The inner-mitochondrial distribution of Oxa1 depends on the growth conditions and on the availability of substrates

The Oxa1 protein is a well-conserved integral protein of the inner membrane of mitochondria. It mediates the insertion of both mitochondrial- and nuclear-encoded proteins from the matrix into the inner membrane. We investigated the distribution of budding yeast Oxa1 between the two subdomains of the contiguous inner membrane--the cristae membrane (CM) and the inner boundary membrane (IBM)--under different physiological conditions. We found that under fermentable growth conditions, Oxa1 is enriched in the IBM, whereas under nonfermentable (respiratory) growth conditions, it is predominantly localized in the CM. The enrichment of Oxa1 in the CM requires mitochondrial translation; similarly, deletion of the ribosome-binding domain of Oxa1 prevents an enrichment of Oxa1 in the CM. The predominant localization in the IBM under fermentable growth conditions is prevented by inhibiting mitochondrial protein import. Furthermore, overexpression of the nuclear-encoded Oxa1 substrate Mdl1 shifts the distribution of Oxa1 toward the IBM. Apparently, the availability of nuclear- and mitochondrial-encoded substrates influences the inner-membrane distribution of Oxa1. Our findings show that the distribution of Oxa1 within the inner membrane is dynamic and adapts to different physiological needs.     

Online video-based resistance training improves the physical capacity of junior basketball athletes

ABSTRACT: Klusemann, MJ, Pyne, DB, Fay, T, and Drinkwater, EJ. Online Video-Based Resistance Training Improves the Physical Capacity of Junior Basketball Athletes. J Strength Cond Res 26(10): 2677-2684, 2012-Junior basketball athletes require a well-designed resistance training program to improve their physical development. Lack of expert supervision and resistance training in junior development pathways may be overcome by implementing an online video-based program. The aim of this study was to compare the magnitude of improvement (change) in physical performance and strength and functional movement patterns of junior basketball athletes using either a fully supervised or an online video-based resistance training program. Thirty-eight junior basketball athletes (males, n = 17; age, 14 ± 1 year; height, 1.79 ± 0.10 m; mass, 67 ± 12 kg; females, n = 21; age, 15 ± 1 year; height, 1.70 ± 0.07 m; mass, 62 ± 8 kg) were randomly assigned into a supervised resistance training group (SG, n = 13), video training group (VG, n = 13) or control group (CG, n = 12) and participated in a 6-week controlled experimental trial. Pre- and posttesting included measures of physical performance (20-m sprint, step-in vertical jump, agility, sit and reach, line drill, and Yo-Yo intermittent recovery level 1), strength (15 s push-up and pull-up), and functional movement screening (FMS). Both SG and VG achieved 3-5% ± 2-4% (mean ± 90% confidence limits) greater improvements in several physical performance measures (vertical jump height, 20-m sprint time, and Yo-Yo endurance performance) and a 28 ± 21% greater improvement in push-up strength compared with the CG. The SG attained substantially larger gains in FMS scores over both the VG (12 ± 10%) and CG (13 ± 8%). Video-based training appears to be a viable option to improve physical performance and strength in junior basketball athletes. Qualified supervision is recommended to improve functional movement patterns in junior athletes.     

Muscle activation strategies during strength training with heavy loading vs. repetitions to failure

Going to failure, or not, has probably been one of the most debated issues during the history of strength training. However, few studies have directly compared the physiological effect of failure vs. nonfailure strength training. The purpose of this study was to evaluate muscle activation strategies with electromyography (EMG) during heavy repetitions vs. repetitions to failure with lighter resistance. Fifteen healthy untrained women performed a set with heavy loading (3 repetition maximum [RM]) and a set of repetitions to failure with lower resistance (～15 RM) during lateral raise with elastic tubing. Electromyographic amplitude and median power frequency of specific shoulder and neck muscles were analyzed, and the BORG CR10 scale was used to rate perceived loading immediately after each set of exercise. During the failure set, normalized EMG was significantly lower during the first repetition and significantly higher during the latter repetitions compared with the heavy 3-RM set (p < 0.05). Normalized EMG for the examined muscles increased throughout the set to failure in a curvilinear fashion--e.g., for the trapezius from 86 to 124% maximal voluntary contraction (p < 0.001)--and reached a plateau during the final 3-5 repetitions before failure. Median power frequency for all examined muscles decreased throughout the set to failure in a linear fashion, indicating progressively increasing fatigue. In conclusion, going to complete failure during lateral raise is not necessary to recruit the entire motor unit pool in untrained women--i.e., muscle activity reached a plateau 3-5 repetitions from failure with an elastic resistance of approximately 15 RM. Furthermore, strengthening exercises performed with elastic tubing seem to be an efficient resistance exercise and a feasible and practical alternative to traditional resistance equipment.     

Prime-boost vaccination with rBCG/rAd35 enhances CD8⁺ cytolytic T-cell responses in lesions from Mycobacterium tuberculosis-infected primates

To prevent the global spread of tuberculosis (TB) infection, a novel vaccine that triggers potent and long-lived immunity is urgently required. A plasmid-based vaccine has been developed to enhance activation of major histocompatibility complex (MHC) class I–restricted CD8+ cytolytic T cells using a recombinant Bacille Calmette-Guérin (rBCG) expressing a pore-forming toxin and the Mycobacterium tuberculosis (Mtb) antigens Ag85A, 85B and TB10.4 followed by a booster with a nonreplicating adenovirus 35 (rAd35) vaccine vector encoding the same Mtb antigens. Here, the capacity of the rBCG/rAd35 vaccine to induce protective and biologically relevant CD8⁺ T-cell responses in a nonhuman primate model of TB was investigated. After prime/boost immunizations and challenge with virulent Mtb in rhesus macaques, quantification of immune responses at the single-cell level in cryopreserved tissue specimen from infected organs was performed using in situ computerized image analysis as a technological platform. Significantly elevated levels of CD3⁺ and CD8⁺ T cells as well as cells expressing interleukin (IL)-7, perforin and granulysin were found in TB lung lesions and spleen from rBCG/rAd35-vaccinated animals compared with BCG/rAd35-vaccinated or unvaccinated animals. The local increase in CD8⁺ cytolytic T cells correlated with reduced expression of the Mtb antigen MPT64 and also with prolonged survival after the challenge. Our observations suggest that a protective immune response in rBCG/rAd35-vaccinated nonhuman primates was associated with enhanced MHC class I antigen presentation and activation of CD8+ effector T-cell responses at the local site of infection in Mtb-challenged animals.     

Characterization of a Novel Population of Low-Density Granulocytes Associated with Disease Severity in HIV-1 Infection

The mechanisms resulting in progressive immune dysfunction during the chronic phase of HIV infection are not fully understood. We have previously shown that arginase, an enzyme with potent immunosuppressive properties, is increased in HIV seropositive (HIV+) patients with low CD4⁺ T cell counts. Here we show that the cells expressing arginase in peripheral blood mononuclear cells of HIV+ patients are low-density granulocytes (LDGs) and that whereas these cells have a similar morphology to normal-density granulocyte, they are phenotypically different. Importantly, our results reveal that increased frequencies of LDGs correlate with disease severity in HIV+ patients.     

Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis

Background

Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury.

Methods and Results

Medline, EMBASE and Cochrane databases were searched for randomized clinical trials comparing remote ischemic conditioning, regardless of timing, with no conditioning. Two investigators independently selected suitable trials, assessed trial quality and extracted data. 23 studies in patients undergoing cardiac surgery (15 studies), percutaneous coronary intervention (four studies) and vascular surgery (four studies), comprising in total 1878 patients, were included in this review. Compared to no conditioning, remote ischemic conditioning did not reduce mortality (odds ratio 1.22 [95% confidence interval 0.48, 3.07]) or major adverse cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as was peak troponin release (standardized mean difference −0.28 [−0.47, −0.09]).

Conclusion

There is no evidence that remote ischemic conditioning reduces mortality associated with ischemic events; nor does it reduce major adverse cardiovascular events. However, remote ischemic conditioning did reduce the incidence of peri-procedural myocardial infarctions, as well as the release of troponin.