Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta

Smad ubiquitination regulatory factor 2 (Smurf2), a ubiquitin ligase for Smads, plays critical roles in the regulation of transforming growth factor-beta (TGF-beta)-Smad signaling via ubiquitin-dependent degradation of Smad2 and Smad7. We found that TGF-beta stimulates Smurf2 expression. TGF-beta activated the Smurf2 promoter in a TGF-beta responsive cell lines, whereas IL-1alpha, PDGF and epidermal growth factor did not. TGF-beta-mediated Smurf2 promoter activation was inhibited by Smad7 or an activin receptor-like kinase 5 inhibitor but not by dominant negative Smad or disruption of Smad-binding elements in the promoter. Moreover, inhibition of the phosphatidil inositol 3 kinase (PI3K)/Akt pathway suppressed TGF-beta-mediated Smurf2 induction. These results suggest that TGF-beta stimulates Smurf2 expression by Smad-independent pathway such as PI3K/Akt pathway via TGF-beta receptor.     

Regulation of food intake by acyl and des-acyl ghrelins in the goldfish

Our recent research has indicated that intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of n-octanoic acid-modified ghrelin (acyl ghrelin) stimulates food intake and locomotor activity in the goldfish. The manner in which peripherally administered acyl ghrelin regulates food intake, however, remains unclear. In contrast to acyl ghrelin, non-acylated ghrelin (des-acyl ghrelin) does not exert an orexigenic action or induce hypermotility. To this extent, the biological role of des-acyl ghrelin in fish is unknown. Given the possible involvement of afferent pathways in mediating the effects of acyl ghrelin, as is known to occur in rodents, we examined the effect of capsaicin, a neurotoxin which destroys primary sensory (vagal and splanchnic) afferents, on the orexigenic activity induced by i.p.-injected acyl ghrelin. Pretreatment with i.p.-injected capsaicin (0.16 micromol/g body weight (BW)) cancelled the orexigenic action of i.p.-injected acyl ghrelin (8 pmol/g BW), although i.p.-injected capsaicin alone did not affect food intake. The effect of des-acyl ghrelin on the orexigenic action of acyl ghrelin in the goldfish was also investigated. The i.c.v. and i.p. injection of des-acyl ghrelin at doses 3-10 times higher than that of acyl ghrelin suppressed the orexigenic action of i.c.v.- and i.p.-injected acyl ghrelin (doses of 1 and 8 pmol/g BW). In contrast, injection of des-acyl ghrelin alone did not show any inhibitory effect on food intake. These results suggest that, as is seen in rodents, circulating acyl ghrelin derived from peripheral tissues acts via primary sensory afferent pathways on feeding centers in the brain. The results also show that des-acyl ghrelin inhibits acyl ghrelin-induced orexigenic activity in goldfish.     

Type V collagen selectively inhibits human endothelial cell proliferation

Type V collagen from human placenta remarkably inhibited human umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner when coated on the culture dishes. Other types of collagen (I, III, IV) and fibronectin enhanced HUVEC proliferation under the same conditions. The inhibitory activity of type V collagen was seen not only when it was coated on the dishes, but also when it was directly added into cell culture. The attachment effect of type V collagen did not differ from that of type I collagen. The inhibitory activity is a phenomenon selective for endothelial cells, since type V collagen did not affect the proliferation of human umbilical vein smooth muscle cells, aortic smooth muscle cells, or nasal mucosa fibroblasts.     

Western equatorial Pacific planktic foraminiferal fluxes and assemblages during a La Niña year (1999)

A correlation between foraminiferal community dynamics and environmental conditions may provide a basis for establishing paleoclimatic proxies. We studied planktic foraminiferal shell fluxes and assemblages in samples collected in three time-series sediment trap deployments in the western equatorial Pacific under La Niña conditions from January to November 1999. Eleven species contributed about 90% of the total flux in all traps. Two sites (MT1, MT3) in the Western Pacific Warm Pool region (WPWP) were characterized by common occurrences of the species Globigerinoides ruber, Globigerinoides sacculifer, Globigerinoides tenellus, and Neogloboquadrina dutertrei. Site MT5 farther to the east in the equatorial upwelling region had common occurrences of Globigerina bulloides, Globigerinita glutinata, and Pulleniatina obliquiloculata. Very high abundances of G. bulloides and G. glutinata at MT5 indicate that equatorial upwelling (EU) occurred during the 1999 La Niña. The two western sites have similar assemblage compositions, but MT1 ( 135°E) has the highest fluxes (up to  3800 tests m^− 2 day^− 1), whereas MT3 ( 145° E) has fluxes below  2200 tests m^− 2 day^− 1. Relatively high fluxes (up to  3000 tests m^− 2 day^− 1) occur at site MT5 ( 176° E), where upwelling occurred.The differences in faunal composition in the WPWP and EU might be attributable to differences in the way in which nutrients are supplied to the phytoplankton: large amounts of suspended material are supplied to the WPWP by advection of waters passing through the coastal region of an archipelago, whereas upwelling of nutrient-rich waters enhances primary production in the EU. At the westernmost site in the WPWP, a peak in the G. bulloides flux coincided with southward flow of the New Guinea Coastal Current (NGCC) in late February, but the highest G. ruber flux coincided with northward flow of this current in late May. Thus, the differences in species dominance at this location may be caused by monsoon-driven variability in the flow direction of the NGGC.     

Focus: Zoonotic Disease: New Series of Imidazoles Showed Promising Growth Inhibitory and Curative Potential Against Trypanosoma Infection

The Trypanosoma spp. cause animal and human trypanosomiasis characterized with appreciable health and economic burden mostly in developing nations. There is currently no effective therapy for this parasitic disease, due to poor drug efficacy, drug resistance, and unwanted toxicity, etc. Therefore, new anti-Trypanosoma agents are urgently needed. This study explored new series of imidazoles for anti-Trypanosoma properties in vitro and in vivo. The imidazoles showed moderate to strong and specific action against growth of T. congolense. For example, the efficacy of the imidazole compounds to restrict Trypanosoma growth in vitro was ≥ 12-fold specific towards T. congolense relative to the mammalian cells. Additionally, the in vivo study revealed that the imidazoles exhibited promising anti-Trypanosoma efficacy corroborating the in vitro anti-parasite capacity. In particular, three imidazole compounds (C1, C6, and C8) not only cleared the systemic parasite burden but cured infected rats after no death was recorded. On the other hand, the remaining five imidazole compounds (C2, C3, C4, C5, and C7) drastically reduced the systemic parasite load while extending survival time of the infected rats by 14 days as compared with control. Untreated control died 3 days post-infection, while the rats treated with diminazene aceturate were cured comparable to the results obtained for C1, C6, and C8. In conclusion, this is the first study demonstrating the potential of these new series of imidazoles to clear the systemic parasite burden in infected rats. Furthermore, a high selectivity index of imidazoles towards T. congolense in vitro and the oral LD₅₀ in rats support anti-parasite specific action. Together, findings support the anti-parasitic prospects of the new series of imidazole derivatives.     

Postglacial environmental change of the Pacific Ocean off the coasts of central Japan

Downcore changes in microfossil assemblages and oxygen isotope ratios in three piston cores recovered from the Northwestern Pacific, off central Japan, show that the subtropical Kuroshio front was located to the south of C-4 core site (Lat. 33° N) during the last glacial. The front then advanced northward, passing over the C-4 site and the C-6 site (34.6° N) at about 13 ka and 10 ka, respectively, and reached the C-1 core site (36° N) at about 7 ka. After 5.5 ka it retreated to the area between the C-1 and C-6 sites. A brief but significant cold event, the readvance of the cold Oyashio Current, is recognized between 11 and 10 ka in the two northern cores, but the current did not reach the southern C-4 site. A contemporaneous cold event is known in the North Atlantic, and the cooling was probably a global phenomenon likely to be associated with lowering of sea level. Contamination of isotopically light water is apparent between 14 and 11 ka in the marked change in isotopic composition of benthic foraminifers. Oxygen isotope ratios of planktonic foraminifers show that prior to the advance of the Kuroshio front, the surface water at these core sites was isotopically lighter than the Kuroshio water at that time.