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Hozumi S.,Hiroshima University | Hirabayashi R.,Hiroshima University | Yoshizawa A.,Hiroshima University | Yoshizawa A.,Nagoya University | And 9 more authors.
PLoS ONE | Year: 2012

Spatially and temporally controlled gene expression, including transcription, several mRNA processing steps, and the export of mature mRNA to the cytoplasm, is essential for developmental processes. It is well known that RNA helicases of the DExD/H-box protein family are involved in these gene expression processes, including transcription, pre-mRNA splicing, and rRNA biogenesis. Although one DExD/H-box protein, Prp5, a homologue of vertebrate Ddx46, has been shown to play important roles in pre-mRNA splicing in yeast, the in vivo function of Ddx46 remains to be fully elucidated in metazoans. In this study, we isolated zebrafish morendo (mor), a mutant that shows developmental defects in the digestive organs and brain, and found that it encodes Ddx46. The Ddx46 transcript is maternally supplied, and as development proceeds in zebrafish larvae, its ubiquitous expression gradually becomes restricted to those organs. The results of whole-mount in situ hybridization showed that the expression of various molecular markers in these organs is considerably reduced in the Ddx46 mutant. Furthermore, splicing status analysis with RT-PCR revealed unspliced forms of mRNAs in the digestive organ and brain tissues of the Ddx46 mutant, suggesting that Ddx46 may be required for pre-mRNA splicing during zebrafish development. Therefore, our results suggest a model in which zebrafish Ddx46 is required for the development of the digestive organs and brain, possibly through the control of pre-mRNA splicing. © 2012 Hozumi et al.

Matsui H.,Kanazawa University | Matsui H.,Biological Research Laboratories | Kakei M.,Kanazawa University | Kakei M.,Translational Medical Center | And 2 more authors.
Journal of Insect Physiology | Year: 2012

During larval-pupal transformation, the anterior silk glands (ASGs) of the silkworm Bombyx mori undergo programmed cell death (PCD) triggered by 20-hydroxyecdysone (20E). Under standard in vitro culture conditions (0.3. ml of medium with 1. μM 20E), ASGs of the fourth-instar larvae do not undergo PCD in response to 20E. Similarly, larvae of the fifth instar do not respond to 20E through day 5 of the instar (V5). However, ASGs of V6 die when challenged by 20E, indicating that the glands might be destined to die before V6 but that a death commitment is not yet present. When we increased the volume of culture medium for one gland from 0.3 to 9. ml, V5 ASGs underwent PCD. We examined the response of ASGs to 20E every day by culturing them in 9. ml of medium and found that ASGs on and after V2 were fully responsive to 20E. Because pupal commitment is associated with juvenile hormone (JH), the corpora allata (a JH secretory organ) were removed on day 3 of the fourth larval instar (IV3), and their ASGs on V0 were cultured with 20E. Removal of the corpora allata allowed the V0 larval ASGs to respond to 20E with PCD. In contrast, topical application of a JH analogue inhibited the response to 20E when applied on or before V5. We conclude that the acquisition of responsiveness to 20E precedes the loss of JH sensitivity, and that the death commitment in ASGs occurs between V5 and 6. © 2012 Elsevier Ltd.

Kamoshita A.,Asian Natural Environmental Science Center | Ikeda H.,University of Tokyo | Ikeda H.,Biological Research Laboratories | Yamagishi J.,University of Tokyo | Ouk M.,Cambodian Agricultural Research and Development Institute
Weed Biology and Management | Year: 2010

Weed infestations are a major cause of yield reduction in rice (Oryza sativa) cultivation, particularly with direct-seeding methods, but the relationship between weed dynamics and water availability in Cambodian paddy fields has not been documented previously. We surveyed the weed abundance and weed seed banks in the soil of paddy fields with inferred differences in their water regime in 22 farm fields in three provinces of Cambodia in the 2005 and 2006 rainy seasons. We studied rain-fed lowland fields in upslope and downslope topographic positions and fields at different distances from the irrigation water source inside an irrigation rehabilitation area. The weed seed banks were estimated by seedling emergence in small containers and weed abundance and vigor were estimated by a simple scoring system. The estimated weed seed bank in the top 5 cm of soil ranged from 52.1 to 167 × 103 seeds m-2 (overall mean of 8.5 × 103 seeds m-2) and contained a high proportion (86%) of sedge species, such as Fimbristylis miliacea L. and Cyperus difformis. Several fields had particularly large seed banks, including one near the reservoir. No clear difference was found in the weed seed banks between the irrigated fields that were located close to (upstream) and distant from (downstream) the water source or between the irrigated and rain-fed lowland fields, but the weed scores were larger in the rain-fed fields and the downstream fields within the irrigated area. A water shortage during the late growing season in 2005 led to a proliferation of weeds in some fields and an associated increase in weed seedbank size in 2006. However, the weed scores in 2006 were more strongly associated with that year's water conditions than with the weed seedbank size. © 2010 The Authors. Journal compilation © 2010 Weed Science Society of Japan.

Nakamura Y.,Lead Discovery and Optimization Research Laboratories i | Fujimoto T.,Lead Discovery and Optimization Research Laboratories i | Ogawa Y.,Lead Discovery and Optimization Research Laboratories i | Sugita C.,Lead Discovery and Optimization Research Laboratories i | And 10 more authors.
ACS Medicinal Chemistry Letters | Year: 2012

A novel orally bioavailable renin inhibitor, DS-8108b (5), showing potent renin inhibitory activity and excellent in vivo efficacy is described. We report herein the synthesis and pharmacological effects of 5 including renin inhibitory activity in vitro, suppressive effects of ex vivo plasma renin activity (PRA) in cynomolgus monkey, pharmacokinetic data, and blood pressure-lowering effects in an animal model. Compound 5 demonstrated inhibitory activities toward human renin (IC50 = 0.9 nM) and human and monkey PRA (IC50 = 1.9 and 6.3 nM, respectively). Oral administration of single doses of 3 and 10 mg/kg of 5 in cynomolgus monkey on pretreatment with furosemide led to dose-dependent significant reductions in ex vivo PRA and sustained lowering of mean arterial blood pressure for more than 12 h. © 2012 American Chemical Society.

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