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181.
182.
Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C 总被引:18,自引:0,他引:18 下载免费PDF全文
Novelli G Muchir A Sangiuolo F Helbling-Leclerc A D'Apice MR Massart C Capon F Sbraccia P Federici M Lauro R Tudisco C Pallotta R Scarano G Dallapiccola B Merlini L Bonne G 《American journal of human genetics》2002,71(2):426-431
Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder, characterized by postnatal growth retardation, craniofacial anomalies, skeletal malformations, and mottled cutaneous pigmentation. The LMNA gene encoding two nuclear envelope proteins (lamins A and C [lamin A/C]) maps to chromosome 1q21 and has been associated with five distinct pathologies, including Dunnigan-type familial partial lipodystrophy, a condition that is characterized by subcutaneous fat loss and is invariably associated with insulin resistance and diabetes. Since patients with MAD frequently have partial lipodystrophy and insulin resistance, we hypothesized that the disease may be caused by mutations in the LMNA gene. We analyzed five consanguineous Italian families and demonstrated linkage of MAD to chromosome 1q21, by use of homozygosity mapping. We then sequenced the LMNA gene and identified a homozygous missense mutation (R527H) that was shared by all affected patients. Patient skin fibroblasts showed nuclei that presented abnormal lamin A/C distribution and a dysmorphic envelope, thus demonstrating the pathogenic effect of the R527H LMNA mutation. 相似文献
183.
Circulating insulin inhibits endogenous glucose production. Here we report that bidirectional changes in hypothalamic insulin signaling affect glucose production. The infusion of either insulin or a small-molecule insulin mimetic in the third cerebral ventricle suppressed glucose production independent of circulating levels of insulin and of other glucoregulatory hormones. Conversely, central antagonism of insulin signaling impaired the ability of circulating insulin to inhibit glucose production. Finally, third-cerebral-ventricle administration of inhibitors of ATP-sensitive potassium channels, but not of antagonists of the central melanocortin receptors, also blunted the effect of hyperinsulinemia on glucose production. These results reveal a new site of action of insulin on glucose production and suggest that hypothalamic insulin resistance can contribute to hyperglycemia in type 2 diabetes mellitus. 相似文献
184.
185.
Tokatlidis K Vial S Luciano P Vergnolle M Clémence S 《Biochemical Society transactions》2000,28(4):495-499
The protein import pathway that targets proteins to the mitochondrial matrix has been extensively characterized in the past 15 years. Variations of this import pathway account for the sorting of proteins to other compartments as well, but the insertion of integral inner membrane proteins lacking a presequence is mediated by distinct translocation machinery. This consists of a complex of Tim9 and Tim10, two homologous, Zn(2+)-binding proteins that chaperone the passage of the hydrophobic precursor across the aqueous intermembrane space. The precursor is then targeted to another, inner-membrane-bound, complex of at least five subunits that facilitates insertion. Biochemical and genetic experiments have identified the key components of this process; we are now starting to understand the molecular mechanism. This review highlights recent advances in this new membrane protein insertion pathway. 相似文献
186.
Two dihydrostyrylpyrones and a styrylpyrone were isolated from Polygala sabulosa, together with five known styrylpyrones. Their structures were established on the basis of spectral evidence as 4-methoxy-6-(11,12-methylenedioxy-14-methoxydihydrostyryl)-2-pyrone, 4-methoxy-6-(11,12-methylenedioxy-10,14-dimethoxydihydrostyryl)-2-pyrone, and 4-methoxy-6-(11,12-methylenedioxy-14-methoxystyryl)-2-pyrone. 相似文献
187.
Intracellular Signal Triggered by Cholera Toxin in Saccharomyces boulardii and Saccharomyces cerevisiae 下载免费PDF全文
Rogelio L. Brando Ieso M. Castro Eduardo A. Bambirra Sheila C. Amaral Luciano G. Fietto Maria Jos M. Tropia Maria Jos Neves Raquel G. Dos Santos Newton C. M. Gomes Jacques R. Nicoli 《Applied microbiology》1998,64(2):564-568
As is the case for Saccharomyces boulardii, Saccharomyces cerevisiae W303 protects Fisher rats against cholera toxin (CT). The addition of glucose or dinitrophenol to cells of S. boulardii grown on a nonfermentable carbon source activated trehalase in a manner similar to that observed for S. cerevisiae. The addition of CT to the same cells also resulted in trehalase activation. Experiments performed separately on the A and B subunits of CT showed that both are necessary for activation. Similarly, the addition of CT but not of its separate subunits led to a cyclic AMP (cAMP) signal in both S. boulardii and S. cerevisiae. These data suggest that trehalase stimulation by CT probably occurred through the cAMP-mediated protein phosphorylation cascade. The requirement of CT subunit B for both the cAMP signal and trehalase activation indicates the presence of a specific receptor on the yeasts able to bind to the toxin, a situation similar to that observed for mammalian cells. This hypothesis was reinforced by experiments with 125I-labeled CT showing specific binding of the toxin to yeast cells. The adhesion of CT to a receptor on the yeast surface through the B subunit and internalization of the A subunit (necessary for the cAMP signal and trehalase activation) could be one more mechanism explaining protection against the toxin observed for rats treated with yeasts. 相似文献
188.
Ramos-Vasconcelos GR Cardoso LA Hermes-Lima M 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2005,140(2):165-174
We investigated the regulation of free radical metabolism in Helix aspersa snails during a cycle of 20-day estivation and 24-h arousal in summer in comparison with estivation/arousal in winter-snails. In winter-snails (J. Exp. Biol. 206, 675-685, 2003), we had already observed an increase in the selenium-dependent glutathione-peroxidase (Se-GPX) activity in foot muscle and hepatopancreas and in the contents of hepatopancreas GSH-equivalents (GSH-eq=GSH+2 GSSG) during estivation compared with 24-h aroused snails. Summer-estivation prompted a 3.6-fold increase in Se-GPX activity in hepatopancreas, though not in foot muscle. Total-superoxide dismutase and catalase activities in hepatopancreas decreased (by 30-40%) during summer-estivation; however, no changes occurred in the activities of glutathione reductase, glutathione S-transferase and glucose-6-phosphate dehydrogenase in the two organs. GSH-eq levels were increased (by 54%) in foot muscle during estivation, but were unchanged in hepatopancreas. In contrast with winter-snails, oxidative stress markers (lipid peroxidation, carbonyl protein, and the GSSG/GSH-eq ratio) were unaltered during estivation/arousal in summer. These results demonstrate that seasonality modulates not only the absolute activities/levels of antioxidants (enzymes and GSH-eq) in H. aspersa, but also the regulatory process that controls the snail's antioxidant capacity during estivation/arousal. These results suggest that H. aspersa has an "internal clock" controlling the regulation of free radical metabolism in the different seasons. 相似文献
189.
Jorge Nei Silva de Freitas Luciano Augusto da Silva Carvalho Charbel Niño El-Hani Pedro Luís Bernardo da Rocha 《Journal of Ethology》2010,28(1):105-112
In a previous paper, we measured the affiliation between male individuals of Trinomys yonenagae and concluded that the intensity of affiliation was high and did not differ between animals from the same social group and
from different social groups. In this paper, we report the results obtained with the same experimental procedure with female
individuals. We also discuss sexual differences in the social interaction of this species. The experimental procedure was
based on 40-min encounters between residents, which remained alone in an arena for 24 h, and introduced intruders, in a round-robin
design. We quantified one variable indicative of activity level (number of squares crossed), one indicative of anxiety (time
in marginal squares), three indicative of affiliation (number of physical contacts, mean distance between rodents, and total
duration of physical contact), and the number of sound emissions. No aggressive behaviors were exhibited. The results indicate
that there is a high level of affiliation mediated by acoustic communication both for males and females and that no anxiety
is associated with social context, especially in females. The evolution of sociality in T. yonenagae was probably linked to an increase of tolerance especially among adult females. We also suggest that predation was a stronger
selective pressure than resource availability in the evolution of sociality in this species. 相似文献
190.
Geographic variation in diapause incidence, life-history traits, and climatic adaptation in Drosophila melanogaster 总被引:3,自引:0,他引:3
Schmidt PS Matzkin L Ippolito M Eanes WF 《Evolution; international journal of organic evolution》2005,59(8):1721-1732
In Drosophila melanogaster, exposure of females to low temperature and shortened photoperiod can induce the expression of reproductive quiescence or diapause. Diapause expression is highly variable within and among natural populations and has significant effects on life-history profiles, including patterns of longevity, fecundity, and stress resistance. We hypothesized that if diapause expression is associated with overwintering mechanisms and adaptation to temperate environments, the frequency of diapause incidence would exhibit a latitudinal cline among natural populations. Because stress resistance and reproductive traits are also clinal in this species, we also examined how patterns of fecundity and longevity varied with geography and how stress resistance and associated traits differed constitutively between diapause and nondiapause lines. Diapause incidence was shown to vary predictably with latitude, ranging from 35% to 90% among natural populations in the eastern United States Survivorship under starvation stress differed between diapause and nondiapause lines; diapause phenotypes were also distinct for total body triglyceride content and the developmental distribution of oocytes in the ovary following stress exposure. Patterns of longevity, fecundity, and ovariole number also varied with geography. The data suggest that, for North American populations, diapause expression is functionally associated with overwintering mechanisms and may be an integral life-history component in natural populations. 相似文献