RGD peptides induce apoptosis by direct caspase-3 activation

Synthetic peptides containing the arginine-glycine-aspartate (RGD) motif have been used extensively as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration, growth and differentiation, because the RGD motif is an integrin-recognition motif found in many ligands. Here we report that RGD-containing peptides are able to directly induce apoptosis without any requirement for integrin-mediated cell clustering or signals. We show that RGD-containing peptides enter cells and directly induce autoprocessing and enzymatic activity of procaspase-3, a pro-apoptotic protein. Using the breast carcinoma cell line MCF-7, which has a functional deletion of the caspase-3 gene, we confirm that caspase-3 is required for RGD-mediated cell death. In addition to an RGD motif, pro-caspase-3 also contains a potential RGD-binding motif, aspartate-aspartate-methionine (DDM), near the site of processing to produce the p12 and p17 subunits. On the basis of the ability of RGD-DDX interactions to trigger integrin activation, we suggest that RGD peptides induce apoptosis by triggering conformational changes that promote pro-caspase-3 autoprocessing and activation. These findings provide an alternative molecular explanation for the potent proapoptotic properties of RGD peptides in models of angiogenesis, inflammation and cancer metastasis.     

Multiple seismic discontinuities near the base of the transition zone in the Earth's mantle

The seismologically defined boundary between the transition zone in the Earth's mantle (410-660 km depth) and the underlying lower mantle is generally interpreted to result from the breakdown of the gamma-spinel phase of olivine to magnesium-perovskite and magnesiowustite. Laboratory measurements of these transformations of olivine have determined that the phase boundary has a negative Clapeyron slope and does indeed occur near pressures corresponding to the base of the transition zone. But a computational study has indicated that, because of the presence of garnet minerals, multiple seismic discontinuities might exist near a depth of 660 km (ref. 4), which would alter the simple negative correlation of changes in temperature with changes in the depth of the phase boundary. In particular, garnet minerals undergo exothermic transformations near this depth, acting to complicate the phase relations and possibly effecting mantle convection processes in some regions. Here we present seismic evidence that supports the existence of such multiple transitions near a depth of 660 km beneath southern California. The observations are consistent with having been generated by garnet transformations coupling with the dissociation of the gamma-spinel phase of olivine. Temperature anomalies calculated from the imaged discontinuity depths--using Clapeyron slopes determined for the various transformations--generally match those predicted from an independent P-wave velocity model of the region.     

A method for the separation and estimation of catechol amines in urine

Zusammenfassung Es wird eine neue Methode zur Bestimmung der Katecholamine im Harn beschrieben. Die Katecholamine werden im Harn acetyliert und die Acetylderivate papierchromatographisch im Bush-?C?-System getrennt. Nach erfolgter Trennung werden die einzelnen Katecholamine mit ?thylendiamin kondensiert und fluorimetrisch untersucht. Eine Spezifit?tserh?hung der Methode durch Anwendung doppelt markierter Isotopen wird in Betracht gezogen.      

Collective synthesis of natural products by means of organocascade catalysis

Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine.     

Periodicity of S35 uptake in rat femurs

Résumé Du radio-soufre a été administré intraveineusement à des rats à 09.00 h et à d'autres à 21.00 h, et ils ont été sacrifiés 2–3, 4, 8 et 12 h après l'injection. L'analyse microdensitométrique d'autoradiographies des fémurs a indiqué que la concentration et la rétention du traceur dans le cartilage de conjugaison étaient plus grandes dans les rats traités à 09.00 h. Les tissus non-cartilagineux n'ont pas montré de changements pareils.

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This work was performed under the auspices of the Atomic Energy Commission.