33 research outputs found

    Na+ current expression in human atrial myofibroblasts: identity and functional roles

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    In the mammalian heart fibroblasts have important functional roles in both healthy conditions and diseased states. During pathophysiological challenges, a closely related myofibroblast cell population emerges, and can have distinct and significant roles.Recently, it has been reported that human atrial myofibroblasts can express a Na+ current, INa. Some of the biophysical properties and molecular features suggest that this INa is due to expression of Nav 1.5, the same Na+ channel α subunit that generates the predominant INa in myocytes from adult mammalian heart. In principle, expression of Nav 1.5 could give rise to regenerative action potentials in the fibroblasts/myofibroblasts. This would suggest an active as opposed to passive role for fibroblasts/myofibroblasts in both the ‘trigger’ and the ‘substrate’ components of cardiac rhythm disturbances.Our goals in this preliminary study were: (i) to confirm and extend the electrophysiological characterization of INa in a human atrial fibroblast/myofibroblast cell population maintained in conventional 2-D tissue culture; (ii) to identify key molecular properties of the α and β subunits of these Na+ channel(s); (iii) to define the biophysical and pharmacological properties of this INa ; (iv) to integrate the available multi-disciplinary data, and attempt to illustrate its functional consequences, using a mathematical model in which the human atrial myocyte is coupled via connexins to fixed numbers of fibroblasts/myofibroblasts in a syncytial arrangement.Our experimental findings confirm that a significant fraction (~40-50%) of these human atrial myofibroblasts can express INa. However, our results suggest that INa may be generated by Nav 1.9, Nav 1.2, and Nav 1.5. Our findings, when complemented with mathematical modeling, provide a background for re-evaluating pharmacological management of supraventricular rhythm disorders, e.g. persistent atrial fibrillation

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    Taxonomy of the order Mononegavirales: update 2017.

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    In 2017, the order Mononegavirales was expanded by the inclusion of a total of 69 novel species. Five new rhabdovirus genera and one new nyamivirus genus were established to harbor 41 of these species, whereas the remaining new species were assigned to already established genera. Furthermore, non-Latinized binomial species names replaced all paramyxovirus and pneumovirus species names, thereby accomplishing application of binomial species names throughout the entire order. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV)

    Measurement of jet fragmentation in Pb+Pb and pppp collisions at sNN=2.76\sqrt{{s_\mathrm{NN}}} = 2.76 TeV with the ATLAS detector at the LHC

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    Comparison of time- and voltage-dependent K +

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    Did community greening reduce crime? Evidence from New Haven, CT, 1996–2007

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    For some volunteers, neighborhood safety is one of the reasons for becoming involved in community greening. For example, many volunteers of the Community Greenspace program at the Urban Resources Initiative in New Haven, Connecticut believe that there is a potential reduction in crime from community greening activities, even though it is not an explicit goal of the program. These types of community-led interventions are distinct from both existing tree canopy and large-scale municipally led initiatives. These types of interventions remain understudied with respect to the potential for reducing crime. We therefore used a quasi-experimental difference-in-differences (DID) approach to test whether more than a decade of street tree planting (1996–2007) in New Haven had an effect on crime levels at planting sites (n = 300) compared to control sites that received no Community Greenspace-planted trees (n = 893). We examined violent, property, and misdemeanor crimes (comprised of vandalism, prostitution, and narcotics crimes) individually and jointly to test for crime-type specific effects, while controlling for sociodemographic factors and spatio-temporal trends. In general, we found a null relationship between trees planted and crime on block faces per year at the p \u3c 0.05 level. Increases in crime were not observed on treatment sites. We discuss implications for tree inventories and monitoring, study design, and techniques to assess impacts of tree planting efforts

    Diversity and epidemiology of plant rhabdoviruses

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    Plant rhabdoviruses are recognized by their large bacilliform particles and for being able to replicate in both their plant hosts and arthropod vectors. This review highlights selected, better studied examples of plant rhabdoviruses, their genetic diversity, epidemiology and interactions with plant hosts and arthropod vectors: Alfalfa dwarf virus is classified as a cytorhabdovirus, but its multifunctional phosphoprotein is localized to the plant cell nucleus. Lettuce necrotic yellows virus subtypes may differentially interact with their aphid vectors leading to changes in virus population diversity. Interactions of rhabdoviruses that infect rice, maize and other grains are tightly associated with their specific leafhopper and planthopper vectors. Future outbreaks of vector-borne nucleorhabdoviruses may be predicted based on a world distribution map of the insect vectors. The epidemiology of coffee ringspot virus and its Brevipalpus mite vector is illustrated highlighting the symptomatology and biology of a dichorhavirus and potential impacts of climate change on its epidemiology.Fil: Dietzgen, Ralf G.. University of Queensland; AustraliaFil: Bejerman, Nicolas. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigaciones Agropecuarias. Instituto de Patología Vegetal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goodin, Michael M.. University of Kentucky; Estados UnidosFil: Higgins, Colleen M.. Auckland University Of Technology; Nueva ZelandaFil: Huot, Ordom B.. North Carolina State University; Estados UnidosFil: Kondo, Hideki. Okayama University; JapónFil: Martin, Kathleen M.. Auburn University.; Estados UnidosFil: Whitfield, Anna E.. North Carolina State University; Estados Unido

    Functional Elements of the Strong psbAI Promoter of Synechococcus elongatus PCC 7942

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    The psbAI gene of the cyanobacterium Synechococcus elongatus PCC 7942 is one of three psbA genes that encode a critical photosystem II reaction center protein, D1. Regulation of the gene family in response to changes in the light environment is complex, occurs at transcriptional and posttranscriptional levels, and results in an interchange of two different forms of D1 in the membrane. Expression of psbAI is downregulated under high-intensity light (high light) in contrast to induction of the other two family members. We show that, in addition to a known accelerated degradation of the psbAI message, promoter activity decreases upon exposure to high light. Unlike the other psbA genes, additional sequences upstream of the psbAI −35 element are required for expression. Mutagenizing the atypical psbAI −10 element from TCTCCT to TATAAT increased the magnitude of expression from both psbAI::lacZ and psbAI::luxAB fusions but did not affect downregulation under high light. Inactivation of group 2 sigma factor genes rpoD2 and sigC, in both wild-type and −10-element mutagenized backgrounds, resulted in elevated psbAI::luxAB expression but did not alter the response to high light. The results are consistent with redundancy of promoter recognition among cyanobacterial group 2 sigma factors. Electrophoretic mobility shift assays showed that the DNA sequence corresponding to the untranslated leader of the psbAI message binds one or more proteins from an S. elongatus extract. The corresponding region of psbAII efficiently competed for this binding activity, suggesting a shared regulatory factor among these disparately regulated genes
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