Haploinsufficiency of myostatin protects against aging‐related declines in muscle function and enhances the longevity of mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/1/acel12339-sup-0003-TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/2/acel12339.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/3/acel12339-sup-0004-TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/4/acel12339-sup-0002-FigureS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/5/acel12339-sup-0001-DataS1.pd

Transcriptome profiling of immune responses to cardiomyopathy syndrome (CMS) in Atlantic salmon

<p>Abstract</p> <p>Background</p> <p>Cardiomyopathy syndrome (CMS) is a disease associated with severe myocarditis primarily in adult farmed Atlantic salmon (<it>Salmo salar </it>L.), caused by a double-stranded RNA virus named piscine myocarditis virus (PMCV) with structural similarities to the <it>Totiviridae </it>family. Here we present the first characterisation of host immune responses to CMS assessed by microarray transcriptome profiling.</p> <p>Results</p> <p>Unvaccinated farmed Atlantic salmon post-smolts were infected by intraperitoneal injection of PMCV and developed cardiac pathology consistent with CMS. From analysis of heart samples at several time points and different tissues at early and clinical stages by oligonucleotide microarrays (SIQ2.0 chip), six gene sets representing a broad range of immune responses were identified, showing significant temporal and spatial regulation. Histopathological examination of cardiac tissue showed myocardial lesions from 6 weeks post infection (wpi) that peaked at 8-9 wpi and was followed by a recovery. Viral RNA was detected in all organs from 4 wpi suggesting a broad tissue tropism. High correlation between viral load and cardiac histopathology score suggested that cytopathic effect of infection was a major determinant of the myocardial changes. Strong and systemic induction of antiviral and IFN-dependent genes from 2 wpi that levelled off during infection, was followed by a biphasic activation of pathways for B cells and MHC antigen presentation, both peaking at clinical pathology. This was preceded by a distinct cardiac activation of complement at 6 wpi, suggesting a complement-dependent activation of humoral Ab-responses. Peak of cardiac pathology and viral load coincided with cardiac-specific upregulation of T cell response genes and splenic induction of complement genes. Preceding the reduction in viral load and pathology, these responses were probably important for viral clearance and recovery.</p> <p>Conclusions</p> <p>By comparative analysis of gene expression, histology and viral load, the temporal and spatial regulation of immune responses were characterised and novel immune genes identified, ultimately leading to a more complete understanding of host-virus responses and pathology and protection in Atlantic salmon during CMS.</p

Restoration of bilateral motor coordination from preserved agonist-antagonist coupling in amputation musculature

Abstract Background Neuroprosthetic devices controlled by persons with standard limb amputation often lack the dexterity of the physiological limb due to limitations of both the user’s ability to output accurate control signals and the control system’s ability to formulate dynamic trajectories from those signals. To restore full limb functionality to persons with amputation, it is necessary to first deduce and quantify the motor performance of the missing limbs, then meet these performance requirements through direct, volitional control of neuroprosthetic devices. Methods We develop a neuromuscular modeling and optimization paradigm for the agonist-antagonist myoneural interface, a novel tissue architecture and neural interface for the control of myoelectric prostheses, that enables it to generate virtual joint trajectories coordinated with an intact biological joint at full physiologically-relevant movement bandwidth. In this investigation, a baseline of performance is first established in a population of non-amputee control subjects ( $$n = 8$$ n = 8 ). Then, a neuromuscular modeling and optimization technique is advanced that allows unilateral AMI amputation subjects ( $$n = 5$$ n = 5 ) and standard amputation subjects ( $$n = 4$$ n = 4 ) to generate virtual subtalar prosthetic joint kinematics using measured surface electromyography (sEMG) signals generated by musculature within the affected leg residuum. Results Using their optimized neuromuscular subtalar models under blindfolded conditions with only proprioceptive feedback, AMI amputation subjects demonstrate bilateral subtalar coordination accuracy not significantly different from that of the non-amputee control group (Kolmogorov-Smirnov test, $$P \ge 0.052$$ P ≥ 0.052 ) while standard amputation subjects demonstrate significantly poorer performance (Kolmogorov-Smirnov test, $$P < 0.001$$ P < 0.001 ). Conclusions These results suggest that the absence of an intact biological joint does not necessarily remove the ability to produce neurophysical signals with sufficient information to reconstruct physiological movements. Further, the seamless manner in which virtual and intact biological joints are shown to coordinate reinforces the theory that desired movement trajectories are mentally formulated in an abstract task space which does not depend on physical limb configurations

Experimental autoimmune uveoretinitis and pinealitis induced by interphotoreceptor retinoid-binding protein and S-antigen: induction of intraretinal and subretinal neovascularization

Experimental autoimmune uveoretinitis (EAU) and pinealitis were induced in Lewis rats following hind foot pad injection of interphotoreceptor retinoid-binding protein (IRBP) or S-antigen. A comparison is made in this study of the in vivo and histological changes in uveoretinitis and pinealitis induced by administering similar doses of highly-purified IRBP and S-antigen emulsified in complete Freund's adjuvant (CFA). The time of onset of ocular inflammation after inoculation was slightly later in S-antigen (14-18 days) as compared with IRBP-inoculated animals (10-14 days), while the severity of the inflammation was lower in the latter group. The distribution of inflammation in the anterior segment was similar in both the S-antigen and IRBP sensitized animals but there was major variation in the location of the posterior segment disease. Vasculitis was a predominant feature of IRBP induced disease while chorioretinitis and photoreceptor destruction was more prominent in the S-antigen sensitized animals. A striking feature of this study is that both antigens induced intraretinal and subretinal neovascularization, an observation which has not been reported previously. Inflammation was induced in all pineal glands and as with EAU the severity was closely related to the type of antigen inoculated

Haploinsufficiency of myostatin protects against aging-related declines in muscle function and enhances the longevity of mice

Summary The molecular mechanisms behind aging-related declines in muscle function are not well understood, but the growth factor myostatin (MSTN) appears to play an important role in this process. Additionally, epidemiological studies have identified a positive correlation between skeletal muscle mass and longevity. Given the role of myostatin in regulating muscle size, and the correlation between muscle mass and longevity, we tested the hypotheses that the deficiency of myostatin would protect oldest-old mice (28-30 months old) from an aging-related loss in muscle size and contractility, and would extend the maximum lifespan of mice. We found that MSTN +/À and MSTN À/À mice were protected from aging-related declines in muscle mass and contractility. While no differences were detected between MSTN +/+ and MSTN À/À mice, MSTN +/À mice had an approximately 15% increase in maximal lifespan. These results suggest that targeting myostatin may protect against aging-related changes in skeletal muscle and contribute to enhanced longevity