New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Probing the Boundaries between Lewis-Basic and Redox Behavior of a Parent Borylene

The parent borylene (CAAC)(Me$_{3}$P)BH, 1 (CAAC=cyclic alkyl(amino)carbene), acts both as a Lewis base and one-electron reducing agent towards group 13 trichlorides (ECl$_{3}$, E=B, Al, Ga, In), yielding the adducts 1-ECl$_{3}$ and increasing proportions of the radical cation [1]$^{•+}$ for the heavier group 13 analogues. With boron trihalides (BX$_{3}$, X=F, Cl, Br, I) 1 undergoes sequential adduct formation and halide abstraction reactions to yield borylboronium cations and shows an increasing tendency towards redox processes for the heavier halides. Calculations confirm that 1 acts as a strong Lewis base towards EX3 and show a marked increase in the B−E bond dissociation energies down both group 13 and the halide group

A Stable N-Heterocyclic Silylene with a 1,1′-Ferrocenediyl Backbone

Gefördert im Rahmen des Projekts DEA

Ferrocene-Based N-Heterocyclic Plumbylenes [Fe{(η⁵- C₅H₄)NSiMe₂R}₂Pb:]: Influence of the Steric Demand of the NSubstituents on Their Dimerization via C-H Activation with Pbᴵᴵ

Gefördert im Rahmen des Projekts DEA

Experimental and Computational Study of a Confirmed Borylene-to-Diborene Dimerization

While the dimerization of heavier group 13 carbene analogues to the corresponding alkene analogues is known and relatively well understood, the dimerization of dicoordinate borylenes (LRB:, L = neutral donor; R = anionic substituent) to the corresponding diborenes (LRBBRL) has never been directly observed. In this study we present the first example of a formal borylene-to-diborene dimerization through abstraction of a labile phosphine ligand from the tricoordinate hydroborylene precursor (CAAC)­(Me3P)­BH (CAAC = cyclic alkyl­(amino)­carbene) by bulky Lewis-acidic dihaloboranes (BX2Y, X = Cl, Br, Y = aryl, boryl), generating the corresponding dihydrodiborene (CAAC)­HBBH­(CAAC) and (Me3P)­BX2Y as the byproduct. An in-depth experimental and computational mechanistic analysis shows that this seemingly simple process (2 LL′BH + 2 BX2Y → LHBBHL + 2 L′BX2Y) is in fact based on a complex sequence of finely tuned processes, involving the one-electron oxidation of and PMe3 abstraction from the borylene precursor by BX2Y, multiple halide transfers between (di)boron intermediates and BX2Y/[BX3Y]−, and multiple one-electron redox processes between diboron intermediates and the borylene precursor, which make the reaction ultimately autocatalytic in [(CAAC)­(Me3P)­BH]•+. The findings suggest that [LBXR]• boryl radicals are more likely coupling partners than dicoordinate LRB: borylenes in the reductive coupling of base-stabilized LBX2R boranes to LRBBRL diborenes

Characterization of the New Serum Protein Reference Material ERM-DA470k/IFCC: Value Assignment by Immunoassay

BACKGROUND: The availability of a suitable matrix reference material is essential for standardization of the immunoassays used to measure serum proteins. The earlier serum protein reference material ERM-DA470 (previously called CRM470), certified in 1993, has led to a high degree of harmonization of the measurement results. A new serum protein material has now been prepared and its suitability in term of homogeneity and stability has been verified; after characterization, the material has been certified as ERM-DA470k/IFCC. METHODS: We characterized the candidate reference material for 14 proteins by applying a protocol that is considered to be a reference measurement procedure, by use of optimized immunoassays. ERM-DA470 was used as a calibrant. RESULTS: For 12 proteins [alpha(2) macroglobulin (A2M), alpha(1) acid glycoprotein (orosomucoid, AAG), alpha(1) antitrypsin (alpha(1)-protease inhibitor, AAT), albumin (ALB), complement 3c (C3c), complement 4 (C4), haptoglobin (HPT), IgA, IgG, IgM, transferrin (TRF), and transthyretin (TTR)], the results allowed assignment of certified values in ERM-DA470k/IFCC. For CRP, we observed a bias between the lyophilized and liquid frozen materials, and for CER, the distribution of values was too broad. Therefore, these 2 proteins were not certified in the ERM-DA470k/IFCC. Different value transfer procedures were tested (open and closed procedures) and found to provide equivalent results. CONCLUSIONS: A new serum protein reference material has been produced, and values have been successfully assigned for 12 proteins. (C) 2010 American Association for Clinical Chemistr

Trapping of a Terminal Intermediate in the Boron-Mediated Dinitrogen Reduction: Mono‑, Tri‑, and Tetrafunctionalized Hydrazines in Two Steps from N₂

The addition of chlorotrimethylsilane to a boron-mediated, transition-metal-free N2 activation reaction leads to the isolation of multiple potassium boryl(silyl)hydrazido species, likely trapping products of a terminal dinitrogen complex of boron. One of these silylated N2 species can be protonated or methylated, providing access to mono- to tetrafunctionalized hydrazines in two steps from N2 and in the absence of transition metals