The pharmacological regulation of cellular mitophagy

Small molecules are pharmacological tools of considerable value for dissecting complex biological processes and identifying potential therapeutic interventions. Recently, the cellular quality-control process of mitophagy has attracted considerable research interest; however, the limited availability of suitable chemical probes has restricted our understanding of the molecular mechanisms involved. Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (for example, FCCP/CCCP) and the use of antimycin A and oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis and therefore limit the scope for dissection of subtle, bioenergy-related regulatory phenomena. Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation. We have summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications

Cerebellar Asymmetry and Cortical Connectivity in Monozygotic Twins with Discordant Handedness

Handedness differentiates patterns of neural asymmetry and interhemispheric connectivity in cortical systems that underpin manual and language functions. Contemporary models of cerebellar function incorporate complex motor behaviour and higher-order cognition, expanding upon earlier, traditional associations between the cerebellum and motor control. Structural MRI defined cerebellar volume asymmetries and correlations with corpus callosum (CC) size were compared in 19 pairs of adult female monozygotic twins strongly discordant for handedness (MZHd). Volume and asymmetry of cerebellar lobules were obtained using automated parcellation.CC area and regional widths were obtained from midsagittal planimetric measurements. Within the cerebellum and CC, neurofunctional distinctions were drawn between motor and higher-order cognitive systems. Relationships amongst regional cerebellar asymmetry and cortical connectivity (as indicated by CC widths) were investigated. Interactions between hemisphere and handedness in the anterior cerebellum were due to a larger right-greater-than-left hemispheric asymmetry in right-handed (RH) compared to left-handed (LH) twins. In LH twins only, anterior cerebellar lobule volumes (IV, V) for motor control were associated with CC size, particularly in callosal regions associated with motor cortex connectivity. Superior posterior cerebellar lobule volumes (VI, Crus I, Crus II, VIIb) showed no correlation with CC size in either handedness group. These novel results reflected distinct patterns of cerebellar-cortical relationships delineated by specific CC regions and an anterior-posterior cerebellar topographical mapping. Hence, anterior cerebellar asymmetry may contribute to the greater degree of bilateral cortical organisation of frontal motor function in LH individuals

Warm-up effects on muscle oxygenation, metabolism and sprint cycling performance

To investigate the effects of warm-up intensity on all-out sprint cycling performance, muscle oxygenation and metabolism, 8 trained male cyclists/triathletes undertook a 30-s sprint cycling test preceded by moderate, heavy or severe warm up and 10-min recovery. Muscle oxygenation was measured by near-infrared spectroscopy, with deoxyhaemoglobin ([HHb]) during the sprint analysed with monoexponential models with time delay. Aerobic, anaerobic-glycolytic and phosphocreatine energy provision to the sprint were estimated from oxygen uptake and lactate production. Immediately prior to the sprint, blood [lactate] was different for each warm up and higher than resting for the heavy and severe warm ups (mod. 0.94 ± 0.36, heavy 1.92 ± 0.64, severe 4.37 ± 0.93 mmol l-1 P < 0.05), although muscle oxygenation was equally raised above rest. Mean power during the sprint was lower following severe compared to moderate warm up (mod. 672 ± 54, heavy 666 ± 56, severe 655 ± 59 W, P < 0.05). The [HHb] kinetics during the sprint were not different among conditions, although the time delay before [HHb] increased was shorter for severe versus moderate warm up (mod. 5.8 ± 0.6, heavy 5.6 ± 0.9, severe 5.2 ± 0.7 s, P < 0.05). The severe warm up was without effect on estimated aerobic metabolism, but increased estimated phosphocreatine hydrolysis, the latter unable to compensate for the reduction in estimated anaerobic-glycolytic metabolism. It appears that despite all warm ups equally increasing muscle oxygenation, and indicators of marginally faster oxygen utilisation at the start of exercise following a severe-intensity warm up, other energy sources may not be able to fully compensate for a reduced glycolytic rate in sprint exercise with potential detrimental effects on performance. © Springer-Verlag 2011

Impacto da atividade física e esportes sobre o crescimento e puberdade de crianças e adolescentes Linear growth and puberty in children and adolescents: effects of physical activity and sports

OBJETIVO: Apresentar revisão atualizada e crítica sobre o impacto do esporte e da atividade física no crescimento, desenvolvimento puberal e mineralização óssea de crianças e adolescentes. FONTES DE DADOS: Pesquisa bibliográfica nos bancos de dados Medline e Lilacs (1987-2007), selecionando os artigos escritos em inglês, português ou espanhol, a partir dos descritores "esportes" e "exercícios", em combinação com "crescimento", "puberdade" e "mineralização óssea". Foram examinados 252 artigos e 48 deles selecionados. SÍNTESE DOS DADOS: Diferentes modalidades esportivas não aumentam ou diminuem a estatura. Ocorre um viés de seleção, no qual fatores constitucionais determinam a seleção de biótipos privilegiados para determinados esportes. O exercício físico leve a moderado estimula o crescimento e deve ser incentivado. A atividade física extenuante, principalmente quando associada à restrição dietética, afeta o crescimento, o desenvolvimento puberal, a função reprodutiva e a mineralização óssea. A musculação praticada por jovens pré-púberes pode ser prejudicial, se não for realizada sob supervisão, já que há um potencial risco de lesão na cartilagem de crescimento. Entretanto, quando bem supervisionada, pode levar a um aumento de força e resistência muscular. CONCLUSÕES: Os efeitos deletérios dos esportes sobre o crescimento e desenvolvimento só foram observados em atletas de elite submetidos a treinamento intensivo e restrição alimentar. Alterações hormonais e de citocinas inflamatórias são parte da fisiopatologia desse processo. É necessário que estudos longitudinais avaliem as repercussões da atividade física recreacional sobre a estatura final.<br>OBJECTIVE: To present an up-to-date critical review about the impact of sports and physical activity on growth, pubertal development and bone mineralization of children and adolescents. DATA SOURCE: Bibliographic search of Medline and Lilacs databases (1987-2007) with selection of studies written in English, Portuguese or Spanish, with the descriptors "sports" and "exercise" in combination with "growth", "puberty" and "bone mineralization". A total of 252 articles were retrieved and 48 of them were selected. DATA SYNTHESIS: Light to moderate physical activity has a beneficial effect on growth and bone development, while intense physical training, specially if associated to dietary restrictions, may attenuate linear growth, pubertal development, reproductive function and bone mineralization. Different sports do not have specific effects on final height. There is a selection bias in which constitutional factors contribute to select favored biotypes to specific sports. Weight-training by pre-pubertal children may be harmful, if not supervised, due to the potential risk of injure to the growth plates; however, if performed under strict supervision, may provide muscle strength and resistance. CONCLUSIONS: Deleterious effects of sports in growth and development of children and adolescents were only observed in elite athletes submitted to intensive training and dietetic restriction. Longitudinal studies are neded to evaluate the effects of recreational physical activity upon linear growth