Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2x10(-201)), ABCG2 (p = 3.1x10(-26)), SLC17A1 (p = 3.0x10(-14)), SLC22A11 (p = 6.7x10(-14)), SLC22A12 (p = 2.0x10(-9)), SLC16A9 (p = 1.1x10(-8)), GCKR (p = 1.4x10(-9)), LRRC16A (p = 8.5x10(-9)), and near PDZK1 (p = 2.7x10(-9)). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0x10(-26)) and propionyl-L-carnitine (p = 5.0x10(-8)) concentrations, which in turn were associated with serum UA levels (p = 1.4x10(-57) and p = 8.1x10(-54), respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.

Manifestação solicitada pelo TCU à CONOF/CD acerca de relatório preliminar, relativo à consulta sobre a aplicação da Lei Complementar nº 141, de 2012, formulada pela Comissão de Seguridade Social e Família/CD : TC 046.061/2012‐6

Avalia o relatório elaborado pelo TCU acerca da consulta formulada pela CSSF/CD(TC 046.061/2012‐6). Procura a pacificação de entendimento no âmbito do Congresso Nacional.

~(143)Dy和~(141)Dy的β缓发质子衰变与自旋指认

分析了143Dy和141Dy的β缓发质子衰变的数据,对比计算了这两种核的核位能面。从中看到了143Dy的衰变包括有1/2+基态和11/2-同核异能态的两种衰变成分,并且确定了它们的半衰期分别为(6.0±1.5)s和(3.0±0.5)s。同时也测定了141Dy的半衰期为(0.9±0.2)s,并指认了它的自旋宇称为9/2-。

~(140)Tb和~(141)Dy的β缓发质子衰变以及~(143)Dy的自旋宇称

利用40Ca+106Cd融合蒸发反应产生了近质子滴线核140Tb和141Dy,配合氦喷嘴带传输系统采用“质子-γ”符合方法观测了它们的β缓发质子衰变,其中包括半衰期、质子能谱和衰变到第二代子核不同低位态的分支比．通过统计理论拟合提取了140Tb和141Dy的基态自旋宇称分别为7±和9／2±．另一方面,用Woods-Saxon Strutinsky方法计算了这两种核限制组态的势能面,由此得到140Tb和141Dy的基态自旋宇称分别为7+和9／2-．此外用同一方法还计算了143Dy的核势能面,从中看出143Dy存在有自旋宇称为1／2+的基态和一个激发能为198keV的11／2-的同质异能态．该结果与2003年Eur．Phys．J． A16:347-351中的143Dy衰变实验数据相符．

~(141)Nd激发态的在束γ谱学研究

通过1 3 0 Te(1 6O ,5nγ) 1 4 1 Nd反应布居了1 4 1 Nd的高自旋态能级 .对反应产生的在束γ射线进行了γ射线单谱和γ -γ符合测量 .建立了激发能达 76 1 4 .5keV的1 4 1 Nd能级纲图 ,新发现了 1 2条γ射线和 1 5个能级 .基于实验测量的γ跃迁各向异性 ,建议了1 4 1 Nd部分能级的自旋值 .用一个h1 1 2 价中子空穴与1 4 2 Nd核芯晕态的耦合可以定性地解释1 4 1 Nd的能级结构

~(141)Nd中的粒子-核芯耦合

通过~(130)Te(~(16)O,5nγ)~(141)Nd反应研究了~(141)Nd的高自旋态。建立了激发能达7614.5keV的~(141)Nd能级纲图,新发现了12条γ射线和15个能级。用粒子-振子模型和半经验壳模型分别计算了~(141)Nd的集体和单粒子激发的能级位置。根据计算的能级位置以及实验测量得到的γ跃迁强度和多极性信息,讨论了~(141)Nd激发态的能级结构。

beta-delayed proton decays and spin assignments for Tb-140, Dy-141 and Dy-143

The proton-rich isotopes Tb-140 and Dy-141 were produced via the fusion evaporation reaction Ca-40+ Cd-106. Their beta-delayed proton decays were studied by p-gamma coincidence in combination with a He-jet tape transport system, and half-lives, proton energy spectra, gamma-transitions following the proton emission, as well as beta-delayed proton branching ratios to the low-lying states in the grand-daughter nuclei were determined. Comparing the experimental data with statistical model calculations, the ground-state spins of Tb-140 and Dy-141 were found to be consistent with 7 and 9/2, respectively. The configuration-constrained nuclear potential energy surfaces (NPES) of Tb-140 and Dy-141 were calculated using the Woods-Saxon-Strutinsky method, which suggest the ground-state spins and parities of Tb-140 and Dy-141 to be 7(+) and 9/2(-), respectively. In addition, the configuration-constrained NPES of Dy-143 were calculated, which predict a 1/2(+) ground state and a 11/2(-) isomer with excitation energy of 198 keV. These findings are consistent with our previous experimental data on Dy-143 reported in Eur. Phys. J. A 16, 347 (2003).

Revisiting human IL-12Rβ1 deficiency: A survey of 141 patients from 30 countries

Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought. © 2010 Lippincott Williams & Wilkins.