Thermal stability of the Z conformation of the hexanucleoside pentaphosphate d(br5CGbr5CGbr5CG): evidence for a conformational transition before melting

The thermal stability of the hexanucleoside pentaphosphate d(br5CGbr5CGbr5CG) has been studied at two nucleotide concentrations, in the presence of 1 M NaClO4. At low nucleotide concentration (7 X 10(-5) M), circular dichroism experiments show a conformational transition from the Z conformation to another conformation, named X, which is not the B conformation, as the temperature is increased from 0 to 35 degrees C. Between 40 and 65 degrees C, another transition is observed which corresponds to the melting of the X conformation. At higher nucleotide concentration (2 X 10(-3) M), circular dichroism and 31P nuclear magnetic resonance experiments show that at low temperature (br5dC-dG)3 adopts the Z conformation. There are associations between the oligonucleotides which progressively disappear as the temperature increases. In the range 35-60 degrees C a transition from the Z conformation to another conformation is observed. This new conformation is the X conformation detected at low nucleotide concentration.     

A Curve-Free Bayesian Decision-Theoretic Design for Phase Ia/Ib Trials Considering Both Safety and Efficacy Outcomes

A curve-free, Bayesian decision-theoretic two-stage design is proposed to select biological efficacious doses (BEDs) for phase Ia/Ib trials in which both t     

Antibodies to adenosine 5'-monophosphate: purification and specificity.

Antibodies to adenosine-5'-monophosphate were produced in rabbits by injecting a conjugate of the nucleotide (oxidized with periodate) with bovine serum albumin. Nucleotide-specific antibodies were isolated by affinity chromatography on oligoadenylic acids/agarose column. Pure immunoglobulin G antibodies were obtained by gel filtration on Sephadex G-200. These antibodies, as analyzed by double diffusion react with adenosine 5'-monophosphate--bovine serum albumin, slightly with inosine-5'-monophosphate conjugate and not at all with the other nucleotide conjugates. The association constants for adenosine-5'-monophosphate--antibody complex formation obtained by dialysis equilibrium and fluorescence measurements, are in good agreement. This latter technique was used to study on one hand the influence of temperture and salt on complex formation, on the other hand the interaction of the antibodies with AMP derivatives. The phosphate group, the ribose and the base are recognized by the antibody, but the C-8 atom of adenine residues is not directly involved in the binding.     

Expression of uncoupling protein 3 in mitochondria protects against stress-induced myocardial injury: a proteomic study

It has been confirmed that stress plays an important role in the induction and development of cardiovascular diseases, but its mechanism and molecular basis remain unknown. In the present study, a myocardial injury model induced by restraint stress was established in rat. To screen for the related proteins involved in stress-induced myocardial injury, proteomic techniques based on 2-DE and mass spectrometry were used. In our results, ten proteins were found to be altered. The expression of eight of these proteins was increased after restraint stress, including cardiac myosin heavy chain, dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial aldehyde dehydrogenase, H⁺-transporting ATP synthase, albumin, and apolipoprotein A-I precursor. The expression of uncoupling protein 3 (UCP3) and mitochondrial aconitase was decreased. Most of the proteins were related to energy metabolism. Further research indicated that UCP3 may mediate the myocardial cell response induced by restraint stress.