Is acetylation a metabolic rheostat that regulates skeletal muscle insulin action?

Skeletal muscle insulin resistance, which increases the risk for developing various metabolic diseases, including type 2 diabetes, is a common metabolic disorder in obesity and aging. If potential treatments are to be developed to treat insulin resistance, then it is important to fully understand insulin signaling and glucose metabolism. While recent large-scale "omics" studies have revealed the acetylome to be comparable in size to the phosphorylome, the acetylation of insulin signaling proteins and its functional relevance to insulin-stimulated glucose transport and glucose metabolism is not fully understood. In this Mini Review we discuss the acetylation status of proteins involved in the insulin signaling pathway and review their potential effect on, and relevance to, insulin action in skeletal muscle

09061 Abstracts Collection -- Combinatorial Scientific Computing

From 01.02.2009 to 06.02.2009, the Dagstuhl Seminar 09061 ``Combinatorial Scientific Computing \u27\u27 was held in Schloss Dagstuhl -- Leibniz Center for Informatics. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available

Children's emergent relations of equivalence using stimuli with opposite verbal labels: Exclusion and minimal training conditions

The present study examined different conditions under which exclusion responding in conditional discrimination tasks would generate emergent equivalence relations in young children based on shared relationships with verbal labels. Both visual stimuli (Sets A, B, C, and D) and auditory stimuli (spoken words, Set N: N1 "correct"; N2: "incorrect") were used. Following a pilot study, three experiments were conducted, each involving eight preschool children. These experiments systematically investigated under which conditions responding by exclusion (i.e., responding away from a designated S - comparison in a matching to sample context) would generate sufficiently stable sample-S + relations for arbitrary stimulus classes to establish. The results showed that young children's exclusion responding under test conditions will only contribute to arbitrary stimulus class formation and expansion when training has already established two arbitrary stimulus classes involving at least two stimuli each. For young children to demonstrate emergent conditional discrimination performances that are indicative of the formation of equivalence relations, it is necessary to have training and/or reinforced exposure to both S + and S - control elements required for deriving the appropriate emergent relations with at least two conditional relations involving different samples. These findings not only contribute to existing research and theory on the conditions under which exclusion responding may contribute to fundamental language and learning processes, they also contribute to the experimental predictability of emergent conditional matching behaviours in preschool children by further unravelling the conditions under which emergent matching based on exclusion generates arbitrary conditional relations of equivalence. </p

Improved insulin sensitivity after weight loss and exercise training is mediated by a reduction in plasma fatty acid mobilization, not enhanced oxidative capacity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65588/1/jphysiol.2009.175489.pd

Expression of a large coding sequence: Gene therapy vectors for Ataxia Telangiectasia

Ataxia telangiectasia is a monogenetic disorder caused by mutations in the ATM gene. Its encoded protein kinase ATM plays a fundamental role in DNA repair of double strand breaks (DSBs). Impaired function of this kinase leads to a multisystemic disorder including immunodeficiency, progressive cerebellar degeneration, radiation sensitivity, dilated blood vessels, premature aging and a predisposition to cancer. Since allogenic hematopoietic stem cell (HSC) transplantation improved disease outcome, gene therapy based on autologous HSCs is an alternative promising concept. However, due to the large cDNA of ATM (9.2 kb), efficient packaging of retroviral particles and sufficient transduction of HSCs remains challenging.We generated lentiviral, gammaretroviral and foamy viral vectors with a GFP.F2A.Atm fusion or a GFP transgene and systematically compared transduction efficiencies. Vector titers dropped with increasing transgene size, but despite their described limited packaging capacity, we were able to produce lentiviral and gammaretroviral particles. The reduction in titers could not be explained by impaired packaging of the viral genomes, but the main differences occurred after transduction. Finally, after transduction of Atm-deficient (ATM-KO) murine fibroblasts with the lentiviral vector expressing Atm, we could show the expression of ATM protein which phosphorylated its downstream substrates (pKap1 and p-p53)

Flight Results of the InflateSail Spacecraft and Future Applications of DragSails

The InflateSail CubeSat, designed and built at the Surrey Space Centre (SSC) at the University of Surrey, UK, for the Von Karman Institute (VKI), Belgium, is one of the technology demonstrators for the QB50 programme. The 3.2 kilogram InflateSail is “3U” in size and is equipped with a 1 metre long inflatable boom and a 10 square metre deployable drag sail. InflateSail\u27s primary goal is to demonstrate the effectiveness of using a drag sail in Low Earth Orbit (LEO) to dramatically increase the rate at which satellites lose altitude and re-enter the Earth\u27s atmosphere. InflateSail was launched on Friday 23rd June 2017 into a 505km Sun-synchronous orbit. Shortly after the satellite was inserted into its orbit, the satellite booted up and automatically started its successful deployment sequence and quickly started its decent. The spacecraft exhibited varying dynamic modes, capturing in-situ attitude data throughout the mission lifetime. The InflateSail spacecraft re-entered 72 days after launch. This paper describes the spacecraft and payload, and analyses the effect of payload deployment on its orbital trajectory. The boom/drag-sail technology developed by SSC will next be used on the RemoveDebris mission, which will demonstrate the applicability of the system to microsat deorbiting

A Ditopic Phosphane-decorated Benzenedithiol as Scaffold for Di- and Trinuclear Complexes of Group-10 Metals and Gold

The ability of 3-(diphenylphosphinomethyl)-benzene-1,2-dithiol (pbdtH(2)) to act as ditopic ligand was probed in reactions with selected group-10-metal complexes. Reactions with [(cod)PdCl2] afforded a mixture of products identified as [Pd(pbdtH)(2)], [Pd-2(mu(2)-pbdt)(2)] and [Pd-3(mu(2)-pbdt)(2)Cl-2]. The polynuclear complexes could be isolated after suitably adjusting the reaction conditions, and heating of a mixture in a microwave reactor effected partial conversion into a further complex [Pd-3(mu(2)-pbdt)(3)]. Reaction of pbdtH(2) with [Ni(H2O)(6)Cl-2] gave rise to a complex [Ni-2(mu(2)-pbdt)(2)], which was shown to undergo two reversible 1e(-)-reduction steps. Reaction of [Pd(pbdtH)(2)] with [Au(PPh3)Cl] afforded heterotrinuclear [PdAu2(mu(2)-pbdt)(2)(PPh3)]. All complexes were characterized by analytical, spectroscopic and single-crystal X-ray diffraction studies. Their molecular structures confirm the ability of the pbdt(2-) unit to support simultaneous P,S- and S,S-chelating coordination to two metal centers.Peer reviewe

Anabolic and catabolic responses of human articular chondrocytes to varying oxygen percentages

Oxygen is a critical parameter proposed to modulate the functions of chondrocytes ex-vivo as well as in damaged joints. This article investigates the effect of low (more physiological) oxygen percentage on the biosynthetic and catabolic activity of human articular chondrocytes (HAC) at different phases of in vitro culture

Paraspinal Muscle Health is Related to Fibrogenic, Adipogenic, and Myogenic Gene Expression in Patients with Lumbar Spine Pathology

BACKGROUND Lumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology. METHODS Multifidus muscle biopsies were obtained from patients (n = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality. RESULTS Relationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI (r = -0.346, p = 0.018, and r = 0.386, p = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area (r = 0.388, p = 0.045). CONCLUSION Fibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population