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61.
The evolutionary rate of mitochondrial DNA (mtDNA) is highly variable across lineages in animals, and particularly in mammals. This variation has been interpreted as reflecting variations in metabolic rate: mitochondrial respiratory activity would tend to generate mutagenic agents, thus increasing the mutation rate. Here we review recent evidence suggesting that a direct, mechanical effect of species metabolic rate on mtDNA evolutionary rate is unlikely. We suggest that natural selection could act to reduce the (somatic) mtDNA mutation rate in long-lived species, in agreement with the mitochondrial theory of ageing.  相似文献   
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A series of 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives was synthesized and their activity screened in vitro against Staphylococcus aureus, Trypanosoma cruzi, and Candida albicans. The bioactivity was expressed as minimum inhibitory concentration (MIC) for S. aureus strains, and as fifty-percent inhibitory concentration (IC(50)) of parasite population growth for T. cruzi. A molecular modeling approach was performed to establish qualitative relationships regarding the biological data and the compounds' physicochemical properties. The 5-(4-OC(4)H(9)Ph, 5l), and 5-(4-CO(2)CH(3)Ph, 5o) derivatives were the most active compounds for S. aureus ATCC 25923 (MIC=1.95-1.25 μg/mL) and T. cruzi (IC(50)=7.91 μM), respectively. Also, a preliminary evaluation against C. albicans involving some compounds was performed and the 5-(4-CH(3)Ph, 5e) derivative was the most active compound (MIC=3.28-2.95 μg/mL). In this preliminary study, all synthesized 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives were active against all microorganisms tested.  相似文献   
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Mycoplasmas contain glycoglycerolipids in their plasma membrane as key structural components involved in bilayer properties and stability. A membrane-associated glycosyltransferase (GT), GT MG517, has been identified in Mycoplasma genitalium, which sequentially produces monoglycosyl- and diglycosyldiacylglycerols. When recombinantly expressed in Escherichia coli, the enzyme was functional in vivo and yielded membrane glycolipids from which Glcβ1,6GlcβDAG was identified as the main product. A chaperone co-expression system and extraction with CHAPS detergent afforded soluble protein that was purified by affinity chromatography. GT MG517 transfers glucosyl and galactosyl residues from UDP-Glc and UDP-Gal to dioleoylglycerol (DOG) acceptor to form the corresponding β-glycosyl-DOG, which then acts as acceptor to give β-diglycosyl-DOG products. The enzyme (GT2 family) follows Michaelis-Menten kinetics. k(cat) is about 5-fold higher for UDP-Gal with either DOG or monoglucosyldioleoylglycerol acceptors, but it shows better binding for UDP-Glc than UDP-Gal, as reflected by the lower K(m), which results in similar k(cat)/K(m) values for both donors. Although sequentially adding glycosyl residues with β-1,6 connectivity, the first glycosyltransferase activity (to DOG) is about 1 order of magnitude higher than the second (to monoglucosyldioleoylglycerol). Because the ratio between the non-bilayer-forming monoglycosyldiacylglycerols and the bilayer-prone diglycosyldiacylglycerols contributes to regulate the properties of the plasma membrane, both synthase activities are probably regulated. Dioleoylphosphatidylglycerol (anionic phospholipid) activates the enzyme, k(cat) linearly increasing with dioleoylphosphatidylglycerol concentration. GT MG517 is shown to be encoded by an essential gene, and the addition of GT inhibitors results in cell growth inhibition. It is proposed that glycolipid synthases are potential targets for drug discovery against infections by mycoplasmas.  相似文献   
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Certain drugs or treatments that are known to affect bone quality or integrity might have side effects on the extracellular matrix of articular cartilage. We investigated the effects of vitamin D and calcium deficiency, estrogen deficiency, and hypercortisolism alone or in combination with bisphosphonates or sodium fluoride in an animal model, viz., the Göttingen miniature pig (n=29). The articular cartilage from knee joints was analyzed for its content of glycosaminoglycans (GAGs, as macromolecules responsible for the elasticity of articular cartilage) by a spectrometric method with dimethylene blue chloride. In cryo- or paraffin sections, alkaline phosphatase (AP, as an enzyme indicating mineralization or reorganization of articular cartilage matrix) was localized by enzyme histochemistry, and positive cells were counted, whereas differently sulfated GAGs were stained histochemically. A significant decrease in GAG content was measured in ovariectomized and long-term glucocorticoid-treated animals compared with untreated animals. In the glucocorticoid/sodium fluoride group, GAGs were significantly diminished, and significantly fewer AP-positive chondrocytes were counted compared with the control. GAG content was slightly higher, and significantly more AP-positive chondrocytes were counted in short-term glucocorticoid-treated animals then in the control group. GAGs, as part of proteoglycans, are responsible for the water-storage capacity that gives articular cartilage its unique property of elasticity. Thus, ovariectomy and long-term glucocorticoid therapy, especially when combined with sodium fluoride, have detrimental effects on this tissue.This work was in part supported by Deutsche Forschungsgemeinschaft (DFG) project no. Schr 430/5–1, 5–2 and G 1289/1–1, 1–2  相似文献   
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The aim of this study was to clarify whether or not arachidonic acid metabolic disorders are caused by a substrate inavailability and whether such disorders might contribute to circulatory disturbances in the diabetic myocardium. Norepinephrine induced a decrease in the conductivity of both coronary arterial bed and myocardial microcirculation in alloxan-diabetic dogs. It was markedly (p < 0.05) attenuated both by indomethacin and acetylsalicylic acid pretreatments indicating an imbalance among the vasoactive prostanoids in diabetes. TXA2 release from the diabetic coronary rings was found to be elevated and could be normalized after the blockade of vascular adrenoceptors by phentolamine (p < 0.05). PGIZ synthesis was also enhanced by adrenergic blockade in the diabetic arterial rings. After pretreatment with l4C arachidonic acid, in order to measure substrate availability, the arachidonic acid metabolic rate was less in the diabetic coronary arteries than in healthy vessels (p < 0.05). Ten µmol/1 norepinephrine decreased arachidonic acid metabolism in the presence of prelabelled substrate in the diabetic animals, compared to an increase observed in metabolically healthy dogs. Therefore diabetes appears to diminish arachidonic acid metabolism and uptake independent of adrenoceptors and to induce an imbalance between vasoconstrictor and vasodilator cyclooxygenase products, resulting in elevated TXA2 release controlled by adrenergic mechanisms which may contribute to an impairment in myocardial microcirculation.Abbreviations 6-oxo-PGF1 6-oxo prostaglandin F1 - HPLC High Pressure Liquid Chromatograph - LAD Left Anterior Descending (coronary artery) - PGI2 Prostacyclin - TXA2 Thromboxane  相似文献   
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Lactic acid bacteria play an important role in the fermentation of different food products. During the fermentation processes, lactobacilli are confronted with many inhibitor factors. These factors by themselves or in combination can influence the growth of lactic acid bacteria and their acidification capacity. The subject of our study was to monitor with a newly developed biosensing technique how the different chemical stress factors influence the survival of lactic acid bacteria. Electrochemical optical waveguide lightmode spectroscopy combines evanescent-field optical sensing with electrochemical control of surface adsorption processes. For optical sensing, a layer of indium tin oxide served as a high refractive index waveguide and as a conductive electrode, as well. Lactobacillus plantarum 2142 suspended in Jerusalem artichoke syrup was used in the experiments. Electrochemical optical waveguide lightmode spectroscopy measurements were undertaken by using OW 2,400c indium tin oxide coated waveguide sensors (MicroVacuum, Budapest, Hungary) and were performed in a flow-injection analyzer system. The bacterial cells were adsorbed in native form without any chemical binding on the surface of the sensor by ensuring polarizing potential (1V) and were exposed to different concentration of acetic acid/Jerusalem artichoke syrup, lactic acid/Jerusalem artichoke syrup and hydrogen peroxide/Jerusalem artichoke syrup solution for 1h, respectively, and the effect on bacteria cells was monitored. Results were compared to the traditional micro-assay method, and it can be assumed that after further investigations this new technique could be used in real-time application.  相似文献   
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Duchenne muscular dystrophy (DMD) is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (1) by promoting the infiltration of BM-derived inflammatory cells; (2) by preventing the excessive deposition of fibrin; and (3) by promoting myoblast migration. Interestingly, genetic loss of the uPA receptor in mdx mice did not exacerbate muscular dystrophy in mdx mice, suggesting that uPA exerts its effects independently of its receptor. These findings underscore the importance of uPA in muscular dystrophy.  相似文献   
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