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71.
Zhong‐Fei Ni Zhi‐Wei Ma Ao‐Ji Xie Xiang‐Shu Cheng Qun Wang Jian‐Zhi Wang Gong‐Ping Liu 《Journal of neurochemistry》2013,124(3):388-396
Hyperhomocysteinemia (Hhcy) may induce memory deficits with β‐amyloid (Aβ) accumulation and tau hyperphosphorylation. Simultaneous supplement of folate and vitamin B12 partially restored the plasma homocysteine level and attenuated tau hyperphosphorylation, Aβ accumulation and memory impairments induced by Hhcy. However, folate and vitamin B12 treatment have no effects on Hhcy which has the methylenetetrahydrofolate reductase genotype mutation. In this study, we investigated the effects of simultaneous supplement of betaine on Alzheimer‐like pathological changes and memory deficits in hyperhomocysteinemic rats after a 2‐week induction by vena caudalis injection of homocysteine (Hcy). We found that supplementation of betaine could ameliorate the Hcy‐induced memory deficits, enhance long‐term potentiation (LTP) and increase dendritic branches numbers and the density of the dendritic spines, with up‐regulation of NR1, NR2A, synaptotagmin, synaptophysin, and phosphorylated synapsin I protein levels. Supplementation of betaine also attenuated the Hcy‐induced tau hyperphosphorylation at multiple AD‐related sites through activation protein phosphatase‐2A (PP2A) with decreased inhibitory demethylated PP2AC at Leu309 and phosphorylated PP2AC at Tyr307. In addition, supplementation of betaine also decreased Aβ production with decreased presenilin‐1 protein levels. Our data suggest that betaine could be a promising candidate for arresting Hcy‐induced AD‐like pathological changes and memory deficits. 相似文献
72.
Hong Wang Urmila Sreenivasan Da-Wei Gong Kelly A. O'Connell Erinne R. Dabkowski Peter A. Hecker Nicoleta Ionica Manige Konig Anup Mahurkar Yezhou Sun William C. Stanley Carole Sztalryd 《Journal of lipid research》2013,54(4):953-965
Presence of ectopic lipid droplets (LDs) in cardiac muscle is associated to lipotoxicity and tissue dysfunction. However, presence of LDs in heart is also observed in physiological conditions, such as when cellular energy needs and energy production from mitochondria fatty acid β-oxidation are high (fasting). This suggests that development of tissue lipotoxicity and dysfunction is not simply due to the presence of LDs in cardiac muscle but due at least in part to alterations in LD function. To examine the function of cardiac LDs, we obtained transgenic mice with heart-specific perilipin 5 (Plin5) overexpression (MHC-Plin5), a member of the perilipin protein family. Hearts from MHC-Plin5 mice expressed at least 4-fold higher levels of plin5 and exhibited a 3.5-fold increase in triglyceride content versus nontransgenic littermates. Chronic cardiac excess of LDs was found to result in mild heart dysfunction with decreased expression of peroxisome proliferator-activated receptor (PPAR)α target genes, decreased mitochondria function, and left ventricular concentric hypertrophia. Lack of more severe heart function complications may have been prevented by a strong increased expression of oxidative-induced genes via NF-E2-related factor 2 antioxidative pathway. Perilipin 5 regulates the formation and stabilization of cardiac LDs, and it promotes cardiac steatosis without major heart function impairment. 相似文献
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L. Gong B. S. Hulke T. J. Gulya S. G. Markell L. L. Qi 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2013,126(1):93-99
Sunflower production in North America has recently suffered economic losses in yield and seed quality from sunflower rust (Puccinia helianthi Schwein.) because of the increasing incidence and lack of resistance to new rust races. RHA 464, a newly released sunflower male fertility restorer line, is resistant to both of the most predominant and most virulent rust races identified in the Northern Great Plains of the USA. The gene conditioning rust resistance in RHA 464 originated from wild Helianthus annuus L., but has not been molecularly marked or determined to be independent from other rust loci. The objectives of this study are to identify molecular markers linked to the rust resistance gene and to investigate the allelism of this gene with the unmapped rust resistance genes present in HA-R6, HA-R8 and RHA 397. Virulence phenotypes of seedlings for the F2 population and F2:3 families suggested that a single dominant gene confers rust resistance in RHA 464, and this gene was designated as R 12 . Bulked segregant analysis identified ten markers polymorphic between resistant and susceptible bulks. In subsequent genetic mapping, the ten markers covered 33.4 cM of genetic distance on linkage group 11 of sunflower. A co-dominant marker CRT275-11 is the closest marker distal to R 12 with a genetic distance of 1.0 cM, while ZVG53, a dominant marker linked in the repulsion phase, is proximal to R 12 with a genetic distance of 9.6 cM. The allelism test demonstrated that R 12 is not allelic to the rust resistance genes in HA-R6, HA-R8 and RHA 397, and it is also not linked to any previously mapped rust resistance genes. Discovery of the R 12 novel rust resistance locus in sunflower and associated markers will potentially support the molecular marker-assisted introgression and pyramiding of R 12 into sunflower breeding lines. 相似文献
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Citrus is the most important tree fruit crop in the world. However, citrus production is affected by both biotic and abiotic stresses, including drought, extreme temperature, salinity, citrus canker, citrus tristeza virus, and Huanglongbing (or citrus greening), among others. These stresses can severely influence growth and development of both rootstocks and/or scions of citrus trees, thus reducing both fruit production and fruit quality. Modern advances in the tools of plant biotechnology and advances in genomics play important roles in understanding how citrus crops can cope with diseases and adverse environmental conditions. Within the last decades, much progress has been made in identifying and cloning of genes involved in resistance to biotic and abiotic stresses as well in genetic transformation of Citrus and its related genera, such as Poncirus trifoliata and Fortunella spp. In this review, we will provide information on advances and insights on genetic transformation protocols as well as availability of characterized genes involved in resistance to both abiotic and biotic stresses. This will be followed with a discussion on perspectives of future developments in this field. 相似文献
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Although molecular dynamics simulations can be accelerated by more than an order of magnitude by implicitly describing the influence of the solvent with a continuum model, most currently available implicit solvent simulations cannot robustly simulate the structure and dynamics of nucleic acids. The difficulties become exacerbated especially for RNAs, suggesting the presence of serious physical flaws in the prior continuum models for the influence of the solvent and counter ions on the nucleic acids. We present a novel, to our knowledge, implicit solvent model for simulating nucleic acids by combining the Langevin–Debye model and the Poisson–Boltzmann equation to provide a better estimate of the electrostatic screening of both the water and counter ions. Tests of the model involve comparisons of implicit and explicit solvent simulations for three RNA targets with 20, 29, and 75 nucleotides. The model provides reasonable agreement with explicit solvent simulations, and directions for future improvement are noted. 相似文献
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Leyi Gong Xiaochun Han Tania Silva Yun-Chou Tan Bindu Goyal Parch Tivitmahaisoon Alejandra Trejo Wylie Palmer Heather Hogg Alam Jahagir Muzaffar Alam Paul Wagner Karin Stein Lubov Filonova Brad Loe Ferenc Makra David Rotstein Lubica Rapatova David Goldstein 《Bioorganic & medicinal chemistry letters》2013,23(12):3565-3569
A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for JNK1 and 20 nM for JNK2, with greater than 40-fold selectivity against other kinases with good physicochemical and pharmacokinetic properties. 相似文献