Un "simposio di sapienza e affetto"

Muscle hypertrophy occurs following increased protein synthesis, which requires activation of the ribosomal complex. Additionally, increased translational capacity via elevated ribosomal RNA (rRNA) synthesis has also been implicated in resistance training-induced skeletal muscle hypertrophy. The time course of ribosome biogenesis following resistance exercise (RE) and the impact exerted by differing recovery strategies remains unknown. In the present study, the activation of transcriptional regulators, the expression levels of pre-rRNA, and mature rRNA components were measured through 48 h after a single-bout RE. In addition, the effects of either low-intensity cycling (active recovery, ACT) or a cold-water immersion (CWI) recovery strategy were compared. Nine male subjects performed two bouts of high-load RE randomized to be followed by 10 min of either ACT or CWI. Muscle biopsies were collected before RE and at 2, 24, and 48 h after RE. RE increased the phosphorylation of the p38-MNK1-eIF4E axis, an effect only evident with ACT recovery. Downstream, cyclin D1 protein, total eIF4E, upstream binding factor 1 (UBF1), and c-Myc proteins were all increased only after RE with ACT. This corresponded with elevated abundance of the pre-rRNAs (45S, ITS-28S, ITS-5.8S, and ETS-18S) from 24 h after RE with ACT. In conclusion, coordinated upstream signaling and activation of transcriptional factors stimulated pre-rRNA expression after RE. CWI, as a recovery strategy, markedly blunted these events, suggesting that suppressed ribosome biogenesis may be one factor contributing to the impaired hypertrophic response observed when CWI is used regularly after exercise

Signal Propagation in Feedforward Neuronal Networks with Unreliable Synapses

In this paper, we systematically investigate both the synfire propagation and firing rate propagation in feedforward neuronal network coupled in an all-to-all fashion. In contrast to most earlier work, where only reliable synaptic connections are considered, we mainly examine the effects of unreliable synapses on both types of neural activity propagation in this work. We first study networks composed of purely excitatory neurons. Our results show that both the successful transmission probability and excitatory synaptic strength largely influence the propagation of these two types of neural activities, and better tuning of these synaptic parameters makes the considered network support stable signal propagation. It is also found that noise has significant but different impacts on these two types of propagation. The additive Gaussian white noise has the tendency to reduce the precision of the synfire activity, whereas noise with appropriate intensity can enhance the performance of firing rate propagation. Further simulations indicate that the propagation dynamics of the considered neuronal network is not simply determined by the average amount of received neurotransmitter for each neuron in a time instant, but also largely influenced by the stochastic effect of neurotransmitter release. Second, we compare our results with those obtained in corresponding feedforward neuronal networks connected with reliable synapses but in a random coupling fashion. We confirm that some differences can be observed in these two different feedforward neuronal network models. Finally, we study the signal propagation in feedforward neuronal networks consisting of both excitatory and inhibitory neurons, and demonstrate that inhibition also plays an important role in signal propagation in the considered networks.Comment: 33pages, 16 figures; Journal of Computational Neuroscience (published

Caffeine increases strength and power performance in resistance‐trained females during early follicular phase

The effects of 4 mg·kg‐1caffeine ingestion on strength and power were investigated for the first time, in resistance‐trained females during the early follicular phase utilizing a randomized, double‐blind, placebo‐controlled, crossover design. Fifteen females (29.8±4.0 years, 63.8±5.5 kg [mean±SD]) ingested caffeine or placebo 60 minutes before completing a test battery separated by 72 hours. One‐repetition maximum (1RM), repetitions to failure (RTF) at 60% of 1RM, were assessed in the squat and bench press. Maximal voluntary contraction torque (MVC) and rate of force development (RFD) were measured during isometric knee‐extensions, while utilizing interpolated twitch technique to measure voluntary muscle activation. Maximal power and jump height were assessed during countermovement jumps (CMJ). Caffeine metabolites were measured in plasma. Adverse effects were registered after each trial. Caffeine significantly improved squat (4.5±1.9%, effect size [ES]: 0.25) and bench press 1RM (3.3±1.4%, ES: 0.20), and squat (15.9±17.9%, ES: 0.31) and bench press RTF (9.8±13.6%, ES: 0.31), compared to placebo. MVC torque (4.6±7.3%, ES: 0.26), CMJ height (7.6±4.0%, ES: 0.50) and power (3.8±2.2%, ES: 0.24) were also significantly increased with caffeine. There were no differences in RFD or muscle activation. Plasma [caffeine] was significantly increased throughout the protocol and mild side‐effects of caffeine were experienced by only 3 participants. This study demonstrated that 4 mg·kg‐1 caffeine ingestion enhanced maximal strength, power and muscular endurance in resistance‐trained and caffeine‐habituated females during the early follicular phase, with few adverse effects. Female strength and power athletes may consider using this dose pre‐competition and ‐training as an effective ergogenic aid

Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% for TBLH-BMD, and 39% for TB-LM, with a shared genetic component of 43%. We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: _WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5_. Variants in the _TOM1L2/SREBF1_ locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that _SREBF1_ is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass

General and variable features of varicosity spacing along unmyelinated axons in the hippocampus and cerebellum

Along unmyelinated central axons, synapses occur at focal swellings called axonal varicosities (boutons). The mechanisms regulating how frequently synapses and varicosities occur along axons remain poorly understood. Here, to investigate varicosity distribution patterns and the extent to which they may be conserved across different axons, we analyzed varicosity numbers and positions along fluorescently labeled axon branches in hippocampal area CA1 (CA3-to-CA1 “Schaffer collateral” axons) and five other synaptic regions of rat hippocampus and cerebellum. Varicosity spacing varied by region; e.g., 3.7 ± 0.6 μm (mean ± SD) for CA3-to-CA1 axons and 5.2 ± 1.0 μm for cerebellar parallel fibers. Surprisingly, when 56 axons from these different regions were pooled into a single heterogeneous group, a general relationship emerged: the spacing variability (SD) was a constant fraction of the mean spacing, suggesting that varicosities along different axons are distributed in a fundamentally similar, scaled manner. Varicosity spacing was neither regular nor random but followed a pattern consistent with random synaptic distributions and the occurrence of multiple-synapse boutons. A quantitative model reproduced the salient features of the data and distinguished between two proposed mechanisms relating axonal morphogenesis and synaptogenesis. Arborizing varicose axons in the central nervous system are complex circuit elements: a single hippocampal CA3 cell axon makes ≈50,000 synapses over ≈0.2 m, all within the hippocampus (1, 2). Understanding connectivity in specific circuits requires detailed quantitative information about axonal synaptic distributions. At the ultrastructural level, synaptic boutons have been characterized as ≈1-μm long (3–5) varicosities that usually occur en passant along the axon, separated from other varicosities by short axonal shaft segments. For CA3-to-CA1 and other axons, the average synapse/varicosity ratio is 1.1–1.7 (4–11), reflecting the occurrence of multiple-synapse boutons (MSBs). MSBs may serve as intermediate or final stages of morphological plasticity associated with long-term synaptic plasticity (12–17). The organization of varicosities and their synapses over longer axonal distances merits quantification for several reasons. First, varicosity spacing is a key aspect of the complex geometry of axon–dendrite interactions. Second, synaptic and varicosity distribution patterns likely reflect fundamental connectivity rules. The report by Hellwig et al. (18) of a purely random pattern along neocortical axons carries numerous implications but has not yet been extended to other axon types. Third, varicosity spacing patterns may hold clues about mechanisms of synaptogenesis and development, an unexplored possibility relevant for synaptic plasticity models invoking varicosity neogenesis (15, 16, 19). Here, we used the strategy of quantifying varicosity spacing and its variability at the single axonal branch level for diverse types of central varicose axons, focusing on hippocampal CA3-to-CA1 axons and cerebellar parallel fibers but also including hippocampal axons in more heterogeneous populations to enable comparisons across a variety of axons

Design of a randomized controlled trial of physical training and cancer (Phys-Can) – the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome

Background: Cancer-related fatigue is a common problem in persons with cancer, influencing health-related quality of life and causing a considerable challenge to society. Current evidence supports the beneficial effects of physical exercise in reducing fatigue, but the results across studies are not consistent, especially in terms of exercise intensity. It is also unclear whether use of behaviour change techniques can further increase exercise adherence and maintain physical activity behaviour. This study will investigate whether exercise intensity affects fatigue and health related quality of life in persons undergoing adjuvant cancer treatment. In addition, to examine effects of exercise intensity on mood disturbance, adherence to oncological treatment, adverse effects from treatment, activities of daily living after treatment completion and return to work, and behaviour change techniques effect on exercise adherence. We will also investigate whether exercise intensity influences inflammatory markers and cytokines, and whether gene expressions following training serve as mediators for the effects of exercise on fatigue and health related quality of life. Methods/design: Six hundred newly diagnosed persons with breast, colorectal or prostate cancer undergoing adjuvant therapy will be randomized in a 2 × 2 factorial design to following conditions; A) individually tailored low-to-moderate intensity exercise with or without behaviour change techniques or B) individually tailored high intensity exercise with or without behaviour change techniques. The training consists of both resistance and endurance exercise sessions under the guidance of trained coaches. The primary outcomes, fatigue and health related quality of life, are measured by self-reports. Secondary outcomes include fitness, mood disturbance, adherence to the cancer treatment, adverse effects, return to activities of daily living after completed treatment, return to work as well as inflammatory markers, cytokines and gene expression. Discussion: The study will contribute to our understanding of the value of exercise and exercise intensity in reducing fatigue and improving health related quality of life and, potentially, clinical outcomes. The value of behaviour change techniques in terms of adherence to and maintenance of physical exercise behaviour in persons with cancer will be evaluated

Exploring moderators of the effect of high vs. low-to-moderate Intensity exercise on cardiorespiratory fitness during breast cancer treatment – Analyses of a subsample from the phys-can RCT

Introduction The results from the physical training and cancer randomized controlled trial (Phys-Can RCT) indicate that high intensity (HI) strength and endurance training during (neo-)adjuvant cancer treatment is more beneficial for cardiorespiratory fitness (CRF, measured as peak oxygen uptake [VO2peak]) than low-to-moderate intensity (LMI) exercise. Adherence to the exercise intervention and demographic or clinical characteristics of patients with breast cancer undergoing adjuvant treatment may moderate the exercise intervention effect on VO2peak. In this study, the objective was to investigate whether baseline values of VO2peak, body mass index (BMI), time spent in moderate- to vigorous-intensity physical activity (MVPA), physical fatigue, age, chemotherapy treatment, and the adherence to the endurance training moderated the effect of HI vs. LMI exercise on VO2peak. Materials and Methods We used data collected from a subsample from the Phys-Can RCT; women who were diagnosed with breast cancer and had a valid baseline and post-intervention VO2peak test were included (n = 255). The exercise interventions from the RCT included strength and endurance training at either LMI, which was continuous endurance training at 40 – 50 % of heart rate reserve (HRR), or at HI, which was interval training at 80–90% of HRR, with similar exercise volume in the two groups. Linear regression analyses were used to investigate moderating effects using a significance level of p \u3c 0.10. Statistically significant interactions were examined further using the Johnson–Neyman (J-N) technique and regions of significance (for continuous variables) or box plots with adjusted means of post-intervention VO2peak (for binary variables). Results Age, as a continuous variable, and adherence, dichotomized into \u3c or \u3e 58% based on median, moderated the effect of HI vs. LMI on CRF (B = −0.08, 95% CI [−0.16, 0.01], pinteraction = 0.06, and B = 1.63, 95% CI [−0.12, 3.38], pinteraction = 0.07, respectively). The J-N technique and regions of significance indicated that the intervention effect (HI vs. LMI) was positive and statistically significant in participants aged 61 years or older. Baseline measurement of CRF, MVPA, BMI, physical fatigue, and chemotherapy treatment did not significantly moderate the intervention effect on CRF. Conclusion Women with breast cancer who are older and who have higher adherence to the exercise regimen may have larger effects of HI exercise during (neo-)adjuvant cancer treatment on CRF

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

Where Does Blood Flow Restriction Fit in the Toolbox of Athletic Development? A Narrative Review of the Proposed Mechanisms and Potential Applications

Blood flow-restricted exercise is currently used as a low-intensity time-efficient approach to reap many of the benefits of typical high-intensity training. Evidence continues to lend support to the notion that even highly trained individuals, such as athletes, still benefit from this mode of training. Both resistance and endurance exercise may be combined with blood flow restriction to provide a spectrum of adaptations in skeletal muscle, spanning from myofibrillar to mitochondrial adjustments. Such diverse adaptations would benefit both muscular strength and endurance qualities concurrently, which are demanded in athletic performance, most notably in team sports. Moreover, recent work indicates that when traditional high-load resistance training is supplemented with low-load, blood flow-restricted exercise, either in the same session or as a separate training block in a periodised programme, a synergistic and complementary effect on training adaptations may occur. Transient reductions in mechanical loading of tissues afforded by low-load, blood flow-restricted exercise may also serve a purpose during de-loading, tapering or rehabilitation of musculoskeletal injury. This narrative review aims to expand on the current scientific and practical understanding of how blood flow restriction methods may be applied by coaches and practitioners to enhance current athletic development models.publishedVersionPaid open acces

Postmenopausal osteoporosis is a musculoskeletal disease with a common genetic trait which responds to strength training: a translational intervention study

https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Background: Clinical evidence suggests that body muscle mass is positively associated with bone mass, of significance for the elderly population at risk of osteoporosis (OP). Furthermore, muscle and bone interact mechanically and functionally, via local interactions as well as remotely via secreted components. Thus, it was of interest to compare muscle transcriptomes in postmenopausal OP and healthy women, and study effects of strength training on the muscle transcriptome, muscle stress proteins and bone mineral density (BMD). Methods: Skeletal muscle histological and genetic properties were compared in postmenopausal healthy (n=18) and OP (n=17) women before and after heavy-load strength training for 13–15weeks. The cohorts were of similar age and body mass index without interfering diseases, medication or difference in lifestyle factors. Muscle biopsies obtained before and after intervention were studied histologically, and stress proteins and transcriptomes analyzed. Results: The OP women showed distinct muscle transcription profiles when compared with healthy women and had higher levels of the stress proteins HSP70 and α-β-crystalline. A set of 12 muscle transcripts, including ACSS3, FZD4, GNAI1 and IGF1, were differentially expressed before and after intervention (false discovery rate⩽0.10, p⩽0.001), and their corresponding bone transcripts were associated with BMD. Experimental data underline and describe the functionality of these genes in bone biology. OP women had 8% (p<0.01) higher proportion of type I fibres, but muscle fibre cross-sectional area did not differ. Muscle strength increased in both groups (p<0.01). Conclusions: Postmenopausal healthy and OP women have distinct muscle transcriptomes [messenger ribonucleic acids (mRNAs) and microRNAs] that are modulated by strength training, translating into key protein alterations and muscle fibre changes. The function of common skeletal muscle and bone genes in postmenopausal OP is suggestive of a shared disease trait.publishedVersionInstitutt for fysisk prestasjonsevne / Department of Physical Performanc