Tempo-spatial variation in feeding activity and density of Aedes albopictus (Diptera: Culicidae) at peridomestic habitat in Nagasaki, Japan.

金沢大学理工研究域　自然システム学系1998年9月, 長崎大学熱帯医学研究所敷地内で家屋周辺の茂み及び裸地においてヒトスジシマカの24時間採集を行い, 周辺環境の異なる採集場所における吸血活動性と密度のちがいを調べた。ヒトスジシマカの密度は茂みで高く, 屋内や裸地で低かった。吸血活動は薄明薄暮に高まり, 夜も高かった。最も活動性が高い薄暮には, 統計的な有意差はみられないが, 昼間や夜間に比べて屋内や裸地で採集される雌個体の割合が高かった。以上の結果からヒトスジシマカの生態における夜間の吸血活動の重要性と薄明薄暮には茂み以外に裸地や屋内などでも吸血される機会が増加することが示唆された。 To clarify the tempo-spatial variation in feeding of Aedes albopictus, a field investigation was conducted in a field where the species heavily infested, in Nagasaki. Feeding activity was observed in the nighttime as well as at dawn and dusk. The density was high at sites with vegetation and low at sites without vegetation and indoors. At sites with vegetation, the proportion of females decreased at dawn and dusk, while it increased at sites without vegetation and indoors. Feeding activity in nighttime is possibly common in Ae. albopictus, and the place of feeding expands from sites with vegetation to sites without vegetation and indoors at dawn and dusk

Preliminary field experiments on exophagy of Aedes albopictus (Diptera: Culicidae) in peridomestic habitat.

金沢大学理工研究域　自然システム学系Preliminary field experiments were conducted to examine the exophagy of Aedes albopictus in peridomestic habitat by using three different types of experimental buildings in Nagasaki, Japan and Chiangmai, Thailand. The density of females collected by suction traps enhanced by CO2 was high inside net-walled buildings and at outdoor sites with vegetation. On the other hand, the densities inside a normal walled building and at outdoor sites without vegetation, the microclimate conditions of both of which were different from the outdoor sites with vegetation, were low. To evaluate the effect of blocking by walls for Ae. albopictus invading to feed, an additional experiment by using a bamboo hut with openings of different sizes in the walls was conducted in Thailand. As the opening in the walls was smaller, the difference in the number of females between inside and outside of the hut became significantly larger. Therefore, the effect of physical blocking by walls was suggested. We proposed the presence of vegetation, the difference in environmental conditions inside buildings from those in vegetation due to blocking, and physical blocking by walls for invasion as ecological factors influencing the exophagy of Ae. albopictus. (author abst.

Iron availability alters ascorbate-induced stress metabolism in Glehnia littoralis root cultures.

Our previous study indicated that formation of furanocoumarin phytoalexins could be induced in Glehnia littoralis root cultures by treatment with 10-40mM ascorbic acid (AsA). This furanocoumarin production is much less evident when G. littoralis roots are treated with AsA under iron-deficient conditions. Instead, two large unknown peaks appeared in the HPLC chromatogram, whose chemical structures were elucidated by spectroscopic methods as being 6, β-dihydroxyphenethyl ferulate (DF) and 6-hydroxyphenethyl ferulate (HF), respectively. Their maximal level of induction was observed at 20mM AsA, and the production of DF always exceeded that of HF. This is the first report of these compounds in G. littoralis and of the modulation of the phytoalexin biosynthetic pathway in G. littoralis by iron deficiency

Predicting the Start of the Aedes albopictus (Diptera: Culicidae) Female Adult Biting Season Using the Spring Temperature in Japan

Aedes albopictus (Skuse) (Diptera: Culicidae) is distributed widely and is common in much of Japan. In Japan, female adults begin to bite in between April and June, except in the southern subtropics where the mosquito has no dormant period. It is difficult to estimate the first Ae. albopictus biting day because it varies annually depending on the location. Over several years, we surveyed the mosquitoes at different locations that covered a range of warmer to cooler areas of Japan. We found an association between the timing of first biting day by Ae. albopictus and spring temperature. In spring months, the strongest correlation was found with mean April temperatures, followed by March. Based on these data, it may, therefore, be possible to apply a simple formula to predict the timing of the first biting day at various geographical locations in Japan. Forecasting maps were created using a simple prediction formula. We found that the first biting day for Ae. albopictus changed depending on early spring temperatures for each year. There was an approximate 20-d difference in first biting day between years with warmer and cooler springs. This prediction model will provide useful insight for planning and practice of Ae. albopictus control programs, targeting larvae and adults, in temperate regions globally.ArticleJournal of Medical Entomology.54(6):1519-1524(2017)journal articl

キサンチンオキシダーゼ阻害薬febuxostatはNrf2を活性化し脂肪細胞分化を抑制する

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine catabolism that acts as a novel regulator of adipogenesis. In pathological states, xanthine oxidoreductase activity increases to produce excess reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical inducer of antioxidants, which is bound and repressed by a kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm. The Keap1-Nrf2 axis appears to be a major mechanism for robust inducible antioxidant defenses. Here, we demonstrate that febuxostat, a xanthine oxidase inhibitor, alleviates the increase in adipose tissue mass in obese mouse models with a high-fat diet or ovariectomy. Febuxostat disrupts in vitro adipocytic differentiation in adipogenic media. Adipocytes appeared at day 7 in absence or presence of febuxostat were 160.8 ± 21.2 vs. 52.5 ± 12.7 (p < 0.01) in 3T3–L1 cells, and 126.0 ± 18.7 vs. 55.3 ± 13.4 (p < 0.01) in 10T1/2 cells, respectively. Adipocyte differentiation was further enhanced by the addition of hydrogen peroxide, which was also suppressed by febuxostat. Interestingly, febuxostat, but not allopurinol (another xanthine oxidase inhibitor), rapidly induced the nuclear translocation of Nrf2 and facilitated the degradation of Keap1, similar to the electrophilic Nrf2 activator omaveloxolone. These results suggest that febuxostat alleviates adipogenesis under oxidative conditions, at least in part by suppressing ROS production and Nrf2 activation. Regulation of adipocytic differentiation by febuxostat is expected to inhibit obesity due to menopause or overeating

LL-Z1640-2 for rheumatoid arthritis

Objectives: Aberrant NLRP3 inflammasome activation has been demonstrated in rheumatoid arthritis (RA), which may contribute to debilitating inflammation and bone destruction. Here, we explored the efficacy of the potent TGF-β-activated kinase-1 (TAK1) inhibitor LL-Z1640-2 (LLZ) on joint inflammation and bone destruction in collagen-induced arthritis (CIA). Methods: LL-Z1640-2 was administered every other day in CIA mice. Clinical and histological evaluation was performed. Priming and activation of NLRP3 inflammasome and osteoclastogenic activity were assessed. Results: NLRP3 inflammasome formation was observed in synovial macrophages and osteoclasts (OCs) in CIA mice. TACE and RANKL were also overexpressed in synovial macrophages and fibroblasts, respectively, in the CIA joints. Treatment with LLZ mitigated all the above changes. As a result, LLZ markedly suppressed synovial hypertrophy and pannus formation to alleviate pain and inflammation in CIA mice. LLZ could block the priming and activation of NLRP3 inflammasome in RAW264.7 macrophage cell line, primary bone marrow macrophages and OCs upon treatment with LPS followed by ATP, thereby suppressing their IL-1β production. LLZ also suppressed LPS-induced production of TACE and TNF-α in bone marrow macrophages and abolished IL-1β-induced production of MMP-3, IL-6 and RANKL in synovial fibroblasts. In addition, LLZ directly inhibits RANKL-mediated OC formation and activation. Conclusion: TAK1 inhibition with LLZ may become a novel treatment strategy to effectively alleviate inflammasome-mediated inflammation and RANKL-induced osteoclastic bone destruction in joints alongside its potent suppression of TNF-α and IL-6 production and proteinase-mediated pathological processes in RA

RANKLが誘導する破骨細胞分化におけるROSの役割と、Febuxostatによる破骨細胞分化抑制効果

Receptor activator of NF-κB ligand (RANKL), a critical mediator of osteoclastogenesis, is upregulated in multiple myeloma (MM). The xanthine oxidase inhibitor febuxostat, clinically used for prevention of tumor lysis syndrome, has been demonstrated to effectively inhibit not only the generation of uric acid but also the formation of reactive oxygen species (ROS). ROS has been demonstrated to mediate RANKL-mediated osteoclastogenesis. In the present study, we therefore explored the role of cancer-treatment-induced ROS in RANKL-mediated osteoclastogenesis and the suppressive effects of febuxostat on ROS generation and osteoclastogenesis. RANKL dose-dependently induced ROS production in RAW264.7 preosteoclastic cells; however, febuxostat inhibited the RANKL-induced ROS production and osteoclast (OC) formation. Interestingly, doxorubicin (Dox) further enhanced RANKL-induced osteoclastogenesis through upregulation of ROS production, which was mostly abolished by addition of febuxostat. Febuxostat also inhibited osteoclastogenesis enhanced in cocultures of bone marrow cells with MM cells. Importantly, febuxostat rather suppressed MM cell viability and did not compromise Dox’s anti-MM activity. In addition, febuxostat was able to alleviate pathological osteoclastic activity and bone loss in ovariectomized mice. Collectively, these results suggest that excessive ROS production by aberrant RANKL overexpression and/or anticancer treatment disadvantageously impacts bone, and that febuxostat can prevent the ROS-mediated osteoclastic bone damage

Host-feeding patterns of Culex tritaeniorhynchus and Anopheles sinensis (Diptera: Culicidae) in a ricefield agroecosystem.

金沢大学理工研究域　自然システム学系水田発生性蚊類成虫の吸血選択を調べるために, 佐賀県西有田町で1996及び1997年の5月から9月に成虫採集を行った。ドライアイス付加ライトトラップと吸虫管により合計31,804頭のコガタアカイエカとシナハマダラカ雌成虫を採集した。調査したすべての牛舎と豚舎ではライトトラップ採集により多数の成虫が捕獲されたが(牛舎7,933,豚6,441,鶏舎5,267), 鶏舎では吸血蚊がほとんど採集されなかった。コガタアカイエカとシナハマダラカの吸血率は, 牛舎と豚舎ではそれぞれ62%(N=7,113), 74%(N=7,261)であったが, 鶏舎では5%以下(N=5,267)であった。ELISAによる吸血源同定の結果, 両種とも鶏よりも牛と豚を選択していることが示された。また, 牛舎と隣接した鶏舎から採集された吸血蚊も90%以上(N=143)が牛を吸血していた。鶏よりも豚と牛から吸血する傾向は採集場所(棚田周辺か平野部), 採集方法(ライトトラップか吸虫管)を問わず観察された。 Adults of rice-field mosquitoes were collected between May and September of 1996 and 1997 in Nishi Arita, Saga Prefecture, Japan, to determine their feeding pattern in an area where animals were available in large numbers. In total, 31,804 female Culex tritaeniorhynchus and Anopheles sinensis were collected from animal sheds using dry ice-baited light traps and mouth aspiration. Light traps in all the animal sheds captured large numbers of mosquitoes (cowsheds 7,933,pigsties 6,441 and chicken sheds 5,267 mosquitoes), although few fed upon the chickens. Overall, 62% (N=7,113) of fed Cx. triaeniorhynchus and 74% (N=7,261) of An. sinensis were caught by light traps at the cowsheds and pigsties compared to less than 5% (N=5,267) at the chickens sheds. The type of animal in the shed was the most important factor determining the feeding rates. Blood-meal identification by direct ELISA indicated that both Cx. tritaeniorhynchus and An. sinensis preferred cows and pigs to chickens. Over 90% (N=143) of the fed mosquitoes collected from one chicken shed had fed upon cows in an adjoining cowshed. The tendency to feed upon cows and pigs more than on chickens was observed both in the hillside (terraced) and lowland ricefields. This trend is shown in the results obtained by both the aspirator and light trap collection methods