Theories of acceleration specific exercise and design of a training device.

Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1982 .D684. Source: Masters Abstracts International, Volume: 40-07, page: . Thesis (M.H.K.)--University of Windsor (Canada), 1982

Kindlin-2 is required for myocyte elongation and is essential for myogenesis

<p>Abstract</p> <p>Background</p> <p>Integrins are required for normal muscle differentiation and disruptions in integrin signaling result in human muscle disease. The intracellular components that regulate integrin function during myogenesis are poorly understood. Unc-112 is an integrin-associated protein required for muscle development in C. elegans. To better understand the intracellular effectors of integrin signaling in muscle, we examined the mammalian homolog of Unc-112, kindlin-2.</p> <p>Results</p> <p>Kindlin-2 expression is upregulated during differentiation and highly enriched at sites of integrin localization. RNAi knockdown of kindlin-2 in C2C12 cells results in significant abnormalities during the early stages of myogenesis. Specifically, differentiating myocytes lacking kindlin-2 are unable to elongate and fail to fuse into multinucleated myotubes. These changes are correlated with decreased cell substratum adhesion and increased cell motility. They are also associated with redistribution of a known kindlin-2 binding partner, integrin linked kinase (ILK), to the membrane insoluble subcellular fraction.</p> <p>Conclusion</p> <p>In all, our study reveals kindlin-2 as a novel integrin adaptor protein important for muscle differentiation, and identifies it particularly as a critical regulator of myocyte elongation.</p

Quality of Life and Autonomy in Emerging Adults with Early‐Onset Neuromuscular Disorders

Emerging adulthood is an important period in the development of one’s identity and autonomy. The ways in which identity and autonomy are viewed by emerging adults and how they impact quality of life (QoL) in individuals with early‐onset neuromuscular conditions is not yet known. This study focused on understanding and exploring relationships between self‐perceptions of emerging adulthood, autonomy, and QoL. Five previously validated measures were incorporated into an online survey and distributed to young adults with early‐onset neuromuscular conditions and unaffected controls. Topics explored included individuals’ views regarding their overall QoL, disease‐specific QoL, components of emerging adulthood, and autonomy. We found that a sense of higher disease impact was associated with a lower Overall General QoL. Additionally, perceptions of key autonomy factors “negativity” and “instability” were uniquely associated with Overall General QoL in the case group as compared to controls, whereas “attitudinal autonomy” (attaining the ability to plan and follow through with goals) was important to this age group regardless of health status. The specific factors of emerging adulthood and autonomy that were significantly correlated with Overall General QoL can be used for developing targeted counseling and interventions to improve QoL for individuals and their families.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146967/1/jgc40713.pd

VALIDATION OF A DXA-BASED METHOD FOR OBTAINING INERTIA TENSORS: 'WHEN PIGS FLY'

This paper examines the accuracy of body segment inertia tensors estimated by combining information from dual-energy X-ray absorptiometry and a three-dimensional modelling technique proposed by Zatsiorsky et al. (1 990) (DXAIVol method). The inertia tensor of a frozen pig cadaver was estimated using the novel DXAlVol method and traditional compound pendulum techniques. The pig cadaver was projected through the air and the experimental 'ground truth kinematics' were recorded. Simulated kinematics of the pig cadaver flight were generated using the inertia tensor derived from the DXAlVol and compound pendulum methods and compared to the ground truth kinematics. Simulations based on the novel D W o l method's inertia tensor traded the experimentally recorded flight of the frozen pig cadaver with superior accuracy

A novel early onset phenotype in a zebrafish model of merosin deficient congenital muscular dystrophy

Merosin deficient congenital muscular dystrophy (MDC1A) is a severe neuromuscular disorder with onset in infancy that is associated with severe morbidities (particularly wheelchair dependence) and early mortality. It is caused by recessive mutations in the LAMA2 gene that encodes a subunit of the extracellular matrix protein laminin 211. At present, there are no treatments for this disabling disease. The zebrafish has emerged as a powerful model system for the identification of novel therapies. However, drug discovery in the zebrafish is largely dependent on the identification of phenotypes suitable for chemical screening. Our goal in this study was to elucidate novel, early onset abnormalities in the candyfloss (caf) zebrafish, a model of MDC1A. We uncovered and characterize abnormalities in spontaneous coiling, the earliest motor movement in the zebrafish, as a fully penetrant change specific to caf mutants that is ideal for future drug testing

Photon number resolution using a time-multiplexed single-photon detector

Photon number resolving detectors are needed for a variety of applications including linear-optics quantum computing. Here we describe the use of time-multiplexing techniques that allows ordinary single photon detectors, such as silicon avalanche photodiodes, to be used as photon number-resolving detectors. The ability of such a detector to correctly measure the number of photons for an incident number state is analyzed. The predicted results for an incident coherent state are found to be in good agreement with the results of a proof-of-principle experimental demonstration.Comment: REVTeX4, 6 pages, 8 eps figures, v2: minor changes, v3: changes in response to referee report, appendix added, 1 reference adde

Influence of Familial Risk on Diabetes Risk–Reducing Behaviors Among U.S. Adults Without Diabetes

OBJECTIVE: To test the association of family history of diabetes with the adoption of diabetes risk–reducing behaviors and whether this association is strengthened by physician advice or commonly known factors associated with diabetes risk. RESEARCH DESIGN AND METHODS: We used cross-sectional data from the 2005–2008 National Health and Nutrition Examination Survey (NHANES) to examine the effects of family history of diabetes on the adoption of selected risk-reducing behaviors in 8,598 adults (aged ≥20 years) without diabetes. We used multiple logistic regression to model three risk reduction behaviors (controlling or losing weight, increasing physical activity, and reducing the amount of dietary fat or calories) with family history of diabetes. RESULTS: Overall, 36.2% of U.S. adults without diabetes had a family history of diabetes. Among them, ~39.8% reported receiving advice from a physician during the past year regarding any of the three selected behaviors compared with 29.2% of participants with no family history (P < 0.01). In univariate analysis, adults with a family history of diabetes were more likely to perform these risk-reducing behaviors compared with adults without a family history. Physician advice was strongly associated with each of the behavioral changes (P < 0.01), and this did not differ by family history of diabetes. CONCLUSIONS: Familial risk for diabetes and physician advice both independently influence the adoption of diabetes risk–reducing behaviors. However, fewer than half of participants with familial risk reported receiving physician advice for adopting these behaviors

Murine Fig4 is dispensable for muscle development but required for muscle function

Abstract Background Phosphatidylinositol phosphates (PIPs) are low-abundance phospholipids that participate in a range of cellular processes, including cell migration and membrane traffic. PIP levels and subcellular distribution are regulated by a series of lipid kinases and phosphatases. In skeletal muscle, PIPs and their enzymatic regulators serve critically important functions exemplified by mutations of the PIP phosphatase MTM1 in myotubular myopathy (MTM), a severe muscle disease characterized by impaired muscle structure and abnormal excitation–contraction coupling. FIG4 functions as a PIP phosphatase that participates in both the synthesis and breakdown of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Mutation of FIG4 results in a severe neurodegenerative disorder in mice and a progressive peripheral polyneuropathy in humans. The effect of FIG4 mutation on skeletal muscle has yet to be examined. Methods Herein we characterize the impact of FIG4 on skeletal muscle development and function using the spontaneously occurring mouse mutant pale tremor (plt), a mouse line with a loss of function mutation in Fig4. Results In plt mice, we characterized abnormalities in skeletal muscle, including reduced muscle size and specific force generation. We also uncovered ultrastructural abnormalities and increased programmed cell death. Conversely, we detected no structural or functional abnormalities to suggest impairment of excitation–contraction coupling, a process previously shown to be influenced by PI(3,5)P2 levels. Conditional rescue of Fig4 mutation in neurons prevented overt muscle weakness and the development of obvious muscle abnormalities, suggesting that the changes observed in the plt mice were primarily related to denervation of skeletal muscle. On the basis of the ability of reduced FIG4 levels to rescue aspects of Mtmr2-dependent neuropathy, we evaluated the effect of Fig4 haploinsufficiency on the myopathy of Mtm1-knockout mice. Male mice with a compound Fig4 +/−/Mtm1 –/Y genotype displayed no improvements in muscle histology, muscle size or overall survival, indicating that FIG4 reduction does not ameliorate the Mtm1-knockout phenotype. Conclusions Overall, these data indicate that loss of Fig4 impairs skeletal muscle function but does not significantly affect its structural development.http://deepblue.lib.umich.edu/bitstream/2027.42/112676/1/13395_2013_Article_83.pd

Neuromuscular effects of G93A-SOD1 expression in zebrafish

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal disorder involving the degeneration and loss of motor neurons. The mechanisms of motor neuron loss in ALS are unknown and there are no effective treatments. Defects in the distal axon and at the neuromuscular junction are early events in the disease course, and zebrafish provide a promising in vivo system to examine cellular mechanisms and treatments for these events in ALS pathogenesis. Results We demonstrate that transient genetic manipulation of zebrafish to express G93A-SOD1, a mutation associated with familial ALS, results in early defects in motor neuron outgrowth and axonal branching. This is consistent with previous reports on motor neuron axonal defects associated with familial ALS genes following knockdown or mutant protein overexpression. We also demonstrate that upregulation of growth factor signaling is capable of rescuing these early defects, validating the potential of the model for therapeutic discovery. We generated stable transgenic zebrafish lines expressing G93A-SOD1 to further characterize the consequences of G93A-SOD1 expression on neuromuscular pathology and disease progression. Behavioral monitoring reveals evidence of motor dysfunction and decreased activity in transgenic ALS zebrafish. Examination of neuromuscular and neuronal pathology throughout the disease course reveals a loss of neuromuscular junctions and alterations in motor neuron innervations patterns with disease progression. Finally, motor neuron cell loss is evident later in the disease. Conclusions This sequence of events reflects the stepwise mechanisms of degeneration in ALS, and provides a novel model for mechanistic discovery and therapeutic development for neuromuscular degeneration in ALS.http://deepblue.lib.umich.edu/bitstream/2027.42/112892/1/13024_2012_Article_367.pd