Maximizing Treatment Fidelity in Public Health Clinical Trials

(First paragraph) In relatively few pages (1), Professor Borelli provides a cogent overview of one of the vexing issues in assessing whether public health interventions “work.” The comprehensiveness of the presentation, covering issues ranging from treatment development through outcome evaluation, makes the article a valuable resource for practitioners and students in a variety of disciplines. Of particular value is the detailed template listing fidelity assessment strategies at the Treatment Design, Provider Training, Treatment Delivery, Treatment Receipt, and Treatment Enactment Stages

THE UNITED STATES AND WORLD COTTON OUTLOOK

Crop Production/Industries,

The United States and World Cotton Outlook

Crop Production/Industries,

Doppler imaging of AR Lacertae at three epochs

Observations from IUE were used to study the structure of the lower chromosphere of AR Lacertae in the light of Mg II k. Sequences of LWR/P-HI images distributed around the binary period at three epochs were obtained. Discrete plage-like regions of enhanced Mg II surface flux in this system are identified. There are temporal variations in the Mg II flux on timescales of hours as well as substantial changes in chromospheric morphology on timescales of years. Even with the limited S/N attainable with the IUE, one can map the gross structures of active stellar atmospheres. With such information, one can begin to study the true 3-D structure of the atmospheres of late-type stars

The United States and World Cotton Outlook

Crop Production/Industries,

The United States and World Cotton Outlook

Crop Production/Industries,

Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA helicase

BACKGROUND: Bloom syndrome is one of the most cancer-predisposing disorders and is characterized by genomic instability and a high frequency of sister chromatid exchange. The disorder is caused by loss of function of a 3' to 5' RecQ DNA helicase, BLM. The exact role of BLM in maintaining genomic integrity is not known but the helicase has been found to associate with several DNA repair complexes and some DNA replication foci. RESULTS: Chromatin immunoprecipitation of BLM complexes recovered telomere and ribosomal DNA repeats. The N-terminus of BLM, required for NB localization, is the same as the telomere association domain of BLM. The C-terminus is required for ribosomal DNA localization. BLM localizes primarily to the non-transcribed spacer region of the ribosomal DNA repeat where replication forks initiate. Bloom syndrome cells expressing the deletion alleles lacking the ribosomal DNA and telomere association domains have altered cell cycle populations with increased S or G2/M cells relative to normal. CONCLUSION: These results identify telomere and ribosomal DNA repeated sequence elements as chromosomal targets for the BLM DNA helicase during the S/G2 phase of the cell cycle. BLM is localized in nuclear bodies when it associates with telomeric repeats in both telomerase positive and negative cells. The BLM DNA helicase participates in genomic stability at ribosomal DNA repeats and telomeres

The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability

BACKGROUND: Bloom syndrome is a rare cancer-prone disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. Bloom syndrome cells have a distinctive high frequency of sister chromatid exchange and quadriradial formation. BLM, the protein altered in BS, is a member of the RecQ DNA helicase family, whose members share an average of 40% identity in the helicase domain and have divergent N-terminal and C-terminal flanking regions of variable lengths. The BLM DNA helicase has been shown to localize to the ND10 (nuclear domain 10) or PML (promyelocytic leukemia) nuclear bodies, where it associates with TOPIIIα, and to the nucleolus. RESULTS: This report demonstrates that the N-terminal domain of BLM is responsible for localization of the protein to the nuclear bodies, while the C-terminal domain directs the protein to the nucleolus. Deletions of the N-terminal domain of BLM have little effect on sister chromatid exchange frequency and chromosome stability as compared to helicase and C-terminal mutations which can increase SCE frequency and chromosome abnormalities. CONCLUSION: The helicase activity and the C-terminal domain of BLM are critical for maintaining genomic stability as measured by the sister chromatid exchange assay. The localization of BLM into the nucleolus by the C-terminal domain appears to be more important to genomic stability than localization in the nuclear bodies