Culinary continuity in central Japan across the transition to agriculture.

Unlabelled: Rice and millet arrived in Western Japan from Korea around 3,000 years ago and spread eastwards across the archipelago in the next 700 years. However, the extent to which agriculture transformed traditional Jōmon hunter-gatherer-fisher communities is debated. Central Japan is a key area of study as remodelling of radiocarbon dates shows a slowdown in the dispersal rate of rice agriculture in this area.

Role of Tyr306 in the C-terminal fragment of Clostridium perfringens enterotoxin for modulation of tight junction.

We previously reported that the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) is a novel type of absorption enhancer that interacts with claudin-4 and that Tyr306 of C-CPE plays a role in ability of C-CPE to modulate barrier of tight junctions. In the current study, to investigate effects of Tyr306 on the C-CPE activity, we prepared some C-CPE mutants substituted Tyr306 with Trp (Y306W), Phe (Y306F) and Lys (Y306K). We found that Y306W and Y306F mutants of C-CPE had claudin-4 binding affinities and effects on the barrier function of tight junctions, whereas both of these properties were greatly reduced with the Y306K mutant.

Role of tyrosine residues in modulation of claudin-4 by the C-terminal fragment of Clostridium perfringens enterotoxin.

The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) modulates the barrier function of claudin-4 via its C-terminal 16 amino acids. In the current study, we investigated the roles of tyrosine residues (Y306, Y310 and Y312) in this region in the modulation of TJs by C-CPE. Single mutations of Y306, Y310 and Y312 to alanine resulted in partial reduction of claudin-4 binding.

Induction of apoptosis by new ent-kaurene-type diterpenoids isolated from the New Zealand liverwort Jungermannia species.

Some diterpenoids show various biological activities, including anti-inflammatory, anti-HIV and anti-tumor activity. Previously, we have focused our research on the apoptosis-inducing properties of diterpenoids and found that some ent-kaurene-type diterpenoids induced apoptosis in human leukemia HL-60 cells. In this study, we have investigated the induction of apoptosis in HL-60 cells by the novel ent-kaurene-type diterpenoids, jungermannenones A (JA), B (JB), C (JC) and D (JD), isolated from the New Zealand liverwort Jungermannia species.

Preparation of a claudin-targeting molecule using a C-terminal fragment of Clostridium perfringens enterotoxin.

Although most malignant tumors are epithelia-derived carcinomas, methods for specific and effective delivery of antitumor agents to carcinomas have not been developed. Recent reports indicate that epithelia overexpress claudin-3 and -4, which are integral membrane proteins of epithelial tight junctions. This suggests that claudins can be targeted for tumor therapy, but there is not currently a method for delivering drugs to claudin-expressing cells.

Role of N-terminal amino acids in the absorption-enhancing effects of the c-terminal fragment of Clostridium perfringens enterotoxin.

We recently found that a polypeptide, the C-terminal of Clostridium perfringens enterotoxin (C-CPE), was a novel type of drug absorption enhancer. The C-terminal of C-CPE is thought to play a role in the binding of C-CPE to its receptor, claudin-4; however, the function of the N-terminal of C-CPE is unclear. In the present study, we evaluated the role of the N-terminal domain of C-CPE in jejunal absorption and claudin-4 binding.

Activation of p38 mitogen-activated protein kinase during ent-11alpha-hydroxy-16-kauren-15-one-induced apoptosis in human leukemia HL-60 cells.

Kaurene-type diterpenes possess various biological activities including antitumor and anti-inflammatory effects. Indeed, we have found that an ent-kaurene diterpene, ent-11alpha-hydroxy-16-kauren-15-one (KD), induced apoptosis via caspase-8 activation in human promyelocytic leukemia HL-60 cells. However, the mechanism of caspase-8 activation by KD is not clear.

An ent-kaurene diterpene enhances apoptosis induced by tumor necrosis factor in human leukemia cells.

Some antitumor agents, including tumor necrosis factor-alpha (TNF-alpha) and camptothecin (CPT), often cause resistance of tumor cells to antitumor agents through activation of the nuclear factor-kappa B (NF-kappa B) pathway that leads to up-regulation of anti-apoptotic proteins. Therefore, co-treatment of an inhibitor of the NF-kappa B pathway with antitumor agents is a useful strategy for chemotherapy. Here we report that ent-11 alpha-hydroxy-16-kauren-15-one (KD) selectively inhibits NF-kappa B-dependent gene expression due to treatment with TNF-alpha.

Kaurene diterpene induces apoptosis in human leukemia cells partly through a caspase-8-dependent pathway.

Defects in apoptosis signaling pathways contribute to tumorigenesis and drug resistance, and these defects are often a cause of failure of chemotherapy. Thus, a major goal in chemotherapy is to find cytotoxic agents that restore the ability of tumor cells to undergo apoptosis. We previously found that an Ent-kaurene diterpene, Ent-11alpha-hydroxy-16-kauren-15-one (KD), induced apoptosis in human promyelocytic leukemia HL-60 cells.