A Pilot, Virtual Exercise Intervention Improves Health and Fitness during the COVID-19 Pandemic

International Journal of Exercise Science 15(7): 1395-1417, 2022. Physical activity levels are low in individuals with chronic disease (e.g., obesity) and have worsened during the COVID-19 pandemic. Purpose: Our pilot study tested a virtual exercise intervention for rural-dwelling adults with chronic disease from January-April 2021 for changes in mental health, physical fitness, and physical activity and for intervention fidelity. Methods: Participants (n = 8 [7 female]; age = 57.5 ± 13.8 years, body mass index = 38.2 ± 8.0 kg/m2) completed an exercise intervention led virtually by collegiate health science majors. Participants attended two 60-minute sessions/week for 12 weeks, completing individually-tailored and progressed aerobic and muscle-strengthening training. A non-randomized control group matched on gender and age continued normal activity during the 12 weeks. Changes in mental health, physical fitness, and physical activity measures were evaluated using a 2x2 (group x time) analysis of covariance. Results: Both groups improved mental health, but only intervention participants lost weight (3.1 ± 1.0 kg; no change in controls). Step test, arm curls, and chair stands improved by 16.1-20.6% in the intervention and 7.8-12.1% in the control groups. Intervention participants did not increase overall physical activity during or after the intervention. Intervention fidelity was high; participants attended ~73% of sessions and rated the sessions 4.7 ± 0.6 (out of 5). Researcher observations rated exercise sessions as meeting 12.7 ± 0.6 of 16 goals. Conclusions: Our virtual exercise program was associated with positive mental health and physical fitness changes. Such programs may provide a method, even beyond the pandemic, to improve fitness in adults with chronic disease

Matrix Product Eigenstates for One-Dimensional Stochastic Models and Quantum Spin Chains

We show that all zero energy eigenstates of an arbitrary $m$--state quantum spin chain Hamiltonian with nearest neighbor interaction in the bulk and single site boundary terms, which can also describe the dynamics of stochastic models, can be written as matrix product states. This means that the weights in these states can be expressed as expectation values in a Fock representation of an algebra generated by $2m$ operators fulfilling $m^2$ quadratic relations which are defined by the Hamiltonian.Comment: 11 pages, Late

Implementation of Epigenetic Variation in Sorghum Selection and Implications for Crop Resilience Breeding

Crop resilience and yield stability are complex traits essential for food security. Sorghum bicolor is an important grain crop that shows promise for its natural resilience to drought and potential for marginal land production. We have developed sorghum lines in the Tx430 genetic background suppressed for MSH1 expression as a means of inducing de novo epigenetic variation, and have used these materials to evaluate changes in plant growth vigor. Plant crossing and selection in two distinct environments revealed features of phenotypic plasticity derived from MSH1 manipulation. Introduction of an epigenetic variation to an isogenic sorghum population, in the absence of selection, resulted in 10% yield increase under ideal field conditions and 20% increase under extreme low nitrogen conditions. However, incorporation of early-stage selection amplified these outcomes to 36% yield increase under ideal conditions and 64% increase under marginal field conditions. Interestingly, the best outcomes were derived by selecting mid-range performance early-generation lines rather than highest performing. Data also suggested that phenotypic plasticity derived from the epigenetic variation was nonuniform in its response to environmental variability but served to reduce genotype x environment interaction. The MSH1-derived growth vigor appeared to be associated with enhanced seedling root growth and altered expression of auxin response pathways, and plants showed evidence of cold tolerance, features consistent with observations made previously in Arabidopsis. These data imply that the MSH1 system is conserved across plant species, pointing to the value of parallel model plant studies to help devise effective plant selection strategies for epigenetic breeding in multiple crops

Inhibiting heat-shock protein 90 reverses sensory hypoalgesia in diabetic mice

Increasing the expression of Hsp70 (heat-shock protein 70) can inhibit sensory neuron degeneration after axotomy. Since the onset of DPN (diabetic peripheral neuropathy) is associated with the gradual decline of sensory neuron function, we evaluated whether increasing Hsp70 was sufficient to improve several indices of neuronal function. Hsp90 is the master regulator of the heat-shock response and its inhibition can up-regulate Hsp70. KU-32 (N-{7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyl-tetrahydro-2H-pyran-2-yloxy]-8-methyl-2-oxo-2H-chromen-3-yl}acetamide) was developed as a novel, novobiocin-based, C-terminal inhibitor of Hsp90 whose ability to increase Hsp70 expression is linked to the presence of an acetamide substitution of the prenylated benzamide moiety of novobiocin. KU-32 protected against glucose-induced death of embryonic DRG (dorsal root ganglia) neurons cultured for 3 days in vitro. Similarly, KU-32 significantly decreased neuregulin 1-induced degeneration of myelinated Schwann cell DRG neuron co-cultures prepared from WT (wild-type) mice. This protection was lost if the co-cultures were prepared from Hsp70.1 and Hsp70.3 KO (knockout) mice. KU-32 is readily bioavailable and was administered once a week for 6 weeks at a dose of 20 mg/kg to WT and Hsp70 KO mice that had been rendered diabetic with streptozotocin for 12 weeks. After 12 weeks of diabetes, both WT and Hsp70 KO mice developed deficits in NCV (nerve conduction velocity) and a sensory hypoalgesia. Although KU-32 did not improve glucose levels, HbA1c (glycated haemoglobin) or insulin levels, it reversed the NCV and sensory deficits in WT but not Hsp70 KO mice. These studies provide the first evidence that targeting molecular chaperones reverses the sensory hypoalgesia associated with DPN.This work was supported by grants from the Juvenile Diabetes Research Foundation and the National Institutes of Health [NS054847 and DK073594] (to R.T.D.) and [CA120458 and CA109265] (to B.S.J.B.)

Engineering an Antibiotic to Fight Cancer: Optimization of the Novobiocin Scaffold to Produce Anti-Proliferative Agents

Development of the DNA gyrase inhibitor, novobiocin, into a selective Hsp90 inhibitor was accomplished through structural modifications to the amide side chain, coumarin ring, and sugar moiety. These species exhibit ~700-fold improved anti-proliferative activity versus the natural product as evaluated by cellular efficacies against breast, colon, prostate, lung, and other cancer cell lines. Utilization of structure–activity relationships established for three novobiocin synthons produced optimized scaffolds, which manifest mid-nanomolar activity against a panel of cancer cell lines and serve as lead compounds that manifest their activities through Hsp90 inhibition