THE CATALYTIC PROPERTIES OF VERMICULITE

Not

Ladder Polyether Synthesis via Epoxide-Opening Cascades Directed by a Disappearing Trimethylsilyl Group

Epoxide-opening cascades offer the potential to construct complex polyether natural products expeditiously and in a manner that emulates the biogenesis proposed for these compounds. Herein we provide a full account of our development of a strategy that addresses several important challenges of such cascades. The centerpiece of the method is a trimethylsilyl (SiMe[subscript 3]) group that serves several purposes and leaves no trace of itself by the time the cascade has come to an end. The main function of the SiMe[subscript 3] group is to dictate the regioselectivity of epoxide opening. This strategy is the only general method of effecting endo-selective cascades under basic conditions.Johnson & Johnson (Fellowship)Boehringer Ingelheim Pharmaceuticals (Fellowship)US-UK Fulbright Commissio

IL-13 in LPS-Induced Inflammation Causes Bcl-2 Expression to Sustain Hyperplastic Mucous cells

Abstract Exposure to lipopolysaccharides (LPS) causes extensive neutrophilic inflammation in the airways followed by mucous cell hyperplasia (MCH) that is sustained by the anti-apoptotic protein, Bcl-2. To identify inflammatory factor(s) that are responsible for Bcl-2 expression, we established an organ culture system consisting of airway epithelial tissue from the rat nasal midseptum. The highest Muc5AC and Bcl-2 expression was observed when organ cultures were treated with brochoalveolar lavage (BAL) fluid harvested from rats 10 h post LPS instillation. Further, because BAL harvested from rats depleted of polymorphonuclear cells compared to controls showed increased Bcl-2 expression, analyses of cytokine levels in lavages identified IL-13 as an inducer of Bcl-2 expression. Ectopic IL-13 treatment of differentiated airway epithelial cells increased Bcl-2 and MUC5AC expression in the basal and apical regions of the cells, respectively. When Bcl-2 was blocked using shRNA or a small molecule inhibitor, ABT-263, mucous cell numbers were reduced due to increased apoptosis that disrupted the interaction of Bcl-2 with the pro-apoptotic protein, Bik. Furthermore, intranasal instillation of ABT-263 reduced the LPS-induced MCH in bik +/+ but not bik −/− mice, suggesting that Bik mediated apoptosis in hyperplastic mucous cells. Therefore, blocking Bcl-2 function could be useful in reducing IL-13 induced mucous hypersecretion