Total synthesis of norzoanthamine

Norzoanthamine, an alkaloid isolated from Zoanthus sp., can suppress the loss of bone weight and strength in ovariectomized mice. Norzoanthamine derivatives can also strongly inhibit the growth of P-388 murine leukemia cell lines and human platelet aggregation. However, norzoanthamine's densely functionalized complex stereostructure and scarce availability from natural sources have proved a synthetic challenge. We report the stereoselective total synthesis of norzoanthamine in 41 steps, with an overall yield of 3.5% (an average of 92% yield each step).     

Neuronal correlates of goal-based motor selection in the prefrontal cortex

Choosing an action that leads to a desired goal requires an understanding of the linkages between actions and their outcomes. We investigated neural mechanisms of such goal-based action selection. We trained monkeys on a task in which the relation between visual cues, action types, and reward conditions changed regularly, such that the monkeys selected their actions based on anticipated reward conditions. A significant number of neurons in the medial prefrontal cortex were activated, after cue presentation and before motor execution, only by particular action-reward combinations. This prefrontal activity is likely to underlie goal-based action selection.     

A new source of basaltic meteorites inferred from Northwest Africa 011

Eucrites are a class of basaltic meteorites that share common mineralogical, isotopic, and chemical properties and are thought to have been derived from the same parent body, possibly asteroid 4 Vesta. The texture, mineralogy, and noble gas data of the recently recovered meteorite, Northwest Africa (NWA) 011, are similar to those of basaltic eucrites. However, the oxygen isotopic composition of NWA011 is different from that of other eucrites, indicating that NWA011 may be derived from a different parent body. The presence of basaltic meteorites with variable oxygen isotopic composition suggests the occurrence of multiple basaltic meteorite parent bodies, perhaps similar to 4 Vesta, in the early solar system.     

Therapeutic effect of anti-TNF-α antibody and levofloxacin (LVFX) in a mouse model of enterohemorrhagic Escherichia coli O157 infection

The ability of an anti-TNF-α antibody to confer protection against enterohaemorrhagic Escherichia coli (EHEC) O157 was investigated in germfree IQI mice. The use of an antibiotic levofloxacin (LVFX) alone or with the antibody was also studied. Protection included an increase in survival rate. Treatment with the anti-TNF-α antibody inhibited the histological signs associated with EHEC infection but did not prevent the colonization of EHEC or production of Shiga toxin (Stx). No clinical signs were observed and EHEC was completely eliminated in the mouse model receiving both anti-TNF-α antibody and LVFX. Anti-TNF-α antibody suppressed inflammatory cytokine response in the mouse kidney and brain by EHEC infection.     

Reproductive phenotypes in mice with targeted disruption of the 20alpha-hydroxysteroid dehydrogenase gene

In the corpus luteum of rats and mice, 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) catalyzes the conversion of progesterone to a biologically inactive metabolite, 20alpha-dihydroprogesterone (20alpha-OHP). The reduction of progesterone by 20alpha-HSD is believed to be important for functional luteolysis in these rodent species. In addition to the corpus luteum, expression of 20alpha-HSD has been demonstrated in tissues such as the placenta, endometrial epithelia, and fetal skin, although the roles it plays in the latter tissues remain to be determined. To determine the contribution of 20alpha-HSD to functional luteolysis and to the rodent reproductive system more generally, we generated a strain of mice with targeted disruption of the 20alpha-HSD gene. In the 20alpha-HSD-/- mice we obtained, which lacked the genomic region essential for catalytic reaction, neither 20alpha-HSD activity in the corpus luteum nor an increase in the serum concentrations of 20alpha-OHP during pseudopregnancy or pregnancy was detected. The durations of the estrous cycle, pseudopregnancy, and pregnancy were significantly prolonged in the 20alpha-HSD-/- mice, although the serum progesterone levels decreased to levels low enough for delivery of pups at term of pregnancy. In addition, the number of pups, especially live pups, was markedly decreased in the 20alpha-HSD-/- mice. These findings suggest that the role of 20alpha-HSD in functional luteolysis is relatively minor but that it is involved in the survival of newborn mice.     

Signature-tagged mutagenesis of Vibrio vulnificus

Vibrio vulnificus is the causative agent of primary septicemia, wound infection and gastroenteritis in immunocompromised people. In this study, signature-tagged mutagenesis (STM) was applied to identify the virulence genes of V. vulnificus. Using STM, 6,480 mutants in total were constructed and divided into 81 sets (INPUT pools); each mutant in a set was assigned a different tag. Each INPUT pool was intraperitoneally injected into iron-overloaded mice, and in vivo surviving mutants were collected from blood samples from the heart (OUTPUT pools). From the genomic DNA of mixed INPUT or OUTPUT pools, digoxigenin-labeled DNA probes against the tagged region were prepared and used for dot hybridization. Thirty tentatively attenuated mutants, which were hybridized clearly with INPUT probes but barely with OUTPUT probes, were negatively selected. Lethal doses of 11 of the 30 mutants were reduced to more than 1/100; of these, the lethal doses of 2 were reduced to as low as 1/100,000. Transposon-inserted genes in the 11 attenuated mutants were those for IMP dehydrogenase, UDP-N-acetylglucosamine-2-epimerase, aspartokinase, phosphoribosylformylglycinamidine cyclo-ligase, malate Na (+) symporter and hypothetical protein. When mice were immunized with an attenuated mutant strain into which IMP dehydrogenase had been inserted with a transposon, they were protected against V. vulnificus infection. In this study, we demonstrated that the STM method can be used to search for the virulence genes of V. vulnificus.     

Proposal of new return flow analysis by replacement-in-order method for paddy irrigation water

Return flow and repeated use of irrigation water for paddies is the most important issue in the Asian monsoon region, because sometimes this water is applied in greater quantity than that of evapotranspiration plus percolation. A new return flow analysis, the “replacement-in-order method”, which introduces a unique numbering system for very complicated irrigation and drainage networks, is proposed for the main canal with the dual purposes of irrigation and drainage. The method is applied to the Shichika irrigation district in the ordinal (season) irrigation period, resulting in a return flow ratio of 45 % for the entire area. Of this amount, 25 % is available for irrigation again. The remaining 20 % is unavailable, because the return flow discharged directly into a canal lacking a diversion weir in the drainage system, or into the Japan Sea. The return flow ratio is very different at the main canal location, from no return flow to 88 %. With the aid of the above method, theoretical analysis of return flow for paddy irrigation water can be done. This includes the deterministic return flow ratio inside and outside the irrigation area, plus precise information of return flow ratios at various main canal locations and routes of irrigation and drainage water.     

Distribution of radioactive cesium in edible parts of cattle

After the disastrous incident of the Fukushima Daiichi Nuclear Power Station, various agricultural, livestock and fishery products have been inspected for radioactive contamination with cesium in Japan. In this study, radioactive cesium was measured in various edible parts of cattle to verify the current inspection method for cattle, in which the neck tissues are generally used as samples. Radioactive cesium concentration in the short plate, diaphragm, liver, lung, omasum, abomasum and small intestine were lower and sirloin, tenderloin, top round meat and tongue were higher than that in the neck. There was no significant difference between the other organs (heart, kidney, lumen and reticulum) and the neck. Ninety‐five percent upper tolerance limits of the relative concentration to the neck were 1.88 for sirloin, 1.74 for tenderloin, 1.87 for top round and 1.45 for tongue. These results suggest that a safety factor of 2 is recommended for the radioactivity inspection of cattle to prevent a marketing of meat with higher cesium than the legal limit. Re‐inspection should be conducted using another part of muscle, for example, top round, when suspicious levels of 50–100 Bq/kg are detected in the neck.     

Evaluation of the effects of irrigation water on groundwater budget by a hydrologic model

Paddy and Water Environment - Groundwater is a valuable water resource, and it is used for domestic, industrial or agricultural use around the world. Especially, water use in paddy fields is very...