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排序方式: 共有161条查询结果,搜索用时 265 毫秒
41.
C Allard V Desgagné J Patenaude M Lacroix L Guillemette MC Battista M Doyon J Ménard JL Ardilouze P Perron L Bouchard MF Hivert 《Epigenetics》2015,10(4):342-351
Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS10) and showed it was an adequate instrumental variable (β = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10−11; N = 467). A higher GRS10 was associated with lower methylation levels at cg12083122 located near LEP (β = −0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS10 and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (β = −0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation. 相似文献
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du Puy L Beqqali A van Tol HT Monshouwer-Kloots J Passier R Haagsman HP Roelen BA 《The International journal of developmental biology》2012,56(4):301-309
SARCOSIN, also named Krp1, has been identified as a protein exclusively expressed in striated muscle tissue. Here we report on the role of SARCOSIN in skeletal muscle development and differentiation. We demonstrate, by means of whole-mount in situ hybridization, that Sarcosin mRNA is expressed in the myotome part of the mature somites in mouse embryos from embryonic day 9.5 onwards. Sarcosin is not expressed in the developing heart at these embryonic stages, and in adult tissues the mRNA expression levels are five times lower in the heart than in skeletal muscle. SARCOSIN protein partially co-localizes with the M-band protein myomesin and between and below laterally fusing myofibrils in adult skeletal muscle tissue. RNA interference mediated knock-down of SARCOSIN in the C2C12 myoblast cell line appeared to be stimulatory in the early phase of differentiation, but inhibitory at a later phase of differentiation. 相似文献
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Ramesh JL Kandimalla Willayat Yousuf Wani Binukumar BK Kiran Dip Gill 《Journal of biomedical science》2012,19(1):2
Background
One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid β protein (Aβ) within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aβ42 or 40 from amyloid β -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs γ-secretase cleavage. 相似文献44.
Linda W. van Laake Robert Passier Krista den Ouden Chantal Schreurs Jantine Monshouwer-Kloots Dorien Ward-van Oostwaard Cees J. van Echteld Pieter A. Doevendans Christine L. Mummery 《Stem cell research》2009,3(2-3):106-112
Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) has been shown to improve the function of the rodent heart 1 month after myocardial infarction (MI). However, the mechanistic basis and optimal delivery strategies are unclear. We investigated the influence of the number of injected cells, resulting graft size, and possible paracrine mechanisms in this process. MI was induced in NOD-SCID mice (n = 84) followed by injection of enriched hESC-CM at different dosages, hESC-non-CM derivatives, culture medium, or no injection. Cardiac function was monitored for 12 weeks with 9.4 T MRI (n = 70). Grafts were identified by epifluorescence of a transgenic GFP marker and characterized by immunofluorescence. Vascularity and paracrine effects were investigated immunohistochemically. Transplantation of differentiated hESCs improved short, mid-, and long-term cardiac performance and survival, although only cardiomyocytes formed grafts. A mid-term (4 weeks) cardiomyocyte-specific enhancement was associated with elevated vascular density around the graft and attenuated compensatory remodeling. However, increasing the number of hESC-CM for injection did not enhance heart function further. Moreover, we observed that small graft size was associated with a better functional outcome. HESC-CM increased myocardial vascularization and enhanced heart function in mice after MI, but larger graft size was associated with reduced functional improvement. Future studies should focus on advanced delivery strategies and mechanisms of action rather than increasing graft size. 相似文献
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Dick J. van der Horst Jan M. van Doorn Paul C. C. M. Passier Michael M. Vork Jan F. C. Glatz 《Molecular and cellular biochemistry》1993,123(1-2):145-152
Since insect flight muscles are among the most active muscles in nature, their extremely high rates of fuel supply and oxidation pose interesting physiological problems. Long-distance flights of species like locusts and hawkmoths are fueled through fatty acid oxidation. The lipid substrate is transported as diacylglycerol in the blood, employing a unique and efficient lipoprotein shuttle system. Following diacylglycerol hydrolysis by a flight muscle lipoprotein lipase, the liberated fatty acids are ultimately oxidized in the mitochondria. Locust flight muscle cytoplasm contains an abundant fatty acid-binding protein (FABP). The flight muscle FABP ofLocusta migratoria is a 15 kDa protein with an isoelectric point of 5.8, binding fatty acids in a 1:1 molar stoichiometric ratio. Binding affinity of the FABP for longchain fatty acids (apparent dissociation constant Kd=5.21±0.16 M) is however markedly lower than that of mammalian FABPs. The NH2-terminal amino acid sequence shares structural homologies with two insect FABPs recently purified from hawkmoth midgut, as well as with mammalian FABPs. In contrast to all other isolated FABPs, the NH2 terminus of locust flight muscle FABP appeared not to be acetylated. During development of the insect, a marked increase in fatty acid binding capacity of flight muscle homogenate was measured, along with similar increases in both fatty acid oxidation capacity and citrate synthase activity. Although considerable circumstantial evidence would support a function of locust flight muscle FABP in intracellular uptake and transport of fatty acids, the finding of another extremely well-flying migratory insect, the hawkmothAcherontia atropos, which employs the same lipoprotein shuttle system, however contains relatively very low amounts of FABP in its flight muscles, renders the proposed function of FABP in insect flight muscles questionable. 相似文献
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