Reduced caloric intake decreases arterial blood pressure in healthy individuals and improves endothelium-dependent vasodilation in obese and overweight individuals. The SIRT1 protein deacetylase mediates many of the effects of calorie restriction (CR) on organismal lifespan and metabolic pathways. However, the role of SIRT1 in regulating endothelium-dependent vasomotor tone is not known. Here we show that SIRT1 promotes endotheliumdependent vasodilation by targeting endothelial nitric oxide synthase (eNOS) for deacetylation. SIRT1 and eNOS colocalize and coprecipitate in endothelial cells, and SIRT1 deacetylates eNOS, stimulating eNOS activity and increasing endothelial nitric oxide (NO). SIRT1-induced increase in endothelial NO is mediated through lysines 496 and 506 in the calmodulin-binding domain of eNOS. Inhibition of SIRT1 in the endothelium of arteries inhibits endothelium-dependent vasodilation and decreases bioavailable NO. Finally, CR of mice leads to deacetylation of eNOS. Our results demonstrate that SIRT1 plays a fundamental role in regulating endothelial NO and endothelium-dependent vascular tone by deacetylating eNOS. Furthermore, our results provide a possible molecular mechanism connecting the effects of CR on the endothelium and vascular tone to SIRT1-mediated deacetylation of eNOS.calorie restriction ͉ vasorelaxation ͉ silent information regulator 2 ͉ resveratrol ͉ deacetylation C aloric restriction (CR) is a well recognized nonpharmacological approach to reducing arterial blood pressure. CR not only is capable of independently controlling blood pressure of patients with mild hypertension, but also allows a reduction in the number and dosage of medications used to treat hypertension (1, 2). CR and weight loss resulting from CR also improve endothelium-dependent vascular relaxation in obese and overweight individuals with hypertension (3, 4).In addition, CR prolongs organismal lifespan. In the budding yeast, Saccharomyces cerevisiae, aging of replicating cells is determined by the SIR2 gene (5). Retardation of yeast aging by CR depends on the product of this gene, Sir2 (silent information regulator 2), a class III NAD-dependent histone deacetylase. The mammalian ortholog of Sir2, SIRTUIN 1 (SIRT1), targets histones and many nonhistone proteins (6-10). Resveratrol, a plant polyphenol that stimulates SIRT1 activity (11), activates endothelial nitric oxide synthase (eNOS) (12), improves endothelial function, prevents elevation in blood pressure, and restores vascular eNOS activity in animal models of endothelial dysfunction (13). Hypothesizing that the effects of CR and resveratrol on vascular function are mediated, in part, by SIRT1, we investigated the role of SIRT1 in regulating eNOS activity and endothelium-dependent vascular tone. Results and DiscussionTo determine whether SIRT1 plays an important role in regulating endothelium-dependent vascular tone, vasomotor function of rat aortic rings, in which wild-type SIRT1 or a dominant negative SIRT1 mutant (to inhibit endogenous SIRT1) was adenovi...

Hydrodeoxygenation (HDO) using heterogeneous catalysts has received considerable attention as a way of converting biomass-derived oxygenates into renewable fuels and chemicals.

The electrochemical hydrogenation and hydrogenolysis (ECH) of furfural (FF) on a copper electrocatalyst has been investigated to produce biofuels and fine chemicals in an H-type batch reactor at room temperature. We report a systematic study of ECH of FF to gain a better understanding of the relationships between products and reaction conditions: current density, electrolyte, and cosolvent ratio in acidic solutions. The acidity of electrolytes had the most significant impact on the product distribution. Mildly acidic electrolytes mainly produced furfuryl alcohol (FA), while strongly acidic electrolytes produced both 2-methyl furan (MF) and FA. Also, the yield of products depended on the current density and reaction time when equivalent charge was transferred to the reaction. However, the mole balance accounting for FF, MF, and FA was not higher than 70% in any reaction condition when the theoretical amount of electrons for complete MF production from FF (e–/FF = 4) was transferred to the system. The investigation of nonelectrochemical homogeneous side reactions suggested that the low mole balance in a mildly acidic electrolyte may be from the charge transfer promoted side reactions on the copper electrode. On the other hand, it was shown that the low mole balance in strongly acidic electrolytes was due to homogeneous side reactions.

Apurinic/apyrimidinic endonuclease-1 (APE1) is an essential enzyme in the base excision repair (BER) pathway. Here, we show that APE1 is a target of the SIRTUIN1 (SIRT1) protein deacetylase. SIRT1 associates with APE1, and this association is increased with genotoxic stress. SIRT1 deacetylates APE1 in vitro and in vivo targeting lysines 6 and 7. Genotoxic insults stimulate lysine acetylation of APE1 which is antagonized by transcriptional upregulation of SIRT1. Knockdown of SIRT1 increases cellular abasic DNA content, sensitizing cells to death induced by genotoxic stress, and this vulnerability is rescued by overexpression of APE1. Activation of SIRT1 with resveratrol promotes binding of APE1 to the BER protein X-ray cross-complementing-1 (XRCC1), while inhibition of SIRT1 with nicotinamide (NAM) decreases this interaction. Genotoxic insult also increases binding of APE1 to XRCC1, and this increase is suppressed by NAM or knockdown of SIRT1. Finally, resveratrol increases APE activity in XRCC1-associated protein complexes, while NAM or knockdown of SIRT1 suppresses this DNA repair activity. These findings identify APE1 as a novel protein target of SIRT1, and suggest that SIRT1 plays a vital role in maintaining genomic integrity through regulation of the BER pathway.

A moderately halophilic actinomycete, designated HA-9 T , was isolated from a saltern in Kunsan, Republic of Korea, and was the subject of polyphasic identification. Analysis of 16S rDNA indicated that the isolate belonged to the genus Nocardiopsis, but differed genetically from other Nocardiopsis species. Strain HA-9T contained meso-diaminopimelic acid, no diagnostic sugars, hexaor octa-hydrogenated menaquinones with 10 isoprene units, straight-chain saturated or monounsaturated, iso-, anteiso-, 10-methyl branched fatty acids with 13-18 carbons and type III phospholipids. All of these characters consistently assign the isolate to the genus Nocardiopsis. All of the validly described Nocardiopsis species, including moderately halophilic Nocardiopsis halophila, can be differentiated from the saltern isolate using morphological and physiological traits. On the basis of polyphasic evidence, the name Nocardiopsis kunsanensis sp. nov. is proposed for strain HA-9 T (l KCTC 9831 T ), which is designated the type strain.Keywords : Nocardiopsis kunsanensis sp. nov., polyphasic taxonomy, 16S rDNA sequencing INTRODUCTIONThe genus Nocardiopsis was created by Meyer (1976) to harbour Actinomadura dassonvillei on the basis of morphological and chemotaxonomic properties. The genus currently comprises seven validly described species, namely Nocardiopsis alba, Nocardiopsis dassonvillei, Nocardiopsis halophila, Nocardiopsis listeri, Nocardiopsis lucentensis, Nocardiopsis prasina and Nocardiopsis synnemataformans Kroppenstedt, 1992 ;Yassin et al., 1993Yassin et al., , 1997. The members of Nocardiopsis are phylogenetically coherent and form a monophyletic clade that is equated with the family Nocardiopsaceae (Rainey et al., 1996). None of the Nocardiopsis species to date have been reported as halophilic except N. halophila, which can grow best at 5-15 % NaCl . In this study, we report the results of polyphasic identification of an actinomycete strain, designated HA-9 T , isolated from a saltern sample. optimally in medium containing 10 % NaCl and showed properties consistent with its classification in the genus Nocardiopsis Meyer 1976 as a new species, of which the name Nocardiopsis kunsanensis sp. nov. is proposed. METHODSBacterial strains. The saltern sample was collected from Kunsan, Republic of Korea. Bacterial strains were isolated by plating serially diluted samples onto Bennett medium based on seawater (2 g glucose, 1 g yeast extract, 1 g malt extract, 2 g peptone, 20 g agar, 1 l aged seawater, pH 7n2). After incubating at 30 mC for 2 weeks, a visible colony, designated HA-9 T , was transferred and subcultured until pure culture was obtained. Complex medium (CM ; 7n5 g Casamino acids, 10 g yeast extract, 3 g sodium citrate, 10 g magnesium sulfate, 2 g potassium chloride, 1 ml 4n98 % iron sulfate, 100 g NaCl, 1 l distilled water, pH 7n4) was used for growing strain HA-9 T and Nocardiopsis halophila KCTC 9825 T (l A.S.4.1195). The strain was maintained as a glycerol suspension (20 %, w\v) at k80 mC. J. Chun and others colonies, ...

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Furfural (FF) is obtained from lignocellulosic biomass and is a promising platform chemical that can produce valuable chemicals including furfuryl alcohol (FA) and 2‐methylfuran (MF). We synthesized both FA and MF using electrochemical hydrogenation and hydrogenolysis (ECH) of FF in acidic electrolyte using a Cu electrode. We investigated the role of concurrent side reactions including the hydrogen evolution reaction (HER) and polymerization of furanic compounds during ECH, as well as the potential dependence of the reaction pathway for ECH of FF. As the magnitude of applied potential increased, both ECH and HER were promoted. Polymerization of furanic compounds was diminished by lowering the initial concentration of FF, but at a cost of increased the HER activity. In contrast, higher concentrations of FF suppressed the HER, though excessive initial concentrations of FF resulted in lowering the activity of both ECH and the HER due to a polymeric film being formed on the electrode. The highest mole balances and faradaic efficiencies towards ECH were achieved at −0.5 V, though at the expense of lower conversions of FF than those obtained at greater overpotentials. We also found that the ECH of FF followed two parallel reactions to independently produce FA and MF on Cu in 0.5 m H2SO4 regardless of the applied potential.

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