Inactivation of muscle chloride channel by transposon insertion in myotonic mice.

MYOTONIA (stiffness and impaired relaxation of skeletal muscle) is a symptom of several diseases caused by repetitive firing of action potentials in muscle membranes. Purely myotonic human diseases are dominant myotonia congenita (Thomsen) and recessive generalized myotonia (Becker), whereas myotonic dystrophy is a systemic disease. Muscle hyperexcitability was attributed to defects in sodium channels and/or to a decrease in chloride conductance (in Becker's myotonia and in genetic animal models). Experimental blockage of Cl- conductance (normally 70-85% of resting conductance in muscle) in fact elicits myotonia. ADR mice are a realistic animal model for recessive autosomal myotonia. In addition to Cl- conductance, many other parameters are changed in muscles of homozygous animals. We have now cloned the major mammalian skeletal muscle chloride channel (ClC-1). Here we report that in ADR mice a transposon of the ETn family has inserted into the corresponding gene, destroying its coding potential for several membrane-spanning domains. Together with the lack of recombination between the Clc-1 gene and the adr locus, this strongly suggests a lack of functional chloride channels as the primary cause of mouse myotonia.     

Probing the Intact Cluster Catalysis Concept by Tetrahedral Clusters With Framework Chirality

In order to bring evidence for or against the hypothesis of catalytic hydrogenation by intact trinuclear arene ruthenium clusters containing an oxo cap, the substrate being hydrogenated inside the hydrophobic pocket spanned by the three arene ligands （“supramolecular cluster catalysis”）, we synthesized cationic Ru30 clusters （See Fig. 1） with three different arene ligands （intrinsically chiral tetrahedra）.     

一种在不对称路由环境下的安全HIP中间系统

随着移动计算技术的高速发展,HIP因其在移动主机支持及安全等方面的优越特性而备受关注.可尽管HIP在保护通信两端方面具有卓越的安全特性,但作为HIP通信节点的中间系统(如NAT/FW系统)却不能得到有效保护,尤其是在不对称路由环境下的HIP中间系统,很容易遭受攻击.本文在分析HIP通信及其中间系统的基础上,结合HIP注册扩展协议,提出一种在不对称路由情况下的安全的基于HTN(HIP through NATs)的HIP中间系统模型.该系统不仅让HIP通信主机可以感知链路上的NAT等中间系统,HIP中间系统也可以通过注册协议,来学习连接状态信息,并验证通信发起主机是否真正感兴趣于成功建立HIP连接,并为后续更新报文的验证提供可信依据,从而有效避免遭受DoS及MitM攻击.     

Room-temperature deposition of yttria-stabilized zirconia buffer layer on metallic substrates by laser ablation

Conclusion We investigated the deposition of YSZ buffer layers on polycrystalline metallic substrate at low temperature and low oxygen pressure. The (100) preferred orientation can be obtained in the YSZ films and was explained by the model of growth-based orientation selection. Optimizations of oxygen partial pressure and target distance were done to offer referable values for IBAD process.     

RIM1alpha is required for presynaptic long-term potentiation.

Two main forms of long-term potentiation (LTP)-a prominent model for the cellular mechanism of learning and memory-have been distinguished in the mammalian brain. One requires activation of postsynaptic NMDA (N-methyl d-aspartate) receptors, whereas the other, called mossy fibre LTP, has a principal presynaptic component. Mossy fibre LTP is expressed in hippocampal mossy fibre synapses, cerebellar parallel fibre synapses and corticothalamic synapses, where it apparently operates by a mechanism that requires activation of protein kinase A. Thus, presynaptic substrates of protein kinase A are probably essential in mediating this form of long-term synaptic plasticity. Studies of knockout mice have shown that the synaptic vesicle protein Rab3A is required for mossy fibre LTP, but the protein kinase A substrates rabphilin, synapsin I and synapsin II are dispensable. Here we report that mossy fibre LTP in the hippocampus and the cerebellum is abolished in mice lacking RIM1alpha, an active zone protein that binds to Rab3A and that is also a protein kinase A substrate. Our results indicate that the long-term increase in neurotransmitter release during mossy fibre LTP may be mediated by a unitary mechanism that involves the GTP-dependent interaction of Rab3A with RIM1alpha at the interface of synaptic vesicles and the active zone.     

Funding of molecular biology

The way that molecular biology is funded in Germany is damaging the universities. Germany policy makers should follow the advice of Wilhelm von Humboldt, and concentrate teaching and research in the universities.     

The C4-dicarboxylate transport system ofRhizobium meliloti and its role in nitrogen fixation during symbiosis with alfalfa (Medicago sativa)

TheRhizobium meliloti C₄-dicarboxylate transport (Dct) system is essential for an effective symbiosis with alfalfa plants. C₄-dicarboxylates are the major carbon source taken up by bacteroids. Genetic analysis of Dct^– mutant strains led to the isolation of thedct carrier genedctA and the regulatory genesdctB anddctD. The carrier genedctA is regulated in free-living cells by the alternative sigma factor RpoN and the two-component regulatory system DctB/D. In addition, DctA is involved in its own regulation, possibly by interacting with DctB. In bacteroids, besides the DctB/DctD system an additional symbiotic activator is thought to be involved indctA expression. Further regulation ofdctA in the free-living state is reflected by diauxic growth of rhizobia, with succinate being the preferred carbon source. The tight coupling of C₄-dicarboxylate transport and nitrogen fixation is revealed by a reduced level of C₄-dicarboxylate transport in nitrogenase negative bacteroids.     

Flow microcalorimetry as a tool for an improved analysis of antibiotic activity: the different stages of chloramphenicol action

Flow microcalorimetry in combination with photometric mass determination of staphylococci in suspension was used to reveal alterations in the intensity, extent and efficiency of bacterial metabolism during inhibition of protein synthesis by chloramphenicol. It could be demonstrated that these three parameters of metabolic activity were distinctly affected by this drug, and that the method described promises to be a more reliable tool for assaying the degree and the mode of bacteriostatic inhibition than the conventional determination of the minimum inhibitory concentration.