Proteomic Profiling of Animal Models of Myotonia and Motor Neuron Disease

Skeletal muscle provides an organism with a means of reacting to its environments. It is a complex and versatile tissue that is capable of change under a variety of conditions. For example extensive literature has shown muscle transformation from slow-to-fast by decreased motor nerve activity, hypogravity, physical inactivity and in diseased states. Similarly muscle transformation from fast-to-slow can be evoked by increased muscle nerve activity or exercise. The multitude of protein changes that has been identified by muscle transformation indicates it is a complex process that can change a wide variety of the muscle tissues architecture, metabolism and function. Proteomic profiling of two very different diseased states has allowed the identification of muscle transformation occurring in opposite directions. Myotonia a common feature found in myotonic dystrophies is characterized by skeletal muscle membrane hyperexcitability. Proteomic profiling was carried out on three independent spontaneous mutant mice and allowed us to compare secondary effects of hyperexcitabilty on skeletal muscle. Severly myotonic mice MTO and ADR displayed a muscle transformation from fast-to-slow. The more mildly affected MTO*5J mutant showed slight changes in proteins associated with fast and slow muscle. In comparison to the myotonic diseased state we carried out proteomic profiling of skeletal muscle tissue from the Wobbler mouse; an animal model of motor neuron degeneration. In contrast to myotonia the WR protein profile displayed a slow-to-fast muscle transformation. The detailed MS-based analysis of diseased skeletal muscle has shown that proteomics is highly suitable to determine change in the isoform expression pattern of muscle proteins. Identified proteins can be used as potential factors for the establishment of comprehensive biomarker signature of myotonic and motor neuron diseases

Biomarkers of inflammatory arthritis and proteomics

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Proteomic Profiling of Mitochondrial Enzymes during Skeletal Muscle Aging

Mitochondria are of central importance for energy generation in skeletal muscles. Expression changes or functional alterations in mitochondrial enzymes play a key role during myogenesis, fibre maturation, and various neuromuscular pathologies, as well as natural fibre aging. Mass spectrometry-based proteomics suggests itself as a convenient large-scale and high-throughput approach to catalogue the mitochondrial protein complement and determine global changes during health and disease. This paper gives a brief overview of the relatively new field of mitochondrial proteomics and discusses the findings from recent proteomic surveys of mitochondrial elements in aged skeletal muscles. Changes in the abundance, biochemical activity, subcellular localization, and/or posttranslational modifications in key mitochondrial enzymes might be useful as novel biomarkers of aging. In the long term, this may advance diagnostic procedures, improve the monitoring of disease progression, help in the testing of side effects due to new drug regimes, and enhance our molecular understanding of age-related muscle degeneration

DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase extraction of young adult versus aged gastrocnemius tissue

Contractile weakness and loss of muscle mass are critical features of the aging process in mammalians. Age-related fibre wasting has a profound effect on muscle metabolism, fibre type distribution and the overall physiological integrity of the neuromuscular system. This study has used mass spectrometry-based proteomics to investigate the fate of the aging rat muscle proteome. Using nonionic detergent phase extraction, this report shows that the aged gastrocnemius muscle exhibits a generally perturbed protein expression pattern in both the detergent-extracted fraction and the aqueous protein complement from senescent muscle tissue. In the detergent-extracted fraction, the expression of ATP synthase, isocitrate dehydrogenase, enolase, tropomyosin and beta-actin was increased. Different isoforms of creatine kinase and prohibitin showed differential changes. In the aqueous fraction, malate dehydrogenase, sulfotransferase, triosephosphate isomerase, aldolase, cofilin-2 and lactate dehydrogenase showed increased levels. Interestingly, differential effects on dissimilar 2-D spots of the same protein species were shown for Cu/Zn superoxide dismutase, albumin, annexin A4 and phosphoglycolate phosphatase. Mitochondrial Hsp60, Hsp71 and nucleoside diphosphate kinase B exhibited a reduced abundance in aged muscle. The majority of altered proteins were found to be involved in mitochondrial metabolism, glycolysis, metabolic transportation, regulatory processes, the cellular stress response, detoxification mechanisms and muscle contraction

Public involvement in the governance of population-level biomedical research: unresolved questions and future directions.

Population-level biomedical research offers new opportunities to improve population health, but also raises new challenges to traditional systems of research governance and ethical oversight. Partly in response to these challenges, various models of public involvement in research are being introduced. Yet, the ways in which public involvement should meet governance challenges are not well understood. We conducted a qualitative study with 36 experts and stakeholders using the World Café method to identify key governance challenges and explore how public involvement can meet these challenges. This brief report discusses four cross-cutting themes from the study: the need to move beyond individual consent; issues in benefit and data sharing; the challenge of delineating and understanding publics; and the goal of clarifying justifications for public involvement. The report aims to provide a starting point for making sense of the relationship between public involvement and the governance of population-level biomedical research, showing connections, potential solutions and issues arising at their intersection. We suggest that, in population-level biomedical research, there is a pressing need for a shift away from conventional governance frameworks focused on the individual and towards a focus on collectives, as well as to foreground ethical issues around social justice and develop ways to address cultural diversity, value pluralism and competing stakeholder interests. There are many unresolved questions around how this shift could be realised, but these unresolved questions should form the basis for developing justificatory accounts and frameworks for suitable collective models of public involvement in population-level biomedical research governance

Proteomic Profiling of Animal Models of Myotonia and Motor Neuron Disease

Skeletal muscle provides an organism with a means of reacting to its environments. It is a complex and versatile tissue that is capable of change under a variety of conditions. For example extensive literature has shown muscle transformation from slow-to-fast by decreased motor nerve activity, hypogravity, physical inactivity and in diseased states. Similarly muscle transformation from fast-to-slow can be evoked by increased muscle nerve activity or exercise. The multitude of protein changes that has been identified by muscle transformation indicates it is a complex process that can change a wide variety of the muscle tissues architecture, metabolism and function. Proteomic profiling of two very different diseased states has allowed the identification of muscle transformation occurring in opposite directions. Myotonia a common feature found in myotonic dystrophies is characterized by skeletal muscle membrane hyperexcitability. Proteomic profiling was carried out on three independent spontaneous mutant mice and allowed us to compare secondary effects of hyperexcitabilty on skeletal muscle. Severly myotonic mice MTO and ADR displayed a muscle transformation from fast-to-slow. The more mildly affected MTO*5J mutant showed slight changes in proteins associated with fast and slow muscle. In comparison to the myotonic diseased state we carried out proteomic profiling of skeletal muscle tissue from the Wobbler mouse; an animal model of motor neuron degeneration. In contrast to myotonia the WR protein profile displayed a slow-to-fast muscle transformation. The detailed MS-based analysis of diseased skeletal muscle has shown that proteomics is highly suitable to determine change in the isoform expression pattern of muscle proteins. Identified proteins can be used as potential factors for the establishment of comprehensive biomarker signature of myotonic and motor neuron diseases

Proteomic Profiling of Animal Models of Myotonia and Motor Neuron Disease

Skeletal muscle provides an organism with a means of reacting to its environments. It is a complex and versatile tissue that is capable of change under a variety of conditions. For example extensive literature has shown muscle transformation from slow-to-fast by decreased motor nerve activity, hypogravity, physical inactivity and in diseased states. Similarly muscle transformation from fast-to-slow can be evoked by increased muscle nerve activity or exercise. The multitude of protein changes that has been identified by muscle transformation indicates it is a complex process that can change a wide variety of the muscle tissues architecture, metabolism and function. Proteomic profiling of two very different diseased states has allowed the identification of muscle transformation occurring in opposite directions. Myotonia a common feature found in myotonic dystrophies is characterized by skeletal muscle membrane hyperexcitability. Proteomic profiling was carried out on three independent spontaneous mutant mice and allowed us to compare secondary effects of hyperexcitabilty on skeletal muscle. Severly myotonic mice MTO and ADR displayed a muscle transformation from fast-to-slow. The more mildly affected MTO*5J mutant showed slight changes in proteins associated with fast and slow muscle. In comparison to the myotonic diseased state we carried out proteomic profiling of skeletal muscle tissue from the Wobbler mouse; an animal model of motor neuron degeneration. In contrast to myotonia the WR protein profile displayed a slow-to-fast muscle transformation. The detailed MS-based analysis of diseased skeletal muscle has shown that proteomics is highly suitable to determine change in the isoform expression pattern of muscle proteins. Identified proteins can be used as potential factors for the establishment of comprehensive biomarker signature of myotonic and motor neuron diseases

Proteomic Profiling of Animal Models of Myotonia and Motor Neuron Disease

Skeletal muscle provides an organism with a means of reacting to its environments. It is a complex and versatile tissue that is capable of change under a variety of conditions. For example extensive literature has shown muscle transformation from slow-to-fast by decreased motor nerve activity, hypogravity, physical inactivity and in diseased states. Similarly muscle transformation from fast-to-slow can be evoked by increased muscle nerve activity or exercise. The multitude of protein changes that has been identified by muscle transformation indicates it is a complex process that can change a wide variety of the muscle tissues architecture, metabolism and function. Proteomic profiling of two very different diseased states has allowed the identification of muscle transformation occurring in opposite directions. Myotonia a common feature found in myotonic dystrophies is characterized by skeletal muscle membrane hyperexcitability. Proteomic profiling was carried out on three independent spontaneous mutant mice and allowed us to compare secondary effects of hyperexcitabilty on skeletal muscle. Severly myotonic mice MTO and ADR displayed a muscle transformation from fast-to-slow. The more mildly affected MTO*5J mutant showed slight changes in proteins associated with fast and slow muscle. In comparison to the myotonic diseased state we carried out proteomic profiling of skeletal muscle tissue from the Wobbler mouse; an animal model of motor neuron degeneration. In contrast to myotonia the WR protein profile displayed a slow-to-fast muscle transformation. The detailed MS-based analysis of diseased skeletal muscle has shown that proteomics is highly suitable to determine change in the isoform expression pattern of muscle proteins. Identified proteins can be used as potential factors for the establishment of comprehensive biomarker signature of myotonic and motor neuron diseases

Proteomic Profiling of Animal Models of Myotonia and Motor Neuron Disease

Skeletal muscle provides an organism with a means of reacting to its environments. It is a complex and versatile tissue that is capable of change under a variety of conditions. For example extensive literature has shown muscle transformation from slow-to-fast by decreased motor nerve activity, hypogravity, physical inactivity and in diseased states. Similarly muscle transformation from fast-to-slow can be evoked by increased muscle nerve activity or exercise. The multitude of protein changes that has been identified by muscle transformation indicates it is a complex process that can change a wide variety of the muscle tissues architecture, metabolism and function. Proteomic profiling of two very different diseased states has allowed the identification of muscle transformation occurring in opposite directions. Myotonia a common feature found in myotonic dystrophies is characterized by skeletal muscle membrane hyperexcitability. Proteomic profiling was carried out on three independent spontaneous mutant mice and allowed us to compare secondary effects of hyperexcitabilty on skeletal muscle. Severly myotonic mice MTO and ADR displayed a muscle transformation from fast-to-slow. The more mildly affected MTO*5J mutant showed slight changes in proteins associated with fast and slow muscle. In comparison to the myotonic diseased state we carried out proteomic profiling of skeletal muscle tissue from the Wobbler mouse; an animal model of motor neuron degeneration. In contrast to myotonia the WR protein profile displayed a slow-to-fast muscle transformation. The detailed MS-based analysis of diseased skeletal muscle has shown that proteomics is highly suitable to determine change in the isoform expression pattern of muscle proteins. Identified proteins can be used as potential factors for the establishment of comprehensive biomarker signature of myotonic and motor neuron diseases