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991.
The membrane insertion and translocation of diphtheria toxin, which is induced in vivo by low pH, is thought to be directed by the hydrophobic alpha-helices of its transmembrane (T) domain. In this study the structure of membrane-associated T domain was examined. Site-directed mutants of the T domain with single Trp residues were prepared at the two naturally occurring positions, 206 (near the N-terminal end of helix TH1) and 281 (within helix TH5), as well as at three residues in helix TH9, in which the substitutions F355W (near the N-terminal end of TH9), I364W (close to the center of TH9), and Y375W (near the C-terminal end of TH9) were made. All these mutants were found to undergo the low-pH-induced conformational change observed with wild-type T domain and insert into model membranes at low pH. The location of Trp residues relative to the lipid bilayer was characterized in model membrane vesicles by fluorescence emission and by quenching with nitroxide-labeled phospholipids. In TH9, residue 375 was shallowly inserted, residue 364 deeply inserted, and residue 355 located at an intermediate depth. Residues 206 and 281 exhibited moderately deep insertion. It was also found, in agreement with our previous study using bimane-labeled protein (Wang et al. (1997) J. Biol. Chem. 272, 25091-25098), that TH9 switches from a relatively shallowly inserted state to a more deeply inserted state when the concentration of the T domain in the membrane is increased or the thickness of the membrane bilayer is decreased. In particular, the depth of residue 355 was found to increase under the conditions giving deeper insertion. In contrast, residue 375 remained shallowly located in both states, as predicted from its location on the polar C-terminus of TH9. It is concluded that TH1 and TH5 insert into the lipid bilayer in both T domain conformations. In addition, Trp depths suggest that even in the shallowly inserted state there is a significant degree of insertion of TH9. These results suggest regions of the T domain in addition to the hydrophobic TH8/TH9 hairpin insert into membranes. Models for the structure of the membrane-inserted T domain are discussed. 相似文献
992.
The effects of pre-hatch light exposure on synaptic development in the intermediate and medial part of the hyperstriatum ventrale (IMHV) of the chick brain were investigated. Quantitative electron microscopical techniques were used to determine the size and numerical density of synapses and it was seen that in light hatched chicks there was a significant increase in the density of synapses in the left IMHV but that the size of synapses in these birds was decreased. These results provide a link between synaptic development and plasticity. 相似文献
993.
A Markov model was used to assess the cost-benefit ratios of six strategies of screening older drivers for mental status, beginning at age 65. Probabilities of motor vehicle collisions (MVCs), injuries, and fatalities were obtained from national data. Dementia prevalence, test characteristics, and costs were obtained from the literature. Costs included lost wages, car ownership, alternative transportation, and injuries. Using a relative risk of MVC for those with dementia of 5 and a 5% annual discounting rate, the average cost per driver ranged from $51,600 (no testing) to $58,400 (testing every five years). The benefit was < one day of life gained, and the benefits of screening cost approximately 2.8 million dollars per life-year gained. Increasing the relative risk from 5 to 20 substantially improved the cost-benefit of mental status screening. However, mental status screening of older drivers would also be cost-beneficial if physician referral costs were lowered to $60 per evaluation. The authors conclude that a dementia screening program for older drivers would be cost-beneficial if physician evaluations were limited or their cost lowered to < or = $60. 相似文献
994.
995.
Current models of telomere replication predict that due to the properties of the polymerases implicated in semiconservative replication of linear DNA, the two daughter molecules have one end that is blunt and one end with a short 3' overhang. Telomerase is thought to extend the short 3' overhang to produce long single-stranded overhangs. Recently, such overhangs, or TG1-3 tails, were shown to occur on both telomeres of replicated linear plasmids in yeast. Moreover, indirect evidence suggested that the TG1-3 tails also occurred in a yeast strain lacking telomerase. We report herein a novel in-gel hybridization technique to probe telomeres for single-stranded DNA. Using this method, it is shown directly that in yeast strains lacking the TLC1 gene encoding the yeast telomerase RNA, TG1-3 single-stranded DNA was generated on chromosomal and plasmid telomeres. The single-stranded DNA only appeared in S phase and was sensitive to digestion with a single-strand-specific exonuclease. These data demonstrate that during replication of telomeres, TG1-3 tails can be generated in a way that is independent of telomerase-mediated strand elongation. In wild-type strains, these TG1-3 tails could subsequently serve as substrates for telomerase and telomere binding proteins on all telomeres. 相似文献
996.
RJ Fielder 《Canadian Metallurgical Quarterly》1996,113(1-3):221-225
The UK Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC) and the related Committee on Mutagenicity provided advice on 1,3-butadiene in 1992. This followed detailed consideration of the available mutagenicity, animal carcinogenicity and epidemiology data plus information on toxicokinetics. They concluded that 1,3-butadiene was an in vivo mutagen, a potent genotoxic animal carcinogen and should be regarded as a probable human carcinogen. The Department of Health is not aware of more recent data warranting reconsideration of these conclusions. General advice on setting air quality standards for carcinogenic air pollutants was given by the COC. Although the prudent assumption of the absence of any safe level for genotoxic carcinogens was preferred, a pragmatic approach based essentially on assessment of the exposure at which no increased risk would be detected, plus a safety factor, was considered reasonable for compounds like butadiene where exposure cannot be totally avoided. This approach, plus recognition that it is unadvisable to allow ambient levels of genotoxic carcinogens to rise, is used in the UK. The procedure by which the Department of Environment's Expert Panel on Air Quality Standards recommended a value of 1 ppb for butadiene based on these principles is described. 相似文献
997.
JL Klein EL Corbett PM Slade RF Miller RJ Coker 《Canadian Metallurgical Quarterly》1998,37(3):252-259
In a sample of 627 healthy German children and adolescents between the age of 1 and 18 years the intake of macronutrients (protein, fat, carbohydrates) and their specific subgroups (animal protein, saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), cholesterol, added sugars, dietary fiber) were assessed from 3d weighed diet records. The medians of the nutrient intake (% of energy) were 13% protein (2/3 animal), 38% fat, 49% carbohydrates, 17% SFA, 16% MUFA, 5% PUFA, 12% added sugars and (per MJ) 34 mg cholesterol, 1.9 g dietary fiber. The macronutrient patterns were almost uniform across the age and sex groups with the exception of lower fat, PUFA, and sugar intakes in the 1 year olds. The findings were almost in accordance with former and current dietary surveys in Germany and neighboring countries. Several findings, particularly the high SFA and low fiber intake, differed considerably from the diet for the prevention of the chronic diseases related to nutrition in western societies which is recommended for this age range. Based on the findings of this study, a preventive dietary concept for German children and adolescents was proposed. 相似文献
998.
999.
RJ Diamond 《Canadian Metallurgical Quarterly》1995,(66):3-18
Coercion in community-based mental health treatment refers to much more than just court-ordered treatment. Mature systems can address these issues and adopt clinical approaches that decreased the need for coercion. 相似文献
1000.
RJ Warburton M Matsui SL Rowland-Jones MC Gammon GE Katzenstein T Wei M Edidin HJ Zweerink AJ McMichael JA Frelinger 《Canadian Metallurgical Quarterly》1994,39(4):261-271
This report documents the introduction of standard-setting in the haemato-oncological reverse-isolation unit of the Kanton hospital, Basle. The topic is the prevention or reduction of nausea, choking and vomiting, and the treatment of patients who are receiving prolonged chemotherapy. The objective was quality assurance in nursing care. The definition of the desired outcome was the well-being and safety of patients. In addition the wish of the staff to increase their security in dealing with antiemetics was taken into consideration. The authors describe the basic problems they encountered in their strategies and actions for standard setting. By extensive use of measurement and evaluation it was possible, in cooperation with medical leadership, to develop instructional leaflets and checklists. Approximation to the intended outcome was achieved. The well being of patients and satisfaction of the safety-needs of staff and patients reached a high level. The report shows that the introduction of nursing standards requires great effort and a high level of commitment of the entire team. It also shows that the effort is worthwhile for patients and staff. 相似文献