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11.
Genomewide significant linkage to recurrent, early-onset major depressive disorder on chromosome 15q 总被引:7,自引:0,他引:7
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Holmans P Zubenko GS Crowe RR DePaulo JR Scheftner WA Weissman MM Zubenko WN Boutelle S Murphy-Eberenz K MacKinnon D McInnis MG Marta DH Adams P Knowles JA Gladis M Thomas J Chellis J Miller E Levinson DF 《American journal of human genetics》2004,74(6):1154-1167
A genome scan was performed on the first phase sample of the Genetics of Recurrent Early-Onset Depression (GenRED) project. The sample consisted of 297 informative families containing 415 independent affected sibling pairs (ASPs), or, counting all possible pairs, 685 informative affected relative pairs (555 ASPs and 130 other pair types). Affected cases had recurrent major depressive disorder (MDD) with onset before age 31 years for probands or age 41 years for other affected relatives; the mean age at onset was 18.5 years, and the mean number of depressive episodes was 7.3. The Center for Inherited Disease Research genotyped 389 microsatellite markers (mean spacing of 9.3 cM). The primary linkage analysis considered allele sharing in all possible affected relative pairs with the use of the Z(lr) statistic computed by the ALLEGRO program. A secondary logistic regression analysis considered the effect of the sex of the pair as a covariate. Genomewide significant linkage was observed on chromosome 15q25.3-26.2 (Zlr=4.14, equivalent LOD = 3.73, empirical genomewide P=.023). The linkage was not sex specific. No other suggestive or significant results were observed in the primary analysis. The secondary analysis produced three regions of suggestive linkage, but these results should be interpreted cautiously because they depended primarily on the small subsample of 42 male-male pairs. Chromosome 15q25.3-26.2 deserves further study as a candidate region for susceptibility to MDD. 相似文献
12.
Protein Degradation, Meiosis and Sporulation in Proteinase-Deficient Mutants of SACCHAROMYCES CEREVISIAE 总被引:17,自引:3,他引:14
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During the process of sporulation, a/α diploids degrade about 50% of their vegetative proteins. This degradation is not sporulation specific, for asporogenous diploids of a/a mating type degrade their vegetative proteins in a fashion similar to that of their a/α counterparts. Diploids lacking carboxypeptidase Y activity, prc1/prc1, show about 80% of wild-type levels of protein degradation, but are unimpaired in the production of normal asci. Diploids lacking proteinase B activity, prb1/prb1, show about 50% of wild-type levels of protein degradation. The effect on degradation of the proteinase B deficiency is epistatic to the degradation deficit attributable to the carboxypeptidase Y deficiency. The prb1 homozygotes undergo meiosis and produce spores, but the asci and, possibly, the spores are abnormal. Diploids homozygous for the pleiotropic pep4–3 mutation show only 30% of the wild-type levels of degradation when exposed to a sporulation regimen, and do not undergo meiosis or sporulation. Neither proteinase B nor carboxypeptidase Y is necessary for germination of spores.——Approximately half of the colonies arising from a/a or α/α diploids exposed to the sporulation regiment that express an initially heterozygous drug-resistance marker (can1) appear to arise from mating-type switches followed by meiosis and sporulation. 相似文献
13.
PEP4 Gene Function Is Required for Expression of Several Vacuolar Hydrolases in SACCHAROMYCES CEREVISIAE 总被引:30,自引:5,他引:25
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The pep4-3 mutation results in a 90–95% reduction in the levels of five vacuolar hydrolases in yeast, including proteinases A and B, carboxypeptidase Y, RNase(s) and the repressible alkaline phosphatase. The mutation is without effect on two secreted glycoproteins, on an enzyme of the vacuolar membrane, and on a proteinase located outside of the vacuole. Mutations at the PEP4 locus exhibit a dosage effect on the levels of some, but not all, of the enzymes whose expression requires the function of the gene. 相似文献
14.
Fluorescence spectroscopy was used to examine the biophysical characteristics of human platelet membranes as a function of subject age. The structural order of membrane lipid domains was determined with the use of 1,6-diphenyl-1,3,5-hexatriene (DPH), a fluorescent probe that preferentially localizes in the hydrocarbon core of synthetic and biological membranes. Over the age range of subjects examined (17 to 86 years) the structural order of platelet membranes, as reflected by the steady-state fluorescence polarization of DPH, increased substantially. The magnitude of the observed increase in membrane structural order is sufficient to affect membrane-related cell functions including platelet aggregation. A major contributor to the increase in structural order of platelet membranes may have been an increase in the concentration of cholesterol in serum and tissue with age. The changes observed here in platelet membranes may be a general phenomenon of aging, as changes of similar type and magnitude have been observed in lymphocyte membranes and brain with age in other studies. 相似文献
15.
An abnormality of membranes, possibly representing an increase in internal membranes, has been reported in fluorescence spectroscopic and electron microscopic studies of platelets of patients with Alzheimer's-type dementia (AD). To further define this abnormality, the cholesterol and phospholipid content of platelet and erythrocyte membranes was determined and compared for patients with AD and matched control subjects. No significant differences in either cholesterol or phospholipid, per se, were observed in comparing platelets from subjects in the two study groups. However, the ratio of cholesterol to phospholipid was significantly lower (p less than 0.01) in the platelets of patients with AD (9.37 +/- 1.11) than in the platelets of control subjects (10.20 +/- 1.04). Furthermore, the cholesterol to phospholipid ratio correlated significantly (rs = 0.53, p less than 0.01) with a separately determined measure of platelet membrane characteristics, the steady-state anisotropy of DPH (diphenylhexatriene). No differences were observed between the study groups for any of the same parameters measured in erythrocytes, which lack internal membranes. The findings suggest that there is no general abnormality of membrane lipids in Alzheimer's-type dementia. Rather, because normal internal membranes are reported to be low in their cholesterol to phospholipid ratio and in anisotropy of DPH, the results of these studies, together with the results of studies employing electron microscopy, suggest that platelets of patients with AD have an increase in internal membranes. Such membranes, while present in excess, may be normal in composition. 相似文献
16.
Based on recent clinical and preclinical research, it is theorized that antimanic and antidepressant effects of clinically available drugs can be produced through their actions on alpha-1 adrenoreceptor-mediated neurotransmission in the central nervous system. The theory suggests that final effects on alpha-1 mediated neurotransmission may be produced not only by drugs which have direct effects on the alpha-1 receptor or its second messenger, but also by drugs having effects on neurotransmitter systems such as acetylcholine, GABA, and serotonin, among others, which modulate the activity of central norepinephrine neurons or, via feedback mechanisms, by drugs having effects on adrenergic receptors other than the alpha-1 receptor itself. 相似文献
17.
David Danko Daniela Bezdan Evan E. Afshin Sofia Ahsanuddin Chandrima Bhattacharya Daniel J. Butler Kern Rei Chng Daisy Donnellan Jochen Hecht Katelyn Jackson Katerina Kuchin Mikhail Karasikov Abigail Lyons Lauren Mak Dmitry Meleshko Harun Mustafa Beth Mutai Russell Y. Neches Stas Zubenko 《Cell》2021,184(13):3376-3393.e17
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18.
A A Fisher Iu M Zubenko R I Poliak 《Biulleten' eksperimental'no? biologii i meditsiny》1977,83(3):268-271
Antrectomy was shown to cause a sharp and stable suppression of the secretory reaction of the fundal glands of the stomach in response to insulin hypoglycemia. Acid and pepsin secretion was reduced two-fold (on the average) as compared to that after histamine stimulation. A tendency to restoration of the secretory parameters was seen in 3 to 5 months; the next 7 months they persisted on a constant level. 相似文献
19.
A.?A.?Zubenko L.?N.?DivaevaEmail author A.?S.?Morkovnik V.?G.?Kartsev Y.?D.?Drobin N.?M.?Serbinovskaya L.?N.?Fetisov A.?N.?Bodryakov M.?A.?Bodryakova L.?A.?Lyashenko 《Russian Journal of Bioorganic Chemistry》2017,43(3):311-316
9-Bromocotarnine in the stable perchlorate form has been obtained by the interaction of cotarnine with bromine. The reaction of 9-bromocotarnine with α-haloketones is accompanied by the extension of the six-membered hetero-ring to seven-membered ring and led to previously unknown 4-acyl-9-bromo-3-methyl-6-methoxy-7,8-methylendioxy-1,2-dihydro-3-benzazepines. Some of these compounds have been shown to have only moderate antibacterial (against Staphylococcus aureus, Escherichia coli) and fungistatic (Penicillium italicum) activities, but none of them has been shown to have a pronounced protistocidal activity against Colpoda steinii. 相似文献
20.