| 1. |
- Smith, HW, et al.
(författare)
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An ErbB2/c-Src axis links bioenergetics with PRC2 translation to drive epigenetic reprogramming and mammary tumorigenesis
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2901-
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Tidskriftsartikel (refereegranskat)abstract
- Dysregulation of histone modifications promotes carcinogenesis by altering transcription. Breast cancers frequently overexpress the histone methyltransferase EZH2, the catalytic subunit of Polycomb Repressor Complex 2 (PRC2). However, the role of EZH2 in this setting is unclear due to the context-dependent functions of PRC2 and the heterogeneity of breast cancer. Moreover, the mechanisms underlying PRC2 overexpression in cancer are obscure. Here, using multiple models of breast cancer driven by the oncogene ErbB2, we show that the tyrosine kinase c-Src links energy sufficiency with PRC2 overexpression via control of mRNA translation. By stimulating mitochondrial ATP production, c-Src suppresses energy stress, permitting sustained activation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which increases the translation of mRNAs encoding the PRC2 subunits Ezh2 and Suz12. We show that Ezh2 overexpression and activity are pivotal in ErbB2-mediated mammary tumourigenesis. These results reveal the hitherto unknown c-Src/mTORC1/PRC2 axis, which is essential for ErbB2-driven carcinogenesis.
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| 3. |
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| 4. |
- Bayley, PJ, et al.
(författare)
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2013 SYR Accepted Poster Abstracts
- 2013
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Ingår i: International journal of yoga therapy. - 1531-2054. ; 23:1, s. 32-53
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Fakhfakh, Maya, et al.
(författare)
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Canadian older adults' intention to use an electronic decision aid for housing decisions : a cross-sectional online survey
- 2023
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Ingår i: JMIR Aging. - : JMIR Publications Inc.. - 2561-7605. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Older adults experiencing disabilities such as loss of autonomy face the decision of whether to stay at home or move to a healthcare facility such as a nursing home. Thus, they may need support for this difficult decision.OBJECTIVE: We assessed Canadian older adults' intention to use an electronic decision aid (eDA) for making housing decisions and identified the factors that influenced their intention.METHODS: We conducted a cross-sectional study using an online survey targeting older adults across the 10 Canadian provinces and 3 territories. We included respondents from an online panel who were aged 65 years or older, understood English or French, had access to an electronic device with an internet connection and had made a housing decision over the past few months or were planning to make a decision in the coming year. We based the online survey on the Unified Theory of Acceptance and Use of Technology (UTAUT). We adapted 17 UTAUT items to measure respondents' intention to use the eDA for housing decisions, as well as items measuring 4 intention constructs (performance expectancy, effort expectancy, social influence and facilitating conditions). We also assessed e-Health literacy using subjective and objective scales. We used descriptive statistics and multivariable linear regression analyses to identify factors influencing the intention to use the eDA.RESULTS: Of the 11,972 eligible panellists, 1,176 met the eligibility criteria and 1,000 (85%) respondents completed the survey. The mean age was 72.5 ± 5.59 years. Most respondents were male (54.8%), white (90.6%), English-speakers (62.9%) and living in Ontario or Quebec (62.8%) in urban areas (85%). Mean scores for subjective e-Health literacy were 27.8 ± 5.88 out of 40 and for objective e-Health literacy, 3.00 ± 0.97 out of 5. In our sample, the intention score was 4.74 ± 1.7 out of 7. Mean scores of intention constructs out of 7 were 5.63 ± 1.28 for facilitating conditions, 4.94 ± 1.48 for performance expectancy, 5.61 ± 1.35 for effort expectancy and 4.76 ± 1.59 for social influence. In the final model, factors associated with intention included mother tongue (β = .30; P <.001), objective e-Health literacy (β = -.06; P =.03), performance expectancy (β = .55; P <.001), social influence (β = .37; P <.001) and facilitating conditions (β = .15; P <.001).CONCLUSIONS: Findings from this pan-Canadian online survey suggest that Canadian older adults' intention to use an eDA to make housing decisions are similar to findings in other studies using UTAUT. Factors identified as influencing intention were mother tongue, objective e-Health literacy, performance expectancy, social influence and facilitating conditions. These will guide future strategies for implementing the eDA.
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| 6. |
- Morita, M, et al.
(författare)
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Hepatic posttranscriptional network comprised of CCR4-NOT deadenylase and FGF21 maintains systemic metabolic homeostasis
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 116:16, s. 7973-7981
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Tidskriftsartikel (refereegranskat)abstract
- Whole-body metabolic homeostasis is tightly controlled by hormone-like factors with systemic or paracrine effects that are derived from nonendocrine organs, including adipose tissue (adipokines) and liver (hepatokines). Fibroblast growth factor 21 (FGF21) is a hormone-like protein, which is emerging as a major regulator of whole-body metabolism and has therapeutic potential for treating metabolic syndrome. However, the mechanisms that control FGF21 levels are not fully understood. Herein, we demonstrate that FGF21 production in the liver is regulated via a posttranscriptional network consisting of the CCR4–NOT deadenylase complex and RNA-binding protein tristetraprolin (TTP). In response to nutrient uptake, CCR4–NOT cooperates with TTP to degrade AU-rich mRNAs that encode pivotal metabolic regulators, including FGF21. Disruption of CCR4–NOT activity in the liver, by deletion of the catalytic subunit CNOT6L, increases serum FGF21 levels, which ameliorates diet-induced metabolic disorders and enhances energy expenditure without disrupting bone homeostasis. Taken together, our study describes a hepatic CCR4–NOT/FGF21 axis as a hitherto unrecognized systemic regulator of metabolism and suggests that hepatic CCR4–NOT may serve as a target for devising therapeutic strategies in metabolic syndrome and related morbidities.
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