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As Zika virus continues to spread , decisions regarding resource allocations to control the outbreak underscore the need for a tool to weigh policies according to their cost and the health burden they could avert . For example , to combat the current Zika outbreak the US President requested the allocation of $1 . 8 bil...
Using data on Zika virus , microcephaly , and Guillain-Barré syndrome cases from Brazil and Colombia , we compute ranges for the probability of a microcephaly outcome in infants born to Zika-infected women ( 0 . 49% to 2 . 10% , based on data from Northeast Brazil ) and the probability of Guillain-Barré syndrome in Zik...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "microcephaly", "pathology", "and", "laboratory", "medicine", "cost-effectiveness", "analysis", "chikungunya", "infection", "demography", "economic", "analysis", "pathogens", "geographical", "locations", "microbiology", "social", "sc...
2016
A Cost-Effectiveness Tool for Informing Policies on Zika Virus Control
Correlations in spike-train ensembles can seriously impair the encoding of information by their spatio-temporal structure . An inevitable source of correlation in finite neural networks is common presynaptic input to pairs of neurons . Recent studies demonstrate that spike correlations in recurrent neural networks are ...
The spatio-temporal activity pattern generated by a recurrent neuronal network can provide a rich dynamical basis which allows readout neurons to generate a variety of responses by tuning the synaptic weights of their inputs . The repertoire of possible responses and the response reliability become maximal if the spike...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "circuit", "models", "computational", "neuroscience", "biology", "computational", "biology", "coding", "mechanisms" ]
2012
Decorrelation of Neural-Network Activity by Inhibitory Feedback
Every year about 3 million tourists from around the world visit Brazil , Argentina and Paraguay´s triple border region where the Iguaçu Falls are located . Unfortunately , in recent years an increasing number of autochthonous canine and human visceral leishmaniasis ( VL ) cases have been reported . The parasite is Leis...
Every year about 3 million tourists from around the world visit Brazil , Argentina and Paraguay´s triple border region where the Iguaçu Falls are located . Unfortunately , in recent years an increasing number of autochthonous canine and human visceral leishmaniasis ( VL ) cases have been reported in this area . Our stu...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "atmospheric", "science", "geographical", "locations", "tropical", "diseases", "vertebrates", "sand", "flies", "parasitic", "diseases", "parasitic", "protozoans", "animals", "mammals", "dogs", "protozoans", "leishmania", "neglected...
2018
Hidden danger: Unexpected scenario in the vector-parasite dynamics of leishmaniases in the Brazil side of triple border (Argentina, Brazil and Paraguay)
Hyaloperonospora arabidopsidis ( Hpa ) is an obligate biotroph oomycete pathogen of the model plant Arabidopsis thaliana and contains a large set of effector proteins that are translocated to the host to exert virulence functions or trigger immune responses . These effectors are characterized by conserved amino-termina...
Oomycete plant pathogens are among the most devastating agricultural pests and employ arsenals of effector proteins to manipulate their plant hosts . Some of these effectors , however , are recognized in the plant and trigger an immune response . Hyaloperonospora arabidopsidis ( Hpa ) causes downy mildew on the model p...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "agriculture", "biology" ]
2012
Computational Prediction and Molecular Characterization of an Oomycete Effector and the Cognate Arabidopsis Resistance Gene
Several strategies have been pursued to increase the extent of exon 7 inclusion during splicing of SMN2 ( survival of motor neuron 2 ) transcripts , for eventual therapeutic use in spinal muscular atrophy ( SMA ) , a genetic neuromuscular disease . Antisense oligonucleotides ( ASOs ) that target an exon or its flanking...
Spinal muscular atrophy ( SMA ) is a severe genetic disease that causes motor-neuron degeneration . SMA patients lack a functional SMN1 ( survival of motor neuron 1 ) gene , but they possess an intact SMN2 gene , which though nearly identical to SMN1 , is only partially functional . The defect in SMN2 gene expression i...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods", "Supporting", "Information" ]
[ "primates", "biochemistry", "cell", "biology", "homo", "(human)", "animals", "neuroscience", "molecular", "biology", "genetics", "and", "genomics" ]
2007
Enhancement of SMN2 Exon 7 Inclusion by Antisense Oligonucleotides Targeting the Exon
Salt fortified with the drug , diethylcarbamazine ( DEC ) , and introduced into a competitive market has the potential to overcome the obstacles associated with tablet-based Lymphatic Filariasis ( LF ) elimination programs . Questions remain , however , regarding the economic viability , production capacity , and effec...
With less than three years remaining for meeting the initial 2020 target set by WHO for accomplishing the global elimination of Lymphatic Filariasis ( LF ) , concerns are emerging regarding the feasibility of meeting this goal using the current tablet-based Mass Drug Administration strategy . Salt fortified with the an...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "cost-effectiveness", "analysis", "chemical", "compounds", "economic", "analysis", "sodium", "chloride", "sociology", "geographical", "locations", "salts", "social", "sciences", "tropical", "diseases", "parasitic", "diseases", "nor...
2019
Economic performance and cost-effectiveness of using a DEC-salt social enterprise for eliminating the major neglected tropical disease, lymphatic filariasis
Quantitative linkages between individual organism movements and the resulting population distributions are fundamental to understanding a wide range of ecological processes , including rates of reproduction , consumption , and mortality , as well as the spread of diseases and invasions . Typically , quantitative data a...
Organism movement is fundamental to how organisms interact with each other and the environment . Such movements are also important on the population level and determine the spread of disease and invasion , reproduction , consumption , and mortality . Theoretical ecologists have sought to predict population dispersal ra...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "ecology/behavioral", "ecology", "biophysics/theory", "and", "simulation", "marine", "and", "aquatic", "sciences", "ecology/environmental", "microbiology", "ecology/theoretical", "ecology" ]
2010
Inherent High Correlation of Individual Motility Enhances Population Dispersal in a Heterotrophic, Planktonic Protist
The final stage of bacterial cell division requires the activity of one or more enzymes capable of degrading the layers of peptidoglycan connecting two recently developed daughter cells . Although this is a key step in cell division and is required by all peptidoglycan-containing bacteria , little is known about how th...
Mycobacteria , like all peptidoglycan-containing bacteria , must extend and cleave the surrounding structurally rigid layer of peptidoglycan to grow and divide . The peptidoglycan hydrolases responsible for this cleavage often have redundant functions , both revealing their importance and making them difficult to study...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases/bacterial", "infections", "microbiology/microbial", "growth", "and", "development", "microbiology/cellular", "microbiology", "and", "pathogenesis", "microbiology/microbial", "physiology", "and", "metabolism" ]
2008
A Mycobacterial Enzyme Essential for Cell Division Synergizes with Resuscitation-Promoting Factor
Lymphatic filariasis ( LF ) is one of the most debilitating neglected tropical diseases ( NTDs ) . It still presents as an important public health problem in many countries in the tropics . In Cameroon , where many NTDs are endemic , only scant data describing the situation regarding LF epidemiology was available . The...
Lymphatic filariasis , commonly known as elephantiasis , is a parasitic disease caused by the filarial nematodes Wuchereria bancrofti , Brugia malayi and Brugia timori . It is widely distributed in the tropics where it results in a chronic and debilitating disease . Nearly 1 . 4 billion people in 73 countries worldwide...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Mapping of Bancroftian Filariasis in Cameroon: Prospects for Elimination
Currently , there are no biomarkers that can predict the incidence of dengue shock and/or organ failure , although the early identification of risk factors is important in determining appropriate management to reduce mortality . Therefore , we sought to determine the factors associated with dengue shock and/or organ fa...
Dengue is a major global health concern , particularly in tropical countries , and affects all age groups . Mortality rates among patients who have been hospitalized with severe dengue are 1 . 6–10 . 9% , and death in adults is mainly due to the development of dengue shock and organ dysfunction . In states of poor tiss...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "clinical", "laboratory", "sciences", "body", "fluids", "pathology", "and", "laboratory", "medicine", "tropical", "diseases", "biomarkers", "regression", "analysis", "bacterial", "diseases", "mathematics", "signs", "and", "sympto...
2016
Serum Procalcitonin and Peripheral Venous Lactate for Predicting Dengue Shock and/or Organ Failure: A Prospective Observational Study
How do neuronal populations in the auditory cortex represent acoustic stimuli ? Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient , recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties . To quantify the relative ...
How do neuronal populations in the auditory cortex represent sounds ? Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient , recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties . We quantified the relative contribu...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "neuroscience" ]
2008
Sparse Representation of Sounds in the Unanesthetized Auditory Cortex
The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ . During organogenesis , the epithelial cells receive essential signals from the overlying mesenchyme . Previous studies , focusing on ex vivo tissue explants or complete knockout mice , have identified an important ...
Embryonic development is a highly complex process that requires tight orchestration of cellular proliferation , differentiation , and migration as cells grow within loosely aggregated mesenchyme and more organized epithelial sheets to form organs and tissues . In addition to intrinsic cell-autonomous signals , these ev...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "Methods" ]
[ "medicine", "growth", "control", "cell", "differentiation", "endocrine", "physiology", "developmental", "biology", "organism", "development", "gastroenterology", "and", "hepatology", "endocrine", "cells", "morphogenesis", "endocrinology", "organogenesis", "diabetes", "and", ...
2011
Pancreatic Mesenchyme Regulates Epithelial Organogenesis throughout Development
Dendritic cells ( DCs ) and macrophages ( Møs ) internalize and process exogenous HIV-derived antigens for cross-presentation by MHC-I to cytotoxic CD8+ T cells ( CTL ) . However , how degradation patterns of HIV antigens in the cross-presentation pathways affect immunodominance and immune escape is poorly defined . He...
Pathogens such as HIV can enter cells by fusion at the plasma membrane for delivery in the cytosol , or by internalization in endolysosomal vesicles . Pathogens can be degraded in these various compartments into peptides ( epitopes ) displayed at the cell surface by MHC-I . The presentation of pathogen-derived peptides...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
Variable Processing and Cross-presentation of HIV by Dendritic Cells and Macrophages Shapes CTL Immunodominance and Immune Escape
The disease phenotype of bovine spongiform encephalopathy ( BSE ) and the molecular/ biological properties of its prion strain , including the host range and the characteristics of BSE-related disorders , have been extensively studied since its discovery in 1986 . In recent years , systematic testing of the brains of c...
For approximately two decades , bovine spongiform encephalopathy ( BSE ) , now termed classical BSE ( BSE-C ) , has been regarded as the only and exclusive prion disorder affecting cattle . However , over the last 4 years , two additional bovine prion strains , bovine amyloidotic spongiform encephalopathy ( BASE , also...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "neurological", "disorders/prion", "diseases" ]
2008
Intraspecies Transmission of BASE Induces Clinical Dullness and Amyotrophic Changes
Ornaments used in courtship often vary wildly among species , reflecting the evolutionary interplay between mate preference functions and the constraints imposed by natural selection . Consequently , understanding the evolutionary dynamics responsible for ornament diversification has been a longstanding challenge in ev...
Animals frequently vary widely in ornamentation , even among closely related species . Understanding the patterns that underlie this variation is a significant challenge , requiring comparisons among drastically different traits—like comparing apples to oranges . Here , we use novel analytical approaches to quantify va...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "taxonomy", "organismal", "evolution", "acoustics", "ecology", "and", "environmental", "sciences", "social", "sciences", "vertebrates", "animals", "animal", "phylogenetics", "phylogenetics", "data", "management", "animal", "behavior", "zoology", "ecological", "metrics", "...
2018
Evolution of correlated complexity in the radically different courtship signals of birds-of-paradise
Our ability to recreate complex biochemical mechanisms in designed , artificial systems provides a stringent test of our understanding of these mechanisms and opens the door to their exploitation in artificial biotechnologies . Motivated by this philosophy , here we have recapitulated in vitro the “target sequestration...
Here we recreate in vitro the sequestration mechanism thought to underlie the extraordinary sensitivity ( the steepness of the input/output function ) of a number of genetic networks . We do so first using fluorescent molecular beacons , a well-established , DNA-based biosensor architecture , as our model system . The ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "systems", "biology", "analytical", "chemistry", "synthetic", "biology", "chemistry", "biology", "computational", "biology", "chemical", "biology", "biophysics", "molecular", "biology", "genetics", "and", "genomics" ]
2011
High-Precision, In Vitro Validation of the Sequestration Mechanism for Generating Ultrasensitive Dose-Response Curves in Regulatory Networks
Adipocyte progenitors reside in the stromal vascular fraction ( SVF ) of adipose tissues that are composed of fibroblasts , immune cells , and endothelial cells . It remains to be elucidated how the SVF regulates adipocyte progenitor fate determination and adipose homeostasis . Here , we report that fibroblast-specific...
White adipose tissue ( WAT ) , which consists mostly of adipocytes , is not only a passive energy storage but also an active metabolic and endocrine organ in the body . The importance of maintaining proper adipose mass is emphasized by the fact that both adipose tissue excess—in obese individuals—and deficiency have ad...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "body", "weight", "medicine", "and", "health", "sciences", "fibroblasts", "animal", "models", "fluorescence-activated", "cell", "sorting", "physiological", "processes", "model", "organisms", "adipocytes", "physiological", "parameters", "homeostasis", "connective", "tissue",...
2018
FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis
Leprosy , caused by Mycobacterium leprae , affects over 200 , 000 people annually worldwide and remains endemic in the ethnically diverse , mountainous and underdeveloped southwestern provinces of China . Delayed diagnosis of leprosy persists in China , thus , additional knowledge to support early diagnosis , especiall...
Leprosy , caused by Mycobacterium leprae , affects over 200 , 000 people annually worldwide and remains endemic in the ethnically diverse , mountainous and underdeveloped southwestern regions of China . Although it is curable , delayed diagnosis of leprosy persists in China , with a disability rate as high as 20% natio...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2019
Host immune responses induced by specific Mycobacterium leprae antigens in an overnight whole-blood assay correlate with the diagnosis of paucibacillary leprosy patients in China
Bordetella adenylate cyclase toxin ( CyaA ) binds the αMβ2 integrin ( CD11b/CD18 , Mac-1 , or CR3 ) of myeloid phagocytes and delivers into their cytosol an adenylate cyclase ( AC ) enzyme that converts ATP into the key signaling molecule cAMP . We show that penetration of the AC domain across cell membrane proceeds in...
The adenylate cyclase toxin ( CyaA ) of pathogenic Bordetellae eliminates the first line of host innate immune defense . It penetrates myeloid phagocytes , such as neutrophils , macrophage or dendritic cells , and subverts their signaling by catalyzing an extremely rapid conversion of intracellular ATP to the key signa...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biochemistry/cell", "signaling", "and", "trafficking", "structures", "microbiology/cellular", "microbiology", "and", "pathogenesis", "biochemistry/membrane", "proteins", "and", "energy", "transduction", "microbiology/innate", "immunity" ]
2010
Bordetella Adenylate Cyclase Toxin Mobilizes Its β2 Integrin Receptor into Lipid Rafts to Accomplish Translocation across Target Cell Membrane in Two Steps
The ability of cells to accurately control gene expression levels in response to extracellular cues is limited by the inherently stochastic nature of transcriptional regulation . A change in transcription factor ( TF ) activity results in changes in the expression of its targets , but the way in which cell-to-cell vari...
In response to environmental changes , cells regulate the activity of transcription factors ( TFs ) , which in turn change the expression of dozens of downstream target genes by binding to their promoters . The response of each target gene is determined by the interplay between TF concentration and the context in which...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "flow", "cytometry", "gene", "regulation", "microbiology", "dna", "transcription", "model", "organisms", "molecular", "genetics", "cytometry", "chromatin", "gene", "expression", "biology", "molecular", "biology", "systems", "biology", "biochemical", "simulations", "cell",...
2013
Promoter Sequence Determines the Relationship between Expression Level and Noise
RNA sequencing provides a new perspective on the genome of Mycobacterium tuberculosis by revealing an extensive presence of non-coding RNA , including long 5’ and 3’ untranslated regions , antisense transcripts , and intergenic small RNA ( sRNA ) molecules . More than a quarter of all sequence reads mapping outside of ...
Tuberculosis bacteria are able to hide quietly inside the body for years or decades before reawakening to cause disease . If we knew more about how the bacteria change from a harmless persistent form to an aggressive disease-causing form , we could develop drugs that would be more effective in treating active tuberculo...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "bacteriology", "microbial", "metabolism", "microbiology", "rna", "synthesis", "bacterial", "pathogens", "microbial", "physiology", "microbial", "pathogens", "biology", "gram", "positive", "biochemistry", "rna", "bacterial", "physiology", "nucleic", "acids" ]
2011
Sequence-Based Analysis Uncovers an Abundance of Non-Coding RNA in the Total Transcriptome of Mycobacterium tuberculosis
The role of APOBEC3 ( A3 ) protein family members in inhibiting retrovirus infection and mobile element retrotransposition is well established . However , the evolutionary effects these restriction factors may have had on active retroviruses such as HIV-1 are less well understood . An HIV-1 variant that has been highly...
The search for new drugs to battle HIV-1 infections is a continuing struggle . APOBEC3G proteins have been shown to deaminate C-residues in HIV-1 minus strand DNA during its synthesis , resulting in G-to-A mutations in the RNA genome . The HIV-1 Vif protein has evolved to counteract APOBEC3G and thereby escape these fr...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "genetics", "and", "genomics/microbial", "evolution", "and", "genomics", "evolutionary", "biology/microbial", "evolution", "and", "genomics", "virology/virus", "evolution", "and", "symbiosis", "virology/immunodeficiency", "viruses", "virology", "infectious", "diseases/hiv", "...
2009
Likely Role of APOBEC3G-Mediated G-to-A Mutations in HIV-1 Evolution and Drug Resistance
Transcriptional activity has been shown to relate to the organization of chromosomes in the eukaryotic nucleus and in the bacterial nucleoid . In particular , highly transcribed genes , RNA polymerases and transcription factors gather into discrete spatial foci called transcription factories . However , the mechanisms ...
The good operation of cells relies on a coordination between chromosome structure and genetic regulation which is yet to be understood . This can be seen in particular from the transcription machinery: in some eukaryotes and bacteria , transcription of highly active genes occurs within discrete foci called transcriptio...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "biophysics/macromolecular", "assemblies", "and", "machines", "physics/interdisciplinary", "physics", "cell", "biology/nuclear", "structure", "and", "function", "physics/condensed", "matter", "biophysics/theory", "and", "simulation", "computational", "biology/molecular", "dynamic...
2010
Spatial and Topological Organization of DNA Chains Induced by Gene Co-localization
Characterizing interactions between drugs is important to avoid potentially harmful combinations , to reduce off-target effects of treatments and to fight antibiotic resistant pathogens , among others . Here we present a network inference algorithm to predict uncharacterized drug-drug interactions . Our algorithm takes...
Over one in four adults older than 57 in the US take five or more prescriptions at the same time; as many as 4% are at risk of a major adverse drug-drug interaction . Potentially beneficial effects of drug combinations , on the other hand , are also important . For example , combinations of drugs with synergistic effec...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2013
A Network Inference Method for Large-Scale Unsupervised Identification of Novel Drug-Drug Interactions
We recently reported that centrosomal protein 164 ( CEP164 ) regulates both cilia and the DNA damage response in the autosomal recessive polycystic kidney disease nephronophthisis . Here we examine the functional role of CEP164 in nephronophthisis-related ciliopathies and concomitant fibrosis . Live cell imaging of RPE...
Nephronophthisis is a leading inherited cause of renal failure in children and young adults . This work contributes to understanding of the disease mechanism of nephronophthisis , which is characterized by multi-cystic and fibrotic kidneys . The genes mutated in patients with nephronophthisis all seem to encode protein...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "chronic", "kidney", "disease", "genetics", "pediatric", "nephrology", "biology", "and", "life", "sciences", "nephrology", "gene", "function" ]
2014
Nephronophthisis-Associated CEP164 Regulates Cell Cycle Progression, Apoptosis and Epithelial-to-Mesenchymal Transition
Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year . Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue , resulting in a continuously increasing number of cases . ...
The four serotypes of dengue virus cause severe outbreaks globally in tropical countries with thousands of patients requiring hospitalization . The health care and indirect economic cost of dengue in endemic countries is huge . Despite this , no clinically approved vaccine or antiviral treatment is currently available ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "infectious", "diseases", "clinical", "immunology", "immunology", "biology" ]
2013
Rational Design of a Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques
The immune response to influenza virus infection comprises both innate and adaptive defenses . NK cells play an early role in the destruction of tumors and virally-infected cells . NK cells express a variety of inhibitory receptors , including those of the Ly49 family , which are functional homologs of human killer-cel...
Influenza virus has developed a number of immune-evasion mechanisms to prolong its survival within the host . Development of functional NK cells is dependent on multiple factors such as the interaction between MHC-I and Ly49 receptors . NK cells that develop in the absence of these interactions are referred to as ‘unli...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "blood", "cells", "flow", "cytometry", "innate", "immune", "system", "medicine", "and", "health", "sciences", "immune", "cells", "immune", "physiology", "pathology", "and", "laboratory", "medicine", "cytokines", "influenza", "pathogens", "immunology", "microbiology", ...
2016
Influenza Virus Targets Class I MHC-Educated NK Cells for Immunoevasion
The inoculation of a low number ( 104 ) of L . amazonensis metacyclic promastigotes into the dermis of C57BL/6 and DBA/2 mouse ear pinna results in distinct outcome as assessed by the parasite load values and ear pinna macroscopic features monitored from days 4 to 22-phase 1 and from days 22 to 80/100-phase 2 . While i...
The rapid and long term establishment of parasites such as L . amazonensis , otherwise known to strictly rely on subversion of macrophage and dendritic leucocyte ( DL ) lineages , is expected to reflect stepwise processes taking place in both the skin dermis where the infective form of the parasite and the skin-drainin...
[ "Abstract", "Introduction", "Methods", "Results", "and", "Discussion" ]
[ "genome", "expression", "analysis", "immune", "cells", "antigen-presenting", "cells", "immunology", "microbiology", "host-pathogen", "interaction", "parasitology", "immune", "defense", "t", "cells", "biology", "pathogenesis", "immune", "response", "immunity", "genomics", ...
2012
Distinct Transcriptional Signatures of Bone Marrow-Derived C57BL/6 and DBA/2 Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes
Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types , such as neurons , and mesodermal cell types , such as smooth muscle . The mechanisms controlling this cell fate choice are not known . The basic Helix-loop-Helix ( bHLH ) transcription factor Twist1 is expressed throughou...
During vertebrate development , a unique population of cells , termed neural crest cells , migrates throughout the developing embryo , generating various cell types , for example , the smooth muscle that divides the aorta and pulmonary artery where they connect to the heart , and the autonomic neurons , which coordinat...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "biology", "molecular", "cell", "biology" ]
2013
Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest
Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures . Rho guanine nucleotide exchange factor ( ARHGEF ) family members are key for controlling the spatiotemporal activation of Rho GTPase , to modulate...
During brain development , localized gene expression is crucial for the formation and function of specific brain regions . Various groups of proteins are known to regulate segmentation through controlled gene expression , among them , the Rho GTPase regulator family . In this study , we identified a frameshift mutation...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "cell", "motility", "medicine", "and", "health", "sciences", "nuclear", "staining", "cell", "cycle", "and", "cell", "division", "cell", "processes", "brain", "precursor", "cells", "neuroscience", "mutation", "developmental", "biology", "hindbrain", "cerebellum", "fram...
2017
Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation
Restless legs syndrome ( RLS ) is a sensorimotor disorder with an age-dependent prevalence of up to 10% in the general population above 65 years of age . Affected individuals suffer from uncomfortable sensations and an urge to move in the lower limbs that occurs mainly in resting situations during the evening or at nig...
Restless legs syndrome ( RLS ) is one of the most common neurological disorders . Patients with RLS suffer from an urge to move the legs and unpleasant sensations located mostly deep in the calf . Symptoms mainly occur in resting situations in the evening or at night . As a consequence , initiation and maintenance of s...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "medicine", "movement", "disorders", "neurological", "disorders", "neurology", "sleep", "disorders" ]
2011
Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1
Marine coccolithophorid phytoplankton are major producers of biogenic calcite , playing a significant role in the global carbon cycle . Predicting the impacts of ocean acidification on coccolithophore calcification has received much recent attention and requires improved knowledge of cellular calcification mechanisms ....
The production of calcium carbonate structures by marine organisms has a major influence on the Earth's carbon cycle and is responsible for the eventual formation of sedimentary rocks such as chalk and limestone . The major contributors to marine calcification are the coccolithophores , a family of unicellular algae wh...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "cell", "physiology", "cellular", "stress", "responses", "molecular", "cell", "biology", "phycology", "cell", "biology", "electrophysiology", "physiology", "marine", "and", "aquatic", "sciences", "biology", "anatomy", "and", "physiology", "marine", "biology" ]
2011
A Voltage-Gated H+ Channel Underlying pH Homeostasis in Calcifying Coccolithophores
The analysis of methylation patterns is a promising approach to investigate the genealogy of cell populations in an organism . In a stem cell–niche scenario , sampled methylation patterns are the stochastic outcome of a complex interplay between niche structural features such as the number of stem cells within a niche ...
The dynamics of the stem cell populations in human colon crypts are of interest to cancer researchers and stem cell biologists alike . One approach to studying stem cell divisions would be to adopt methods from population genetics: cells are sampled from crypts , DNA markers such as single nucleotide polymorphisms are ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "mathematics", "gastroenterology", "and", "hepatology", "computational", "biology", "homo", "(human)" ]
2007
The Stem Cell Population of the Human Colon Crypt: Analysis via Methylation Patterns
Bacterial endosymbionts of insects play a central role in upgrading the diet of their hosts . In certain cases , such as aphids and tsetse flies , endosymbionts complement the metabolic capacity of hosts living on nutrient-deficient diets , while the bacteria harbored by omnivorous carpenter ants are involved in nitrog...
Bacterial endosymbionts from insects are subjected to a process of genome reduction from the moment they interact with their host , especially when the symbiosis is strict ( the partners live together permanently ) and the endosymbiont is maternally inherited . The type of genes that are retained correlates with specif...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/genome", "projects", "genetics", "and", "genomics/microbial", "evolution", "and", "genomics", "evolutionary", "biology/microbial", "evolution", "and", "genomics", "evolutionary", "biology/evolutionary", "and", "comparative", "genetics" ]
2009
Evolutionary Convergence and Nitrogen Metabolism in Blattabacterium strain Bge, Primary Endosymbiont of the Cockroach Blattella germanica
The FANTOM5 consortium utilised cap analysis of gene expression ( CAGE ) to provide an unprecedented insight into transcriptional regulation in human cells and tissues . In the current study , we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived ma...
Macrophages are immune cells that form the first line of defense against pathogens , but also mediate tissue damage in inflammatory disease . Macrophages initiate inflammation by recognising and responding to components of bacterial cells . Macrophages of the wall of the gut are constantly replenished from the blood . ...
[ "Abstract", "Introduction", "Results", "Discussion", "Conclusions", "Methods" ]
[ "blood", "cells", "medicine", "and", "health", "sciences", "immune", "cells", "gene", "regulation", "regulatory", "proteins", "immunology", "dna-binding", "proteins", "dna", "transcription", "gastroenterology", "and", "hepatology", "transcription", "factors", "inflammator...
2017
Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease
Recent studies suggest that deep Convolutional Neural Network ( CNN ) models show higher representational similarity , compared to any other existing object recognition models , with macaque inferior temporal ( IT ) cortical responses , human ventral stream fMRI activations and human object recognition . These studies ...
The primate inferior temporal ( IT ) cortex is considered to be the final stage of visual processing that allows for object recognition , identification and categorization of objects . Electrophysiology studies suggest that an object’s shape is a strong determinant of the neuronal response patterns in IT . Here we exam...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "medicine", "and", "health", "sciences", "diagnostic", "radiology", "functional", "magnetic", "resonance", "imaging", "neural", "networks", "visual", "object", "recognition", "vertebrates", "social", "sciences", "neuroscience", "animals", "mammals", "learning", "and", "...
2018
Representations of regular and irregular shapes by deep Convolutional Neural Networks, monkey inferotemporal neurons and human judgments
In man , infection with South American Andes virus ( ANDV ) causes hantavirus cardiopulmonary syndrome ( HCPS ) . HCPS due to ANDV is endemic in Southern Chile and much of Argentina and increasing numbers of cases are reported all over South America . A case-fatality rate of about 36% together with the absence of succe...
In man , hantavirus cardiopulmonary syndrome ( HCPS ) caused by Andes Virus ( ANDV ) is endemic in the Southern cone of Chile and Argentina but cases of HCPS are being increasingly reported all over South America since 1995 . HCPS is characterized by fulminant pulmonary edema which progresses to shock and death in abou...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "infectious", "diseases/neglected", "tropical", "diseases", "immunology/immune", "response", "virology/emerging", "viral", "diseases", "infectious", "diseases/viral", "infections", "infectious", "diseases/respiratory", "infections", "immunology/immunity", "to", "infections", "vir...
2010
Highly Differentiated, Resting Gn-Specific Memory CD8+ T Cells Persist Years after Infection by Andes Hantavirus
The accurate identification of the route of transmission taken by an infectious agent through a host population is critical to understanding its epidemiology and informing measures for its control . However , reconstruction of transmission routes during an epidemic is often an underdetermined problem: data about the lo...
In order to most effectively control the spread of an infectious disease , we need to better understand how pathogens spread within a host population , yet this is something we know remarkably little about . Cases close together in their locations and timing are often thought to be linked , but timings and locations al...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "systems", "biology", "computer", "science", "computer", "modeling", "veterinary", "epidemiology", "ecology", "evolutionary", "modeling", "theoretical", "ecology", "biology", "computational", "biology", "veterinary", "science" ]
2012
A Bayesian Inference Framework to Reconstruct Transmission Trees Using Epidemiological and Genetic Data
Inner ear sensory hair cell death is observed in the majority of hearing and balance disorders , affecting the health of more than 600 million people worldwide . While normal aging is the single greatest contributor , exposure to environmental toxins and therapeutic drugs such as aminoglycoside antibiotics and antineop...
Loss of sensory hair cells in the inner ear is observed in the majority of hearing and balance disorders , affecting the health of more than 600 million people worldwide . Exposure to environmental toxins and certain pharmaceutical drugs such as aminoglycoside antibiotics and some cancer chemotherapy agents account for...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/animal", "genetics", "neuroscience/sensory", "systems", "cell", "biology/cellular", "death", "and", "stress", "responses", "genetics", "and", "genomics/disease", "models", "otolaryngology/ear", "pathologies" ]
2008
Identification of Genetic and Chemical Modulators of Zebrafish Mechanosensory Hair Cell Death
Neuronal activity in cortex is variable both spontaneously and during stimulation , and it has the remarkable property that it is Poisson-like over broad ranges of firing rates covering from virtually zero to hundreds of spikes per second . The mechanisms underlying cortical-like spiking variability over such a broad c...
Neurons in cortex fire irregularly and in an irreproducible way under repeated presentations of an identical stimulus . Where is this spiking variability coming from ? One unexplored possibility is that cortical variability originates from the amplification of a particular type of noise that is present throughout corte...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "computational", "neuroscience", "biology", "and", "life", "sciences", "computational", "biology", "neuroscience", "coding", "mechanisms" ]
2014
Poisson-Like Spiking in Circuits with Probabilistic Synapses
Intestinal L-cells sense glucose and other nutrients , and in response release glucagon-like peptide 1 ( GLP-1 ) , peptide YY and other hormones with anti-diabetic and weight-reducing effects . The stimulus-secretion pathway in L-cells is still poorly understood , although it is known that GLP-1 secreting cells use sod...
Metabolic diseases are to a great extent because of disturbances in hormone secretion . Endocrine cells releasing hormones with a role in metabolism typically possess a refined molecular system for nutrient sensing , which allows them to respond in an appropriate manner to changes in e . g . glucose levels . The gut is...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[]
2015
Mathematical Modeling of Interacting Glucose-Sensing Mechanisms and Electrical Activity Underlying Glucagon-Like Peptide 1 Secretion
During meiosis , the Msh4-Msh5 complex is thought to stabilize single-end invasion intermediates that form during early stages of recombination and subsequently bind to Holliday junctions to facilitate crossover formation . To analyze Msh4-Msh5 function , we mutagenized 57 residues in Saccharomyces cerevisiae Msh4 and ...
In meiosis , sex cells that become eggs or sperm undergo a single round of DNA replication followed by two consecutive chromosomal divisions . In most organisms , the segregation of chromosomes at the first meiotic division is dependent upon at least one genetic exchange , or crossover event , between homologous chromo...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "molecular", "biology/recombination", "genetics", "and", "genomics/nuclear", "structure", "and", "function", "molecular", "biology/chromosome", "structure", "genetics", "and", "genomics/chromosome", "biology", "genetics", "and", "genomics", "molecular", "biology/dna", "repair...
2010
Genetic Analysis of Baker's Yeast Msh4-Msh5 Reveals a Threshold Crossover Level for Meiotic Viability
In 2010 , the World Health Organization released a new cholera vaccine position paper , which recommended the use of cholera vaccines in high-risk endemic areas . However , there is a paucity of data on the burden of cholera in endemic countries . This article reviewed available cholera surveillance data from Uganda an...
Uganda has reported cholera cases to the World Health Organization every year since 1997 . Thus , the country may consider the introduction of a WHO-prequalified oral cholera vaccine . This article reviews cholera surveillance data from 1997–2010 with a focus on the 2005–2010 time period to identify high risk populatio...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2013
The Burden of Cholera in Uganda
Information processing is a major aspect of the evolution of animal behavior . In foraging , responsiveness to local feeding opportunities can generate patterns of behavior which reflect or “recognize patterns” in the environment beyond the perception of individuals . Theory on the evolution of behavior generally negle...
Animals differ in how they sense and process information obtained from the environment . An important part of this information processing is used to find food . In terms of foraging , local decision making determines how successful individuals are at finding food on longer timescales . Using an artificial-world model ,...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "theoretical", "biology", "ecology", "biology", "computational", "biology", "evolutionary", "biology" ]
2011
Local Orientation and the Evolution of Foraging: Changes in Decision Making Can Eliminate Evolutionary Trade-offs
Trans-splicing of leader sequences onto the 5′ends of mRNAs is a widespread phenomenon in protozoa , nematodes and some chordates . Using parallel sequencing we have developed a method to simultaneously map 5′splice sites and analyze the corresponding gene expression profile , that we term spliced leader trapping ( SLT...
Some organisms like the human and animal parasite Trypanosoma brucei add a leader sequence to their mRNAs through a reaction called trans-splicing . Until now the splice sites for most mRNAs were unknown in T . brucei . Using high throughput sequencing we have developed a method to identify the splice sites and at the ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "computational", "biology/alternative", "splicing", "molecular", "biology/mrna", "stability", "molecular", "biology/rna", "splicing", "molecular", "biology/bioinformatics", "microbiology/parasitology", "infectious", "diseases/protozoal", "infections" ]
2010
Spliced Leader Trapping Reveals Widespread Alternative Splicing Patterns in the Highly Dynamic Transcriptome of Trypanosoma brucei
Extremely AT-rich DNA sequences present a challenging template for specific recognition by RNA polymerase . In bacteria , this is because the promoter −10 hexamer , the major DNA element recognised by RNA polymerase , is itself AT-rich . We show that Histone-like Nucleoid Structuring ( H-NS ) protein can facilitate cor...
The information required to build and maintain a cell is written into an organism's DNA in the form of genes . When individual genes are “read , ” the DNA code is transcribed into an mRNA molecule by RNA polymerase . Hence , the DNA sequence adjacent to the start of a gene must contain a signal to recruit RNA polymeras...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "genetics", "biochemistry", "biology", "microbiology" ]
2013
H-NS Can Facilitate Specific DNA-binding by RNA Polymerase in AT-rich Gene Regulatory Regions
Transposons are discrete segments of DNA that have the distinctive ability to move and replicate within genomes across the tree of life . ‘Cut and paste’ DNA transposition involves excision from a donor locus and reintegration into a new locus in the genome . We studied molecular events following the excision steps of ...
Transposons ( “jumping genes” ) are ubiquitous , mobile genetic elements that make up significant fraction of genomes , and are best described as molecular parasites . During ‘cut and paste’ transposition , the excised transposon relocates from one genomic location to another . Here we focus on the molecular events fol...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biotechnology", "bioengineering", "genetics", "biology", "evolutionary", "biology", "engineering" ]
2014
Suicidal Autointegration of Sleeping Beauty and piggyBac Transposons in Eukaryotic Cells
Leprosy is remaining prevalent in the poorest areas of the world . Intensive control programmes with multidrug therapy ( MDT ) reduced the number of registered cases in these areas , but transmission of Mycobacterium leprae continues in most endemic countries . Socio-economic circumstances are considered to be a major ...
Although intensive control programs reduced the prevalence of leprosy worldwide , new cases of this infectious disease are still detected in several of the poorest areas of the world . Therefore the disease is known as a disease of poverty . To be able to control the disease it is important to know which aspects of pov...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "infectious", "diseases", "socioeconomic", "aspects", "of", "health", "non-clinical", "medicine", "nutrition", "neglected", "tropical", "diseases", "leprosy", "infectious", "disease", "control" ]
2011
Recent Food Shortage Is Associated with Leprosy Disease in Bangladesh: A Case-Control Study
The extracellular matrix plays a critical role in orchestrating the events necessary for wound healing , muscle repair , morphogenesis , new blood vessel growth , and cancer invasion . In this study , we investigate the influence of extracellular matrix topography on the coordination of multi-cellular interactions in t...
A cell migrating in the extracellular matrix environment has to pull on the matrix fibers to move . When the matrix is too dense , the cell secretes enzymes to degrade the matrix proteins in order to get through . And when the matrix is too sparse , the cell produces matrix proteins to locally increase the “foothold” ....
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "cardiovascular", "disorders/vascular", "biology", "developmental", "biology/morphogenesis", "and", "cell", "biology", "cell", "biology/morphogenesis", "and", "cell", "biology", "cell", "biology/cell", "growth", "and", "division", "mathematics", "cell", "biology/cell", "adh...
2009
Topography of Extracellular Matrix Mediates Vascular Morphogenesis and Migration Speeds in Angiogenesis
All of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in culture or in rodents . Drugs against sleeping sickness must however treat trypanosomes in humans . We here compare the transcriptomes of Trypanosoma brucei rhodesiense from the blood and cerebrospinal fluid of...
African trypanosomes cause sleeping sickness in humans and various diseases of domestic and wild animals . Until now , all of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in in vitro culture or in rodents . Drugs against sleeping sickness must however treat trypano...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Methods" ]
[ "sequencing", "techniques", "medicine", "and", "health", "sciences", "body", "fluids", "messenger", "rna", "parasitic", "diseases", "parasitic", "protozoans", "trypanosoma", "brucei", "protozoans", "genome", "analysis", "molecular", "biology", "techniques", "rna", "sequ...
2018
Transcriptomes of Trypanosoma brucei rhodesiense from sleeping sickness patients, rodents and culture: Effects of strain, growth conditions and RNA preparation methods
Dengue viruses ( DENV ) are the causative agents of dengue , the world’s most prevalent arthropod-borne disease with around 40% of the world’s population at risk of infection annually . Wolbachia pipientis , an obligate intracellular bacterium , is being developed as a biocontrol strategy against dengue because it limi...
Dengue is endemic in more than 100 countries and is transmitted by the mosquito Aedes aegypti . The use of the symbiotic bacterium Wolbachia has become a potential biocontrol approach against dengue virus for two reasons . First , Wolbachia spreads rapidly through populations by manipulating host reproduction to its ad...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Wolbachia Reduces the Transmission Potential of Dengue-Infected Aedes aegypti
Fungi are a large group of eukaryotes found in nearly all ecosystems . More than 250 fungal genomes have already been sequenced , greatly improving our understanding of fungal evolution , physiology , and development . However , for the Pezizomycetes , an early-diverging lineage of filamentous ascomycetes , there is so...
Fungi are a morphologically and physiologically diverse group of organisms with huge impacts on nearly all ecosystems . In recent years , genomes of many fungal species have been sequenced and have greatly improved our understanding of fungal biology . Ascomycetes are the largest fungal group with the highest number of...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[]
2013
The Genome and Development-Dependent Transcriptomes of Pyronema confluens: A Window into Fungal Evolution
MicroRNAs belonging to the miR-34 family have been proposed as critical modulators of the p53 pathway and potential tumor suppressors in human cancers . To formally test these hypotheses , we have generated mice carrying targeted deletion of all three members of this microRNA family . We show that complete inactivation...
MicroRNAs ( miRNAs ) are small , non-coding RNAs that broadly regulate gene expression . MicroRNA deregulation is a common feature of human cancers , and numerous miRNAs have oncogenic or tumor suppressive properties . Members of the miR-34 family ( miR-34a , miR-34b , and miR-34c ) have been widely speculated to be im...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "animal", "models", "cancer", "genetics", "model", "organisms", "genetics", "biology", "mouse", "genetics", "and", "genomics", "gene", "function" ]
2012
Intact p53-Dependent Responses in miR-34–Deficient Mice
A form of dwarfism known as Meier-Gorlin syndrome ( MGS ) is caused by recessive mutations in one of six different genes ( ORC1 , ORC4 , ORC6 , CDC6 , CDT1 , and MCM5 ) . These genes encode components of the pre-replication complex , which assembles at origins of replication prior to S phase . Also , variants in two ad...
The origin recognition complex ( ORC ) is essential for licensing replication origins during M/G1 for their firing in the subsequent S phase . Individuals with a rare form of dwarfism called Meier-Gorlin syndrome ( MGS ) have mutations in proteins required for origin activation , including various subunits of ORC . To ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "molecular", "probe", "techniques", "cell", "cycle", "and", "cell", "division", "cell", "processes", "fungi", "model", "organisms", "dna", "replication", "experimental", "organism", "systems", "dna", "molecular", "biology", "techniques", "synthesis", "phase", "cellula...
2017
Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast
Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial , as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism . In contrast to vertebrates that harbor...
Type II topoisomerases ( Topo II ) are enzymes that disentangle DNA molecules during essential cellular processes such as DNA replication , chromosome condensation and mitotic cell division . Topo II is a major component of mitotic chromosomes and it is a well known target for cancer chemotherapy . Topo II inhibitors b...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "cell", "biology", "biology", "and", "life", "sciences" ]
2014
The Analysis of Mutant Alleles of Different Strength Reveals Multiple Functions of Topoisomerase 2 in Regulation of Drosophila Chromosome Structure
In higher eukaryotes , replication program specification in different cell types remains to be fully understood . We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late repli...
DNA replication in human cells requires the parallel progression along the genome of thousands of replication machineries . Comprehensive knowledge of genetic inheritance at different development stages relies on elucidating the mechanisms that regulate the location and progression of these machineries throughout the d...
[ "Abstract", "Introduction", "Results/Discussion", "Materials", "and", "Methods" ]
[ "physics", "genomics", "nucleic", "acids", "genetics", "epigenetics", "biology", "computational", "biology", "dna", "biophysics", "genetics", "and", "genomics" ]
2012
Replication Fork Polarity Gradients Revealed by Megabase-Sized U-Shaped Replication Timing Domains in Human Cell Lines
Multiple endocrine neoplasia type 2B ( MEN2B ) is a highly aggressive thyroid cancer syndrome . Since almost all sporadic cases are caused by the same nucleotide substitution in the RET proto-oncogene , the calculated disease incidence is 100–200 times greater than would be expected based on the genome average mutation...
Multiple endocrine neoplasia type 2B ( MEN2B ) is a highly aggressive thyroid cancer syndrome . MEN2B offspring with unaffected parents almost always received a new mutation from the father . Moreover , this mutation is almost always at the same nucleotide in the RET proto-oncogene . Thus MEN2B's incidence should equal...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "biology", "computational", "biology", "evolutionary", "biology", "population", "biology", "genetics", "and", "genomics" ]
2012
Positive Selection for New Disease Mutations in the Human Germline: Evidence from the Heritable Cancer Syndrome Multiple Endocrine Neoplasia Type 2B
The relative proportion of additive and non-additive variation for complex traits is important in evolutionary biology , medicine , and agriculture . We address a long-standing controversy and paradox about the contribution of non-additive genetic variation , namely that knowledge about biological pathways and gene net...
Genetic variation in quantitative or complex traits can be partitioned into many components due to additive , dominance , and interaction effects of genes . The most important is the additive genetic variance because it determines most of the correlation of relatives and the opportunities for genetic change by natural ...
[ "Abstract", "Model", "Results/Discussion" ]
[ "genetics", "and", "genomics/complex", "traits", "evolutionary", "biology", "genetics", "and", "genomics", "genetics", "and", "genomics/medical", "genetics", "genetics", "and", "genomics/population", "genetics" ]
2008
Data and Theory Point to Mainly Additive Genetic Variance for Complex Traits
In addition to their biological function , protein complexes reduce the exposure of the constituent proteins to the risk of undesired oligomerization by reducing the concentration of the free monomeric state . We interpret this reduced risk as a stabilization of the functional state of the protein . We estimate that pr...
The folded form of proteins is only marginally stable in vivo and constantly faces the risk of aggregation , unfolding/misfolding , and other aberrant interactions . For most proteins , the folded form is also the functionally relevant one and forces of natural selection strongly modulate its stability . In vivo , prot...
[ "Abstract", "Introduction", "Results", "Methods" ]
[ "evolutionary", "modeling", "biology", "computational", "biology" ]
2013
Evolutionary Capacitance and Control of Protein Stability in Protein-Protein Interaction Networks
Gram-negative bacterial pathogens deliver a variety of virulence proteins through the type III secretion system ( T3SS ) directly into the host cytoplasm . These type III secreted effectors ( T3SEs ) play an essential role in bacterial infection , mainly by targeting host immunity . However , the molecular basis of the...
Many Gram-negative bacterial pathogens rely on the type III secretion system , which is a specialized protein secretion apparatus , to inject virulence proteins , called effectors , into the host cells . The type III secreted effectors ( T3SEs ) directly target host substrates in order to promote bacterial colonization...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
Bacterial Effector Activates Jasmonate Signaling by Directly Targeting JAZ Transcriptional Repressors
Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection . Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses . Since the emergence of the pandemic 2009 A ( H1N1 ) influenza virus ( A (...
Antimicrobial resistance is an increasing problem for the treatment of infectious diseases . In 2007–2008 human seasonal A ( H1N1 ) influenza viruses rapidly acquired resistance to the most commonly used anti-influenza drug oseltamivir , via a H275Y amino acid mutation within the neuraminidase ( NA ) protein . In 2009 ...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "antimicrobials", "animal", "models", "of", "infection", "organismal", "evolution", "infectious", "diseases", "microbial", "mutation", "medicine", "and", "health", "sciences", "emerging", "infectious", "diseases", "viral", "persistence", "and", "latency", "microbial", "...
2014
Estimating the Fitness Advantage Conferred by Permissive Neuraminidase Mutations in Recent Oseltamivir-Resistant A(H1N1)pdm09 Influenza Viruses
Clostridium botulinum neurotoxin ( BoNT ) causes flaccid paralysis by disabling synaptic exocytosis . Intoxication requires the tri-modular protein to undergo conformational changes in response to pH and redox gradients across endosomes , leading to the formation of a protein-conducting channel . The ∼50 kDa light chai...
Botulinum neurotoxin , widely acknowledged to be the most potent toxin known , is a modular nanomachine and a marvel of protein design . This neurotoxin exploits a modular design to achieve its potent toxicity , which relies on one of its modules—the heavy chain channel—to operate as a specific protein translocating tr...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[ "biophysics/protein", "folding", "cell", "biology/cell", "signaling", "biotechnology/protein", "chemistry", "and", "proteomics", "biochemistry/protein", "folding", "neurological", "disorders", "cell", "biology/membranes", "and", "sorting", "physiology/cell", "signaling", "neuro...
2008
Botulinum Neurotoxin Devoid of Receptor Binding Domain Translocates Active Protease
Race , specifically African ancestry , and obesity are important risk factors for uterine fibroids , and likely interact to provide the right conditions for fibroid growth . However , existing studies largely focus on the main-effects rather than their interaction . Here , we firstly provide evidence for interaction be...
Although it is postulated that obesity and non-modifiable risk factors such as race or genetic ancestry may interact to jointly influence uterine fibroid growth , most existing studies have not evaluated their interaction . In this study we exhibit evidence for interaction across several tiers of investigation . We fir...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "body", "weight", "medicine", "and", "health", "sciences", "african", "americans", "surgical", "and", "invasive", "medical", "procedures", "ethnicities", "physiological", "parameters", "mathematics", "statistics", "(mathematics)", "chromosome", "mapping", "obesity", "mole...
2017
African genetic ancestry interacts with body mass index to modify risk for uterine fibroids
Feathers have complex forms and are an excellent model to study the development and evolution of morphologies . Existing chicken feather mutants are especially useful for identifying genetic determinants of feather formation . This study focused on the gene F , underlying the frizzle feather trait that has a characteri...
With the availability of a sequenced chicken genome , the reservoir of variant plumage genes found in domestic chickens can provide insight into the molecular mechanisms underlying the diversity of feather forms . In this paper , we identify the molecular basis of the distinctive frizzle ( F ) feather phenotype that is...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "developmental", "biology", "physiology", "genetics", "biology", "anatomy", "and", "physiology", "genetics", "and", "genomics" ]
2012
The Chicken Frizzle Feather Is Due to an α-Keratin (KRT75) Mutation That Causes a Defective Rachis
RNA-protein interaction plays important roles in post-transcriptional regulation . Recent advancements in cross-linking and immunoprecipitation followed by sequencing ( CLIP-seq ) technologies make it possible to detect the binding peaks of a given RNA binding protein ( RBP ) at transcriptome scale . However , it is st...
It is important to identify the functional targets of RBPs , which are essential regulators in post-transcriptional processes . PRAS aims to predict RBP targets based on the intensities and positions of the binding peaks obtained from CLIP-seq studies . We demonstrate that PRAS score outperforms other existing methods ...
[ "Abstract", "Introduction", "Design", "and", "implementation", "Results", "and", "discussions", "Availability", "and", "future", "directions" ]
[ "rna-binding", "proteins", "chemical", "bonding", "3'", "utr", "messenger", "rna", "dna", "transcription", "untranslated", "regions", "genome", "analysis", "physical", "chemistry", "proteins", "gene", "expression", "chemistry", "cross-linking", "gene", "ontologies", "bi...
2019
PRAS: Predicting functional targets of RNA binding proteins based on CLIP-seq peaks
Tsetse flies transmit trypanosomes , the causative agent of human and animal African trypanosomiasis . The tsetse vector is extensively distributed across sub-Saharan Africa . Trypanosomiasis maintenance is determined by the interrelationship of three elements: vertebrate host , parasite and the vector responsible for ...
Trypanosomiasis is a vector-borne disease transmitted to both humans and animals by the tsetse fly . The tsetse vector is distributed across sub-Saharan Africa . Trypanosomiasis maintenance is determined by the interrelationship of three elements: vertebrate host , parasite and the vector responsible for transmission ....
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2015
Tsetse Fly (G.f. fuscipes) Distribution in the Lake Victoria Basin of Uganda
An increased incidence of skin inflammatory diseases is frequently observed in organtransplanted patients being treated with calcineurin inhibitor-based immunosuppressive agents . The mechanism of increased skin inflammation in this context has however not yet been clarified . Here we report an increased inflammation f...
It is known that a higher incidence of skin squamous cell carcinoma ( SCC ) development , as well as increased chronic skin inflammation , occurs in organ transplant patients with long-term use of calcineurin inhibitors as immunosuppressive drugs . Whether the increased skin inflammation contributes to the development ...
[ "Abstract", "Introduction", "Results", "Discussions", "Methods" ]
[ "dermatology", "innate", "immune", "system", "keratinocytes", "medicine", "and", "health", "sciences", "immune", "physiology", "cytokines", "pathology", "and", "laboratory", "medicine", "gene", "regulation", "skin", "tumors", "immunology", "cancer", "treatment", "cancer...
2018
The ARE-binding protein Tristetraprolin (TTP) is a novel target and mediator of calcineurin tumor suppressing function in the skin
Tens of millions of dengue cases and approximately 500 , 000 life-threatening complications occur annually . New tools are needed to distinguish dengue from other febrile illnesses . In addition , the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined . Data from...
Dengue virus causes an estimated 50 million dengue cases and approximately 500 , 000 life-threatening complications annually . New tools are needed to distinguish dengue from other febrile illnesses . In addition , the natural history of pediatric dengue early in illness in a community-based setting has not been well-d...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "infectious", "diseases", "public", "health", "and", "epidemiology", "clinical", "research", "design", "epidemiology" ]
2012
Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis
The d-arabinan-containing polymers arabinogalactan ( AG ) and lipoarabinomannan ( LAM ) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis . Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl ( Araf ) transferases whose structures are largely ...
Tuberculosis ( TB ) , an infectious disease caused by the bacillus Mycobacterium tuberculosis , burdens large swaths of the world population . Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol . This front line compound inhibits a se...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "biochemistry", "infectious", "diseases/antimicrobials", "and", "drug", "resistance", "microbiology" ]
2011
The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module
The stable infection of host macrophages by Mycobacterium tuberculosis ( Mtb ) involves , and depends on , the attenuation of the diverse microbicidal responses mounted by the host cell . This is primarily achieved through targeted perturbations of the host cellular signaling machinery . Therefore , in view of the depe...
The adaptation of Mycobacterium tuberculosis ( Mtb ) involves dynamic interactions with the molecular components of the host cellular machinery . Therefore , targeting relevant host factors may provide an alternate approach for the chemotherapy of tuberculosis ( TB ) . To test this , we first performed an siRNA screen ...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "immunology/cellular", "microbiology", "and", "pathogenesis", "infectious", "diseases/bacterial", "infections", "cell", "biology/cell", "signaling" ]
2010
Identification of Host-Dependent Survival Factors for Intracellular Mycobacterium tuberculosis through an siRNA Screen
The importance of Zika virus ( ZIKV ) has increased noticeably since the outbreak in the Americas in 2015 , when the illness was associated with congenital disorders . Although there is evidence of sexual transmission of the virus , the mosquito Aedes aegypti is believed to be the main vector for transmission to humans...
Zika virus is a flavivirus transmitted by mosquitoes , isolated for the first time in the Ziika Forest in Uganda in 1947 from a rhesus macaque monkey . The disease is usually asymptomatic , but sometimes it causes a mild illness that comes with fever , rash , joint pain , and conjunctivitis . The World Health Organizat...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "invertebrates", "medicine", "and", "health", "sciences", "body", "fluids", "pathology", "and", "laboratory", "medicine", "viral", "transmission", "and", "infection", "pathogens", "geographical", "locations", "microbiology", "argentina", "saliva", "animals", "viral", "v...
2019
Vector competence of Aedes aegypti for different strains of Zika virus in Argentina
Finely tuned changes in cytosolic free calcium ( [Ca2+]c ) mediate numerous intracellular functions resulting in the activation or inactivation of a series of target proteins . Palmitoylation is a reversible post-translational modification involved in membrane protein trafficking between membranes and in their function...
Palmitoylation is a reversible post-translational modification catalyzed by palmitoyl acyltransferases ( PATs ) and proteins that undergo this modification are involved in numerous intracellular functions . Yeast Akr1p was the first characterized PAT whilst HIP14 , an Akr1p homolog in human , is one of the most highly ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "chemical", "compounds", "aspergillus", "organic", "compounds", "membrane", "proteins", "aspergillus", "nidulans", "physiological", "processes", "fungi", "model", "organisms", "homeostasis", "amino", "acids", "calcium", "signaling"...
2016
Palmitoylation of the Cysteine Residue in the DHHC Motif of a Palmitoyl Transferase Mediates Ca2+ Homeostasis in Aspergillus
Understanding the control of epigenetic regulation is key to explain and modify the aging process . Because histone-modifying enzymes are sensitive to shifts in availability of cofactors ( e . g . metabolites ) , cellular epigenetic states may be tied to changing conditions associated with cofactor variability . The ai...
Cell reprogramming , a process that allows differentiated cells to re-acquire stem-like properties , is increasingly considered a critical phenomenon in tissue regeneration , aging and cancer . In light of the importance of metabolism in controlling cell fate , we designed a computational model capable of predicting th...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "cell", "physiology", "medicine", "and", "health", "sciences", "enzymes", "cancer", "risk", "factors", "enzymology", "cell", "metabolism", "oncology", "stem", "cells", "enzyme", "metabolism", "epigenetics", "enzyme", "chemistry", "chromatin", "cell", "potency", "chrom...
2018
Epigenetic regulation of cell fate reprogramming in aging and disease: A predictive computational model
One ultimate goal of metabolic network modeling is the rational redesign of biochemical networks to optimize the production of certain compounds by cellular systems . Although several constraint-based optimization techniques have been developed for this purpose , methods for systematic enumeration of intervention strat...
Mathematical modeling has become an essential tool for investigating metabolic networks . One ultimate goal of metabolic network modeling is the rational redesign of biochemical networks to optimize the production of certain compounds by cellular systems . Accordingly , several optimization techniques have been propose...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[]
2014
Enumeration of Smallest Intervention Strategies in Genome-Scale Metabolic Networks
Hepatitis C virus ( HCV ) is an oncogenic virus associated with the onset of hepatocellular carcinoma ( HCC ) . The present study investigated the possible link between HCV infection and Netrin-1 , a ligand for dependence receptors that sustains tumorigenesis , in particular in inflammation-associated tumors . We show ...
Viruses and bacteria are implicated in 15%–20% of total cancer occurrences . Hepatitis C virus ( HCV ) infection is one of the main causative agents of liver cancer . “Dependence receptors” are a class of receptors that auto-activate and trigger apoptosis in the absence of their ligands , and “dependence receptor” liga...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "and", "health", "sciences", "pathology", "and", "laboratory", "medicine", "molecular", "probe", "techniques", "gene", "regulation", "hepacivirus", "pathogens", "messenger", "rna", "microbiology", "immunoblotting", "viral", "structure", "viruses", "rna", "vi...
2016
Epidermal Growth Factor Receptor-Dependent Mutual Amplification between Netrin-1 and the Hepatitis C Virus
Cell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity , and they have been linked to cognitive function in adult animals . We have previously developed a mimetic peptide ( FGL ) from the neural cell adhesion molecule ( NCAM ) that enhances sp...
The human brain contains trillions of neuronal connections , called synapses , whose pattern of activity controls all our cognitive functions . These synaptic connections are dynamic and constantly changing in their strength and properties , and this process of synaptic plasticity is essential for learning and memory ....
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biology", "neuroscience" ]
2012
Facilitation of AMPA Receptor Synaptic Delivery as a Molecular Mechanism for Cognitive Enhancement
Hepatitis C virus ( HCV ) infection develops into chronicity in 80% of all patients , characterized by persistent low-level replication . To understand how the virus establishes its tightly controlled intracellular RNA replication cycle , we developed the first detailed mathematical model of the initial dynamic phase o...
Hepatitis C is a severe disease and a prime cause for liver transplantation . Up to 3% of the world's population are chronically infected with its causative agent , the Hepatitis C virus ( HCV ) . This capacity to establish long ( decades ) lasting persistent infection sets HCV apart from other plus-strand RNA viruses ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "hepatitis", "c", "medicine", "systems", "biology", "infectious", "diseases", "hepatitis", "theoretical", "biology", "biology", "computational", "biology", "viral", "diseases" ]
2013
Replication Vesicles are Load- and Choke-Points in the Hepatitis C Virus Lifecycle
Liver fibrosis was viewed as a reversible process . The activation of hepatic stellate cells ( HSCs ) is a key event in the process of liver fibrosis . The induction of senescence of HSCs would accelerate the clearance of the activated HSCs . Previously , we demonstrated that soluble egg antigens ( SEA ) of Schistosoma...
Activation of hepatic stellate cells ( HSCs ) is a key event of liver fibrosis . Induction of activated HSCs apoptosis and inhibition of activated HSCs proliferation are the common anti-fibrotic strategies to block liver fibrosis . The induction of senescence of HSCs is responsible for the clearance of the activated HS...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "schistosoma", "invertebrates", "medicine", "and", "health", "sciences", "cell", "cycle", "inhibitors", "senescence", "helminths", "gene", "regulation", "cell", "cycle", "and", "cell", "division", "cell", "processes", "animals", "liver", "diseases", "plasmid", "constr...
2016
Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway
Learning has been studied extensively in the context of isolated individuals . However , many organisms are social and consequently make decisions both individually and as part of a collective . Reaching consensus necessarily means that a single option is chosen by the group , even when there are dissenting opinions . ...
Learning is ubiquitous among animal species , allowing individuals to adjust their behavior in response to their environment to improve their chances of survival and reproduction . However , while many animals live and make decisions within social groups , it is not well understood how associative learning functions wi...
[ "Abstract", "Introduction", "Model", "Results", "Discussion" ]
[ "psychology", "ecology", "and", "environmental", "sciences", "animal", "behavior", "zoology", "ecology", "cognition", "behavior", "biology", "and", "life", "sciences", "sensory", "perception", "social", "sciences", "evolutionary", "biology", "cognitive", "science", "neu...
2014
Collective Learning and Optimal Consensus Decisions in Social Animal Groups
In the fission yeast Schizosaccharomyces pombe , the transcriptional-regulatory network that governs flocculation remains poorly understood . Here , we systematically screened an array of transcription factor deletion and overexpression strains for flocculation and performed microarray expression profiling and ChIP–chi...
Flocculation is a process that involves yeast cells adhering to one another to form clumps called flocs . This trait is important for industrial yeast applications as it provides a cost-effective and efficient method to remove yeast cells . The adherence between cells occurs by the binding of glycoproteins known as flo...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genomics", "functional", "genomics", "model", "organisms", "gene", "expression", "genetics", "molecular", "genetics", "biology", "computational", "biology", "yeast", "and", "fungal", "models", "microbiology", "genetics", "and", "genomics" ]
2012
Deciphering the Transcriptional-Regulatory Network of Flocculation in Schizosaccharomyces pombe
The microsomal , membrane-bound , human cytochrome P450 ( CYP ) 2C9 is a liver-specific monooxygenase essential for drug metabolism . CYPs require electron transfer from the membrane-bound CYP reductase ( CPR ) for catalysis . The structural details and functional relevance of the CYP-membrane interaction are not under...
We describe the first atomic-detail models and simulations of a full-length , membrane-bound mammalian cytochrome P450 . To date , all the structural studies of microsomal , drug-metabolizing cytochrome P450s have been performed using engineered , solubilized forms of the enzymes and it is not yet understood how the me...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "biology", "computational", "biology" ]
2011
Structure and Dynamics of the Membrane-Bound Cytochrome P450 2C9
Eradication of tuberculosis ( TB ) , the world's leading cause of death due to infectious disease , requires a highly efficacious TB vaccine . Many TB vaccine candidates are in pre-clinical and clinical development but only a few can be advanced to large-scale efficacy trials due to limited global resources . We aimed ...
Tuberculosis ( TB ) causes more deaths than any other single infectious disease , and a new , improved vaccine is needed to control the epidemic . Many new TB vaccine candidates are in clinical development , but only one or two can be advanced to expensive efficacy trials . In this study , we compared magnitude and fun...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "blood", "cells", "t", "helper", "cells", "innate", "immune", "system", "medicine", "and", "health", "sciences", "immune", "cells", "immune", "physiology", "cytokines", "immunology", "tropical", "diseases", "vaccines", "bacterial", "diseases", "developmental", "biolog...
2019
A comparison of antigen-specific T cell responses induced by six novel tuberculosis vaccine candidates
The Chicxulub bolide impact caused the end-Cretaceous mass extinction of plants , but the associated selectivity and ecological effects are poorly known . Using a unique set of North Dakota leaf fossil assemblages spanning 2 . 2 Myr across the event , we show among angiosperms a reduction of ecological strategies and s...
Sixty-six million years ago the Chicxulub bolide impacted the Earth , marking the Cretaceous–Paleogene boundary ( KPB ) . This event caused the planet's most recent mass extinction , but the selectivity and functional consequences of the extinction on terrestrial plants has been largely unknown . A key untested hypothe...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "paleoclimatology", "ecology", "and", "environmental", "sciences", "ecological", "niches", "paleobiology", "ecology", "ecophysiology", "earth", "sciences", "paleontology", "biology", "and", "life", "sciences", "plant", "ecology", "paleoecology", "biodiversity", "macroecolog...
2014
Plant Ecological Strategies Shift Across the Cretaceous–Paleogene Boundary
In addition to their protein coding function , exons can also serve as transcriptional enhancers . Mutations in these exonic-enhancers ( eExons ) could alter both protein function and transcription . However , the functional consequence of eExon mutations is not well known . Here , using massively parallel reporter ass...
Exons that code for protein can also have additional functions , such as regulating gene transcription through enhancer activity . Here , we changed every nucleotide in three different exons that also function as enhancers , and examined their enhancer activity to test whether nucleotide changes in these exons can affe...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "sequencing", "techniques", "genome", "expression", "analysis", "functional", "genomics", "animal", "genetics", "genome", "evolution", "gene", "function", "genome", "sequencing", "mutation", "genome", "analysis", "molecular", "genetics", "molecular", "biology", "technique...
2014
Systematic Dissection of Coding Exons at Single Nucleotide Resolution Supports an Additional Role in Cell-Specific Transcriptional Regulation
Haploinsufficiency , wherein a single functional copy of a gene is insufficient to maintain normal function , is a major cause of dominant disease . Human disease studies have identified several hundred haploinsufficient ( HI ) genes . We have compiled a map of 1 , 079 haplosufficient ( HS ) genes by systematic identif...
Humans , like most complex organisms , have two copies of most genes in their genome , one from the mother and one from the father . This redundancy provides a back-up copy for most genes , should one copy be lost through mutation . For a minority of genes , one functional copy is not enough to sustain normal human fun...
[ "Abstract", "Introduction", "Results", "Discussion", "Methods" ]
[ "genetics", "and", "genomics/genetics", "of", "disease", "genetics", "and", "genomics/population", "genetics", "evolutionary", "biology/genomics" ]
2010
Characterising and Predicting Haploinsufficiency in the Human Genome
The trimeric envelope ( Env ) spike is the focus of vaccine design efforts aimed at generating broadly neutralizing antibodies ( bNAbs ) to protect against HIV-1 infection . Three recent developments have facilitated a thorough investigation of the antigenic structure of the Env trimer: 1 ) the isolation of many bNAbs ...
The discovery of new broadly neutralizing antibodies against various epitopes on the HIV-1 envelope glycoprotein trimer and increased knowledge of its structure are guiding vaccine design . To increase our understanding of the interrelationships among the different epitopes , we generated a detailed antigenic map of th...
[ "Abstract", "Introduction", "Results", "and", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer
Despite its relatively poor efficacy , Bacillus Calmette-Guérin ( BCG ) has been used as a tuberculosis ( TB ) vaccine since its development in 1921 . BCG induces robust T helper 1 ( Th1 ) immune responses but , for many individuals , this is not sufficient for host resistance against Mycobacterium tuberculosis ( M . t...
Tuberculosis is a global health problem , with one-third of the global population infected with tubercle bacteria . Numerous studies have shown that Th1 cell responses are indispensable for protective immunity against TB . However , while the vaccine strain BCG induces sufficient Th1 cell response , this response does ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "biology" ]
2011
Early Secreted Antigen ESAT-6 of Mycobacterium tuberculosis Promotes Protective T Helper 17 Cell Responses in a Toll-Like Receptor-2-dependent Manner
In contrast to existing estimates of approximately 200 murine imprinted genes , recent work based on transcriptome sequencing uncovered parent-of-origin allelic effects at more than 1 , 300 loci in the developing brain and two adult brain regions , including hundreds present in only males or females . Our independent r...
Typically both copies of mammalian genes are expressed , but in some cases , “imprinting” restricts expression to the maternal or paternal copy . Having two copies of each gene is considered advantageous since in enables compensation when one does not function properly . Why imprinting evolved and its utility to each s...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "medicine", "dementia", "genomics", "neurological", "disorders", "neurology", "genetics", "biology", "computational", "biology", "genetics", "and", "genomics" ]
2012
Critical Evaluation of Imprinted Gene Expression by RNA–Seq: A New Perspective
To investigate the clinical features , clinical course of granuloma , serologic findings , treatment outcome , and probable infection sources in adult patients with ocular toxocariasis ( OT ) . In this retrospective cohort study , we examined 101 adult patients diagnosed clinically and serologically with OT . Serial fu...
Toxocariasis is one of America's most common neglected infections of poverty and a helminthiasis of global importance . Little is known about the epidemiologic , demographic , and clinical features of ocular toxocariasis ( OT ) in adult patients , and the treatment regimen for OT has not been standardized . We conducte...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "helminth", "infections", "infectious", "diseases", "medicine", "and", "health", "sciences", "toxocariasis", "larva", "migrans", "neglected", "tropical", "diseases", "tropical", "diseases", "parasitic", "diseases" ]
2014
Clinical Features and Course of Ocular Toxocariasis in Adults
All types of small RNAs in plants , piwi-interacting RNAs ( piRNAs ) in animals and a subset of siRNAs in Drosophila and C . elegans are subject to HEN1 mediated 3’ terminal 2’-O-methylation . This modification plays a pivotal role in protecting small RNAs from 3’ uridylation , trimming and degradation . In Arabidopsis...
Small silencing RNAs are key regulators of gene expression in both plants and animals . HEN1-mediated 3’ terminal 2’-O-methylation plays a crucial role in small RNA stability control . In the absence of HEN1 , several types of small RNAs become frequently uridylated ( non-templated uridine addition ) and trimmed , a ph...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2015
Synergistic and Independent Actions of Multiple Terminal Nucleotidyl Transferases in the 3’ Tailing of Small RNAs in Arabidopsis
The Plasmodium vivax vaccine candidate Duffy Binding Protein ( DBP ) is a protein necessary for P . vivax invasion of reticulocytes . The polymorphic nature of DBP induces strain-specific immune responses that pose unique challenges for vaccine development . DEKnull is a synthetic DBP based antigen that has been engine...
Plasmodium vivax is an oft neglected causative agent of human malaria . It inflicts tremendous burdens on public health infrastructures and causes significant detrimental effects on socio-economic growth throughout the world . P . vivax Duffy Binding Protein ( DBP ) is a surface protein that the parasite uses to invade...
[ "Abstract", "Introduction", "Materials", "and", "Methods", "Results", "Discussion" ]
[]
2015
Structural Analysis of the Synthetic Duffy Binding Protein (DBP) Antigen DEKnull Relevant for Plasmodium vivax Malaria Vaccine Design
Osteoporosis is a major public health problem . It is mainly characterized by low bone mineral density ( BMD ) and/or low-trauma osteoporotic fractures ( OF ) , both of which have strong genetic determination . The specific genes influencing these phenotypic traits , however , are largely unknown . Using the Affymetrix...
Osteoporosis is a major health concern worldwide . It is a highly heritable disease characterized mainly by low bone mineral density ( BMD ) and/or osteoporotic fractures . However , the specific genetic variants determining risk for low BMD or OF are largely unknown . Here , taking advantage of recent technological ad...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "genetics", "and", "genomics/genetics", "of", "disease", "genetics", "and", "genomics/complex", "traits" ]
2010
Genome-Wide Association Study Identifies ALDH7A1 as a Novel Susceptibility Gene for Osteoporosis
Between 2014 and 2016 more than 3 , 800 imported human cases of chikungunya fever in Florida highlight the high risk for local transmission . To examine the potential for sustained local transmission of chikungunya virus ( CHIKV ) in Florida we tested whether local populations of Aedes aegypti and Aedes albopictus show...
The emergence of mosquito-borne chikungunya virus in the Americas starting in 2013 has been associated with geographically widespread outbreaks of human illness . Transmission of chikungunya virus in the U . S . is a major public health risk , especially in Florida where the environmental conditions are favorable for t...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "dominican", "republic", "united", "states", "invertebrates", "medicine", "and", "health", "sciences", "body", "fluids", "legs", "pathology", "and", "laboratory", "medicine", "togaviruses", "chikungunya", "infection", "pathogens", "tropical", "diseases", "microbiology", ...
2017
Transmission risk of two chikungunya lineages by invasive mosquito vectors from Florida and the Dominican Republic
To get beyond the “low-hanging fruits” so far identified by genome-wide association ( GWA ) studies , new methods must be developed in order to discover the numerous remaining genes that estimates of heritability indicate should be contributing to complex human phenotypes , such as obesity . Here we describe a novel in...
Obesity has a strong genetic component and an estimated 45%–85% of the variation in adult relative weight is genetically determined . Many genes have recently been identified in genome-wide association studies . The individual effects of the identified genes , however , have been very modest , and their identification ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "diabetes", "and", "endocrinology/obesity", "genetics", "and", "genomics/complex", "traits", "genetics", "and", "genomics/gene", "discovery", "genetics", "and", "genomics/gene", "expression" ]
2010
Use of Genome-Wide Expression Data to Mine the “Gray Zone” of GWA Studies Leads to Novel Candidate Obesity Genes
Why most of the in vivo experiments do not find the 30-nm chromatin fiber , well studied in vitro , is a puzzle . Two basic physical inputs that are crucial for understanding the structure of the 30-nm fiber are the stiffness of the linker DNA and the relative orientations of the DNA entering/exiting nucleosomes . Base...
The fate of a cell is not just decided by the genetic code but also by the nature of the 3D organization of the protein-bound DNA , known as chromatin . Chromatin packaging is believed to be in a hierarchical manner , and one of the crucial stages in the packaging is argued to be having a zig-zag structure with specifi...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]
[ "protein", "interactions", "dna-binding", "proteins", "protein", "structure", "epigenetics", "dna", "dna", "structure", "chromatin", "chromosome", "biology", "proteins", "gene", "expression", "histones", "molecular", "biology", "nucleosomes", "biochemistry", "biochemical", ...
2017
Binding of DNA-bending non-histone proteins destabilizes regular 30-nm chromatin structure
Mycobacterium ulcerans , the causative agent of Buruli ulcer in humans , is unique among the members of Mycobacterium genus due to the presence of the virulence determinant megaplasmid pMUM001 . This plasmid encodes multiple virulence-associated genes , including mup011 , which is an uncharacterized Ser/Thr protein kin...
Mycobacterium ulcerans is a slow growing pathogen , which is prevalent in many tropical and sub-tropical countries . M . ulcerans possesses unique signaling pathways with only 13 STPK containing genes . This is strikingly different from its closest homolog Mycobacterium marinum and surprisingly closer to the human path...
[ "Abstract", "Introduction", "Methods", "Results", "Discussion" ]
[ "medicine", "and", "health", "sciences", "protein", "interactions", "enzymes", "regulatory", "proteins", "enzymology", "microbiology", "emerging", "infectious", "diseases", "protein", "structure", "enzyme", "chemistry", "bacterial", "pathogens", "infectious", "diseases", ...
2014
Identification of Ser/Thr kinase and Forkhead Associated Domains in Mycobacterium ulcerans: Characterization of Novel Association between Protein Kinase Q and MupFHA
Lentiviruses can infect non-dividing cells , and various cellular transport proteins provide crucial functions for lentiviral nuclear entry and integration . We previously showed that the viral capsid ( CA ) protein mediated the dependency on cellular nucleoporin ( NUP ) 153 during HIV-1 infection , and now demonstrate...
Lentiviruses such as HIV-1 possess mechanisms to bypass the nuclear envelope and reach the nuclear interior for viral DNA integration . Numerous nuclear transport proteins are important for HIV-1 infection , suggesting the viral nucleoprotein complex enters the nucleus by passing through nuclear pore complexes . HIV-1 ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[]
2013
Nucleoporin NUP153 Phenylalanine-Glycine Motifs Engage a Common Binding Pocket within the HIV-1 Capsid Protein to Mediate Lentiviral Infectivity
Natural genetic transformation is widely distributed in bacteria and generally occurs during a genetically programmed differentiated state called competence . This process promotes genome plasticity and adaptability in Gram-negative and Gram-positive bacteria . Transformation requires the binding and internalization of...
Natural genetic transformation , first discovered in Streptococcus pneumoniae by Griffith in 1928 , is observed in many Gram-negative and Gram-positive bacteria . This process promotes genome plasticity and adaptability . In particular , it enables many human pathogens such as Streptococcus pneumoniae , Staphylococcus ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "bacteriology", "microbial", "pathogens", "biology", "microbiology", "bacterial", "pathogens" ]
2013
A Type IV Pilus Mediates DNA Binding during Natural Transformation in Streptococcus pneumoniae
Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes . The mechanisms behind these disturbances are unknown . Here we show the specificity of the pre-autoimmune...
We have recently found that distinct metabolic disturbances precede β-cell autoimmunity in children who later progress to type 1 diabetes ( T1D ) . Here we performed a murine study using non-obese diabetic ( NOD ) mice that recapitulated the protocol used in human , followed up by independent studies where NOD mice wer...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "Methods" ]
[ "systems", "biology", "medicine", "clinical", "immunology", "autoimmune", "diseases", "diabetes", "mellitus", "type", "1", "biology", "computational", "biology", "metabolic", "networks", "immunology" ]
2011
Metabolic Regulation in Progression to Autoimmune Diabetes
Infection with the helminth Schistosoma ( S . ) mansoni drives the development of interleukin ( IL ) -10-producing regulatory B ( Breg ) cells in mice and man , which have the capacity to reduce experimental allergic airway inflammation and are thus of high therapeutic interest . However , both the involved antigen and...
Infection with helminth parasites is known to be inversely associated with hyper-inflammatory disorders . While Schistosoma ( S . ) mansoni has been described to exert its down-modulatory effects on inflammation by inducing a network of regulatory immune cells such as regulatory B ( Breg ) , the mechanisms of Breg cell...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "blood", "cells", "flow", "cytometry", "schistosoma", "invertebrates", "schistosoma", "mansoni", "innate", "immune", "system", "medicine", "and", "health", "sciences", "immune", "cells", "immune", "physiology", "cytokines", "helminths", "immunology", "light", "microscop...
2017
Schistosome egg antigens, including the glycoprotein IPSE/alpha-1, trigger the development of regulatory B cells