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Identification of a major gene responsible for type 1 diabetes in the Komeda diabetes-prone rat. 总被引:2,自引:0,他引:2
Norihide Yokoi 《Experimental Animals》2005,54(2):111-115
Type 1 diabetes mellitus is an autoimmune disease involving both environmental and genetic factors. Genetic analyses in humans and rodents have shown that the major histocompatibility complex (MHC) is a major genetic factor and that several other genes may be involved in the development of the disease. We performed genetic analysis of type 1 diabetes in a newly established animal model, the Komeda diabetes-prone (KDP) rat, and found that most of the genetic predisposition to diabetes is accounted for by two major susceptibility genes, MHC and Iddm/kdp1. In addition, we identified a nonsense mutation in the Casitas B-lineage lymphoma b (Cblb) gene by positional cloning of Iddm/kdp1. In this paper, I review our positional cloning analysis of Iddm/kdp1 and propose a two-gene model of the development of type 1 diabetes in which two major susceptibility genes, Cblb and MHC, determine autoimmune reaction and tissue specificity to pancreatic beta-cells, respectively. 相似文献
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Yokoi N Fujiwara Y Wang HY Kitao M Hayashi C Someya T Kanamori M Oiso Y Tajima N Yamada Y Seino Y Ikegami H Seino S 《Biochemical and biophysical research communications》2008,368(1):37-42
Casitas B-lineage lymphoma b (Cblb) is a negative regulator of T-cell activation and dysfunction of Cblb in rats and mice results in autoimmunity. In particular, a nonsense mutation in Cblb has been identified in a rat model of autoimmune type 1 diabetes. To clarify the possible involvement of CBLB mutation in type 1 diabetes in humans, we performed mutation screening of CBLB and characterized functional properties of the mutations in Japanese subjects. Six missense mutations (A155V, F328L, N466D, K837R, T882A, and R968L) were identified in one diabetic subject each, excepting N466D. Of these mutations, F328L showed impaired suppression of T-cell activation and was a loss-of-function mutation. These data suggest that the F328L mutation is involved in the development of autoimmune diseases including type 1 diabetes, and also provide insight into the structure-function relationship of CBLB protein. 相似文献
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Chinese hamster ovary (CHO) cells were cultivated in a compact loop bioreactor using MEM-alpha medium supplemented with 10% fetal calf serum. Effects of physical and chemical environments, i.e., pH in the medium, stirring speed of impellers, temperature and partial pressure of oxygen (pO2) upon growth of suspended cells in the bioreactor were determined in batch cultures. Growth behavior was characterized by specific rates of growth (mu), glucose consumption (qG) and lactate production (qL), and the yield coefficients (cell yield from glucose, YX/G, and lactate yield from glucose, YL/G). An effect of medium osmolality was also evaluated with T-flask monolayer cultivation. The best growth was observed at pH 7.6, 37 degrees C, 400 rpm, 50-100% saturation with oxygen and 320 mOsmol kg-1. Corresponding to the previous work with a human melanoma cell line, the sophisticated cultivation and process control systems have been improved for CHO cells. 相似文献
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David Wari Jun Yamashita Yoko Kataoka Yoko Kohara Norihide Hinomoto Hidenari Kishimoto Shingo Toyoshima Shoji Sonoda 《Experimental & applied acarology》2014,63(3):313-332
A population survey of phytoseiid mites and spider mites was conducted on peach leaves and wild plants in Japanese peach orchards having different pesticide practices. The phytoseiid mite species composition on peach leaves and wild plants, as estimated using quantitative sequencing, changed during the survey period. Moreover, it varied among study sites. The phytoseiid mite species compositions were similar between peach leaves and some wild plants, such as Veronica persica, Paederia foetida, Persicaria longiseta, and Oxalis corniculata with larger quantities of phytoseiid mites, especially after mid-summer. A PCR-based method to detect the ribosomal ITS sequences of Tetranychus kanzawai and Panonychus mori from phytoseiid mites was developed. Results showed that Euseius sojaensis (specialized pollen feeder/generalist predator) uses both spider mites as prey in the field. 相似文献
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Inhibition of photosynthesis by intracellular carbonic anhydrase in microalgae under excess concentrations of CO2 总被引:2,自引:0,他引:2
When cells of Chlorococcum littorale that had been grown in air (air-grown cells) were transferred to extremely high CO2 concentrations (>20%), active photosynthesis resumed after a lag period which lasted for 1–4 days. In contrast, C. littorale cells which had been grown in 5% CO2 (5% CO2-grown cells) could grow in 40% CO2 without any lag period. When air-grown cells were transferred to 40% CO2, the quantum efficiency of PS II (ΦII) decreased greatly, while no decrease in ΦII was apparent when the 5% CO2-grown cells were transferred to 40% CO2. In contrast to air-grown cells, 5% CO2-grown cells showed neither extracellular nor intracellular carbonic anhydrase (CA) activity. Upon the acclimation of 5% CO2-grown cells to air, photosynthetic susceptibility to 40% CO2 was induced. This change was associated with the induction of CA. In addition, neither suppression of photosynthesis nor
arrest of growth was apparent when ethoxyzolamide (EZA), a membrane-permeable inhibitor of CA, had been added before transferring
air-grown cells of C. littorale to 40% CO2. The intracellular pH value (pHi) decreased from 7.0 to 6.4 when air-grown C. littorale cells were exposed to 40% CO2 for 1–2 h, but no such decrease in pHi was apparent in the presence of EZA. Both air- and 5% CO2-grown cells of Chlorella sp. UK001, which was also resistant to extremely high CO2 concentrations, grew in 40% CO2 without any lag period. The activity of CA was much lower in air-grown cells of this alga than those in air-grown C. littorale cells. These results prompt us to conclude that intracellular CA caused intracellular acidification and hence inhibition
of photosynthetic carbon fixation when air-grown C. littorale cells were exposed to excess concentrations of CO2. No such harmful effect of intracellular CA was observed in Chlorella sp. UK001 cells.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
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p53-dependent S-phase damage checkpoint and pronuclear cross talk in mouse zygotes with X-irradiated sperm 下载免费PDF全文
Shimura T Inoue M Taga M Shiraishi K Uematsu N Takei N Yuan ZM Shinohara T Niwa O 《Molecular and cellular biology》2002,22(7):2220-2228
One difficulty in analyzing the damage response is that the effect of damage itself and that of cellular response are hard to distinguish in irradiated cells. In mouse zygotes, damage can be introduced by irradiated sperm, while damage response can be studied in the unirradiated maternal pronucleus. We have analyzed the p53-dependent damage responses in irradiated-sperm mouse zygotes and found that a p53-responsive reporter was efficiently activated in the female pronucleus. [(3)H]thymidine labeling experiments indicated that irradiated-sperm zygotes were devoid of G(1)/S arrest, but pronuclear DNA synthesis was suppressed equally in male and female pronuclei. p53(-/-) zygotes lacked this suppression, which was corrected by microinjection of glutathione S-transferase-p53 fusion protein. In contrast, p21(-/-) zygotes exhibited the same level of suppression upon fertilization by irradiated sperm. About a half of the 6-Gy-irradiated-sperm zygotes managed to synthesize a full DNA content by prolonging S phase, while the other half failed to do so. Regardless of the DNA content, all the zygotes cleaved to become two-cell-stage embryos. These results revealed the presence of p53-dependent pronuclear cross talk and a novel function of p53 in the S-phase DNA damage checkpoint of mouse zygotes. 相似文献
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The ability of a photobioreactor to fix CO2 was evaluated with the thermophilic cyanobacterium, Synechocystis aquatilis SI-2. The reactor consisted of three to five flat plates of transparent acrylic plastic standing upright and in parallel
and giving a 0.015-m light path. The reactor was 0.8 m high and 1 m long with 9 l working volume. The effects of the orientation
of the vertical bioreactor, distance between the plates, and culture temperature on the productivity of biomass were investigated
during the summer of 1998 in Kamaishi (39°N, 142°E), Japan. When the illuminated surface reactor was placed in an east–west-facing
orientation, the biomass productivity was roughly 1.4-fold higher than that obtained in a north–south-facing orientation,
because the former received more solar energy than the latter. The productivity based on the overall land area was the same
for plates set either 0.25 m or 0.5 m apart. However, the volumetric productivity of the reactor in which the plates were
set 0.25 m apart was lower than that when the plates were set 0.5 m apart, since the former plates received relatively lower
solar irradiation because of severe mutual shading. When the culture temperature was maintained in its optimal range (37–43 °C),
the productivity was 50% greater than that obtained in a culture at ambient temperature (20–44 °C). The biomass productivity
and CO2 fixation rate were investigated under various experimental conditions. The maximum rate of 53 g CO2 m−2 day−1 was achieved in the temperature-regulated culture with the reactor set in an east–west-facing orientation, the distance between
plates being 0.25 m.
Received: 6 may 1999 / Received revision: 14 June 1999 / Accepted 5 July 1999 相似文献