PSM/SH2-B has been described as a cellular partner of the FceRI receptor, insulin receptor (IR), insulin-like growth factor-I (IGF-I) receptor (IGF-IR), and nerve growth factor receptor (TrkA). A function has been proposed in neuronal dierentiation and development but its role in other signaling pathways is still unclear. To further elucidate the physiologic role of PSM we have identi®ed additional mitogenic receptor tyrosine kinases as putative PSM partners including platelet-derived growth factor (PDGF) receptor (PDGFR) beta, hepatocyte growth factor receptor (Met), and ®broblast growth factor receptor. We have mapped Y740 as a site of PDGFR beta that is involved in the association with PSM. We have further investigated the putative role of PSM in mitogenesis with three independent experimental strategies and found that all consistently suggested a role as a positive, stimulatory signaling adapter in normal NIH3T3 and baby hamster kidney ®broblasts. (1) PSM expression from cDNA using an ecdysone-regulated transient expression system stimulated PDGF-BB-, IGF-I-, and insulin-but not EGF-induced DNA synthesis in an ecdysone dose-responsive fashion; (2) Microinjection of the (dominant negative) PSM SH2 domain interfered with PDGF-BB-and insulin-induced DNA synthesis; and (3) A peptide mimetic of the PSM Prorich putative SH3 domain-binding region interfered with PDGF-BB-, IGF-I-, and insulin-but not with EGFinduced DNA synthesis in NIH3T3 ®broblasts. This experiment was based on cell-permeable fusion peptides with the Drosophila antennapedia homeodomain which eectively traverse the plasma membrane of cultured cells. These experimental strategies independently suggest that PSM functions as a positive, stimulatory, mitogenic signaling mediator in PDGF-BB, IGF-I, and insulin but not in EGF action. This function appears to involve the PSM SH2 domain as well as the Pro-rich putative SH3 domain binding region. Our ®ndings support the model that PSM participates as an adapter in various mitogenic signaling mechanisms by linking an activated (receptor) phospho-tyrosine to the SH3 domain of an unknown cellular partner. Oncogene (2000) 19, 39 ± 50.

Bicarbonate/chloride (HCO 3؊ /Cl ؊ ) exchangers regulate intracellular pH in the alkaline range. Previously, it has been shown that mouse embryos at the two-cell stage exhibit this activity, but that the otherwise ubiquitous mechanisms for regulating intracellular pH in the acidto-neutral range are undetectable. We have examined mouse embryos during preimplantation development (one-cell zygote through blastocyst) to determine whether HCO 3 ؊ /Cl ؊ exchange activity exists at all stages, whether it is necessary for preimplantation development, and whether messenger RNAs from the known HCO 3 ؊ /Cl ؊ exchanger genes are expressed. We have found that all stages of preimplantation embryo have detectable HCO 3 ؊ /Cl ؊ exchange activity. In addition, inhibition of this activity with the stilbene anion exchange inhibitor DIDS (4,4-diisothiocyanostilbene-2,2-disulfonic acid) disrupts intracellular pH homeostasis and markedly inhibits embryo development from the twocell stage to blastocysts in culture under conditions of moderately high external pH. Finally, mRNA encoding two members of the band 3-related AE anion exchanger gene family are expressed in preimplantation embryos.

HCO3-/Cl- exchanger activity, which regulates intracellular pH (pHi) in the alkaline range, has been shown to be present throughout preimplantation mouse embryo development and to be necessary for embryo viability. We have characterized HCO3-/Cl- exchange activity and its regulation of pHi throughout preimplantation development (1-cell, 2-cell, morula, and blastocyst stages). Embryos at each stage can recover from alkalosis. Recovery was dependent on external [Cl-], activated by increased pHi, and inhibited by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and external HCO3-. Dependence of exchanger activity on external [Cl-] and pHi remained unchanged during preimplantation development. However, the concentration at which DIDS inhibits the maximal response by 50% increased significantly (by approximately 5-fold) after the one-cell stage. In addition, HCO3-/Cl- exchange activity decreased over the course of development, with significantly lower activity at the morula and blastocyst stages relative to the one- and two-cell stages, coinciding with the movement of embryo from the high pH environment of the oviduct to the lower pH environment of the uterus.

No abstract

Debris flows represent major hazards in most mountainous regions of the world where they repeatedly result in disasters. In order to protect people and infrastructure against future debris flows, many debris flow catchments have been artificially intervened by employing various mitigation measures, including civil engineering works. However, the commonly adapted engineering measures, such as check dams, are not effective for every debris flow catchment, and the failure of such measures even causes more damage, e.g. the Sanyanyu debris flow catchment in Zhouqu, China, killed 1756 people. In order to research the effectiveness of engineering strategies and explore much more effective mitigation works for debris flows in the mountainous regions, we took the Bailong River catchment of Southern Gansu of China as study area, with special emphasis on Sanyanyu debris flow catchment (with civil engineering works) and Goulinping debris flow catchment (without civil engineering works), and comparatively analysed the two catchments. The comparative results show that both catchments have similar material source, geomorphological/environmental and climatic conditions, however, vegetation cover and rock hardness are poorer in Goulinping than in Sanyanyu, the catchment that underwent larger-scale debris flows, suggesting that the mitigation measures had been applied in Sanyanyu catchment were inappropriate. Subsequently, we simulated the effectiveness of controlling debris flow peak discharge with check dams at the lower part of Sanyanyu and Goulinping catchment using the Kanako simulator, and summarised argument based on the hypothesis and facts from positive and negative aspects. We draw the conclusion that it is not reasonable to build check dams in the two catchments and instead, drainage channels should be primarily considered for reducing debris flow hazards in such densely populated areas. Finally, we undertook detailed field investigations and experiments on the native plants in the region, and found that the ecological mitigation measure with planting Robinia Pseudoacacia on the debris flow deposits is an effective method to alleviate debris flow hazards. It is concluded that channel works combined with ecological measures are the preferable approaches to minimize the debris flow damage in debris flow catchments characterised with high mountains, concentrated rainfalls and active neotectonic movement.