Engineering topics

Booth, Frank W.

Publications and source records attributed to Booth, Frank W..

8 records

DOE OSTI2024

Temporal dynamics of the multi-omic response to endurance exercise training

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood. Here, the Molecular Transducers of Physical Activity Consortium profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository (https://motrpac-data.org/).

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1997

Gene Regions Responding to Skeletal Muscle Atrophy

Our stated specific aims for this project were: 1) Identify the region(s) of the mouse IIb myosin heavy chain (MHC) promoter necessary for in vivo expression in mouse fast-twitch muscle, and 2) Identify the region(s) of the mouse IIb MHC promoter responsive to immobilization in mouse slow-twitch muscle in vivo. We sought to address these specific aims by introducing various MHC IIb promoter/reporter gene constructs directly into the tibialis anterior and gastrocnemius muscles of living mice. Although the method of somatic gene transfer into skeletal muscle by direct injection has been successfully used in our laboratory to study the regulation of the skeletal alpha actin gene in chicken skeletal muscle, we had many difficulties utilizing this procedure in the mouse. Because of the small size of the mouse soleus and the difficulty in obtaining consistent results, we elected not to study this muscle as first proposed. Rather, our MHC IIb promoter deletion experiments were performed in the gastrocnemius. Further, we decided to use hindlimb unloading via tail suspension to induce an upregulation of the MHC IIb gene, rather than immobilization of the hindlimbs via plaster casts. This change was made because tail suspension more closely mimics spaceflight, and this procedure in our lab results in a smaller loss of overall body mass than the mouse hindlimb immobilization procedure. This suggests that the stress level during tail suspension is less than during immobilization. This research has provided an important beginning point towards understanding the molecular regulation of the MHC lIb gene in response to unweighting of skeletal muscle Future work will focus on the regulation of MHC IIb mRNA stability in response to altered loading of skeletal muscle

Booth, Frank W.↗

NASA NTRS1995

Satellite cell proliferation in adult skeletal muscle

Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

Booth, Frank W.↗

NASA NTRS1995

Stimulation of Myofibrillar Protein Synthesis in Hindlimb Suspended Rats by Resistance Exercise and Growth Hormone

The objective of this study was to determine the ability of a single bout of resistance exercise alone or in combination with recombinant human growth hormone (rhGH) to stimulate myofibrillar protein synthesis (Ks) in hindlimb suspended (HLS) adult female rats. Plantar flexor muscles were stimulated with resistance exercise, consisting of 10 repetitions of ladder climbing on a 1 m grid (85 deg.), carrying an additional 50% of their body weight attached to their tails. Saline or rhGH (1 mg/kg) was administered 30' prior to exercise, and Ks was determined with a constant infusion of H-3-Leucine at 15', 60', 180', and 360' following exercise. Three days of HLS depressed Ks is approx. equal to 65% and 30-40% in the soleus and gastrocnemius muscles, respectively (p is less than or equal to 0.05). Exercise increased soleus Ks in saline-treated rats 149% 60' following exercise (p less than or equal to 0.05), decaying to that of non-exercised animals during the next 5 hours. Relative to suspended, non-exercised rats rhGH + exercise increased soleus Ks 84%, 108%, and 72% at 15', 60' and 360' following exercise (p is less than or equal to 0.05). Gastrocnemius Ks was not significantly increased by exercise or the combination of rhGH and exercise up to 360' post-exercise. Results from this study indicate that resistance exercise stimulated Ks 60' post-exercise in the soleus of HLS rats, with no apparent effect of rhGH to enhance or prolong exercise-induced stimulation. Results suggests that exercise frequency may be important to maintenance of the slow-twitch soleus during non-weightbearing, but that the ability of resistance exercise to maintain myofibrillar protein content in the gastrocnemius of hindlimb suspended rats cannot be explained by acute stimulation of synthesis.

Linderman, Jon K.↗

NASA NTRS1992

Eccentric exercise training as a countermeasure to non-weight-bearing soleus muscle atrophy

This investigation tested whether eccentric resistance training could prevent soleus muscle atrophy during non-weight bearing. Adult female rats were randomly assigned to either weight bearing +/- intramuscular electrodes or non-weight bearing +/- intramuscular electrodes groups. Electrically stimulated maximal eccentric contractions were performed on anesthetized animals at 48-h intervals during the 10-day experiment. Non-weight bearing significantly reduced soleus muscle wet weight (28-31 percent) and noncollagenous protein content (30-31 percent) compared with controls. Eccentric exercise training during non-weight bearing attenuated but did not prevent the loss of soleus muscle wet weight and noncollagenous protein by 77 and 44 percent, respectively. The potential of eccentric exercise training as an effective and highly efficient counter-measure to non-weight-bearing atrophy is demonstrated in the 44 percent attenuation of soleus muscle noncollagenous protein loss by eccentric exercise during only 0.035 percent of the total non-weight-bearing time period.

Kirby, Christopher R.↗

NASA NTRS1992

Intermittent acceleration as a countermeasure to soleus muscle atrophy

The effectiveness of using intermittent acceleration as a countermeasure to muscle atrophy was investigated in rats subjected to 7 days of hindlimb suspension interrupted by daily periods of 1.2 g acceleration, for 15-min periods evenly spaced over 12-hr interval. It was found that this regimen, when repeated for 7 days, failed to completely maintain the mass of soleus muscle, which was 84 percent of control.

D'Aunno, Dominick S.↗

NASA NTRS1990

Centrifugal intensity and duration as countermeasures to soleus muscle atrophy

The effects of artificially induced gravity on the atrophy process of slow-twitch soleus muscle are studied in order to determine whether centrifugation could be an effective countermeasure to nonweight bearing at 1 G. It is observed that the soleus muscle atrophied 32 percent during seven days of nonweight bearing without countermeasures, and centrifugation treatment did not completely prevent atrophy relative to precontrol wet weight of the soleus muscle. Nonweight-bearing groups receiving treatments of 1, 1.5, or 2.6 G had 48, 56, and 65 percent, respectively, of the atrophy observed in a nonweight-bearing-only group compared with the precontrol group. It is concluded that, as a countermeasure to nonweight-bearing-induced atrophy of the soleus muscle, centrifugation at 2.6 G is no more effective than exposure to 1 or 1.5 G.

D'Aunno, Dominick S.↗

NASA NTRS1990

Atrophy of the soleus muscle by hindlimb unweighting

This paper reviews data derived from the animal hindlimb unweighting model. The review presents the following information about the unweighted soleus muscle: electromyogram activity, the amount and type of protein lost, capillarization, oxidative capacity, glycolytic enzyme activities, fiber cross section, contractile properties, glucose uptake, sensitivity to insulin, the rates of protein synthesis and degradation, the glucocorticoid receptor numbers, the responses of specific mRNAs, and changes in metabolic concentrations. Data of all these studies show that the stress response of the animal to hindlimb suspension is transient and minimal in magnitude (though somewhat variable) and that, after one week of unweighting, the animal exhibits no chronic signs of stress.

Thomason, Donald B.↗