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1.
Nat Cell Biol ; 22(10): 1239-1251, 2020 10.
Article in English | MEDLINE | ID: mdl-32958857

ABSTRACT

The contribution of ribosome heterogeneity and ribosome-associated proteins to the molecular control of proteomes in health and disease remains unclear. Here, we demonstrate that survival motor neuron (SMN) protein-the loss of which causes the neuromuscular disease spinal muscular atrophy (SMA)-binds to ribosomes and that this interaction is tissue-dependent. SMN-primed ribosomes are preferentially positioned within the first five codons of a set of mRNAs that are enriched for translational enhancer sequences in the 5' untranslated region (UTR) and rare codons at the beginning of their coding sequence. These SMN-specific mRNAs are associated with neurogenesis, lipid metabolism, ubiquitination, chromatin regulation and translation. Loss of SMN induces ribosome depletion, especially at the beginning of the coding sequence of SMN-specific mRNAs, leading to impairment of proteins that are involved in motor neuron function and stability, including acetylcholinesterase. Thus, SMN plays a crucial role in the regulation of ribosome fluxes along mRNAs encoding proteins that are relevant to SMA pathogenesis.


Subject(s)
Motor Neurons/pathology , Muscular Atrophy, Spinal/pathology , Protein Biosynthesis , Proteome/analysis , RNA, Messenger/metabolism , Ribosomes/metabolism , Survival of Motor Neuron 1 Protein/metabolism , Animals , Disease Models, Animal , Gene Expression Regulation , Mice , Motor Neurons/metabolism , Muscular Atrophy, Spinal/genetics , Muscular Atrophy, Spinal/metabolism , RNA, Messenger/genetics , Ribosomes/genetics , Survival of Motor Neuron 1 Protein/genetics , Transcriptome
2.
J Aging Phys Act ; 28(1): 149-154, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31629356

ABSTRACT

The authors compared the linear and nonlinear heart rate variability dynamics from rest through maximal exercise in postmenopausal women who trained at either moderate or high intensities. The outcome variables included the RR triangular index, TINN, SD1, SD2, SD1/SD2, DFA α1, DFA α2, and α1/α2. Maximal exercise reduced SD1, SD2, DFA α1, DFA α2, α1/α2, RRTri, and TINN in both groups and increased SD1/SD2 (p < .05). Two minutes of active recovery produced significant increases in SD1, SD2, DFA α1, and TINN, compared with exercise in both groups (p < .0001). There was also a significant main effect between groups for RRTri during exercise recovery, with the moderate group achieving higher levels (p < .04). The authors have shown that both moderate and vigorous exercise training can lead to a healthy response to maximal exercise and recovery, with the moderate group having a slightly improved recovery in the triangular index.


Subject(s)
Exercise/physiology , Heart Rate/physiology , Menopause/physiology , Female , Health Status , Humans , Middle Aged , Rest
3.
Sports Med Int Open ; 1(5): E166-E171, 2017 Aug.
Article in English | MEDLINE | ID: mdl-30539103

ABSTRACT

Postmenopausal women have an increased risk for cardiovascular disease through many factors, such as a sedentary lifestyle and reduced heart rate variability (HRV). Endurance training improves coronary risk but the role of exercise intensity is unclear. The purpose of this observational study was to evaluate the effects of moderate versus vigorous exercise on cardiovascular disease risk in postmenopausal women. Thirty-six postmenopausal women who self-reported training at moderate (3-5.9 METS; n=18; age 58.9±4.4yr) or vigorous intensities (>6 METS; n=18; age 59.7±5.2yr) participated. C-reactive protein (CRP), HRV, VO 2 max, and stress (Perceived Stress Survey, Menopause Rating Scale) were measured. Groups were compared using independent samples t- tests, and associations of exercise intensities with CRP and HRV were assessed using multiple regression. CRP, HRV, and VO 2 max were similar ( p >0.05). Vigorous exercise had lower stress subscale scores ( p <0.01) and higher counter-stress subscale scores compared to moderate ( p <0.05). There was a positive association between time spent in vigorous exercise and HRV ( p <0.05).Vigorous exercise may not confer additional benefits in CRP and HRV over moderate, except for stress reduction. However, more time spent in vigorous exercise was associated with higher HRV. Therefore, increased parasympathetic tone may provide cardioprotection after menopause.

4.
J Strength Cond Res ; 22(1): 310-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18296991

ABSTRACT

This study assessed the mechanical reliability and validity of the INRTEK iSAM 9000 isokinetic dynamometer, and compared the obtained torque values of the prototype device with those from a traditional device. Sixty volunteers (40 men and 20 women) were tested at 60 degrees per second for shoulder, knee, and trunk flexion, and extension on both the Cybex 6000 and a new isokinetic dynamometer (iSAM 9000). Intraclass correlation coefficients (ICC) and standard errors of measurement (SEM) revealed a high level of reproducibility and precision in the device's torque measurements (ICC range = 0.94-0.98; SEM range = 5.2-29.7). Pearson r values revealed very high relationships between the two instruments (set 1: r = 0.84-0.93; set 2: r = 0.87-0.93; P < 0.05). Significantly higher peak torque for both sets of left and right knee flexion and extension, right shoulder extension and trunk extension was found for the iSAM 9000 compared to the Cybex 6000 (P < 0.05). The strong ICCs and small SEMs support the device's mechanical reliability and validity. The high correlation coefficients between the prototype dynamometer and the Cybex 6000 support the new device's validity in the measurement of isokinetic torque. The findings of this study will be used to refine the next generation of the INRTEK isokinetic device with respect to test protocols and the reliability of measuring human muscle performance.


Subject(s)
Exercise Test/instrumentation , Muscle Strength Dynamometer , Muscle Strength/physiology , Muscle, Skeletal/physiology , Physical Exertion/physiology , Adult , Anthropometry , Cohort Studies , Equipment Design , Equipment Safety , Exercise , Female , Humans , Lower Extremity , Male , Middle Aged , Range of Motion, Articular/physiology , Reproducibility of Results , Torque , Upper Extremity
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