704 research outputs found

    SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2.

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    SIRT1 and SIRT3 are NAD+-dependent protein deacetylases that are evolutionarily conserved across mammals. These proteins are located in the cytoplasm/nucleus and mitochondria, respectively. Previous reports demonstrated that human SIRT1 deacetylates Acetyl-CoA Synthase 1 (AceCS1) in the cytoplasm, whereas SIRT3 deacetylates the homologous Acetyl-CoA Synthase 2 (AceCS2) in the mitochondria. We recently showed that 3-hydroxy-3-methylglutaryl CoA synthase 2 (HMGCS2) is deacetylated by SIRT3 in mitochondria, and we demonstrate here that SIRT1 deacetylates the homologous 3-hydroxy-3-methylglutaryl CoA synthase 1 (HMGCS1) in the cytoplasm. This novel pattern of substrate homology between cytoplasmic SIRT1 and mitochondrial SIRT3 suggests that considering evolutionary relationships between the sirtuins and their substrates may help to identify and understand the functions and interactions of this gene family. In this perspective, we take a first step by characterizing the evolutionary history of the sirtuins and these substrate families

    Characterization of the roles of Blt1p in fission yeast cytokinesis

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    Spatial and temporal regulation of cytokinesis is essential for cell division, yet the mechanisms that control the formation and constriction of the contractile ring are incompletely understood. In the fission yeast Schizosaccharomyces pombe proteins that contribute to the cytokinetic contractile ring accumulate during interphase in nodes—precursor structures around the equatorial cortex. During mitosis, additional proteins join these nodes, which condense to form the contractile ring. The cytokinesis protein Blt1p is unique in being present continuously in nodes from early interphase through to the contractile ring until cell separation. Blt1p was shown to stabilize interphase nodes, but its functions later in mitosis were unclear. We use analytical ultracentrifugation to show that purified Blt1p is a tetramer. We find that Blt1p interacts physically with Sid2p and Mob1p, a protein kinase complex of the septation initiation network, and confirm known interactions with F-BAR protein Cdc15p. Contractile rings assemble normally in blt1Δ cells, but the initiation of ring constriction and completion of cell division are delayed. We find three defects that likely contribute to this delay. Without Blt1p, contractile rings recruited and retained less Sid2p/Mob1p and Clp1p phosphatase, and β-glucan synthase Bgs1p accumulated slowly at the cleavage site

    RISK MANAGEMENT FOR CHIROPRACTORS AND OSTEOPATHS: Neck Manipulation & Vertebrobasilar Stroke

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    Although rare, vertebrobasilar stroke is the best known of the possible side effects of cervical manipulation. Due to the serious sequelae that may result from cervical manipulation, chiropractors and osteopaths must take the appropriate steps to ensure the risk is minimised. This article outlines how the astute practitioner can minimise this risk. Practitioners must decide on the options for treatment of a patient with neck problems. Practitioners must also advise the patient of these options as part of an appropriate informed consent

    Computing Discrete Logarithms in an Interval

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    The discrete logarithm problem in an interval of size NN in a group GG is: Given g,hGg, h \in G and an integer N N to find an integer 0nN0 \le n \le N, if it exists, such that h=gnh = g^n. Previously the best low-storage algorithm to solve this problem was the van Oorschot and Wiener version of the Pollard kangaroo method. The heuristic average case running time of this method is (2+o(1))N(2 + o(1)) \sqrt{N} group operations. We present two new low-storage algorithms for the discrete logarithm problem in an interval of size NN. The first algorithm is based on the Pollard kangaroo method, but uses 4 kangaroos instead of the usual two. We explain why this algorithm has heuristic average case expected running time of (1.715+o(1))N(1.715 + o(1)) \sqrt{N} group operations. The second algorithm is based on the Gaudry-Schost algorithm and the ideas of our first algorithm. We explain why this algorithm has heuristic average case expected running time of (1.661+o(1))N(1.661 + o(1)) \sqrt{N} group operations. We give experimental results that show that the methods do work close to that predicted by the theoretical analysis. This is a revised version since the published paper that contains a corrected proof of Theorem 6 (the statement of Theorem 6 is unchanged). We thank Ravi Montenegro for pointing out the errors

    Risk Management for Chiropractors and Osteopaths. Informed consent: A Common Law Requirement

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    Obtaining the informed consent of a patient before undertaking chiropractic or osteopathic treatment is a common law requirement in Australia. This paper outlines the essential elements of informed consent and provides some practice tips on streamlining the process

    RISK MANAGEMENT FOR CHIROPRACTORS AND OSTEOPATHS: Imaging Guidelines for Conditions Commonly Seen in Practice

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    This article is the second in a series of articles dealing with risk management in the practise of chiropractic and osteopathy, prepared by the COCA Risk Management Subcommittee
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