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Limb-girdle muscular dystrophy 2i (LGMD2i) is a dystroglycanopathy that compromises myofiber integrity and primarily reduces power output in limb muscles but can influence cardiac muscle as well. Previous studies of LGMD2i made use of a transgenic mouse model in which a proline-to-leucine (P448L) mutation in fukutin-related protein severely reduces glycosylation of α-dystroglycan. Muscle function is compromised in P448L mice in a manner similar to human patients with LGMD2i. In situ studies reported lower maximal twitch force and depressed force-velocity curves in medial gastrocnemius (MG) muscles from male P448L mice. Here, we measured Ca 2+ -activated force generation and cross-bridge kinetics in both demembranated MG fibers and papillary muscle strips from P448L mice. Maximal activated tension was 37% lower in MG fibers and 18% lower in papillary strips from P448L mice than controls. We also found slightly faster rates of cross-bridge recruitment and detachment in MG fibers from P448L than control mice. These increases in skeletal cross-bridge cycling could reduce the unitary force output from individual cross bridges by lowering the ratio of time spent in a force-bearing state to total cycle time. This suggests that the decreased force production in LGMD2i may be due (at least in part) to altered cross-bridge kinetics. This finding is notable, as the majority of studies germane to muscular dystrophies have focused on sarcolemma or whole muscle properties, whereas our findings suggest that the disease pathology is also influenced by potential downstream effects on cross-bridge behavior.

Current fascia research is allowing for an interdisciplinary understanding of the body's anatomical, biomechanical, and neurological connectivity via the fascial network. Fascial research and its application has been validated and established in various clinical areas of research. The purpose of this study was to apply the current knowledge of the fascial system to general exercise protocols. This study involved 20 women, ages 30-60 years, who were novice weight trainers, mostly sedentary, and with no injuries, excessive pain or disease. The 10-week study compared strength gain changes between a strength training regimen control group (10) and a treatment group (10) with the same strength routine along with a fascial system exercise protocol. Statistical analysis was completed using a repeated measure design to determine differences between baseline and final measures of strength between groups. The repeated measures analysis of variance revealed no significant differences between treatment and control groups between pre and post trials. The analysis did find significant differences in strength across trials for both groups in the variables of leg press (Treatment =+62 lbs., Control = +67 lbs.), leg extension (Treatment =+61 lbs., Control = +45.5 lbs.), and chest press (Treatment =+19.5 lbs., Control = +16.5 lbs.). These results may be attributed to the control group receiving sufficient stimulus to the fascial system to produce similar results to that of the treatment group or due to training time was not sufficient to elicit an effect of the fascial training.

Circulating myostatin-attenuating agents are being developed to treat muscle-wasting disease despite their potential to produce serious off-target effects, as myostatin/activin receptors are widely distributed among many nonmuscle tissues. Our studies suggest that the myokine not only inhibits striated muscle growth but also regulates pituitary development and growth hormone (GH) action in the liver. Using a novel myostatin-null label-retaining model (Jekyll mice), we determined that the heterogeneous pool of pituitary stem, transit-amplifying, and progenitor cells in Jekyll mice depletes more rapidly after birth than the pool in wild-type mice. This correlated with increased levels of GH, prolactin, and the cells that secrete these hormones, somatotropes and lactotropes, respectively, in Jekyll pituitaries. Recombinant myostatin also stimulated GH release and gene expression in pituitary cell cultures although inhibiting prolactin release. In primary hepatocytes, recombinant myostatin blocked GH-stimulated expression of two key mediators of growth, insulin-like growth factor (IGF)1 and the acid labile subunit and increased expression of an inhibitor, IGF-binding protein-1. The significance of these findings was demonstrated by smaller muscle fiber size in a model lacking myostatin and liver IGF1 expression (LID-o-Mighty mice) compared with that in myostatin-null (Mighty) mice. These data together suggest that myostatin may regulate pituitary development and function and that its inhibitory actions in muscle may be partly mediated by attenuating GH action in the liver. They also suggest that circulating pharmacological inhibitors of myostatin could produce unintended consequences in these and possibly other tissues.

Recent high-profile studies report conflicting data on the age-related change in circulating growth/differentiation factor 11 (GDF11) and myostatin as well as the former's influence on muscle regeneration. Both ligands bind and activate ActRIIB receptors with similar affinities and should therefore have similar actions, yet these studies suggest that GDF11 activates muscle regeneration whereas myostatin is well known to inhibit it. They also suggest that circulating GDF11 levels, but not those of myostatin, decline with age. We performed a careful assessment of the ELISA used to quantify circulating myostatin in these studies and determined that assay reagents significantly cross react with each protein, each of which is highly homologous. Circulating myostatin levels decreased with age and estimates of GDF11 levels using myostatin null mice indicate that they were almost 500 times lower than those for myostatin. This suggests that circulating GDF11 has little physiological relevance as it could not outcompete myostatin for ActRIIB binding sites. Together, these results further suggest that the previously reported aging muscle, heart, and brain phenotypes attributed to reduced circulating GDF11 should be reconsidered.

We investigated the effects of several modifications of the Western diet on a medium-sized rodent, Neotoma micropus, that lives in the area of the wildland-urban interface. We conducted a laboratory study of the response of N. micropus to high fat-high fructose (HFHF), high fat-high sucrose (HFHS), high fat-low sugar (HFLSu) and control (low fat-low sugar) diets. We found a significant increase in hepatic lipid deposition and a significant decrease in podocytes in those animals that consumed the HFHF and HFLSu diets compared to those on the HFHS and control diets. We found no significant differences in Bowman's space or hepatic collagen formation. We predict that N. micropus in the wild, with access to anthropogenic resources, will show similar effects as a result of the consumption of anthropogenic resources., (Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.)

A small library of amino acid ester prodrugs of 6-β-naltrexol (NTXOL, 1) was prepared in order to investigate the candidacy of these prodrugs for microneedle-enhanced transdermal delivery. Six amino acid ester prodrugs were synthesized (6a-f). 6b, 6d, and 6 e were stable enough at skin pH (pH 5.0) to move forward to studies in 50% human plasma. The lead compound (6 e) exhibited the most rapid bioconversion to NTXOL in human plasma (t1/2 = 2.2 ± 0.1h)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Dystrophinopathy in the young mdx mouse model of Duchenne muscular dystrophy is comparatively mild, requires induction, and is rarely assessed with tests of systemic muscle function in whole animals., Methods: A modified TREAT-NMD induction protocol was used to evaluate respiratory and exercise performance, starting and ending with maximum oxygen consumption (VO2max ) tests., Results: The initial and/or final VO2max , time to exhaustion, speed at exhaustion, and total expended calories were significantly lower in mdx mice. Episodic VO2 and VCO2 fluctuations occurred during training and resulted in dissociated patterns of VO2 and respiratory exchange ratio (RER). These fluctuations further resulted in significantly greater VO2 coefficient of variation and RER values and lower minimal VO2 values., Conclusions: Quantifying respiratory performance during exercise is a potentially useful means for studying pathophysiology in mdx mice, as it assesses intact animals over time, is more sensitive than some histological markers, and assesses systemic muscle function., (© 2014 Wiley Periodicals, Inc.)

The purpose of these studies was to determine if a Büchi Mini Spray Dryer B-290 (Büchi Corporation, New Castle, DE, USA) could be used to prepare blackberry extract powders containing mannitol as a thermoprotectant without extensively degrading anthocyanins and polyphenols in the resulting powders. Three blackberry puree extract samples were each prepared by sonication of puree in 30/70% ethanol/water containing 0.003% HCl. Blackberry puree extract sample 1 (S1) contained no mannitol, while blackberry puree extract sample 2 (S2) contained 3.0:1 (w/w) mannitol:berry extract, and blackberry puree extract sample 3 (S3) contained 6.3:1 (w/w) mannitol:berry extract. The levels of anthocyanins and polyphenols in reconstituted spray-dried powders produced from S1-S3 were compared to solutions of S1-S3 that were held at 4°C as controls. All extract samples could be spray-dried using the Büchi Mini Spray Dryer B-290. S1, with no mannitol, showed a 30.8% decrease in anthocyanins and a 24.1% decrease in polyphenols following spray-drying. However, S2 had a reduction in anthocyanins of only 13.8%, while polyphenols were reduced by only 6.1%. S3, with a ratio of mannitol to berry extract of 6.3:1, exhibited a 12.5% decrease in anthocyanins while the decrease in polyphenols after spray-drying was not statistically significant (P=.16). Collectively, these data indicate that a Büchi Mini Spray Dryer B-290 is a suitable platform for producing stable berry extract powders, and that mannitol is a suitable thermoprotectant that facilitates retention of thermosensitive polyphenolic species in berry extracts during spray-drying.

Modern resistive pulse sensing techniques can be used to measure nanoparticle electrophoretic mobility, and hence ζ-potential. In contrast to conventional light scattering methods, resistive pulse sensing produces particle-by-particle data. We have used tunable resistive pulse sensing (TRPS) to compare methods for measuring the ζ-potential of carboxylated polystyrene nanoparticles. The five particle sets studied had nominal surface charge density (σ) between 0 and -0.67 C m(-2), and diameters in the range 160-230 nm. Data were collected with pressure in the range ±500 Pa applied across a tunable pore. In each experiment, pressure was varied either continuously or in discrete steps. Calculations of the ζ-potential were obtained by analysing both the rate and the full-width half maximum duration of resistive pulses. Data obtained from duration analyses were more reproducible than rate methods, yielding typical variations smaller than ±5 mV. When σ was greater (less negative) than -0.32 C m(-2), all of the analysis methods studied yielded a monotonic relationship between ζ-potential and σ. Complicated pulse data were observed near the pressure at which the net particle flux is zero, and these observations have been explored by examining competition between electrokinetic and pressure-driven transport. The typical difference between ζ-potentials obtained using TRPS and phase analysis light scattering was 15% (<5 mV), with an experimental error of ∼10% attributable to both techniques., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The Toronto Charter for Physical Activity (2010) and several national physical activity plans advocate sports participation as an important part of population targeted physical activity for youth. Emerging research evidence also suggests that sports participation during adolescents is linked to significant positive correlations with academic and behavioral performance. The purpose of this study was to compare academic and behavioral performance between male and female public school athletes (Total N=11,139; 38% Female) and non-athletes (Total N=23,891; 52% Female) in a convenient, ethnicity diverse, sample (grades 7-12) from the state of Texas (USA). We examined the passing rates of individual athletes and non-athletes on standardized tests (Texas Assessment of Knowledge and Skills, TAKS) for math, language arts, reading, writing, science, and social studies. We also examined the percentage of athletes and non-athletes for being "at risk," for dropping out of school and for the total average number of disciplinary actions. Chi-Square statistical analyses comparing athletes to non-athletes showed that athletes scored significantly better ( p <0.05) on all standardized tests compared to non-athletes (passing rate ranges ranged from 77.1% to 92.9% versus 27.7% to 66.5% respectively). Athletes were at lower risk for dropout compared to non-athletes (35.6% versus 49.24%; p <0.05), and they had fewer disciplinary actions (mean of 0.85 per athletes per year versus 1.23 for non-athletes; ANOVA, p <0.05). Our results support the research findings of others that participation in school sports is positively correlated to better academic and behavioral performances for athletes compared to non-athletes.

Objective: We developed a modified Phalen's test (MPT), which uses sensory testing in Phalen's position, as a diagnostic screening tool for carpal tunnel syndrome (CTS). This study was designed to determine the sensitivity, specificity, and receiver operating characteristic (ROC) curve of the MPT for diagnosis of CTS., Methods: Electrodiagnostic nerve conduction studies (EDS) were used as the gold standard. MPT was performed by a blinded examiner on patients prior to EDS. MPT was recorded as either positive or negative based on the presence or absence of a median nerve sensory deficit while the hand was in Phalen's position., Results: Sixty-six hands were included in this study. Chi-square for the MPT compared to EDS as the gold standard was 41.449 (P < 0.001), and the validity coefficient (phi) was 0.792 (P < 0.01). The traditional Phalen's test (TPT) compared to the EDS demonstrated a chi-square of 15.349 (P < 0.001) and a phi coefficient of 0.482 (P < 0.01). ROC curve estimates for the MPT revealed a sensitivity of 84.4% compared to 50% for the TPT. The standard error of the estimate for sensitivity was 3.3% for the MPT and 5.8% for the TPT., Conclusion: The MPT is a highly useful screening diagnostic tool for CTS. The MPT demonstrates greater accuracy than the TPT for predicting CTS. The MPT also demonstrates greater sensitivity than the TPT in predicting a positive electrodiagnostic test for CTS., (Copyright © 2012 by the American College of Rheumatology.)

Electromyography is a commonly used method to determine relative effort and neuromuscular drive to skeletal muscle. A limitation of the interpretation of EMG within the literature is the many methods used to determine the intensity of muscle activation. In the current study, ten healthy young adults performed a level walking task while EMG was recorded from the tibialis anterior, medial gastrocnemius and fibularis longus. The EMG data were rectified and smoothed using the root mean squared (RMS). Peak RMS (pRMS), mean RMS (mRMS) and integrated EMG (iEMG) were normalized to the peak value within the subject and were used to determine EMG amplitude. A 3×3 repeated measures analysis of variance was used to determine significant differences between the methods of determining EMG amplitude. The findings of the current study show that pRMS produced significantly lower EMG amplitudes than mRMS or iEMG values. Furthermore, mRMS and iEMG produced nearly identical normalized EMG amplitudes. Based on the findings of this study and the components of each measurement of EMG amplitude, it is suggested to use mRMS to determine EMG amplitude.

This pilot study tested the effectiveness of transcutaneous electric acupoint stimulation (TEAS) as an adjunctive treatment for inpatients receiving opioid detoxification with buprenorphine-naloxone at a private psychiatric hospital. Participants (N = 48) were randomly assigned to active or sham TEAS and received three 30-minute treatments daily for 3 to 4 days. In active TEAS, current was set to maximal tolerable intensity (8-15 mA); in sham TEAS, it was set to 1 mA. By 2 weeks postdischarge, participants in active TEAS were less likely to have used any drugs (35% vs. 77%, p < .05). They also reported greater improvements in pain interference (F = 4.52, p < .05) and physical health (F = 4.84, p < .01) over time. TEAS is an acceptable, inexpensive adjunctive treatment that is feasible to implement on an inpatient unit and may be a beneficial adjunct to pharmacological treatments for opioid detoxification.

The Rhadinovirus ovine herpesvirus-2 (OvHV-2) is the most common causative agent of malignant catarrhal fever (MCF) in clinically susceptible ruminants including cattle and bison. American bison (Bison bison) are highly susceptible to clinical MCF. Nevertheless, approximately 20% of bison on ranches or in feedlots become infected with the virus without developing clinical disease. Defining the genetic basis for differences in susceptibility between bison could facilitate development of improved control strategies for MCF. One genetic region that influences susceptibility to infectious diseases is the major histocompatibility complex (MHC). In this study, a Bison bison (Bibi) DRB3 oligonucleotide microarray was used to type 189 bison from 10 herds where MCF outbreaks had occurred. Binary logistic regression was used to classify DRB3 alleles as resistant (R), susceptible (S) or neutral (N). Animals were reclassified using six DRB3 genotype categories: N/N, N/R, N/S, R/S, R/R and S/S. Analysis of homogeneity across herds showed that there was a herd effect. Consequently, a penalized logistic regression model was run with herd and genotype categories as the explanatory variables. The R/R genotype was associated with resistance to MCF (P = 0.0327), while the S/S genotype was associated with clinical MCF (P = 0.0069). This is the first evidence that MHC class IIa polymorphism is associated with resistance or susceptibility to OvHV-2-induced MCF.

Problem: During the third trimester of pregnancy bovine trophoblast cells in the interplacentomal and arcade regions of the placenta express major histocompatibility complex class I (MHC-I) antigens. At parturition immunological recognition of MHC-I antigens appears to contribute to normal placental release. Therefore, we hypothesized that during late pregnancy bovine trophoblast cells express polymorphic, classical MHC-I antigens., Method of Study: Cloning, microarray screening and sequencing of cDNA were used to study transcription of MHC-I genes in peripheral blood mononuclear cells (PBMC) and interplacentomal, trophoblast cells. Real-time reverse transcription, polymerase chain reaction (RT-PCR) was used to compare the abundance of MHC-I transcripts in PBMC and trophoblast cells., Results: Screening of cloned MHC-I cDNA on MHC-I microarrays indicated that in PBMC 90-98% of MHC-I transcripts were encoded by classical MHC-I genes with the remainder encoded by non-classical MHC-I genes. In contrast, 21-66% of MHC-I transcripts from interplacentomal trophoblast cells were from classical genes and 34-79% were from non-classical genes. Transcripts from four non-classical MHC-I loci were identified by sequence analysis. Real-time RT-PCR indicated that the overall levels of MHC-I gene expression in PBMC and trophoblast were similar., Conclusion: Bovine interplacentomal trophoblast cells express both classical and non-classical MHC-I genes, but the relative level of expression varies considerably.

American bison (Bison bison) and domestic cattle (Bos taurus and Bos indicus) evolved from a common ancestor 1-1.4 million years ago. Nevertheless, they show dramatic differences in their susceptibility to infectious diseases, including malignant catarrhal fever (MCF). Although bison are highly susceptible to ovine herpesvirus-2 (OvHV-2) associated MCF, about 20% of healthy domesticated and wild bison are positive for OvHV-2 antibody. We are interested in testing the hypothesis that, within the bison population, the polymorphism of major histocompatibility complex (MHC) class II genes influences resistance to MCF. However, since little was known about the MHC class II genes of bison, it was necessary to first characterize class II haplotypes present in Bi. bison (Bibi). Thus, the MHC class II haplotypes carried by 14 bison were characterized by the PCR-based cloning and sequencing of their DRB3, DQA, and DQB alleles. Twelve MHC class II haplotypes were identified in the 14 bison. These haplotypes comprised six previously reported and six new Bibi-DRB3 alleles, along with 11 Bibi-DQA and 10 Bibi-DQB alleles. For each bison class II allele, it was possible to identify closely related cattle sequences. The closest bison and bovine DQA, DQB, and DRB3 alleles, on average, differed by only 1.3, 3.5, and 5.8 amino acids, respectively. Furthermore, bison MHC haplotypes with both nonduplicated and duplicated DQ genes were identified; these haplotypes appear to have originated from the same ancestral haplotypes as orthologous cattle haplotypes.

In viviparous animals, regulation of expression of major histocompatibility complex (MHC) class I antigens by the trophoblast cells, which constitute the outermost layer of the placenta, seems to be critical for maternal immunological acceptance of an allogeneic fetus. Cattle are unusual in this regard, since the bovine trophoblast cells, in specific regions of the uterine/placental interface, normally express MHC class I antigens during the third trimester of gestation. This expression appears to be biologically relevant as MHC class I compatibility between a cow and her fetus has been associated with an increased incidence of placental retention. We have found significant differences in lymphocyte populations, cytokine production, and trophoblast cell apoptosis in the placentomes of MHC-compatible and -incompatible pregnancies at parturition. This suggests that maternal immunological recognition of fetal MHC class I proteins triggers an immune/inflammatory response that contributes to placental separation at parturition in cattle. Early in pregnancy, a complete shutdown of MHC class I expression by trophoblast cells appears to be critical for normal placental development and fetal survival. In bovine somatic cell nuclear transfer (SCNT) pregnancies, there is an extremely high rate of fetal loss between days 30 and 90 of pregnancy. We have shown that in bovine SCNT pregnancies, between days 34 and 63 of gestation, there is both abnormal expression of MHC class I antigens by trophoblast cells and an abnormal accumulation of lymphocytes within the uterine stroma. Consequently, it is likely that activation of the maternal mucosal immune system, within the uterus at the same time when placentomes are being established, interferes with the process of placentome development and leads to immune-mediated abortion. Our data suggest that bovine MHC-compatible pregnancies provide a unique model for studying regulation of the uterine immune system, as well as immune-mediated placental rejection.

Distance run tests are often used to estimate peak oxygen uptake (peak VO2) in children. This study examined the concurrent validity of a 20-min steady-state jog (20MSSJ). The sample consisted of 43 boys and 32 girls who performed a 20MSSJ and completed a maximal treadmill test 1 week later. Peak VO2 was measured by indirect calorimetry. Subject characteristics were as follows: boys, mean age = 15.1 +/- 1.0 years, mean peak VO2 = 46.4 +/- 7.7 ml.kg-1 x min-1, mean 20MSSJ = 2.3 +/- 0.5 miles; girls, mean age = 15.3 +/- 1.1 years, mean peak VO2 = 40.4 +/- 5.1 ml.kg-1 x min-1, mean 20MSSJ = 2.1 +/- 0.5 miles. The correlation between 20MSSJ and peak VO2 was .68 across boys and girls. The regression slopes of the boys and girls were common, but the intercepts differed, F (1, 72) = 10.9, p < .05. The influence of weight and skinfold fat was examined. Separate models were developed, and the R for each was increased to .79 (SEE = 4.45 ml.kg-1 x min-1) for the model using weight and .80 (SEE = 4.36 ml.kg-1 x min-1) for the model using sum of skinfolds. The regression equations are as follows: peak VO2 = 35.10 + 6.19 (Run) + 2.96 (Gender) -0.26 (Skinfold fat) peak VO2 = 33.94 + 7.64 (Run) + 5.84 (Gender) -0.18 (Weight) (Run = 20MSSJ performance in miles; Gender; females = 0, males = 1; Skinfold fat = sum of two-site skinfolds in mm; Weight = body weight in kg).(ABSTRACT TRUNCATED AT 250 WORDS)