Moorwood on Muscle
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Moorwood on Muscle
Things I'm reading about muscle biology and muscular dystrophy
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Bigger, slower, stronger: Wnt7a treatment ameliorates muscular dystrophy

Catherine Moorwood's insight:

Wnt7a is a glycoprotein that is secreted by cells and, among other functions, causes muscles to grow bigger. In this study, the authors treat mdx mice, a model for DMD, with Wnt7a, and find that their muscles get bigger. They also find that the muscles change their properties, becoming more 'slow', like postural muscles, rather than 'fast' like muscles used for sprinting. This may protect the muscles from damage, although this was not tested directly. Surprisingly, the bigger, slower muscles were also stronger, even when taking their increased size into account - but the authors don't suggest any explanation for this.

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Cincinnati Children’s Announces Major Advancement In Treatment of Duchenne Muscular Dystrophy

Cincinnati Children’s Announces Major Advancement In Treatment of Duchenne Muscular Dystrophy | Moorwood on Muscle | Scoop.it

This is an exciting new development in Duchenne muscular dystrophy care.

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Exon skipping with a twist

Exon skipping with a twist | Moorwood on Muscle | Scoop.it

This paper is from some of my former coworkers at Oxford. Exon-skipping for designed for DMD uses oligonucleotides to interfere with dystrophin mRNA splicing, converting a mutant mRNA that will produce a nonfunctional dystrophin protein to one that produces a functional dystrophin with just a small piece missing.

 

Here, the oligonucleotide is made more efficient by attaching it to a small nuclear RNA, which protects it from degradation and helps it to accumulate in the nucleus, where splicing occurs. This proves very effective at restoring dystrophin expression and muscle function, in a severely affected mouse model for muscular dystrophy, which is missing both dystrophin and its compensating homologue, utrophin. Of note, dystrophin is restored in the heart, which is important as cardiomyopathy is an increasing problem in older DMD patients.

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Clinical outcome measures for trials in Duchenne muscular dystrophy

Clinical outcome measures for trials in Duchenne muscular dystrophy | Moorwood on Muscle | Scoop.it

What should you measure in a clinical trial? This is a report from an international working group on clinical outcome measures for DMD. Key questions include: which are the most consistent and reliable measures, and how do they relate to disease milestones that are relevant to patients and their familes?

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Skipping of multiple dystrophin exons in mice

Exon-skipping is a promising therapeutic approach that is in clinical trials for DMD (e.g. see recent press release from Sarepta: http://tinyurl.com/d73uq2x). However, a challenge is the variety of different dystrophin mutations that cause DMD, each potentially requiring a new antisense oligonucleotide drug. This paper presents successful skipping of dystrophin exons 45-55 in mice, an approach that would theoretically work for 60% of DMD patients. The treatment worked well in skeletal muscles, but did not appear to have much effect on the heart.

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The Satellite Cell in Male and Female, Developing and Adult Mouse Muscle: Distinct Stem Cells for Growth and Regeneration

The Satellite Cell in Male and Female, Developing and Adult Mouse Muscle: Distinct Stem Cells for Growth and Regeneration | Moorwood on Muscle | Scoop.it

Detailed characterisation of muscle precursor (satellite) cells in male and female mice across their lifespan. There is no difference in the success of stem cell grafts from male and female donors, which has implications for stem cell therapy.

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Artificial Muscle To Suck Up Shocks

Artificial Muscle To Suck Up Shocks | Moorwood on Muscle | Scoop.it
The idea of artificial muscles sounds like the future of medicine, with people getting new muscles built for them in a lab. But they may have applications beyond the human body. One you might not expect is absorbing shock and generating energy.

Via SustainOurEarth
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Performance of Repetitive Tasks Induces Decreased Grip Strength and Increased Fibrogenic Proteins in Skeletal Muscle: Role of Force and Inflammation

Performance of Repetitive Tasks Induces Decreased Grip Strength and Increased Fibrogenic Proteins in Skeletal Muscle: Role of Force and Inflammation | Moorwood on Muscle | Scoop.it

Repetetive tasks lead to a decrease in muscle strength, which can be partially prevented by anti-inflammatory treatment

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Genetic risk factors for cardiomyopathy

American Heart Association, BCVS 2012 - Thomas L. Force, MD (Temple University, Philadelphia, PA) and Elizabeth McNally, MD, PhD (The University of Chicago discuss the surprisingly high prevalence of genetic risk factors for cardiovascular disease.

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Delayed Recovery of Skeletal Muscle Mass following Hindlimb Immobilization in mTOR Heterozygous Mice

Delayed Recovery of Skeletal Muscle Mass following Hindlimb Immobilization in mTOR Heterozygous Mice | Moorwood on Muscle | Scoop.it

mTOR is more important for re-gaining muscle after immobilisation than for preventing its loss

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Meeting Synopsis: Advances in Skeletal Muscle Biology in Health and Disease (Gainesville, Florida, February 22nd to 24th 2012) – Day 2

Meeting Synopsis: Advances in Skeletal Muscle Biology in Health and Disease (Gainesville, Florida, February 22nd to 24th 2012) – Day 2 | Moorwood on Muscle | Scoop.it

Adult skeletal muscle adaptations in health and disease should receive more attention

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Mental Stress and Exercise Training Response: Stress-sleep Connection may be Involved

Mental Stress and Exercise Training Response: Stress-sleep Connection may be Involved | Moorwood on Muscle | Scoop.it

Stress and sleep deprivation may reduce the effect of exercise on fitness

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Big Players in Muscular Dystrophy Drug Discovery

Big Players in Muscular Dystrophy Drug Discovery | Moorwood on Muscle | Scoop.it
Catherine Moorwood's insight:

There are now significant numbers of companies developing a variety of treatments for muscular dystrophy, including 'big pharma' like GSK. This article gives a great overview of the latest developments and the players involved.

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Are there valid concerns for completing a marathon at 39 weeks of pregnancy?

Are there valid concerns for completing a marathon at 39 weeks of pregnancy? | Moorwood on Muscle | Scoop.it

The application of some science to a controversial media story.

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Mechanotransduction in skeletal muscle

Mechanotransduction in skeletal muscle | Moorwood on Muscle | Scoop.it

This is a great review on how physical forces get translated into biochemical signals in skeletal muscle, with a good description of the mechanical concepts involved.

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Novel Meta-Analysis Reveals Potential Drug Targets and Biomarkers in Duchenne Muscular Dystrophy

Novel Meta-Analysis Reveals Potential Drug Targets and Biomarkers in Duchenne Muscular Dystrophy | Moorwood on Muscle | Scoop.it

The authors conducted a meta-analysis of publicly available microarray gene expression data from DMD patients compared to healthy people. They identified genes that were consistently changed among multiple studies, some of which had previously been linked to DMD, others of which had not. These genes could be potential new drug targets, and could also serve as biomarkers, which are badly needed to assist in assessing the effects of experimental treatments in clinical trials.

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Sarcopenia, Dynapenia, and the Impact of Advancing Age on Human Skeletal Muscle Size and Strength; a Quantitative Review

Sarcopenia, Dynapenia, and the Impact of Advancing Age on Human Skeletal Muscle Size and Strength; a Quantitative Review | Moorwood on Muscle | Scoop.it

Review of age-related changes in muscle in human beings. Loss of strength is more significant than loss of mass; exercise can help.

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Lab-engineered muscle implants restore function in animals

Lab-engineered muscle implants restore function in animals | Moorwood on Muscle | Scoop.it
New research shows that exercise is a key step in building a muscle-like implant in the lab with the potential to repair muscle damage from injury or disease.

Via Gerd Moe-Behrens
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Scientists built artificial jellyfish from silicone and muscle cells from a rat's heart

Scientists built artificial jellyfish from silicone and muscle cells from a rat's heart | Moorwood on Muscle | Scoop.it

Bioengineers have made an artificial jellyfish using silicone and muscle cells from a rat’s heart. The synthetic creature, dubbed a medusoid, looks like a flower with eight petals. When placed in an electric field, it pulses and swims exactly like its living counterpart. Reverse-engineered life forms in general could be used to test drugs and avoid animal experiments in future.


Via Dr. Stefan Gruenwald
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Modular dispensability of dysferlin′s C2 domains reveals rational design for mini-dysferlin molecules

Like dystrophin, dysferlin has a repetative structure with some redundancy. Mini-dysferlins can work as well as the real thing, and are small enough to fit into a virus for gene therapy.

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New roles for calcium in the heart

Yibin Wang, PhD and Steven Houser, PhD, FAHA discuss some of the new developments in Calcium Signaling research that will be presented at BCVS 2012 in New Orleans

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Assessment of the structural and functional impact of in-frame mutations of the DMD gene, using the tools included in the eDystrophin online database

Assessment of the structural and functional impact of in-frame mutations of the DMD gene, using the tools included in the eDystrophin online database | Moorwood on Muscle | Scoop.it

Really interesting look at the structural effects of different in-frame dystrophin deletions. And they made a database:

http://edystrophin.genouest.org/index.php?page=knowledge&box=gene

 

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Meeting Synopsis: Advances in Skeletal Muscle Biology in Health and Disease (Gainesville, Florida, February 22nd to 24th 2012) – Day 1

Meeting Synopsis: Advances in Skeletal Muscle Biology in Health and Disease (Gainesville, Florida, February 22nd to 24th 2012) – Day 1 | Moorwood on Muscle | Scoop.it

Including mention of muscle hypertrophy in the absence of satellite cells

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Recent Insights into Muscle Fatigue at the Cross-Bridge Level

Recent Insights into Muscle Fatigue at the Cross-Bridge Level | Moorwood on Muscle | Scoop.it

New insights into the molecular basis of muscle fatigue

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