Identification of receptor contact site involved in receptor-G protein coupling

The mammalian G proteins transduce information from extracellular signals, including neurotransmitters, hormones and sensory stimuli, into regulation of effector enzymes or ion channels within cells. Triggered by appropriate extracellular signals, receptor proteins specifically activate members of the G protein family by catalysing replacement of GDP by GTP at the guanine nucleotide binding site. Like the receptor proteins, the heterotrimeric G proteins exhibit impressive structural similarities, suggesting that all receptor-G protein interactions use homologous structural elements and a single molecular mechanism. Topologically equivalent portions of each G protein may therefore interact with the appropriate receptor. We recently predicted the secondary structure of a composite G protein alpha-chain and proposed that a predicted amphipathic alpha-helix at the extreme carboxy-terminus of the polypeptide directly contacts receptors. This proposal has now been confirmed by sequencing complementary DNAs of the gene that encodes the alpha-chain (alpha s) of the stimulatory regulator (Gs) of adenylyl cyclase in wild-type cells and in a mutant mouse S49 lymphoma cell line, unc, in which Gs cannot be activated by hormone receptors. The sequences reveal a point mutation in the unc gene that substitutes a proline residue for an arginine near the carboxy-terminus of the alpha s-polypeptide. Expression of recombinant alpha s-unc in genetically alpha s-deficient S49 cells reproduces the unc phenotype.     

GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours

A subset of growth hormone-secreting human pituitary tumours carries somatic mutations that inhibit GTPase activity of a G protein alpha chain, alpha(s). The resulting activation of adenylyl cyclase bypasses the cells' normal requirement for trophic hormone. Amino acids substituted in the putative gsp oncogene identify a domain of G protein alpha-chains required for intrinsic ability to hydrolyse GTP. This domain may serve as a built-in counter-part of the separate GTPase-activating proteins required for GTP hydrolysis by small GTP-binding proteins such as p21ras.     

The effect of phenazine methosulfate on the activity of dehydrogenases as studied by starch gel electrophoresis

Résumé L'effet de la phenazine methosulfate (PMS) sur l'activité de plusieurs enzymes oxydatifs a été étudié. En tant que transporteur d'électron, la PMS a un rôle important sur la coloration des isoenzymes séparés par électrophorèse en gel d'amidon. En ce qui concerne la déshydrogénase lactique, un excès de PMS provoque une coloration diffuse, alors que dans le cas de la déshydrogénase succinique on observe l'apparition de «bandes négatives» qui n'ont pas encore été décrites.

---

---

This work was supported by grants Nos. HEO4553, HeO45691, and FRO0165 of the National Institute of Health. The technical assistance of Mr. R.Hernandez is gratefully acknowledged.     

Positive and negative effects of widespread badger culling on tuberculosis in cattle

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. For three decades, European badgers (Meles meles) have been culled by the British government in a series of attempts to limit the spread of Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Despite these efforts, the incidence of TB in cattle has risen consistently, re-emerging as a primary concern for Britain's cattle industry. Recently, badger culling has attracted controversy because experimental studies have reached contrasting conclusions (albeit using different protocols), with culled areas showing either markedly reduced or increased incidence of TB in cattle. This has confused attempts to develop a science-based management policy. Here we use data from a large-scale, randomized field experiment to help resolve these apparent differences. We show that, as carried out in this experiment, culling reduces cattle TB incidence in the areas that are culled, but increases incidence in adjoining areas. These findings are biologically consistent with previous studies but will present challenges for policy development.     

Cattle grazing behavior regulates tick populations

Summary Analysis of field population data showed that host-seeking larvae of the tickBoophilus microplus were less successful in attaching to their hosts when larval densities were high. Experimental results showed that cattle hosts detected and avoided high densities of larvae in pasture. The finding reveals a previously unknown population-regulating mechanism for ticks, which are important pests of livestock.Acknowledgment. The authors wish to thank G. Maywald, D. Stegeman, R. Tozer, A. Voll, G. Milne and J. Osborne who helped with the observations. The Australian Meat Research Committee (AMRC) and the Australian Centre for International Agricultural Research (ACIAR) provided some financial support for the project and A. Edwards assisted greatly with the photography.     

工作流引擎在继电保护管理系统中的应用

继电保护管理系统中关键业务的应用开发离不开工作流技术的支持。针对于此,通过对系统的实际开发需求的分析,在传统的关系数据库的基础上,提出了一个适用于关键业务开发的基于关系数据库的轻量级工作流引擎的框架结构。深入讨论了采用关系数据库来设计工作流引擎的原因,并详细地给出了相关的设计原理以及具体的表示和实现方法。其原型已经应用到实际的继电保护管理系统中。实践证明,利用此工作流引擎可以显著地缩短业务的开发周期。