Genetic analyses of smoking initiation, persistence, quantity, and age-at-onset of regular cigarette use in Brazilian families: the Baependi Heart Study

Background: The purpose of this study was to estimate the genetic influences on the initiation of cigarette smoking, the persistence, quantity and age-at-onset of regular cigarette use in Brazilian families. Methods: The data set consisted of 1,694 individuals enrolled in the Baependi Heart Study. The heritability and the heterogeneity in genetic and environmental variance components by gender were estimated from variance components approaches, using the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package. The mixed-effects Cox model was used for the genetic analysis of the age-at onset of regular cigarette use. Results: The heritability estimates were high (> 50%) for smoking initiation and were intermediate, ranging from 23.4 to 31.9%, for smoking persistence and quantity. Significant evidence for heterogeneity in variance components by gender was observed for smoking initiation and age-at-onset of regular cigarette use. Genetic factors play an important role in the interindividual variation of these phenotypes in females, while in males there is a predominant environmental component, which could be explained by greater social influences in the initiation of tobacco use. Conclusions: Significant heritabilities were observed in smoking phenotypes for both males and females from the Brazilian population. These data add to the literature and are concordant with the notion of significant biological determination in smoking behavior. Samples from the Baependi Heart Study may be valuable for the mapping of genetic loci that modulate this complex biological trait.

Collybistin and gephyrin are novel components of the eukaryotic translation initiation factor 3 complex

Abstract Background Collybistin (CB), a neuron-specific guanine nucleotide exchange factor, has been implicated in targeting gephyrin-GABAA receptors clusters to inhibitory postsynaptic sites. However, little is known about additional CB partners and functions. Findings Here, we identified the p40 subunit of the eukaryotic translation initiation factor 3 (eIF3H) as a novel binding partner of CB, documenting the interaction in yeast, non-neuronal cell lines, and the brain. In addition, we demonstrated that gephyrin also interacts with eIF3H in non-neuronal cells and forms a complex with eIF3 in the brain. Conclusions Together, our results suggest, for the first time, that CB and gephyrin associate with the translation initiation machinery, and lend further support to the previous evidence that gephyrin may act as a regulator of synaptic protein synthesis.

Testing the influence of far-field topographic forcing on subduction initiation at a passive margin

Despite favourable gravitational instability and ridge-push, elastic and frictional forces prevent subduction initiation fromarising spontaneously at passive margins. Here,we argue that forces arising fromlarge continental topographic gradients are required to initiate subduction at passivemargins. In order to test this hypothesis,we use 2Dnumerical models to assess the influence of the Andean Plateau on stressmagnitudes and deformation patterns at the Brazilian passive margin. The numerical results indicate that “plateau-push” in this region is a necessary additional force to initiate subduction. As the SE Brazilianmargin currently shows no signs of self-sustained subduction, we examined geological and geophysical data to determine if themargin is in the preliminary stages of subduction initiation. The compiled data indicate that the margin is presently undergoing tectonic inversion, which we infer as part of the continental–oceanic overthrusting stage of subduction initiation. We refer to this early subduction stage as the “Brazilian Stage”, which is characterized by N10 kmdeep reverse fault seismicity at themargin, recent topographic uplift on the continental side, thick continental crust at themargin, and bulging on the oceanic side due to loading by the overthrusting continent. The combined results of the numerical simulations and passivemargin analysis indicate that the SE Brazilian margin is a prototype candidate for subduction initiation.