Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Preparation of Dess-Martin periodinane - The role of the morphology of 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide precursor

1-Hydroxy-1,2-benziodoxol-3(1H)-one I-oxide prepared by oxidation of o-iodobenzoic acid with potassium bromate forms either a microcrystalline powder, a macrocrystalline material, or a mixture of both forms. This difference in physical form is the source of the difficulty in reproducibly converting 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide to the corresponding I-triacetoxy derivative. A simple method is given for conversion of crystalline 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide to the more reactive powder form, The microcrystalline powder and macrocrystalline material are characterised by X-ray diffraction.

Quiescent and flaring X-ray emission from the nearby M/T dwarf binary SCR 1845-6357

Aims: X-ray emission is an important diagnostics to study magnetic activity in very low mass stars that are presumably fully convective and have an effectively neutral photosphere. Methods: We investigate an XMM-Newton observation of SCR 1845-6357, a nearby, ultracool M 8.5 / T 5.5 dwarf binary. The binary is unresolved in the XMM detectors, but the X-ray emission is very likely from the M 8.5 dwarf. We compare its flaring emission to those of similar very low mass stars and additionally present an XMM observation of the M 8 dwarf VB 10. Results: We detect quasi-quiescent X-ray emission from SCR 1845-6357 at soft X-ray energies in the 0.2-2.0 keV band, as well as a strong flare with a count rate increase of a factor of 30 and a duration of only 10 min. The quasi-quiescent X-ray luminosity of log LX = 26.2 erg/s and the corresponding activity level of log LX/Lbol = -3.8 point to a fairly active star. Coronal temperatures of up to 5 MK and frequent minor variability support this picture. During the flare, which is accompanied by a significant brightening in the near-UV, plasma temperatures of 25-30 MK are observed and an X-ray luminosity of LX = 8 × 1027 erg/s is reached. Conclusions: The source SCR 1845-6357 is a nearby, very low mass star that emits X-rays at detectable levels in quasi-quiescence, implying the existence of a corona. The high activity level, coronal temperatures and the observed large flare point to a rather active star, despite its estimated age of a few Gyr.

Dos décadas de una atormentada relación: Martin Heidegger y Edmund Husserl 1909-1929

La publicación reciente de documentos y la consulta directa en archivos posibilita un acercamiento renovado a la conflictiva relación entre Edmund Husserl y Martin Heidegger. El artículo lleva a cabo esto mediante una revisión del camino académico de Heidegger a la sombra de su protector Husserl. De ese modo se dejan ver las escisiones anímicas del joven Heidegger, su apropiación de la fenomenología husserliana y a la vez su distanciamiento del maestro. Con ello también se muestra que el rompimiento entre ambos pensadores no tiene su origen en los compromisos políticos de Heidegger en 1933, sino que era algo que latía desde el inicio de la relación.

Europa : paisagem e pensamento : um excurso sobre Teixeira de Pascoaes, Friedrich Hölderlin, José Marinho e Martin Heidegger

Tese de doutoramento, Filosofia (Filosofia em Portugal), Universidade de Lisboa, Faculdade de Letras, 2014

Robert Crawford, Baritone, August 16, 1937

Concert Program for Robert Crawford, Baritone, August 16, 1937

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.