Akt signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy

Skeletal muscle size is tightly regulated by the synergy between anabolic and catabolic signalling pathways which, in humans, have not been well characterized. Akt has been suggested to play a pivotal role in the regulation of skeletal muscle hypertrophy and atrophy in rodents and cells. Here we measured the amount of phospho-Akt and several of its downstream anabolic targets (glycogen synthase kinase-3β (GSK-3β), mTOR, p70s6k and 4E-BP1) and catabolic targets (Foxo1, Foxo3, atrogin-1 and MuRF1). All measurements were performed in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy-stimulating resistance training and atrophy-stimulating de-training. Following resistance training a muscle hypertrophy (∼10%) and an increase in phospho-Akt, phospho-GSK-3β and phospho-mTOR protein content were observed. This was paralleled by a decrease in Foxo1 nuclear protein content. Following the de-training period a muscle atrophy (5%), relative to the post-training muscle size, a decrease in phospho-Akt and GSK-3β and an increase in Foxo1 were observed. Atrogin-1 and MuRF1 increased after the hypertrophy and decreased after the atrophy phases. We demonstrate, for the first time in human skeletal muscle, that the regulation of Akt and its downstream signalling pathways GSK-3β, mTOR and Foxo1 are associated with both the skeletal muscle hypertrophy and atrophy processes.

Gradient edge map features for frontal face recognition under extreme illumination changes

Our aim in this paper is to robustly match frontal faces in the presence of extreme illumination changes, using only a single training image per person and a single probe image. In the illumination conditions we consider, which include those with the dominant light source placed behind and to the side of the user, directly above and pointing downwards or indeed below and pointing upwards, this is a most challenging problem. The presence of sharp cast shadows, large poorly illuminated regions of the face, quantum and quantization noise and other nuisance effects, makes it difficult to extract a sufficiently discriminative yet robust representation. We introduce a representation which is based on image gradient directions near robust edges which correspond to characteristic facial features. Robust edges are extracted using a cascade of processing steps, each of which seeks to harness further discriminative information or normalize for a particular source of extra-personal appearance variability. The proposed representation was evaluated on the extremely difficult YaleB data set. Unlike most of the previous work we include all available illuminations, perform training using a single image per person and match these also to a single probe image. In this challenging evaluation setup, the proposed gradient edge map achieved 0.8% error rate, demonstrating a nearly perfect receiver-operator characteristic curve behaviour. This is by far the best performance achieved in this setup reported in the literature, the best performing methods previously proposed attaining error rates of approximately 6–7%.

Common variants of the resistance mechanism in the Smith Machine: analysis of mechanical loading characteristics and application to strength-oriented and hypertrophy-oriented training

The Smith machine is a pervasive weight-training apparatus, used extensively by a wide population of weight trainers, from novices to high-level athletes. The advantages of using a Smith machine over free-weight resistance are disputed, with conflicting findings reported in the literature. In this study, we are interested in practical differences between 3 types of loading mechanisms found in modern Smith machines. In addition to the basic design comprising a constrained weighted barbell, alterations with a counterweight and a viscous resistance component are examined. The approach taken is that of employing a recently proposed representation of force characteristics that may be exhibited by a trainee and a predictive model of thus effected adaptation. A computer simulation is used to predict the effects of the 3 linear Smith machine designs in the framework of different exercise protocols. Our results demonstrate that each resistance component, vertically constrained load, counterweight, and viscous, can be matched with a particular training context, in which it should be preferred. Thus, a number of practical guidelines for weight-training practitioners are recommended. In summary, (a) at low intensities (55–75% of 1 repetition maximum [1RM]) used in strength-endurance training, a viscous resistance containing the Smith machine was found to offer advantages over both a constrained load only and counterweighted designs; (b) at medium intensities (75–85% of 1RM) typically employed in hypertrophy-specific training, the counterweighted Smith machine design was found to offer the best choice in terms of high-force development and total external work performed; finally, (c) at high training intensity (90–100% of 1RM), the optimal prescription was found to be more dependent on the specific athlete’s weaknesses, highlighting the need for continual monitoring of the athlete’s force production capabilities. To ensure that appropriate adjustments are made to the athlete’s training regimen, the practitioner should consider the full set of findings of this article and the accompanying discussion.

Glomerular hypertrophy in subjects with low nephron number: contributions of sex, body size and race

Background. We have shown that low nephron number (Nglom) is a strong determinant of individual glomerular volume (IGV) in male Americans. However, whether the same pattern is present in female Americans remains unclear. The contributions of body surface area (BSA) and race to IGV in the context of Nglom also require further evaluation. Methods. Kidneys without overt renal disease were collected at autopsy in Mississippi, USA. The extremes of female Nglom were used to define high and low N glom for both sexes. Nglom and IGV were estimated by design-based stereology. A total of 24 African and Caucasian American females (n = 12 per race; 6 per Nglom extreme) were included. These subjects were subsequently matched to 24 comparable males by age and Nglom and to 18 additional males by age, Nglom and BSA. Results. IGV average and variance were very similar in female African and Caucasian Americans with high and low Nglom. Males with low Nglom from both races showed greater IGV average and variance than comparable females matched by age and Nglom. These differences in IGV between sexes were not observed in Caucasian Americans with low Nglom that were matched by age, Nglom and BSA. In contrast, glomeruli from African Americans were larger than those from Caucasian Americans, especially in subjects with high Nglom. Conclusions. While female Americans with low Nglom did not show glomerular hypertrophy, comparable males with low Nglom showed marked glomerular hypertrophy that was closely associated with high BSA. Glomerular size in African Americans may be confounded by multiple additional factors. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Hypertrophy in the cervical muscles and thoracic discs in bed rest?

The impact of prolonged bed rest on the cervical and upper thoracic spine is unknown. In the 2nd Berlin BedRest Study (BBR2-2), 24 male subjects underwent 60-day bed rest and performed either no exercise, resistive exercise, or resistive exercise with whole body vibration. Subjects were followed for 2 yr after bed rest. On axial cervical magnetic resonance images from the skull to T3, the volumes of the semispinalis capitis, splenius capitis, spinalis cervicis, longus capitis, longus colli, levator scapulae, sternocleidomastoid, middle and posterior scalenes, and anterior scalenes were measured. Disc height, anteroposterior width, and volume were measured from C2/3 to T6/7 on sagittal images. The volume of all muscles, with the exception of semispinalis capitis, increased during bed rest (P < 0.025). There were no significant differences between the groups for changes in the muscles. Increased upper and midthoracic spine disc height and volume (P < 0.001) was seen during bed rest, and disc height increases persisted at least 6 mo after bed rest. Increases in thoracic disc height were greater (P = 0.003) in the resistive vibration exercise group than in control. On radiological review, two subjects showed new injuries to the mid-lower thoracic spine. One of these subjects reported a midthoracic pain incident during maximal strength testing before bed rest and the other after countermeasure exercise on day 3 of bed rest. We conclude that bed rest is associated with increased disc size in the thoracic region and increases in muscle volume at the neck. The exercise device needs to be modified to ensure that load is distributed in a more physiological fashion.

Telomere dynamics during aging in polygenic left ventricular hypertrophy.

Short telomeres are associated with increased risk of cardiovascular disease. Here we studied cardiomyocyte telomere length at key ages during the ontogeny of cardiac hypertrophy and failure in the hypertrophic heart rat (HHR), and compared these with the normal heart rat (NHR) control strain. Key ages corresponded with the pathophysiological sequence beginning with fewer cardiomyocytes (2-days), leading to left ventricular hypertrophy (LVH) (13-weeks) and subsequently progression to heart failure (38-weeks). We measured telomere length, tissue activity of telomerase, mRNA levels of telomerase reverse transcriptase (Tert) and telomerase RNA component (Terc), and expression of the telomeric regulator microRNA miR-34a. Cardiac telomere length was longer in the HHR compared to the control strain at 2-days and 38-weeks, but shorter at 13-weeks. Neonatal HHR had higher cardiac telomerase activity and expression of Tert and miR-34a. Telomerase activity was not different at 13- or 38-weeks. Tert mRNA and Terc RNA were over-expressed at 38-weeks, while miR-34a was over-expressed at 13-weeks but down-regulated at 38-weeks. Circulating leukocytes were strongly correlated with cardiac telomere length in the HHR only. The longer neonatal telomeres in HHR are likely to reflect fewer foetal and early postnatal cardiomyocyte cell divisions and explain the reduced total cardiomyocyte complement that predisposes to later hypertrophy and failure. Although shorter telomeres were a feature of cardiac hypertrophy at 13-weeks, they were not present at the progression to heart failure at 38-weeks.

Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22

BACKGROUND: Left ventricular (LV) hypertrophy is a risk factor for cardiovascular death, but the genetic factors determining LV size and predisposition to hypertrophy are not well understood. We have previously linked the quantitative trait locus cardiac mass 22 (Cm22) on chromosome 2 with cardiac hypertrophy independent of blood pressure in the spontaneously hypertensive rat. From an original cross of spontaneously hypertensive rat with F344 rats, we derived a normotensive polygenic model of spontaneous cardiac hypertrophy, the hypertrophic heart rat (HHR) and its control strain, the normal heart rat (NHR).

METHODS AND RESULTS: To identify the genes and molecular mechanisms underlying spontaneous LV hypertrophy we sequenced the HHR genome with special focus on quantitative trait locus Cm22. For correlative analyses of function, we measured global RNA transcripts in LV of neonatal HHR and NHR and 198 neonatal rats of an HHR × NHR F2 crossbred population. Only one gene within locus Cm22 was differentially expressed in the parental generation: tripartite motif-containing 55 (Trim55), with mRNA downregulation in HHR (P < 0.05) and reduced protein expression. Trim55 mRNA levels were negatively correlated with LV mass in the F2 cross (r = -0.16, P = 0.025). In exon nine of Trim55 in HHR, we found one missense mutation that functionally alters protein structure. This mutation was strongly associated with Trim55 mRNA expression in F2 rats (F = 10.35, P < 0.0001). Similarly, in humans, we found reduced Trim55 expression in hearts of subjects with idiopathic dilated cardiomyopathy.

CONCLUSION: Our study suggests that the Trim55 gene, located in Cm22, is a novel candidate gene for polygenic LV hypertrophy independent of blood pressure.