Abstract:
This study examined the association of HP genotypes with subclinical CVD, T2DM risk, and associated risk factors in a T2DM-enriched sample. Haptoglobin genotypes were determined in 1208 European Americans (EA) from 473 Diabetes Heart Study (DHS) families via PCR. Three promoter SNPs (rs5467, rs5470, and rs5471) were also genotyped.Analyses revealed association between HP2-2 duplication and increased carotid intima-media thickness (IMT; p？=？0.001). No association between HP and measures of calcified arterial plaque were observed, but the HP polymorphism was associated with triglyceride concentrations (p？=？0.005) and CVD mortality (p？=？0.04). We found that the HP2-2 genotype was associated with increased T2DM risk with an odds ratio (OR) of 1.49 (95% CI 1.18-1.86, p？=？6.59x10-4). Promoter SNPs were not associated with any traits.This study suggests association between the HP duplication and IMT, triglycerides, CVD mortality, and T2DM in an EA population enriched for T2DM. Lack of association with atherosclerotic calcified plaque likely reflect differences in the pathogenesis of these CVD phenotypes. HP variation may contribute to the heritable risk for CVD complications in T2DM.Cardiovascular disease (CVD) is one of the major complications associated with type 2 diabetes mellitus (T2DM). As of 2011, 25.8 million Americans had diagnosed T2DM [1]. More than 50% of individuals with T2DM had coronary heart disease, stroke, or cardiac disease [2]. T2DM is an independent risk factor for development of CVD with the relative risk of CVD mortality of 2.1 in men and 4.9 in women, relative to non-T2DM affected individuals [3,4]. There is increasing evidence that genetic and environmental factors contribute to this risk.Haptoglobin (HP) is a 54 kDa protein, found abundantly in the serum [5,6]. The HP gene has two major alleles: HP1, (containing five exons) and HP2, (containing seven exons) which likely arose from a duplication event involving exons 3 and 4, producing a 61 kDa pro

Abstract:
The Science of molecular size machines and its engineering designs and constructions until late 1980s were not considered practicable. Nanotechnology, according to the leading exponents of that time were neither feasible nor viable, due to the fact of total structural difference of the constituent of nano-molecular device i.e. Atoms from the mechanical objects of every day life. The essential components of engineering mechanics i.e. cogwheels, gears or motors could not be imagined to have formed by means of atoms, that are characterized by fuzzy and unsubstantial contents having no definite location position.

Abstract:
CAC was measured using the Agatston score with multidetector computed tomography. Information on CAC and MCP-1 was obtained in 2246 whites and 470 African Americans (mean age 55 years) without a history of coronary heart disease (CHD). Information on sICAM-1 was obtained for white participants only.In whites, after adjustment for age and gender, the odds ratios (ORs) of CAC (CAC > 0) associated with the second, third, fourth, and fifth quintiles of sICAM-1 compared to the first quintile were 1.22 (95% confidence interval [CI]: 0.91–1.63), 1.15 (0.84–1.58), 1.49 (1.09–2.05), and 1.72 (1.26–2.36) (p = 0.0005 for trend test), respectively. The corresponding ORs for the second to fifth quintiles of MCP-1 were 1.26 (0.92–1.73), 0.99 (0.73–1.34), 1.42 (1.03–1.96), and 2.00 (1.43–2.79) (p < 0.0001 for trend test), respectively. In multivariable analysis that additionally adjusted for other CHD risk factors, the association of CAC with sICAM-1 and MCP-1 was attenuated and no longer statistically significant. In African Americans, the age and gender-adjusted ORs of CAC associated with the second and third tertiles of MCP-1 compared to the first tertile were 1.16 (0.64–2.08) and 1.25 (0.70–2.23) (p = 0.44 for trend test), respectively. This result did not change materially after additional adjustment for other CHD risk factors. Test of race interaction showed that the magnitude of association between MCP-1 and CAC did not differ significantly between African Americans and whites. Similar results were obtained when CAC ≥ 10 was analyzed as an outcome for both MCP-1 and sICAM-1.This study suggests that sICAM-1 and MCP-1 are biomarkers of coronary atherosclerotic burden and their association with CAC was mainly driven by established CHD risk factors.Response of the endothelium to injuries to the arterial wall, including increased expression of inflammatory markers, is a well-recognized component of atherosclerosis [1]. Critical steps involved in the early phase of atherosclerosi

Abstract:
Background Coronary heart disease (CHD) incidence has declined significantly in the US, as have levels of major coronary risk factors, including LDL-cholesterol, hypertension and smoking, but whether trends in subclinical atherosclerosis mirror these trends is not known. Methods and Findings To describe recent secular trends in subclinical atherosclerosis as measured by serial evaluations of coronary artery calcification (CAC) prevalence in a population over 10 years, we measured CAC using computed tomography (CT) and CHD risk factors in five serial cross-sectional samples of men and women from four race/ethnic groups, aged 55–84 and without clinical cardiovascular disease, who were members of Multi-Ethnic Study of Atherosclerosis (MESA) cohort from 2000 to 2012. Sample sizes ranged from 1062 to 4837. After adjusting for age, gender, and CT scanner, the prevalence of CAC increased across exams among African Americans, whose prevalence of CAC was 52.4% in 2000–02, 50.4% in 2003–04, 60.0% is 2005–06, 57.4% in 2007–08, and 61.3% in 2010–12 (p for trend <0.001). The trend was strongest among African Americans aged 55–64 [prevalence ratio for 2010–12 vs. 2000–02, 1.59 (95% confidence interval 1.06, 2.39); p = 0.005 for trend across exams]. There were no consistent trends in any other ethnic group. Risk factors generally improved in the cohort, and adjustment for risk factors did not change trends in CAC prevalence. Conclusions There was a significant secular trend towards increased prevalence of CAC over 10 years among African Americans and no change in three other ethnic groups. Trends did not reflect concurrent general improvement in risk factors. The trend towards a higher prevalence of CAC in African Americans suggests that CHD risk in this population is not improving relative to other groups.

Abstract:
The protein Keap1 is central to the regulation of the Nrf2-mediated cytoprotective response, and is increasingly recognized as an important target for therapeutic intervention in a range of diseases involving excessive oxidative stress and inflammation. The BTB domain of Keap1 plays key roles in sensing environmental electrophiles and in mediating interactions with the Cul3/Rbx1 E3 ubiquitin ligase system, and is believed to be the target for several small molecule covalent activators of the Nrf2 pathway. However, despite structural information being available for several BTB domains from related proteins, there have been no reported crystal structures of Keap1 BTB, and this has precluded a detailed understanding of its mechanism of action and interaction with antagonists. We report here the first structure of the BTB domain of Keap1, which is thought to contain the key cysteine residue responsible for interaction with electrophiles, as well as structures of the covalent complex with the antagonist CDDO/bardoxolone, and of the constitutively inactive C151W BTB mutant. In addition to providing the first structural confirmation of antagonist binding to Keap1 BTB, we also present biochemical evidence that adduction of Cys 151 by CDDO is capable of inhibiting the binding of Cul3 to Keap1, and discuss how this class of compound might exert Nrf2 activation through disruption of the BTB-Cul3 interface.

Abstract:
Advances in white clover research and biological nitrogen fixation as reflected in the proceedings of the XIII International botanical Congress, Sydney, Australia, 21-28 Aug., 1981. Abstract, collected and produced by D. J. Carr.

Abstract:
We discuss spherically symmetric perfect fluid solutions of Einstein's equations which have equation of state ($p=\alpha \mu$) and which are self-similar in the sense that all dimensionless variables depend only upon $z\equiv r/t$. For each value of $\alpha$, such solutions are described by two parameters and have now been completely classified. There is a 1-parameter family of solutions asymptotic to the flat Friedmann model at large values of z. These represent either black holes or density perturbations which grow as fast as the particle horizon; the underdense solutions may be relevant to the existence of large-scale cosmic voids. There is also a 1-parameter family of solutions asymptotic to a self-similar Kantowski-Sachs model at large z. These are probably only physically realistic for $-1<\alpha<-1/3$, in which case they may relate to the formation of bubbles in an inflationary universe. There is a 2-parameter family of solutions associated with a self-similar static solution at large z. This family contains solutions with naked singularities and this includes the ``critical'' solution discovered in recent collapse calculations for $\alpha < 0.28$. Finally, for $\alpha >1/5$, there is a family of solutions which are asymptotically Minkowski. These asymptote either to infinite z, in which case they are described by one parameter, or to a finite value of z, in which case they are described by two parameters and this includes the ``critical'' solution for $\alpha >0.28$. We discuss the stability of spherically symmetric similarity solutions to more general (non-self-similar) spherically symmetric perturbations.

Abstract:
We classify all spherically symmetric dust solutions of Einstein's equations which are self-similar in the sense that all dimensionless variables depend only upon $z\equiv r/t$. We show that the equations can be reduced to a special case of the general perfect fluid models with equation of state $p=\alpha \mu$. The most general dust solution can be written down explicitly and is described by two parameters. The first one (E) corresponds to the asymptotic energy at large $|z|$, while the second one (D) specifies the value of z at the singularity which characterizes such models. The E=D=0 solution is just the flat Friedmann model. The 1-parameter family of solutions with z>0 and D=0 are inhomogeneous cosmological models which expand from a Big Bang singularity at t=0 and are asymptotically Friedmann at large z; models with E>0 are everywhere underdense relative to Friedmann and expand forever, while those with E<0 are everywhere overdense and recollapse to a black hole containing another singularity. The black hole always has an apparent horizon but need not have an event horizon. The D=0 solutions with z<0 are just the time reverse of the z>0 ones. The 2-parameter solutions with D>0 again represent inhomogeneous cosmological models but the Big Bang singularity is at $z=-1/D$, the Big Crunch singularity is at $z=+1/D$, and any particular solution necessarily spans both z<0 and z>0. While there is no static model in the dust case, all these solutions are asymptotically ``quasi-static'' at large $|z|$. As in the D=0 case, the ones with $E \ge 0$ expand or contract monotonically but the latter may now contain a naked singularity. The ones with E<0 expand from or recollapse to a second singularity, the latter containing a black hole.

Abstract:
Primordial black holes (PBHs) are of special interest because of the crucial role of quantum effects in their formation and evaporation. This means that they provide a unique probe of the early universe, high-energy physics and quantum gravity. We highlight some recent developments in the subject, including improved limits on the fraction of the Universe going into evaporating PBHs in the mass range $10^{9} - 10^{17}$ g and the possibility of using PBHs to probe a cosmological bounce.

Abstract:
Cosmological nucleosynthesis calculations imply that many of the baryons in the Universe must be dark. We discuss the likelihood that some of these dark baryons may reside in the discs or halos of galaxies. If they were in the form of compact objects, they would then be natural MACHO candidates, in which case they are likely to be the remnants of a first generation of pregalactic or protogalactic Population III stars. Various candidates have been proposed for such remnants - brown dwarfs, red dwarfs, white dwarfs, neutron stars or black holes - and we review the many types of observations (including microlensing searches) which can be used to constrain or exclude them.