4,522 research outputs found

    The role of myokines in muscle health and disease.

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    This article updates on the concept that muscle-derived cytokines (myokines) play important roles in muscle health and disease.Interleukin-6 (IL-6) is released from normal skeletal muscle in response to exercise, mediating both anti-inflammatory responses and metabolic adaptations, actions contradictory to the prevailing view that IL-6 is a proinflammatory cytokine that is inducing and propagating disease. The anti-inflammatory effects of IL-6 result from its trans-membrane signalling capability, via membrane-bound receptors, whereas its proinflammatory effects result instead from signalling via the soluble IL-6 receptor and gp130. IL-15 is elevated following exercise, promoting muscle fibre hypertrophy in some circumstances, while inducing fibre apoptosis in others. This functional divergence appears because of variations in expression of IL-15 receptor isoforms. Decorin, a recently described myokine, is also elevated following exercise in normal muscle, and promotes muscle fibre hypertrophy by competitively binding to, and thus inhibiting, myostatin, a negative regulator of muscle protein synthesis. Exercise-induced myostatin downregulation thus promotes muscle fibre growth, prompting recent trials of a biological myostatin inhibitor in inclusion body myositis.Myokines appear to exert diverse beneficial effects, though their mechanistic roles in myositis and other myopathologies remain poorly understood

    Blood methylomic signatures of presymptomatic dementia in elderly subjects with type 2 diabetes mellitus

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    Author version of article. The version of record is avilable from the publisher via doi: doi:10.1016/j.neurobiolaging.2014.12.023. Copyright © 2015 Elsevier Inc. All rights reserved.Available online 24 December 2014Due to an aging population, the incidence of dementia is steadily rising. The ability to identify early markers in blood, which appear before the onset of clinical symptoms is of considerable interest to allow early intervention, particularly in "high risk" groups such as those with type 2 diabetes. Here, we present a longitudinal study of genome-wide DNA methylation in whole blood from 18 elderly individuals with type 2 diabetes who developed presymptomatic dementia within an 18-month period following baseline assessment and 18 age-, sex-, and education-matched controls who maintained normal cognitive function. We identified a significant overlap in methylomic differences between groups at baseline and follow-up, with 8 CpG sites being consistently differentially methylated above our nominal significance threshold before symptoms at baseline and at 18 months follow up, after a diagnosis of presymptomatic dementia. Finally, we report a significant overlap between DNA methylation differences identified in converters, only after they develop symptoms of dementia, with differences at the same loci in blood samples from patients with clinically diagnosed Alzheimer's disease compared with unaffected control subjects.National Institute for Health Research (NIHR)Helen Bader FoundationLeroy Schecter FoundationBrightFocus Foundatio

    The use of microsatellite polymorphism in genetic mapping of the ostrich (Struthio camelus)

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    The aim of this study was to determine microsatellite polymorphism in ostriches and using it in creation the genetic map of the ostrich. The polymorphism analysis covered 30 microsatellite markers characteristic of ostrich, for the CAU (China Agricultural University) group. The material consisted of 150 ostriches (Struthio camelus). The 30 microsatellite loci was examined and a total of 343 alleles was identified. The number of alleles at a single locus ranged from 5 at locus CAU78 to 34 at locus CAU85. The values for the observed heterozygosity Ho ranged from 0.467 (locus CAU78) to 0.993 (locus CAU16), whereas for the expected heterozygosity He - from 0.510 (locus CAU78) to 0.953 (locus CAU85). Analyzing the individual loci, the highest PIC value, more than 0.7 was observed for: loci CAU85 (0.932), CAU64 (0.861) and CAU32, 75 (0.852), respectively. It should be noted, that the microsatellite markers used in our study were very polymorphic as evidenced by the large number of detected alleles and high rates of heterozygosity, PIC and PE as well. The analysed microsatellite markers may be used in genetic linkage mapping of ostrich, the construction of a comparative genetic map with other ratites, such as emu and rhea, and population genetics studies or phylogenetic studies of these birds

    The process of establishing implementing and maintaining a social support infant feeding programme

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    Objective To describe the process of establishing and implementing a social support infant feeding intervention. Design This paper outlines the initial stages of a randomised controlled trial which assessed the effectiveness of a social support intervention on a range of infant feeding outcomes. Details are presented of the processes involved in recruiting, training and supporting a group of volunteers who provided support to the study sample. Setting Camden and Islington, London, UK. Results Initial networking with local agencies and organisations provided invaluable information and contacts. Employing a dedicated volunteer co-ordinator is vitally important in the recruitment, training and support of volunteers. Providing child care and travel expenses is an essential incentive for volunteers with young children. Advertisements placed in local newspapers were the most successful means of recruiting volunteers. Appropriate training is needed to equip volunteers with the necessary knowledge and skills to provide effective support. Particular emphasis in the training focused upon developing the necessary interpersonal skills and self-confidence. The evaluation of the training programme demonstrated that it improved volunteers’ knowledge and reported confidence. The provision of ongoing support is also essential to maintain volunteers’ interest and enthusiasm. The retention of volunteers is, however, a key challenge. Conclusions The processes outlined in this paper have demonstrated the feasibility of successfully establishing, implementing and maintaining a community-based social support infant feeding programme. The experiences described provide useful insights into the practical issues that need to be addressed in setting up a social support intervention

    An international comparative study of blood pressure in populations of European vs. African descent

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    Background: The consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue. Methods: Using a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants). Results: The range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks. Conclusions: These data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated

    What influences the speed of prototyping? An empirical investigation of twenty software startups

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    It is essential for startups to quickly experiment business ideas by building tangible prototypes and collecting user feedback on them. As prototyping is an inevitable part of learning for early stage software startups, how fast startups can learn depends on how fast they can prototype. Despite of the importance, there is a lack of research about prototyping in software startups. In this study, we aimed at understanding what are factors influencing different types of prototyping activities. We conducted a multiple case study on twenty European software startups. The results are two folds, firstly we propose a prototype-centric learning model in early stage software startups. Secondly, we identify factors occur as barriers but also facilitators for prototyping in early stage software startups. The factors are grouped into (1) artifacts, (2) team competence, (3) collaboration, (4) customer and (5) process dimensions. To speed up a startups progress at the early stage, it is important to incorporate the learning objective into a well-defined collaborative approach of prototypingComment: This is the author's version of the work. Copyright owner's version can be accessed at doi.org/10.1007/978-3-319-57633-6_2, XP2017, Cologne, German

    Measuring new product and service portfolio advantage

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    The current study introduces the concept of new product and service portfolio (NPSP) advantage by creating and validating a three-dimensional measurement method that reflects novelty, meaningfulness and superiority – the three characteristics of NPSP advantage. Based on industry-wide homogeneous generalizable quantitative data from 108 manufacturing companies, the results indicate that these three characteristics of NPSP – novelty, meaningfulness and superiority – are distinct characteristics that together constitute NPSP advantage. This paper contributes to the literature on new product development, as its findings suggest that when measuring the concept of NPSP advantage, the three-dimensional construct that includes the three aforementioned characteristics has a better fit to the data than the unidimensional structure. Because it considers both new products and services, the current study offers an integrated approach to measure the desired innovation process outcome (NPSP advantage). In this way, this paper bridges the research on new product development with that on new service development.fi=vertaisarvioitu|en=peerReviewed

    Testing in the incremental design and development of complex products

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    Testing is an important aspect of design and development which consumes significant time and resource in many companies. However, it has received less research attention than many other activities in product development, and especially, very few publications report empirical studies of engineering testing. Such studies are needed to establish the importance of testing and inform the development of pragmatic support methods. This paper combines insights from literature study with findings from three empirical studies of testing. The case studies concern incrementally developed complex products in the automotive domain. A description of testing practice as observed in these studies is provided, confirming that testing activities are used for multiple purposes depending on the context, and are intertwined with design from start to finish of the development process, not done after it as many models depict. Descriptive process models are developed to indicate some of the key insights, and opportunities for further research are suggested
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