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1.
Front Bioeng Biotechnol ; 12: 1355723, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38807649

RESUMO

Introduction: Osteoarthritis (OA) and rotator cuff tear (RCT) pathologies have distinct scapular morphologies that impact disease progression. Previous studies examined the correlation between scapular morphology and glenohumeral joint biomechanics through critical shoulder angle (CSA) variations. In abduction, higher CSAs, common in RCT patients, increase vertical shear force and rotator cuff activation, while lower CSAs, common in OA patients, are associated with higher compressive force. However, the impact of the complete patient-specific scapular morphology remains unexplored due to challenges in establishing personalized models. Methods: CT data of 48 OA patients and 55 RCT patients were collected. An automated pipeline customized the AnyBody™ model with patient-specific scapular morphology and glenohumeral joint geometry. Biomechanical simulations calculated glenohumeral joint forces and instability ratios (shear-to-compressive forces). Moment arms and torques of rotator cuff and deltoid muscles were analyzed for each patient-specific geometry. Results and discussion: This study confirms the increased instability ratio on the glenohumeral joint in RCT patients during abduction (mean maximum is 32.80% higher than that in OA), while OA patients exhibit a higher vertical instability ratio in flexion (mean maximum is 24.53% higher than that in RCT) due to the increased inferior vertical shear force. This study further shows lower total joint force in OA patients than that in RCT patients (mean maximum total force for the RCT group is 11.86% greater than that for the OA group), attributed to mechanically advantageous muscle moment arms. The findings highlight the significant impact of the glenohumeral joint center positioning on muscle moment arms and the total force generated. We propose that the RCT pathomechanism is related to force magnitude, while the OA pathomechanism is associated with the shear-to-compressive loading ratio. Overall, this research contributes to the understanding of the impact of the complete 3D scapular morphology of the individual on shoulder biomechanics.

2.
Cell Rep ; 43(1): 113593, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38113140

RESUMO

Nuclear mRNA export via nuclear pore complexes is an essential step in eukaryotic gene expression. Although factors involved in mRNA transport have been characterized, a comprehensive mechanistic understanding of this process and its regulation is lacking. Here, we use single-RNA imaging in yeast to show that cells use mRNA retention to control mRNA export during stress. We demonstrate that, upon glucose withdrawal, the essential RNA-binding factor Nab2 forms RNA-dependent condensate-like structures in the nucleus. This coincides with a reduced abundance of the DEAD-box ATPase Dbp5 at the nuclear pore. Depleting Dbp5, and consequently blocking mRNA export, is necessary and sufficient to trigger Nab2 condensation. The state of Nab2 condensation influences the extent of nuclear mRNA accumulation and can be recapitulated in vitro, where Nab2 forms RNA-dependent liquid droplets. We hypothesize that cells use condensation to regulate mRNA export and control gene expression during stress.


Assuntos
Complexo de Proteínas Formadoras de Poros Nucleares , Proteínas de Saccharomyces cerevisiae , Transporte Ativo do Núcleo Celular , Núcleo Celular/metabolismo , RNA Helicases DEAD-box/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Proteínas de Transporte Nucleocitoplasmático/genética , Proteínas de Transporte Nucleocitoplasmático/metabolismo , RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
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