ATP-sensitive potassium channels mediate survival during infection in mammals and insects

Specific homeostatic mechanisms confer stability in innate immune responses, preventing injury or death from infection. Here we identify, from a screen of N-ethyl-N-nitrosourea-mutagenized mice, a mutation causing both profound susceptibility to infection by mouse cytomegalovirus and approximately 20,000-fold sensitization to lipopolysaccharide (LPS), poly(I.C) and immunostimulatory (CpG) DNA. The LPS hypersensitivity phenotype is not suppressed by mutations in Myd88, Trif, Tnf, Tnfrsf1a, Ifnb, Ifng or Stat1, genes contributing to LPS responses, and results from an abnormality extrinsic to hematopoietic cells. The phenotype is due to a null allele of Kcnj8, encoding Kir6.1, a protein that combines with SUR2 to form an ATP-sensitive potassium channel (K(ATP)) expressed in coronary artery smooth muscle and endothelial cells. In Drosophila melanogaster, suppression of dSUR by RNA interference similarly causes hypersensitivity to infection by flock house virus. Thus, K(ATP) evolved to serve a homeostatic function during infection, and in mammals it prevents coronary artery vasoconstriction induced by cytokines dependent on TLR and/or MDA5 immunoreceptors.     

α2δ expression sets presynaptic calcium channel abundance and release probability

Synaptic neurotransmitter release is driven by Ca(2+) influx through active zone voltage-gated calcium channels (VGCCs). Control of active zone VGCC abundance and function remains poorly understood. Here we show that a trafficking step probably sets synaptic VGCC levels in rats, because overexpression of the pore-forming α1(A) VGCC subunit fails to change synaptic VGCC abundance or function. α2δs are a family of glycosylphosphatidylinositol (GPI)-anchored VGCC-associated subunits that, in addition to being the target of the potent neuropathic analgesics gabapentin and pregabalin (α2δ-1 and α2δ-2), were also identified in a forward genetic screen for pain genes (α2δ-3). We show that these proteins confer powerful modulation of presynaptic function through two distinct molecular mechanisms. First, α2δ subunits set synaptic VGCC abundance, as predicted from their chaperone-like function when expressed in non-neuronal cells. Second, α2δs configure synaptic VGCCs to drive exocytosis through an extracellular metal ion-dependent adhesion site (MIDAS), a conserved set of amino acids within the predicted von Willebrand A domain of α2δ. Expression of α2δ with an intact MIDAS motif leads to an 80% increase in release probability, while simultaneously protecting exocytosis from blockade by an intracellular Ca(2+) chelator. α2δs harbouring MIDAS site mutations still drive synaptic accumulation of VGCCs; however, they no longer change release probability or sensitivity to intracellular Ca(2+) chelators. Our data reveal dual functionality of these clinically important VGCC subunits, allowing synapses to make more efficient use of Ca(2+) entry to drive neurotransmitter release.     

Multi-Disciplinary North-South Collaboration in Participatory Action Research on Food Value Chains: a German-Tanzanian Case Study on Perceptions,Experiences and Challenges

Systemic Practice and Action Research - Upgrading local food value chains is a promising approach to invigorating African food systems. This endeavour warrants multi-disciplinary North-South...     

基于DSP56F807的μC/OS-II移植和实现

首先分析实时操作系统μC/OS-II的系统结构和DSP56F807硬件平台特性,其次编写与硬件相关的代码,将μC/OS-II实时内核移植到DSP56F807上,并进行移植后的测试,最后提出一些在μC/OS-II移植过程中的问题。     

A gene in the multidrug and toxic compound extrusion (MATE) family confers aluminum tolerance in sorghum

Crop yields are significantly reduced by aluminum toxicity on highly acidic soils, which comprise up to 50% of the world's arable land. Candidate aluminum tolerance proteins include organic acid efflux transporters, with the organic acids forming non-toxic complexes with rhizosphere aluminum. In this study, we used positional cloning to identify the gene encoding a member of the multidrug and toxic compound extrusion (MATE) family, an aluminum-activated citrate transporter, as responsible for the major sorghum (Sorghum bicolor) aluminum tolerance locus, Alt(SB). Polymorphisms in regulatory regions of Alt(SB) are likely to contribute to large allelic effects, acting to increase Alt(SB) expression in the root apex of tolerant genotypes. Furthermore, aluminum-inducible Alt(SB) expression is associated with induction of aluminum tolerance via enhanced root citrate exudation. These findings will allow us to identify superior Alt(SB) haplotypes that can be incorporated via molecular breeding and biotechnology into acid soil breeding programs, thus helping to increase crop yields in developing countries where acidic soils predominate.     

An Action Research Study for Elaborating and Implementing an Electronic Waste Collection Program in Brazil

The objective of this study was to conduct Action Research (AR) to create and implement a WEEE management program that was in line with the BNPSW regulations. The city chosen for this study was São João del Rei (SJDR) located in the state of Minas Gerais, Brazil. Using AR it was possible to structure a WEEE management program that involved stakeholders from the city administration, the Federal University of São João del Rei, and representatives from the private sector. The program ultimately collected 1710 kg of WEEE that received an environmentally appropriate destination. Although no major difficulties were observed with respect to the AR process itself, some challenges were encountered. Lack of infrastructure and hesitance on behalf of the public with respect to implementing WEEE Reverse Logistics were complicating factors. The action research as methodology proved to be highly efficient in dealing with e-waste reverse logistics. It resulted in faster decision making, in turn generating better results. Good decisions were repeated and errors were corrected. The Action Research project highlighted the need for raising public awareness about WEEE disposal. It also showed that the public was ultimately interested in participating and contributing to the proposed WEEE management program. The awareness of the population has led to a significant increase in the amount of collected waste. The model resulting from this research serve as a reference for decision makers in implementing similar programs around the world and to contribute to the existing body of knowledge on the subject.

     

胶粉改性沥青桥面防水层铺装结构黏弹性力学分析

胶粉改性沥青桥面防水层具有抗高低温性能好、抗施工损伤特性好、具有与沥青混凝土铺装层和水泥混凝土桥面板黏结性能好、环保等优点,利用黏弹性力学原理对设有胶粉改性沥青防水层的铺装结构进行受力特性分析,研究了防水层厚度、桥面铺装层厚度对桥面铺装结构抗剪性能的影响,并与室内试验结果进行了对比,结果符合良好.分析结果表明:随防水层厚度增加,最大剪应力值τmax会增大;随沥青混凝土铺装层厚度增加,τmax呈现先减小后增大趋势.沥青混凝土面层的厚度为13 cm时产生的τmax值最小.