The trans-activation domain of the sporulation response regulator Spo0A revealed by X-ray crystallography

Sporulation in Bacillus involves the induction of scores of genes in a temporally and spatially co-ordinated programme of cell development. Its initiation is under the control of an expanded two-component signal transduction system termed a phosphorelay. The master control element in the decision to sporulate is the response regulator, Spo0A, which comprises a receiver or phosphoacceptor domain and an effector or transcription activation domain. The receiver domain of Spo0A shares sequence similarity with numerous response regulators, and its structure has been determined in phosphorylated and unphosphorylated forms. However, the effector domain (C-Spo0A) has no detectable sequence similarity to any other protein, and this lack of structural information is an obstacle to understanding how DNA binding and transcription activation are controlled by phosphorylation in Spo0A. Here, we report the crystal structure of C-Spo0A from Bacillus stearothermophilus revealing a single alpha -helical domain comprising six alpha -helices in an unprecedented fold. The structure contains a helix-turn-helix as part of a three alpha -helical bundle reminiscent of the catabolite gene activator protein (CAP), suggesting a mechanism for DNA binding. The residues implicated in forming the sigma (A)-activating region clearly cluster in a flexible segment of the polypeptide on the opposite side of the structure from that predicted to interact with DNA. The structural results are discussed in the context of the rich array of existing mutational data

Decision aids for localized prostate cancer in diverse minority men: Primary outcome results from a multicenter cancer care delivery trial (Alliance A191402CD)

Background: Decision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within-visit and previsit DAs for localized prostate cancer, and minority men were oversampled. Methods: The interventions were delivered in urology practices affiliated with the NCI Community Oncology Research Program Alliance Research Base. The primary outcome was prostate cancer knowledge (percent correct on a 12-item measure) assessed immediately after a urology consultation. Results: Four sites administered the previsit DA (39 patients), 4 sites administered the within-visit DA (44 patients), 3 sites administered both previsit and within-visit DAs (25 patients), and 4 sites provided usual care (50 patients). The median percent correct in prostate cancer knowledge, based on the postvisit knowledge assessment after the intervention delivery, was as follows: 75% for the pre+within-visit DA study arm, 67% for the previsit DA only arm, 58% for the within-visit DA only arm, and 58% for the usual-care arm. Neither the previsit DA nor the within-visit DA had a significant impact on patient knowledge of prostate cancer treatments at the prespecified 2.5% significance level (P =.132 and P =.977, respectively). Conclusions: DAs for localized prostate cancer treatment provided at 2 different points in the care continuum in a trial that oversampled minority men did not confer measurable gains in prostate cancer knowledge

Anxiety sensitivity and cannabis use problems, perceived barriers for quitting, and fear of quitting

Cannabis is among the most widely used psychoactive substances in the United States, and rates of cannabis use and cannabis-related problems are increasing. Anxiety sensitivity, or the fear of aversive interoceptive sensations, may be relevant to better understanding cannabis use problems and other significant cannabis use processes (e.g., beliefs about quitting). Previous research has primarily focused on the global anxiety sensitivity construct; however, anxiety sensitivity lower-order facets (Cognitive Concerns, Physical Concerns, and Social Concerns) tend to be differentially related to substance use processes in non-cannabis specific studies. The current study therefore explored anxiety sensitivity lower-order facets in relation to cannabis use problems, perceived barriers for cannabis cessation, and abstinence phobia (fear of not using cannabis) among a community sample of 203 cannabis-using adults. Results indicated that anxiety sensitivity Cognitive Concerns were significantly associated with each of the dependent measures and these effects were not explained by shared variance with the other lower-order factors or a range of other covariates (e.g., tobacco use). The present findings suggest future work may benefit from focusing on the role of anxiety sensitivity Cognitive Concerns in the maintenance of cannabis use