CMB anisotropies from vector perturbations in the bulk

The vector perturbations induced on the brane by gravitational waves propagating in the bulk are studied in a cosmological framework. Cosmic expansion arises from the brane motion in a non-compact five-dimensional anti-de Sitter spacetime. By solving the vector perturbation equations in the bulk, for generic initial conditions, we find that they give rise to growing modes on the brane in the Friedmann-Lema\^{\i}tre era. Among these modes, we exhibit a class of normalizable perturbations, which are exponentially growing with respect to conformal time on the brane. The presence of these modes is, at least, strongly constrained by the current observations of the cosmic microwave background (CMB). We estimate the anisotropies they induce in the CMB, and derive quantitative constraints on the allowed amplitude of their primordial spectrum. Our results provide stringent constraints for all braneworld models with bulk inflation.Comment: 17 pages, ReVTeX4, submitted to Phys.Rev.

On T-Duality in Brane Gas Cosmology

In the context of homogeneous and isotropic superstring cosmology, the T-duality symmetry of string theory has been used to argue that for a background space-time described by dilaton gravity with strings as matter sources, the cosmological evolution of the Universe will be nonsingular. In this Letter we discuss how T-duality extends to brane gas cosmology, an approximation in which the background space-time is again described by dilaton gravity with a gas of branes as a matter source. We conclude that the arguments for nonsingular cosmological evolution remain valid.Comment: 8 pages, Appendix adde

Dynamical Instabilities of the Randall-Sundrum Model

We derive dynamical equations to describe a single 3-brane containing fluid matter and a scalar field coupling to the dilaton and the gravitational field in a five dimensional bulk. First, we show that a scalar field or an arbitrary fluid on the brane cannot evolve to cancel the cosmological constant in the bulk. Then we show that the Randall-Sundrum model is unstable under small deviations from the fine-tuning between the brane tension and the bulk cosmological constant and even under homogeneous gravitational perturbations. Implications for brane world cosmologies are discussed.Comment: 12 pages, 2 figure

Perturbations on a moving D3-brane and mirage cosmology

We study the evolution of perturbations on a moving probe D3-brane coupled to a 4-form field in an AdS$_5$-Schwarzschild bulk. The unperturbed dynamics are parametrised by a conserved energy $E$ and lead to Friedmann-Robertson-Walker `mirage' cosmology on the brane with scale factor $a(\tau)$. The fluctuations about the unperturbed worldsheet are then described by a scalar field $\phi(\tau,\vec{x})$. We derive an equation of motion for $\phi$, and find that in certain regimes of $a$ the effective mass squared is negative. On an expanding BPS brane with E=0 superhorizon modes grow as $a^4$ whilst subhorizon modes are stable. When the brane contracts, all modes grow. We also briefly discuss the case when $E>0$, BPS anti-branes as well as non-BPS branes. Finally, the perturbed brane embedding gives rise to scalar perturbations in the FRW universe. We show that $\phi$ is proportional to the gauge invariant Bardeen potentials on the brane.Comment: 26 pages, 5 figures, to appear in Phys.Rev.D, comments and minor corrections adde

Co-expressed immune and metabolic genes in visceral and subcutaneous adipose tissue from severely obese individuals are associated with plasma HDL and glucose levels: a microarray study

<p>Abstract</p> <p>Background</p> <p>Excessive accumulation of body fat, in particular in the visceral fat depot, is a major risk factor to develop a variety of diseases such as type 2 diabetes. The mechanisms underlying the increased risk of obese individuals to develop co-morbid diseases are largely unclear.</p> <p>We aimed to identify genes expressed in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) that are related to blood parameters involved in obesity co-morbidity, such as plasma lipid and glucose levels, and to compare gene expression between the fat depots.</p> <p>Methods</p> <p>Whole-transcriptome SAT and VAT gene expression levels were determined in 75 individuals with a BMI >35 kg/m². Modules of co-expressed genes likely to be functionally related were identified and correlated with BMI, plasma levels of glucose, insulin, HbA_1c, triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol.</p> <p>Results</p> <p>Of the approximately 70 modules identified in SAT and VAT, three SAT modules were inversely associated with plasma HDL-cholesterol levels, and a fourth module was inversely associated with both plasma glucose and plasma triglyceride levels (p < 5.33 × 10^-5). These modules were markedly enriched in immune and metabolic genes. In VAT, one module was associated with both BMI and insulin, and another with plasma glucose (p < 4.64 × 10^-5). This module was also enriched in inflammatory genes and showed a marked overlap in gene content with the SAT modules related to HDL. Several genes differentially expressed in SAT and VAT were identified.</p> <p>Conclusions</p> <p>In obese subjects, groups of co-expressed genes were identified that correlated with lipid and glucose metabolism parameters; they were enriched with immune genes. A number of genes were identified of which the expression in SAT correlated with plasma HDL cholesterol, while their expression in VAT correlated with plasma glucose. This underlines both the singular importance of these genes for lipid and glucose metabolism and the specific roles of these two fat depots in this respect.</p

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Cosmology of brane universes and brane gases

Nous étudions le comportement dynamique et perturbateur de certains modèles cosmologiques inspirés par la théorie des cordes. Celle-ci est une théorie de la gravité quantique qui est fort probablement nécessaire pour comprendre l'origine de notre univers. Ses prédictions (l'existence des dimensions supplémentaires et des p-branes) sont très intéressantes pour la cosmologie. D'abord, notre univers est identifié avec une 3-brane plongée dans un espace-temps cinq-dimensionnel. Nous montrons que le modèle de Randall-Sundrum se base sur un fine-tuning qui pose de graves problèmes dans un contexte cosmologique. Nous estimons également les anisotropies du CMB pour des univers branaires anti-de Sitter. Il se trouve qu'elles ne sont pas compatibles avec un univers homogène et isotrope. Ensuite nous étudions la cosmologie des gaz de branes. Ce scénario permet d'éviter la singularité initiale du big bang et, en même temps, il offre une explication du pourquoi nous vivons dans un univers tri-dimensionnel