Feasibility and tolerability of whole-body, low-intensity vibration and its effects on muscle function and bone in patients with dystrophinopathies: a pilot study.

IntroductionDystrophinopathies are X-linked muscle degenerative disorders that result in progressive muscle weakness complicated by bone loss. This study's goal was to evaluate feasibility and tolerability of whole-body, low-intensity vibration (WBLIV) and its potential effects on muscle and bone in patients with Duchenne or Becker muscular dystrophy.MethodsThis 12-month pilot study included 5 patients (age 5.9-21.7 years) who used a low-intensity Marodyne LivMD plate vibrating at 30-90 Hz for 10 min/day for the first 6 months. Timed motor function tests, myometry, and peripheral quantitative computed tomography were performed at baseline and at 6 and 12 months.ResultsMotor function and lower extremity muscle strength remained either unchanged or improved during the intervention phase, followed by deterioration after WBLIV discontinuation. Indices of bone density and geometry remained stable in the tibia.ConclusionsWBLIV was well tolerated and appeared to have a stabilizing effect on lower extremity muscle function and bone measures. Muscle Nerve 55: 875-883, 2017

Editorial : New Insights into Estrogen/Estrogen Receptor Effects in the Cardiac and Skeletal Muscle

Funding Information: We thank the authors of this Research Topic for their contributions and the reviewers for their evaluations. Funding. DL acknowledges support from the National Institutes of Health (R01AG031743 and R01AG062899). GK acknowledges support from the DZHK (German Centre for Cardiovascular Research) and the BMBF (German Ministry for Education and Research)

Estrogen Regulates Estrogen Receptors and Antioxidant Gene Expression in Mouse Skeletal Muscle

Background: Estrogens are associated with the loss of skeletal muscle strength in women with age. Ovarian hormone removal by ovariectomy in mice leads to a loss of muscle strength, which is reversed with 17β-estradiol replacement. Aging is also associated with an increase in antioxidant stress, and estrogens can improve antioxidant status via their interaction with estrogen receptors (ER) to regulate antioxidant gene expression. The purpose of this study was to determine if ER and antioxidant gene expression in skeletal muscle are responsive to changes in circulating estradiol, and if ERs regulate antioxidant gene expression in this tissue. Methodology/Principal Findings: Adult C57BL/6 mice underwent ovariectomies or sham surgeries to remove circulating estrogens. These mice were implanted with placebo or 17β-estradiol pellets acutely or chronically. A separate experiment examined mice that received weekly injections of Faslodex to chronically block ERs. Skeletal muscles were analyzed for expression of ER genes and proteins and antioxidant genes. ERα was the most abundant, followed by Gper and ERβ in both soleus and EDL muscles. The loss of estrogens through ovariectomy induced ERα gene and protein expression in the soleus, EDL, and TA muscles at both the acute and chronic time points. Gpx3 mRNA was also induced both acutely and chronically in all 3 muscles in mice receiving 17β-estradiol. When ERs were blocked using Faslodex, Gpx3 mRNA was downregulated in the soleus muscle, but not the EDL and TA muscles. Conclusions/Significance: These data suggest that Gpx3 and ERα gene expression are sensitive to circulating estrogens in skeletal muscle. ERs may regulate Gpx3 gene expression in the soleus muscle, but skeletal muscle regulation of Gpx3 via ERs is dependent upon muscle type. Further work is needed to determine the indirect effects of estrogen and ERα on Gpx3 expression in skeletal muscle, and their importance in the aging process

Expression of Pro-inflammatory Chemokines CXCL1 and CXCL5 is Rapidly Upregulated Following Traumatic Injury

When a traumatic skeletal muscle injury occurs, such as crushing, contusion, laceration, or freezing, the body must mount an inflammatory response in order to clear muscle debris and fully regenerate the damaged muscle. This response is made up primarily of an innate immune response, which is amplified by the release of pro-inflammatory cytokines and chemokines and leads to the activation of several specific myeloid cell populations. The neutrophil, the first myeloid cell to infiltrate injured muscle, is attracted by the cytokines IFN-γ and TNF-α and the chemokines CXCL1 and CXCL5. However, the timing and magnitude of CXCL1 and CXCL5 signaling following muscle injury have not been carefully examined. Using a freeze injury model to induce a traumatic injury to muscle and real-time PCR, we showed that CXCL1 and CXCL5 expression is rapidly upregulated, within 60 minutes and 3 hours, respectively, in mouse tibialis anterior (TA) muscles following injury. This finding serves as a starting point in the characterization of pro-inflammatory chemokines’ impacts on the muscle injury inflammatory response.This research was supported by the Undergraduate Research Opportunities Program (UROP)

Transgenic overexpression of γ-cytoplasmic actin protects against eccentric contraction-induced force loss in mdx mice

<p>Abstract</p> <p>Background</p> <p>γ-cytoplasmic (γ-_cyto) actin levels are elevated in dystrophin-deficient <it>mdx </it>mouse skeletal muscle. The purpose of this study was to determine whether further elevation of γ-_cytoactin levels improve or exacerbate the dystrophic phenotype of <it>mdx </it>mice.</p> <p>Methods</p> <p>We transgenically overexpressed γ-_cytoactin, specifically in skeletal muscle of mdx mice (<it>mdx</it>-TG), and compared skeletal muscle pathology and force-generating capacity between <it>mdx </it>and <it>mdx</it>-TG mice at different ages. We investigated the mechanism by which γ-_cytoactin provides protection from force loss by studying the role of calcium channels and stretch-activated channels in isolated skeletal muscles and muscle fibers. Analysis of variance or independent <it>t</it>-tests were used to detect statistical differences between groups.</p> <p>Results</p> <p>Levels of γ-_cytoactin in <it>mdx</it>-TG skeletal muscle were elevated 200-fold compared to <it>mdx </it>skeletal muscle and incorporated into thin filaments. Overexpression of γ-_cytoactin had little effect on most parameters of <it>mdx </it>muscle pathology. However, γ-_cytoactin provided statistically significant protection against force loss during eccentric contractions. Store-operated calcium entry across the sarcolemma did not differ between <it>mdx </it>fibers compared to wild-type fibers. Additionally, the omission of extracellular calcium or the addition of streptomycin to block stretch-activated channels did not improve the force-generating capacity of isolated extensor digitorum longus muscles from <it>mdx </it>mice during eccentric contractions.</p> <p>Conclusions</p> <p>The data presented in this study indicate that upregulation of γ-_cytoactin in dystrophic skeletal muscle can attenuate force loss during eccentric contractions and that the mechanism is independent of activation of stretch-activated channels and the accumulation of extracellular calcium.</p

Low Intensity, High Frequency Vibration Training to Improve Musculoskeletal Function in a Mouse Model of Duchenne Muscular Dystrophy

The objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups. In vivo and ex vivo contractile function of the anterior crural and extensor digitorum longus muscles, respectively, were assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for histological and triglyceride analyses and subcutaneous and visceral fat pads were excised and weighed. Tibial bones were dissected and analyzed by micro-computed tomography for trabecular morphometry at the metaphysis, and cortical geometry and density at the mid-diaphysis. Three-point bending tests were used to assess cortical bone mechanical properties and a subset of tibiae was processed for dynamic histomorphometry. Vibration training for 8 wks did not alter trabecular morphometry, dynamic histomorphometry, cortical geometry, or mechanical properties (P≥0.34). Vibration did not alter any measure of muscle contractile function (P≥0.12); however the preservation of muscle function and morphology in mdx mice indicates vibration is not deleterious to muscle lacking dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher intramuscular triglyceride concentrations (P = 0.03). These data suggest that vibration training at 45 Hz and 0.6 g did not significantly impact the tibial bone and the surrounding musculature, but may influence fat distribution in mice

Small and mighty: adaptation of superphylum Patescibacteria to groundwater environment drives their genome simplicity.

BackgroundThe newly defined superphylum Patescibacteria such as Parcubacteria (OD1) and Microgenomates (OP11) has been found to be prevalent in groundwater, sediment, lake, and other aquifer environments. Recently increasing attention has been paid to this diverse&nbsp;superphylum including &gt;&nbsp;20 candidate phyla&nbsp;(a large part of the candidate phylum radiation, CPR) because it refreshed our view of the tree of life. However, adaptive traits contributing to its prevalence are still not well known.ResultsHere, we investigated the genomic features and metabolic pathways of Patescibacteria in groundwater through genome-resolved metagenomics analysis of &gt; 600 Gbp sequence data. We observed that, while the members of Patescibacteria have reduced genomes (~ 1 Mbp) exclusively, functions essential to growth and reproduction such as genetic information processing were retained. Surprisingly, they have sharply reduced redundant and nonessential functions, including specific metabolic activities and stress response systems. The Patescibacteria have ultra-small cells and simplified membrane structures, including flagellar assembly, transporters, and two-component systems. Despite the lack of CRISPR viral defense, the bacteria may evade predation through deletion of common membrane phage receptors and other alternative strategies, which may explain the low representation of prophage proteins in their genomes and lack of CRISPR. By establishing the linkages between bacterial features and the groundwater environmental conditions, our results provide important insights into the functions and evolution of this CPR group.ConclusionsWe found that Patescibacteria has streamlined many functions while acquiring advantages such as avoiding phage invasion, to adapt to the groundwater environment. The unique features of small genome size, ultra-small cell size, and lacking CRISPR of this large lineage are bringing new understandings on life of Bacteria. Our results provide important insights into the mechanisms for adaptation of the superphylum in the groundwater environments, and demonstrate a case where less is more, and small is mighty

Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle

Force loss in skeletal muscle exposed to eccentric contraction is often attributed to injury. We show that EDL muscles from dystrophin-deficient mdx mice recover 65% of lost force within 120 min of eccentric contraction and exhibit minimal force loss when the interval between contractions is increased from 3 to 30 min. A proteomic screen of mdx muscle identified an 80% reduction in the antioxidant peroxiredoxin-2, likely due to proteolytic degradation following hyperoxidation by NADPH Oxidase 2. Eccentric contraction-induced force loss in mdx muscle was exacerbated by peroxiredoxin-2 ablation, and improved by peroxiredoxin-2 overexpression or myoglobin knockout. Finally, overexpression of γcyto- or βcyto-actin protects mdx muscle from eccentric contraction-induced force loss by blocking NADPH Oxidase 2 through a mechanism dependent on cysteine 272 unique to cytoplasmic actins. Our data suggest that eccentric contraction-induced force loss may function as an adaptive circuit breaker that protects mdx muscle from injurious contractions

A guide to naming human non-coding RNA genes.

Research on non-coding RNA (ncRNA) is a rapidly expanding field. Providing an official gene symbol and name to ncRNA genes brings order to otherwise potential chaos as it allows unambiguous communication about each gene. The HUGO Gene Nomenclature Committee (HGNC, www.genenames.org) is the only group with the authority to approve symbols for human genes. The HGNC works with specialist advisors for different classes of ncRNA to ensure that ncRNA nomenclature is accurate and informative, where possible. Here, we review each major class of ncRNA that is currently annotated in the human genome and describe how each class is assigned a standardised nomenclature

The Siren Site and the Long Transition from Archaic to Late Prehistoric Lifeways on the Eastern Edwards Plateau of Central Texas

On behalf of the Texas Department of Transportation (TxDOT), SWCA Environmental Consultants (SWCA) conducted testing and data recovery investigations at the Siren site (41WM1126), a prehistoric multi-component site in the Interstate Highway 35 right-of-way along the South Fork of the San Gabriel River in Williamson County, Texas. The work was done to fulfill TxDOT’s compliance obligations under the National Historic Preservation Act and the Antiquities Code of Texas. The testing investigations were conducted under Antiquities Permit 3834, and the subsequent data recovery was under Permit 3938. Kevin Miller served as Principal Investigator on both permits. Though the site extends far beyond the area of potential effects both horizontally and vertically, the investigations focused on Late Archaic and Late Prehistoric components within a relatively limited area that would be subject to project impacts. The investigations were conducted in February 2006. The investigations identified five isolable components that were intermittently laid down from approximately 2600 to 900 years ago. A substantial Late Prehistoric Austin phase occupation is represented by Scallorn projectile points, stone tools, burned rock, faunal materials, and radiocarbon dates from cooking features. The component feature assemblage includes a cluster of discrete, well-preserved burned rock features that range from small fire-cracked rock concentrations to a large, slab-lined feature that dominates the cluster. The underlying components include four cultural strata representing a series of phases in the final millennium or so of the long Archaic period. These components span approximately 2600 to 1500 b.p., though earlier, deeply buried components were also noted on the site. These deeper deposits were not the focus of the investigations, however, since they would not be affected by the project. The Archaic components revealed a suite of small side-notched dart points such as Ensor, Fairland, and Frio, as well as many earlier broad-bladed styles such as Castroville, Montell, Marshall, and Pedernales. These robust components contained numerous burned rock features of varying size and function, abundant tools, well-preserved faunal materials, macrobotanical remains including geophytes from several earth ovens, and a large suite of radiocarbon dates. The features include an incipient burned rock midden, burned rock clusters, a debitage reduction area, a biface cache, slab-lined hearths, basin-shaped hearths, and small circular hearths. The distributions of artifacts and features within the Archaic components across the excavation blocks showed significant variations. These differences reflect sequential components that provide a view of diachronic trends in technology, subsistence, economy, and a suite of other behaviors and activities during the long transition from Archaic to Late Prehistoric adaptations. As previously determined by the testing excavations and further substantiated by the data recovery investigations, the Siren site, most notably the Late Archaic and Late Prehistoric components, is eligible for the National Register of Historic Places under Criterion D, 36 CFR 60.4, and eligible for State Archeological Landmark designation under Criteria 1 and 2 of the Rules of Practice and Procedure for the Antiquities Code of Texas, 13 TAC 26.8. The excavations and subsequent analysis have mitigated the adverse effects of the bridge construction by recovering the vast majority of the affected components within the area of potential effect. No further archaeological work is recommended. Portions of the site outside the area of potential effects have not been fully evaluated, and any future impacts beyond the mitigated areas warrant further assessment