Molecular interactions of fission yeast Skp1 and its role in the DNA damage checkpoint

Skp1 is a central component of the E3 ubiquitin ligase SCF (Skp1-Cullin-1-F-box). It forms an adapter bridge between Cullin-1 and the substrate-determining component, the F-box protein. In order to establish the role of Skp1, a temperature sensitive (ts) screen was carried out using mutagenic PCR (polymerase chain reaction) and 9 independent ts mutants were isolated. Mapping the mutated residues on the 3-D structure of human Skp1 suggested that the mutants would be compromised in binding to F-box proteins but not Cullin-1 (Pcu1). In order to assess the binding properties of ts Skp1, 12 F-box proteins and Pcu1 were epitope-tagged, and co-immunoprecipitation performed. This systematic analysis showed that ts Skp1 retains binding to Pcu1. However, binding to three specific F-box proteins, essential Pof1, Pof3 involved in maintaining genome integrity, and nonessential Pof10, was reduced. skp1ts cells exhibit a G2 cell cycle delay, which is attributable to activation of the DNA damage checkpoint. Intriguingly, contrary to pof3 mutants, in which this checkpoint is required for survival, checkpoint abrogation in skp1(ts) suppresses a G2 delay and furthermore almost rescues the ts phenotype. The activation mechanism of the DNA damage checkpoint therefore differs between pof3Delta and skp1(ts), implicating a novel role for Skp1 in the checkpoint-signalling cascade.     

Antigenic interrelationships among mite allergens (Blomia andDermatophagoides spp)

Conclusions Asthma can occur as a result of allergy to both house dust mites and to storage mites. Many people worldwide are exposed to more than one mite species in the domestic environment. The most common domestic mites areD. pteronyssinus, D. farinae, E. maynei, andB. tropicalis; other storage mites are found in homes much less frequently, even in tropical climates. Because of the ready availability of allergen extracts for skin testing and immunotherapy, patients with respiratory symptoms are generally evaluated for sensitization toD. pteronyssinus andD. farinae only. The evidence reviewed here suggests, however, that, although there are crossreactive allergens between many mite species, most species have specific allergens that can be an important cause of IgE responses. Therefore, the role ofB. tropicalis andE. maynei in the etiology of asthma merits further investigation. Identification of species-specific and crossreactive allergens and production of recombinant allergens would be useful tools in allergy practice. By skin-testing patients, physicians would then be able to evaluate whether patients recognize crossreactive allergens or species-specific allergens and whether or not there is a need for immunotherapy to more than one mite species.     

Giant cell granuloma of the orbit with intracranial extension

An 8-year-old boy presented with acute proptosis of the right eye. Examination revealed 8 mm of exophthalmos, limitation of upward gaze, optic disc swelling, and normal visual acuity, but an inferonasal quadrantic visual field defect. Orbital ultrasound and computed tomographic scanning demonstrated a superotemporal tumor of the right orbit with intracranial extension. At operation, this proved to be a "reparative" giant cell granuloma. After partial resection, the remaining mass resolved spontaneously without further specific treatment. There had been no recurrence at the 1-year follow-up examination.     

An odor discrimination model with application to kin recognition in social insects

The problem of discriminating between a number of similar, nonspecific odors is discussed with special reference to the phenomenon of kin and nestmate discrimination in social insects. Guided by the basic physiological and anatomical features of the olfactory sensory receptors and neural pathways in insects, a model is presented for the process of odor discrimination. The model hypothesizes neural processing capabilities that include the logarithmic transformations of electrical potentials to generate a scalar quantity representing the "similarity" of two multivalued signals. The model thereby quantifies the notion of phenotype matching that appears in the kin recognition literature, and makes the concept of a recognition template more precise. The hypotheses underlying the model suggest a number of neurophysiological studies that should be undertaken, while the model itself provides a basis for integrating several areas of research pertaining to kin recognition in particular species of animals.     

Evaluation of the Sydney "Quit. For Life" anti-smoking campaign. Part 1. Achievement of intermediate goals

The "Quit. For Life" campaign was a media-based programme that was aimed at reducing the prevalence of smoking in Sydney. The programme committee set four intermediate goals which it felt had to be met for such a change in prevalence to occur. From households selected at random in Sydney and Melbourne, 5713 people were interviewed to assess whether the campaign attained these goals. The television commercials that were designed for the campaign, their frequency and the timing of their screening produced a higher recall of the commercial's message and the use of campaign back-up services than were specified originally in the goals. During the campaign there was a progressive increase in the number of smokers in Sydney who reported that they were likely to quit; this was significantly different from Melbourne data by the end of the campaign and thus fulfilled another campaign goal. However, shortly after the campaign ended, the proportion of smokers who intended to quit smoking was the same in the two cities. A cohort study of 949 people from the baseline study showed that, during the 12-month period of follow-up, 66% of Sydney smokers tried to stop or to reduce their smoking. In the control city, Melbourne, 60% of smokers reported making such attempts. Of the original smokers, 23% in Sydney and 9% in Melbourne quit during the follow-up period--a statistically significant difference. As well, 10% of the original ex-smokers in Sydney and 11% in Melbourne relapsed, while 4% of nonsmokers in both cities began smoking by the end of the second survey.     

Hypolipidemic Agents of Phthalimide Derivatives 6. Effects of Aromatic vs. Non-Aromatic Imides

A number of substituted phthalimide, 1, 8-naphthalimide, succinimide and glutarimide derivatives demonstrated significant hypolipidemic activity at 20 mg/kg/ day, I.P. after 16 days dosing. The N-(n-pentyl) succinimide proved to be the most potent analogue of the new compounds, lowering serum triglyceride levels 51 % and serum cholesterol 47 % after 16 days dosing in mice. For the N-substituted derivatives, i. e., n-butyl, butanone, and propionic acid, of these four cyclic imides, there appeared to be no obvious trend in ability to reduce serum lipid levels. In general, the 1,8-naphthalimide and glutarimide derivatives appeared to be less active than phthalimide and succinimide. However, the -phenylsuccinimide afforded less activity than the -phenylglutarimide. Most of the derivatives at 20mg/kg/day demonstrated improved activity over clofibrate at 150mg/kg/day.     

教授对作假行为失查而受处罚

上周 ,英国伦敦帝国大学口腔医学院临床生化系教授ＴｉｍｏｔｈｙＰｅｔｅｒｓ被判定犯有严重的失职罪。他之所以遭到英国国家医学委员会的严厉谴责是因为他指导的一名低年资医师ＡｎｊａｎＢａｎｅｒｊｅｅ发表了一篇捏造的研究报告 ,而他却失于督查和阻止。ＡｎｊａｎＢａｎｅｒｊｅｅ医生现年 4 1岁 ,曾于1988年至 1991年期间在帝国大学医院作低年资医师 ,当时Ｐｅｔｅｒｓ教授是他的科研项目负责人。去年 ,他在《英国医学杂志》(ＢＭＪ 2 0 0 0 ;32 1:14 2 9)上发表了一篇伪造的研究报告 ,经英国国家医学委员会核实 ,认为存在欺骗行为 ,…