BMP signaling in the development of the mouse esophagus and forestomach.

The stratification and differentiation of the epidermis are known to involve the precise control of multiple signaling pathways. By contrast, little is known about the development of the mouse esophagus and forestomach, which are composed of a stratified squamous epithelium. Based on prior work in the skin, we hypothesized that bone morphogenetic protein (BMP) signaling is a central player. To test this hypothesis, we first used a BMP reporter mouse line harboring a BRE-lacZ allele, along with in situ hybridization to localize transcripts for BMP signaling components, including various antagonists. We then exploited a Shh-Cre allele that drives recombination in the embryonic foregut epithelium to generate gain- or loss-of-function models for the Bmpr1a (Alk3) receptor. In gain-of-function (Shh-Cre;Rosa26(CAG-loxpstoploxp-caBmprIa)) embryos, high levels of ectopic BMP signaling stall the transition from simple columnar to multilayered undifferentiated epithelium in the esophagus and forestomach. In loss-of-function experiments, conditional deletion of the BMP receptor in Shh-Cre;Bmpr1a(flox/flox) embryos allows the formation of a multilayered squamous epithelium but this fails to differentiate, as shown by the absence of expression of the suprabasal markers loricrin and involucrin. Together, these findings suggest multiple roles for BMP signaling in the developing esophagus and forestomach.

Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

OBJECTIVE: To investigate the effect of statin use after radical prostatectomy (RP) on biochemical recurrence (BCR) in patients with prostate cancer who never received statins before RP. PATIENTS AND METHODS: We conducted a retrospective analysis of 1146 RP patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analyses were used to examine differences in risk of BCR between post-RP statin users vs nonusers. To account for varying start dates and duration of statin use during follow-up, post-RP statin use was treated as a time-dependent variable. In a secondary analysis, models were stratified by race to examine the association of post-RP statin use with BCR among black and non-black men. RESULTS: After adjusting for clinical and pathological characteristics, post-RP statin use was significantly associated with 36% reduced risk of BCR (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47-0.87; P = 0.004). Post-RP statin use remained associated with reduced risk of BCR after adjusting for preoperative serum cholesterol levels. In secondary analysis, after stratification by race, this protective association was significant in non-black (HR 0.49, 95% CI 0.32-0.75; P = 0.001) but not black men (HR 0.82, 95% CI 0.53-1.28; P = 0.384). CONCLUSION: In this retrospective cohort of men undergoing RP, post-RP statin use was significantly associated with reduced risk of BCR. Whether the association between post-RP statin use and BCR differs by race requires further study. Given these findings, coupled with other studies suggesting that statins may reduce risk of advanced prostate cancer, randomised controlled trials are warranted to formally test the hypothesis that statins slow prostate cancer progression.

The island-scale internal wave climate of Moorea, French Polynesia

Analysis of five-year records of temperatures and currents collected at Moorea reveal strong internal wave activity at predominantly semi-diurnal frequencies impacting reef slopes at depths 30m around the entire island. Temperature changes of 1.5C to 3C are accompanied by surges of upward and onshore flow and vertical shear in onshore currents. Superimposed on annual temperature changes of approximately 3C, internal wave activity is high from Oct-May and markedly lower from Jun-Sep. The offshore pycnocline is broadly distributed with continuous stratification to at least 500m depth, and a subsurface fluorescence maximum above the strong nutricline at approximately 200m. Minimum buoyancy periods range from 4.8 to 6min, with the maximum density gradient occurring at 50 to 60m depth in summer and deepening to approximately 150 to 200m in winter. The bottom slope angle around all of Moorea is super-critical relative to the vertical stratification angle suggesting that energy propagating into shallow water is only a portion of total incident internal wave energy. Vertical gradient Richardson numbers indicate dominance by density stability relative to current shear with relatively limited diapycnal mixing. Coherence and lagged cross-correlation of semi-diurnal temperature variation indicate complex patterns of inter-site arrival of internal waves and no clear coherence or lagged correlation relationships among island sides. Semi-diurnal and high frequency internal wave packets likely arrive on Moorea from a combination of local and distant sources and may have important impacts for nutrient and particle fluxes in deep reef environments. © 2012 American Geophysical Union. All Rights Reserved.