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排序方式: 共有217条查询结果,搜索用时 78 毫秒
91.
Zhi H. Huang Catherine A. Reardon Papasani V. Subbaiah Godfrey S. Getz Theodore Mazzone 《Journal of lipid research》2013,54(1):202-213
The synthesis of apoE by adipocytes has profound effects on adipose tissue lipid flux and gene expression. Using adipose tissue transplantation from wild-type (WT) to apoE knockout (EKO) mice, we show that adipose tissue also contributes to circulating apoE. Different from circulating apoE produced by bone marrow transplantation (BMT), however, adipose tissue-derived apoE does not correct hyperlipidemia or suppress atherosclerosis. ApoE secreted by macrophages has a more acidic isoform distribution, and it increases binding of reconstituted VLDL particles to hepatocytes and fibroblasts more effectively than apoE secreted by adipocytes. The incremental binding can be entirely accounted for by binding to the LDL receptor. After BMT into EKO hosts, plasma cholesterol and macrophage-derived apoE are largely within IDL/LDL- and HDL-sized particles. After adipose tissue transplantation, most cholesterol and adipocyte apoE remain in VLDL. After BMT, circulating apoE no longer demonstrates predominance of acidic isoforms compared with that circulating after fat transplantation. In conclusion, fat transplantation provides circulating apoE levels similar to those provided by bone marrow transplantation, but it does not suppress hyperlipidemia or atherosclerosis. A potential mechanism contributing to this difference is differential binding to cell surface lipoprotein receptors. 相似文献
92.
B. Cobucci-Ponzano F. Conte M. Mazzone E. Bedini M. M. Corsaro M. Rossi 《Biocatalysis and Biotransformation》2013,31(1-2):18-24
Glycosynthases are mutant glycosidases, which in the presence of activated glycosides and suitable reaction conditions, synthesize oligosaccharides without hydrolysing them. This feature makes these catalysts promising tools for the large scale synthesis of carbohydrates. However, despite the popularity of the glycosynthetic approach, the number of enzymes effecting glycosynthetic reactions is still limited. We report here on the design of novel reaction conditions for a thermophilic α-l-fucosidase mutant, which might provide a route for the production of novel glycosynthases. 相似文献
93.
94.
Excitotoxicity triggered by over-activation of glutamate receptors is thought to be an early mechanism of extensive neuronal
death with consequent loss of function following lesion of spinal networks. One important process responsible for excitotoxic
death is ‘parthanatos’ caused by hyperactivation of poly(ADP-ribose) polymerase (PARP) enzyme 1. Using rat organotypic spinal
slices as in vitro models, the present study enquired if 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2yl)acetamide (PJ 34), a pharmacological inhibitor of PARP-1, could counteract the excitotoxic
damage evoked by transient application (1 h) of kainate, a potent analogue of glutamate. Kainate induced dose-dependent (1 μM
threshold) neuronal loss (without damage to astrocytes) detected 24 h later via a PARP-1 dependent process that had peaked
at 4 h after washout kainate. All spinal regions (ventral, central and dorsal) were affected, even though the largest damage
was found in the dorsal area. Whereas PJ 34 did not protect against a large concentration (100 μM) of kainate, it significantly
inhibited neuronal losses evoked by 10 μM kainate as long as it was co-applied with this glutamate agonist. When the application
of PJ 34 was delayed to the washout time, neuroprotection was weak and regionally restricted. These data suggest that kainate-induced
parthanatos developed early and was prevented by PJ 34 only when it was co-applied together with excitotoxic stimulus. Our
results highlight the difficulty to arrest parthanatos as a mechanism of spinal neuron death in view of its low threshold
of activation by kainate, its widespread distribution, and relatively fast development. 相似文献
95.
The present study deals with the phenomenon of insular speciation and discusses, as a case study, the debated taxonomical issue of the status of Onthophagus massai (Coleoptera, Sarabaeidae) as an endemic species vicarious to Onthophagus fracticornis in Sicily. The authors investigated the differentiation patterns between an insular population belonging to the supposed species O. massai (collected in its locus typicus, Piano Battaglia) and three Italian O. fracticornis populations (collected along a N–S latitudinal gradient). These patterns are described and analysed using multiple approaches: the qualitative inspection of the microsculpture of elytral surfaces, considered a diagnostic character for O. massai identification; the comparison of horn static allometries, known to be a good indicator of divergence processes between closely related species or isolated populations of the same species; the comparison of the patterns of shape and size difference of the head, epipharynx and genitalia attained with a combination of traditional and geometric (landmark and semilandmark) morphometric methods; and, finally, the estimation of the genetic relationships between Sicilian and continental populations obtained by analysing cytochrome oxidase subunit 1 mitochondrial gene sequences. The integration of the results of these approaches indicates that there is not sufficient evidence to vindicate the species status for O. massai, which should more likely be considered a small-sized version of O. fracticornis (a possible case of insular dwarfism). However, the complex pattern of shape, size and genetic variation observed between the populations analysed hinted at the possibility that a diversification process is ongoing, but not only between insular and continental populations; each population showed a tendency to evolve as an evolutionarily independent unit. 相似文献
96.
Franco De Crescenzo Marco Armando Luigi Mazzone Mario Ciliberto Marco Sciannamea Caroline Figueroa Luigi Janiri Digby Quested Stefano Vicari 《Attention deficit and hyperactivity disorders》2014,6(1):49-58
Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood. There is an increasing need to find objective measures and markers of the disorder in order to assess the efficacy of the therapy and to improve follow-up strategies. Actigraphy is an objective method for recording motor activity and sleep parameters using small, computerized, watch-like devices worn on the body, and it has been used in many clinical trials to assess methylphenidate efficacy and adverse effects in ADHD. Our article aim is to systematically review and perform a meta-analysis of the current evidence on the role of actigraphy in both the detection of changes in activity and in sleep patterns in randomized clinical trials that compared methylphenidate against placebo in the treatment of ADHD. A comprehensive literature search of PubMed/MEDLINE, Scopus, Embase, Cochrane Library, CINHAL and PsycINFO databases was carried out to find randomized clinical trials comparing methylphenidate versus placebo in children with ADHD, using actigraphic measures as an outcome. No start date limit was used and the search was updated until June 2013. The primary outcome measures were ‘total sleep time’ and daytime ‘activity mean’. As secondary outcomes, we analyzed ‘sleep onset latency’, ‘sleep efficiency’ and ‘wake after sleep onset’. Eight articles comprising 393 patients were included in the analysis. Children with ADHD using MPH compared to placebo have a significant difference of a large effect with a diminishing value in the activity mean. For the total sleep time, we found a significant and large effect in the decrease in sleep in MPH group. This study shows that MPH may effectively reduce mean activity in ADHD children, but it may negatively affect total sleep time. 相似文献
97.
SA Ohnmacht M Micco V Petrucci AK Todd AP Reszka M Gunaratnam MA Carvalho M Zloh S Neidle 《Bioorganic & medicinal chemistry letters》2012,22(18):5930-5935
The HSP90 protein is an important target in cancer. We report here that stable quadruplex DNAs can be formed from a promoter sequence in the HSP90 gene, on the basis of melting, circular and NMR studies, and show that these can be selectively targeted by non-macrocyclic quadruplex-stabilizing phenyl bis-oxazole derivatives. These do not bind significantly to duplex DNA and show low stabilization of the human telomeric quadruplex. These results suggest an approach to targeting HSP90 at the DNA level. 相似文献
98.
Shentu TP Singh DK Oh MJ Sun S Sadaat L Makino A Mazzone T Subbaiah PV Cho M Levitan I 《Journal of lipid research》2012,53(7):1348-1358
Endothelial dysfunction is a key step in atherosclerosis development. Our recent studies suggested that oxLDL-induced increase in endothelial stiffness plays a major role in dyslipidemia-induced endothelial dysfunction. In this study, we identify oxysterols, as the major component of oxLDL, responsible for the increase in endothelial stiffness. Using Atomic Force Microscopy to measure endothelial elastic modulus, we show that endothelial stiffness increases with progressive oxidation of LDL and that the two lipid fractions that contribute to endothelial stiffening are oxysterols and oxidized phosphatidylcholines, with oxysterols having the dominant effect. Furthermore, endothelial elastic modulus increases as a linear function of oxysterol content of oxLDL. Specific oxysterols, however, have differential effects on endothelial stiffness with 7-ketocholesterol and 7α-hydroxycholesterol, the two major oxysterols in oxLDL, having the strongest effects. 27-hydroxycholesterol, found in atherosclerotic lesions, also induces endothelial stiffening. For all oxysterols, endothelial stiffening is reversible by enriching the cells with cholesterol. oxLDL-induced stiffening is accompanied by incorporation of oxysterols into endothelial cells. We find significant accumulation of three oxysterols, 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 7-ketocholesterol, in mouse aortas of dyslipidemic ApoE−/− mice at the early stage of atherosclerosis. Remarkably, these are the same oxysterols we have identified to induce endothelial stiffening. 相似文献
99.
100.
The aim of the present report was to investigate whether, in the mammalian spinal cord, cell death induced by transient excitotoxic stress could trigger activation and proliferation of endogenous neuroprogenitor cells as a potential source of a lesion repair process and the underlying time course. Because it is difficult to address these issues in vivo, we used a validated model of spinal injury based on rat organotypic slice cultures that retain the fundamental tissue cytoarchitecture and replicate the main characteristics of experimental damage to the whole spinal cord. Excitotoxicity evoked by 1 h kainate application produced delayed neuronal death (40%) peaking after 1 day without further losses or destruction of white matter cells for up to 2 weeks. After 10 days, cultures released a significantly larger concentration of endogenous glutamate, suggesting functional network plasticity. Indeed, after 1 week the total number of cells had returned to untreated control level, indicating substantial cell proliferation. Activation of progenitor cells started early as they spread outside the central area, and persisted for 2 weeks. Although expression of the neuronal progenitor phenotype was observed at day 3, peaked at 1 week and tapered off at 2 weeks, very few cells matured to neurons. Astroglia precursors started proliferating later and matured at 2 weeks. These data show insult-related proliferation of endogenous spinal neuroprogenitors over a relatively brief time course, and delineate a narrow temporal window for future experimental attempts to drive neuronal maturation and for identifying the factors regulating this process. 相似文献