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排序方式: 共有124条查询结果,搜索用时 15 毫秒
21.
Kari M. Wojtanik Keith Edgemon Srikant Viswanadha Brigette Lindsey Martin Haluzik Weiping Chen George Poy Marc Reitman Constantine Londos 《Journal of lipid research》2009,50(6):1068-1079
We investigated the role of LMNA in adipose tissue by developing a novel mouse model of lipodystrophy. Transgenic mice were generated that express the LMNA mutation that causes familial partial lipodystrophy of the Dunnigan type (FPLD2). The phenotype observed in FPLD-transgenic mice resembles many of the features of human FPLD2, including lack of fat accumulation, insulin resistance, and enlarged, fatty liver. Similar to the human disease, FPLD-transgenic mice appear to develop normally, but after several weeks they are unable to accumulate fat to the same extent as their wild-type littermates. One poorly understood aspect of lipodystrophies is the mechanism of fat loss. To this end, we have examined the effects of the FPLD2 mutation on fat cell function. Contrary to the current literature, which suggests FPLD2 results in a loss of fat, we found that the key mechanism contributing to the lack of fat accumulation involves not a loss, but an apparent inability of the adipose tissue to renew itself. Specifically, preadipocytes are unable to differentiate into mature and fully functional adipocytes. These findings provide insights not only for the treatment of lipodystrophies, but also for the study of adipogenesis, obesity, and insulin resistance. 相似文献
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24.
F. Reitman 《BMJ (Clinical research ed.)》1948,2(4589):1064-1065
25.
Jimenez HN Liu KG Hong SP Reitman MS Uberti MA Bacolod MD Cajina M Nattini M Sabio M Doller D 《Bioorganic & medicinal chemistry letters》2012,22(9):3235-3239
4-(1-Phenyl-1H-pyrazol-4-yl)quinoline (1) was identified by screening the Lundbeck compound collection, and characterized as having mGlu4 receptor positive allosteric modulator properties. Compound 1 is selective over other mGlu receptors and a panel of GPCRs, ion channels and enzymes, but has suboptimal lipophilicity and high plasma and brain non-specific binding. In view of the challenges at the hit-to-lead stage previously reported in the development of mGlu4 receptor positive allosteric modulators (PAMs), a thorough structure-mGlu4 PAM activity relationship study was conducted to interrogate the chemical tractability of this chemotype. The central pyrazole ring tolerates the addition of one or two methyl groups. The C-7 position of the quinoline ring provides a site tolerant to hydrophilic substituents, enabling the design of diverse analogs with good in vitro mGlu4 PAM potency and efficacy, as well as improved microsomal turnover in vitro, compared to 1. In spite of the excellent ligand efficiency of 1 (LE=0.43), optimization of in vitro potency for this series reached a plateau around EC(50)=200 nM. 相似文献
26.
27.
Intermediate filaments in nervous tissues 总被引:59,自引:30,他引:29
Intermediate filaments have been isolated from rabbit intradural spinal nerve roots by the axonal flotation method. This method was modified to avoid exposure of axons to low ionic strength medium. The purified filaments are morphologically 75-80 percent pure. The gel electrophoretogram shows four major bands migrating at 200,000, 145,000, 68,000, and 60,000 daltons, respectively. A similar preparation from rabbit brain shows four major polypeptides with mol wt of 200,000 145,000, 68,000, and 51,000 daltons. These results indicate that the neurofilament is composed of a triplet of polypepetides with mol wt of 200,000, 145,000, and 68,000 daltons. The 51,000-dalton band that appears in brain filament preparations as the major polypeptide seems to be of glial origin. The significance of the 60,000- dalton band in the nerve root filament preparation is unclear at this time. Antibodies raised against two of the triplet proteins isolated from calf brain localize by immunofluorescence to neurons in central and peripheral nerve. On the other hand, an antibody to the 51,000-dalton polypeptide gives only glial staining in the brain, and very weak peripheral nerve staining. Prolonged exposure of axons to low ionic strength medium solubilizes almost all of the triplet polypeptides, leaving behind only the 51,000- dalton component. This would indicate that the neurofilament is soluble at low ionic strength, whereas the glial filament is not. These results indicate that neurofilaments and glial filaments are composed of different polypeptides and have different solubility characteristics. 相似文献
28.
Nucleotide sequence analysis of the lemur beta-globin gene family: evidence for major rate fluctuations in globin polypeptide evolution 总被引:1,自引:0,他引:1
Lemur beta-related globin genes have been isolated and sequenced. Orthology
of prosimian and human epsilon-, gamma-, and beta-related globin genes was
established by dot-matrix analysis. All of these lemur globin genes
potentially encode functional beta-related globin polypeptides, though
precisely when the gamma-globin gene is expressed remains unknown. The
organization of the 18-kb brown lemur beta-globin gene cluster (5'
epsilon-gamma-[psi eta-delta]-beta 3') is consistent with its evolution by
contraction via unequal crossing-over from the putative ancestral mammalian
beta-globin gene cluster (5' epsilon-gamma- eta-delta-beta 3'). The dwarf
lemur nonadult globin genes are arranged as in the brown lemur. Similar
levels of synonymous (silent) nucleotide substitutions and noncoding DNA
sequence differences have accumulated between species in all of these
genes, suggesting a uniform rate of noncoding DNA divergence throughout
primate beta-globin gene clusters. These differences are comparable with
those observed in the nonfunctional psi eta pseudogene and have therefore
accumulated at the presumably maximal neutral rate. In contrast,
nonsynonymous (replacement) nucleotide substitutions show a significant
heterogeneity in distribution for both the same gene in different lineages
and different genes in the same lineage. These major fluctuations in
replacement but not silent substitution rates cannot be attributed to
changes in mutation rate, suggesting that changes in the rate of globin
polypeptide evolution in primates is not governed solely by variable
mutation rates.
相似文献
29.
ML Jones 《Biotechnic & histochemistry》2013,88(3):155-159
The discovery of formaldehyde for preserving tissue structures produced a new dimension in microscopy. Preserving structure and morphology became important; therefore, identifying a proper fixing agent for particular structures, chemical entities, and tissues, also became important. The methods for demonstrating tissue structures evolved and were implemented with careful observation and documentation of the results and outcomes. Formalin was incorporated into many techniques, and provided helpful results in many cases and hindrances in others. The effects of formalin on the outcomes of routine and special staining techniques are reported here. 相似文献
30.
Nitric oxide (NO) has been reported to act both as a destructive and a protective agent in the pathogenesis of the injuries
that occur during hypoxia/reoxygenation (H/R). It has been suggested that this dual role of NO depends directly on the isoform
of NO synthase (NOS) involved. In this work, we investigate the role that NO derived from endothelial NOS (eNOS) plays in
cardiac H/R-induced injury. Wistar rats were submitted to H/R (hypoxia for 30 min; reoxygenation of 0 h, 12 h and 5 days),
with or without prior treatment using the selective eNOS inhibitor l-NIO (20 mg/kg). Lipid peroxidation, apoptosis and protein nitration, as well as NO production (NOx), were analysed. The results
showed that l-NIO administration lowered NOx levels in all the experimental groups. However, no change was found in the lipid peroxidation
level, the percentage of apoptotic cells or nitrated protein expression, implying that eNOS-derived NO may not be involved
in the injuries occurring during H/R in the heart. We conclude that l-NIO would not be useful in alleviating the adverse effects of cardiac H/R. 相似文献