The transition of hematopoiesis from the fetal liver (FL) to the bone marrow (BM) is incompletely characterized. We demonstrate that the Wiskott-Aldrich syndrome verprolin-homologous protein (WAVE) complex 2 is required for this transition, as complex degradation via deletion of its scaffold Hem-1 causes the premature exhaustion of neonatal BM hematopoietic stem cells (HSCs). This exhaustion of BM HSC is due to the failure of BM engraftment of Hem-1-/- FL HSCs, causing early death. The Hem-1-/- FL HSC engraftment defect is not due to the lack of the canonical function of the WAVE2 complex, the regulation of actin polymerization, because FL HSCs from Hem-1-/- mice exhibit no defects in chemotaxis, BM homing, or adhesion. Rather, the failure of Hem-1-/- FL HSC engraftment in the marrow is due to the loss of c-Abl survival signaling from degradation of the WAVE2 complex. However, c-Abl activity is dispensable for the engraftment of adult BM HSCs into the BM. These findings reveal a novel function of the WAVE2 complex and define a mechanism for FL HSC fitness in the embryonic BM niche.
Activation of the IKK-NFκB pathway increases the resistance of cancer cells to ionizing radiation (IR). This effect has been largely attributed to the induction of anti-apoptotic proteins by NFκB. Since efficient repair of DNA double strand breaks (DSBs) is required for the clonogenic survival of irradiated cells, we investigated if activation of the IKK-NFκB pathway also regulates DSB repair to promote cell survival after IR. We found that inhibition of the IKK-NFκB pathway with a specific IKKβ inhibitor significantly reduced the repair of IR-induced DSBs in MCF-7 cells. The repair of DSBs was also significantly inhibited by silencing IKKβ expression with IKKβ shRNA. However, down-regulation of IKKα expression with IKKα shRNA had no significant effect on the repair of IR-induced DSBs. Similar findings were also observed in IKKα and/or IKKβ knockout mouse embryonic fibroblasts (MEFs). More importantly, inhibition of IKKβ with an inhibitor or down-regulation of IKKβ with IKKβ shRNA sensitized MCF-7 cells to IR-induced clonogenic cell death. DSB repair function and resistance to IR were completely restored by IKKβ reconstitution in IKKβ-knockdown MCF-7 cells. These findings demonstrate that IKKβ can regulate the repair of DSBs, a previously undescribed and important IKKβ kinase function; and inhibition of DSB repair may contribute to cance cell radiosensitization induced by IKKβ inhibition. As such, specific inhibition of IKKβ may represents a more effective approach to sensitize cancer cells to radiotherapy.
It has been little known about gastropods in Raoping of Guangdong Province. Gastropods reported by this paper are mainly marine forms, and accordingly they are important for indicating sedimentary environment of this area. The gastropods diagnosed consist of 30 species they attributed to 25 genera and 16 families. Excepting Tarebia granifera (Lamarck) and Semisulcospira sp. being freshwater species, others are marine species mostly distributed in marine area south of the Zhejiang Province. Only few species appear in northern sea area of the Yellow Sea. These species are also distributed in many maritime areas of tropic Pacific Ocean. Therefore, they represent a tropic fauna. This fauna include a part of species having longer evolutionary history, for instance, Batellaria zonalis (Bruguiere), Cerithidea cingulata (Gmelin), Neverita didyma (Roeding), Plinices melanostomus (Gmelin), Polinices peselephanti (Link) and Tahis luteostoma (Holten) occurring in the Quaternary of Taiwan and Japan etc., Batellaria zonalis (Bruguiere), Cantharus cecillei (Philippi), Eunaticina papilla (Gmelin), Inquisitor flavidula (Lamarck), Nassarius siquijorensis (A. Adamas), Neverita didyma (Roeding), Oliva mustelina Lamarck, Plinices melanostomus (Gmelin), Polinices peselephanti (Link) and Rapana bezoar (Linnaeus) in Tertiary of Taiwan, Japan, Java, Philippine and Indonesia. Ecologically, a majority of species lives on sandy mud or muddy sand bottoms from low tidal zone to shallow sea. It should note that some of species, as such Cantharus cecillei (Philippi), Cerithidea cingulata (Gmelin), Cuma gradata (Born), Cyrineum natator (Roeding), Mitra chinensis Gray, Neverita didyma (Roeding), are typical of tide zone. Moreover, some species live at rocky reef of intertidal zone. Therefore, the fauna may reflect a condition of shallow water and higher energy. In particular, Batellaria zonalis (Bruguiere) an indicator of seawater/freshwater interaction zone, was found, reflecting that this area was near estuary not far from coast at that time. Additionally, most shells look fresh and complete. In overall, this fauna assemblage can be placed in the Holocene in age.
