The vitamin D receptor polymorphism in the translation initiation codon is a risk factor for insulin resistance in glucose tolerant Caucasians

BACKGROUND: Although vitamin D receptor (VDR) polymorphisms have been shown to be associated with abnormal glucose metabolism, the reported polymorphisms are unlikely to have any biological consequences. The VDR gene has two potential translation initiation sites. A T-to-C polymorphism has been noted in the first ATG (f allele), abolishing the first translation initiation site and resulting in a peptide lacking the first three amino acids (F allele). We examined the role of this polymorphism in insulin sensitivity and beta cell function. This study included 49 healthy Caucasian subjects (28 females, age 28 ± 1 years old, body mass index 24.57 ± 0.57 kg/m(2), waist-hip ratio 0.81 ± 0.01 cm/cm). They were all normotensive (less than 140/90 mmHg) and glucose tolerant, which was determined by a standard 75-gm oral glucose tolerance test. Their beta cell function (%B) and insulin sensitivity (%S) were calculated based on the Homeostasis Model Assessment (HOMA). Their genotypes were determined by a polymerase chain reaction-restriction fragment length polymorphism analysis. Phenotypes were compared between genotypic groups. RESULTS: There were 18 FF, 21 Ff, and 10 ff subjects. Since only 10 ff subjects were identified, they were pooled with the Ff subjects during analyses. The FF and Ff/ff groups had similar glucose levels at each time point before and after a glucose challenge. The Ff/ff group had higher insulin levels than the FF group at fasting (P=0.006), 30 minutes (P=0.009), 60 minutes (P=0.049), and 90 minutes (P=0.042). Furthermore, the Ff/ff group also had a larger insulin area under the curve than the FF group (P=0.009). While no difference was noted in %B, the Ff/ff group had a lower %S than the FF group (0.53 vs. 0.78, P=0.006). A stepwise regression analysis confirmed that the Fok I polymorphism was an independent determinant for %S, accounting for 29.3% of variation in %S when combined with waist-hip ratio. CONCLUSIONS: We report that the Fok I polymorphism at the VDR gene locus is associated with insulin sensitivity, but has no influence on beta cell function in healthy Caucasians. Although this polymorphism has been shown to affect the activation of vitamin D-dependent transcription, the molecular basis of the association between this polymorphism and insulin resistance remains to be determined

Communication calls produced by electrical stimulation of four structures in the guinea pig brain

One of the main central processes affecting the cortical representation of conspecific vocalizations is the collateral output from the extended motor system for call generation. Before starting to study this interaction we sought to compare the characteristics of calls produced by stimulating four different parts of the brain in guinea pigs (Cavia porcellus). By using anaesthetised animals we were able to reposition electrodes without distressing the animals. Trains of 100 electrical pulses were used to stimulate the midbrain periaqueductal grey (PAG), hypothalamus, amygdala, and anterior cingulate cortex (ACC). Each structure produced a similar range of calls, but in significantly different proportions. Two of the spontaneous calls (chirrup and purr) were never produced by electrical stimulation and although we identified versions of chutter, durr and tooth chatter, they differed significantly from our natural call templates. However, we were routinely able to elicit seven other identifiable calls. All seven calls were produced both during the 1.6 s period of stimulation and subsequently in a period which could last for more than a minute. A single stimulation site could produce four or five different calls, but the amygdala was much less likely to produce a scream, whistle or rising whistle than any of the other structures. These three high-frequency calls were more likely to be produced by females than males. There were also differences in the timing of the call production with the amygdala primarily producing calls during the electrical stimulation and the hypothalamus mainly producing calls after the electrical stimulation. For all four structures a significantly higher stimulation current was required in males than females. We conclude that all four structures can be stimulated to produce fictive vocalizations that should be useful in studying the relationship between the vocal motor system and cortical sensory representation

Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies

Type 2 diabetes mellitus (T2DM) influences bone metabolism, but the relation of T2DM with bone mineral density (BMD) remains inconsistent across studies. The objective of this study was to perform a meta-analysis and meta-regression of the literature to estimate the difference in BMD (g/cm2) between diabetic and non-diabetic populations, and to investigate potential underlying mechanisms. A literature search was performed in PubMed and Ovid extracting data from articles prior to May 2010. Eligible studies were those where the association between T2DM and BMD measured by dual energy X-ray absorptiometry was evaluated using a cross-sectional, cohort or case–control design, including both healthy controls and subjects with T2DM. The analysis was done on 15 observational studies (3,437 diabetics and 19,139 controls). Meta-analysis showed that BMD in diabetics was significantly higher, with pooled mean differences of 0.04 (95% CI: 0.02, 0.05) at the femoral neck, 0.06 (95% CI: 0.04, 0.08) at the hip and 0.06 (95% CI: 0.04, 0.07) at the spine. The differences for forearm BMD were not significantly different between diabetics and non-diabetics. Sex-stratified analyses showed similar results in both genders. Substantial heterogeneity was found to originate from differences in study design and possibly diabetes definition. Also, by applying meta-regression we could establish that younger age, male gender, higher body mass index and higher HbA1C were positively associated with higher BMD levels in diabetic individuals. We conclude that individuals with T2DM from both genders have higher BMD levels, but that multiple factors influence BMD in individuals with T2DM

The importance of the altricial – precocial spectrum for social complexity in mammals and birds:A review

Various types of long-term stable relationships that individuals uphold, including cooperation and competition between group members, define social complexity in vertebrates. Numerous life history, physiological and cognitive traits have been shown to affect, or to be affected by, such social relationships. As such, differences in developmental modes, i.e. the ‘altricial-precocial’ spectrum, may play an important role in understanding the interspecific variation in occurrence of social interactions, but to what extent this is the case is unclear because the role of the developmental mode has not been studied directly in across-species studies of sociality. In other words, although there are studies on the effects of developmental mode on brain size, on the effects of brain size on cognition, and on the effects of cognition on social complexity, there are no studies directly investigating the link between developmental mode and social complexity. This is surprising because developmental differences play a significant role in the evolution of, for example, brain size, which is in turn considered an essential building block with respect to social complexity. Here, we compiled an overview of studies on various aspects of the complexity of social systems in altricial and precocial mammals and birds. Although systematic studies are scarce and do not allow for a quantitative comparison, we show that several forms of social relationships and cognitive abilities occur in species along the entire developmental spectrum. Based on the existing evidence it seems that differences in developmental modes play a minor role in whether or not individuals or species are able to meet the cognitive capabilities and requirements for maintaining complex social relationships. Given the scarcity of comparative studies and potential subtle differences, however, we suggest that future studies should consider developmental differences to determine whether our finding is general or whether some of the vast variation in social complexity across species can be explained by developmental mode. This would allow a more detailed assessment of the relative importance of developmental mode in the evolution of vertebrate social systems

DFB laser with integrated waveguide taper grown by shadow masked MOVPE.

A

On the C∗C^*-algebraic approach to topological phases for insulators

International audienceThe notion of a topological phase of an insulator is based on the concept of homotopy between Hamiltonians. It therefore depends on the choice of a topological space to which the Hamiltonians belong. We advocate that this space should be the $C^*$ -algebra of observables. We relate the symmetries of insulators to graded real structures on the observable algebra and classify the topological phases using van Daele’s formulation of K-theory. This is related but not identical to Thiang’s recent approach to classify topological phases by K-groups in Karoubi’s formulation