Circadian disruption and remedial interventions: effects and interventions for jet lag for athletic peak performance.

Jet lag has potentially serious deleterious effects on performance in athletes following transmeridian travel, where time zones are crossed eastwards or westwards; as such, travel causes specific effects related to desynchronization of the athlete's internal body clock or circadian clock. Athletes are particularly sensitive to the effects of jet lag, as many intrinsic aspects of sporting performance show a circadian rhythm, and optimum competitive results require all aspects of the athlete's mind and body to be working in tandem at their peak efficiency. International competition often requires transmeridian travel, and competition timings cannot be adjusted to suit individual athletes. It is therefore in the interest of the individual athlete and team to understand the effects of jet lag and the potential adaptation strategies that can be adopted. In this review, we describe the underlying genetic and physiological mechanisms controlling the circadian clock and its inherent ability to adapt to external conditions on a daily basis. We then examine the fundamentals of the various adaptation stimuli, such as light, chronobiotics (e.g. melatonin), exercise, and diet and meal timing, with particular emphasis on their suitability as strategies for competing athletes on the international circuit. These stimuli can be artificially manipulated to produce phase shifts in the circadian rhythm to promote adaptation in the optimum direction, but care must be taken to apply them at the correct time and dose, as the effects produced on the circadian rhythm follow a phase-response curve, with pronounced shifts in direction at different times. Light is the strongest realigning stimulus and careful timing of light exposure and avoidance can promote adjustment. Chronobiotics such as melatonin can also be used to realign the circadian clock but, as well as timing and dosage issues, there are also concerns as to its legal status in different countries and with the World Anti-Doping Agency. Experimental data concerning the effects of food intake and exercise timing on jet lag is limited to date in humans, and more research is required before firm guidelines can be stated. All these stimuli can also be used in pre-flight adaptation strategies to promote adjustment in the required direction, and implementation of these is described. In addition, the effects of individual variability at the behavioural and genetic levels are also discussed, along with the current limitations in assessment of these factors, and we then put forward three case studies, as examples of practical applications of these strategies, focusing on adaptations to travel involving competition in the Rugby Sevens World Cup and the 2016 Summer Olympics in Rio de Janeiro, Brazil. Finally, we provide a list of practice points for optimal adaptation of athletes to jet lag.

Expression analyses of the mitochondrial complex I 75-kDa subunit in early onset schizophrenia and autism spectrum disorder: increased levels as a potential biomarker for early onset schizophrenia.

Searching for a peripheral biological marker for schizophrenia, we previously reported on elevated mitochondrial complex I 75-kDa subunit mRNA-blood concentrations in early onset schizophrenia (EOS). The aim of this study was to further evaluate the utility of this gene as a potential marker for schizophrenia. Both-schizophrenia and autism-are suggested to be neuronal maldevelopmental disorders with reports of mitochondrial dysfunction and increased oxidative stress. Therefore we have investigated the expression levels of mitochondrial complex I 75-kDa subunit mRNA in whole blood of children with autistic spectrum disorder (ASD) and a group of adolescent acute first-episode EOS patients in comparison to matched controls. We have found that compared to the respective controls only the group of EOS patients-and not the ASD group-showed a significantly altered expression of the complex I 75-kDa subunit mRNA. Although further studies are necessary to test for the specificity of this marker, our findings point to the potential use of the mitochondrial complex I as a biomarker for schizophrenia.

Comparison of differential gene expression of hot and cold thyroid nodules with primary epithelial cell culture models by investigation of co-regulated gene sets.

Both autonomously functioning thyroid nodules (AFTNs) and cold thyroid nodules (CTNs) are characterized by an increased proliferation, however, they have opposite functional activities. Therefore, with the aim to further understand the distinct molecular pathology of each entity and to discover common mechanisms like those leading to increased proliferation in both, AFTNs and CTNs, we now compared gene expression of AFTNs and CTNs with in vitro model systems (TSH-stimulated and ras-transfected primary cultures (PC)) whose gene expression patterns can be attributed to specific molecular alterations. Since combinations of co-regulated genes are more likely to reveal molecular mechanisms, we used a procedure which groups co-regulated genes within "gene sets". We found a co-regulated gene set in the AFTNs that overlaps with differential expression in TSH-stimulated PCs but not in CTNs or ras-transfected PCs. In addition to thyroid peroxidase and sialyltransferase 1, this set of co-regulated genes comprises metallothioneins and the G-protein-coupled receptor 56. Although their role in the thyroid is unknown so far, their appearance in one group indicates a functional relevance in TSH-TSH receptor-stimulated mechanisms. Furthermore, we identified down-regulated gene sets with concordant expression patterns in AFTNs, CTNs and ras-transfected PCs. However, these expression patterns are not of relevance in the TSH-stimulated PCs. These findings suggest that TSH-stimulated PCs can be used as a model of increased thyroid function (AFTNs), whereas the ras-transfected PCs better reflect the increased proliferation of both AFTNs and CTNs.