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Triathlon is a multisport composed of swim, cycle, and run segments and two transition periods. The swim-to-cycle transition is considered a critical period for the change in body position and the modifications in physiological (heart rate, VO2, lactate) and biomechanical parameters (cycling power and cadence, swimming stroke rate). Therefore, the aim of this review was to summarize the current evidence regarding the physiological and biomechanical changes and their interlink during the swim-to-cycle transition hinting at practical recommendations for coaches and athletes. The influence of the swim segment on cycle one is more evident for short-distance events. Greater modifications occur in athletes of lower level. The modulation of intensity during the swim segment affects the changes in the physiological parameters (heart rate, blood lactate, core temperature), with a concomitant influence on cycling gross efficiency. However, gross efficiency could be preserved by wearing a wetsuit or by swimming in a drafting position. A higher swim leg frequency during the last meters of the segment induces a higher cadence during the cycle segment. Training should be directed to the maintenance of a swimming intensity around 80–90% of a previous maximal swim test and with the use of a positive pacing strategy. When athletes are intended to train consecutively only swim and cycle segments, for an optimal muscle activation during cycling, triathletes could adopt a lower cadence (about 60–70% of their typical cadence), although an optimal pedaling cadence depends on the level and type of athlete. Future research should be focused on the combined measurements of physiological and biomechanical parameters using an intervention study design to evaluate training adaptations on swim kick rate and their effects on cycling performance. Coaches and athletes could benefit from the understanding of the physiological and biomechanical changes occurring during the swim-to-cycle transition to optimize the overall triathlon performance.

Non-sport-specific strength training is a way to increase endurance performance; however, which kind of exercise (maximal, plyometric, explosive or resistance strength training) gives the best results is still under debate. Scientific publications were analyzed according to the PRISMA checklist and statement. The initial search yielded 500 studies, 17 of which were included in this review using the PEDro Scale. Maximal strength training boosted the ability to express strength particularly in cross-country skiing and cycling, increasing endurance performance, measured as a decrease of the endurance performance tests. In running, explosive strength training did not generate advantages, whereas plyometric strength training led to an improvement in the endurance performance tests and work economy. In running it was possible to compare different types of non sport-specific strength training and the plyometric one resulted the best training methodology to enhance performance. However, studies on other sports only investigated the effects of maximal strength training. It resulted more effective in cross-country skiing (although only one study was eligible according to the inclusion criteria) and in the cycling component of the triathlon and, by contrast, induced modest effects on cyclists’ performance, suggesting different type of strength would probably be more effective. In conclusion, each sport might optimize performance by using appropriate non sport-specific strength training, which, however, should be studied individually.

Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them 'guide' cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the forming myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regeneration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:22 issue:4 ispartof: location:Switzerland status: published

Reactive Oxygen Species (ROS) are molecules naturally produced by cells. If their levels are too high, the cellular antioxidant machinery intervenes to bring back their quantity to physiological conditions. Since aging often induces malfunctioning in this machinery, ROS are considered an effective cause of age-associated diseases. Exercise stimulates ROS production on one side, and the antioxidant systems on the other side. The effects of exercise on oxidative stress markers have been shown in blood, vascular tissue, brain, cardiac and skeletal muscle, both in young and aged people. However, the intensity and volume of exercise and the individual subject characteristics are important to envisage future strategies to adequately personalize the balance of the oxidant/antioxidant environment. Here, we reviewed the literature that deals with the effects of physical activity on redox balance in young and aged people, with insights into the molecular mechanisms involved. Although many molecular pathways are involved, we are still far from a comprehensive view of the mechanisms that stand behind the effects of physical activity during aging. Although we believe that future precision medicine will be able to transform exercise administration from wellness to targeted prevention, as yet we admit that the topic is still in its infancy.

PKCe is implicated in T cell activation and proliferation and is overexpressed in CD4+ -T cells from patients with autoimmune Hashimoto's thyroiditis. Although this might induce the suspicion that PKCe takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCe expression in circulating CD4+ -T cells from patients with psoriasis, a skin disorder characterized by an increased amount of Th17 cells, a CD4+ subset that is critical in the development of autoimmunity. Although the mechanisms that underlie Th17 differentiation in humans are still unclear, we here show that: (i) PKCe is overexpressed in CD4+ -T cells from psoriatic patients, and its expression positively correlates with the severity of the disease, being reduced by effective phototherapy; (ii) PKCe interacts with Stat3 during Th17 differentiation and its overexpression results in an enhanced expression of Stat3 and pStat3(Ser727); iii) conversely, when PKCe is forcibly downregulated, CD4+ -T cells show lower levels of pStat3(Ser727) expression and defective in vitro expansion into the Th17-lineage. These data provide a novel insight into the molecular mechanisms of Th17 cell polarization that is known to play a crucial role in autoimmunity, pinpointing PKCe as a potential target in Th17-mediated diseases.

The COVID-19 pandemic has now affected around 190 million people worldwide, accounting for more than 4 million confirmed deaths. Besides ongoing global vaccination, finding protective and therapeutic strategies is an urgent clinical need. SARS-CoV-2 mostly infects the host organism via the respiratory system, requiring angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) to enter target cells. Therefore, these surface proteins are considered potential druggable targets. Hydrogen sulfide (H2S) is a gasotransmitter produced by several cell types and is also part of natural compounds, such as sulfurous waters that are often inhaled as low-intensity therapy and prevention in different respiratory conditions. H2S is a potent biological mediator, with anti-oxidant, anti-inflammatory, and, as more recently shown, also anti-viral activities. Considering that respiratory epithelial cells can be directly exposed to H2S by inhalation, here we tested the in vitro effects of H2S-donors on TMPRSS2 and ACE2 expression in human upper and lower airway epithelial cells. We showed that H2S significantly reduces the expression of TMPRSS2 without modifying ACE2 expression both in respiratory cell lines and primary human upper and lower airway epithelial cells. Results suggest that inhalational exposure of respiratory epithelial cells to natural H2S sources may hinder SARS-CoV-2 entry into airway epithelial cells and, consequently, potentially prevent the virus from spreading into the lower respiratory tract and the lung.

In the last 15 years, it emerged that the practice of regular physical activity reduces the risks of many diseases (cardiovascular diseases, diabetes, etc.) and it is fundamental in weight control and energy consuming to contrast obesity. Different groups proposed many molecular mechanisms as responsible for the positive effects of physical activity in healthy life. However, many points remain to be clarified. In this mini-review we reported the latest observations on the effects of physical exercise on healthy skeletal and cardiac muscle focusing on muscle stem cells. The last ones represent the fundamental elements for muscle regeneration post injury, but also for healthy muscle homeostasis. Interestingly, in both muscle tissues the morphological consequence of physical activity is a physiological hypertrophy that depends on different phenomena both in differentiated cells and stem cells. The signaling pathways for physical exercise effects present common elements in skeletal and cardiac muscle, like activation of specific transcription factors, proliferative pathways, and cytokines. More recently, post translational (miRNAs) or epigenetic (DNA methylation) modifications have been demonstrated. However, several points remain unresolved thus requiring new research on the effect of exercise on muscle stem cells.

Background: With age, aortic valve cusps undergo varying degrees of sclerosis which, sometimes, can progress to calcific aortic valve stenosis (AVS). To perform a retrospective clinico-pathologic investigation in patients with calcific AVS.Methods: We characterized and graded the structural remodeling in 236 aortic valves (200 tricuspid and 36 bicuspid) from patients with calcific AVS (148 males; average 72 years); possible relationships between general/clinical/echocardiographic characteristics and the histopathologic changes were explored. Twenty autopsy aortic valves served as controls. In 40 cases, we also tested the immunohistochemical expression of metalloproteinases and cytokines, and characterized the inflammatory infiltrate. In 5 cases, we cultured cusp stem cells and explored their potential to differentiate into osteoblasts/adipocytes.Results: AVS cusps showed structural remodeling as severe fibrosis (100%), calcific nodules (100%), neoangiogenesis (81%), inflammation (71%), bone metaplasia with or without hematopoiesis (6% and 53%, respectively), adipose metaplasia (16%), and cartilaginous metaplasia (7%). At multivariate analysis, AVS degree and interventricular septum thickness were the only predictors of remodeling (barring inflammation). All the tested metalloproteinases (except MMP-13) and cytokines were expressed in AVS cusps. Inflammation mainly consisted of B and T lymphocytes (CD4+/CD8+ cell ratio 3:1) and plasma cells. AVS changes were mostly different from typical atherosclerosis. Cultured mesenchymal cusp stem cells could differentiate into osteoblasts/adipocytes.Conclusions: Structural remodeling in AVS is peculiar and considerable, and is related to the severity of the disease. However, the different newly formed tissues-where "valvular interstitial cells" play a key role-and their wellknown slow turnover suggest a reverse structural remodeling improbable. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Background: The bench press exercise (BP) is commonly practiced in both recreational and professional training. The weight is lowered from a position where the elbows are at a 90&deg, angle at the start and &lt, 90&deg, at the end of eccentric phase, and then returned to the elbows extended position. In order to focus the exercise more on the triceps brachii (TB) rather than the pectoralis major (PM), the inter-handle distance (IHD) is decreased diminishing the involvement of the PM in favor of the TB. Purpose: To improve performance of the exercise by reducing force dissociation and transmitting 100% of the external load to the muscle tissue we propose a prototype of the barbell with a bar on which two sleeves are capable of sliding. The dynamic modifications of the IHD keep the elbow flexion angle constant at 90&deg, Results: Analysis of the inter-handle distance (IHD) signals of the upper body muscles showed a marked increase in muscle activity using the experimental barbell for the PM (19.5%) and for the biceps brachii (173%). Conclusions: The experimental barbell increased the muscle activity typical of the bench press exercise, obtaining the same training induction with a lower load and consequently preventing articular stress.

Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression model used to combine the gene expression in a STEMI vs healthy donors score showed an AUC of 0.95. The same five differentially expressed genes were externally validated using platelet gene expression data from patients with coronary atherosclerosis but without thrombosis. Platelet gene expression profile highlights five genes able to identify STEMI patients and to discriminate them in the background of atherosclerosis. Consequently, early signals of an imminent acute myocardial infarction are likely to be found by platelet gene expression profiling before the infarction occurs.

While correlations between postural stability deficits and schizophrenia are well documented, information on dynamic motor alterations in schizophrenia are still scarce, and no data on their onset are available yet. Therefore, the aim of this study was i) to measure gait pattern(s) in patients with schizophrenia; ii) to identify posture and gait alterations which could potentially be used as a predictive clinical tool of the onset of the disorder. Body composition, posture and gait parameters were assessed in a group of 30 patients with schizophrenia and compared to 25 healthy subjects. Sway area was significantly higher in the schizophrenia group compared to controls regardless of whether the participants were in eyes open or eyes closed condition. Gait cadence and speed were significantly lower in patients with schizophrenia, while stride length was similar. We concluded that the combination of an increased sway area (independent from eye closure) and a gait cadence reduction—in the presence of normal gait speed and stride length—might be considered peculiar postural and gait profile characteristic of early schizophrenia.

Summary Objective Osteoarthritis (OA) is a common and highly debilitating degenerative disease whose complex pathogenesis and the multiplicity of the molecular processes involved, hinder its complete understanding. Protein Kinase C (PKC) novel isozyme PKCe recently proved to be an interesting molecule for further investigations as it can represent an intriguing, new actor in the acquisition of a OA phenotype by the chondrocyte. Design PKCe was modulated in primary chondrocytes from human OA patient knee cartilage samples by means of short hairpin RNA (ShRNA) and the expression of cartilage specific markers observed at mRNA and protein level. The involvement of Histone deacetylases (HDACs) signaling pathway was also investigated through the use of specific inhibitors MS-275 and Inhibitor VIII. Results PKCe loss induces up-regulation of Runt-domain transcription factor (RUNX2), Metalloproteinase 13 (MMP13) and Collagen X (COL10) as well as an enhanced calcium deposition in OA chondrocyte cultures. In parallel, PKCe knock-down also leads to SOX9 and Collagen II (COL2) down-modulation and to a lower deposition of glycosaminoglycans (GAGs) in the extracellular matrix (ECM). This novel regulatory role of PKCe over cartilage hypertrophic phenotype is exerted via an HDAC-mediated pathway, as HDAC2 and HDAC4 expression is modulated by PKCe. HDAC2 and HDAC4, in turn, are at least in part responsible for the modulation of the master transcription factors RUNX2 and SOX9, key regulators of chondrocyte phenotype. Conclusions PKCe prevents the phenotypic progression of the OA chondrocyte, acting on cartilage specific markers through the modulation of the transcription factors SOX9 and RUNX2. The loss of PKCe enhances, in fact, the OA hypertrophic phenotype, with clear implications in the pathophysiology of the disease.

Reactive oxygen species (ROS) and mitochondria play a pivotal role in regulating platelet functions. Platelet activation determines a drastic change in redox balance and in platelet metabolism. Indeed, several signaling pathways have been demonstrated to induce ROS production by NAPDH oxidase (NOX) and mitochondria, upon platelet activation. Platelet-derived ROS, in turn, boost further ROS production and consequent platelet activation, adhesion and recruitment in an auto-amplifying loop. This vicious circle results in a platelet procoagulant phenotype and apoptosis, both accounting for the high thrombotic risk in oxidative stress-related diseases. This review sought to elucidate molecular mechanisms underlying ROS production upon platelet activation and the effects of an altered redox balance on platelet function, focusing on the main advances that have been made in platelet redox biology. Furthermore, given the increasing interest in this field, we also describe the up-to-date methods for detecting platelets, ROS and the platelet bioenergetic profile, which have been proposed as potential disease biomarkers.

Most of the requests of authorisation to the use of health claims pursuant to Regulation EC 1924/2006 related to the gastrointestinal (GI) tract have received a negative opinion by the European Food Safety Authority (EFSA), mainly because of an insufficient substantiation of the claimed effect (CE). The present manuscript refers to the collection, collation and critical analysis of outcome variables (OVs) and methods of measurement (MMs) related to the GI tract compliant with Regulation 1924/2006. The critical evaluation of OVs and MMs was based on the literature review, with the final aim of defining their appropriateness in the context of a specific CE. The results obtained are relevant for the choice of the best OVs and MMs to be used in randomised controlled trials aimed to substantiate the claims on the GI tract. Moreover, the results can be used by EFSA for updating the guidance for the scientific requirements of such health claims.

Objective Some of the requests of authorization to apply health claims in the context of oral health have received a negative scientific opinion from the European Food Safety Authority (EFSA). The main reasons refer to the design of human intervention studies, including the inappropriate choice of outcome variables (OVs) and of their methods of measurement (MMs). The present manuscript reports the results of an investigation aimed at collecting, collating and critically analysing the information in relation to claimed effects, OVs and MMs, in the area of oral health and compliant with Regulation (EC) 1924/2006. Methods Claimed effects, OVs and the related MMs were collected from EFSA guidance documents and from the scientific opinions on the substantiation of health claims under Articles 13.5 and 14. The collection, collation and critical analysis of the relevant scientific literature consisted in a definition of the keywords, PubMed search strategies and in the creation of databases of references. Results and conclusions The critical analysis of the OVs and their MMs was performed on the basis of the literature review and was aimed at defining the appropriateness of OVs and MMs in the context each specific claimed effect. Clinical significance The information provided in this document could serve to EFSA for the development of further guidance on the scientific requirements for health claims related to oral health, as well as to the stakeholders for the identification of existing and design of novel randomized controlled trials aimed at substantiating such health claims.

Adequate visual function has a strong impact on the quality of life of people. Several foods and food components have been hypothesized to play a role in the maintenance of normal visual function and in the prevention of eye diseases. Some of these foods/food components have been the object of a request of authorization for use of health claims under Articles 13(5) or 14 of the Regulation (EC) 1924/2006. Most of these requests have received a negative opinion from the European Food Safety Authority (EFSA) due to the choice of inappropriate outcome variables (OVs) and/or methods of measurement (MMs) applied in the studies used to substantiate the claims. This manuscript refers to the collection, collation and critical analysis of OVs and MMs related to vision. Guidance document and requests for authorization of health claims were used to collect OVs and MMs related to vision. A literature review was performed to critically analyse OVs and MMs, with the aim of defining their appropriateness in the context of a specific claimed effect related to vision. The results highlight the importance of adequate choices of OVs and MMs for an effective substantiation of claims related to visual function.

Several foods or food components have been the object of application for authorization of health claims on bone health, pursuant to Regulation (EC) 1924/2006. For most of them, the European Food Safety Authority (EFSA) has issued negative opinions mainly for reasons pertaining to an insufficient substantiation of the claim, incluiding the choice of not appropriate outcome variables (OVs) and methods of measurement (MMs). The present manuscript refers to the collection, collation and critical analysis of OVs and MMs related to bone health compliant with the Regulation. The definition of the keywords, the PubMed search strategies and the creation of databases of references were performed to critically analyse the OVs and their MMs on the basis of the literature review. The assessment of each OV and related MM was defined according to its appropriatness in relation to the claimed effects proposed. The results obtained are relevant for the choice of the best OVs and MMs, to be used not only for the substantiation of health claims on bone health, but also in general research performed with different purposes. Moreover, the results can be used by EFSA during the update of guidance for the scientific requirements of health claims on bone health.

Evidence suggests a protective role for several nutrients and foods in the maintenance of skin function. Nevertheless, all the requests for authorization to use health claims under Article 13(5) in the framework of maintenance of skin function presented to the European Food Safety Authority (EFSA) have received a negative opinion. Reasons for such failures are mainly due to an insufficient substantiation of the claimed effects, including the choice of inappropriate outcome variables (OVs) and methods of measurement (MMs). The present paper reports the results of an investigation aimed at collecting, collating and critically analyzing the information with relation to claimed effects (CEs), OVs and MMs related to skin health compliance with Regulation 1924/2006. CEs, OVs and MMs were collected from both the EFSA Guidance document and from the authorization requests of health claims under Article 13(5). The critical analysis of OVs and MMs was based on a literature review, and was aimed at defining their appropriateness (alone or in combination with others) in the context of a specific CE. The results highlight the importance of an adequate choice of OVs and MMs for an effective substantiation of the claims.

Introduction Satellite cells are muscle resident stem cells and are responsible for muscle regeneration. In this study we investigate the involvement of PKCe during muscle stem cell differentiation in vitro and in vivo. Here, we describe the identification of a previously unrecognized role for the PKCe–HMGA1 signaling axis in myoblast differentiation and regeneration processes. Methods PKCe expression was modulated in the C2C12 cell line and primary murine satellite cells in vitro, as well as in an in vivo model of muscle regeneration. Immunohistochemistry and immunofluorescence, RT-PCR and shRNA silencing techniques were used to determine the role of PKCe and HMGA1 in myogenic differentiation. Results PKCe expression increases and subsequently re-localizes to the nucleus during skeletal muscle cell differentiation. In the nucleus, PKCe blocks Hmga1 expression to promote Myogenin and Mrf4 accumulation and myoblast formation. Following in vivo muscle injury, PKCe accumulates in regenerating, centrally-nucleated myofibers. Pharmacological inhibition of PKCe impairs the expression of two crucial markers of muscle differentiation, namely MyoD and Myogenin, during injury induced muscle regeneration. Conclusion This work identifies the PKCe–HMGA1 signaling axis as a positive regulator of skeletal muscle differentiation.

Rationale Vessel formation is a crucial event in tissue repair after injury. Thus, one assumption of innovative therapeutic approaches is the understanding of its molecular mechanisms. Notwithstanding our knowledge of the role of Protein Kinase C epsilon (PKCe) in cardio-protection and vascular restenosis, its role in vessel progenitor differentiation remains elusive. Objective Given the availability of PKCe pharmacological modulators already tested in clinical trials, the specific aim of this study is to unravel the role of PKCe in vessel progenitor differentiation, with implications in vascular pathology and vasculogenesis. Methods and results Mouse Peri-Vascular Adipose Tissue (PVAT) was used as source of mesenchymal vessel progenitors. VEGF-induced differentiation of PVAT cells down-regulates both PKCe and p-PAK1 protein expression levels. PKCe overexpression and activation: i) reduced the expression levels of SMA and PECAM in endothelial differentiation of PVAT cells; ii) completely abrogated tubules formation in collagen gel assays; iii) increased the expression of p-PAK1. Conclusion PKCe negatively interferes with vessel progenitor differentiation via interaction with PAK-1.

Most requests for authorization to bear health claims under Articles 13(5) and 14 related to blood glucose and insulin concentration/regulation presented to the European Food Safety Authority (EFSA) receive a negative opinion. Reasons for such decisions are mainly ascribable to poor substantiation of the claimed effects. In this scenario, a project was carried out aiming at critically analysing the outcome variables (OVs) and methods of measurement (MMs) to be used to substantiate health claims, with the final purpose to improve the quality of applications provided by stakeholders to EFSA. This manuscript provides a position statement of the experts involved in the project, reporting the results of an investigation aimed to collect, collate and critically analyse the information relevant to claimed effects (CEs), OVs and MMs related to blood glucose and insulin levels and homoeostasis compliant with Regulation 1924/2006. The critical analysis of OVs and MMs was performed with the aid of the pertinent scientific literature and was aimed at defining their appropriateness (alone or in combination with others) to support a specific CE. The results can be used to properly select OVs and MMs in a randomized controlled trial, for an effective substantiation of the claims, using the reference method(s) whenever available. Moreover, results can help EFSA in updating the guidance for the scientific requirements of health claims.

All the requests for authorisation to bear health claims under Articles 13(5) and 14 in the context of appetite ratings and weight management have received a negative opinion by the European Food Safety Authority (EFSA), mainly because of the insufficient substantiation of the claimed effects (CEs). This manuscript results from an investigation aimed to collect, collate and critically analyse the information related to outcome variables (OVs) and methods of measurement (MMs) in the context of appetite ratings and weight management compliant with Regulation 1924/2006. Based on the literature review, the appropriateness of OVs and MMs was evaluated for specific CEs. This work might help EFSA in the development of updated guidance addressed to stakeholders interested in bearing health claims in the area of weight management. Moreover, it could drive the applicants during the design of randomised controlled trials aimed to substantiate such claims.

Background: Myogenic progenitor cells (activated satellite cells) are able to express both HGF and its receptor cMet. After muscle injury, HGF-Met stimulation promotes activation and primary division of satellite cells. MAGIC-F1 (Met-Activating Genetically Improved Chimeric Factor-1) is an engineered protein that contains two human Met-binding domains that promotes muscle hypertrophy. MAGIC-F1 protects myogenic precursors against apoptosis and increases their fusion ability enhancing muscle differentiation. Hemizygous and homozygous Magic-F1 transgenic mice displayed constitutive muscle hypertrophy. Methods: Here we describe microarray analysis on Magic-F1 myogenic progenitor cells showing an altered gene signatures on muscular hypertrophy and angiogenesis compared to wild-type cells. In addition, we performed a functional analysis on Magic-F1+/+ transgenic mice versus controls using treadmill test. Results: We demonstrated that Magic-F1+/+ mice display an increase in muscle mass and cross-sectional area leading to an improvement in running performance. Moreover, the presence of MAGIC-F1 affected positively the vascular network, increasing the vessel number in fast twitch fibers. Finally, the gene expression profile analysis of Magic-F1+/+ satellite cells evidenced transcriptomic changes in genes involved in the control of muscle growth, development and vascularisation. Conclusion: We showed that MAGIC-F1-induced muscle hypertrophy affects positively vascular network, increasing vessel number in fast twitch fibers. This was due to unique features of mammalian skeletal muscle and its remarkable ability to adapt promptly to different physiological demands by modulating the gene expression profile in myogenic progenitors.

Background and aims The high number of negative opinions from the European Food Safety Authority (EFSA) to the requests for authorization of health claims is largely due to the design of human intervention studies, including the inappropriate choice of outcome variables (OVs) and of their methods of measurement (MMs). The present manuscript reports the results of an investigation aimed to collect, collate and critically analyse the information in relation to claimed effects, OVs and MMs, in the context of protection against oxidative damage and cardiovascular health compliant with Regulation 1924/2006. Methods and results Claimed effects, OVs and the related MMs were collected from EFSA Guidance documents and applications for authorization of health claims under Articles 13.5 and 14. The OVs and their MMs were evaluated only if the claimed effect was sufficiently defined and was considered beneficial by EFSA. The collection, collation and critical analysis of the relevant scientific literature consisted in the definition of the keywords, the PubMed search strategies and the creation of databases of references. The critical analysis of the OVs and their MMs was performed on the basis of the literature review and was aimed at defining the appropriateness of OVs and MMs in the context of the specific claimed effects. Conclusions The information provided in this document could serve to EFSA for the development of further guidance on the scientific requirements for health claims, as well as to the stakeholders for the proper design of human intervention studies aimed to substantiate such health claims.

Maximal oxygen consumption (VO2max) and oxygen consumption at anaerobic threshold (VO2AT) are commonly measured parameters to test elite soccer players; however, studies relating metabolic parameters of professional soccer players with performance and best fitting to the field role are scarce. Our aim was to study the relations of VO2max and VO2AT with the field role of elite soccer players to generate a robust dataset with a solid statistical analysis. Over a 12-year period we performed 953 field evaluation tests of VO2 max and VO2AT on 450 elite soccer players of 13 professional teams by incremental, continuous and exhausting test modified from Conconi’s test. Statistical analysis was performed by one-way ANOVA followed—when appropriate—by Tukey post hoc test. Effect size was evaluated by the Cohen D test and η partial squared test. Statistical significance was set for p

Joint mobility is a fundamental part in physical activity program for children, but a scientific characterization of the methods to improve the articular mobility in healthy children is still poor. The aim of this study was to investigate whether joint mobility/muscular elasticity were related to a merely active lifestyle or could be significantly improved in the presence of a collective, easy-to-perform, but specifically designed and professionally guided program. Specific functional and anthropometric parameters were single-blind tested on 277 children (aged 9–11 years). 148 were randomly assigned to a physical education program specifically designed to increase elasticity and supervised by professionals (treated group), while 129 (control group) continued their usual physical activity at school, with no specific program. Specific tests were performed and showed a significant improvement of joint mobility compared to non-specific physical activity in 9- to 11-year children. As a secondary end-point, this program was effective also in children of overweight/obese BMI category. These results, building on those from this and other groups, should orientate decision-makers in the area of physical exercise for primary school children towards specifically designed programs based on demographic and anthropometric data.

Mainly known for its cardioprotective properties, protein kinase C isoform ε (PKCε) is also progressively coming of age in terms of its role in hematopoiesis regulation, particularly that is related to erythropoiesis, megakaryocytopoiesis, and platelet production. Data available to date show that PKCε is differentially regulated in erythrocyte and megakaryocyte progenitors, strongly suggesting an addressing role toward maturation of either lineage. This function appears to be played by either selecting progenitors or conducting maturation toward a specific fate. Inappropriate expression of PKCε in human mature platelets is discussed as a recently described example of functional modification that may acquire pathophysiologic relevance in major thrombotic diseases. Preliminary evidence suggests that PKCε expression may be used as a surrogate marker for thrombotic risk stratification and as a possible target for antiplatelet therapy in patients with thrombotic disorders.

Whole body vibration (WBV) is a very widespread mechanical stimulus used in physical therapy, rehabilitation and fitness centres. It has been demonstrated that vibration induces improvements in muscular strength and performance and increases bone density. We investigated the effects of low-amplitude, high frequency vibration (HFV) at the cellular and tissue levels in muscle. We developed a system to produce vibrations adapted to test several parameters in vitro and in vivo. For in vivo experiments, we used newborn CD1 wild-type mice, for in vitro experiments, we isolated satellite cells from 6-day-old CD1 mice, while for proliferation studies, we used murine cell lines. Animals and cells were treated with high frequency vibration at 30 Hz. We analyzed the effects of mechanical stimulation on muscle hypertrophy/atrophy pathways, fusion enhancement of myoblast cells and modifications in the proliferation rate of cells. Results demonstrated that mechanical vibration strongly down-regulates atrophy genes both in vivo and in vitro. The in vitro experiments indicated that mechanical stimulation promotes fusion of satellite cells treated directly in culture compared to controls. Finally, proliferation experiments indicated that stimulated cells had a decreased growth rate compared to controls. We concluded that vibration treatment at 30 Hz is effective in suppressing the atrophy pathway both in vivo and in vitro and enhances fusion of satellite muscle cells.

The City Council of Parma and allied partners launched a programme based on professionally guided physical exercise and nutritional education in all primary schools of the metropolitan area, with a total of 7,000 children involved, ranging from 6 to 10 years of age. One scientific end-point of the programme was the definition of the parameter(s) most associated with increased physical activity and potential modification of eating habits. To this purpose we studied in a cohort of 2,151 9-year-old children the associations among BMI, fat mass (FM), breakfast eating and the amount of physical activity, the most relevant variables that characterize lifestyle. There was a consistent significant inverse correlation between FM and physical activity and a significant correlation between FM and breakfast skipping. When sorted by BMI, an inverse significant correlation was found between FM and physical activity in boys, except in those underweight. In girls, a significant correlation was found in those of normal weight, but not in those overweight or obese. The number of sports practised was related to FM only in overweight and obese boys. Breakfast skipping was significantly correlated with FM only in underweight girls. Taken together, our data show that FM can be used to accurately evaluate physical activity and eating habits in children, and suggest that, in preventive health programmes, the fundamental parameter to pay attention to is the amount rather than the type of physical activity.

Vestibular schwannomas, also known as acoustic neuromas, are benign tumors, which originate from myelin-forming Schwann cells. They develop in the vestibular branch of the eighth cranial nerve in the internal auditory canal or cerebellopontine angle. The clinical progression of the condition involves slow and progressive growth, eventually resulting in brainstem compression. The objective of the present study was to investigate the expression level and the localization of the pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), as well as the adhesion molecules, intracellular adhesion molecule-1 and vascular endothelial growth factor (VEGF), in order to determine whether these factors are involved in the transformation and development of human vestibular schwannoma. The present study investigated whether changes in inflammation are involved in tumor growth and if so, the mechanisms underlying this process. The results of the current study demonstrated that pro-inflammatory cytokines, including TGF-β1, IL-1β and IL-6 exhibited increased expression in human vestibular schwannoma tissue compared with normal vestibular nerve samples. TNF-α was weakly expressed in Schwann cells, confirming that a lower level of this cytokine is involved in the proliferation of Schwann cells. Neoplastic Schwann cells produce pro-inflammatory cytokines that may act in an autocrine manner, stimulating cellular proliferation. In addition, the increased expression of VEGF in vestibular schwannoma compared with that in normal vestibular nerve tissue, suggests that this factor may induce neoplastic growth via the promotion of angiogenesis. The present findings suggest that inflammation may promote angiogenesis and consequently contribute to tumor progression. In conclusion, the results of the present study indicated that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in vestibular schwannoma. Further studies are necessary to confirm the involvement of these factors in the growth of neoplasms and to develop inhibitors of pro-inflammatory cytokines as a potential treatment option in the future.

Building biological devices to perform computational and signal processing tasks is one of the main research issues in synthetic biology. Herein, two modular biological systems that could mimic multiplexing and demultiplexing logic functions are proposed and discussed. These devices, called multiplexer (mux) and demultiplexer (demux), respectively, have a remarkable importance in electronic, telecommunication, and signal processing systems and, similarly, they could play a crucial role if implemented in a living organism, such as Escherichia coli. BioBrick standard parts were used to design mux and demux and to construct two genetic circuits that could carry out the desired tasks. A modular approach, mimicking basic logic gates (AND, OR, and NOT) with protein/autoinducer or protein/DNA interactions and interconnecting them to create the final circuits, was adopted. A mathematical model of the designed gene networks was been defined and simulations performed to validate the expected behavior of the systems. In addition, circuit subparts were tested in vivo and the results used to determine some of the parameters of the mathematical model. According to both the experimental and simulated results, guidelines for future finalization of mux and demux are provided. ispartof: Biotechnology Journal vol:6 issue:7 pages:784-795 ispartof: location:Germany status: published

Curtius Rufus, Histories of Alexander the Great book 10. Introduction and historical commentary by J. E. Atkinson. Translated by J. C. Yardley. Oxford: Oxford UP 2009. XIV, 274 S. (Claredon Ancient History Series.) 70 £.

Engineering of the cellular microenvironment has become an attractive strategy to guide cellular activities such as spreading, motility, proliferation and differentiation. From a technological perspective, the physical crosstalk between a cell and its surrounding represents a design parameter that may be modulated to achieve desired osseointegration in orthopedic and dental implants. In this study we use a surface engineering approach to tap into the interaction between the cell and its surroundings in order to modulate osteogenic adhesion-dependent differentiation and bone tissue formation. The effectiveness of this approach was studied by observing the in vitro cellular behavior of human osteoblastic cells (SaOs-2) seeded on silicon substrates with different nano-scale surface patterns. Our findings suggest that substrate nanopattern geometry can differentially control early cell differentiation decisions. Interestingly, rescue of the differentiation process by supplementation of growth medium with soluble differentiation factors did not appear to compensate for the differences in the early cellular fate decisions observed on the different patterns. Critically, combining surface topography and soluble differentiation factors appeared to modulate the speed of the differentiation process and its shut down at the end of terminal differentiation. Taken together, our findings suggest that cells recognize physical nano-scale topography as an instructive signal that is integrated to fine-tune the multimodal control and guidance of cell behavior and cell fate. This information may find utility in the design of orthopedic and dental implants or innovative bio-materials for regenerative medicine.

Protein Kinase Cs (PKCs) are a family of 10 isoenzymes with critical roles in cell physiological processes like proliferation, differentiation, apoptosis. Muscular dystrophies are a heterogenous group of genetic degenerative diseases that affect skeletal and cardiac muscles. In the development of muscular dystrophies, several transduction pathways have been studied. A possible link between muscular dystrophies and PKCs have been recently proposed. After a brief description of the possible transduction pathways that are involved in the development of these genetic diseases, we summarize recent evidence on the role of PKC proteins in muscular dystrophies, with the aim to review possible candidates in molecular therapy of these pathologies.

Valerius Flaccus’ Argonautica Book 1. Edited with introduction, translation and commentary by Andrew Zissos. Oxford: Oxford UP 2008. LXX, 450 S., 100 £.