AIM:It is unknown how the heart distinguishes various overloads, such as exercise or hypertension, causing either physiological or pathological hypertrophy. We hypothesize that alpha-calcitonin-gene-related peptide (αCGRP), known to be released from contracting skeletal muscles, is key at this remodelling.METHODS:The hypertrophic effect of αCGRP was measured in vitro (cultured cardiac myocytes) and in vivo (magnetic resonance imaging) in mice. Exercise performance was assessed by determination of maximum oxygen consumption and time to exhaustion. Cardiac phenotype was defined by transcriptional analysis, cardiac histology and morphometry. Finally, we measured spontaneous activity, body fat content, blood volume, haemoglobin mass and skeletal muscle capillarization and fibre composition.RESULTS:While αCGRP exposure yielded larger cultured cardiac myocytes, exercise-induced heart hypertrophy was completely abrogated by treatment with the peptide antagonist CGRP(8-37). Exercise performance was attenuated in αCGRP(-/-) mice or CGRP(8-37) treated wild-type mice but improved in animals with higher density of cardiac CGRP receptors (CLR-tg). Spontaneous activity, body fat content, blood volume, haemoglobin mass, muscle capillarization and fibre composition were unaffected, whereas heart index and ventricular myocyte volume were reduced in αCGRP(-/-) mice and elevated in CLR-tg. Transcriptional changes seen in αCGRP(-/-) (but not CLR-tg) hearts resembled maladaptive cardiac phenotype.CONCLUSIONS:Alpha-calcitonin-gene-related peptide released by skeletal muscles during exercise is a hitherto unrecognized effector directing the strained heart into physiological instead of pathological adaptation. Thus, αCGRP agonists might be beneficial in heart failure patients.

High-intensity interval training (HIIT) blocks lasting 1-2 weeks improve the maximal aerobic capacity (VO2max) in trained athletes. The aim of this study was to investigate the effects of a HIIT-block on VO2max, running economy (RE), blood volume (BV) and total haemoglobin mass (tHbm). Fourteen junior soccer players were assigned to intervention (HIIT, n=8) and control (KON, n=6) groups. HUT underwent 13 HUT sessions within ten days. Sessions consisted of four sets of 8x15/15 sec intermittent running and 4x4 min playing small sided games. The target intensity was 90-95% of the maximal heart rate (HRmax). KON underwent a conventional training program. Before, two and seven days after intervention, VO2max, RE, BV and tHbm were assessed. The HIIT group reached lactate levels of 6.6 +/- 1.6 mmol/L and 93.4 +/- 2.2% of HRmax, during intermittent running and lactate levels of 6.1 +/- 2.0 mmol/L and 90.9 +/- 2.1% of HRmax small sided games. There were no significant differences between the three time points in VO2max, RE, BV or tHbm. Our finding that a HIIT block had no effect on VO2max is in contrast to other investigations using the same prescribed intensity but greater overall training volume. Because no changes to tHbm By and VO2max occurred with our intervention, it is not possible to establish a relationship between these variables.

After 17 years as an Editor of The Journal of Experimental Biology , Bill Harvey is retiring to dedicate more time to his main scientific passion: the study of V-ATPases. Harvey's connection with the journal began in 1967 when he published his first paper with the JEB, and we suspect that although

Eccentric cycling, where the goal is to resist the pedals, which are driven by a motor, increases muscle strength and size in untrained subjects. We hypothesized that it could also be beneficial for athletes, particularly in alpine skiing, which involves predominantly eccentric contractions at longer muscle lengths. We investigated the effects of replacing part of regular weight training with eccentric cycling in junior male alpine skiers using a matched-pair design. Control subjects (n = 7) executed 1-h weight sessions 3 times per week, which included 4-5 sets of 4 leg exercises. The eccentric group (n = 8) performed only 3 sets, followed by continuous sessions on the eccentric ergometer for the remaining 20 min. After 6 weeks, lean thigh mass increased significantly only in the eccentric group. There was a group x time effect on squat-jump height favouring the eccentric group, which also experienced a 6.5% improvement in countermovement-jump height. The ability to finely modulate muscle force during variable eccentric cycling improved 50% (p = 0.004) only in the eccentric group. Although eccentric cycling did not significantly enhance isometric leg strength, we believe it is beneficial for alpine skiers because it provides an efficient means for hypertrophy while closely mimicking the type of muscle actions encountered while skiing.

Les maladies cardiovasculaires sont l’une des plus im­ portantes causes de décès dans le monde occidental. Un taux élevé de cholestérol favorise notablement leur manifestation. Les statines, qui inhibent la production endogène de cholestérol, en sont le traitement reconnu. Mais 5 à 10% des patients ressentiront des douleurs musculaires comme effet indésirable [1]. La situation s’améliore en général après diminution de la dose ou un changement de médicament. Mais parce que la ma­ ladie de base persiste, une diminution de la dose, voire une interruption complète du traitement, n’est la plu­ part du temps pas indiquée. La forme la plus grave de myopathie chez les patients traités par statines, la rhabdomyolyse, est très rare. Elle ne touche statistiquement que moins d’un patient sur 100000. Mais si rare qu’elle soit, la rhabdomyolyse est une complication potentiellement très dangereuse [1]. Des douleurs moindres sont plus fréquentes, sur­ tout à l’effort physique, de même qu’une myasthénie. De tels effets indésirables discrets ne sont malheureu­ sement pas pris au sérieux, pas plus par les patients que par leurs médecins traitants.

Every year at the Society for Integrative and Comparative Biology (SICB) meeting–held in a different city annually–the Executive Committee decide the location of the meeting 2 years hence. On most occasions this is an uncontroversial decision, but when SICB President Richard Satterlie and the

Over the past 10 years, manuscript submissions to The Journal of Experimental Biology (JEB) have risen from ∼500 per year to almost 1000. Within the first six months of 2007, we have already received over 600 manuscripts and will, in all likelihood, break the 1000 submissions barrier for the first time this year. This is basically good news, as it shows that JEB is an attractive place to publish. However, there are also downsides to this development. The greatly increased number of submissions is obviously increasing the workload on administrative staff, editors and reviewers. In order to control production costs, the annual page allocation in JEB is fixed,and therefore to keep within the space constraints of the journal we must reject more of the submitted manuscripts. Ten years ago, our rejection rate was less than 40% of submitted manuscripts; it is now more than 60%.This steep increase in rejection rates has created lively discussions at JEB Editors' Meetings, as we have strived to find ways of maximizing the use of available space and defining criteria for manuscript acceptance. One unanimous decision was that the current range of subject areas should be maintained. This means that JEB will continue to cover all aspects of animal physiology, although with an increased emphasis on aspects that are more generally relevant to most `comparative physiologists'. We also wish to feature work employing molecular techniques for investigating physiological phenomena of interest. To help us monitor the spread of scientific fields across the journal, we have introduced a list of `subject categories' for the author to choose from at submission. It has also been decided that JEB should focus specifically on hypothesis-driven research, i.e. research aimed at elucidating novel physiological mechanisms rather than descriptive or theoretical studies. The Editors are reluctant to introduce a maximum length for manuscripts, as stipulated by some other journals. However, manuscript size is scrutinized and we urge reviewers to check that manuscripts are no longer than necessary.Rejection rates of >60% of the submitted manuscripts have introduced a number of problems. The most obvious is that we now have to reject manuscripts that have received positive reviews. In many of these cases, studies have been well carried out but do not lead to particularly exciting or novel results. This is something that is difficult to convey to authors, as the crucial information is usually contained in the comments only seen by the Editors as well as being reflected in a low-priority ranking of the manuscript by the reviewers. Moreover, it is self-evident that we all perceive our own work to be of special interest, being aware of all specific problems and questions relating to our closest field of scientific concern. We are also aware that the necessity of having to reject `sound' manuscripts introduces a measure of arbitrariness into the editorial process. This starts with the selection of reviewers. We usually select at least one reviewer proposed by the author and do generally respect any requests from authors to exclude particular individuals from the reviewing process. It is sometimes surprising that the most scornful verdicts are from people proposed by the authors themselves! We do rely on a solid core of reviewers that we know well and that have supplied us with insightful judgment on manuscripts in the past. These reviewers are one of the most valuable resources of JEB, as they guarantee the quality of the research published in the Journal. In all cases, Editors are free to make the final decision on whether to accept or reject a particular manuscript, and in areas of doubt we have a system whereby more than one Editor is involved in taking that final decision.The steep rise in rejection rates on JEB over the past few years has aggravated many authors who have seen manuscripts rejected that would have been accepted a few years earlier. It has also been a challenge to Editors and reviewers, who face the task of selecting the most promising manuscripts from an increasing number of excellent articles submitted to the Journal. Maintaining the balance between the many fields that JEB has covered successfully in the past and attracting good manuscripts from the emerging field of `molecular physiology' is the major challenge to JEB in the future.

Muscle pain and weakness are frequent complaints in patients receiving 3‐hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin‐induced skeletal muscle damage, skeletal muscle biopsies from statin‐treated and non‐statin‐treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin‐treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T‐tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin‐treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro . These findings support the hypothesis that statin‐induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The expressional profile of mitochondrial transcripts and of genes involved in the mitochondrial biogenesis pathway induced by ALCAR daily supplementation in soleus muscle of control and unloaded 3-month-old rats has been analyzed. It has been found that ALCAR treatment is able to upregulate the expression level of mitochondrial transcripts (COX I, ATP6, ND6, 16 S rRNA) in both control and unloaded animals. Interestingly, ALCAR feeding to unloaded rats resulted in the increase of transcript level for master factors involved in mitochondrial biogenesis (PGC-1alpha, NRF-1, TFAM). It also prevented the unloading-induced downregulation of mRNA levels for kinases able to transduce metabolic (AMPK) and neuronal stimuli (CaMKIIbeta) into mitochondrial biogenesis. No significant effect on the expressional level of such genes was found in control ALCAR-treated rats. In addition, ALCAR feeding was able to prevent the loss of mitochondrial protein content due to unloading condition. Correlation analysis revealed a strong coordination in the expression of genes involved in mitochondrial biogenesis only in ALCAR-treated suspended animals, supporting a differentiated effect of ALCAR treatment in relation to the loading state of the soleus muscle. In conclusions, we demonstrated the ability of ALCAR supplementation to promote only in soleus muscle of hindlimb suspended rats an orchestrated expression of genes involved in mitochondrial biogenesis, which might counteract the unloading-induced metabolic changes, preventing the loss of mitochondrial proteins.

Another landmark year has passed. The journal has gained Hans Hoppeler as its sixth Editor-in-Chief while sadly saying goodbye to Malcolm Burrows, who served as a dedicated editor for more than ten years. Malcolm will be greatly missed by all who worked with him, but we are fortunate that Ken Lukowiak, a long-standing member of the JEB community, has agreed to join the team of editors in Malcolm's stead and will continue Malcolm's work with many authors from the field of neurobiology. While the journal has seen many editorial changes during the last twelve months, the production office has also seen some new appointments. Production Editor Michaela Handel and News and Views Editor Kathryn Phillips both began periods of maternity leave in late 2004 and have been temporarily replaced by Rachel Wood and Yfke van Bergen. However,despite the many changes at all levels throughout the journal, Margaret Clements continued to oversee peer review, and the journal continued to be published seamlessly.Hopefully 2005 will see the journal entering a more peaceful period, and with this, the Editors would like to announce the launch of `The Bob Boutilier Memorial Best Paper Prize', to acknowledge annually the most outstanding scientific contribution to the journal. The award of £500 will be made to the first author of the paper judged by the journal's editors to be the most outstanding contribution to the field of integrative biology, published in the JEB. All papers published in 2005 will be eligible for consideration,and the winner announced in the final issue of the year.Other advances at the journal include the development of a new facility on the journal's website, which allows users to automatically download PowerPoint slides of all of the figures published in the journal since the new website was launched in 2001. Every slide will be delivered intact with a title and reference, and can be easily slotted into your next presentation or lecture,taking all the effort out of downloading figures from the website and importing them into PowerPoint. All you have to do is click on the figure in the paper to go to the figure's webpage, and then click the `PowerPoint slide for teaching' button, which will download the slide in approximately 30 seconds. We hope you will find this facility useful.We are also looking forward to the launch of the JEB Archive online at the journal's HighWire website. Every paper that the journal has ever published will be available as a scanned pdf file, and will be accessible to all users free of charge. So keep watching for announcements of this new and exciting development some time in 2005.