Torrey Pines Institute for Molecular Studies

About: Torrey Pines Institute for Molecular Studies is a nonprofit organization based out in San Diego, California, United States. It is known for research contribution in the topics: T cell & Antigen. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.

Vitamin D receptor alleles and rates of bone loss : influences of years since menopause and calcium intake

Abstract: A genetic marker for the 1,25-dihydroxyvitamin D receptor (VDR) is reported to account for much of the heritable component of bone density. It is not known whether VDR genotype influences bone accretion or loss, or how it is related to calcium metabolism. The VDR genotype was determined in 229 healthy postmenopausal women who previously participated in a calcium trial. VDR alleles were designated according to presence (b) or absence (B) of the BsmI restriction enzyme cutting site. There were 83 bb, 102 Bb, and 44 BB individuals. Two-thirds of the women took 500 mg of calcium supplement (mean calcium intake = 892 mg/day) and one-third a placebo (mean = 376 mg/day). Bone mineral density (BMD) at the femoral neck, spine, and radius were measured by dual- and single-photon absorptiometry at baseline and after 1 and 2 years. Among women more than 10 years postmenopausal, those with the BB genotype had the lowest femoral neck BMD. Rates of bone loss over 2 years were greater in the BB group at all sites (e.g., at the femoral neck, bb, 0.45 ± 0.43; Bb, -0.01 ± 0.40; BB, -0.99 ± 0.50%/year; BB vs. bb, p = 0.01), and this trend was found both in women <10 years since menopause (e.g., at the radius, bb, 0.43 ± 0.47; Bb, -0.37 ± 0.42; BB, -1.20 ± 0.59% per year; BB vs. bb, p = 0.02) and those ≥10 years (radius, bb, -0.71 ± 0.41; Bb, 0.08 ± 0.39; BB, -1.41 ± 0.49% per year; BB vs. Bb, p < 0.01). At the femoral neck, bone loss appeared to be modified by calcium intake (e.g., in the BB genotype: +0.03 ± 0.61 in supplemented vs. -2.01 ± 0.75%/year in placebo, in bb: 0.57 ± 0.58 vs. 0.32 ± 0.47%/year; interaction term p = 0.09), and this trend was also present in both early and late menopause. Rates of change at the radius and spine in BB were not significantly influenced by calcium at the intake levels of this study group. These results indicate that postmenopausal bone loss is influenced by the VDR genotype and suggest the adverse effect of the susceptible allele at the hip may be reduced by raising calcium intake.

From exogenous to endogenous: the inevitable imprint of mass spectrometry in metabolomics.

Abstract: Mass spectrometry (MS) is an established technology in drug metabolite analysis and is now expanding into endogenous metabolite research. Its utility derives from its wide dynamic range, reproducible quantitative analysis, and the ability to analyze biofluids with extreme molecular complexity. The aims of developing mass spectrometry for metabolomics range from understanding basic biochemistry to biomarker discovery and the structural characterization of physiologically important metabolites. In this review, we will discuss the techniques involved in this exciting area and the current and future applications of this field.

Rac recruits high-affinity integrin αvβ3 to lamellipodia in endothelial cell migration

Abstract: Integrin alphavbeta3 has an important role in the proliferation, survival, invasion and migration of vascular endothelial cells. Like other integrins, alphavbeta3 can exist in different functional states with respect to ligand binding. These changes involve both affinity modulation, by which conformational changes in the integrin heterodimer govern affinity for individual extracellular matrix proteins, and avidity modulation, by which changes in lateral mobility and integrin clustering affect the binding of cells to multivalent matrices. Here we have used an engineered monoclonal antibody Fab (antigen-binding fragment) named WOW-1, which binds to activated integrins alphavbeta3 and alphavbeta5 from several species, to investigate the role of alphavbeta3 activation in endothelial cell behaviour. Because WOW-1 is monovalent, it is insensitive to changes in integrin clustering and therefore reports only changes in affinity. WOW-1 contains an RGD tract in its variable region and binds only to unoccupied, high-affinity integrins. By using WOW-1, we have identified the selective recruitment of high-affinity integrins as a mechanism by which lamellipodia promote formation of new adhesions at the leading edge in cell migration.