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961.
Haiyan Xia Yun Cao Xiaoman Dai Zvonimir Marelja Di Zhou Ran Mo Sahar Al-Mahdawi Mark A. Pook Silke Leimkühler Tracey A. Rouault Kuanyu Li 《PloS one》2012,7(10)
Friedreich ataxia (FRDA) is an inherited neurodegenerative disease caused by frataxin (FXN) deficiency. The nervous system and heart are the most severely affected tissues. However, highly mitochondria-dependent tissues, such as kidney and liver, are not obviously affected, although the abundance of FXN is normally high in these tissues. In this study we have revealed two novel FXN isoforms (II and III), which are specifically expressed in affected cerebellum and heart tissues, respectively, and are functional in vitro and in vivo. Increasing the abundance of the heart-specific isoform III significantly increased the mitochondrial aconitase activity, while over-expression of the cerebellum-specific isoform II protected against oxidative damage of Fe-S cluster-containing aconitase. Further, we observed that the protein level of isoform III decreased in FRDA patient heart, while the mRNA level of isoform II decreased more in FRDA patient cerebellum compared to total FXN mRNA. Our novel findings are highly relevant to understanding the mechanism of tissue-specific pathology in FRDA. 相似文献
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964.
Construction of recombinant DNA from multiple fragments is widely required in molecular biology, especially for synthetic biology purposes. Here we describe a new method, successive hybridization assembling (SHA) which can rapidly do this in a single reaction in vitro. In SHA, DNA fragments are prepared to overlap one after another, so after simple denaturation-renaturation treatment they hybridize in a successive manner and thereby assemble into a recombinant molecule. In contrast to traditional methods, SHA eliminates the need for restriction enzymes, DNA ligases and recombinases, and is sequence-independent. We first demonstrated its feasibility by constructing plasmids from 4, 6 and 8 fragments with high efficiencies, and then applied it to constructing a customized vector and two artificial pathways. As SHA is robust, easy to use and can tolerate repeat sequences, we expect it to be a powerful tool in synthetic biology. 相似文献
965.
Yunxue Guo Yaosheng Chen Yun Zhang Yue Zhang Luxi Chen Delin Mo 《International journal of biological sciences》2012,8(10):1408-1417
Generally, most miRNAs that were up-regulated during differentiation promoted adipogenesis, but our research indicated that up-regulation of miR-145 in porcine preadipocytes did not promote but inhibit adipogenesis. In this study, miR-145 was significantly up-regulated during porcine dedifferentiated fat (DFAT) cells differentiation. In miR-145 overexpressed DFAT cells, adipogenesis was inhibited and triglycerides accumulation was decreased after hormone stimulation (P<0.05). Furthermore, up-regulation of miR-145 expression repressed induction of mRNA levels of adipogenic markers, such as CCAAT/enhancer-binding protein α (C/EBPα), and peroxisome proliferator-activated receptor γ2 (PPARγ2). These effects caused by miR-145 overexpression were mediated by Insulin receptor substrate 1 (IRS1) as a mechanism. These data suggested that induced miR-145 expression during differentiation could inhibit adipogenesis by targeting IRS1, and miR-145 may be novel agent for adipose tissue engineering. 相似文献
966.
Shengrong Liu Qingping Wu Jumei Zhang Shuping Mo 《Biotechnology and Bioprocess Engineering》2012,17(6):1205-1212
?-Poly-l-lysine (?-PL), produced by Streptomyces or Kitasatospora strains, is a homo-poly-amino acid of l-lysine, which is used as a safe food preservative. In this study, the effects of l-lysine and its isomer, d-lysine, on ?-PL biosynthesis and their metabolites by the ?-PL-producing strain Streptomyces ahygroscopicus GIM8 were determined. The results indicated that l-lysine added into the fermentation medium in the production phase mainly served as a precursor for ?-PL biosynthesis during the flask culture phase, leading to greater ?-PL production. At an optimum level of 3 mM l-lysine, a ?-PL yield of 1.16 g/L was attained, with a 41.4% increment relative to the control of 0.78 g/L. Regarding d-lysine, the production of ?-PL increased by increasing its concentrations up to 6 mM in the initial fermentation medium. Interestingly, ?-PL production (1.20 g/L) with the addition of 3 mM d-lysine into the initial fermentation medium in flasks was higher than that of the initial addition of 3 mM L-lysine (1.06 g/L). The mechanism by which d-lysine improves ?-PL biosynthesis involves its utilization that leads to greater biomass. After S. ahygroscopicus GIM8 was cultivated in the defined medium with L-lysine, several key metabolites, including 5-aminovalerate, pipecolate, and l-2-aminoadipate formed in the cells, whereas only l-2-aminoadipate was observed after d-lysine metabolism. This result indicates that l-lysine and d-lysine undergo different metabolic pathways in the cells. Undoubtedly, the results of this study are expected to aid the understanding of ?-PL biosynthesis and serve as reference for the formulation of an alternative approach to improve ?-PL productivity using l-lysine as an additional substrate in the fermentation medium. 相似文献
967.
The use of antiretroviral therapy has proven to be remarkably effective in controlling the progression of human immunodeficiency virus (HIV) infection and prolonging patient's survival. Therapy however may fail and therefore these benefits can be compromised by the emergence of HIV strains that are resistant to the therapy. In view of these facts, the question of finding the reason for which drug-resistant strains emerge during therapy has become a worldwide problem of great interest. This paper presents a deterministic HIV-1 model to examine the mechanisms underlying the emergence of drug-resistance during therapy. The aim of this study is to determine whether, and how fast, antiretroviral therapy may determine the emergence of drug resistance by calculating the basic reproductive numbers. The existence, feasibility and local stability of the equilibriums are also analyzed. By performing numerical simulations we show that Hopf bifurcation may occur. The model suggests that the individuals with drug-resistant infection may play an important role in the epidemic of HIV. 相似文献
968.
969.
Impaired apoptosis in immune effector cells such as macrophages has been implicated in the development of autoimmune disease by promoting the breakdown of self-tolerance and the sustained production of cytotoxic molecules. Macrophages from nonobese diabetic (NOD) mouse, an animal model of human autoimmune diabetes, exhibit several defects that are causally linked to the onset and progression of the disease. In this context, we investigated whether NOD macrophages have a defect in a cell death pathway, and if that is the case, the mechanism underlying such dysregulation of cell death. We found that NOD macrophages were resistant to treatment with a broad spectrum of cell death stimuli, triggering both apoptotic and non-apoptotic death. Through analysis of intracellular signaling pathways along with the expression of apoptosis-related proteins, we found that atypical resistance to cell death was associated with an elevated expression of anti-apoptotic Bcl-X(L) but not the NF-κB signaling pathway in NOD macrophages. Further, ABT-737, which can inhibit Bcl-X(L) function, sensitized NOD macrophages to apoptosis induced by diverse apoptotic stimuli, thus restoring sensitivity to cell death. Taken together, our results suggest a macrophage-intrinsic defect in cell death as a potential mechanism that promotes an immune attack towards pancreatic β-cells and the development of autoimmune diabetes in NOD mice. 相似文献
970.
Niu J Mo Q Wang H Li M Cui J Li Z Li Z 《Biochemical and biophysical research communications》2012,422(1):80-84
Metastasis remains the primary cause of lung cancer. The molecules involved in metastasis may be candidates for new targets in the therapy of lung cancer. The MEK/ERK signaling pathway has been highlighted in a number of studies on invasiveness and metastasis. In this paper, we show that the MEK inhibitor U0126 induces flattened morphology, remodels the actin-based cytoskeleton, and potently inhibits chemotaxis and Matrigel invasion in the human lung cancer A549 cell line. Furthermore, downregulation of ERK by small interfering RNA significantly inhibits the invasion of A549 cells and induces stress fiber formation. Taken together, our findings provide the first evidence that the inhibition of invasion of lung cancer A549 cells by inhibiting MEK/ERK signaling activity is associated with remodeling of the actin cytoskeleton, suggesting a novel link between MEK/ERK signaling-mediated cell invasion and the actin-based cytoskeleton. 相似文献