Interaction between the basolateral K+ and apical Na+ conductances in Necturus urinary bladder

Experimental modulation of the apical membrane Na+ conductance or basolateral membrane Na+-K+ pump activity has been shown to result in parallel changes in the basolateral K+ conductance in a number of epithelia. To determine whether modulation of the basolateral K+ conductance would result in parallel changes in apical Na+ conductance and basolateral pump activity, Necturus urinary bladders stripped of serosal muscle and connective tissue were impaled through their basolateral membranes with microelectrodes in experiments that allowed rapid serosal solution changes. Exposure of the basolateral membrane to the K+ channel blockers Ba2+ (0.5 mM/liter), Cs+ (10 mM/liter), or Rb+ (10 mM/liter) increased the basolateral resistance (Rb) by greater than 75% in each case. The increases in Rb were accompanied simultaneously by significant increases in apical resistance (Ra) of greater than 20% and decreases in transepithelial Na+ transport. The increases in Ra, measured as slope resistances, cannot be attributed to nonlinearity of the I-V relationship of the apical membrane, since the measured cell membrane potentials with the K+ channel blockers present were not significantly different from those resulting from increasing serosal K+, a maneuver that did not affect Ra. Thus, blocking the K+ conductance causes a reduction in net Na+ transport by reducing K+ exit from the cell and simultaneously reducing Na+ entry into the cell. Close correlations between the calculated short-circuit current and the apical and basolateral conductances were preserved after the basolateral K+ conductance pathways had been blocked. Thus, the interaction between the basolateral and apical conductances revealed by blocking the basolateral K+ channels is part of a network of feedback relationships that normally serves to maintain cellular homeostasis during changes in the rate of transepithelial Na+ transport

Characterization of the basolateral membrane conductance of Necturus urinary bladder

Necturus urinary bladders stripped of serosal muscle and connective tissue were impaled through their basolateral membranes with microelectrodes in experiments that permitted rapid changes in the ion composition of the serosal solution. The transepithelial electrical properties exhibited a marked seasonal variation that could be attributed to variations in the conductance of the shunt pathway, apical membrane selectivity, and basolateral Na+ transport. In contrast, the passive electrical properties of the basolateral membrane remained constant throughout the year. The apparent transference numbers (Ti) of the basolateral membrane for K+ and Cl- were determined from the effect on the basolateral membrane equivalent electromotive force of a sudden increase in the serosal K+ concentration from 2.5 to 50 mM/liter or a decrease in the Cl- concentration from 101 to 10 mM/liter. TK and TCl were 0.71 +/- 0.05 and 0.04 +/- 0.01, respectively. The basolateral K+ conductance could be blocked by Ba2+ (0.5 mM), Cs+ (10 mM), or Rb+ (10 mM), but was unaffected by 3,4- diaminopyridine (100 microM), decamethonium (100 microM), or tetraethylammonium (10 mM). We conclude that a highly selective K+ conductance dominates the electrical properties of the basolateral membrane and that this conductance is different from those found in nerve and muscle membranes

MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP

The MOZ-TIF2 fusion is associated with acute myeloid leukemia (AML) with inv(8)(p11q13). MOZ is a MYST family histone acetyltransferase (HAT), whereas TIF2 is a nuclear receptor coactivator that associates with CREB binding protein (CBP). Here we demonstrate that MOZ-TIF2 has transforming properties in vitro and causes AML in a murine bone marrow transplant assay. The C2HC nucleosome recognition motif of MOZ is essential for transformation, whereas MOZ HAT activity is dispensable. However, MOZ-TIF2 interaction with CBP through the TIF2 CBP interaction domain (CID) is essential for transformation. These results indicate that nucleosomal targeting by MOZ and recruitment of CBP by TIF2 are critical requirements for MOZ-TIF2 transformation and indicate that MOZ gain of function contributes to leukemogenesis

Socio-economic and lifestyle factors associated with overweight in Flemish adult men and women

<p>Abstract</p> <p>Background</p> <p>Changes in lifestyles and in the environment over the last decades are probably the most important cause of the overweight epidemic, but the findings are inconsistent among studies. The purpose of this study was to investigate the association of several socio-economic and lifestyle factors with overweight in Flemish adults, using BMI ≥ 25 kg/m², waist circumference (WC) ≥ 94 cm (men) or ≥ 80 cm (women) and the combination of BMI and WC for identifying overweight.</p> <p>Methods</p> <p>This cross-sectional epidemiological study was conducted by the Flemish Policy Research Centre Sport, Physical Activity and Health between October 2002 and February 2004 in 46 Flemish communities. A total of 4903 Flemish adults (2595 men and 2308 women), aged 18 to 75 years, from a population-based random sample were included in the analysis. Body weight, height and WC were measured, and socio-economic and lifestyle factors were reported by means of validated questionnaires.</p> <p>Results</p> <p>The results of the logistic regressions revealed that age is positively associated with overweight in both genders. Alcohol consumption is associated with overweight only in men. Men smoking in the past and watching TV >11 h/week have significantly higher OR's for overweight, while men who participate in health related sports >4 h/week have significantly lower OR's for overweight. In women, watching TV >9 h/week was positively associated with overweight. Women who are current smokers or participate in health related sports >2.5 h/week or with a higher educational level have significantly lower odds for overweight. Different results are observed between the first (BMI) and the second model (WC) in both genders. In men, the models differ for education and health related sports, while in women they differ for smoking status and leisure time physical activity.</p> <p>Conclusion</p> <p>The present study confirms the contention that overweight is a multifactorial problem. Age and TV viewing are positively associated with overweight, while educational level and health related sports are negatively related to overweight in both genders. In men, alcohol consumption and smoking in the past are also among the lifestyle factors associated with overweight. This study also indicates that BMI and WC do not have the same discriminative function regarding different lifestyle factors.</p