Influences of temperature change on the relaxation and amplitude inhibition by noradrenaline in the rabbit jejunum

Summary In the rabbit jejunum, the elevation of temperature within the range of 25–37°C diminished the sensitivity to noradrenaline (NA) for both the relaxation and amplitude inhibition. The relaxation by NA was mainly mediated via adrenergic -receptors at 25, 30 or 37°C. The amplitude inhibition was mediated via -receptors at 37°C, and both - and -receptors at 30 or 25°C.     

Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production

Systems for protein degradation are essential for tight control of the inflammatory immune response. Autophagy, a bulk degradation system that delivers cytoplasmic constituents into autolysosomes, controls degradation of long-lived proteins, insoluble protein aggregates and invading microbes, and is suggested to be involved in the regulation of inflammation. However, the mechanism underlying the regulation of inflammatory response by autophagy is poorly understood. Here we show that Atg16L1 (autophagy-related 16-like 1), which is implicated in Crohn's disease, regulates endotoxin-induced inflammasome activation in mice. Atg16L1-deficiency disrupts the recruitment of the Atg12-Atg5 conjugate to the isolation membrane, resulting in a loss of microtubule-associated protein 1 light chain 3 (LC3) conjugation to phosphatidylethanolamine. Consequently, both autophagosome formation and degradation of long-lived proteins are severely impaired in Atg16L1-deficient cells. Following stimulation with lipopolysaccharide, a ligand for Toll-like receptor 4 (refs 8, 9), Atg16L1-deficient macrophages produce high amounts of the inflammatory cytokines IL-1beta and IL-18. In lipopolysaccharide-stimulated macrophages, Atg16L1-deficiency causes Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF)-dependent activation of caspase-1, leading to increased production of IL-1beta. Mice lacking Atg16L1 in haematopoietic cells are highly susceptible to dextran sulphate sodium-induced acute colitis, which is alleviated by injection of anti-IL-1beta and IL-18 antibodies, indicating the importance of Atg16L1 in the suppression of intestinal inflammation. These results demonstrate that Atg16L1 is an essential component of the autophagic machinery responsible for control of the endotoxin-induced inflammatory immune response.     

LAMP架构下的律师事务所网站建设方案

企业通常会通过网站介绍和发布信息,但是拥有一个独立主机的网站维护费用比较昂贵。租赁一个虚拟主机,可以大幅度降低成本。开源的LAMP在软件方面的投资成本较低,从网站的流量上看,全世界70%以上的访问流量是LAMP来提供的,LAMP是最强大的网站解决方案之一。在建设律师事务所网站时,使用LAMP架构,降低了开发成本,实现了网站内容的动态更新,后期的维护成本很低。嵌入了CKEditor,CKFinder,jQuery等开源软件,增强了网站的整体功能。     

Slip zone and energetics of a large earthquake from the Taiwan Chelungpu-fault Drilling Project

Determining the seismic fracture energy during an earthquake and understanding the associated creation and development of a fault zone requires a combination of both seismological and geological field data. The actual thickness of the zone that slips during the rupture of a large earthquake is not known and is a key seismological parameter in understanding energy dissipation, rupture processes and seismic efficiency. The 1999 magnitude-7.7 earthquake in Chi-Chi, Taiwan, produced large slip (8 to 10 metres) at or near the surface, which is accessible to borehole drilling and provides a rare opportunity to sample a fault that had large slip in a recent earthquake. Here we present the retrieved cores from the Taiwan Chelungpu-fault Drilling Project and identify the main slip zone associated with the Chi-Chi earthquake. The surface fracture energy estimated from grain sizes in the gouge zone of the fault sample was directly compared to the seismic fracture energy determined from near-field seismic data. From the comparison, the contribution of gouge surface energy to the earthquake breakdown work is quantified to be 6 per cent.     

Influence of Flux and Sulfur on YAG Laser Welding

1　IntroductionYAGlaserweldingprocesscanbeconductedbyarobotusinganopticalfibertotransferthelaserenergyontoaworkpieceduetoitssmallwavelength (1.0 6mm ) .ThustheweldingautomationlevelcanbehighlyincreasedcomparedwithCO2 laserwelding .Therefore ,recentlyyears ,YAGlaserweldingprocesshasbeenquicklydevelopedandappliedformanufac turingofautomobileandchemicalvesselsetc .Gener ally ,thepowerofaCWYAGlaserisnotsohigh (sofarupto 10kW )duetoitslowefficiencyofenergyconversion .Whenweldingwithamiddleorl…     

Structure and function of a membrane component SecDF that enhances protein export

Protein translocation across the bacterial membrane, mediated by the secretory translocon SecYEG and the SecA ATPase, is enhanced by proton motive force and membrane-integrated SecDF, which associates with SecYEG. The role of SecDF has remained unclear, although it is proposed to function in later stages of translocation as well as in membrane protein biogenesis. Here, we determined the crystal structure of Thermus thermophilus SecDF at 3.3?? resolution, revealing a pseudo-symmetrical, 12-helix transmembrane domain belonging to the RND superfamily and two major periplasmic domains, P1 and P4. Higher-resolution analysis of the periplasmic domains suggested that P1, which binds an unfolded protein, undergoes functionally important conformational changes. In vitro analyses identified an ATP-independent step of protein translocation that requires both SecDF and proton motive force. Electrophysiological analyses revealed that SecDF conducts protons in a manner dependent on pH and the presence of an unfolded protein, with conserved Asp and Arg residues at the transmembrane interface between SecD and SecF playing essential roles in the movements of protons and preproteins. Therefore, we propose that SecDF functions as a membrane-integrated chaperone, powered by proton motive force, to achieve ATP-independent protein translocation.     

Structural comparisons of isomorphic breeding nests between closely allied spiders Cheiracanthium japonicum and Cheiracanthium lascivum (Araneae: Eutichuridae)

Closely allied spider species Cheiracanthium japonicum and Cheiracanthium lascivum make a closed breeding nest for egg laying and parental care. The nest provides the internal climatic stability required for suitable development of eggs and the physical durability required for protection against intruders. Although the breeding nests of these two spiders are quite similar in structure and appearance, their climatic stability and physical durability seem to be empirically different. Such physical features of the nests of these two spiders were compared based on a balance between the inner and outer air temperature and humidity of the nest as well as on the amount and size of spider silks lining the nest. In addition, the female’s relative energy allocation to egg production versus nest construction was examined based on the number or weight of eggs versus the climatic stability and physical durability of the nest. According to the results, the stability of temperature and humidity was maintained better in the breeding nest of C. japonicum than in that of C. lascivum. Furthermore, the nest of C. japonicum was more strongly constructed, with a greater volume and size of silks, than that of C. lascivum. On the other hand, the number or weight of eggs in relation to the female’s body weight in C. japonicum was smaller than that in C. lascivum. These results suggested that the reproductive effort towards nest construction for the purpose of egg and juvenile care in C. japonicum was larger than that in C. lascivum. In contrast, the effort towards egg production in C. japonicum was smaller than that in C. lascivum. Consequently, it is likely that the structural differences in breeding nests between these two spiders are responsible for the discrepancies in the female’s relative energy allocation to nest construction.     

Loss of autophagy in the central nervous system causes neurodegeneration in mice

Protein quality-control, especially the removal of proteins with aberrant structures, has an important role in maintaining the homeostasis of non-dividing neural cells. In addition to the ubiquitin-proteasome system, emerging evidence points to the importance of autophagy--the bulk protein degradation pathway involved in starvation-induced and constitutive protein turnover--in the protein quality-control process. However, little is known about the precise roles of autophagy in neurons. Here we report that loss of Atg7 (autophagy-related 7), a gene essential for autophagy, leads to neurodegeneration. We found that mice lacking Atg7 specifically in the central nervous system showed behavioural defects, including abnormal limb-clasping reflexes and a reduction in coordinated movement, and died within 28 weeks of birth. Atg7 deficiency caused massive neuronal loss in the cerebral and cerebellar cortices. Notably, polyubiquitinated proteins accumulated in autophagy-deficient neurons as inclusion bodies, which increased in size and number with ageing. There was, however, no obvious alteration in proteasome function. Our results indicate that autophagy is essential for the survival of neural cells, and that impairment of autophagy is implicated in the pathogenesis of neurodegenerative disorders involving ubiquitin-containing inclusion bodies.