Aims/hypothesisFTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.MethodsAll studies published on the association between FTO-rs9939609 (or proxy [r2 > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.ResultsThe FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10−19), overweight by 1.13-fold/allele (p = 1.0 × 10−11) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10−5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10−17), WHR by 0.003/allele (p = 1.2 × 10−6), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations.Conclusions/interpretationFTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Rapid proton migration is a key process in hydrocarbon photochemistry. Charge migration and subsequent proton motion can mitigate radiation damage when heavier atoms absorb X-rays. If rapid enough, this can improve the fidelity of diffract-before-destroy measurements of biomolecular structure at X-ray-free electron lasers. Here we study X-ray-initiated isomerization of acetylene, a model for proton dynamics in hydrocarbons. Our time-resolved measurements capture the transient motion of protons following X-ray ionization of carbon K-shell electrons. We Coulomb-explode the molecule with a second precisely delayed X-ray pulse and then record all the fragment momenta. These snapshots at different delays are combined into a 'molecular movie' of the evolving molecule, which shows substantial proton redistribution within the first 12 fs. We conclude that significant proton motion occurs on a timescale comparable to the Auger relaxation that refills the K-shell vacancy.
Composites consisting of polylactide (PLA) and poly(ε-caprolactone) (PCL) filled with acid-oxidized multiwalled carbon nanotubes (A-MWCNTs) were prepared through melt compounding. Phase morphologies of PLA/PCL/A-MWCNT composites with different contents of filled A-MWCNTs and PCL compositions were mainly observed by scanning electron microscope. The results show that A-MWCNTs are selectively dispersed in the PCL phase, regardingless of PCL phase domain sizes. For PLA/PCL/A-MWCNT composites with fixed PLA/PCL ratio of 95/5, the dispersed PCL phase domain sizes in the PLA matrix decrease even though a small content of A-MWCNTs is added, compared with PLA/PCL blend with the same composition, indicating that A-MWCNTs effectively prevent from coalescence of the dispersed PCL phase domains. With filling of 1.0 wt % A-MWCNTs, an interesting change of electrical conductivity for PLA/PCL/A-MWCNT composites is observed, in which the maximum conductivity is observed for PLA/PCL/A-MWCNT composite with PLA/PCL ratio of 60/40. The result is well-explained by the formed cocontinuous phase morphology and effective A-MWCNT content.
Silicon‐based anodes with high theoretical capacity have intriguing potential applications for next‐generation high‐energy lithium‐ion batteries, but suffer from huge volumetric change that causes pulverization of electrodes. Rational design and construction of effective electrode structures combined with versatile binders remain a significant challenge. Here, a unique natural binder of konjac glucomannan (KGM) is developed and an amorphous protective layer of SiO2 is fabricated on the surface of Si nanoparticles (Si@SiO2) to enhance the adhesion. Benefiting from a plethora of hydroxyl groups, the KGM binder with inherently high adhesion and superior mechanical properties provides abundant contact sites to active materials. Molecular mechanics simulations and experimental results demonstrate that the enhanced adhesion between KGM and Si@SiO2 can bond the particles tightly to form a robust electrode. In addition to bridging KGM molecules, the SiO2‐functionalized surface may serve as a buffer layer to alleviate the stresses of Si nanoparticles resulting from the volume change. The as‐fabricated KGM/Si@SiO2 electrode exhibits outstanding structural stability upon long‐term cycles. A highly reversible capacity of 1278 mAh g−1 can be achieved over 1000 cycles at a current density of 2 A g−1, and the capacity decay is as small as 0.056% per cycle.
The X-ray crystallographic structures of a trimeric all-alkyl-substituted 1,4-dilithio-1,3-butadiene with a Li 6 pseudooctahedron and a dimeric Me 3 Si-substituted 1,4-dilithio-1,3-butadiene with a Li 4 tetrahedron are reported. The reactions of theses compounds with CO were investigated.
Aims/hypothesisMost genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.MethodsWe performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.ResultsWe identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 × 10−5 from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (pmeta = 2.6 × 10−8; OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (pmeta = 2.3 × 10−10) and a population of European descent (p = 8.6 × 10−3). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.Conclusions/interpretationOur study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-013-2874-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Agkisacucetin is a snake C-type lectin isolated from the venom of Agkistrodon acutus (A. acutus). It binds specifically to the platelet glycoprotein (GP) Ib and prevents the von Willebrand factor (VWF) accessing it. We determined the crystal structure of agkisacucetin to 1.9Å resolution. The structure of agkisacucetin has an (αβ) fold similar to another GPIb-binding protein, flavocetin-A, but lacks the C-terminal cysteine in the β-subunit, does not form (βα)(4) tetramers, and does not cluster GPIbs, like flavocetin-A.
Precisely controlled organic one-dimensional (1D) and two-dimensional (2D) materials with unique optoelectronic properties have attracted wide interests. By the introduction of chlorine into the poly(p-phenylenevinylene) (PPV) core, we produced a series of 1D rod-like micelles, whose sizes were controlled by the concentrations of solutions, using self-assembly (SA) of conjugated copolymers (PPV−Cl 20% ) 10 -b-P2VP 20 . The transformation from 1D rod-like micelles to 2D uniform diamondlike micelles was achieved by the thermally induced nucleation SA. The sizes of the 2D diamond-like micelles could be tuned by the annealing temperature and the ratio of unimer to seed. It is demonstrated that the morphology transformation from rod-like micelles to diamond-like micelles was based on energetics including thermodynamic and kinetic points.
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