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36 results on '"Clynes, Michael"'

14. Insights into the residence in lipid rafts of adenylyl cyclase AC8 regulation by capacitative calcium entry

Author

Pagano, Mario, Clynes, Michael A., Masada, Nanako, Ciruela, Antonio, Ayling, Laura-Jo, Wachten, Sebastian, and Cooper, Dermot M.F.

Subjects
Adenylate cyclase -- Properties, Calcium channels -- Properties, Biological transport, Active -- Research, Biological control systems -- Research, Biological sciences
Abstract

Adenylyl cyclases (ACs) are a family of critically important signaling molecules that are regulated by multiple pathways. Adenylyl cyclase 8 (AC8) is a [Ca.sup.2+] stimulated isoform that displays a selective regulation by capacitative [Ca.sup.2+] entry (CCE), the process whereby the entry of [Ca.sup.2+] into cells is triggered by the emptying of intracellular stores. This selectivity was believed to be achieved through the localization of AC8 in lipid raft microdomains, along with components of the CCE apparatus. In the present study, we show that an intact leucine zipper motif is required for the efficient N-linked glycosylation of AC8, and that this N-linked glycosylation is important to target AC8 into lipid rafts. Disruption of the leucine zipper by site-directed mutagenesis results in the elimination of N-glycosylated forms and their exclusion from lipid rafts. Mutants of AC8 that cannot be N-glycosylated are not demonstrably associated with rafts, although they can still be regulated by CCE; however, raft integrity is required for the regulation of these mutants. These findings suggest that raft localized proteins in addition to AC8 are needed to mediate its regulation by CCE. lipid rafts; leucine zipper; capacitative [Ca.sup.2+] entry; N-glycosylation

Published
2009

19. The epidemiology of osteoporosis

Author

Clynes, Michael A, primary, Harvey, Nicholas C, primary, Curtis, Elizabeth M, primary, Fuggle, Nicholas R, primary, Dennison, Elaine M, primary, and Cooper, Cyrus, primary

Published
2020
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23. A diagnosis of knee osteoarthritis does not predict physical activity two years later in older adults: findings from the Hertfordshire Cohort Study

Author

Clynes, Michael, Parsons, Camille, Edwards, Mark, Tobias, Jonathan H., Deere, Kevin C., Cooper, Cyrus, and Dennison, Elaine

Abstract

Osteoarthritis (OA) can negatively impact levels of physical activity (PA), although current clinical advice promotes the benefits of staying active in preventing joint degeneration. In this study, we examine how knee OA, assessed by self-report, clinical assessment and radiographic assessment, impacts upon objectively measured PA 2 years later. The study population is comprised of 114 subjects from the Hertfordshire Cohort Study (HCS). The presence of OA at the knee was determined from self-report, and clinical and radiological examination, defined according to American College of Rheumatology (ACR) criteria and Kellgren and Lawrence grading system. Two years later, Gulf Coast Data Concepts (GCDC) tri-axial accelerometers were used to measure day-to-day levels of PA. Vertical acceleration peaks over 7 days, expressed in g units, were categorised into low (0.5 ≤ g

Published
2019

30. Osteosarcopenia: where osteoporosis and sarcopenia collide.

Author

Clynes, Michael A, Gregson, Celia L, Bruyère, Olivier, Cooper, Cyrus, and Dennison, Elaine M

Subjects
*OSTEOPOROSIS prevention, *ACCIDENTAL falls, *BONE fractures, *INSTITUTIONAL care, *OSTEOPOROSIS, *SARCOPENIA, *DISEASE complications, *DISEASE risk factors, MORTALITY risk factors
Abstract

The coexistence of osteoporosis and sarcopenia has been recently considered in some groups as a syndrome termed 'osteosarcopenia'. Osteoporosis describes low bone mass and deterioration of the micro-architecture of the bone, whereas sarcopenia is the loss of muscle mass, strength and function. With an ageing population the prevalence of both conditions is likely to increase substantially over the coming decades and is associated with significant personal and societal burden. The sequelae for an individual suffering from both conditions together include a greater risk of falls, fractures, institutionalization and mortality. The aetiology of 'osteosarcopenia' is multifactorial with several factors linking muscle and bone function, including genetics, age, inflammation and obesity. Several biochemical pathways have been identified that are facilitating the development of several promising therapeutic agents, which target both muscle and bone. In the current review we outline the epidemiology, pathogenesis and clinical consequences of 'osteosarcopenia' and explore current and potential future management strategies. [ABSTRACT FROM AUTHOR]

Published
2021
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