Increase In Number Of Fibers Research Articles

Overexpression of TIAM2S, a Critical Regulator for the Hippocampal-Medial Prefrontal Cortex Network, Progresses Age-Related Spatial Memory Impairment.

TIAM Rac1-associated GEF 2 short-form protein (TIAM2S) is abundant in specific brain tissues, especially in the hippocampus, a brain region critical for processing and consolidation of spatial memory. However, how TIAM2S plasticizes the microstructure and circuits of the hippocampus to shape spatial memory as a neuroplastic regulator during aging remains to be determined. In this study, transgenic mice overexpressing human TIAM2S protein (TIAM2S-TG mice) were included, and interdisciplinary approaches, such as spatial memory tests and multiparametric magnetic resonance imaging sequences, were conducted to determine the role and the mechanism of TIAM2S in age-related spatial memory deficits. Despite no changes in their neural and glial markers and neuropathological hallmark expression of the hippocampus, behavioral tests showed that the TIAM2S-TG mice, and not wild-type (WT) mice, developed spatial memory impairment at 18 months old. The T2-weighted and diffusion tensor image analyses were performed to further study the possible role of TIAM2S overexpression in altering the hippocampal structure or neuronal circlets of the mice, increasing their vulnerability to developing spatial memory deficits during aging. The results revealed that the 12-month-old TIAM2S-TG mice had hippocampal dysplasticity, with larger volume, increased fiber numbers, and changed mean fractional anisotropy compared to those in the age-matched WT mice. The fiber tractography analysis exhibited significantly attenuated structural connectivity between the hippocampus and medial prefrontal cortex in the TIAM2S-TG mice. In conclusion, overexpression of TIAM2S, a detrimental factor affecting hippocampus plasticity, causes attenuation of the connectivity within hippocampus-mPFC circuits, leading to age-related spatial memory impairment.

Using an HDAC Inhibitor to Alter Muscle Growth in Fetal Pigs

A broad spectrum histone deacetylase (HDAC) inhibitor, butyrate, has been shown to promote increased myofiber size by altering satellite cell (SC) activity. The use of dietary supplementation of butyrate to affect muscle development has been hampered by its technical and pharmacokinetic properties. Most of these can be overcome with the use of tributyrin (TB), a butyrate prodrug. Dietary supplementation of TB was able to promote muscle growth by increasing myofiber size in neonatal pigs. We hypothesized that muscle growth during fetal development may be improved by increased fiber number through the dietary supplementation of TB to gestating sows. Nine sows of 53.6 ±1.08 gestational days (gd) were randomly assigned to one of three dietary treatment groups (n=3). These dietary treatments were a basal diet, basal diet + 1% TB, and the basal diet + 2% TB. All diets were made isocaloric with the addition of oil and wheat flour. Fetal piglets were removed at 107.6 ±1.5 gd. Weights and body lengths were recorded for all fetuses. Sections of Longissimus dorsi and Psoas major were collected from the median male, median female, the smallest, and the largest piglets of each litter and frozen for future histological analysis. Two novel methods for objective description of muscle fiber organization were evaluated, including fiber eccentricity (measure of elongation), and proportion of primary myofibers. The most significant difference in cross sectional area (CSA) was found within LD muscle with TB supplementation causing a significant reduction compared to control animals (p value < 0.05). Fibers from 1% TB animals were significantly more elongated than control (p value < 0.05). The proportion of primary to secondary myofibers was significantly higher in muscle from 2% TB treated piglets compared to control (p value < 0.05). The smaller CSA together with a similar body weight across individual piglets (p >0.05) suggest that TB supplementation increased myofiber number. The increased fiber count may be further supported by more elongated myofibers suggesting alterations to muscle fiber organization and an improved development of primary fibers. Further studies to elucidate the impact of TB supplementation during gestation and early postnatal life are warranted.

Jute Felt for Noise Reduction: Understanding Effect of Pore Size Distribution

ABSTRACT Effect of pore size and its distribution on the noise reduction coefficient of jute felt were studied through capillary flow porometer and impedance tube. The inter-criteria correlation method was used to optimize the type of jute felts to obtain noise reduction coefficient of 0.5. The porometry study of the needle punched jute felt suggested the gradient pore structure of felt due to presence of needling induced inverted cone of pores within fibrous mass. The jute felt with an areal density 796.5 g/m2 with mean pore diameter 60.32 µm offered optimum noise reduction coefficient of 0.5. The percentage weight of pore distribution in the range of 45≥ ∅ <25 µm was 44.61%, indicated that to achieve an objective of NRC≥ 0.5 the most influential pore diameter range was 45≥ ∅ 25.The increased number of jute fiber per unit area of felts from 55 to 430 resulted in narrowing of inter fiber spaces and consequently reduced the mean pore size. Further increase in number of fibers ultimately leads to blocking of spaces within fibers and get compacted like a solid fibrous mass.

Modeling pre-combustion CO2 capture with tubular membrane contactor using ionic liquids at elevated temperatures

A pre-combustion carbon capture process at high temperatures in membrane contactor setup using ionic liquid 1-Butyl-3-methlyimidazolium tricyanomethanide ([Bmim][TCM]) as an absorbent was studied here by developing a comprehensive mathematical model. A detailed 2D mass transport model based on finite element analysis was presented for this purpose. The model considers molecular diffusion in both axially and radially. The effects of various operational parameters were studied for CO2 absorption flux. A comparative study was carried out among different membrane contactor modules having different number of fibers. The increase in number of fibers has significantly enhanced the CO2 absorption process. An increase of 31% in the CO2 separation efficiency was observed by increasing the number of fibers from 1 to 10. Furthermore, the transient state behavior of CO2 concentration during the absorption process until reaching a steady state was systematically studied for various operating temperatures and gas flow rates.

Effects of gene mutation and disease progression on representative neural circuits in familial Alzheimer\u2019s disease

BackgroundAlthough structural and functional changes of the striatum and hippocampus are present in familial Alzheimer’s disease, little is known about the effects of specific gene mutation or disease progression on their related neural circuits. This study was to evaluate the effects of known pathogenic gene mutation and disease progression on the striatum- and hippocampus-related neural circuits, including frontostriatal and hippocampus-posterior cingulate cortex (PCC) pathways.MethodsA total of 102 healthy mutation non-carriers, 40 presymptomatic mutation carriers (PMC), and 30 symptomatic mutation carriers (SMC) of amyloid precursor protein (APP), presenilin 1 (PS1), or presenilin 2 gene, with T1 structural MRI, diffusion tensor imaging, and resting-state functional MRI were included. Representative neural circuits and their key nodes were obtained, including bilateral caudate-rostral middle frontal gyrus (rMFG), putamen-rMFG, and hippocampus-PCC. Volumes, diffusion indices, and functional connectivity of circuits were compared between groups and correlated with neuropsychological and clinical measures.ResultsIn PMC, APP gene mutation carriers showed impaired diffusion indices of caudate-rMFG and putamen-rMFG circuits; PS1 gene mutation carriers showed increased fiber numbers of putamen-rMFG circuit. SMC showed increased diffusivity of the left hippocampus-PCC circuit and volume reduction of all regions as compared with PMC. Imaging measures especially axial diffusivity of the representative circuits were correlated with neuropsychological measures.ConclusionsAPP and PS1 gene mutations affect frontostriatal circuits in a different manner in familial Alzheimer’s disease; disease progression primarily affects the structure of hippocampus-PCC circuit. The structural connectivity of both frontostriatal and hippocampus-PCC circuits is associated with general cognitive function. Such findings may provide further information about the imaging biomarkers for early identification and prognosis of familial Alzheimer’s disease, and pave the way for early diagnosis, gene- or circuit-targeted treatment, and even prevention.

Exogenous Expression of an Alternative Splicing Variant of Myostatin Prompts Leg Muscle Fiber Hyperplasia in Japanese Quail.

Myostatin (MSTN) negatively regulates muscle growth and development through inhibiting myoblast proliferation and differentiation. Five alternative splicing isoforms of MSTN (MSTN-A to MSTN-E) have been discovered in domestic avian species. MSTN-A has high expression in skeletal muscle and encodes the full-length peptide with anti-myogenic activity. Another isoform, MSTN-B, is also highly expressed in skeletal muscle and encodes a truncated peptide that has pro-myogenic capabilities in vitro, which include promoting the proliferation and differentiation of quail muscle precursor cells. The objective of this study was to investigate overexpression of MSTN-B in vivo by using two independent lines of transgenic Japanese quail with expression directed in the skeletal muscle. Unexpectedly, the chicken skeletal muscle alpha actin 1 (cACTA1) promoter resulted in restricted exogenous MSTN-B protein expression to certain skeletal muscles, such as the gastrocnemius and tibialis anterior, but not the pectoralis major muscle. Gastrocnemius weight as a percentage of body weight in transgenic quail was increased compared to non-transgenic quail at posthatch day 21 (D21) and posthatch D42. An increase in the size of the gastrocnemius in transgenic quail was attributed to an increase in fiber number but not fiber cross-sectional area (CSA). During embryonic development, paired box 7 (PAX7) expression was prolonged in the transgenic embryos, but other myogenic regulatory factors (MRFs) were unchanged after MSTN-B overexpression. Taken together, these data provide novel insights into the regulation of skeletal muscle development by alternative splicing mechanisms in avians.

The effect of specific surface area of macro fibers on energy absorption capacity of concrete

Energy absorption capacity is the salient property of concrete. Reinforcement of concrete with macro fibers is one of the techniques that has led to enhancement of this important feature of concrete. However, the effect of specific surface area of melt-spun polypropylene macro fibers has hardly been studied so far. In this work, the effect of this parameter on mechanical behavior of fiber reinforced concrete (FRC) was investigated. Diameter of macro fibers was varied by changing the melt feeding rate and fiber draw ratio. Changes in fibers diameter affect fibers specific surface area, which in turn influences the adhesion of fibers to the matrix in FRCs. In order to evaluate the FRCs behavior, bending tests were conducted and the area under load-displacement curves was studied. It was found that increase in specific surface area of fibers results in considerable increase in energy absorption capacity of the FRCs. Concrete reinforced with the larger diameter fibers exhibited 6× energy absorption capacity than the reference sample. This was found to be in line with the 14× energy absorption capacity of sample which was reinforced by smaller diameter fibers. This was attributed to the increase in total contact area between the finer fibers and the matrix as a direct consequence of the increase in number of fibers for a given fiber volume fraction.

Muscle fiber growth in olive flounder, Paralichthys olivaceus: Fiber hyperplasia at a specific body weight period and continuous hypertrophy

The objective of this study was to investigate muscle fiber growth‐related attributes, especially fiber hyperplasia and hypertrophy, and their relation to growth characteristics in olive flounder. After a conditioning period, juvenile olive flounder (214 g of initial body weight) were weighed after 0, 4, 8, 12, and 24 weeks of a feeding trial and were selected based on mean body weight at each period (G1, G2, G3, G4, and G5, respectively). During the 3.0‐fold increase in body weight (363.1–1,071 g, p &lt; 0.001), the fiber area was increased approximately 2.2 times (p &lt; 0.05), and the median area increased from the G1 to G5 groups (p &lt; 0.05). The G3 group exhibited a greater fiber number than the G2 group (p &lt; 0.05) as the G3 group exhibited a higher percentage of smaller fiber and mosaic hyperplasia. In addition, a higher percentage of centered nuclei and deoxyribonucleic acid amount in the G2 group were accompanied by an increase in fiber number in the G3 group. Therefore, the muscle growth of olive flounder was influenced by continued fiber area growth and a significant number increase by mosaic hyperplasia during a specific period (G2 to G3 groups; from 512.7 to 670.3 g).

Effect of carbon fiber type on monotonic and fatigue properties of orthopedic grade PEEK

Carbon-fiber reinforced (CFR) PEEK implants are used in orthopedic applications ranging from fracture fixation plates to spinal fusion cages. Documented implant failures and increasing volume and variety of CFR PEEK implants warrant a clearer understanding of material behavior under monotonic and cyclic loading. To address this issue, we conducted monotonic and fatigue crack propagation (FCP) experiments on orthopedic grade unfilled PEEK and two formulations of CFR PEEK (PAN- and pitch-based carbon fibers). The effect of annealing on FCP behavior was also studied. Under monotonic loading, fiber type had a statistically significant effect on elastic modulus (12.5 ± 1.3 versus 18.5 ± 2.3 GPa, pitch versus PAN CFR PEEK, AVG ± SD) and on ultimate tensile strength (145 ± 9 versus 192 ± 17 MPa, pitch versus PAN CFR PEEK, AVG ± SD). Fiber type did not have a significant effect on failure strain. Under cyclic loading, PAN CFR PEEK demonstrated an increased resistance to FCP compared with unfilled and pitch CFR PEEK, and this improvement was enhanced following annealing. Pitch CFR PEEK exhibited FCP behavior similar to unfilled PEEK, and neither material was appreciably affected by annealing. The improvements in monotonic and FCP behavior of PAN CFR PEEK is attributed to a compound effect of inherent fiber properties, increased fiber number for an equivalent wt% reinforcement, and fiber aspect ratio. FCP was shown to proceed via cyclic modes during stable crack growth, which transitioned to static modes (more akin to monotonic fracture) at longer crack lengths. The mechanisms of fatigue crack propagation appear similar between carbon-fiber types.

Age-related remodelling of the myotendinous junction in the mouse soleus muscle

The age-related loss of muscle mass and function predominantly affect muscles of the lower limbs and have largely been associated with decline in muscle fibre size and number, although the exact mechanisms underlying these losses are poorly understood. In addition, consistent reports that the loss of muscle strength exceeds that which can be explained by declines in muscle mass has widened the search for causes of sarcopenia to include supporting tissues such as the extracellular matrix and tendons. Although the changes to both muscle and tendon with age are well characterised, little work has focused on the interface between these two tissues, the myotendinous junction (MTJ). Given the crucial role for this structure in force transfer between muscle and tendon, we asked whether the myotendinous junction underwent structural changes with age in lower limb muscle. We used whole muscle to assess gross muscle and tendon morphology, and immunohistochemistry to determine fibre and MTJ profile number in young (6 months), middle aged (18 months) and elderly (24 months) C57BL/6 female mice. MTJ length was quantified using serial cross sections of the soleus muscle. We found an apparent 3.5-fold increase in MTJ profiles per cross section with no increase in fibre number in old mice, and found this to be a result of a doubling in length of the MTJ region with age. This coincided with an increase in proximal tendon length (31%), as well as an increase in collagen deposition between 6 and 24-months of age consistent with an expansion of the fibre termination area. These findings uncover a previously undescribed effect of ageing on the MTJ and open up new lines of investigation into the role of this structure in the age-related loss of muscle function.

Muscle satellite cells are functionally impaired in myasthenia gravis: consequences on muscle regeneration.

Myasthenia gravis (MG) is a neuromuscular disease caused in most cases by anti-acetyl-choline receptor (AChR) autoantibodies that impair neuromuscular signal transmission and affect skeletal muscle homeostasis. Myogenesis is carried out by muscle stem cells called satellite cells (SCs). However, myogenesis in MG had never been explored. The aim of this study was to characterise the functional properties of myasthenic SCs as well as their abilities in muscle regeneration. SCs were isolated from muscle biopsies of MG patients and age-matched controls. We first showed that the number of Pax7+ SCs was increased in muscle sections from MG and its experimental autoimmune myasthenia gravis (EAMG) mouse model. Myoblasts isolated from MG muscles proliferate and differentiate more actively than myoblasts from control muscles. MyoD and MyoG were expressed at a higher level in MG myoblasts as well as in MG muscle biopsies compared to controls. We found that treatment of control myoblasts with MG sera or monoclonal anti-AChR antibodies increased the differentiation and MyoG mRNA expression compared to control sera. To investigate the functional ability of SCs from MG muscle to regenerate, we induced muscle regeneration using acute cardiotoxin injury in the EAMG mouse model. We observed a delay in maturation evidenced by a decrease in fibre size and MyoG mRNA expression as well as an increase in fibre number and embryonic myosin heavy-chain mRNA expression. These findings demonstrate for the first time the altered function of SCs from MG compared to control muscles. These alterations could be due to the anti-AChR antibodies via the modulation of myogenic markers resulting in muscle regeneration impairment. In conclusion, the autoimmune attack in MG appears to have unsuspected pathogenic effects on SCs and muscle regeneration, with potential consequences on myogenic signalling pathways, and subsequently on clinical outcome, especially in the case of muscle stress.

Effects of sarcolipin deletion on skeletal muscle adaptive responses to functional overload and unload.

Overexpression of sarcolipin (SLN), a regulator of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs), stimulates calcineurin signaling to enhance skeletal muscle oxidative capacity. Some studies have shown that calcineurin may also control skeletal muscle mass and remodeling in response to functional overload and unload stimuli by increasing myofiber size and the proportion of slow fibers. To examine whether SLN might mediate these adaptive responses, we performed soleus and gastrocnemius tenotomy in wild-type (WT) and Sln-null (Sln-/-) mice and examined the overloaded plantaris and unloaded/tenotomized soleus muscles. In the WT overloaded plantaris, we observed ectopic expression of SLN, myofiber hypertrophy, increased fiber number, and a fast-to-slow fiber type shift, which were associated with increased calcineurin signaling (NFAT dephosphorylation and increased stabilin-2 protein content) and reduced SERCA activity. In the WT tenotomized soleus, we observed a 14-fold increase in SLN protein, myofiber atrophy, decreased fiber number, and a slow-to-fast fiber type shift, which were also associated with increased calcineurin signaling and reduced SERCA activity. Genetic deletion of Sln altered these physiological outcomes, with the overloaded plantaris myofibers failing to grow in size and number, and transition towards the slow fiber type, while the unloaded soleus muscles exhibited greater reductions in fiber size and number, and an accelerated slow-to-fast fiber type shift. In both the Sln-/- overloaded and unloaded muscles, these findings were associated with elevated SERCA activity and blunted calcineurin signaling. Thus, SLN plays an important role in adaptive muscle remodeling potentially through calcineurin stimulation, which could have important implications for other muscle diseases and conditions.

Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness.

In the setting of profound ocular blindness, numerous lines of evidence demonstrate the existence of dramatic anatomical and functional changes within the brain. However, previous studies based on a variety of distinct measures have often provided inconsistent findings. To help reconcile this issue, we used a multimodal magnetic resonance (MR)-based imaging approach to provide complementary structural and functional information regarding this neuroplastic reorganization. This included gray matter structural morphometry, high angular resolution diffusion imaging (HARDI) of white matter connectivity and integrity, and resting state functional connectivity MRI (rsfcMRI) analysis. When comparing the brains of early blind individuals to sighted controls, we found evidence of co-occurring decreases in cortical volume and cortical thickness within visual processing areas of the occipital and temporal cortices respectively. Increases in cortical volume in the early blind were evident within regions of parietal cortex. Investigating white matter connections using HARDI revealed patterns of increased and decreased connectivity when comparing both groups. In the blind, increased white matter connectivity (indexed by increased fiber number) was predominantly left-lateralized, including between frontal and temporal areas implicated with language processing. Decreases in structural connectivity were evident involving frontal and somatosensory regions as well as between occipital and cingulate cortices. Differences in white matter integrity (as indexed by quantitative anisotropy, or QA) were also in general agreement with observed pattern changes in the number of white matter fibers. Analysis of resting state sequences showed evidence of both increased and decreased functional connectivity in the blind compared to sighted controls. Specifically, increased connectivity was evident between temporal and inferior frontal areas. Decreases in functional connectivity were observed between occipital and frontal and somatosensory-motor areas and between temporal (mainly fusiform and parahippocampus) and parietal, frontal, and other temporal areas. Correlations in white matter connectivity and functional connectivity observed between early blind and sighted controls showed an overall high degree of association. However, comparing the relative changes in white matter and functional connectivity between early blind and sighted controls did not show a significant correlation. In summary, these findings provide complimentary evidence, as well as highlight potential contradictions, regarding the nature of regional and large scale neuroplastic reorganization resulting from early onset blindness.

Preparation and Mechanical Properties of Jute Fiber Reinforced Epoxy Composites

Nowadays, scientist and engineers working in the field of materials are too concerned with sustainability issues and environmental protection. Due to environmental friendly, bio degradability and sustainability, natural fiber composites are preferred as compared to conventional synthetic fiber based composites. An Epoxy piece and Jute fiber-epoxy composite is prepared using hand lay- up technique. For this purpose, an open type mould made of mild steel plate has been used. It is revealed that the jute epoxy composite exhibited better tensile and compressive strength. Bundle strength of fibers decreases with increase in number of fibers in a Bundle. Tensile and compressive strength increases with Jute fiber reinforcement.

Comparison of Muscle Fiber and Meat Quality Characteristics in Different Japanese Quail Lines.

The aim of this study was to compare the growth performance, fiber characteristics of the pectoralis major muscle, and meat quality characteristics in the heavy weight (HW) and random bred control (RBC) quail lines and genders. The HW male exhibited more than two times greater body (245.7 vs 96.1 g, p<0.05) and pectoralis major muscle (PMW; 37.1 vs 11.1 g, p<0.05) weights compared to the RBC female. This growth performance in the HW line was associated with a greater muscle fiber area (1,502 vs 663.0 μm2, p<0.001) compared to the RBC line. Greater muscle mass of the HW male was accompanied by a higher percentage of type IIB fiber compared to the HW female (64.0% vs 51.0%, p<0.05). However, muscle fiber hyperplasia (increase in fiber number) has had a somewhat limited effect on PMW between the two lines. On the other hand, the HW line harboring a higher proportion of type IIB fiber showed rapid pH decline at the early postmortem period (6.23 vs 6.41, p<0.05) and lighter meat surface (53.5 vs 47.3, p<0.05) compared to the RBC line harboring a lower proportion of type IIB fiber. There were no significant differences observed in the measurement of water-holding capacity including drip loss (2.74% vs 3.07%, p>0.05) and cooking loss (21.9% vs 20.4%, p>0.05) between the HW and RBC lines. Therefore, the HW quail line developed by selection from the RBC quail, was slightly different in the meat quality characteristics compared to the RBC line, and a marked difference was found in growth performance between the two quail lines.

Proliferation of Multiple Cell Types in the Skeletal Muscle Tissue Elicited by Acute p21 Suppression

Although in the last decades the molecular underpinnings of the cell cycle have been unraveled, the acquired knowledge has been rarely translated into practical applications. Here, we investigate the feasibility and safety of triggering proliferation in vivo by temporary suppression of the cyclin-dependent kinase inhibitor, p21. Adeno-associated virus (AAV)-mediated, acute knockdown of p21 in intact skeletal muscles elicited proliferation of multiple, otherwise quiescent cell types, notably including satellite cells. Compared with controls, p21-suppressed muscles exhibited a striking two- to threefold expansion in cellularity and increased fiber numbers by 10 days post-transduction, with no detectable inflammation. These changes partially persisted for at least 60 days, indicating that the muscles had undergone lasting modifications. Furthermore, morphological hyperplasia was accompanied by 20% increases in maximum strength and resistance to fatigue. To assess the safety of transiently suppressing p21, cells subjected to p21 knockdown in vitro were analyzed for γ-H2AX accumulation, DNA fragmentation, cytogenetic abnormalities, ploidy, and mutations. Moreover, the differentiation competence of p21-suppressed myoblasts was investigated. These assays confirmed that transient suppression of p21 causes no genetic damage and does not impair differentiation. Our results establish the basis for further exploring the manipulation of the cell cycle as a strategy in regenerative medicine.

Activation of less affected corticospinal tract and poor motor outcome in hemiplegic pediatric patients: a diffusion tensor tractography imaging study.

The less affected hemisphere is important in motor recovery in mature brains. However, in terms of motor outcome in immature brains, no study has been reported on the less affected corticospinal tract in hemiplegic pediatric patients. Therefore, we examined the relationship between the condition of the less affected corticospinal tract and motor function in hemiplegic pediatric patients. Forty patients with hemiplegia due to perinatal or prenatal injury (13.7 ± 3.0 months) and 40 age-matched typically developing controls were recruited. These patients were divided into two age-matched groups, the high functioning group (20 patients) and the low functioning group (20 patients) using functional level of hemiplegia scale. Diffusion tensor tractography images showed that compared with the control group, the patient group of the less affected corticospinal tract showed significantly increased fiber number and significantly decreased fractional anisotropy value. Significantly increased fiber number and significantly decreased fractional anisotropy value in the low functioning group were observed than in the high functioning group. These findings suggest that activation of the less affected hemisphere presenting as increased fiber number and decreased fractional anisotropy value is related to poor motor function in pediatric hemiplegic patients.

Immersion bath treatment of tilapia fry with myostatin-1 prodomain does not affect tilapia growth at market size

Myostatin (MSTN), a member of the transforming growth factor-b (TGF-b) superfamily, is a potent negative regulator of skeletal muscle growth in mammalian species (Lee 2004). Recent studies have also indicated that fish MSTN negatively regulates muscle growth in fish (Xu, Wu, Zohar & Du 2003; Amali, Lin, Chen, Wang, Gong, Lee, Ko, Lu, Her, Chen & Wu 2004; Acosta, Carpio, Borroto, Gonzalez & Estrada 2005; Lee, Hu, Gong, Chen, Lu & Wu 2009; Medeiros, Phelps, Fuentes & Bradley 2009; Lee et al. 2010; Lee, Cho, Kim, Kim & Jin 2011). Because of the prominent role of MSTN in regulating muscle mass, there has been much interest in developing MSTN-based strategies to improve skeletal muscle growth in agriculturally important animal species, including fish (Tsuchida 2008).The MSTN prodomain (MSTNpro), the Nterminal part of MSTN precursor molecule, has been shown to be a potent suppressor of MSTN activity in mammalian species (Lee & McPherron 1999; Yang, Ratovitski, Brady, Solomon, Wells & Wall 2001; Matsakas, Foster, Otto, Macharia, Elashry, Feist, Graham, Foster, Yaworsky, Walsh, Dickson & Patel 2009; Hu, Chen, Sheng, Sun, Cao & Qiao 2010; Li, Zhao, Kim, Hu & Yang 2010). Fish MSTNpro also appears to suppress MSTN activity. The MSTN-1 prodomain (MSTN1pro) of the marine fish Sparus aurata suppressed MSTN activity in vitro (Rebhan & Funkenstein 2008). An increase in fibre number was observed in transgenic zebrafish overexpressing MSTN1pro (Xu et al. 2003). Recently, it was also observed that immersion bath treatment with flatfish (Paralichthys olivaceus) MSTN1pro (poMSTN1pro) expressed in an Escherichia coli system improved the growth of young juvenile rainbow trout (Lee et al. 2010), indicating the potential of fish MSTN-1 prodomain as an agent to improve the growth of commercially important aquaculture species. Similarly, immersion bath treatment of African catfish, goldfish and tilapia larvae with a soluble form of MSTN receptor (activin type IIB receptor) improved body mass growth of those fish (Carpio, Acosta, Morales, Santisteban, Sanchez & Estrada 2009). These studies, however, examined the growth response only during the 28–35 days treatment period, and did not follow the growth response to market size. Thus, it is not known whether the enhanced weight gain induced by treatment with MSTN inhibitor at the early stage of fish growth would last to later growth stages, resulting in heavier market weight when harvested at a fixed growth period. The current study was designed to address this question.

Prolonged endurance exercise decreases fiber loss and fiber atrophy in aged male rats

Sarcopenia is the age‐related loss of muscle mass and function. Effects of long‐term exercise training on sarcopenia have not been well defined. In this study we assessed skeletal muscle adaptations to prolonged exercise training in rats from late‐middle age to old age. Male rats, 24 mo of age, trained on a treadmill at three levels of intensity: high (HI: 13m/min, 5% incline for 30 min, 5 days per week), moderate (MI: 13m/min, 0% incline for 30 min, 5 days per week), minimally active (MA: 5m/min, for 5 min, 2 days per week) and a sedentary group (S). Rats ran for one year until the rats were age 36 months. The rectus femoris (RF) muscle from 24‐month Controls (C), and 36‐month HI, MI, MA, and S. The RF was weighed, bisected, frozen, sectioned and stained with hematoxylin and eosin. Digital images of RF cross‐sections were used to determine muscle area, fiber number and fiber diameter. Aging significantly reduced muscle mass, muscle area, fiber number and fiber diameter, (24‐month C compared to any of the 36‐month old S, MA, MI or HI). Among the 36‐mo. rats (HI, MI, MA, and S), no differences were observed in muscle mass or muscle area. However, there was a significant increase in fiber number and fiber diameter in all exercise groups (HI, MI, and MA) compared to S. These results indicate that any level of exercise, even minimal levels of activity is capable of decreasing the effects of sarcopenia in aging rats.Supported by NIH AG 030423.

The Role of mTOR in Mechanical Load Induced Skeletal Muscle Hypertrophy and Hyperplasia

Placing a chronic mechanical load on skeletal muscle induces a hypertrophic response and several studies have demonstrated that systemic administration of rapamycin will block this event. Since rapamycin is considered to be a highly specific inhibitor of mTOR, it has been widely concluded that mTOR is the rapamycin-sensitive element that confers the hypertrophic effects of mechanical loading. However, like most pharmacological inhibitors, rapamycin can exert non-specific (mTOR-independent) actions. Furthermore, systemic administration of rapamycin would be expected to inhibit mTOR signaling in all cells throughout the body, and therefore, it is not clear if the anti-hypertrophic effects of rapamycin are specifically due to inhibition of mTOR signaling in skeletal muscle cells. To address these points, we have employed transgenic mice with muscle specific expression of various rapamycin-resistant mutants of mTOR. With these mice we have confirmed that mTOR is the rapamycin-sensitive element, in skeletal muscle, that confers mechanical load induced hypertrophy, and that mTOR kinase activity is necessary for this event. Furthermore, the mechanical loading model employed in this study (synergist ablation) induced robust hyperplasia (59% increase in fiber number after 14 days), but surprisingly, the hyperplasia was elicited through an mTOR-independent mechanism.