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91.
Shin-ichi Takenaka Shinjiro Kaieda Tomotaka Kawayama Masanobu Matsuoka Yoichiro Kaku Takashi Kinoshita Yuki Sakazaki Masaki Okamoto Masaki Tominaga Katsuya Kanesaki Asako Chiba Sachiko Miyake Hiroaki Ida Tomoaki Hoshino 《Biochemistry and Biophysics Reports》2015
The newly characterized cytokine IL-38 (IL-1F10) belongs to the IL-1 family of cytokines. Previous work has demonstrated that IL-38 inhibited Candida albicans-induced IL-17 production from peripheral blood mononuclear cells. However, it is still unclear whether IL-38 is an inflammatory or an anti-inflammatory cytokine. We generated anti-human IL-38 monoclonal antibodies in order to perform immunohistochemical staining and an enzyme-linked immunosorbent assay. While human recombinant IL-38 protein was not cleaved by recombinant caspase-1, chymase, or PR3 in vitro, overexpression of IL-38 cDNA produced a soluble form of IL-38 protein. Furthermore, immunohistochemical analysis showed that synovial tissues obtained from RA patients strongly expressed IL-38 protein. To investigate the biological role of IL-38, C57BL/6 IL-38 gene-deficient (?/?) mice were used in an autoantibody-induced rheumatoid arthritis (RA) mouse model. As compared with control mice, IL-38 (?/?) mice showed greater disease severity, accompanied by higher IL-1β and IL-6 gene expression in the joints. Therefore, IL-38 acts as an inhibitor of the pathogenesis of autoantibody-induced arthritis in mice and may have a role in the development or progression of RA in humans. 相似文献
92.
Asako Kaise Kiminori Ohta Shinya Fujii Akifumi Oda Tokuhito Goto Yasuyuki Endo 《Bioorganic & medicinal chemistry》2018,26(13):3805-3811
Based on the co-crystal structure of bicalutamide with a T877A-mutated androgen receptor (AR), glycerol and aminoglycerol derivatives were designed and synthesized as a novel type of carborane-containing AR modulators. The (R)-isomer of 6c, whose chirality is derived from the glycerol group, showed 20 times more potent cell inhibitory activity against LNCaP cell lines expressing T877A-mutated AR than the corresponding (S)-isomer. Docking studies of both isomers with AR suggested that (R)-6c is in closer spatial proximity to helix-12 of the AR than (S)-6c, which is the most important common motif in the secondary structure of AR for the expression of antagonistic activity. 相似文献
93.
Summary The 5 and 3 flanking regions of the soybean glycinin gene, Gy1, responsible for expression in seeds, were analyzed by quantitative transient expression assay. The construct containing the -glucuronidase (uidA) reporter gene under the control of the 1.12 kb Gy1 promoter and 0.74 kb Gy1 terminator was introduced into immature soybean seeds and leaves by particle bombardment. To normalize the variability of introduction efficiency, a second reporter gene, firefly luciferase, was cobombarded as an internal standard, and relative activities (GUS/luciferase) were measured. There was a seed-specific -glucuronidase (GUS) expression, as observed by X-Gluc staining. Compared with the nopaline synthase gene (nos) terminator, the Gy1 terminator enhanced the level of expression in immature seeds, indicating that the terminator region of the glycinin gene is involved in the activation of the gene expression in these seeds. To identify cis-regulatory elements in the glycinin gene upstream sequence, deleted derivatives of the promoter were fused to the luciferase reporter gene. The expression could be measured with a higher accuracy, and constructs were introduced with the internal reporter uidA gene into immature seeds. The results suggest the presence of a positive regulatory element in the –620 to ––380 region of the Gy1 promoter. A deletion which eliminates the legumin box with its RY element led to increased relative activity, suggesting that this box is negatively regulating expression of the seed storage protein gene. Analysis of mutant promoters also suggest that the RY element involves negative regulation in seeds. This quantitative transient expression assay using particle bombardment provides a reliable system for the study of seed-specific gene expression in soybeans.Abbreviations GUS
-glucuronidase
-
Gy1
glycinin AlaB2 gene
- CaMV
cauliflower mosaic virus
-
nos
nopaline synthase gene
-
uidA
-glucuronidase gene
- X-Gluc
5-bromo-4-chloro-3-indolyl glucuronide 相似文献
94.
95.
Motoaki Seki Yoshibumi Komeda Asako Iida Yasuyuki Yamada Hiromichi Morikawa 《Plant molecular biology》1991,17(2):259-263
Successful transient expression of -glucuronidase (GUS) in Arabidopsis thaliana leaves and roots and Brassica napus stems was obtained after gene delivery with a pneumatic particle gun driven by compressed air. Effects of the pneumatic pressure used to accelerate the particles (accelerating pressure; 85 to 200 kg/cm2) and of preculture periods of plant tissues (0 to 6 days) on the efficiency of gene delivery were studied. In A. thaliana leaves, best results were obtained at 115 kg/cm2 of accelerating pressure and 3 days of preculture. In A. thaliana roots, the optimum was at 200 kg/cm2 of accelerating pressure and 3 days of preculture. These results indicate that both preculture period and accelerating pressure are vital factors that determine the efficiency of gene delivery by particle gun. 相似文献
96.
Kimiko Yamakawa Hisako Yanagi Keijiro Saku Jun Sasaki Takaaki Okafuji Yae Shimakura Koichi Kawai Shigeru Tsuchiya Kohki Takada Setsuya Naito Kikuo Arakawa Hideo Hamaguchi 《Human genetics》1991,86(5):445-449
Summary To assess the relationship between relatively severe hereditary hypercholesterolemia with Achilles tendon xanthomas and the defect of the low density lipoprotein (LDL) receptor gene, family studies were carried out in 17 hypercholesterolemic families. In 16 out of the 17 families, hypercholesterolemia co-segregated with four different gross rearrangements, six different restriction fragment length polymorphism (RFLP) haplotypes, or an abnormal TaqI band of the LDL receptor gene. These findings are compatible with the interpretation that hypercholesterolemia is caused by defective LDL receptor genes, and that the origin of the mutant LDL receptor genes in Japanese generally differs among different pedigrees. In the remaining family, the proband and his sibling, both having relatively severe hypercholesterolemia and Achilles tendon xanthomas, shared an RFLP haplotype, although the proband's other sibling with moderate hypercholesterolemia but without Achilles tendon xanthomas did not. The mutant gene for familial defective apolipoprotein B-100 was not detected in the 17 probands. These data suggest that most, if not all, of the relatively severe hereditary hypercholesterolemia associated with Achilles tendon xanthomas is caused by a defect of the LDL receptor gene. 相似文献
97.
98.
99.
Shinji Hadano Asako Otomo Ryota Kunita Kyoko Suzuki-Utsunomiya Akira Akatsuka Masato Koike Masashi Aoki Yasuo Uchiyama Yasuto Itoyama Joh-E Ikeda 《PloS one》2010,5(3)
Background
ALS2/alsin is a guanine nucleotide exchange factor for the small GTPase Rab5 and involved in macropinocytosis-associated endosome fusion and trafficking, and neurite outgrowth. ALS2 deficiency accounts for a number of juvenile recessive motor neuron diseases (MNDs). Recently, it has been shown that ALS2 plays a role in neuroprotection against MND-associated pathological insults, such as toxicity induced by mutant Cu/Zn superoxide dismutase (SOD1). However, molecular mechanisms underlying the relationship between ALS2-associated cellular function and its neuroprotective role remain unclear.Methodology/Principal Findings
To address this issue, we investigated the molecular and pathological basis for the phenotypic modification of mutant SOD1-expressing mice by ALS2 loss. Genetic ablation of Als2 in SOD1H46R, but not SOD1G93A, transgenic mice aggravated the mutant SOD1-associated disease symptoms such as body weight loss and motor dysfunction, leading to the earlier death. Light and electron microscopic examinations revealed the presence of degenerating and/or swollen spinal axons accumulating granular aggregates and autophagosome-like vesicles in early- and even pre-symptomatic SOD1H46R mice. Further, enhanced accumulation of insoluble high molecular weight SOD1, poly-ubiquitinated proteins, and macroautophagy-associated proteins such as polyubiquitin-binding protein p62/SQSTM1 and a lipidated form of light chain 3 (LC3-II), emerged in ALS2-deficient SOD1H46R mice. Intriguingly, ALS2 was colocalized with LC3 and p62, and partly with SOD1 on autophagosome/endosome hybrid compartments, and loss of ALS2 significantly lowered the lysosome-dependent clearance of LC3 and p62 in cultured cells.Conclusions/Significance
Based on these observations, although molecular basis for the distinctive susceptibilities to ALS2 loss in different mutant SOD1-expressing ALS models is still elusive, disturbance of the endolysosomal system by ALS2 loss may exacerbate the SOD1H46R-mediated neurotoxicity by accelerating the accumulation of immature vesicles and misfolded proteins in the spinal cord. We propose that ALS2 is implicated in endolysosomal trafficking through the fusion between endosomes and autophagosomes, thereby regulating endolysosomal protein degradation in vivo. 相似文献100.