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  • Oxford University Press (OUP)  (3)
  • 1
    Online Resource
    Online Resource
    Mst1/2 Is Necessary for Satellite Cell Differentiation to Promote Muscle Regeneration
    Oxford University Press (OUP) ; 2022
    In:  Stem Cells Vol. 40, No. 1 ( 2022-03-03), p. 74-87
    Details
    In: Stem Cells, Oxford University Press (OUP), Vol. 40, No. 1 ( 2022-03-03), p. 74-87
    Abstract: The diminished ability for muscle to regenerate is associated with aging, diabetes, and cancers. Muscle regeneration depends on the activation and differentiation of satellite cells (SCs). Inactivation of Mst1/2 promotes cell proliferation by activating Yap, and that has been reported as a potential therapeutic target for improving many organ regeneration. However, the function of Mst1/2 in SCs fate decision and that effect on muscle regeneration remain unknown. By using inducible conditional knockout Mst1/2 in the SCs of mice and an inhibitor of Mst1/2, we found that inhibition of Mst1/2 in SCs significantly decrease Yap phosphorylation, thus causing Yap to accumulate in the nucleus and impairing SC differentiation; Mst1/2 were slightly elevated by irisin stimulation during SC differentiation; but inhibiting Mst1/2 in SCs significantly impaired irisin-induced muscle regeneration. These results indicate that Mst1/2 is necessary for SC differentiation and inhibiting Mst1/2 as a therapeutic target has potential risks for muscle regeneration.
    Type of Medium: Online Resource
    ISSN: 1066-5099 , 1549-4918
    URL: Article
    DOI: 10.1093/stmcls/sxab010
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2030643-X
    detail.hit.zdb_id: 1143556-2
    detail.hit.zdb_id: 605570-9
    SSG: 12
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  • 2
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    Ensemble learning for poor prognosis predictions: A case study on SARS-CoV-2
    Oxford University Press (OUP) ; 2021
    In:  Journal of the American Medical Informatics Association Vol. 28, No. 4 ( 2021-03-18), p. 791-800
    Details
    In: Journal of the American Medical Informatics Association, Oxford University Press (OUP), Vol. 28, No. 4 ( 2021-03-18), p. 791-800
    Abstract: Risk prediction models are widely used to inform evidence-based clinical decision making. However, few models developed from single cohorts can perform consistently well at population level where diverse prognoses exist (such as the SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] pandemic). This study aims at tackling this challenge by synergizing prediction models from the literature using ensemble learning. Materials and Methods In this study, we selected and reimplemented 7 prediction models for COVID-19 (coronavirus disease 2019) that were derived from diverse cohorts and used different implementation techniques. A novel ensemble learning framework was proposed to synergize them for realizing personalized predictions for individual patients. Four diverse international cohorts (2 from the United Kingdom and 2 from China; N = 5394) were used to validate all 8 models on discrimination, calibration, and clinical usefulness. Results Results showed that individual prediction models could perform well on some cohorts while poorly on others. Conversely, the ensemble model achieved the best performances consistently on all metrics quantifying discrimination, calibration, and clinical usefulness. Performance disparities were observed in cohorts from the 2 countries: all models achieved better performances on the China cohorts. Discussion When individual models were learned from complementary cohorts, the synergized model had the potential to achieve better performances than any individual model. Results indicate that blood parameters and physiological measurements might have better predictive powers when collected early, which remains to be confirmed by further studies. Conclusions Combining a diverse set of individual prediction models, the ensemble method can synergize a robust and well-performing model by choosing the most competent ones for individual patients.
    Type of Medium: Online Resource
    ISSN: 1527-974X
    URL: Article
    DOI: 10.1093/jamia/ocaa295
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2018371-9
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  • 3
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    Reinforcement of CHH methylation through RNA-directed DNA methylation ensures sexual reproduction in rice
    Oxford University Press (OUP) ; 2022
    In:  Plant Physiology Vol. 188, No. 2 ( 2022-02-04), p. 1189-1209
    Details
    In: Plant Physiology, Oxford University Press (OUP), Vol. 188, No. 2 ( 2022-02-04), p. 1189-1209
    Abstract: DNA methylation is an important epigenetic mark that regulates the expression of genes and transposons. RNA-directed DNA methylation (RdDM) is the main molecular pathway responsible for de novo DNA methylation in plants. Although the mechanism of RdDM has been well studied in Arabidopsis (Arabidopsis thaliana), most mutations in RdDM genes cause no remarkable developmental defects in Arabidopsis. Here, we isolated and cloned Five Elements Mountain 1 (FEM1), which encodes RNA-dependent RNA polymerase 2 (OsRDR2) in rice (Oryza sativa). Mutation in OsRDR2 abolished the accumulation of 24-nt small interfering RNAs, and consequently substantially decreased genome-wide CHH (H = A, C, or T) methylation. Moreover, male and female reproductive development was disturbed, which led to sterility in osrdr2 mutants. We discovered that OsRDR2-dependent DNA methylation may regulate the expression of multiple key genes involved in stamen development, meiosis, and pollen viability. In wild-type (WT) plants but not in osrdr2 mutants, genome-wide CHH methylation levels were greater in panicles, stamens, and pistils than in seedlings. The global increase of CHH methylation in reproductive organs of the WT was mainly explained by the enhancement of RdDM activity, which includes OsRDR2 activity. Our results, which revealed a global increase in CHH methylation through enhancement of RdDM activity in reproductive organs, suggest a crucial role for OsRDR2 in the sexual reproduction of rice.
    Type of Medium: Online Resource
    ISSN: 0032-0889 , 1532-2548
    URL: Article
    DOI: 10.1093/plphys/kiab531
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2004346-6
    detail.hit.zdb_id: 208914-2
    SSG: 12
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