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951.
Hisashi Hashimoto Rieko Miyamoto Naoki Watanabe Dai Shiba Kenjiro Ozato Chikako Inoue Yuko Kubo Akihiko Koga Tomoko Jindo Takanori Narita Kiyoshi Naruse Kazuko Ohishi Keiko Nogata Tadasu Shin-I Shuichi Asakawa Nobuyoshi Shimizu Tomotsune Miyamoto Toshio Mochizuki Takahiko Yokoyama Hiroshi Hori Hiroyuki Takeda Yuji Kohara Yuko Wakamatsu 《PloS one》2009,4(7)
Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients. 相似文献
952.
Junichi Soh Naoki Okumura William W. Lockwood Hiromasa Yamamoto Hisayuki Shigematsu Wei Zhang Raj Chari David S. Shames Ximing Tang Calum MacAulay Marileila Varella-Garcia T?nu Vooder Ignacio I. Wistuba Stephen Lam Rolf Brekken Shinichi Toyooka John D. Minna Wan L. Lam Adi F. Gazdar 《PloS one》2009,4(10)
953.
Caenorhabditis elegans FOS-1 and JUN-1 Regulate plc-1 Expression in the Spermatheca to Control Ovulation 下载免费PDF全文
Susan M. Hiatt Holli M. Duren Y. John Shyu Ronald E. Ellis Naoki Hisamoto Kunihiro Matsumoto Ken-ichi Kariya Tom K. Kerppola Chang-Deng Hu 《Molecular biology of the cell》2009,20(17):3888-3895
Fos and Jun are components of activator protein-1 (AP-1) and play crucial roles in the regulation of many cellular, developmental, and physiological processes. Caenorhabditis elegans fos-1 has been shown to act in uterine and vulval development. Here, we provide evidence that C. elegans fos-1 and jun-1 control ovulation, a tightly regulated rhythmic program in animals. Knockdown of fos-1 or jun-1 blocks dilation of the distal spermathecal valve, a critical step for the entry of mature oocytes into the spermatheca for fertilization. Furthermore, fos-1 and jun-1 regulate the spermathecal-specific expression of plc-1, a gene that encodes a phospholipase C (PLC) isozyme that is rate-limiting for inositol triphosphate production and ovulation, and overexpression of PLC-1 rescues the ovulation defect in fos-1(RNAi) worms. Unlike fos-1, regulation of ovulation by jun-1 requires genetic interactions with eri-1 and lin-15B, which are involved in the RNA interference pathway and chromatin remodeling, respectively. At least two isoforms of jun-1 are coexpressed with fos-1b in the spermatheca, and different AP-1 dimers formed between these isoforms have distinct effects on the activation of a reporter gene. These findings uncover a novel role for FOS-1 and JUN-1 in the reproductive system and establish C. elegans as a model for studying AP-1 dimerization. 相似文献
954.
Kentaro Morita Tomoyuki Yamamoto Naoki Fusada Mamoru Komatsu Haruo Ikeda Nobutaka Hirano Hideo Takahashi 《Molecular genetics and genomics : MGG》2009,282(6):607-616
We have previously shown that, in vivo, the integration system based on the gene encoding the TG1 integrase and the corresponding
attB
TG1
and attP
TG1
sites works well not only in Streptomyces strains, but also in Escherichia coli. Furthermore, the attachment sites for TG1 integrase are distinct from those of ϕC31 integrase. In this report, we expressed
TG1 integrase as a GST-TG1 integrase fusion protein and then used affinity separation and specific cleavage to release purified
integrase. Conditions for in vitro recombination were established using the purified TG1 integrase and its cognate attP
TG1
and attB
TG1
sites. TG1 integrase efficiently catalyzed a site-specific recombination between attB
TG1
and attP
TG1
sites irrespective of their substrate topology. The minimal sequences of attP
TG1
and attB
TG1
sites required for the substrates of TG1 integrase were demonstrated to be 43 and 39-bp, respectively. These results provide
the basic features of the TG1 integrase system to be used as biotechnological tools, as well as to unravel the mechanism of
the serine integrase. 相似文献
955.
Yojiro Anzai Yohei Iizaka Wei Li Naoki Idemoto Shu-ichi Tsukada Kazuo Koike Kenji Kinoshita Fumio Kato 《Journal of industrial microbiology & biotechnology》2009,36(8):1013-1021
Some of the polyketide-derived bioactive compounds contain sugars attached to the aglycone core, and these sugars often impart
specific biological activity to the molecule or enhance this activity. Mycinamicin II, a 16-member macrolide antibiotic produced
by Micromonospora griseorubida A11725, contains a branched lactone and two different deoxyhexose sugars, d-desosamine and d-mycinose, at the C-5 and C-21 positions, respectively. The d-mycinose biosynthesis genes, mycCI, mycCII, mycD, mycE, mycF, mydH, and mydI, present in the M. griseorubida A11725 chromosome were introduced into pSET152 under the regulation of the promoter of the apramycin-resistance gene aac(3)IV. The resulting plasmid pSETmycinose was introduced into Micromonospora rosaria IFO13697 cells, which produce the 16-membered macrolide antibiotic rosamicin containing a branched lactone and d-desosamine at the C-5 position. Although the M. rosaria TPMA0001 transconjugant exhibited low rosamicin productivity, two new compounds, IZI and IZII, were detected in the ethylacetate
extract from the culture broth. IZI was identified as a mycinosyl rosamicin derivative, 23-O-mycinosyl-20-deoxo-20-dihydro-12,13-deepoxyrosamicin (MW 741), which has previously been synthesized by a bioconversion technique.
This is the first report on production of mycinosyl rosamicin-derivatives by a engineered biosynthesis approach. The integration
site ΦC31attB was identified on M. rosaria IFO13697 chromosome, and the site lay within an ORF coding a pirin homolog protein. The pSETmycinose could be useful for
stimulating the production of “unnatural” natural mycinosyl compounds by various actinomycete strains using the bacteriophage
ΦC31 att/int system. 相似文献
956.
Taoka Y Nagano N Okita Y Izumida H Sugimoto S Hayashi M 《Marine biotechnology (New York, N.Y.)》2009,11(3):368-374
The growth, lipid content, and fatty acid composition of Aurantiochytrium sp. strain mh0186 at different temperatures were investigated. Strain mh0186 grew well at 15–30°C, but weakly at 10°C. The
biomass at 15–30°C was significantly higher than at 10 and 35°C, and the total lipid at 15–35°C was significantly higher than
that at 10°C. The amount of DHA in the total fatty acid was highest at 10°C and decreased in response to temperature increase.
The content of DHA (mg/g-dry cell weight) at 15–30°C were significantly higher than those at 35°C and those at 15–25°C were
significantly higher than those at 10 and 35°C. The DHA yield at 15–35°C was significantly higher than those at 10 and 35°C.
Unsaturation of fatty acid was regulated by temperature and was enhanced in response to temperature decrease. The ratio of
DHA to DPA varied at different temperatures. 相似文献
957.
A set of microsatellites markers were developed for Livistona chinensis var. boninensis, an endemic palm tree of the Bonin Islands. We obtained 123 sequences containing unique microsatellites from an enriched
library. Twelve loci were screened for their feasibility using 32 trees. They showed polymorphisms with two to nine alleles
per locus. No significant deviation from Hardy–Weinberg equilibrium was observed for 11 loci. No genotypic disequilibrium
was detected between any two of the loci. Total exclusionary powers for the first and the second parents were 0.978774 and
0.998987, respectively. These markers will allow us to investigate the gene flow within/among populations of the species. 相似文献
958.
Junco Nagata Youichi Sonoda Keiko Hamaguchi Naoki Ohnishi Soh Kobayashi Ken Sugimura Fumio Yamada 《Conservation Genetics》2009,10(4):1121-1123
We report on the isolation and characterization of eight polymorphic and five monomorphic microsatellites in the Amami rabbit
(Pentalagus furnessi). Microsatellite polymorphism was determined using 25 individuals. There were 2–11 alleles for each polymorphic locus with
heterozygosity ranging between 0.08 and 0.76. Linkage disequilibrium was not suggested between any pairs among the eight polymorphic
loci. We suggest that these primers be used in future studies to monitor population size, determine dispersal patterns, and
genetic diversity within and between populations of this and related species. 相似文献
959.
Yu L Ikeda K Kato A Adachi I Godin G Compain P Martin O Asano N 《Bioorganic & medicinal chemistry》2006,14(23):7736-7744
The most common lysosomal storage disorder, Gaucher disease, is caused by inefficient folding and trafficking of certain variants of lysosomal beta-glucosidase (beta-Glu, also known as beta-glucocerebrosidase). Recently, Sawker et al. reported that the addition of subinhibitory concentrations (10 microM) of the pharmacological chaperone N-nonyl-1-deoxynojirimycin (NN-DNJ) (10) to Gaucher patient-derived cells leads to a 2-fold increase in activity of mutant (N370S) enzyme [Proc. Natl. Acad. Sci. U.S.A.2002, 99, 15428]. However, we found that the addition of NN-DNJ at 10 microM lowered the lysosomal alpha-glucosidase (alpha-Glu) activity by 50% throughout the assay period in spite of the excellent chaperoning activity in N370S fibroblasts. Hence, we prepared a series of DNJ derivatives with an alkyl chain at the C-1alpha position and evaluated their in vitro inhibitory activity and potential as pharmacological chaperones for Gaucher cell lines. Among them, alpha-1-C-octyl-DNJ (CO-DNJ) (15) showed 460-fold stronger in vitro inhibitory activity than DNJ toward beta-Glu, while NN-DNJ enhanced in vitro inhibitory activity by 360-fold. Treatment with CO-DNJ (20 microM) for 4 days maximally increased intracellular beta-Glu activity by 1.7-fold in Gaucher N370 cell line (GM0037) and by 2.0-fold in another N370 cell line (GM00852). The addition of 20 microM CO-DNJ to the N370S (GM00372) culture medium for 10 days led to 1.9-fold increase in the beta-Glu activity without affecting the intracellular alpha-Glu activity for 10 days. Only CO-DNJ showed a weak beta-Glu chaperoning activity in the L444P type 2 variant, with 1.2-fold increase at 5-20 microM, and furthermore maximally increased the alpha-Glu activity by 1.3-fold at 20 microM. These experimental results suggest that CO-DNJ is a significant pharmacological chaperone for N370S Gaucher variants, minimizing the potential for undesirable side effects such as alpha-Glu inhibition. 相似文献
960.