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  1. Article ; Online: Chromatin proteins

    Karen T Smith / Jerry L Workman

    PLoS Biology, Vol 10, Iss 7, p e

    key responders to stress.

    2012  Volume 1001371

    Abstract: Environments can be ever-changing and stresses are commonplace. In order for organisms to survive, they need to be able to respond to change and adapt to new conditions. Fortunately, many organisms have systems in place that enable dynamic adaptation to ... ...

    Abstract Environments can be ever-changing and stresses are commonplace. In order for organisms to survive, they need to be able to respond to change and adapt to new conditions. Fortunately, many organisms have systems in place that enable dynamic adaptation to immediate stresses and changes within the environment. Much of this cellular response is coordinated by modulating the structure and accessibility of the genome. In eukaryotic cells, the genome is packaged and rolled up by histone proteins to create a series of DNA/histone core structures known as nucleosomes; these are further condensed into chromatin. The degree and nature of the condensation can in turn determine which genes are transcribed. Histones can be modified chemically by a large number of proteins that are thereby responsible for dynamic changes in gene expression. In this Primer we discuss findings from a study published in this issue of PLoS Biology by Weiner et al. that highlight how chromatin structure and chromatin binding proteins alter transcription in response to environmental changes and stresses. Their study reveals the importance of chromatin in mediating the speed and amplitude of stress responses in cells and suggests that chromatin is a critically important component of the cellular response to stress.
    Keywords Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Recruitment strategies for sarcopenia trials

    Miles D. Witham / Marcus Achison / Terry J. Aspray / Alison Avenell / Margaret M. Band / Peter T. Donnan / Jacob George / Adrian Hapca / Cheryl Hume / Paul Kemp / Kristina Pilvinyte / Avan A. Sayer / Karen T. Smith / Allan D. Struthers / Deepa Sumukadas

    JCSM Rapid Communications, Vol 4, Iss 2, Pp 93-

    lessons from the LACE randomized controlled trial

    2021  Volume 102

    Abstract: Abstract Background Sarcopenia is rarely diagnosed and is not recorded electronically in routine clinical care, posing challenges to trial recruitment. We describe the performance of four components of a strategy to efficiently recruit participants with ... ...

    Abstract Abstract Background Sarcopenia is rarely diagnosed and is not recorded electronically in routine clinical care, posing challenges to trial recruitment. We describe the performance of four components of a strategy to efficiently recruit participants with sarcopenia to a trial of perindopril and/or leucine for sarcopenia: primary care vs. hospital recruitment, a comparison of central vs. local telephone pre‐screening, performance of a questionnaire on physical function conducted as part of the pre‐screening telephone call, and performance of bioimpedance measurement to identify low muscle mass. Methods Hospital‐based recruitment took place through inpatient and outpatient geriatric medicine services. Local research nurses reviewed medical notes and approached potentially eligible patients. Primary care recruitment reviewed primary care lists from collaborating practices, sending mailshots to patients aged 70 and over who were not taking angiotensin‐converting enzyme inhibitors. Telephone pre‐screening was conducted either by research nurses at each site or centrally by Tayside Clinical Trials Unit. The 10‐point SARC‐F questionnaire was used for pre‐screening. De‐identified recruitment information was held on a central electronic tracking system and analysed using SPSS. Bioimpedance was measured using the Akern BIA 101 system, with the Sergi equation used to estimate lean mass. Results Fourteen UK sites recruited to the trial. The 1202 sets of notes in hospital‐based care were reviewed at these sites; 7 participants (0.6% of total notes screened) were randomized. From primary care, 13 808 invitations were sent; 138 (1.0% of total invited) were randomized. 633/2987 primary care respondents were pre‐screened centrally; the mean number of calls per respondent was 2.3. For 10 sites where central and local pre‐screening could be compared, the conversion rate from pre‐screening to randomization was 18/588 (3.1%) for centralized calls, compared with 73/1814 (4.0%) for local pre‐screening calls (P = 0.29). A weak ...
    Keywords Sarcopenia ; Randomized controlled trial ; Screening ; Recruitment ; Body composition ; Internal medicine ; RC31-1245
    Subject code 360
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial)

    Margaret M. Band / Deepa Sumukadas / Allan D. Struthers / Alison Avenell / Peter T. Donnan / Paul R. Kemp / Karen T. Smith / Cheryl L. Hume / Adrian Hapca / Miles D. Witham

    Trials, Vol 19, Iss 1, Pp 1-

    study protocol for a randomised controlled trial

    2018  Volume 11

    Abstract: Abstract Background Sarcopenia (the age-related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing ... ...

    Abstract Abstract Background Sarcopenia (the age-related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exist from small studies for both interventions, but neither has yet been tested in adequately powered randomised trials in patients with sarcopenia. Methods Leucine and ACE inhibitors in sarcopenia (LACE) is a multicentre, masked, placebo-controlled, 2 × 2 factorial randomised trial evaluating the efficacy of leucine and perindopril (angiotensin converting enzyme inhibitor (ACEi)) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on bioimpedance analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual-energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including microRNAs, neurohormones, ...
    Keywords Older people ; Perindopril ; Leucine ; Sarcopenia ; Physical function ; Quality of life ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia

    Christos Rossios / Tufail Bashir / Marcus Achison / Simon Adamson / Asangaedem Akpan / Terry Aspray / Alison Avenell / Margaret M Band / Louise A Burton / Vera Cvoro / Peter T Donnan / Gordon W Duncan / Jacob George / Adam L Gordon / Celia L Gregson / Adrian Hapca / Cheryl Hume / Thomas A Jackson / Simon Kerr /
    Alixe Kilgour / Tahir Masud / Andrew McKenzie / Emma McKenzie / Harnish Patel / Kristina Pilvinyte / Helen C Roberts / Avan A Sayer / Karen T Smith / Roy L Soiza / Claire J Steves / Allan D Struthers / Divya Tiwari / Julie Whitney / Miles D Witham / Paul R Kemp

    PLoS ONE, Vol 18, Iss 10, p e

    Results from the LACE trial.

    2023  Volume 0292402

    Abstract: Background Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to ... ...

    Abstract Background Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study. Methods Sarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables. Results Allele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial

    Tufail Bashir / Marcus Achison / Simon Adamson / Asangaedem Akpan / Terry Aspray / Alison Avenell / Margaret M. Band / Louise A. Burton / Vera Cvoro / Peter T. Donnan / Gordon W. Duncan / Jacob George / Adam L. Gordon / Celia L. Gregson / Adrian Hapca / Cheryl Hume / Thomas A. Jackson / Simon Kerr / Alixe Kilgour /
    Tahir Masud / Andrew McKenzie / Emma McKenzie / Harnish Patel / Kristina Pilvinyte / Helen C. Roberts / Christos Rossios / Avan A. Sayer / Karen T. Smith / Roy L. Soiza / Claire J. Steves / Allan D. Struthers / Divya Tiwari / Julie Whitney / Miles D. Witham / Paul R. Kemp

    PLoS ONE, Vol 18, Iss

    2023  Volume 11

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

    Tufail Bashir / Marcus Achison / Simon Adamson / Asangaedem Akpan / Terry Aspray / Alison Avenell / Margaret M Band / Louise A Burton / Vera Cvoro / Peter T Donnan / Gordon W Duncan / Jacob George / Adam L Gordon / Celia L Gregson / Adrian Hapca / Cheryl Hume / Thomas A Jackson / Simon Kerr / Alixe Kilgour /
    Tahir Masud / Andrew McKenzie / Emma McKenzie / Harnish Patel / Kristina Pilvinyte / Helen C Roberts / Christos Rossios / Avan A Sayer / Karen T Smith / Roy L Soiza / Claire J Steves / Allan D Struthers / Divya Tiwari / Julie Whitney / Miles D Witham / Paul R Kemp

    PLoS ONE, Vol 18, Iss 11, p e

    2023  Volume 0294330

    Abstract: Background Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle ... ...

    Abstract Background Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. Methods We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. Results Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. Conclusion These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.
    Keywords Medicine ; R ; Science ; Q
    Subject code 796
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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