Search

Prohibitin-2 (PHB2) is a scaffold protein that has pleiotropic functions, which include interacting with γ-glutamylcyclotransferase (GGCT) in the cytoplasm and repressing the transcriptional activities of the p21Waf1/Cip (p21) gene in the nucleus. The cytotoxic drug fluorizoline binds to PHB1/2 and exerts antiproliferative actions on cancer cells. However, the precise mechanism underlying the antiproliferative effects of fluorizoline is not fully elucidated. In the present study, we first show that fluorizoline induces p21 expression in several human cancer cell lines,including MCF7 breast cancer cells. Treatment of MCF7 cells with fluorizoline suppressed proliferation and prevented cells from entering into theDNA synthesis phase.Knockdown of p21 rescued the suppressed proliferation, indicating that fluorizoline inhibited MCF7 cell growth via the induction of p21. Overexpression of PHB2 in MCF7 cells prevented the induction of p21 expression by fluorizoline, and restored the antiproliferative effects and blockade of cell cycle progression. Moreover, treatment of MCF7 cells with fluorizoline inhibited the interaction between endogenous PHB2 and GGCT proteins, and reduced the level of nuclear localization of PHB2 proteins. These results indicate that targeting PHB2 with fluorizoline induces the expression of p21 and consequently blocks proliferation of cancer cells. Significance Statement This study shows that fluorizoline may be a promising novel anticancer drug candidate that induces p21 expression and blocks cell-cycle progression in human cancer cell lines. In addition, we show that fluorizoline inhibits the interaction between PHB2 and GGCT and reduces the nuclear localization of PHB2 proteins that regulates p21 expression.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Although many types of drug are used, clinical outcomes are still unsatisfactory. Previous studies have suggested that intestinal bacteria are involved in the pathogenesis of IBD. Accordingly, in an IBD model we evaluated the therapeutic effects of OPS-2071, a low-absorption quinolone antibacterial agent indicated for intestinal infection, and investigated its mechanism of action. The therapeutic effects of OPS-2071 and comparison therapies were evaluated using naive CD4 + T cell-transfer IBD model mice. In vitro inhibition of LPS-induced TNF-α production and inhibitory effects on T cell responses stimulated using anti-CD3/CD28 antibody-loaded beads were evaluated using mouse splenocytes and human peripheral blood mononuclear cells. In addition, in vitro activities against bacteria implicated in IBD pathogenesis were tested. OPS-2071 dose-dependently decreased both colonic weight/length ratio and the colitis histological score as compared with the vehicle group. The therapeutic effect of OPS-2071 was equivalent to that of anti-IL-12/23 (p40) antibody. In vitro, OPS-2071 suppressed TNF-α production induced by LPS stimulation and T cell responses in a dose-dependent manner. At high concentrations, these effects were comparable to those of existing immunosuppressive agents, such as prednisolone, in both mouse and human cells. OPS-2071 also showed antibacterial activity against IBD-related bacteria. Our results suggest that OPS-2071 had both immunosuppressive and antibacterial effects. This dual effect makes OPS-2071 a unique and promising candidate for IBD.

Significance Guinea yam is an important staple tuber crop in West Africa, where it contributes to the sustenance and sociocultural lives of millions of people. Understanding the genetic diversity of Guinea yam and its relationships with wild relatives is important for improving this important crop using genomic information. A recent genomics study proposed that Guinea yam originated from a wild relative, the rainforest species Dioscorea praehensilis . Our results based on sequencing of 336 Guinea yam accessions do not support this notion; rather, our results indicate a hybrid origin of Dioscorea rotundata from crosses between the savannah species Dioscorea abyssinica and D. praehensilis.

Inhibition of gamma-glutamylcyclotransferase (GGCT), which is highly expressed in various cancer tissues, exerts anticancer effects both in vitro and in vivo. Previous studies have shown that depletion of GGCT blocks the growth of MCF7 breast cancer cells via upregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21); in addition, induction of autophagy plays a role in the upregulation of p21 upon GGCT knockdown. However, the mechanisms underlying induction of p21 in cancer cells are not fully understood. Here, we show that GGCT knockdown in PC3 human prostate cancer and A172 glioblastoma cells upregulates the mRNA and nuclear protein levels of Forkhead box O transcription factor 3a (FOXO3a), a transcriptional factor involved in tumor suppression. Simultaneous knockdown of FOXO3a and GGCT in PC3 and A172 cells attenuated upregulation of p21, followed by growth inhibition and cell death. Furthermore, simultaneous knockdown of GGCT and AMP-activated protein kinase (AMPK) α, a metabolic stress sensor, in PC3 and A172 cells led to marked attenuation of cellular responses induced by GGCT knockdown, including an increase in FOXO3a phosphorylation at Ser413, upregulation of p21, growth inhibition, and cell death. These results indicate that the AMPK–FOXO3a–p21 axis plays an important role in inhibition of cancer cell growth by depletion of GGCT.

Background/aim γ-Glutamylcyclotransferase (GGCT) is highly expressed in many forms of cancer, and is a promising therapeutic target. The present study investigated whether inhibition of GGCT enhanced the antiproliferative effects of the drug docetaxel in prostate cancer cells. Materials and methods Immunohistochemistry and western blot analysis were conducted to measure GGCT expression in prostate cancer tissue samples and cell lines. GGCT was inhibited using RNAi and a novel enzymatic inhibitor, pro-GA, and cell proliferation was evaluated with single and combination treatments of GGCT inhibitors and docetaxel. Results GGCT was highly expressed in cultured prostate cancer cells and patient samples. GGCT inhibition alone inhibited prostate cancer cell line proliferation and induced cellular senescence. GGCT inhibition in combination with apoptosis-inducing docetaxel had more potent antiproliferative effects than either drug used alone. Conclusion GGCT inhibition may potentiate anticancer drug efficacy.

Significance Guinea yam is an important staple tuber crop in West Africa, where it contributes to the sustenance and sociocultural lives of millions of people. Understanding the genetic diversity of Guinea yam and its relationships with wild relatives is important for improving this important crop using genomic information. A recent genomics study proposed that Guinea yam originated from a wild relative, the rainforest species Dioscorea praehensilis. Our results based on sequencing of 336 Guinea yam accessions do not support this notion; rather, our results indicate a hybrid origin of Dioscorea rotundata from crosses between the savannah species Dioscorea abyssinica and D. praehensilis., White Guinea yam (Dioscorea rotundata) is an important staple tuber crop in West Africa. However, its origin remains unclear. In this study, we resequenced 336 accessions of white Guinea yam and compared them with the sequences of wild Dioscorea species using an improved reference genome sequence of D. rotundata. In contrast to a previous study suggesting that D. rotundata originated from a subgroup of Dioscorea praehensilis, our results suggest a hybrid origin of white Guinea yam from crosses between the wild rainforest species D. praehensilis and the savannah-adapted species Dioscorea abyssinica. We identified a greater genomic contribution from D. abyssinica in the sex chromosome of Guinea yam and extensive introgression around the SWEETIE gene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improving this crop through molecular breeding.

White Guinea yam (Dioscorea rotundata) is an important staple tuber crop of West Africa. However, its origin remains unclear. In this study, we re-sequenced 336 accessions of white Guinea yam and compared them with the sequences of the wildDioscoreaspecies using an improved reference genome sequence ofD. rotundata. Our results suggest a hybrid origin of white Guinea yam from crosses between the rainforest wild speciesD. praehensilisand the savannah-adaptedD. abyssinica. We identified a higher genomic contribution fromD. abyssinicain the sex chromosome of Guinea yam and an extensive introgression around theSWEETIEgene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improvement of this crop through molecular breeding.

Background Crohn’s disease (CD) is a form of chronic inflammatory bowel disease (IBD). Although CD is an immune-mediated condition of unknown etiology, many studies suggested that abnormal immune responses against certain intestinal bacteria may trigger development of chronic inflammation. The T cell-mediated colitis model is a well characterized adaptive transfer murine model of chronic small bowel and colonic inflammation that resembles human CD (e.g., diarrhea, a heavily inflamed colon, loss of mucus from goblet cells, Th1/Th17 dominated cytokine profile). OPS-2071, a novel agent synthesized by Otsuka Pharmaceutical Co., Ltd, has broad and strong antibacterial activity with low systemic absorption. In this study, we have evaluated the therapeutic effect of OPS-2071 on murine T cell-mediated colitis and in vitro activity on T cell activation, cytokine production and antibacterial activity. Methods T cell-mediated colitis was induced via naive T cell (CD4+CD62L+CD44-) injection into T and B cell deficient recipient mice. Two weeks following T cell transfer, OPS-2071 or vehicle solution was administered orally for 3 weeks, followed by harvesting of colon tissue and assessment of efficacy evaluation by histological score and inflammatory index (colon weight/ length). In vitro inhibitory action for TNF-α production was assayed by ELISA using LPS-stimulated human peripheral blood cells. The effect on T cell activation and cytokine production (TNF-α, IFN-γ), was examined using human peripheral blood mononuclear cells and, mouse spleen which were stimulated by anti-CD2/CD3/CD28 antibody-loaded beads. In vitro activity against bacteria considered to be the cause of IBD was also tested. Results In the murine T cell transfer model, OPS-2071 significantly reduced both histological score (control: 9.2, OPS: 2.7, p128 mg/mL, respectively. Conclusion OPS-2071 demonstrated significant therapeutic effects on colon inflammation in the murine T cell-medicated colitis model, suppressed TNF-a production in vitro and showed in vitro activity against bacteria related to CD. The dual effect of anti-inflammatory effects and antibacterial activity of the novel agent OPS-2071 demonstrated in this study, provide rationale for exploring the impact of this compound on human CD in clinical trials.

Dioecy (distinct male and female individuals) combined with scarce to non-flowering are common features of cultivated yam (Dioscorea spp.). However, the molecular mechanisms underlying flowering and sex determination in Dioscorea are unknown. We conducted SuperSAGE transcriptome profiling of male, female and monoecious individuals to identify flowering and sex-related genes in white Guinea yam (D. rotundata). SuperSAGE analysis generated a total of 20,236 unique tags, of which 13,901 were represented by a minimum of 10 tags. Of these, 88 tags were significantly differentially expressed in male, female and monoecious plants. Of the 88 differentially expressed SuperSAGE tags, 18 corresponded to genes previously implicated in flower development and sex determination in multiple plant species. We validated the SuperSAGE data with quantitative real-time PCR (qRT-PCR)-based analysis of the expression of four candidate genes. Our findings suggest that mechanisms of flowering and sex determination are likely conserved in Dioscorea. We further investigated the flowering patterns of 1938 D. rotundata accessions representing diverse geographical origins over two years, revealing that over 85% of the accessions are either male or non-flowering, and that less than 15% are female, while monoecious plants are rare. Intensity of flowering appeared to be a function of sex, with male plants flowering more abundantly than female ones. Candidate genes identified in this study can be targeted with the aim to induce regular flowering in poor to non-flowering cultivars. Findings of the study provide important inputs for further studies aiming to overcome the challenge of flowering in yams and to improve the efficiency of yam breeding.

The use of antimicrobial agents in food-producing animals may lead to the emergence and spread of antimicrobial resistance in bacteria of animal origin. The use of antimicrobial agents in pigs in 2018 in Japan was evaluated in terms of the weight of active ingredient and number of defined daily doses (DDD), using annual sales data of veterinary antimicrobials sold for use in pigs. In addition, the use of antimicrobial agents in the Japanese pig sector in 2008 to 2017 was evaluated to determine whether or not there were any differences in temporal change pattern by use of different metrics. In 2018, 447 metric tons of active ingredient, corresponding to 77,379 × 106 kg-days (Japanese DDD) and 34,903 × 106 kg-days (European DDD) were sold. The proportion of the sales amount of sulfonamides, trimethoprim and lincosamides to the total sales amount was significantly different depending on the metric used. For most antimicrobial classes, the number of Japanese DDDs was greater than the number of European DDDs. These results indicate that the DDD-based metric, which is more reflective of the selective pressure of antimicrobials, is recommended for use in monitoring the antimicrobial use in pigs in Japan. The differences in the number of Japanese DDDs and European DDDs appear to confirm the need for Japanese DDDs.

Background OPS-2071 is a novel fluoroquinolone that is currently in Phase 2 clinical trials for the evaluation of Crohn’s disease (CD) as an add-on therapy to standard of care. OPS-2071 has broad and potent antibacterial activity with low systemic absorption. It was previously investigated for the treatment of enteric infections, including Clostridium difficile. CD is an immune-mediated condition of unknown aetiology; however, studies suggest that an abnormal immune response against certain intestinal bacteria may trigger the development of chronic inflammation. In this study, we have evaluated the effect of OPS-2071 on both the murine T-cell-mediated colitis as well as its in vitro effect on the activity of immune cells. Methods Transfer of naïve T cells (CD4+CD62L+CD44−) into immunodeficiency mice induces autoimmune colitis. Two weeks following T-cell transfer, OPS-2071, sulfasalazine and anti-IL12/23 p40 antibody were administered for 3 weeks, followed by assessment of efficacy evaluation by histological score and inflammatory index. In vitro inhibitory action for TNF-α production was assayed using LPS-stimulated human peripheral blood cells and THP-1 macrophages. The effect on T-cell activation and cytokine production (TNF-α, IFN-γ) was examined using anti-CD2/CD3/CD28 antibody-loaded beads-stimulated human peripheral blood mononuclear cells. In vitro activity against bacteria considered to be a potential cause of IBD such as M. avium sub. paratuberculosis, Klebsiella pneumonia, etc., was also tested. Results OPS-2071 and anti-IL12/23 p40 antibody significantly reduced both histological score (control: 9.0, OPS: 4.7, anti-IL12: 4.3, p < 0.01) and inflammatory index (control: 58.3 ± 3.7 mg/cm, OPS: 25.9 ± 1.4 mg/cm, anti-IL12: 41.1 ± 2.4 mg/cm, p < 0.01) at a dose of 10 and 25 mg/kg, respectively. OPS-2071 suppressed TNF-α production in T cells, as well as macrophage activity in a dose-dependent fashion. OPS-2071 also suppressed human T-cell activation and proliferation. At high OPS-2071 concentrations, these effects were comparable to prednisolone. The minimum inhibitory concentration against IBD-related bacteria for: OPS-2071, ciprofloxacin, and metronidazole were 0.015–0.5, 0.25–8 and 0.03–>128 mg/ml, respectively. Conclusion OPS-2071 demonstrated significant therapeutic effect on colonic inflammation, suppressed TNF-α production in vitro and showed in vitro activity against bacteria related to CD. From these in vitro results, it can be concluded that OPS-2071 has anti-inflammatory activity, independent of its antibacterial activity. The dual effects demonstrated by this novel agent, OPS-2071, provided a rationale for exploring the impact of this compound on human CD in clinical trials.

Yam (Dioscorea spp.) is a major staple crop widely cultivated for its starchy tubers. To date, very few marker resources are publicly avail - able as tools for genetic and genomic studies of this economically important crop. In this study, 90 simple sequence repeat (SSr) markers were developed from an enriched genomic library of yellow Guinea yam (D. cayenensis Lam.). Cross- amplification revealed that 85 (94.4%) and 51 (56.7%) of these SSrs could be successfully transferred to the two major cultivated species of D. rotundata poir. and D. alata L., respec - tively. polymorphisms in 30 markers selected on the basis of reliability and reproducibility of DNA bands were evaluated using a panel of 12 D. cayenensis, 48 D. rotundata, and 48 D. alata accessions. Accordingly, number of alleles per locus ranged from 2 to 8 in D. cayenensis (mean = 3.9), 3 to 30 in D. rotundata (mean = 13.9), and 2 to 22 in D. alata (mean = 12.1). The average observed and expected heterozygosi- ties were 0.156 and 0.634 ( D. cayenensis), 0.326 and 0.853 (D. rotundata), and 0.247 and 0.836 (D. alata), respectively. Clustering based on six SSrs that were polymorphic in at least four of the five cultivated Dioscorea species studied, including D. cayenensis, D. rotundata, D. alata, D. dumetorum (Kunth) pax., and D. bulbifera L., detected groups consistent with the phyloge - netic relationships of the species except for D. dumetorum. These new SSr markers are invalu - able resources for applications such as genetic diversity analysis and marker-assisted breeding.

Cowpea is traditionally important as an affordable source of protein and minerals and of cash income in sub-Saharan Africa, especially for small-scale farmers who have limited options for food and cash crops. The development and deployment of cowpea varieties with improved nutrition and quality that meet the needs of farmers and consumers should enhance cowpea consumption and production in the region. We have identified genetic diversity in various grain quality-related traits of cowpea and relationships among the traits. Wide genetic variation and strong correlations among crude protein, Fe and Zn contents suggest the possibility of improving the concentrations of these nutritional factors simultaneously. Low associations among physical and nutritional properties of grain indicate the possibility of introgressing favorable traits utilizing identified genetic resources. However, narrow variation in amino acid (AA) composition suggests a lesser possibility of improving the contents of specific AAs in cowpea, but it gave a reliable nitrogen-to-protein conversion factor of 5.45 for the estimation of crude protein content. Several improved breeding lines were identified with low concentrations of flatulence-causing oligosaccharides and various favorable agronomic traits and nutrient contents. TVu-12802 had the highest contents of crude protein and high contents of micronutrients, with a low ratio of phytic acid to Fe and Zn contents.

SUMMARYNucleotide-binding, leucine-rich repeat receptors (NLRs) are conserved cytosolic receptors that recognize pathogen effectors and trigger immunity in plants. Recent studies indicate that NLRs function in pairs. Rice resistance gene Pii has been known to confer resistance against rice blast pathogen Magnaporthe oryzae carrying AVR-Pii. Previously we reported isolation of Pii gene from the rice cultivar Hitomebore (Takagi et al. 2013). To further understand rice components required for Pii-mediated resistance, we screened 5,600 mutant lines of Hitomebore cultivar and identified two mutants that lost Pii resistance without any changes in Pii gene sequence. Application of MutMap-Gap, the whole genome sequencing-based method of mutation identification, to the two mutants revealed that they have mutations in another NLR gene located close to Pii. The F1 plants derived from a cross of the two mutants showed pii phenotype, demonstrating that the newly identified NLR gene is indeed a component of Pii resistance. We thus designate the previously isolated Pii gene as Pii-1 and the newly isolated NLR gene as Pii-2.

Background Root and tuber crops are a major food source in tropical Africa. Among these crops are several species in the monocotyledonous genus Dioscorea collectively known as yam, a staple tuber crop that contributes enormously to the subsistence and socio-cultural lives of millions of people, principally in West and Central Africa. Yam cultivation is constrained by several factors, and yam can be considered a neglected “orphan” crop that would benefit from crop improvement efforts. However, the lack of genetic and genomic tools has impeded the improvement of this staple crop. Results To accelerate marker-assisted breeding of yam, we performed genome analysis of white Guinea yam (Dioscorea rotundata) and assembled a 594-Mb genome, 76.4% of which was distributed among 21 linkage groups. In total, we predicted 26,198 genes. Phylogenetic analyses with 2381 conserved genes revealed that Dioscorea is a unique lineage of monocotyledons distinct from the Poales (rice), Arecales (palm), and Zingiberales (banana). The entire Dioscorea genus is characterized by the occurrence of separate male and female plants (dioecy), a feature that has limited efficient yam breeding. To infer the genetics of sex determination, we performed whole-genome resequencing of bulked segregants (quantitative trait locus sequencing [QTL-seq]) in F1 progeny segregating for male and female plants and identified a genomic region associated with female heterogametic (male = ZZ, female = ZW) sex determination. We further delineated the W locus and used it to develop a molecular marker for sex identification of Guinea yam plants at the seedling stage. Conclusions Guinea yam belongs to a unique and highly differentiated clade of monocotyledons. The genome analyses and sex-linked marker development performed in this study should greatly accelerate marker-assisted breeding of Guinea yam. In addition, our QTL-seq approach can be utilized in genetic studies of other outcrossing crops and organisms with highly heterozygous genomes. Genomic analysis of orphan crops such as yam promotes efforts to improve food security and the sustainability of tropical agriculture. Electronic supplementary material The online version of this article (doi:10.1186/s12915-017-0419-x) contains supplementary material, which is available to authorized users.

In Japan veterinary antimicrobials are used most in the pig production sector. However, there is a paucity of data on the quantity of antimicrobials used on pig farms in Japan. This study describes antimicrobial use on Japanese pig farms in 2015, 2016 and 2017 in terms of mg of active ingredient per kg of PCU (population correction unit). Data on antimicrobial use from a total of 72 farrow-to finish farms over these three years were used in the study. The results revealed that the average use of antimicrobials in 2015, 2016 and 2017 was 304.8 (SD = 226.3), 311.2 (SD = 241.0) and 342.9 (SD = 291.3) mg/kg PCU, respectively. Most (97%) of the antimicrobials were administered orally. The most commonly used antimicrobials were tetracyclines, followed by macrolides, penicillins and sulfonamides. Tohoku was the region in which the lowest quantities of antimicrobial were used whilst South Kanto was the region in which the largest amount was used. The use of antimicrobials was on the increase in the North Kanto, South Kanto and Kyushu regions.

In sugarcane (Saccharum spp. hybrid) breeding, introgression of useful genes via intergeneric hybridization is a powerful strategy for improving the crop productivity. Erianthus arundinaceus shows great potential in terms of useful traits; however, little is known about the cytogenetic and agronomic characteristics of intergeneric hybrids between these two species. Here, we examine the cytogenetic and agronomic characteristics, and relationships between the two in intergeneric F1 hybrids between modern sugarcane cultivar and E. arundinaceus identified by amplification of 5S rDNA markers and morphological characteristics. The nuclear DNA content of the hybrids varied from 6.07 to 8.94 pg/2C, with intra-clonal variation in DNA content and 5S rDNA sites. Genomic in situ hybridization revealed 53 to 82 chromosomes in the hybrids, with 53 to 56 derived from sugarcane and 1 to 29 from E. arundinaceus. There were significant positive correlations between the number of E. arundinaceus chromosomes and dry matter yield, millable stalk weight, single stalk weight, and stalk diameter, but not sucrose content, reducing sugar content, sucrose/reducing sugar ratio or fiber content. This detailed information on intergeneric F1 hybrids between modern sugarcane cultivar and E. arundinaceus will contribute to effective utilization of E. arundinaceus in sugarcane breeding.

Genetic analysis of vernalization and photoperiod responses was carried out using eight wheat cultivars, in order to investigate the relationship between their genotype and the earliness of heading in the southwestern part of Japan. Allelism test of the genes for the vernalization response showed that three wheat cultivars, 'Fukuwasekomugi', 'Zenkoujikomugi' and 'Schomburgk', harboured Vrn-Dl, Vrn-Dl and Vrn-A1, respectively. Among the eight cultivars tested, 'Haruhikari' was sensitive to short photoperiod, while the others were insensitive. Segregation analysis of the photoperiod response in the F 2 and B 1 F 1 populations showed that the very late heading cultivar 'Haruhikari' did not harbour major genes for insensitivity to photoperiod. Six cultivars characterized by medium to late heading, 'Norin 61', 'Zenkoujikomugi', 'Saitama 27', 'Schomburgk', 'Norin 59' and 'Norin 67', carried a single gene for insensitivity, Ppd-S, in common. The extremely early heading cultivar 'Fukuwasekomugi' was found to carry two genes for insensitivity, Ppd-S and Ppd-F, the latter displaying a stronger effect for insensitivity to photoperiod. The present study revealed that the earliness of heading in the southwestern part of Japan was closely related to the Ppd genotype of wheat cultivars, whereas it was independent of the Vrn genotype.

To clarify the potential usefulness of non-steroidal anti-inflammatory drugs, NSAIDs, for patients with overactive bladder, we examined the effect of NSAIDs on urodynamic parameters in normal and cystitis rats and compared their ulcerogenic activity in the gastrointestinal mucosa. Cystometry was performed after administration of the conventional NSAIDs, aspirin, indomethacin, or ketoprofen. Prostaglandin levels were measured in the bladder of cystitis rats pretreated with NSAIDs. Furthermore, the ulcerogenic responses were examined. NSAIDs increased bladder capacity without any effect on micturition pressure in normal rats in the following rank order of potency: ketoprofen ≥ indomethacin ≥ aspirin. In cystitis rats, bladder capacity was increased and micturition frequency was decreased. The levels of prostaglandin were significantly increased in cystitis rats. All NSAIDs inhibited the increment of prostaglandin levels at doses equal to that effective in the improvement of bladder functions. When administered intraduodenally, both ketoprofen and indomethacin induced lesions in the gastrointestinal mucosa. However, aspirin had no significant effect. We demonstrate that NSAIDs are effective in animal models of disease, most likely by suppressing by prostaglandin synthesis. Since aspirin, in contrast to ketoprofen or indomethacin, did not cause any gastrointestinal lesions, aspirin might be the NSAIDs treatment of choice for overactive bladder. Keywords:: aspirin, non-steroidal anti-inflammatory drug, overactive bladder, urodynamic parameter, gastrointestinal lesion

Synthesis of (-)-codonopsinine (2) was accomplished in seven steps that involved an addition of five-membered cyclic nitrone 1, readily obtained from L-xylose, with the Grignard reagent. Nitrone 1 also underwent intermolecular cycloaddition with several α,β-unsaturated esters 12 to afford cycloadducts 13, one of which, 13c, was elaborated to the key intermediate 17 for (+)-hyacinthacines A 1 (3a) and A 2 (3b).

札幌市内に分布する低地と丘陵地の2地区で, アーバンフリンジを事例とした景観評価を行った。レパートリーグリッド発展法の結果.2地区とも「緑の多さ」が好ましい景観の評価項目であった。またSD法の結果を因子分析したところ, 4つの因子軸が抽出され3つが評価軸だった。3つの評価軸は特有の景観構成要素と有意な相関を示した: 快適性軸一低木 (正相関), 開放性軸一山 (正)・荒地 (正)・人工物 (負), 特徴性軸一高木 (正)・住宅 (負)・雑草地 (負)。又, 景観の総合評価である嗜好度に対して, 快適性因子が最も強い影響を持っていた。以上のことから, 景観の総合評価には緑量と低木との相関があることが明らかになった。

非漢字系日本語学習者の漢字学習を巡る先行研究では、まず漢字の「字形」に対するパターン認識能力が漢字学習に影響を与えるのではないかという結果 を得ている。しかし、パターン認識能力がどのように漢字学習に影響を及ぼすのか、またどのようにすればパターン認識能力が促進されるのかは明確でなかった。そこで本研究では、パターン認識能力と漢字学習の関係を明らかにする目的で、実験という枠組みの中で、非漢字系日本語学習者の漢字パターン認識能力を調べ、さらに漢字パターン認識能力が促進されるであろう教授項目を取り込み、指導を行なった。実験計画は1要因、2水準の被験者内計画(要因名:パターン認識能力を促進させる漢字指導法)である。実験の結果 、非漢字系日本語学習者の漢字学習では、漢字の「字形」に対するパターン認識能力を促進することが漢字習得を高めるということが分かった。また、指導法の効果 も認められたことから、非漢字系日本語学習者に対する漢字指導では、漢字パターン認識能力が促進するような教授項目を含める必要があると思われる。, Past studies of the comprehension of kanji among non-kanji-area students reached the conclusion that the ability to recognize kanji shape patterns played a role in kanji acquisition. Nevertheless, issues such as the manner in which pattern recognition affected the learning progress and how such pattern recognition could be enhanced remained outstanding questions. The objective of this study was to clarify the connection between pattern recognition and the learning process itself. It was carried out by testing the capacity of non-kanji area students to recognize kanji Patterns under an experimental format and by trying out instructional approaches that incorporated modes that were expected to boost kanji-pattern recognition. The experiment rated the efficacy of the instructional methodology for kanji-pattern recognition as a factor in kanji acquisition on the basis of pre- and post-instructional test scores. It can be concluded from this study that increasing the kanji pattern recognition among non-kanji area students will boost their acquisition and comprehension of kanji. These findings underscore the need for the introduction of methodologies aimed to boost the the pattern-recognition capacity of such students in the course of their studies of kanji.

「テレビニュースを中心とした日本語学習用コースウェアの開発－学習内容の選択と整理－」に続いて、テレビニュースを聞けるようになるための聴解学習用CAIコースウェアを、授業設計の視点に立って開発した。実際のテレビニュースを録画したものを利用し、コースウェアの中で映像として提示した。また、単語や例文、練習問題を音声情報として、CRT画面 上の文字と同時に提示した。テレビニュースの視聴、やさしく直したニュースの聴解、単語の学習と記憶、表現の学習と練習、構文の練習を組み合わせ、数レッスンの学習によってテレビニュースが聞いてわかるようになることをめざした。, Based on "Development of Course-ware for Japanese-Language Learning on Television News: Selection and Organization of Learning Items," this study continues to develop a CAI system in this area. Television news broadcasts are presented by video, and vocabulary, example sentences, and exercises are presented on computer display together with audio presentation. The material consists of one shot of a television news broadcast, simplified news recorded by an instructor, vocabulary learning, expression learning, and structure learning. This material is designed to practice listening comprehension of television news through the completion of several lessons.

Synthesis of (-)-codonopsinine (2) was accomplished in seven steps that involved an addition of five-membered cyclic nitrone 1, readily obtained from L-xylose, with the Grignard reagent. Nitrone 1 also underwent intermolecular cycloaddition with several α,β-unsaturated esters 12 to afford cycloadducts 13, one of which, 13c, was elaborated to the key intermediate 17 for (+)-hyacinthacines A 1 (3a) and A 2 (3b).

Taro [Colocasia esculenta L. Schott] is one of the three important root crops of the monocotyledonous family Araceae. The other two comprise species of the genera Alocasia and Xanthosoma. The Greek name colocasia was derived from the Arabic “qolquas” and the Malay name “tallas” gave rise to the Polynesian taro (Porteres 1960). There are confusions in the taxonomy of different edible Colocasia cultivars. Based on the morphology of the sterile appendage within the spathe, some researchers recognize two species, namely, C. esculenta and C. antiquorum. Others consider only one species, C. esculenta. Currently, many workers recognize C. esculenta but with two varieties, var. esculenta (syn. var. typica A. E Hill) or “dasheen” type and var. antiquorum (Schott) Hubbard and Rehder (syn. var. globulifera Engl. and Krause) or “eddoe” type (Purseglove 1975). Generally, the main difference between these two varieties lies in the form of their corm (“tuber”). Variety esculenta has a main large corm with few small side cormels while var. antiquorum produces a relatively small central corm but with many side cormels.

An acidic polysaccharide, called pinellian PA, was isolated from the tuber of Pinellia ternata BRETT. It was homogeneous on electrophoresis and gel chromatography, and its molecular mass was estimated to be 11.8×104. Pinellian PA is composed of L-arabinose : D-galactose : L-rhamnose : D-galacturonic acid : D-glucuronic acid in the molar ratio of 5 : 15 : 1 : 3 : 3, in addition to small amounts of O-acetyl groups and peptide moieties. Reduction of carboxyl groups, methylation analysis and nuclear magnetic resonance studies show that the core structural features include a backbone chain composed of β-1, 3-linked D-galactose units. Some of the galactose units in the backbone carry β-1, 6-linked D-galactosyl side-chains at position 6. Pinellian PA produces significant potentiation of the reticuloendothelial system, as shown by a carbon clearance test, and also exhibits potent anti-complementary activity.

Using hematoxylin staininba method (Table 1), 125 wheat varieties registered in Japan and their 80 ancestral varieties were examined for their aluminum tolerance (Tables 2 and 3). There were no highly tolerant (Score 1) or highly susceptible (Score 9) varieties in the Japanese registered varieties as Shown in Table 2. Among these registered varieties, however, thirteen have fairly high tolerant ability (Score 3). From their pedigree data, it was proved that their Al tolerance was derived from an American variety "Turkey Red II" and/or Japanese local variety "Shiro Sanjaku". Most of these tolerant registered varieties were originated from the northern Ando soil area (Fig.1). Almost all of Japanese field soils are acidic and more or less aluminous, neverthless 88.0% of the reglstered vanetles have Score 5 (Intermedrate) and Score 7 (Susceptible), and the frequency of susceptible varieties have been increasing recently (Fig.2). These results suggest that aluminum tolerance is not a serious problem to the Japanese wheat breeding, because Japanese field soils had been ameriolated. The tolerant (Score 3) varieties were also selected for earliness, dwarfness and highly yielding ability as a result of general soil acidic conditions when soil acidity of their breeding nursery has not yet been improved.

Paralleled experimental studies of radioisotopic bone marrow imaging, bone scanning, and skeletal radiologic survey were undertaken upon the intramedullary-implanted and hematogenously metastatic VX-2 rabbit bone carcinoma in order to see their temporal relationship in delineating such lesions. Both bone and bone marrow scans turned positive far earlier than the x-rays. Moreover, lesion-depicting marrow scans were obtainable before the bone scans became positive. Radiocolloidal marrow scanning appears to be one of the techniques of choice in the early diagnosis of metastatic skeletal malignancies.