Catalytic Approach toward Chiral P,N-Chelate Complexes Utilizing the Asymmetric Hydrophosphination Protocol.

A synthetic procedure for obtaining a chiral P,N ligand was developed by exploiting the versatility of the asymmetric hydrophosphination protocol catalyzed by a phosphapalladacycle complex. The addition of the synthesized ligand to various metal sources led to the generation of chiral and enantioenriched chelate complexes, which can be useful prototypes for catalyst design in the future. The resulting coordination compounds were comprehensively characterized by solid-state (X-ray crystallography) and solution-based (one- and two-dimensional NMR spectroscopy) techniques and natural bond orbital (density functional theory) analysis to determine their structural and key electronic features.

Effects of weld damage on the dynamics of energy-absorbing lanyards.

Manufacturers recommend removing fall protection system components from service for any indication of weld spatter or tool damage; however, little is known about the specific effects of lanyard damage on fall arrest dynamics. Thirty-two energy-absorbing lanyards were drop tested after being damaged with weld spatter, plasma torches and cutting tools and compared with new, undamaged lanyards. Two lanyards damaged with a plasma torch failed completely without deploying the energy absorber while weld spatter damage and tool cuts, up to two-thirds through the width of the webbing, had no effect on fall arrest dynamics. The results highlight the catastrophic implications of high-temperature damage to lanyard webbing resulting from plasma torches - which require immediate removal from service. In addition, the integrated energy absorber design in bungee-style lanyards makes them more susceptible to damage anywhere along the length. We therefore recommended against bungee lanyards for ironworkers and welders.

Calcium-dependent mitochondrial cAMP production enhances aldosterone secretion.

Glomerulosa cells secrete aldosterone in response to agonists coupled to Ca(2+) increases such as angiotensin II and corticotrophin, coupled to a cAMP dependent pathway. A recently recognized interaction between Ca(2+) and cAMP is the Ca(2+)-induced cAMP formation in the mitochondrial matrix. Here we describe that soluble adenylyl cyclase (sAC) is expressed in H295R adrenocortical cells. Mitochondrial cAMP formation, monitored with a mitochondria-targeted fluorescent sensor (4mtH30), is enhanced by HCO3(-) and the Ca(2+) mobilizing agonist angiotensin II. The effect of angiotensin II is inhibited by 2-OHE, an inhibitor of sAC, and by RNA interference of sAC, but enhanced by an inhibitor of phosphodiesterase PDE2A. Heterologous expression of the Ca(2+) binding protein S100G within the mitochondrial matrix attenuates angiotensin II-induced mitochondrial cAMP formation. Inhibition and knockdown of sAC significantly reduce angiotensin II-induced aldosterone production. These data provide the first evidence for a cell-specific functional role of mitochondrial cAMP.

Extramitochondrial OPA1 and adrenocortical function.

We have previously described that silencing of the mitochondrial protein OPA1 enhances mitochondrial Ca(2+) signaling and aldosterone production in H295R adrenocortical cells. Since extramitochondrial OPA1 (emOPA1) was reported to facilitate cAMP-induced lipolysis, we hypothesized that emOPA1, via the enhanced hydrolysis of cholesterol esters, augments aldosterone production in H295R cells. A few OPA1 immunopositive spots were detected in ∼40% of the cells. In cell fractionation studies OPA1/COX IV (mitochondrial marker) ratio in the post-mitochondrial fractions was an order of magnitude higher than that in the mitochondrial fraction. The ratio of long to short OPA1 isoforms was lower in post-mitochondrial than in mitochondrial fractions. Knockdown of OPA1 failed to reduce db-cAMP-induced phosphorylation of hormone-sensitive lipase (HSL), Ca(2+) signaling and aldosterone secretion. In conclusion, OPA1 could be detected in the post-mitochondrial fractions, nevertheless, OPA1 did not interfere with the cAMP - PKA - HSL mediated activation of aldosterone secretion.