The Voltage–gated Proton Channel, Hv1, Enhances Brain Damage from Ischemic Stroke

Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. Here we show that NOX–mediated damage can be inhibited by suppression of the voltage-gated proton channel, Hv1. Hv1 is required for full NOX activity since it compensates for loss of NOX–exported charge. We show that Hv1 is required for NOX–dependent ROS generation in brain microglia in situ and in vivo. Mouse and human brain microglia, but not neurons or astrocytes, express large Hv1-mediated currents. Mice lacking Hv1 were protected from NOX–mediated neuronal death and brain damage 24 hours after stroke. These results demonstrate that Hv1–dependent ROS production is responsible for a significant fraction of brain damage at early time points after ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the treatment of ischemic stroke

City of El Campo Downtown Revitalization Plan

The Revitalization Plan for Downtown El Campo is a planning document that provides guidance for the development of Downtown El Campo. This planning document includes an overview and analysis of the existing conditions in the City of El Campo and the El Campo Downtown Revitalization Area, a design proposal with vision, goals, and objectives for enhancing Downtown El Campo and a detailed implementation chapter for successful execution of the plan.This planning document presents the revitalization plan for downtown El Campo, Texas. This document was developed by Texas Target Communities (TTC) in partnership with the City of El Campo. The City of El Campo collaborated with Texas Target Communities in fall 2016 through the summer of 2017 to create a plan for revitalization of downtown El Campo. The purpose of the collaboration was to assess current community conditions, develop goals, objectives, and implementation strategies related to future development & growth strategies, through a public participatory process, in order to help guide the future growth of the City

City of El Campo Downtown Revitalization Plan

The Revitalization Plan for Downtown El Campo is a planning document that provides guidance for the development of Downtown El Campo. This planning document includes an overview and analysis of the existing conditions in the City of El Campo and the El Campo Downtown Revitalization Area, a design proposal with vision, goals, and objectives for enhancing Downtown El Campo and a detailed implementation chapter for successful execution of the plan.This planning document presents the revitalization plan for downtown El Campo, Texas. This document was developed by Texas Target Communities (TTC) in partnership with the City of El Campo. The City of El Campo collaborated with Texas Target Communities in fall 2016 through the summer of 2017 to create a plan for revitalization of downtown El Campo. The purpose of the collaboration was to assess current community conditions, develop goals, objectives, and implementation strategies related to future development & growth strategies, through a public participatory process, in order to help guide the future growth of the City

Tre1, a G Protein-Coupled Receptor, Directs Transepithelial Migration of Drosophila Germ Cells

In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG) is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR), Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target

Lack of an Antibacterial Response Defect in Drosophila Toll-9 Mutant

Toll and Toll-like receptors represent families of receptors involved in mediating innate immunity response in insects and mammals. Although Drosophila proteome contains multiple Toll paralogs, Toll-1 is, so far, the only receptor to which an immune role has been attributed. In contrast, every single mammalian TLR is a key membrane receptor upstream of the vertebrate immune signaling cascades. The prevailing view is that TLR-mediated immunity is ancient. Structural analysis reveals that Drosophila Toll-9 is the most closely related to vertebrate TLRs and utilizes similar signaling components as Toll-1. This suggests that Toll-9 could be an ancestor of TLR-like receptors and could have immune function. Consistently, it has been reported that over-expression of Toll-9 in immune tissues is sufficient to induce the expression of some antimicrobial peptides in flies. These results have led to the idea that Toll-9 could be a constitutively active receptor that maintain significant levels of antimicrobial molecules and therefore provide constant basal protection against micro-organisms. To test theses hypotheses, we generated and analyzed phenotypes associated with a complete loss-of-function allele of Toll-9. Our results suggest that Toll-9 is neither required to maintain a basal anti-microbial response nor to mount an efficient immune response to bacterial infection

The first achievement of the double feedback control of the detachment in the long-pulse plasma on EAST

EAST implements the double feedback control experiments of the detachment by using two control systems at the same time to explore the new detachment control way. We hire two PID controllers and two gas puffing valves dividedly to inject impurity gases from different locations, increasing the radiated power of the bulk plasma and reducing the divertor electron temperature (Te,t) simultaneously. This control method is applied in the EAST long-pulse H-mode plasma, the controlled variables of the radiative feedback control is the local radiative intensity and the total radiated power respectively. In the experiments, the longest double control duration has been up to 13.5 s, the divertor heat flux is reduced significantly in the control duration, while the particle flux has an overall drop at the end of the control phase. The chosen impurity species in the control system are Neon (Ne) and Argon (Ar): Ne is injected from the upper divertor to raise the core radiated power, and the Ar is injected from the lower divertor to reduce the Te,t beneath 8 eV. However, the Ar injection is not only decreasing the Te,t, but also generates an unfavorable increment of the core radiated power. This increment makes the bulk radiated power is higher than the target value, the radiative feedback control thus is paused for a long time. This mechanism results in the double feedback control back to the sequential implementations of the two feedback controls, which does not accord with the original expection(the both controls run at the same time), and degrades the control precision. In the future, many mitigating ways will be tested to improve the control effect. We will also develop a dynamic response model of the impurity seeding to simulate the time evolution of the divertor heat load with two kinds of impurities. The modeling results will be used to optimize the double feedback control system to gain a better experimental results