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  • 1
    In: The Journal of Physiology, Wiley, Vol. 600, No. 8 ( 2022-04), p. 1969-1989
    Abstract: Muscle fibre denervation and declining numbers of muscle stem (satellite) cells are defining characteristics of ageing skeletal muscle. The aim of this study was to investigate the potential for lifelong recreational exercise to offset muscle fibre denervation and compromised satellite cell content and function, both at rest and under challenged conditions. Sixteen elderly lifelong recreational exercisers (LLEX) were studied alongside groups of age‐matched sedentary (SED) and young subjects. Lean body mass and maximal voluntary contraction were assessed, and a strength training bout was performed. From muscle biopsies, tissue and primary myogenic cell cultures were analysed by immunofluorescence and RT‐qPCR to assess myofibre denervation and satellite cell quantity and function. LLEX demonstrated superior muscle function under challenged conditions. When compared with SED, the muscle of LLEX was found to contain a greater content of satellite cells associated with type II myofibres specifically, along with higher mRNA levels of the beta and gamma acetylcholine receptors (AChR). No difference was observed between LLEX and SED for the proportion of denervated fibres or satellite cell function, as assessed in vitro by myogenic cell differentiation and fusion index assays. When compared with inactive counterparts, the skeletal muscle of lifelong exercisers is characterised by greater fatigue resistance under challenged conditions in vivo , together with a more youthful tissue satellite cell and AChR profile. Our data suggest a little recreational level exercise goes a long way in protecting against the emergence of classic phenotypic traits associated with the aged muscle. Key points The detrimental effects of ageing can be partially offset by lifelong self‐organized recreational exercise, as evidence by preserved type II myofibre‐associated satellite cells, a beneficial muscle innervation status and greater fatigue resistance under challenged conditions. Satellite cell function ( in vitro ), muscle fibre size and muscle fibre denervation determined by immunofluorescence were not affected by recreational exercise. Individuals that are recreationally active are far more abundant than master athletes, which sharply increases the translational perspective of the present study. Future studies should further investigate recreational activity in relation to muscle health, while also including female participants.
    Type of Medium: Online Resource
    ISSN: 0022-3751 , 1469-7793
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1475290-6
    SSG: 12
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  • 2
    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 3
    In: International Journal of Imaging Systems and Technology, Wiley, Vol. 33, No. 3 ( 2023-05), p. 985-998
    Abstract: The UNet has become the golden standard method for the segmentation of 2D medical images that any new method must be validated against. In recent years, a number of variations to the seminal UNet have been proposed with promising results in the papers introducing them. However, there is no clear consensus if any of these architectures generalize as well and the UNet currently remains the methodological golden standard. For the segmentation of 3D scans, UNet‐inspired methods are also dominant, but there is a larger variety across applications. By evaluating the architectures in a different dimensionality, embedded in a different method, and for a different task, we aimed to evaluate if any of these UNet alternatives are promising as a new golden standard that generalizes even better than the UNet. The purpose of this study was to compare UNet inspired models for generalized 3D segmentation. To efficiently segment the 3D scans, we employed each UNet variant architecture as the central 2D segmentation core in the multi‐planar UNet 3D segmentation method that previously demonstrated excellent generalization in the MICCAI Segmentation Decathlon. It would strongly support a claim of generalizability, if a promising UNet‐variant consistently outperforms the UNet in this quite different setting. The experimental results show that the multi‐planar‐based UNet2+ (MPUNet2+) method outperforms other variants including the original multi‐planar UNet (MPUNet).
    Type of Medium: Online Resource
    ISSN: 0899-9457 , 1098-1098
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2009087-0
    SSG: 11
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  • 4
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 20, No. 11 ( 2018-10-09), p. 1462-1474
    Abstract: Glioblastoma ranks among the most lethal cancers, with current therapies offering only palliation. Paracrine vascular endothelial growth factor (VEGF) signaling has been targeted using anti-angiogenic agents, whereas autocrine VEGF/VEGF receptor 2 (VEGFR2) signaling is poorly understood. Bevacizumab resistance of VEGFR2-expressing glioblastoma cells prompted interrogation of autocrine VEGF-C/VEGFR2 signaling in glioblastoma. Methods Autocrine VEGF-C/VEGFR2 signaling was functionally investigated using RNA interference and exogenous ligands in patient-derived xenograft lines and primary glioblastoma cell cultures in vitro and in vivo. VEGF-C expression and interaction with VEGFR2 in a matched pre- and post-bevacizumab treatment cohort were analyzed by immunohistochemistry and proximity ligation assay. Results VEGF-C was expressed by patient-derived xenograft glioblastoma lines, primary cells, and matched surgical specimens before and after bevacizumab treatment. VEGF-C activated autocrine VEGFR2 signaling to promote cell survival, whereas targeting VEGF-C expression reprogrammed cellular transcription to attenuate survival and cell cycle progression. Supporting potential translational significance, targeting VEGF-C impaired tumor growth in vivo, with superiority to bevacizumab treatment. Conclusions Our results demonstrate VEGF-C serves as both a paracrine and an autocrine pro-survival cytokine in glioblastoma, promoting tumor cell survival and tumorigenesis. VEGF-C permits sustained VEGFR2 activation and tumor growth, where its inhibition appears superior to bevacizumab therapy in improving tumor control.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2094060-9
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