Associations of common polymorphisms in GCKR with type 2 diabetes and related traits in a Han Chinese population: a case-control study

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that variants in the glucokinase regulatory protein gene (<it>GCKR</it>) were associated with type 2 diabetes and dyslipidemia. The purpose of this study was to examine whether tag single nucleotide polymorphisms (SNPs) in the <it>GCKR </it>region were associated with type 2 diabetes and related traits in a Han Chinese population and to identify the potential mechanisms underlying these associations.</p> <p>Methods</p> <p>We investigated the association of polymorphisms in the <it>GCKR </it>gene with type 2 diabetes by employing a case-control study design (1118 cases and 1161 controls). Four tag SNPs (rs8179206, rs2293572, rs3817588 and rs780094) with pairwise r²> 0.8 and minor allele frequency > 0.05 across the <it>GCKR </it>gene and its flanking regions were studied and haplotypes were constructed. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using a MassARRAY platform.</p> <p>Results</p> <p>The G alleles of <it>GCKR </it>rs3817588 and rs780094 were associated with an increased risk of type 2 diabetes after adjustment for year of birth, sex and BMI (OR = 1.24, 95% CI 1.08-1.43, p = 0.002 and OR = 1.22, 95% CI 1.07-1.38, p = 0.002, respectively). In the non-diabetic controls, the GG carriers of rs3817588 and rs780094 were nominally associated with a lower plasma triglyceride level compared to the AA carriers after adjustment for year of birth, sex and BMI (p for trend = 0.00004 and 0.03, respectively). Furthermore, the association of rs3817588 with plasma triglyceride level was still significant after correcting for multiple testing.</p> <p>Conclusions</p> <p>The rs3817588 A/G polymorphism of the <it>GCKR </it>gene was associated with type 2 diabetes and plasma triglyceride level in the Han Chinese population.</p

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Human genetics in troubled times and places

Abstract The development of human genetics world-wide during the twentieth century, especially across Europe, has occurred against a background of repeated catastrophes, including two world wars and the ideological problems and repression posed by Nazism and Communism. The published scientific literature gives few hints of these problems and there is a danger that they will be forgotten. The First World War was largely indiscriminate in its carnage, but World War 2 and the preceding years of fascism were associated with widespread migration, especially of Jewish workers expelled from Germany, and of their children, a number of whom would become major contributors to the post-war generation of human and medical geneticists in Britain and America. In Germany itself, eminent geneticists were also involved in the abuses carried out in the name of ‘eugenics’ and ‘race biology’. However, geneticists in America, Britain and the rest of Europe were largely responsible for the ideological foundations of these abuses. In the Soviet Union, geneticists and genetics itself became the object of persecution from the 1930s till as late as the mid 1960s, with an almost complete destruction of the field during this time; this extended also to Eastern Europe and China as part of the influence of Russian communism. Most recently, at the end of the twentieth century, China saw a renewal of government sponsored eugenics programmes, now mostly discarded. During the post-world war 2 decades, human genetics research benefited greatly from recognition of the genetic dangers posed by exposure to radiation, following the atomic bomb explosions in Japan, atmospheric testing and successive accidental nuclear disasters in Russia. Documenting and remembering these traumatic events, now largely forgotten among younger workers, is essential if we are to fully understand the history of human genetics and avoid the repetition of similar disasters in the future. The power of modern human genetic and genomic techniques now gives a greater potential for abuse as well as for beneficial use than has ever been seen in the past

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Discovery That Theonellasterol a Marine Sponge Sterol Is a Highly Selective FXR Antagonist That Protects against Liver Injury in Cholestasis

Background: The farnesoid-x-receptor (FXR) is a bile acid sensor expressed in the liver and gastrointestinal tract. Despite FXR ligands are under investigation for treatment of cholestasis, a biochemical condition occurring in a number of liver diseases for which available therapies are poorly effective, mice harboring a disrupted FXR are protected against liver injury caused by bile acid overload in rodent models of cholestasis. Theonellasterol is a 4-methylene-24-ethylsteroid isolated from the marine sponge Theonella swinhoei. Here, we have characterized the activity of this theonellasterol on FXR-regulated genes and biological functions. Principal Findings: Interrogation of HepG2 cells, a human hepatocyte cell line, by microarray analysis and transactivation assay shows that theonellasterol is a selective FXR antagonist, devoid of any agonistic or antagonistic activity on a number of human nuclear receptors including the vitamin D receptor, PPARs, PXR, LXRs, progesterone, estrogen, glucorticoid and thyroid receptors, among others. Exposure of HepG2 cells to theonellasterol antagonizes the effect of natural and synthetic FXR agonists on FXR-regulated genes, including SHP, OSTa, BSEP and MRP4. A proof-of-concept study carried out to investigate whether FXR antagonism rescues mice from liver injury caused by the ligation of the common bile duct, a model of obstructive cholestasis, demonstrated that theonellasterol attenuates injury caused by bile duct ligation as measured by assessing serum alanine aminostrasferase levels and extent of liver necrosis at histopathology. Analysis of genes involved in bile acid uptake and excretion by hepatocytes revealed that theonellasterol increases the liver expression of MRP4, a basolateral transporter that is negatively regulated by FXR. Administering bile duct ligated mice with an FXR agonist failed to rescue from liver injury and downregulated the expression of MRP4. Conclusions: FXR antagonism in vivo results in a positive modulation of MRP4 expression in the liver and is a feasible strategy to target obstructive cholestasis