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  • 1
    Online Resource
    Online Resource
    American Physiological Society ; 2018
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 315, No. 5 ( 2018-11-01), p. R1003-R1016
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 315, No. 5 ( 2018-11-01), p. R1003-R1016
    Abstract: It remains unclear whether high-intensity interval exercise (HIIE) elicits distinct molecular responses to traditional endurance exercise relative to the total work performed. We aimed to investigate the influence of exercise intensity on acute perturbations to skeletal muscle mitochondrial function (respiration and reactive oxygen species) and metabolic and redox signaling responses. In a randomized, repeated measures crossover design, eight recreationally active individuals (24 ± 5 yr; V̇o 2peak : 48 ± 11 ml·kg −1 ·min −1 ) undertook continuous moderate-intensity [CMIE: 30 min, 50% peak power output (PPO)], high-intensity interval (HIIE: 5 × 4 min, 75% PPO, work matched to CMIE), and low-volume sprint interval (SIE: 4 × 30 s) exercise, ≥7 days apart. Each session included muscle biopsies at baseline, immediately, and 3 h postexercise for high-resolution mitochondrial respirometry ( Jo 2 ) and H 2 O 2 emission ( Jh 2 o 2 ) and gene and protein expression analysis. Immediately postexercise and irrespective of protocol, Jo 2 increased during complex I + II leak/state 4 respiration but Jh 2 o 2 decreased ( P 〈 0.05). AMP-activated protein kinase and acetyl co-A carboxylase phosphorylation increased ~1.5 and 2.5-fold respectively, while thioredoxin-reductase-1 protein abundance was ~35% lower after CMIE vs. SIE ( P 〈 0.05). At 3 h postexercise, regardless of protocol, Jo 2 was lower during both ADP-stimulated state 3 OXPHOS and uncoupled respiration ( P 〈 0.05) but Jh 2 o 2 trended higher ( P 〈 0.08) and PPARGC1A mRNA increased ~13-fold, and peroxiredoxin-1 protein decreased ~35%. In conclusion, intermittent exercise performed at high intensities has similar dynamic effects on muscle mitochondrial function compared with endurance exercise, irrespective of whether total workload is matched. This suggests exercise prescription can accommodate individual preferences while generating comparable molecular signals known to promote beneficial metabolic adaptations.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2018
    detail.hit.zdb_id: 1477297-8
    SSG: 12
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  • 2
    In: BMC Biology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-12)
    Abstract: Mitochondria have an essential role in regulating metabolism and integrate environmental and physiological signals to affect processes such as cellular bioenergetics and response to stress. In the metabolically active skeletal muscle, mitochondrial biogenesis is one important component contributing to a broad set of mitochondrial adaptations occurring in response to signals, which converge on the biogenesis transcriptional regulator peroxisome proliferator-activated receptor coactivator 1-alpha (PGC-1α), and is central to the beneficial effects of exercise in skeletal muscle. We investigated the role of long non-coding RNA (lncRNA) taurine-upregulated gene 1 ( TUG1 ), which interacts with PGC-1α in regulating transcriptional responses to exercise in skeletal muscle. Results In human skeletal muscle, TUG1 gene expression was upregulated post-exercise and was also positively correlated with the increase in PGC-1α gene expression ( PPARGC1A ). Tug1 knockdown (KD) in differentiating mouse myotubes led to decreased Ppargc1a gene expression, impaired mitochondrial respiration and morphology, and enhanced myosin heavy chain slow isoform protein expression. In response to a Ca 2+ -mediated stimulus, Tug1 KD prevented an increase in Ppargc1a expression. RNA sequencing revealed that Tug1 KD impacted mitochondrial Ca 2+ transport genes and several downstream PGC-1α targets. Finally, Tug1 KD modulated the expression of ~300 genes that were upregulated in response to an in vitro model of exercise in myotubes, including genes involved in regulating myogenesis. Conclusions We found that TUG1 is upregulated in human skeletal muscle after a single session of exercise, and mechanistically, Tug1 regulates transcriptional networks associated with mitochondrial calcium handling, muscle differentiation and myogenesis. These data demonstrate that lncRNA Tug1 exerts regulation over fundamental aspects of skeletal muscle biology and response to exercise stimuli.
    Type of Medium: Online Resource
    ISSN: 1741-7007
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2133020-7
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Wiley ; 2018
    In:  Clinical Endocrinology Vol. 89, No. 6 ( 2018-12), p. 683-699
    In: Clinical Endocrinology, Wiley, Vol. 89, No. 6 ( 2018-12), p. 683-699
    Abstract: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting reproductive‐aged women with adverse reproductive, metabolic and psychological outcomes. It has a complex pathophysiology and therefore requires a multidiscipline clinical approach. However, there remains limited research synthesizing the broad clinical implications of PCOS which would assist clinicians in the management of PCOS. Objective To summarize and appraise methodological quality of systematic reviews and meta‐analyses evaluating complications and comorbidities associated with PCOS. Methods A literature search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed until 15 September 2017. Article selection, data extraction and quality appraisal of included reviews using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool were performed in duplicate. A narrative synthesis of the findings was conducted. Results Twenty‐three reviews were included. All reviews were of low (n = 2) to moderate quality (n = 21). PCOS was associated with adverse pregnancy outcomes (n = 2), impaired glucose tolerance (n = 6), insulin resistance (n = 6), increased risk of type 2 diabetes (n = 1), cardiovascular disease (n = 10), metabolic syndrome (n = 2), psychological stress (n = 7), endometrial cancer (n = 1) and vitamin D deficiency (n = 1). Obesity exacerbates many of these outcomes. Conclusions There is a large body of reliable evidence for adverse metabolic outcomes and smaller, but consistent evidence for psychological issues in PCOS. We identified a shortage of systematic reviews regarding pregnancy outcomes of PCOS and significant gaps in knowledge of the association between PCOS and subclinical hyperthyroidism, vitamin D levels and cancers which future studies could aim to address.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2004597-9
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  • 4
    In: Clinical Endocrinology, Wiley, Vol. 89, No. 5 ( 2018-11), p. 535-553
    Abstract: Polycystic ovary syndrome ( PCOS ) affects up to 13% women and is associated with significant complications. The quality of evidence supporting the recommendations on treatment of nonreproductive outcomes in PCOS is unknown. Objective To summarize and appraise the methodological quality of systematic reviews and meta‐analyses evaluating pharmacological and surgical treatments for nonreproductive outcomes in PCOS . Methods A literature search from MEDLINE , EMBASE , CINAHL PLUS and PROSPERO was performed from inception until 15th of September 2017. Article selection, data extraction and quality appraisal of included reviews were performed in duplicate. A narrative synthesis of the findings was conducted. Results This overview included 31 reviews. The quality was low for 7 (23%), moderate for sixteen (52%) and high for 8 reviews (26%). Two reviews assessed psychological outcomes. Metformin improved anthropometric (7 of 10 reviews), metabolic (4 of 14 reviews) and endocrine outcomes (3 of twelve reviews). Thiazolidinediones improved metabolic (2 of 5 reviews) and endocrine outcomes (one of 5 reviews) but worsened weight gain (5 of 5 reviews). Combined oral contraceptive pill ( COCP ) improved clinical hyperandrogenism (2 of 2 reviews). Statins improved lipid profile (3 of 3 reviews) and testosterone level (2 of 3 reviews). There was no conclusive evidence from included systematic reviews regarding the use of other interventions. Conclusions There is reliable evidence regarding the use of metformin for anthropometric outcomes and COCP s for hyperandrogenism in women with PCOS but not for other interventions. There is significant gap in knowledge regarding the management of psychological outcomes in women with PCOS which needs further evaluation.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2004597-9
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  • 5
    In: Fertility and Sterility, Elsevier BV, Vol. 109, No. 3 ( 2018-03), p. 532-539
    Type of Medium: Online Resource
    ISSN: 0015-0282
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 1500469-7
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A353-A354
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A353-A354
    Abstract: Polycystic ovary syndrome (PCOS) is a common and complex endocrinopathy with significant metabolic and reproductive manifestations, carrying a major health and economic burden. Consistent improvements in clinical outcomes have been reported as a result of exercise training, but shortfalls with exercise prescription are evident. Research suggests that high-intensity intermittent training (HIIT) is feasible, well tolerated and enjoyable for people with or at risk of chronic disease and can address many of the shortfalls and barriers to exercise participation. To investigate the effects of high-intensity exercise on cardio-metabolic health, twenty-four reproductive aged, overweight or obese, sedentary women with PCOS were recruited from the community and randomised to complete either 12 weeks of moderate intensity continuous cycling training (MICT; 60–65% of maximal heart rate [HRmax]; n=11) or HIIT (90–100% HRmax; n=13). All exercise was supervised by an exercise physiologist and completed 3 times per week on a cycle ergometer. Baseline and post-testing measures consisted of peak oxygen consumption (VO2peak) determined by a graded maximal exercise test, body composition by DXA scan and insulin sensitivity determined by euglycaemic-hyperinsulinaemic clamp. Significant improvements in VO2peak were seen after both HIIT (P & lt;0.001) and MICT (P & lt;0.013) with a significant between-group interaction favouring HIIT (P = 0.014). The insulin sensitivity index significantly improved after HIIT (P = 0.009) with no changes observed after MICT (P = 0.860), also resulting in a significant between-group difference favouring HIIT (P = 0.046). No changes were observed for body weight, BMI or fat mass, however, there was a significant increase in percentage of lean mass after HIIT (P = 0.026). The present study is the first to compare current exercise recommendations of moderate and vigorous intensities in women with PCOS. The results of this study provide preliminary validation of HIIT, suggesting that vigorous intensity exercise should be considered in order to improve cardio-metabolic health in women with PCOS.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
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  • 7
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii115-vii115
    Abstract: DNA methylation profiling provides robust classification of nervous system tumors, but mechanisms driving epigenetic identity of individual tumor types are incompletely understood. Integrating DNA methylation profiling (n=76), RNA sequencing (n=24), single-cell RNA-sequencing (n=9), and mass cytometry (n=9), we discovered vestibular schwannomas are comprised of two epigenetic groups distinguished by neural crest development pathways or repair and regeneration pathways driving immune infiltration. Analyses of preoperative magnetic resonance imaging studies (n=66) or paired primary and recurrent schwannomas (n=13) suggested radiotherapy was sufficient but not necessary for epigenetic reprogramming of neural crest enriched schwannomas into immune enriched schwannomas. In support of this hypothesis, DNA methylation profiling, RNA sequencing, single-cell RNA sequencing, proteomic mass spectrometry, and lymphocyte migration assays demonstrated radiotherapy epigenetically reprogramed viable schwannoma cells to secrete immunomodulatory signals and recruit lymphocytes in vitro. Genome-wide CRISPRi screens identified histone acetyltransferases or DNA methyltransferases driving schwannoma radiotherapy responses, including the epigenetic regulators KDM5C or KDM1A. CRISPRi and lymphocyte migration assays ± radiotherapy confirmed KDM5C drives schwannoma immune infiltration whereas KDM1A inhibits schwannoma immune infiltration. To define genomic mechanisms underlying epigenetic group identity, we performed pooled CRISPRi screening coupled with single-cell RNA sequencing (Perturb-seq) of 44 schwannoma markers. In parallel, we developed single nuclei profiling of chromatin accessibility through paired ATAC sequencing and RNA sequencing coupled with pooled CRISPRi screening (snARC-seq) of 54 epigenetic regulators identified by our genome-wide CRISPRi screen. Functional genomic approaches revealed the tyrosine phosphatase PTPRG as a regulator of survival, and KDM5C and KDM1A as regulators of inflammation. In summary, we report two epigenetic groups of schwannomas and mechanisms underlying epigenetic group identity using a new functional genomic technique allowing for simultaneous interrogation of single-cell epigenetic and gene expression changes in the context of genetic and therapeutic perturbations. These data elucidate a novel epigenetic mechanism of action of radiotherapy.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2094060-9
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  • 8
    Online Resource
    Online Resource
    SAGE Publications ; 2023
    In:  Therapeutic Advances in Endocrinology and Metabolism Vol. 14 ( 2023-01), p. 204201882311783-
    In: Therapeutic Advances in Endocrinology and Metabolism, SAGE Publications, Vol. 14 ( 2023-01), p. 204201882311783-
    Abstract: Many transgender (trans) individuals utilize gender-affirming hormone therapy (GAHT) to promote changes in secondary sex characteristics to affirm their gender. Participation rates of trans people in sport are exceedingly low, yet given high rates of depression and increased cardiovascular risk, the potential benefits of sports participation are great. In this review, we provide an overview of the evidence surrounding the effects of GAHT on multiple performance-related phenotypes, as well as current limitations. Whilst data is clear that there are differences between males and females, there is a lack of quality evidence assessing the impact of GAHT on athletic performance. Twelve months of GAHT leads to testosterone concentrations that align with reference ranges of the affirmed gender. Feminizing GAHT in trans women increases fat mass and decreases lean mass, with opposite effects observed in trans men with masculinizing GAHT. In trans men, an increase in muscle strength and athletic performance is observed. In trans women, muscle strength is shown to decrease or not change following 12 months of GAHT. Haemoglobin, a measure of oxygen transport, changes to that of the affirmed gender within 6 months of GAHT, with very limited data to suggest possible reductions in maximal oxygen uptake as a result of feminizing GAHT. Current limitations of this field include a lack of long-term studies, adequate group comparisons and adjustment for confounding factors (e.g. height and lean body mass), and small sample sizes. There also remains limited data on endurance, cardiac or respiratory function, with further longitudinal studies on GAHT needed to address current limitations and provide more robust data to inform inclusive and fair sporting programmes, policies and guidelines.
    Type of Medium: Online Resource
    ISSN: 2042-0188 , 2042-0196
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2554822-0
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