endocrine regulator [ 5 ] . The active form of VD, 1α,25(OH) 2 D or calcitriol, is synthesised from precursor cholesterol by metabolic steps in skin, liver, and kidney. The primary metabolite, 25OHD, is the most abundant form of VD in blood and therefore established for measuring VD status. Various studies have shown an association of VD status and T2D [ 6 ] . Low 25OHD is found more often in patients with T2D [ 7 , 8 ] and correlates with a higher risk for T2D [ 6 , 9 , 10 ] . Furthermore, the 25OHD serum concentration is negatively associated with components of the metabolic syndrome, such as obesity, hyperglycaemia [ 11 -13 ] , and high body mass index (BMI) [ 9 , 14 -16 ] . Finally, many studies confi rmed an inverse correlation between 25OHD and parameters of insulin resistance: fasting glucose, glucose tolerance, insulin levels, and homeostasis model assessment-index (HOMA-I) [ 17 -24 ] . In addition, interventional studies showed benefi cial eff ects of VD on glucose status, insulin sensitivity, and insulin resistance [ 25 -27 ] . Introduction ▼According to the International Diabetes Federation, more than 300 million people worldwide are currently aff ected by diabetes mellitus ( http://www.idf.org/diabetesatlas/5e/the-globalburden ). A further increase of diabetes prevalence is expected, in particular due to the growing population in developing countries, the increasing industrialisation, urbanisation, and life style changes [ 1 , 2 ] . Diabetes pathophysiology is believed to result from environmental factors on a genetic background, but the causal genes remain complex and exert low hazard risk ratios [ 3 ] . The prevalence of type 2 diabetes (T2D) is infl uenced by multiple environmental factors, one of them may lie in the vitamin D system [ 4 ] . During recent years, vitamin D (VD), mainly known for its eff ects on bone and mineral metabolism, is growingly perceived as a pleiotropic

Rett Syndrome (RTT) is caused in more than 60% of cases by nonsense mutations in the MECP2 gene. So far, no curative therapy for RTT has become available. In other genetic disorders, it has been shown that aminoglycosides can cause a read-through of nonsense mutations with an efficiency of up to 20%. The aim of this study was to evaluate if this therapeutic concept is applicable to RTT. HeLa cells were transfected with eukaryotic expression vectors carrying mutant alleles of frequently occurring MECP2 nonsense mutations that were N-terminally fused to a FLAG tag. Transfected cells were incubated 24 h in the presence of gentamicin. The expression of full-length protein was analyzed by Western blotting and immunofluorescent cell staining. In the presence of gentamicin a read-through varying between 10 and 21.8% was found, depending on the nucleotide sequence context of the nonsense mutations. The full-length protein was located correctly in the nucleus. We have shown that aminoglycoside-mediated read-through of nonsense mutations in the MECP2 gene can be achieved in vitro with efficiency comparable with that seen in other disorders.

Vitamin D (VD) has been implicated in type 1 diabetes (T1D) by genetic and epidemiological studies. Individuals living in regions with low sunlight exposure have an increased T1D risk and VD supplementation reduced the risk in human individuals and mouse models. One possibility of how VD influences the pathogenesis of T1D is its immunomodulatory effect on dendritic cells (DC), which then preferentially activate regulatory T cells (T(regs) ). In the present pilot study, we collected blood samples from a small cohort of patients with T1D at baseline and months 6 and 12. VD-deficient patients were advised to supplement with 1000 IU/day VD. We found a considerable variation in the VD plasma level at baseline and follow-up. However, with higher VD plasma levels, a lower frequency of interleukin (IL)-4-producing CD8 T cells was observed. We further performed a comprehensive genotyping of 13 VD-related polymorphisms and found an association between VD plasma level and the genotype of the VD binding protein (DBP). The frequency of DC and T cell subsets was variable in patients of all subgroups and in individual patients over time. Nevertheless, we found some significant associations, including the 1,25-dihydroxyvitamin D(3) hydroxylase (CYP27B1) genotype with the frequency of DC subtypes. In summary, our preliminary results indicate only a limited influence of the VD plasma level on the immune balance in patients with T1D. Nevertheless, our pilot study provides a basis for a follow-up study with a larger cohort of patients.