Search

The Na+/K+/2Cl- cotransporter (BSC1/NKCC2) is the major transporter mediating sodium chloride and ammonium absorption in the medullary thick ascending limb. A loss-of-function mutation of BSC1 is responsible for Bartter's syndrome. We previously showed both in vivo and in vitro that acidosis increases the expression and activity of BSC1 and that acid pH enhances the stability of BSC1 mRNA by mechanisms involving its 3'-untranslated region (UTR). zeta-Crystallin is a pH response factor that protects the mitochondrial glutaminase mRNA by a specific interaction with AU-rich motifs. Here we identified the molecular determinant(s) within the 3'-UTR that are responsible for BSC1-mRNA expression and assessed the involvement of zeta-crystallin in this regulation. Deleting three out of six conserved AU-rich motifs drastically reduced the expression of BSC1-mRNA with maximal effect for motif 3 at position 870 of the 3'UTR. This motif was responsible for pH and zeta-crystallin-induced stability of BSC1 mRNA. The abundance of zeta-crystallin was increased by acid pH and its overexpression increased the stability of BSC1 mRNA, but its RNA silencing inhibited acid pH-induced BSC1 expression. Therefore the 3'UTR of BSC1-mRNA is a target for zeta-crystallin. The induction of zeta-crystallin by an acid pH plays an important role in preventing BSC1 mRNA decay, thus increasing its expression and activity. [ABSTRACT FROM AUTHOR]

The Al2O3−10 wt% ZrO2 composites were subjected to hardness tests using a Vickers diamond indenter up to 98.1 N. The microstructure observation using a transmission electron microscopy technique helped to identify up to four zones differing in defect level and character. The densest dislocation tangles, twins accumulation and frequent presence of three slip systems were found in regions that were in contact with the sides of the diamond pyramid. The second zone, characterized by two, or at least one, active slip systems, started at the bottom of the indentation mark and extended up to a distance comparable with the depth of indentation. In the third zone, with a thickness comparable to that above, only some α-Al2O3 crystallites showed the presence of dislocations, whereas other crystallites were defect free. In the last zone the alumina crystals were left unaffected but the ZrO2 crystallites showed twinning characteristic of strain-induced transformation. [ABSTRACT FROM AUTHOR]

The article informs that due to great thermodynamic stability, high hardness and compression strength ceramics with TiC or TiN additives have better cutting properties in comparison to pure oxide ceramics. In spite of many attractive properties of carbide reinforced composite ceramics, one of the primary disadvantages is their brittle nature, characterized by low-fracture toughness. In this work, fracture toughness was obtained by means of indentation induced crack growth in bending and for comparison the conventional method based on single edge notched beam specimens was used.

Ti(C,N)-reinforced alumina-zirconia composites with different ratios of C to N in titanium carbonitride solid solutions, such as Ti(C 0.3 ,N 0.7 ) (C:N = 30:70) and Ti(C 0.5 ,N 0.5 ) (C:N = 50:50), were tested to improve their mechanical properties. Spark plasma sintering (SPS) with temperatures ranging from 1600 °C to 1675 °C and pressureless sintering (PS) with a higher temperature of 1720 °C were used to compare results. The following mechanical and physical properties were determined: Vickers hardness, Young's modulus, apparent density, wear resistance, and fracture toughness. A composite with the addition of Ti(C 0.5 ,N 0.5 )n nanopowder exhibited the highest Vickers hardness of over 19.0 GPa, and its fracture toughness was at 5.0 Mpa·m 1/2 . A composite with the Ti(C 0.3 ,N 0.7 ) phase was found to have lower values of Vickers hardness (by about 10%), friction coefficient, and specific wear rate of disc (Ws d ) compared to the composite with the addition of Ti(C 0.5 ,N 0.5 ). The Vickers hardness values slightly decreased (from 5% to 10%) with increasing sintering temperature. The mechanical properties of the samples sintered using PS were lower than those of the samples that were spark plasma sintered. This research on alumina-zirconia composites with different ratios of C to N in titanium carbonitride solid solution Ti(C,N), sintered using an unconventional SPS method, reveals the effect of C/N ratios on improving mechanical properties of tested composites. X-ray analysis of the phase composition and an observation of the microstructure was carried out.

To be appropriately excreted in urine, NH4+ , the major component of urinary acid excretion, must be synthesized by proximal tubular cells, secreted into the proximal tubular fluid, reabsorbed by the medullary thick ascending limb (MTAL) to accumulate in the medullary interstitium, and finally be secreted in the medullary collecting ducts. Each of the various steps of this particular renal pathway is highly regulated, and the control of gene expression explains how the renal handling of NH 4 + becomes fully adapted to chronic acid-base changes. Several targets have been identified to account for the adaptation of renal NH 4 + synthesis and transport in response to an acid load. These are the key enzymes of ammoniagenesis and the apical Na+/H+ (NH4+) exchanger NHE3 in the proximal tubule, the apical Na + -K + (NH 4 + )-2Cl - cotransporter of the MTAL, and the basolateral Na+-K+ (NH4+)-2Cl- cotransporter and the epithelial Rh B and C glycoproteins in the collecting ducts. An acid pH appears to be a major factor in the control of gene expression during metabolic acidosis probably through the activation of pH sensors. Glucocorticoids can contribute to coordinate the adaptation of various tubular cell types. This review focuses on some new aspects of NH3/NH4+ transport and of gene expression regulation that have recently emerged.

To be appropriately excreted in urine, NH4+, the major component of urinary acid excretion, must be synthesized by proximal tubular cells, secreted into the proximal tubular fluid, reabsorbed by the medullary thick ascending limb (MTAL) to be accumulated in the medullary interstitium, and finally secreted in medullary collecting ducts. Several targets have been identified to account at the gene expression level for the adaptation of renal NH4+ synthesis and transport in response to a chronic acid load. These targets are the key enzymes of ammoniagenesis (mitochondrial glutaminase and glutamate dehydrogenase) and gluconeogenesis (phosphoenolpyruvate carboxykinase) and the Na+/H+(NH4+) exchanger NHE3 in the proximal tubule, the apical Na+-K+(NH4+)-2Cl- cotransporter of the MTAL, the basolateral Na+-K+(NH4+)-2Cl- cotransporter, and likely the epithelial Rh B and C glycoproteins in the collecting ducts. An acid pH per se appears to be a major factor in the control of the expression of these genes during metabolic acidosis probably through activation of pH sensors. Glucocorticoids may also act in concert with an acid pH to coordinate the adaptation of various tubular cell types. The present review focuses on some new aspects of NH3/ NH4+ transport and of regulations of gene expression that have recently emerged., (Copyright 2005 S. Karger AG, Basel.)