Expression and Function of Osteopontin in Vascular Adventitial Fibroblasts and Pathological Vascular Remodeling

Osteopontin is known to play important roles in various diseases including vascular disorders. However, little is known about its expression and function in vascular adventitial fibroblasts. Adventitial fibroblasts have been shown to play a key role in pathological vascular remodeling associating with various vascular disorders. In this study, we measured activation of Osteopontin and its biological functions in cultured adventitial fibroblasts and injured rat carotid injury arteries induced by balloon angioplasty. Our results showed that angiotensin II and aldosterone increased Osteopontin expression in adventitial fibroblasts in a time- and concentration-dependent manner. MAPKs and AP-1 pathways were involved in Osteopontin upregulation. In addition, Adventitial fibroblast migration stimulated by Angiotensin II and aldosterone required OPN expression. Perivascular delivery of antisense oligonucleotide for Osteopontin suppressed neointimal formation post-injury. We concluded that upregulation of Osteopontin expression in adventitial fibroblasts might be important in the pathogenesis of vascular remodeling after arterial injury

The exocyclic functionalisation of bis(thiosemicarbazonate) complexes of zinc and copper: the synthesis of monomeric and dimeric species.

This paper reports the synthesis of bimetallic zinc thiosemicarbazone complexes with rigid aromatic linkers, using either 1,3- or 1,4- benzenediamines or 1,3- or 1,4- benzenedialdehydes as the basis of the linking groups. Non-rigid aliphatic diamines and dialdehydes were also used to link the zinc chelating units. Reaction of a bis(thiosemicarbazone) with a pendant NHNH(2) group with monoaldehydes or ketones gives a range of monomeric complexes with exocylic imine groups bearing a range of substituents. The zinc complexes can be quantitatively and rapidly transmetallated to the corresponding copper complexes and this route or direct reaction with the free ligand can be used to radiolabel the monomeric species with (64)Cu. In vivo and in vitro studies of one of the (64)Cu imine complexes shows substantial hypoxic selectivity and high tumour uptake in a murine model

New bimetallic compounds based on the bis(thiosemicarbazonato) motif.

Zinc and copper bis(thiosemicarbazonato) complexes containing more than one metal centre have been prepared with a view to examining their application for molecular imaging. The zinc complexes are fluorescent with excitation and emission at relatively long wavelengths. The dinuclear copper complex undergoes two sequential, quasi-reversible reductions

Convex Global Underestimation For Molecular Structure Prediction

Key problems in computational biology, including protein and RNA folding and drug docking, involve conformational searching. Current search methods -- Monte Carlo, Molecular Dynamics, Simulated Annealing, and Genetic Algorithms -- are too slow for protein folding by many orders of magnitude. They get stuck in kinetic traps. We describe a global optimization method, the CGU method, which appears to be very promising. We know the method always finds the same conformation from 100 different starting points, indicating that it finds the unique global minimum for the many different sequences we have tried. We know the CGU doesn't get stuck in kinetic traps because the search time is independent of the shapes of the landscapes (amino acid sequence and composition). We know that the method is much faster than a standard Simulated Annealing algorithm that we have tested: the SA method doesn't find global minima for chains longer than 10 residues, and the performance advantage of the CGU method increases with chain length. And computational results show that the computer time scales with n 4 where n is the number of degrees of freedom, and we consistently reach the global minimum of the model energy function for PPT, a 36-amino acid peptide (n = 72), in less than 3 hours on a 32 processor Cray T3E. Keywords: Convex Global Underestimation, Protein Folding, Simulated Annealing, Computational Biology, Molecular Structure 1 2 1.