Inhibition of transglutaminase activity reduces extracellular matrix accumulation induced by high glucose levels in proximal tubular epithelial cells

Diabetic nephropathy affects 30-40% of diabetics leading to end-stage kidney failure through progressive scarring and fibrosis. Previous evidence suggests that tissue transglutaminase (tTg) and its protein cross-link product epsilon(gamma-glutamyl)lysine contribute to the expanding renal tubulointerstitial and glomerular basement membranes in this disease. Using an in vitro cell culture model of renal proximal tubular epithelial cells we determined the link between elevated glucose levels with changes in expression and activity of tTg and then, by using a highly specific site directed inhibitor of tTg (1,3-dimethyl-2[(oxopropyl)thio]imidazolium), determined the contribution of tTg to glucose-induced matrix accumulation. Exposure of cells to 36 mm glucose over 96 h caused an mRNA-dependent increase in tTg activity with a 25% increase in extracellular matrix (ECM)-associated tTg and a 150% increase in ECM epsilon(gamma-glutamyl)lysine cross-linking. This was paralleled by an elevation in total deposited ECM resulting from higher levels of deposited collagen and fibronectin. These were associated with raised mRNA for collagens III, IV, and fibronectin. The specific site-directed inhibitor of tTg normalized both tTg activity and ECM-associated epsilon(gamma-glutamyl)lysine. Levels of ECM per cell returned to near control levels with non-transcriptional reductions in deposited collagen and fibronectin. No changes in transforming growth factor beta1 (expression or biological activity) occurred that could account for our observations, whereas incubation of tTg with collagen III indicated that cross-linking could directly increase the rate of collagen fibril/gel formation. We conclude that Tg inhibition reduces glucose-induced deposition of ECM proteins independently of changes in ECM and transforming growth factor beta1 synthesis thus opening up its possible application in the treatment other fibrotic and scarring diseases where tTg has been implicated.

A regional analysis of contraction rate in written Standard American English

The goal of this study is to determine if various measures of contraction rate are regionally patterned in written Standard American English. In order to answer this question, this study employs a corpus-based approach to data collection and a statistical approach to data analysis. Based on a spatial autocorrelation analysis of the values of eleven measures of contraction across a 25 million word corpus of letters to the editor representing the language of 200 cities from across the contiguous United States, two primary regional patterns were identified: easterners tend to produce relatively few standard contractions (not contraction, verb contraction) compared to westerners, and northeasterners tend to produce relatively few non-standard contractions (to contraction, non-standard not contraction) compared to southeasterners. These findings demonstrate that regional linguistic variation exists in written Standard American English and that regional linguistic variation is more common than is generally assumed.

Thermal detemplation of SBA-15 mesophases. Effect of the activation protocol on the framework contraction

The potential use of the solvothermal extraction (SE) as a preliminary step to calcination for detemplating SBA-15 mesophases is investigated; aiming to reduce the amount of organics to be burnt and thereby the corresponding structural shrinkage. A systematic study was carried out by soxhlet extraction on mesophases hydrothermally aged between 90 and 130 C. The mesophases containing variable amounts of template were then treated by calcination or pyrolysis/calcination. TGA was applied to quantify the template amount after the various treatments. The as obtained materials were characterized by SAXS and Ar ad/desorption for structural and textural information while 1H NMR gave information about the integrity of the as-recycled template. The study shows that solvothermal conditions remove considerably the template, typically from 50 to 10-20 wt.%, mainly extracted from the primary mesopores. Possible reuse of the extracted template is questionable as it is poor in polyethyleneoxide compared to the synthesis block-copolymer, Pluronic P123. For all thermal protocols applied (direct calcination, calcination after solvent-extraction or pyrolysis/calcination after solvent extraction), the thermal shrinkage decreases with the aging temperature; that is consistent with the condensation degree of the silica. For each mesophase, it was found that the thermal shrinkage becomes less pronounced when the material is fully templated; thus the template can serve as structural support or can control the mass transfer of O2 and thereby the oxidation rate of the template burning. © 2013 Elsevier Inc. All rights reserved.