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排序方式: 共有123条查询结果,搜索用时 15 毫秒
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Stephen A. Martin Tyler M. DeMuth Karl N. Miller Thomas D. Pugh Michael A. Polewski Ricki J. Colman Kevin W. Eliceiri Timothy Mark Beasley Sterling C. Johnson Rozalyn M. Anderson 《Aging cell》2016,15(1):100-110
The hippocampus is critical for cognition and memory formation and is vulnerable to age‐related atrophy and loss of function. These phenotypes are attenuated by caloric restriction (CR), a dietary intervention that delays aging. Here, we show significant regional effects in hippocampal energy metabolism that are responsive to age and CR, implicating metabolic pathways in neuronal protection. In situ mitochondrial cytochrome c oxidase activity was region specific and lower in aged mice, and the impact of age was region specific. Multiphoton laser scanning microscopy revealed region‐ and age‐specific differences in nicotinamide adenine dinucleotide (NAD)‐derived metabolic cofactors. Age‐related changes in metabolic parameters were temporally separated, with early and late events in the metabolic response to age. There was a significant regional impact of age to lower levels of PGC‐1α, a master mitochondrial regulator. Rather than reversing the impact of age, CR induced a distinct metabolic state with decreased cytochrome c oxidase activity and increased levels of NAD(P)H. Levels of hippocampal PGC‐1α were lower with CR, as were levels of GSK3β, a key regulator of PGC‐1α turnover and activity. Regional distribution and colocalization of PGC‐1α and GSK3β in mouse hippocampus was similar in monkeys. Furthermore, the impact of CR to lower levels of both PGC‐1α and GSK3β was also conserved. The studies presented here establish the hippocampus as a highly varied metabolic environment, reveal cell‐type and regional specificity in the metabolic response to age and delayed aging by CR, and suggest that PGC‐1α and GSK3β play a role in implementing the neuroprotective program induced by CR. 相似文献
23.
Ana S. Fernandes João Serejo Jorge Gaspar Fátima Cabral Ana F. Bettencourt José Rueff Matilde Castro Judite Costa Nuno G. Oliveira 《Cell biology and toxicology》2010,26(2):91-101
Oxidative cell injury could be induced by different reactive oxygen species (ROS) operating in multiple pathways. The present
work is focused on three different models of oxidative stress: the xanthine/xanthine oxidase system (XXO), an extracellular
superoxide anion generator; tert-butylhydroperoxide (TBHP), an analogue of lipid hydroperoxides; and doxorubicin (Dox), an anticancer drug. Superoxide and
peroxyl radicals, among other ROS, could be effectively scavenged by MnTM-4-PyP, a polyfunctional catalytic antioxidant. In
this report, we have addressed the role of MnTM-4-PyP on the protection against the cytotoxicity induced by the three aforementioned
oxidants. The effect of MnTM-4-PyP (0.1–100 μM) was evaluated in V79 fibroblasts using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide reduction and the crystal violet assays, as well as the mitotic index. Also, the generation of intracellular
ROS was studied by the fluorescent probe dihydroethidium. MnTM-4-PyP has shown significant protective effects against the
cytotoxicity of XXO and TBHP, increasing the cell viability in approximately 40% and reducing the intracellular level of ROS.
However, no considerable protection occurred against Dox. The three oxidants caused a mitotic index reduction that was not
altered by MnTM-4-PyP. In summary, MnTM-4-PyP appears to be a promising agent for the protection against oxidative injury.
However, it has shown differential responses, reinforcing the need to study different experimental models for the adequate
evaluation of its potentialities as a catalytic antioxidant. 相似文献
24.
During their aquatic life cycle, nanoparticles are subject to environmentally driven surface modifications (e.g. agglomeration or coating) associated with aging. Although the ecotoxicological potential of nanoparticles might be affected by these processes, only limited information about the potential impact of aging is available. In this context, the present study investigated acute (96 h) and chronic (21 d) implications of systematically aged titanium dioxide nanoparticles (nTiO2; ~90 nm) on the standard test species Daphnia magna by following the respective test guidelines. The nTiO2 were aged for 0, 1, 3 and 6 d in media with varying ionic strengths (Milli-Q water: approx. 0.00 mmol/L and ASTM: 9.25 mmol/L) in the presence or absence of natural organic matter (NOM). Irrespective of the other parameters, aging in Milli-Q did not change the acute toxicity relative to an unaged control. In contrast, 6 d aged nTiO2 in ASTM without NOM caused a fourfold decreased acute toxicity. Relative to the 0 d aged particles, nTiO2 aged for 1 and 3 d in ASTM with NOM, which is the most environmentally-relevant setup used here, significantly increased acute toxicity (by approximately 30%), while a toxicity reduction (60%) was observed for 6 d aged nTiO2. Comparable patterns were observed during the chronic experiments. A likely explanation for this phenomenon is that the aging of nTiO2 increases the particle size at the start of the experiment or the time of the water exchange from <100 nm to approximately 500 nm, which is the optimal size range to be taken up by filter feeding D. magna. If subjected to further agglomeration, larger nTiO2 particles, however, cannot be retained by the daphnids’ filter apparatus ultimately reducing their ecotoxicological potential. This non-linear pattern of increasing and decreasing nTiO2 related toxicity over the aging duration, highlights the knowledge gap regarding the underlying mechanisms and processes. This understanding seems, however, fundamental to predict the risks of nanoparticles in the field. 相似文献
25.
Bettencourt C Montiel R Santos C Pavão ML Viegas-Crespo AM Lopes PA Lima M 《Human biology; an international record of research》2006,78(4):509-512
Our aim in this study is to report on the polymorphism of the APOE gene in the Azores Islands (Portugal) to obtain a population baseline of the existing variation in this locus, known to be one of the genetic determinants of plasma lipid levels. One hundred twenty-six Azorean individuals were typed for the APOE polymorphism using standard PCR-RFLP. Allele frequencies obtained for APOE*2, APOE*3, and APOE*4 were 6.75%, 83.73%, and 9.52%, respectively. The APOE*3/*3 genotype presented the highest frequency (69.84%), and the APOE*4/*4 genotype had the lowest frequency (0.79%). Genotype frequencies were in conformity with Hardy-Weinberg expectations. The observed genotype and allele frequencies were similar to those reported for other Iberian samples. Furthermore, Nei's gene diversity (H = 0.2864 +/- 0.0351) was similar to that reported for samples from mainland Portugal. The data generated from this study will be of importance in the context of ongoing studies concerning the factors that influence lipid levels in the Azorean population. 相似文献
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E.M.V. Bettencourt C.M. Bettencourt P. Ferreira E. Oliveira A. Rocha 《Theriogenology》2009,71(6):947-958
Controlled slow freezing and vitrification have been successfully used for ovine embryo cryopreservation. Selection of embryos for transfer is based on stereomicroscopical embryo scoring after thawing, but the subjectivity inherent to this selection step has been demonstrated by ultrastructural studies of controlled slow frozen, in vivo produced ovine morulae and blastocysts. These studies have shown that certain abnormalities remain undetected by stereomicroscopy only. In the present study, using ovine in vivo produced morulae and blastocysts, we have studied the ultrastructural alterations induced by open pulled straw vitrification (OPS) and controlled slow freezing, compared stereomicroscopical embryo scoring with light microscopy evaluation of embryo's semithin sections, and related the ultrastructural cellular damage with the embryo classification by stereomicroscopical embryo scoring of embryos’ and semithin section evaluation by light microscopy. The ultrastructural lesions found for OPS-vitrified and controlled slow frozen embryos were similar, independently of embryo stage. A significant higher number of grade 3 embryos was found at stereomicroscopical scoring after controlled slow freezing (P = 0.02), and a significant higher number of grade 3 blastocysts was found at semithin sectioning after OPS vitrification (P = 0.037). The extension of ultrastructural damage, especially of mitochondria and cytoskeleton, was related to the semithin classification but not to stereomicroscopical scoring at thawing. This suggests that semithin scoring is a useful tool for predicting ultrastructural lesions and new improvements in cryopreservation and thawing methods of ovine embryos are still warranted, including in the case of blastocysts cryopreserved by OPS vitrification. 相似文献
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29.
Gresl TA Colman RJ Havighurst TC Byerley LO Allison DB Schoeller DA Kemnitz JW 《American journal of physiology. Regulatory, integrative and comparative physiology》2003,285(6):R1340-R1354
The minimal model of glucose disappearance (MINMOD version 3; MM3) and both the one-compartment (1CMM) and the two-compartment (2CMM) minimal models were used to analyze stable isotope-labeled intravenous glucose tolerance test (IVGTT) data from year 10 of a study of the effect of dietary restriction (DR) in male rhesus monkeys. Adult monkeys were energy restricted (R; n = 12) on a semipurified diet to approximately 70% of control (C) intake (ad libitum-fed monkeys; n = 12). Under ketamine anesthesia, fasting insulin levels were greater among C monkeys. Insulin sensitivity estimates from all models were greater in R than C monkeys, whereas glucose effectiveness estimates were not consistently greater in R monkeys. Fasting plasma glucose as well as hepatic glucose production and clearance rates did not differ between groups. Body fat, in part, statistically mediated the effect of DR to enhance insulin sensitivity indexes. Precision of estimation and intermodel relationships among insulin sensitivity and glucose effectiveness estimates were in the ranges of those reported previously for humans and dogs, suggesting that the models may provide valid estimates for rhesus monkeys as well. The observed insulin sensitivity indexes from all models, elevated among R vs. C monkeys, may be explained, at least in part, by the difference in body fat content between these groups after chronic DR. 相似文献
30.
Annotation of the Drosophila melanogaster euchromatic genome: a systematic review 总被引:1,自引:0,他引:1 下载免费PDF全文
Misra S Crosby MA Mungall CJ Matthews BB Campbell KS Hradecky P Huang Y Kaminker JS Millburn GH Prochnik SE Smith CD Tupy JL Whitfied EJ Bayraktaroglu L Berman BP Bettencourt BR Celniker SE de Grey AD Drysdale RA Harris NL Richter J Russo S Schroeder AJ Shu SQ Stapleton M Yamada C Ashburner M Gelbart WM Rubin GM Lewis SE 《Genome biology》2002,3(12):research0083.1-8322