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121.
Three point mutations in the CFTR gene in French cystic fibrosis patients: Identification by denaturing gradient gel electrophoresis 总被引:18,自引:4,他引:14
Michel Vidaud Pascale Fanen Josiane Martin Nada Ghanem Sylvaine Nicolas Michel Goossens 《Human genetics》1990,85(4):446-449
Summary The cystic fibrosis (CF) gene was recently identified as a gene spanning 250 kilobases (kbp) and coding for a 1480 amino acid
protein, cystic fibrosis transmembrane conductance regulator (CFTR). Approximately 70% of CF mutations involve a three-base-pair
deletion in CFTR exon 10, resulting in the loss of a phenylalanine at position 508 in the gene product (ΔF508). In order to
screen for other molecular defects, we have used a strategy based on denaturing gradient gel electrophoresis (DGGE) of polymerase
chain reaction (PCR)-amplified gene segments. This method, which permits rapid detection of any sequence change in a given
DNA stretch, was used successfully to analyse 61 non-ΔF508 CF chromosomes from French CF patients. A study of CFTR exons 10,
11, 14a, 15 and 20 detected three mutations located in exons 14a, 15 and 20, along with several nucleotide sequence polymorphisms.
These nucleotide changes were identified by direct sequencing of PCR fragments displaying altered electrophoretic behaviour,
together with some of the polymorphisms and mutations previously characterized by others. The strategy presented here constitutes
a valuable tool for the development of carrier testing for individuals or couples with a family history of cystic fibrosis,
and will contribute to deciphering the functionally important regions of the CFTR gene. 相似文献
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123.
Tadeusz Wroblewski Sylvaine Coulibaly Jan Sadowski Carlos F. Quiros 《Molecular phylogenetics and evolution》2000,16(3):440
Our objective was to analyze the evolutionary paths of cultivated diploid Brassica species and a few related wild species (tribe Brassiceae) in relation to Arabidopsis thaliana (tribe Arabidae), using the Rps2 sequence. Rps2 confers resistance to Pseudomonas syringae in A. thaliana. We found that similar to Arabidopsis, the Rps2 homolog in Brassica species is present in a single copy. Primers based in the Rps2 sequence amplified Rps2 homologs from the other species. Maximum-parsimony analysis based on number of nucleotide substitutions yielded a single tree, grouping the species as expected from other evolutionary inferences. Age of divergence between the two tribes was within the range of previous estimates. Indels in the different sequences were also useful for distinguishing some of the species. The Rps2 gene is a useful phylogenetic tool for more comprehensive studies of the species of Brasicaceae. 相似文献
124.
Semiempirical and density functional calculations have been carried out to discuss the origin of the closed [5,6]-aza-bridged adduct obtained as a minor product in the reaction of singlet nitrenes with C60. The results indicated that the most likely source is the direct addition of singlet nitrenes to a [5,6]-bond of C60, in contradiction to the common belief that the [5,6]-bonds are not attacked in cycloaddition reactions to C60.Electronic Supplementary Material available. 相似文献
125.
Dussillol-Godar F Brissard-Zahraoui J Limbourg-Bouchon B Boucher D Fouix S Lamour-Isnard C Plessis A Busson D 《Developmental biology》2006,291(1):53-66
The Suppressor of fused (Su(fu)) protein is known to be a negative regulator of Hedgehog (Hh) signal transduction in Drosophila imaginal discs and embryonic development. It is antagonized by the kinase Fused (Fu) since Su(fu) null mutations fully suppress the lack of Fu kinase activity. In this study, we overexpressed the Su(fu) gene in imaginal discs and observed opposing effects depending on the position of the cells, namely a repression of Hh target genes in cells receiving Hh and their ectopic expression in cells not receiving Hh. These effects were all enhanced in a fu mutant context and were suppressed by cubitus interruptus (Ci) overexpression. We also show that the Su(fu) protein is poly-phosphorylated during embryonic development and these phosphorylation events are altered in fu mutants. This study thus reveals an unexpected role for Su(fu) as an activator of Hh target gene expression in absence of Hh signal. Both negative and positive roles of Su(fu) are antagonized by Fused. Based on these results, we propose a model in which Su(fu) protein levels and isoforms are crucial for the modulation of the different Ci states that control Hh target gene expression. 相似文献
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127.
Marta Palomo Manel Vera Susana Martin Sergi Torramad‐Moix Julia Martinez‐Sanchez Ana Belen Moreno Enric Carreras Gins Escolar Aleix Cases Maribel Díaz‐Ricart 《Journal of cellular and molecular medicine》2020,24(2):1713-1723
Endothelial dysfunction is an earlier contributor to the development of atherosclerosis in chronic kidney disease (CKD), in which the role of epigenetic triggers cannot be ruled out. Endothelial protective strategies, such as defibrotide (DF), may be useful in this scenario. We evaluated changes induced by CKD on endothelial cell proteome and explored the effect of DF and the mechanisms involved. Human umbilical cord vein endothelial cells were exposed to sera from healthy donors (n = 20) and patients with end‐stage renal disease on haemodialysis (n = 20). Differential protein expression was investigated by using a proteomic approach, Western blot and immunofluorescence. HDAC1 and HDAC2 overexpression was detected. Increased HDAC1 expression occurred at both cytoplasm and nucleus. These effects were dose‐dependently inhibited by DF. Both the HDACs inhibitor trichostatin A and DF prevented the up‐regulation of the endothelial dysfunction markers induced by the uraemic milieu: intercellular adhesion molecule‐1, surface Toll‐like receptor‐4, von Willebrand Factor and reactive oxygen species. Moreover, DF down‐regulated HDACs expression through the PI3/AKT signalling pathway. HDACs appear as key modulators of the CKD‐induced endothelial dysfunction as specific blockade by trichostatin A or by DF prevents endothelial dysfunction responses to the CKD insult. Moreover, DF exerts its endothelial protective effect by inhibiting HDAC up‐regulation likely through PI3K/AKT. 相似文献
128.
Alvin Ibarra Naisheng BaiKan He Antoine BilyJulien Cases Marc RollerShengmin Sang 《Phytomedicine》2011,18(6):479-485
Purpose
The aim of this study was to determine whether a Fraxinus excelsior L. seed extract, FraxiPure™ (0.5% in the diet), limits weight gain and hyperglycemia in mice. In a previous report, we identified several secoiridoids in FraxiPure™, some of which activated peroxisome proliferator-activated receptor alpha (PPARα) in vitro and inhibited the differentiation of 3T3-L1 preadipocyte cells. In a separate study, FraxiPure™ reduced glycemia in healthy volunteers, following an oral glucose tolerance test. These findings suggest that FraxiPure™ has antiobesity and antihyperglycemia effects.Materials and methods
FraxiPure™ was tested in mice that were fed a high-fat diet over 16 weeks and compared with low-fat and high-fat diet controls. Weight gain, omental and retroperitoneal fat, fasting blood glucose, and fasting blood insulin were measured.Results
FraxiPure™ reduced gains in body weight by 32.30% (p < 0.05), omental fat by 17.92%, and retroperitoneal fat by 17.78%. FraxiPure™ also lowered fasting blood glucose levels by 76.52% (p < 0.001) and plasma insulin levels by 53.43% (p < 0.05) after 16 weeks. Moreover, FraxiPure™ lowered liver weight gains by 63.62% (p < 0.05) and the incidence of fatty livers by 66.67%.Conclusions
Our novel results demonstrate the antiobesity effects of chronic administration of an F. excelsior seed extract and confirm its ability to regulate glycemia and insulinemia. In addition, this extract, which is rich in secoiridoid glucosides, protects against obesity-related liver steatosis. 相似文献129.
Juan Salazar-Ortiz Sylvaine Camous Christine Briant Lionel Lardic Didier Chesneau Daniel Guillaume 《Reproductive biology and endocrinology : RB&E》2011,9(1):1-16
Background
Mares have an annual reproductive rhythm, with a phase of inactivity in midwinter. The aim of this study was to determine the impact of food restriction on physiological and metabolic hallmarks of this rhythm.Methods
Over three successive years, 3 groups of 10 mares were kept under natural photoperiod. A 'well-fed' group was fed to maintain the mares in good body condition; a 'restricted' group received a diet calculated to keep the mares thin and a 'variable' group was fed during some periods like the 'restricted' group and during some other periods like the 'well-fed' group, with the aim of mimicking the natural seasonal variation of pasture availability, but a few months in advance of this natural rhythm.Results
Winter ovarian inactivity always occurred and was long in the restricted group. In contrast, in the 'well-fed' group, 40% of mares showed this inactivity, which was shorter than in the other groups. Re-feeding the 'variable' group in autumn and winter did not advance the first ovulation in spring, compared with the 'restricted' group. Measurements of glucose and insulin concentrations in mares from the 'restricted' group during two 24 h periods of blood sampling, revealed no post-prandial peaks. For GH (Growth hormone), IGF-1 and leptin levels, large differences were found between the 'well-fed' group and the other groups. The glucose, insulin, GH and leptin levels but not melatonin level are highly correlated with the duration of ovulatory activity.Conclusions
The annual rhythm driven by melatonin secretion is only responsible for the timing of the breeding season. The occurrence and length of winter ovarian inactivity is defined by metabolic hormones. 相似文献130.
Olivier Cases Aitana Perea-Gomez Diego P. Aguiar Anders Nykjaer Sabine Amsellem Jacqueline Chandellier Muriel Umbhauer Silvia Cereghini Mette Madsen Jér?me Collignon Pierre Verroust Jean-Fran?ois Riou Sophie E. Creuzet Renata Kozyraki 《The Journal of biological chemistry》2013,288(23):16655-16670
Cubilin (Cubn) is a multiligand endocytic receptor critical for the intestinal absorption of vitamin B12 and renal protein reabsorption. During mouse development, Cubn is expressed in both embryonic and extra-embryonic tissues, and Cubn gene inactivation results in early embryo lethality most likely due to the impairment of the function of extra-embryonic Cubn. Here, we focus on the developmental role of Cubn expressed in the embryonic head. We report that Cubn is a novel, interspecies-conserved Fgf receptor. Epiblast-specific inactivation of Cubn in the mouse embryo as well as Cubn silencing in the anterior head of frog or the cephalic neural crest of chick embryos show that Cubn is required during early somite stages to convey survival signals in the developing vertebrate head. Surface plasmon resonance analysis reveals that fibroblast growth factor 8 (Fgf8), a key mediator of cell survival, migration, proliferation, and patterning in the developing head, is a high affinity ligand for Cubn. Cell uptake studies show that binding to Cubn is necessary for the phosphorylation of the Fgf signaling mediators MAPK and Smad1. Although Cubn may not form stable ternary complexes with Fgf receptors (FgfRs), it acts together with and/or is necessary for optimal FgfR activity. We propose that plasma membrane binding of Fgf8, and most likely of the Fgf8 family members Fgf17 and Fgf18, to Cubn improves Fgf ligand endocytosis and availability to FgfRs, thus modulating Fgf signaling activity. 相似文献