Conditional deletion of Npt2b in phosphate transport

Background Hyperphosphatemia is common in chronic kidney disease and is associated with morbidity and mortality. The intestinal Na+-dependent phosphate transporter Npt2b is thought to be an important molecular target for the prevention of hyperphosphatemia. The role of Npt2b in the net absorption of inorganic phosphate (Pi), however, is controversial. Methods In the present study, we made tamoxifen-inducible Npt2b conditional knockout (CKO) mice to analyze systemic Pi metabolism, including intestinal Pi absorption. Results Although the Na+-dependent Pi transport in brush-border membrane vesicle uptake levels were significantly decreased in the distal intestine of Npt2b CKO mice compared with control mice, plasma Pi and fecal Pi excretion levels were not significantly different. Data obtained using the intestinal loop technique showed that Pi uptake in Npt2b CKO mice was not affected at a Pi concentration of 4 mM, which is considered the typical luminal Pi concentration after meals in mice. Claudin, which may be involved in paracellular pathways, as well as claudin-2, 12, and 15 protein levels were significantly decreased in the Npt2b CKO mice. Thus, Npt2b deficiency did not affect Pi absorption within the range of Pi concentrations that normally occurs after meals. Conclusion These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency

Complex microseismic activity and depth-dependent stress field changes in Wakayama, southwestern Japan

Abstract We examined the spatial relationship between seismicity and upper crustal structure in the Wakayama region, northwestern Kii Peninsula, Japan, by investigating microearthquake focal mechanisms and the local stress field. The focal mechanisms of most events studied fall into three categories: (1) normal faulting with N–S-oriented T-axes mainly occurring at shallow depths, (2) reverse faulting with E–W-oriented P-axes dominating at intermediate depths, and (3) strike-slip faulting with N–S-oriented T-axes and E–W-oriented P-axes mainly seen at greater depths. The stress field varies with depth: the shallow part is characterized by a strike-slip-type stress regime with N–S tension and E–W compression, while the deep part is characterized by an E–W compressional stress regime consistent with reverse faulting. The depth-dependent stress regime can be explained by thermal stress caused by a heat source, as expected from geophysical observations. Geologic faults, acting as weak planes, might contribute to generate shallow normal fault-type and deeper strike-slip fault-type microearthquakes. Graphical Abstrac