Low Cell pH Depresses Peak Power in Rat Skeletal Muscle Fibres at Both 30°C and 15°C: Implications for Muscle Fatigue

Historically, an increase in intracellular H+ (decrease in cell pH) was thought to contribute to muscle fatigue by direct inhibition of the cross-bridge leading to a reduction in velocity and force. More recently, due to the observation that the effects were less at temperatures closer to those observed in vivo, the importance of H+ as a fatigue agent has been questioned. The purpose of this work was to re-evaluate the role of H+ in muscle fatigue by studying the effect of low pH (6.2) on force, velocity and peak power in rat fast-and slow-twitch muscle fibres at 15°C and 30°C. Skinned fast type IIa and slow type I fibres were prepared from the gastrocnemius and soleus, respectively, mounted between a force transducer and position motor, and studied at 15°C and 30°C and pH 7.0 and 6.2, and fibre force (P0), unloaded shortening velocity (V0), force–velocity, and force–power relationships determined. Consistent with previous observations, low pH depressed the P0 of both fast and slow fibres, less at 30°C (4–12%) than at 15°C (30%). However, the low pH-induced depressions in slow type I fibre V0 and peak power were both significantly greater at 30°C (25% versus 9% for V0 and 34% versus 17% for peak power). For the fast type IIa fibre type, the inhibitory effect of low pH on V0 was unaltered by temperature, while for peak power the inhibition was reduced at 30°C (37% versus 18%). The curvature of the force–velocity relationship was temperature sensitive, and showed a higher a/P0 ratio (less curvature) at 30°C. Importantly, at 30°C low pH significantly depressed the ratio of the slow type I fibre, leading to less force and velocity at peak power. These data demonstrate that the direct effect of low pH on peak power in both slow-and fast-twitch fibres at near-in vivo temperatures (30°C) is greater than would be predicted based on changes in P0, and that the fatigue-inducing effects of low pH on cross-bridge function are still substantial and important at temperatures approaching those observed in vivo

Functional and Structural Adaptations of Skeletal Muscle to Microgravity

Our purpose is to summarize the major effects of space travel on skeletal muscle with particular emphasis on factors that alter function. The primary deleterious changes are muscle atrophy and the associated decline in peak force and power. Studies on both rats and humans demonstrate a rapid loss of cell mass with microgravity. In rats, a reduction in muscle mass of up to 37% was observed within 1 week. For both species, the antigravity soleus muscle showed greater atrophy than the fast-twitch gastrocnemius. However, in the rat, the slow type I fibers atrophied more than the fast type II fibers, while in humans, the fast type II fibers were at least as susceptible to space-induced atrophy as the slow fiber type. Space flight also resulted in a significant decline in peak force. For example, the maximal voluntary contraction of the human plantar flexor muscles declined by 20–48% following 6 months in space, while a 21 % decline in the peak force of the soleus type I fibers was observed after a 17-day shuttle flight. The reduced force can be attributed both to muscle atrophy and to a selective loss of contractile protein. The former was the primary cause because, when force was expressed per cross-sectional area (kNm-2), the human fast type II and slow type I fibers of the soleus showed no change and a 4% decrease in force, respectively. Microgravity has been shown to increase the shortening velocity of the plantar flexors. This increase can be attributed both to an elevated maximal shortening velocity (V0) of the individual slow and fast fibers and to an increased expression of fibers containing fast myosin. Although the cause of the former is unknown, it might result from the selective loss of the thin filament actin and an associated decline in the internal drag during cross-bridge cycling. Despite the increase in fiber V0, peak power of the slow type I fiber was reduced following space flight. The decreased power was a direct result of the reduced force caused by the fiber atrophy. In addition to fiber atrophy and the loss of force and power, weightlessness reduces the ability of the slow soleus to oxidize fats and increases the utilization of muscle glycogen, at least in rats. This substrate change leads to an increased rate of fatigue. Finally, with return to the 1 g environment of earth, rat studies have shown an increased occurrence of eccentric contraction-induced fiber damage. The damage occurs with re-loading and not in-flight, but the etiology has not been established

Concurrent muscle and bone deterioration in a murine model of cancer cachexia

Cachexia is defined as an excessive, involuntary loss of fat and lean tissue. We tested the validity of the Lewis lung carcinoma (LLC) as a model of cancer cachexia and examined its effect on the two major lean tissue components, skeletal muscle and bone. LLC cells (0.75 × 106) were injected into the left thigh of C57BL/6 mice. Control mice received an equal volume injection of growth media. Tumors were observed in all LLC-injected animals 21 and 25 days post inoculation. LLC-injected animals showed significant reductions in fat and lean mass despite having the same average daily caloric intake as media-treated mice. Global bone mineral density (BMD) had fallen by 5% and 6% in the LLC animals at 21 and 25 days, respectively, compared to a BMD increase of 5% in the 25-day media-treated animals. Extensor digitorum longus (EDL) muscles (isolated from the noninjected hindlimb) showed earlier and quantitatively greater losses in mass, physiological cross-sectional area (pCSA), and tetanic force compared to soleus muscles from the same hindlimb. By the 25th day post-LLC inoculation, EDL force/pCSA was reduced by 19% versus media treatment. This loss in specific force was not trivial as it accounted for about one-third of the reduction in EDL absolute force at this time point. Muscle strips dissected from the diaphragm of LLC mice also exhibited significant reductions in force/pCSA at day 25. We conclude that LLC is a valid model of cachexia that induces rapid losses in global BMD and in limb and respiratory muscle function

The Function of Second-Order Male Alliances in St. Johns River Dolphins (Tursiops truncatus)

Bottlenose dolphins (Tursiops truncatus) have a sexually segregated fission-fusion society, in which males and females form different types of social groups for different purposes. Social interactions among dolphins are frequent, and group composition changes just as often. Male-male association patterns reveal the formation of alliances, which range in complexity. Recently, second-order alliance formation was confirmed in the St. Johns River, but the function of these alliances is unknown. To investigate their function, this research analyzes the seasonality of first and second-order alliance formation, and whether female presence plays a role. It was hypothesized that higher level male alliances form in order to improve mating opportunities in a society dominated by male-male competition. It follows then that more male alliances will form during the breeding season, including second-order alliances, and alliances of both levels will form more often in the presence of females. By analyzing boat-based photo-identification survey data, it was found that the average number of alliances was 1.5 per group in all seasons, if there was at least one alliance present. More alliances were sighted in groups with females, and this trend followed for the second-order alliances. The percent of sightings with first-order alliances was higher in the breeding season as expected. However, most of the second-order alliances were sighted in the non-breeding season, which correlates with increased aggression in the non-breeding season. This suggests that second-order alliances may be integral in establishing male dominance prior to the start of the breeding season

Optimal Policies for the Management of a Plug-In Hybrid Electric Vehicle Swap Station

Optimizing operations at plug-in hybrid electric vehicle (PHEV) battery swap stations is internally motivated by the movement to make transportation cleaner and more efficient. A PHEV swap station allows PHEV owners to quickly exchange their depleted PHEV battery for a fully charged battery. The PHEV-Swap Station Management Problem (PHEV-SSMP) is introduced, which models battery charging and discharging operations at a PHEV swap station facing nonstationary, stochastic demand for battery swaps, nonstationary prices for charging depleted batteries, and nonstationary prices for discharging fully charged batteries. Discharging through vehicle-to-grid is beneficial for aiding power load balancing. The objective of the PHEV-SSMP is to determine the optimal policy for charging and discharging batteries that maximizes expected total profit over a fixed time horizon. The PHEV-SSMP is formulated as a finite-horizon, discrete-time Markov decision problem and an optimal policy is found using dynamic programming. Structural properties are derived, to include sufficiency conditions that ensure the existence of a monotone optimal policy. A computational experiment is developed using realistic demand and electricity pricing data. The optimal policy is compared to two benchmark policies which are easily implementable by PHEV swap station managers. Two designed experiments are conducted to obtain policy insights regarding the management of PHEV swap stations. These insights include the minimum battery level in relationship to PHEVs in a local area, the incentive necessary to discharge, and the viability of PHEV swap stations under many conditions

Emerging global markets: A Five-country comparative study

In 2005, the GDP of the emerging economies of the world accounted for more than 50% of the total world’s GDP (measured at purchasing power parity). This means that the rich countries (i.e., United States, the European Union, Japan) no longer control the world economy. When combined with the impact of digital technologies, this continuing shift in economic power means that the printing industry is increasingly focusing on emerging markets seeking opportunities and profits. This exploratory study focuses on five of the largest emerging markets: China, India, Russia, Brazil, and Mexico. The study includes two phases. Phase one involves gathering public and industry macro- and micro-economic data in each of these emerging market countries. Phase two involved interviewing local printing experts in each country. In addition to individual country industry profiles the study looks at several common challenges facing the printing industry in all five countries. These include overcapacity of aging production facilities, fierce price competition for basic commodity products and services, the impact of the Internet on print media consumption, monetary and taxation policies, national industrial and international trade strategies, and changes in educational policies and literacy rates. Comparisons among the five countries result in a number of interesting observations. For example, it is clear that tariff and tax policies in each country strongly influence the rate of development of the globalizing part of the industry. These observations combined with macroeconomic and industry-specific data from each country have led the researchers to a better understanding of how these countries will likely participate in the emerging global print communications industry. In each of these five countries there are two distinct segments of the printing industry. First, the old indigenous industry that serves traditional domestic markets with products and services that often is price-driven and usually falls short of meeting the needs of domestic companies seeking export business or of multinational corporations doing business domestically. And second, an emerging industry that provides value-intense and world class manufactured goods and services. These include products such as the leading national newspapers manufactured in India, packaging materials manufactured in Mexico, and high-end books manufactured in China

In vivo gene editing in dystrophic mouse muscle and muscle stem cells

Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the mutated transcript can produce an in-frame mRNA and a truncated, but still functional, protein. In this study, we developed and tested a direct gene-editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored the Dmd reading frame in myofibers, cardiomyocytes, and muscle stem cells after local or systemic delivery. AAV-Dmd CRISPR treatment partially recovered muscle functional deficiencies and generated a pool of endogenously corrected myogenic precursors in mdx mouse muscle.National Institute of General Medical Sciences (U.S.) (Grant T2GM007753)National Institute of Mental Health (U.S.) (Grant 5DP1-MH100706)National Institutes of Health (U.S.) (Grant 5R01DK097768-03

Peak Force and Maximal Shortening Velocity of Soleus Fibers after Non-Weight-bearing and Resistance Exercise

Widrick, Jeffrey J., and Robert H. Fitts. Peak force and maximal shortening velocity of soleus fibers after non-weight-bearing and resistance exercise. J. Appl. Physiol. 82(1): 189–195, 1997.—This study examined the effectiveness of resistance exercise as a countermeasure to non-weight-bearing-induced alterations in the absolute peak force, normalized peak force (force/fiber cross-sectional area), peak stiffness, and maximal shortening velocity (V o) of single permeabilized type I soleus muscle fibers. Adult rats were subjected to one of the following treatments: normal weight bearing (WB), non-weight bearing (NWB), or NWB with exercise treatments (NWB+Ex). The hindlimbs of the NWB and NWB+Ex rats were suspended for 14 days via tail harnesses. Four times each day, the NWB+Ex rats were removed from suspension and performed 10 climbs (∼15 cm each) up a steep grid with a 500-g mass (∼1.5 times body mass) attached to their tail harness. NWB was associated with significant reductions in type I fiber diameter, absolute force, normalized force, and stiffness. Exercise treatments during NWB attenuated the decline in fiber diameter and absolute force by almost 60% while maintaining normalized force and stiffness at WB levels. Type I fiberV oincreased by 33% with NWB and remained at this elevated level despite the exercise treatments. We conclude that in comparison to intermittent weight bearing only (J. J. Widrick, J. J. Bangart, M. Karhanek, and R. H. Fitts. J. Appl. Physiol. 80: 981–987, 1996), resistance exercise was more effective in attenuating alterations in type I soleus fiber absolute force, normalized force, and stiffness but was less effective in restoring type I fiberV oto WB levels

Fuel for the work required: a practical approach to amalgamating train-low paradigms for endurance athletes.

Using an amalgamation of previously studied "train-low" paradigms, we tested the effects of reduced carbohydrate (CHO) but high leucine availability on cell-signaling responses associated with exercise-induced regulation of mitochondrial biogenesis and muscle protein synthesis (MPS). In a repeated-measures crossover design, 11 males completed an exhaustive cycling protocol with high CHO availability before, during, and after exercise (HIGH) or alternatively, low CHO but high protein (leucine enriched) availability (LOW + LEU). Muscle glycogen was different (P < 0.05) pre-exercise (HIGH: 583 ± 158, LOW + LEU: 271 ± 85 mmol kg(-1) dw) but decreased (P < 0.05) to comparable levels at exhaustion (≈100 mmol kg(-1) dw). Despite differences (P < 0.05) in exercise capacity (HIGH: 158 ± 29, LOW + LEU: 100 ± 17 min), exercise induced (P < 0.05) comparable AMPKα2 (3-4-fold) activity, PGC-1α (13-fold), p53 (2-fold), Tfam (1.5-fold), SIRT1 (1.5-fold), Atrogin 1 (2-fold), and MuRF1 (5-fold) gene expression at 3 h post-exercise. Exhaustive exercise suppressed p70S6K activity to comparable levels immediately post-exercise (≈20 fmol min(-1) mg(-1)). Despite elevated leucine availability post-exercise, p70S6K activity remained suppressed (P < 0.05) 3 h post-exercise in LOW + LEU (28 ± 14 fmol min(-1) mg(-1)), whereas muscle glycogen resynthesis (40 mmol kg(-1) dw h(-1)) was associated with elevated (P < 0.05) p70S6K activity in HIGH (53 ± 30 fmol min(-1) mg(-1)). We conclude: (1) CHO restriction before and during exercise induces "work-efficient" mitochondrial-related cell signaling but; (2) post-exercise CHO and energy restriction maintains p70S6K activity at basal levels despite feeding leucine-enriched protein. Our data support the practical concept of "fuelling for the work required" as a potential strategy for which to amalgamate train-low paradigms into periodized training programs

An ecophysiological investigation of the effects of macroalgae on juvenile corals and larvae on coral reefs in the Pacific and Caribbean

On macroalgal-dominated reefs, the continuation of coral populations is dependent on successful recruitment and post-settlement success, both of which may be challenged by the presence of macroalgae. This study considers how the environment, particularly macroalgal abundance, contributes to the growth and survival of juvenile corals in two regions in the tropics: the South Pacific and the Caribbean. To determine how juvenile corals and coral larvae are affected by macroalgae in the back reef of Moorea, surveys and manipulative experiments were used to test the hypotheses that proximity to macroalgae with and without contact, or cover of macroalgae, will impact the survival and growth of early life stages of corals. Survival of Pocillopora damicornis larvae did not differ when they were incubated in situ adjacent to coral, macroalgae, or rock. Growth of juvenile colonies of massive Porites spp. and Pocillopora spp. were unaffected by centimeter-scale proximity to macroalgae. Additionally, growth was not affected by cover of macroalgae in 4-m2 plots, or by cages, which protected coral from macroalgal abrasion. Caged corals tended to grow faster, although this was not significant, and I hypothesize that this was related to protection from fish predation on lower cover plots, and from algae on higher cover plots. Macroalgae may not decrease Porites and Pocillopora growth through chemical effects, but factors including macroalgal cover may have indirect effects on the fish community that adversely affect exposed coral colonies. In St. John, US Virgin Islands, 12 sites distributed between White Point and Cabritte were selected and analyzed for benthic cover, herbivore abundance, rugosity, and rock type. Surveys of juvenile corals were conducted to determine whether the abundance and distribution of juvenile colonies within three types of microhabitats were affected by site characteristics, including macroalgae cover, and herbivore abundance. While the characteristics analyzed at the site level explained 75.9% of the variation between sites, these characteristics were not predictive of juvenile microhabitat distribution; ~ 75% of juvenile corals were found on exposed habitats at every site. While juvenile coral distribution among microhabitats was not related to site variation, survival rates within microhabitats may still vary among these sites.California State University, Northridge. Department of Biology