Effects of high and low velocity muscle contraction on myosin heavy chain mRNA and protein expression in conjunction with muscle performance in the elderly

Title: Effects of high and low velocity muscle contraction on myosin heavy chain mRNA and protein expression in conjunction with muscle performance in the elderly Introduction: Aging decreases skeletal muscle mass and contractile ability. This decreases the capacity for an individual to successfully carry out activities of daily living, eventually leading to physical disability. Recent research demonstrates that when compared to conventional resistance training, high velocity resistance training (HVRT) may be more effective in slowing or reversing age related declines in skeletal muscle. However, there is currently a paucity of research which has aimed to investigate the transcriptional and translational events taking place within senescent skeletal muscle in response to HVRT. Purpose: To examine the velocity specificity of resistance training by directly comparing changes in muscle transcription, translation, performance, and function in older adults. Methods: Twenty-six older adults were randomized to partake in 6 weeks of either low velocity resistance training (LVRT) or HVRT. Subjects underwent pre- and post-training strength and functional testing. A subsample of subjects also underwent subcutaneous needle biopsies of the vastus lateralis pre- and post-training. Results: From baseline to post-training, there were several significant (P \u3c 0.05) differences in muscle performance and functional characteristics in LVRT (n = 13) and HVRT (n = 13) groups. Our results demonstrate HVRT provides a greater number of muscular enhancements when compared to LVRT, particularly under conditions of high velocity muscle contraction. MyHc-a mRNA showed a significant (P \u3c 0.01) decrease (.93-fold ± 0.12) in LVRT and a significant (P \u3c 0.01) increase (2.0-fold ± .62) in HVRT. MyHc-IIa mRNA showed a significant (P \u3c 0.05) increase (1.2-fold ± 0.01) in HVRT. MyHc-IIx mRNA showed a significant (P \u3c 0.01) decrease (0.99-fold ± 0.004) in LVRT). MyHc-b/slow had a significant (P\u3c 0.05) decrease in HVRT (1.0 ± 0.12 vs 0.84 ± 0.13, pre v post). MyHc-IIx decreased (P \u3c 0.01) in LVRT (1.0 ± 0.06 vs 0.87 ± 0.06, pre vs post). Conclusion: HVRT is emerging as the optimal training stimulus for the older adult. The present study demonstrates, in addition to increased muscular performance and functional outcomes, HVRT may also evoke a favorable (i.e., slow-to-fast) transcriptional and translational response in MyHC

Towards Distributed Quantum Computing by Qubit and Gate Graph Partitioning Techniques

Distributed quantum computing is motivated by the difficulty in building large-scale, individual quantum computers. To solve that problem, a large quantum circuit is partitioned and distributed to small quantum computers for execution. Partitions running on different quantum computers share quantum information using entangled Bell pairs. However, entanglement generation and purification introduces both a runtime and memory overhead on distributed quantum computing. In this paper we study that trade-off by proposing two techniques for partitioning large quantum circuits and for distribution to small quantum computers. Our techniques map a quantum circuit to a graph representation. We study two approaches: one that considers only gate teleportation, and another that considers both gate and state teleportation to achieve the distributed execution. Then we apply the METIS graph partitioning algorithm to obtain the partitions and the number of entanglement requests between them. We use the SeQUeNCe quantum communication simulator to measure the time required for generating all the entanglements required to execute the distributed circuit. We find that the best partitioning technique will depend on the specific circuit of interest.Comment: Presented at IEEE Quantum Week 2023 (QCE23

Scalable Quantum Networks: Congestion-Free Hierarchical Entanglement Routing with Error Correction

We introduce Quantum Tree Networks (QTN), an architecture for hierarchical multi-flow entanglement routing. The network design is a $k$-ary tree where end nodes are situated on the leaves and routers at the internal nodes, with each node connected to $k$ nodes in the child layer. The channel length between nodes grows with a rate $a_k$, increasing as one ascends from the leaf to the root node. This construction allows for congestion-free and error-corrected operation with qubit-per-node overhead to scale sublinearly with the number of end nodes, $N$. The overhead for a $k$-ary QTN scales as $\mathcal{O}(N^{\log_k a_k} \cdot \log_k N)$ and is sublinear for all $k$ with minimal surface-covering end nodes. More specifically, the overhead of quarternary ($k=4$) QTN is $\sim \mathcal{O}(N^{0.25}\cdot\log_4 N)$. Alternatively, when end nodes are distributed over a square lattice, the quaternary tree routing gives the overhead $\sim \mathcal{O}(\sqrt{N}\cdot\log_4 N)$. Our network-level simulations demonstrate a size-independent threshold behavior of QTNs. Moreover, tree network routing avoids the necessity for intricate multi-path finding algorithms, streamlining the network operation. With these properties, the QTN architecture satisfies crucial requirements for scalable quantum networks.Comment: 13 pages, 5 figure

Myonuclear Domain Flexibility Challenges Rigid Assumptions on Satellite Cell Contribution to Skeletal Muscle Fiber Hypertrophy

Satellite cell-mediated myonuclear accretion is thought to be required for skeletal muscle fiber hypertrophy, and even drive hypertrophy by preceding growth. Recent studies in humans and rodents provide evidence that challenge this axiom. Specifically, Type 2 muscle fibers reliably demonstrate a substantial capacity to hypertrophy in the absence of myonuclear accretion, challenging the notion of a tightly regulated myonuclear domain (i.e., area that each myonucleus transcriptionally governs). In fact, a “myonuclear domain ceiling”, or upper limit of transcriptional output per nucleus to support hypertrophy, has yet to be identified. Satellite cells respond to muscle damage, and also play an important role in extracellular matrix remodeling during loading-induced hypertrophy. We postulate that robust satellite cell activation and proliferation in response to mechanical loading is largely for these purposes. Future work will aim to elucidate the mechanisms by which Type 2 fibers can hypertrophy without additional myonuclei, the extent to which Type 1 fibers can grow without myonuclear accretion, and whether a true myonuclear domain ceiling exists

Myonuclear Transcriptional Dynamics in Response to Exercise Following Satellite Cell Depletion

Skeletal muscle is composed of post-mitotic myofibers that form a syncytium containing hundreds of myonuclei. Using a progressive exercise training model in the mouse and single nucleus RNA-sequencing (snRNA-seq) for high-resolution characterization of myonuclear transcription, we show myonuclear functional specialization in muscle. After 4 weeks of exercise training, snRNA-seq reveals that resident muscle stem cells, or satellite cells, are activated with acute exercise but demonstrate limited lineage progression while contributing to muscle adaptation. In the absence of satellite cells, a portion of nuclei demonstrates divergent transcriptional dynamics associated with mixed-fate identities compared with satellite cell replete muscles. These data provide a compendium of information about how satellite cells influence myonuclear transcription in response to exercise

Supplemental Nutrition Assistance Program (SNAP)-authorized retailers received a low score using the Business Impact Assessment for Obesity and population-level nutrition (BIA-Obesity) tool

Background: The Supplemental Nutrition Assistance Program (SNAP) supports Americans with lower income to purchase dietary products at authorized retailers. This research aimed to evaluate SNAP-authorized retailers’ public commitments in support of nutrition security and to examine differences between traditional grocers and nontraditional (e.g., convenience, drug, dollar) SNAP-authorized retailers’ public commitments. Methods: Prominent United States (U.S.) SNAP-authorized retailers nationally and in two U.S. states (California and Virginia) were identified based on number of store locations (n = 61). Public information available in grey literature were reviewed and scored using the Business Impact Assessment for Obesity and population-level nutrition (BIA-Obesity) tool. SNAP-authorized retailers were classified as traditional (e.g., grocery) or nontraditional (e.g., non-grocery) retailers. Total BIA-Obesity from 0 to 615, representing low to optimal support) and category scores were calculated for corporate strategy, relationships with external organizations, product formulation, nutrition labeling, product and brand promotion, and product accessibility. Descriptive statistics were used to describe BIA-Obesity scores overall and by category. Mann–Whitney U was used to test for potential differences in median BIA-Obesity total scores between traditional and nontraditional SNAP-authorized retailers (a priori, p \u3c 0.05). Results: Average total BIA-Obesity scores for SNAP-authorized retailers ranged from 0 to 112 (16.5 ± 23.3). Total BIA-Obesity scores for traditional SNAP-authorized retailers (32.7 ± 33.6; median 25) were higher than nontraditional SNAP-authorized retailer scores (11.2 ± 16; median 5) (p = 0.008). For BIA-Obesity categories, average scores were highest for the category relationships with external organizations (8.3 ± 10.3) and lowest for promotion practices (0.6 ± 2.1). Conclusions: Results of this research underscore a dearth of available evidence and substantial opportunity for improvement regarding SNAP-authorized retailer strategies to support nutrition security among Americans with lower income

Deep Learning with Coherent VCSEL Neural Networks

Deep neural networks (DNNs) are reshaping the field of information processing. With their exponential growth challenging existing electronic hardware, optical neural networks (ONNs) are emerging to process DNN tasks in the optical domain with high clock rates, parallelism and low-loss data transmission. However, to explore the potential of ONNs, it is necessary to investigate the full-system performance incorporating the major DNN elements, including matrix algebra and nonlinear activation. Existing challenges to ONNs are high energy consumption due to low electro-optic (EO) conversion efficiency, low compute density due to large device footprint and channel crosstalk, and long latency due to the lack of inline nonlinearity. Here we experimentally demonstrate an ONN system that simultaneously overcomes all these challenges. We exploit neuron encoding with volume-manufactured micron-scale vertical-cavity surface-emitting laser (VCSEL) transmitter arrays that exhibit high EO conversion (<5 attojoule/symbol with $V_\pi$=4 mV), high operation bandwidth (up to 25 GS/s), and compact footprint (<0.01 mm$^2$ per device). Photoelectric multiplication allows low-energy matrix operations at the shot-noise quantum limit. Homodyne detection-based nonlinearity enables nonlinear activation with instantaneous response. The full-system energy efficiency and compute density reach 7 femtojoules per operation (fJ/OP) and 25 TeraOP/(mm$^2\cdot$ s), both representing a >100-fold improvement over state-of-the-art digital computers, with substantially several more orders of magnitude for future improvement. Beyond neural network inference, its feature of rapid weight updating is crucial for training deep learning models. Our technique opens an avenue to large-scale optoelectronic processors to accelerate machine learning tasks from data centers to decentralized edge devices.Comment: 10 pages, 5 figure

A Novel Tetracycline-Responsive Transgenic Mouse Strain for Skeletal Muscle-Specific Gene Expression

Background: The tetracycline-responsive system (Tet-ON/OFF) has proven to be a valuable tool for manipulating gene expression in an inducible, temporal, and tissue-specific manner. The purpose of this study was to create and characterize a new transgenic mouse strain utilizing the human skeletal muscle α-actin (HSA) promoter to drive skeletal muscle-specific expression of the reverse tetracycline transactivator (rtTA) gene which we have designated as the HSA-rtTA mouse. Methods: To confirm the HSA-rtTA mouse was capable of driving skeletal muscle-specific expression, we crossed the HSA-rtTA mouse with the tetracycline-responsive histone H2B-green fluorescent protein (H2B-GFP) transgenic mouse in order to label myonuclei. Results: Reverse transcription-PCR confirmed skeletal muscle-specific expression of rtTA mRNA, while single-fiber analysis showed highly effective GFP labeling of myonuclei in both fast- and slow-twitch skeletal muscles. Pax7 immunohistochemistry of skeletal muscle cross-sections revealed no appreciable GFP expression in satellite cells. Conclusions: The HSA-rtTA transgenic mouse allows for robust, specific, and inducible gene expression across muscles of different fiber types. The HSA-rtTA mouse provides a powerful tool to manipulate gene expression in skeletal muscle

Deletion of SA β-Gal+ Cells Using Senolytics Improves Muscle Regeneration in Old Mice

Systemic deletion of senescent cells leads to robust improvements in cognitive, cardiovascular, and whole-body metabolism, but their role in tissue reparative processes is incompletely understood. We hypothesized that senolytic drugs would enhance regeneration in aged skeletal muscle. Young (3 months) and old (20 months) male C57Bl/6J mice were administered the senolytics dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi-weekly for 4 months. Tibialis anterior (TA) was then injected with 1.2% BaCl2 or PBS 7- or 28 days prior to euthanization. Senescence-associated β-Galactosidase positive (SA β-Gal+) cell abundance was low in muscle from both young and old mice and increased similarly 7 days following injury in both age groups, with no effect of D+Q. Most SA β-Gal+ cells were also CD11b+ in young and old mice 7- and 14 days following injury, suggesting they are infiltrating immune cells. By 14 days, SA β-Gal+/CD11b+ cells from old mice expressed senescence genes, whereas those from young mice expressed higher levels of genes characteristic of anti-inflammatory macrophages. SA β-Gal+ cells remained elevated in old compared to young mice 28 days following injury, which were reduced by D+Q only in the old mice. In D+Q-treated old mice, muscle regenerated following injury to a greater extent compared to vehicle-treated old mice, having larger fiber cross-sectional area after 28 days. Conversely, D+Q blunted regeneration in young mice. In vitro experiments suggested D+Q directly improve myogenic progenitor cell proliferation. Enhanced physical function and improved muscle regeneration demonstrate that senolytics have beneficial effects only in old mice