protein synthesis . These errors lead to amino acid substitutions that give rise to abnormal proteins . Experiments suggest that such errors are quite common . We present a model to study the effect of phenotypic mutation rates on the amount of abnormal proteins in a ce...
A functional protein machinery , built from genetic information , is central to every living organism . Surprisingly , the decoding of genes into amino acid sequences is fairly inaccurate . Errors in this process ( phenotypic mutations ) are several orders of magnitude more frequent than errors during DNA replication (...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion", "Mutation", "Rates", "at", "Equilibrium", "Effect", "of", "Initial", "Values", "and", "Parameters", "on", "the", "Simulation", "Results" ]
[ "computational", "biology", "evolutionary", "biology", "saccharomyces" ]
2007
Phenotypic Mutation Rates and the Abundance of Abnormal Proteins in Yeast
Cyclic nucleotide signalling is a major regulator of malaria parasite differentiation . Phosphodiesterase ( PDE ) enzymes are known to control cyclic GMP ( cGMP ) levels in the parasite , but the mechanisms by which cyclic AMP ( cAMP ) is regulated remain enigmatic . Here , we demonstrate that Plasmodium falciparum pho...
Cyclic nucleotide signalling pathways are ubiquitous in eukaryotes and regulate a plethora of cellular processes . Pathway components include cyclases and phosphodiesterases that synthesise and break down the intracellular second messengers cyclic AMP ( cAMP ) and cyclic GMP ( cGMP ) ; the signal is translated into a c...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "phosphorylation", "parasite", "groups", "medicine", "and", "health", "sciences", "body", "fluids", "plasmodium", "enzymes", "enzymology", "plasmodium", "falciparum", "parasitic", "protozoans", "parasitology", "apicomplexa", "protozoans", "sequence", "motif", "analysis", ...
2019
Phosphodiesterase beta is the master regulator of cAMP signalling during malaria parasite invasion
In most settings , the diagnosis of scabies is reliant on time-consuming and potentially intrusive clinical examination of all accesible regions of skin . With the recent recognition of scabies as a neglected tropical disease by the World Health Organization there is a need for standardised approaches to disease mappin...
Scabies , caused by infestation with the microscopic mite Sarcoptes scabiei , is a major public health problem worldwide , particularly in low- and middle-income tropical settings . The diagnosis of scabies is reliant on detection of characteristic signs on clinical examination . Examination of the whole body is time-c...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "legs", "feet", "decision", "making", "tropical", "diseases", "social", "sciences", "parasitic", "diseases", "neuroscience", "cognitive", "psychology", "ectoparasitic", "infections", "sexually", "transmitted", "diseases", "cognitio...
2018
Exploration of a simplified clinical examination for scabies to support public health decision-making
A facile and efficient method for the precise editing of large viral genomes is required for the selection of attenuated vaccine strains and the construction of gene therapy vectors . The type II prokaryotic CRISPR-Cas ( clustered regularly interspaced short palindromic repeats ( CRISPR ) -associated ( Cas ) ) RNA-guid...
The clustered regularly interspaced short palindromic repeats ( CRISPR ) -associated ( Cas ) system was discovered as a component of the bacterial acquired immune system that cleaves foreign DNA . This system is now used for site-specific genome editing in a wide range of organisms , including bacteria , yeasts , plant...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biotechnology", "medicine", "and", "health", "sciences", "viral", "transmission", "and", "infection", "virology", "epidemiology", "vector", "biology", "biology", "and", "life", "sciences", "microbiology", "disease", "vectors", "genetic", "engineering", "viral", "vector...
2014
High-Efficiency Targeted Editing of Large Viral Genomes by RNA-Guided Nucleases
For two decades , onchocerciasis control has been based on mass treatment with ivermectin ( IVM ) , repeated annually or six-monthly . This drug kills Onchocerca volvulus microfilariae ( mf ) present in the skin and the eyes ( microfilaricidal effect ) and prevents for 3–4 months the release of new mf by adult female w...
Onchocerciasis , also known as river blindness , is a parasitic disease due to the filarial nematode Onchocerca volvulus . It affects more than 37 million people worldwide , most of them ( 99% ) living in Africa . The control of river blindness is , up to now , based on annual or six-monthly mass treatment with ivermec...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "helminth", "infections", "infectious", "diseases", "medicine", "and", "health", "sciences", "neglected", "tropical", "diseases", "tropical", "diseases", "infectious", "disease", "control", "onchocerciasis", "parasitic", "diseases" ]
2014
Reproductive Status of Onchocerca volvulus after Ivermectin Treatment in an Ivermectin-Naïve and a Frequently Treated Population from Cameroon
Most humans harbor both CD177neg and CD177pos neutrophils but 1–10% of people are CD177null , placing them at risk for formation of anti-neutrophil antibodies that can cause transfusion-related acute lung injury and neonatal alloimmune neutropenia . By deep sequencing the CD177 locus , we catalogued CD177 single nucleo...
Expression of the neutrophil-specific antigen CD177 varies across the population . 1–10% of humans are CD177null . CD177pos neonates born to CD177null mothers are susceptible to alloimmune neutropenia . Interestingly , CD177pos and CD177neg populations of neutrophils often exist together within individuals . The reason...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "blood", "cells", "sequencing", "techniques", "pseudogenes", "medicine", "and", "health", "sciences", "immune", "cells", "immunology", "variant", "genotypes", "alleles", "genetic", "mapping", "gene", "types", "molecular", "biology", "techniques", "dna", "gene", "conve...
2016
Heterogeneity of Human Neutrophil CD177 Expression Results from CD177P1 Pseudogene Conversion
In most bacteria , Clp protease is a conserved , non-essential serine protease that regulates the response to various stresses . Mycobacteria , including Mycobacterium tuberculosis ( Mtb ) and Mycobacterium smegmatis , unlike most well studied prokaryotes , encode two ClpP homologs , ClpP1 and ClpP2 , in a single opero...
Due to the significant and rapid rise in multidrug resistant Mycobacterium tuberculosis ( Mtb ) , there is an urgent need to validate novel drug targets for the treatment of tuberculosis . Here , we show that Clp protease is an ideal potential target . Mtb encodes two ClpP genes , ClpP1 and ClpP2 , which associate toge...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "biology" ]
2012
Mycobacterium tuberculosis ClpP1 and ClpP2 Function Together in Protein Degradation and Are Required for Viability in vitro and During Infection
The larval salivary gland of Drosophila melanogaster synthesizes and secretes glue glycoproteins that cement developing animals to a solid surface during metamorphosis . The steroid hormone 20-hydroxyecdysone ( 20E ) is an essential signaling molecule that modulates most of the physiological functions of the larval gla...
During animal development the physiological response of individual tissues is often “reprogrammed” in response to signaling molecules . One important example is the activity of nuclear-hormone receptors that are controlled by small lipid compounds such as steroids and retinoids . Thus , understanding how tissue-specifi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "molecular", "biology/transcription", "initiation", "and", "activation", "genetics", "and", "genomics/gene", "expression", "cell", "biology/cell", "signaling", "cell", "biology/developmental", "molecular", "mechanisms", "genetics", "and", "genomics/gene", "function", "develop...
2008
A Novel Ecdysone Receptor Mediates Steroid-Regulated Developmental Events during the Mid-Third Instar of Drosophila
Dengue is the most prevalent arboviral disease in humans and a major public health problem worldwide . Systemic plasma leakage , leading to hypovolemic shock and potentially fatal complications , is a critical determinant of dengue severity . Recently , we and others described a novel pathogenic effect of secreted deng...
Dengue is the most prevalent mosquito-borne disease in humans and represents a major public health problem worldwide . Leakage of fluids and molecules from the bloodstream into tissues can lead to shock and potentially death and is a critical determinant of dengue disease severity . Recently , we showed that a secreted...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "binding", "cell", "physiology", "medicine", "and", "health", "sciences", "nuclear", "staining", "pathology", "and", "laboratory", "medicine", "pathogens", "endothelial", "cells", "permeability", "microbiology", "light", "microscopy", "epithelial", "cells", "vir...
2016
Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability
Viral attachment to target cells is the first step in infection and also serves as a determinant of tropism . Like many viruses , mammalian reoviruses bind with low affinity to cell-surface carbohydrate receptors to initiate the infectious process . Reoviruses disseminate with serotype-specific tropism in the host , wh...
Receptor utilization plays an important role in viral disease . Viruses must recognize a receptor or sometimes multiple receptors to infect a cell . Mammalian orthoreoviruses ( reoviruses ) serve as useful models for studies of viral receptor binding and pathogenesis . The reovirus experimental system allows manipulati...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biomacromolecule-ligand", "interactions", "biochemistry", "proteins", "virology", "protein", "structure", "biology", "microbiology", "host-pathogen", "interaction", "biophysics" ]
2012
The GM2 Glycan Serves as a Functional Coreceptor for Serotype 1 Reovirus
Chromodomains are found in many regulators of chromatin structure , and most of them recognize methylated lysines on histones . Here , we investigate the role of the Drosophila melanogaster protein Corto's chromodomain . The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene e...
Chromatin , the combination of DNA and histones , strongly impacts transcriptional regulation of genes . This is achieved thanks to various protein complexes that bind chromatin and remodel its structure . These complexes bind specific motifs , also called epigenetic marks , through specific protein domains . Among the...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "molecular", "development", "genetics", "gene", "expression", "epigenetics", "biology", "molecular", "genetics", "gene", "regulation", "chromatin", "genetics", "and", "genomics", "dna", "transcription", "gene", "function" ]
2012
New Partners in Regulation of Gene Expression: The Enhancer of Trithorax and Polycomb Corto Interacts with Methylated Ribosomal Protein L12 Via Its Chromodomain
ES cells are defined as self-renewing , pluripotent cell lines derived from early embryos . Cultures of ES cells are also characterized by the expression of certain markers thought to represent the pluripotent state . However , despite the widespread expression of key markers such as Oct4 and the appearance of a charac...
Embryonic stem ( ES ) cells are karyotypically normal , embryo-derived cell lines that are pluripotent , i . e . capable of generating all the cell types of the future organism , but not the extra-embryonic lineages . What gives ES cells this unique capacity ? Here , we use a fluorescent reporter cell line that employs...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "developmental", "biology/stem", "cells", "cell", "biology/cell", "signaling", "genetics", "and", "genomics/gene", "expression", "cell", "biology/developmental", "molecular", "mechanisms", "developmental", "biology/cell", "differentiation", "cell", "biology/gene", "expression" ...
2010
Functional Heterogeneity of Embryonic Stem Cells Revealed through Translational Amplification of an Early Endodermal Transcript
Superoxide dismutase-1 ( SOD1 ) maturation comprises a string of posttranslational modifications which transform the nascent peptide into a stable and active enzyme . The successive folding , metal ion binding , and disulphide acquisition steps in this pathway can be catalysed through a direct interaction with the copp...
Cellular complexity necessitates an equally complex network of courier proteins to internalise , sort , and deliver biologically useful metals like copper . These relay systems negotiate a landscape of metal-binding sites through handshake–handoff interactions , but the mechanisms that impart a necessary transience are...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "chemical", "bonding", "chemical", "compounds", "oxides", "enzymes", "enzymology", "dismutases", "organisms", "fungi", "crystals", "materials", "science", "sequence", "motif", "analysis", "oligomers", "hydrogen", "bonding", "physical", "chemistry", "research", "and", "a...
2019
Molecular recognition and maturation of SOD1 by its evolutionarily destabilised cognate chaperone hCCS
Bam32 , a 32 kDa adaptor molecule , plays important role in B cell receptor signalling , T cell receptor signalling and antibody affinity maturation in germinal centres . Since antibodies against trypanosome variant surface glycoproteins ( VSG ) are critically important for control of parasitemia , we hypothesized that...
African trypanosomiasis continues to be a major threat to human health and economic development in sub-Saharan Africa . Despite intense studies , the immunopathogenesis of the disease remains poorly understood . Understanding the factors that regulate disease pathogenesis would be important in designing effective immun...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
The B Cell Adaptor Molecule Bam32 Is Critically Important for Optimal Antibody Response and Resistance to Trypanosoma congolense Infection in Mice
The localization of specific mRNAs can establish local protein gradients that generate and control the development of cellular asymmetries . While all evidence underscores the importance of the cytoskeleton in the transport and localization of RNAs , we have limited knowledge of how these events are regulated . Using a...
The localization of messenger RNA is a major mechanism to generate local asymmetries in protein activities and is utilized in a diverse array of biological functions . mRNA localization and the resultant protein gradients are critical for the establishment of embryonic axes , the polarized motility of cells and neurons...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion", "Supporting", "Information" ]
[ "drosophila", "cell", "biology" ]
2008
Motility Screen Identifies Drosophila IGF-II mRNA-Binding Protein—Zipcode-Binding Protein Acting in Oogenesis and Synaptogenesis
The recently developed ‘two-step’ behavioural task promises to differentiate model-based from model-free reinforcement learning , while generating neurophysiologically-friendly decision datasets with parametric variation of decision variables . These desirable features have prompted its widespread adoption . Here , we ...
Planning is the use of a predictive model of the consequences of actions to guide decision making . Planning plays a critical role in human behaviour , but isolating its contribution is challenging because it is complemented by control systems which learn values of actions directly from the history of reinforcement , r...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Simple Plans or Sophisticated Habits? State, Transition and Learning Interactions in the Two-Step Task
The cellular PI3K/Akt and/or MEK/ERK signaling pathways mediate the entry process or endosomal acidification during infection of many viruses . However , their roles in the early infection events of group A rotaviruses ( RVAs ) have remained elusive . Here , we show that late-penetration ( L-P ) human DS-1 and bovine N...
Viral particles must transport their genome into the cytoplasm or the nucleus of host cells to initiate successful infection . Knowledge of how viruses may pirate host cell signaling cascades or molecules to promote their own replication can facilitate the development of antiviral drugs . Group A rotavirus ( RVA ) is a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "immune", "physiology", "gene", "regulation", "immunology", "microbiology", "signal", "inhibition", "immunoprecipitation", "antibodies", "research", "and", "analysis", "methods", "erk", "signaling", "cascade", "small", "interfering...
2018
Activation of PI3K, Akt, and ERK during early rotavirus infection leads to V-ATPase-dependent endosomal acidification required for uncoating
Segment 7 of influenza A virus produces up to four mRNAs . Unspliced transcripts encode M1 , spliced mRNA2 encodes the M2 ion channel , while protein products from spliced mRNAs 3 and 4 have not previously been identified . The M2 protein plays important roles in virus entry and assembly , and is a target for antiviral...
Influenza A virus is a pathogen capable of infecting a wide range of avian and mammalian hosts , causing seasonal epidemics and pandemics in humans . In recent years , the unexpected coding capacity of the virus has begun to be unravelled , with the identification of three more protein products ( PB1-F2 , PB1-N40 and P...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "biochemistry", "public", "health", "and", "epidemiology", "immunology", "biology", "molecular", "cell", "biology", "public", "health" ]
2012
Identification of a Novel Splice Variant Form of the Influenza A Virus M2 Ion Channel with an Antigenically Distinct Ectodomain
The rise of resistance together with the shortage of new broad-spectrum antibiotics underlines the urgency of optimizing the use of available drugs to minimize disease burden . Theoretical studies suggest that coordinating empirical usage of antibiotics in a hospital ward can contain the spread of resistance . However ...
The rise of antibiotic resistance is a major concern for public health . In hospitals , frequent usage of antibiotics leads to high resistance levels; at the same time the patients are especially vulnerable . We therefore urgently need treatment strategies that limit resistance without compromising patient care . Here ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "organismal", "evolution", "medicine", "and", "health", "sciences", "infectious", "disease", "epidemiology", "microbiology", "bacterial", "diseases", "emerging", "infectious", "diseases", "population", "modeling", "microbial", "evolution", "population", "biology", "infectio...
2014
Cycling Empirical Antibiotic Therapy in Hospitals: Meta-Analysis and Models