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At least 451 records · Page 25
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ~70%–75% VO 2 max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1–2 wk and improvements in maximum run speed and maximal oxygen uptake by 4–8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

The Ahr2-Dependent wfikkn1 Gene Influences Zebrafish Transcriptome, Proteome, and Behavior

The aryl hydrocarbon receptor (AHR) is required for vertebrate development and is also activated by exogenous chemicals, including polycyclic aromatic hydrocarbons (PAHs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AHR activation is well-understood, but roles of downstream molecular signaling events are largely unknown. From previous transcriptomics in 48 h postfertilization (hpf) zebrafish exposed to several PAHs and TCDD, we found wfikkn1 was highly coexpressed with cyp1a (marker for AHR activation). Thus, we hypothesized wfikkn1’s role in AHR signaling, and showed that wfikkn1 expression was Ahr2 (zebrafish ortholog of human AHR)-dependent in developing zebrafish exposed to TCDD. To functionally characterize wfikkn1, we made a CRISPR-Cas9 mutant line with a 16-bp deletion in wfikkn1’s exon, and exposed wildtype and mutants to dimethyl sulfoxide or TCDD. 48-hpf mRNA sequencing revealed over 700 genes that were differentially expressed (p < .05, log 2 FC > 1) between each pair of treatment combinations, suggesting an important role for wfikkn1 in altering both the 48-hpf transcriptome and TCDD-induced expression changes. Mass spectrometry-based proteomics of 48-hpf wildtype and mutants revealed 325 significant differentially expressed proteins. Functional enrichment demonstrated wfikkn1 was involved in skeletal muscle development and played a role in neurological pathways after TCDD exposure. Mutant zebrafish appeared morphologically normal but had significant behavior deficiencies at all life stages, and absence of Wfikkn1 did not significantly alter TCDD-induced behavior effects at all life stages. In conclusion, wfikkn1 did not appear to be significantly involved in TCDD’s overt toxicity but is likely a necessary functional member of the AHR signaling cascade.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment

The ability of cells to organize into tissues with proper structure and function requires the effective coordination of proliferation, migration, polarization, and differentiation across length scales. Skeletal muscle is innately anisotropic; however, few biomaterials can emulate mechanical anisotropy to determine its influence on tissue patterning without introducing confounding topography. Here, we demonstrate that substrate stiffness anisotropy coordinates contractility-driven collective cellular dynamics resulting in C2C12 myotube alignment over millimeter-scale distances. When cultured on mechanically anisotropic liquid crystalline polymer networks (LCNs) lacking topography, C2C12 myoblasts collectively polarize in the stiffest direction. Cellular coordination is amplified through reciprocal cell-ECM dynamics that emerge during fusion, driving global myotube-ECM ordering. Conversely, myotube alignment was restricted to small local domains with no directional preference on mechanically isotropic LCNs of the same chemical formulation. These findings provide valuable insights for designing biomaterials that mimic anisotropic microenvironments and underscore the importance of stiffness anisotropy in orchestrating tissue morphogenesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Dual incorporation of non-canonical amino acids enables production of post-translationally modified selenoproteins

Post-translational modifications (PTMs) can occur on almost all amino acids in eukaryotes as a key mechanism for regulating protein function. The ability to study the role of these modifications in various biological processes requires techniques to modify proteins site-specifically. One strategy for this is genetic code expansion (GCE) in bacteria. The low frequency of post-translational modifications in bacteria makes it a preferred host to study whether the presence of a post-translational modification influences a protein’s function. Genetic code expansion employs orthogonal translation systems engineered to incorporate a modified amino acid at a designated protein position. Selenoproteins, proteins containing selenocysteine, are also known to be post-translationally modified. Selenoproteins have essential roles in oxidative stress, immune response, cell maintenance, and skeletal muscle regeneration. Their complicated biosynthesis mechanism has been a hurdle in our understanding of selenoprotein functions. As technologies for selenocysteine insertion have recently improved, we wanted to create a genetic system that would allow the study of post-translational modifications in selenoproteins. By combining genetic code expansion techniques and selenocysteine insertion technologies, we were able to recode stop codons for insertion of N ε -acetyl- l -lysine and selenocysteine, respectively, into multiple proteins. The specificity of these amino acids for their assigned position and the simplicity of reverting the modified amino acid via mutagenesis of the codon sequence demonstrates the capacity of this method to study selenoproteins and the role of their post-translational modifications. Moreover, the evidence that Sec insertion technology can be combined with genetic code expansion tools further expands the chemical biology applications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Applications of Decellularized Plant Tissues in Regenerative Medicine and Tissue Engineering

The development of biomaterials capable of supporting complex tissue growth remains a central challenge in regenerative medicine and tissue engineering, particularly in replicating the structural, mechanical, and transport functions of native extracellular matrices. While decellularized animal tissues have demonstrated significant success as scaffolds for tissue engineering, they are still constrained by cost, immunogenicity, and ethical concerns. In recent years, decellularized plant tissues have emerged as a compelling alternative scaffold platform due to their inherent vascular architectures, ethical sourcing, tunable mechanical properties, cytocompatibility, and sustainability. This review summarizes current strategies for the decellularization of plant tissues, including chemical, enzymatic, and physical approaches, and discusses how these methods preserve plant cell wall structure while removing immunogenic components. Advances in surface loading and functionalization, including protein coatings, oxidation, nanoparticle incorporation, peptide conjugation, and bioactive molecule loading, have further enhanced cell adhesion, differentiation, biodegradability, and immunomodulation. Recent applications of decellularized plant scaffolds in cardiac, skeletal muscle, bone, nerve, and wound healing contexts are reviewed, highlighting proof-of-concept successes and remaining challenges. Beyond therapeutic applications, plant-derived scaffolds have also enabled physiologically relevant in vitro models for vascular biology, mechanotransduction, cancer, metabolic tissues, and drug response studies. Collectively, these advances position decellularized plant tissues as versatile, low-cost, and ethically favorable biomaterials with growing relevance for both regenerative medicine and tissue modeling.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1971

Tissue enzyme studies in Macaca nemestrina monkeys.

Total enzyme activities in fresh tissue specimens from major organs of Macaca nemestrina were analyzed for lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and aldolase. The concentration of these enzymes varied among the different tissue with skeletal muscle, heart, and brain having the highest activities. LDH isozymes determinations for the various tissues were also made. The spectrum of LDH isozyme distribution appears to be quite specific and characteristic for at least some of the tissues analyzed.

Hubbard, R. W.↗
NASA NTRS1972

Effect of chronic centrifugation on body composition in the rat.

Two groups of adult female rats were chronically centrifuged for 60 days (2.76 G, 4.15 G, controls at 1.00 G). Live weights of centrifugal rats decreased about 20 g (6%) per Delta 1 G above control. This weight loss comprised reductions in both body fat and fat-free body weight (FFBW) as determined by body-composition studies on eight rats per group killed at the end of centrifugation. Of nine components constituting the FFBW, only skeletal muscle, liver, and heart changed significantly in weight. Chemical composition showed reductions (compared with controls) in the fat fraction of most components and increases in the water fraction of liver and gut. Identical measurements were made on the remaining eight rats per group killed 43 days after return to 1 G. Neither centrifuged group had reached the control body-weight level at this time. No statistically significant effect of previous G level was found in any of the body-composition parameters. The possible involvment of physiological regulation was considered.

Pitts, G. C.↗
NASA NTRS1973

Brain blood-flow changes during motion sickness

The possibility of diminished blood flow in the brain is studied as one of the factors resulting from an increase in skeletal muscle blood volume concomitant with other characteristics of motion sickness. Thermistors are implanted in the thalamus of dogs and blood flow changes are recorded while they are subjected to sinusoidal movement on a two pole swing. Results of these initial steps in a proposed long term exploration of different areas of the brain are presented.

Johnson, W. H.↗
NASA NTRS1976

Body size and chronic acceleration

Experiments were conducted to study body composition as a function of acceleration (1-4.7 G) in mice and rats. It is shown that fat-free body mass is a predictable function of acceleration, and that of nine components of the fat-free body mass only skeletal muscle, liver and heart contributed to observed changes induced by delta G. Fat-free body mass was found to pass through a maximum at 1 G when it was plotted vs G for mice, rats and monkeys (1-4.7 G) and men (0-1 G).

Pitts, G. C.↗
NASA NTRS1976

A role for glucose in hypothermic hamsters

Hypothermic hamsters at a rectal temperature of 7 C showed a fivefold increase in survival times from 20 to 100.5 hr when infused with glucose which maintained a blood level at about 45 mg/100 ml. A potential role for osmotic effects of the infusion was tested and eliminated. There was no improvement in survival of 3-O-methylglucose or dextran 40-infused animals. The fact that death eventually occurs even in the glucose-infused animal after about 4 days and that oxygen consumption undergoes a slow decrement in that period suggests that hypothermic survival is not wholly substrate limited. Radioactive tracer showed that localization of the C-14 was greatest in brain tissue and diaphragm, intermediate in heart and kidney, and lowest in skeletal muscle and liver. The significance of the label at sites important to respiration and circulation was presented.

Resch, G. E.↗
NASA NTRS1977

The Orbiting Primate Experiment (OPE)

Instrumentation and life support systems are described for an experiment to determine the physiological effects of long term space flight on unrestrained, minimally instrumented rhesus macaques flown in orbit for periods up to six months or one year. On return from orbit, vestibular, cardiovascular, and skeletal muscle function will be tested. Blood chemistry and hematological studies will be conducted as well as tests of the immunological competence of selected animals. Nasal, rectal, and throat swabs will be used for bacterial and viral studies, and histopathological and histochemical investigations will be be made of all organs using light and electron microscopy. The experiment is being considered as a payload for the biomedical experiment scientific satellite.

Bourne, G. H.↗
NASA NTRS1978

The rate of synthesis and decomposition of tissue proteins in hypokinesia and increased muscular activity

During hypokinesia and physical loading (swimming) of rats, the radioactivity of skeletal muscle, liver, kidney, heart, and blood proteins was determined after administration of radioactive amino acids. Tissue protein synthesis decreased during hypokinesia, and decomposition increased. Both synthesis and decomposition increased during physical loading, but anabolic processes predominated in the total tissue balance. The weights of the animals decreased in hypokinesia and increased during increased muscle activity.

Fedorov, I. V.↗
NASA NTRS1980

Rat reaction to hypokinesia after prior adaptation to hypoxia

The effect of prior hypoxia adaptation on body tolerance to hypokinesia was investigated. Rats trained to a 50 day period of hypokinesia and hypoxia with a preliminary month of adaptation to hypoxia showed less weight loss, higher indices for red blood content, heightened reactivity of the overall organism and the central nervous system to acute hypoxia, and decreased modification of the skeletal muscles compared to rats subjected to hypokinesia alone.

Barashova, Z. I.↗
NASA NTRS1979

Mechanism of disorder of plastic processes in tissue during prolonged hypokinesia

The subcellular structures of the myocardium, skeletal muscles, liver and kidneys of adult rats subjected to hypokinesia (in immobilization chambers) for 15, 30, and 45 days were studied. An anabolyser (retabolil) and vitamin D (a Ca metabolism regulator) were administered to two groups of rats. On the second week of hypokinesia, inhibition of synthesis processes was observed. Administration of retabolil increased protein synthesis both in the normal and hypokinesia-subjected rats; however, in the latter group, synthesis did not completely normalize, especially in the myocardium. Administration of vitamin D also stimulated protein synthesis, apparently by normalizing Ca tissue metabolism. The combined action of both preparations was the most effective in normalizing protein synthesis intensity. It was concluded that inhibition of synthesis is related to weakening of hormone synthesis induction and disorder of Ca metabolism.

Makarov, G. A.↗
NASA NTRS1982

Effect of prolonged hypokinesia on resistance of resistive vessels in rats

Under the effect of prolonged hypokinesia, the perfusion pressure in resistive vessels, measured under conditions of deep anesthesia and complete denervation, increased by approximately the same degree as arterial pressure in non-anesthetized animals. The increase in arterial, perfusion pressure and the resistance of resistive vessels in animals subjected to prolonged hypokinesia was accompanied by an increase in adrenoreactivity. During prolonged hypokinesia, partial obliteration of the vascular bed of the skeletal muscles plays a significant role in the observed increase in resistance of vessels of the extremities. The increase in adrenoreactivity of the vessels during hypokinesia may be realized as a partial case of an increase in the adrenoreactivity of structures whose innervation is disturbed.

Saltykova, V. A.↗