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排序方式: 共有452条查询结果,搜索用时 781 毫秒
111.
112.
Zhang Q Bengtsson M Partridge C Salehi A Braun M Cox R Eliasson L Johnson PR Renström E Schneider T Berggren PO Göpel S Ashcroft FM Rorsman P 《Nature cell biology》2007,9(4):453-460
Pancreatic islets have a central role in blood glucose homeostasis. In addition to insulin-producing beta-cells and glucagon-secreting alpha-cells, the islets contain somatostatin-releasing delta-cells. Somatostatin is a powerful inhibitor of insulin and glucagon secretion. It is normally secreted in response to glucose and there is evidence suggesting its release becomes perturbed in diabetes. Little is known about the control of somatostatin release. Closure of ATP-regulated K(+)-channels (K(ATP)-channels) and a depolarization-evoked increase in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) have been proposed to be essential. Here, we report that somatostatin release evoked by high glucose (>or=10 mM) is unaffected by the K(ATP)-channel activator diazoxide and proceeds normally in K(ATP)-channel-deficient islets. Glucose-induced somatostatin secretion is instead primarily dependent on Ca(2+)-induced Ca(2+)-release (CICR). This constitutes a novel mechanism for K(ATP)-channel-independent metabolic control of pancreatic hormone secretion. 相似文献
113.
114.
Gilbert JA Gianoukakis AG Salehi S Moorhead J Rao PV Khan MZ McGregor AM Smith TJ Banga JP 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(8):5084-5092
The thyroid target Ag for disease-inducing autoantibodies in Graves' disease is the receptor for thyroid-stimulating hormone (TSH), but little is known about the molecular basis of this pathogenic Ab response. We describe the characteristics of two high- affinity mAbs developed from an experimental murine model of hyperthyroid Graves' disease that exhibit potent thyroid-stimulating activity. Nanogram concentrations of the IgG mAbs KSAb1 and KSAb2 and their Fab induce full stimulation of the TSH receptor that is matched by the ligand TSH and, thus, act as full agonists for the receptor. However, KSAb1 and KSAb2 display differential activities in their ability to block TSH-mediated stimulation of the receptor, indicating subtle differences in their biological properties. In displacement studies, IgG and Fabs of KSAb1 and KSAb2 compete with Graves' disease autoantibodies as well as thyroid-blocking Abs present in some hypothyroid patients, indicating a close relationship between these autoimmune determinants on the receptor. In passive transfer studies, single injections of microgram quantities of KSAb1 or KSAb2 IgG led to rapid elevation of serum thyroxine and a hyperthyroid state that was maintained for a number of days. The thyroid glands showed evidence of cell necrosis, but there was no accompanying mononuclear cell infiltrate. In studying their receptor activation pathways, both KSAb1 and KSAb2 provoked phosphorylation of the intracellular ERK1/2 pathway in primary thyrocytes, indicating that multiple signaling pathways may participate in the pathogenesis of Graves' disease. In summary, our findings emphasize the similarities of the experimental mouse model in reproducing the human disorder and provide improved means for characterizing the molecular basis of this pathogenic response. 相似文献
115.
Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration 总被引:15,自引:0,他引:15
Salehi A Delcroix JD Belichenko PV Zhan K Wu C Valletta JS Takimoto-Kimura R Kleschevnikov AM Sambamurti K Chung PP Xia W Villar A Campbell WA Kulnane LS Nixon RA Lamb BT Epstein CJ Stokin GB Goldstein LS Mobley WC 《Neuron》2006,51(1):29-42
Degeneration of basal forebrain cholinergic neurons (BFCNs) contributes to cognitive dysfunction in Alzheimer's disease (AD) and Down's syndrome (DS). We used Ts65Dn and Ts1Cje mouse models of DS to show that the increased dose of the amyloid precursor protein gene, App, acts to markedly decrease NGF retrograde transport and cause degeneration of BFCNs. NGF transport was also decreased in mice expressing wild-type human APP or a familial AD-linked mutant APP; while significant, the decreases were less marked and there was no evident degeneration of BFCNs. Because of evidence suggesting that the NGF transport defect was intra-axonal, we explored within cholinergic axons the status of early endosomes (EEs). NGF-containing EEs were enlarged in Ts65Dn mice and their App content was increased. Our study thus provides evidence for a pathogenic mechanism for DS in which increased expression of App, in the context of trisomy, causes abnormal transport of NGF and cholinergic neurodegeneration. 相似文献
116.
Majid Moghadam Shahram Tangestaninejad Valiollah Mirkhani Iraj Mohammadpoor-baltork Narges Sirjanian Somayeh Parand 《Bioorganic & medicinal chemistry》2009,17(9):3394-3398
In this report, highly efficient oxidative decarboxylation of carboxylic acids with sodium periodate catalyzed by a supported manganese(III) porphyrin is described. In the presence of manganese(III) tetra(4-pyridyl)porphyrin supported on cross-linked chloromethylated polystyrene, [Mn(T4PyP)-CMP], as catalyst, carboxylic acids were converted to their corresponding carbonyl compounds via oxidative decarboxylation with sodium periodate using imidazole as axial ligand. The oxidation of anti-inflammatory drugs such Indomethacin and Ibuprofen was carried out successfully and the decarboxylated products were obtained. This catalyst can be reused several times without loss of its catalytic activity in the oxidation reactions. 相似文献
117.
Shu-Biao Wu Iraj Tavassolian Gholamreza Rabiei Peter Hunt Michelle Wirthensohn John P. Gibson Christopher M. Ford Margaret Sedgley 《Molecular genetics and genomics : MGG》2009,282(3):273-281
Peach and almond have been considered as model species for the family Rosaceae and other woody plants. Consequently, mapping
and characterisation of genes in these species has important implications. High-resolution melting (HRM) analysis is a recent
development in the detection of SNPs and other markers, and proved to be an efficient and cost-effective approach. In this
study, we aimed to map genes corresponding to known proteins in other species using the HRM approach. Prunus unigenes were searched and compared with known proteins in the public databases. We developed single-nucleotide polymorphism
(SNP) markers, polymorphic in a mapping population produced from a cross between the cloned cultivars Nonpareil and Lauranne.
A total of 12 SNP-anchored putative genes were genotyped in the population using HRM, and mapped to an existing linkage map.
These genes were mapped on six linkage groups, and the predicted proteins were compared to putative orthologs in other species.
Amongst those genes, four were abiotic stress-responsive genes, which can provide a starting point for construction of an
abiotic resistance map. Two allergy and detoxification related genes, respectively, were also mapped and analysed. Most of
the investigated genes had high similarities to sequences from closely related species such as apricot, apple and other eudicots,
and these are putatively orthologous. In addition, it was shown that HRM can be an effective means of genotyping populations
for the purpose of constructing a linkage map. Our work provides basic genomic information for the 12 genes, which can be
used for further genetic and functional studies. 相似文献
118.
Shadab Gharaati Shahram Tangestaninejad Valiollah Mirkhani Iraj Mohammadpoor-Baltork Farshid Kosari 《Inorganica chimica acta》2010,363(9):1995-646
An efficient and selective method for methoxymethylation of alcohols and phenols with formaldehyde dimethyl acetal (FDMA) catalyzed by electron deficient tin(IV)tetraphenylporphyrinato trifluoromethanesulfonate, [SnIV(TPP)(OTf)2], is reported. A variety of primary, secondary and tertiary alcohols as well as phenols were converted to their corresponding methoxymethyl ethers with FDMA in the presence of a high-valent tin(IV) porphyrin. This catalyst can be used for selective methoxymethylation of primary, secondary and tertiary alcohols in the presence of phenols or tertiary alcohols. The present method offers several advantages such as short reaction times, high yields, simple procedure, selectivity and applicability for both alcohols and phenols. 相似文献
119.
Oriental beech (Fagus orientalis Lipsky) is a widespread monoecious and wind-pollinated tree species. It is one of the major components of the Hyrcanian forests
of Iran and it is of both ecological and economical importance. Twelve beech stands were surveyed at 9 chloroplast (cp) and
6 nuclear (n) polymorphic microsatellite loci (simple sequence repeats, SSR) to provide information on distribution of genetic
diversity within and among populations and on gene conservation and silvicultural management of this species. High levels
of genetic differentiation were detected for the chloroplast genome (F
ST = 0.80 and R
ST = 0.95), in sharp contrast to the nuclear genome (F
ST = 0.06, R
ST = 0.05). The analysis of molecular variance (AMOVA) showed that 48% of the total cpSSR variation was attributable to differences
among regions and 30% to differences among populations within regions, suggesting multiple origins of beech populations in
Hyrcanian forests. Nuclear SSRs confirmed the presence of significant differentiation among populations and among geographic
regions, even if, as expected, this was less pronounced than that found with cpSSRs (based on AMOVA, differences among regions
and among populations within regions each contribute 5% to total nSSR variance). A highly significant correlation between
genetic (nSSRs) and geographic distances (R
2 = 0.522) was estimated, thus showing an isolation by distance effect. The application of spatial analysis of molecular variance
(SAMOVA) using both marker data allowed identification of genetically homogeneous groups of populations. Possible applications
of these results for the certification of provenances and/or seed lots and for designing conservation programs are presented
and discussed. 相似文献
120.
Stefanie Obermüller Federico Calegari Angus King Anders Lindqvist Ingmar Lundquist Albert Salehi Maura Francolini Patrizia Rosa Patrik Rorsman Wieland B. Huttner Sebastian Barg 《PloS one》2010,5(1)
Granins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter of debate. Work in cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking chromogranin B (CgB-ko), which were viable and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced insulin release, but normal insulin sensitivity in vivo. CgB-ko islets lacked specifically the rapid initial phase of stimulated secretion, had elevated basal insulin release, and stored and released twice as much proinsulin as wildtype (wt) islets. Stimulated release of glucagon and somatostatin was reduced as well. Surprisingly, biogenesis, morphology and function of insulin granules were normal, and no differences were found with regard to β-cell stimulus-secretion coupling. We conclude that CgB is not required for normal insulin granule biogenesis or maintenance in vivo, but is essential for adequate secretion of islet hormones. Consequentially CgB-ko animals display some, but not all, hallmarks of human type-2 diabetes. However, the molecular mechanisms underlying this defect remain to be determined. 相似文献