Concentration-dependent structural transitions of human telomeric DNA sequences.

Oligodeoxyribonucleotides (ODNs) that have four repeats of the human telomeric sequence d(TTAGGG)(n) can assume multiple monomolecular G-quadruplex topologies. These are determined by the cation species present, the bases at the 5' or 3' end, and the sample preparation technique. In this work, we report our studies of the concentration dependence of the circular dichroism (CD) and the vibrational modes probed by Raman scattering of three previously characterized monomolecular G-quadruplexes: H-Tel, d[5'-A(GGGTTA)(3)GGG-3']; hybrid-1, d[5'-AAA(GGGTTA)(3)GGGAA-3']; and hybrid-2, d[5'-TTA(GGGTTA)(3)GGGTT-3']. At high (millimolar) ODN concentrations, we observed a transformation of the CD spectrum of H-Tel, with a relaxation time on the order of 10 h. Analysis of the kinetics of this process is consistent with the formation of an aggregated complex of folded H-Tel monomers. Upon dilution, the aggregates dissociate rapidly, yielding spectra identical to those of monomeric H-Tel. Both hybrid sequences undergo a similar transition under high-salt (1 M) conditions. The measurements suggest that for these ODN concentrations, which are typically used in high-resolution spectroscopies, the monomolecular G-quadruplex structures undergo a transition to multimolecular structures at room temperature. Guided by our findings, we propose that the terminal bases of the hybrid-1 and hybrid-2 ODNs impede the formation of these aggregates; however, in solutions containing 1 M salt, the hybrid oligonucleotides aggregate.

The relationship between the financial status of sole community independent pharmacies and their broader involvement with other rural providers.

PURPOSE: To document sole community pharmacists' involvement with other local health care organizations, these pharmacies' current financial status, and to determine whether financial position was associated with the provision of pharmacy services to other local health care providers. METHODS: We conducted semistructured interviews with pharmacist-owners of 401 sole community pharmacies randomly selected using data from the National Council for Prescription Drug Programs, Inc. Bivariate and multivariate analyses of responses were conducted to examine associations between pharmacy characteristics, financial position, and involvement with other local health care providers. FINDINGS: About 4 in 5 pharmacies provided services to at least 1 local health care organization. Most respondents (70%) described their store's overall financial position as good or very good, but about one-third reported that their financial conditions had deteriorated since the previous year. Providing services to other organizations was associated with higher prescription sales volume. After controlling for prescription volume, there was no association between providing services to other organizations and pharmacist-owners' self-assessed financial position. CONCLUSION: Sole community pharmacists provide important pharmaceutical support services to other health care organizations. Other than increased volume of business, this support often does not translate directly to an improved financial position for the pharmacy. The survival of sole community pharmacies not only ensures retail access to pharmaceuticals and patient counseling, but it also, in many cases, plays a key role in supporting other local health care providers, helping to preserve access to important services that are particularly needed in communities with limited health care options.