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61.
62.
Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta 总被引:1,自引:0,他引:1
Ohashi N Yamamoto T Uchida C Togawa A Fukasawa H Fujigaki Y Suzuki S Kitagawa K Hattori T Oda T Hayashi H Hishida A Kitagawa M 《FEBS letters》2005,579(12):2557-2563
Smad ubiquitination regulatory factor 2 (Smurf2), a ubiquitin ligase for Smads, plays critical roles in the regulation of transforming growth factor-beta (TGF-beta)-Smad signaling via ubiquitin-dependent degradation of Smad2 and Smad7. We found that TGF-beta stimulates Smurf2 expression. TGF-beta activated the Smurf2 promoter in a TGF-beta responsive cell lines, whereas IL-1alpha, PDGF and epidermal growth factor did not. TGF-beta-mediated Smurf2 promoter activation was inhibited by Smad7 or an activin receptor-like kinase 5 inhibitor but not by dominant negative Smad or disruption of Smad-binding elements in the promoter. Moreover, inhibition of the phosphatidil inositol 3 kinase (PI3K)/Akt pathway suppressed TGF-beta-mediated Smurf2 induction. These results suggest that TGF-beta stimulates Smurf2 expression by Smad-independent pathway such as PI3K/Akt pathway via TGF-beta receptor. 相似文献
63.
Madelon Van de Kerk Stephen Arthur Mark Bertram Bridget Borg Jim Herriges James Lawler Buck Mangipane Catherine Lambert Koizumi Brad Wendling Laura Prugh 《The Journal of wildlife management》2020,84(6):1127-1138
Understanding how species respond to environmental conditions can assist with conservation strategies and harvest management, especially in arctic and boreal regions that are experiencing rapid climate change. Although climatic influences on species distributions have been studied, broad-scale effects of climate on survival are less well known. We examined the interactive effects of meteorological and remotely sensed environmental variables on survival of Dall's sheep (Ovis dalli dalli) lambs and adults by synthesizing radio-telemetry data across their range. We used data from 9 studies of adult sheep and 2 studies of lambs that were conducted between 1997 and 2012 at sites spanning the species' range in Alaska, USA, and northwestern Canada. We obtained environmental variables throughout the range of Dall's sheep, including the normalized difference vegetation index (NDVI) from optical remote sensing, freeze-thaw frequency (FTF) from passive microwave remote sensing, and gridded climate variables such as snow water equivalent, temperature, and precipitation. We used Cox proportional hazard regression to investigate the effects of environmental variables recorded during summer, winter, and the previous winter on annual survival rates of Dall's sheep lambs and adults. Summer NDVI was the most influential environmental factor affecting lamb survival, with improved lamb survival occurring in years with a high maximum NDVI. Also, lamb predation by coyotes (Canis latrans) and golden eagles (Aquila chrysaetos) decreased substantially with increasing NDVI. The previous winter FTF had the strongest effect on adult survival, with decreased survival occurring after winters with high FTF. In addition, these remotely sensed environmental factors interacted with meteorological factors to affect survival, such that effects of winter temperature depended on summer NDVI and winter FTF. Warm winters increased lamb survival only when preceded by summers with high NDVI, and warm winters increased adult survival only when winter FTF was low. Thus, potential benefits of climate warming may be counteracted if wintertime freeze-thaw events markedly increase. Correlations among environmental variables across sites were low, and regional climate cycles such as the Pacific Decadal Oscillation (PDO) had weak effects, indicating substantial local variability in climatic conditions experienced by Dall's sheep across their range. These findings can help managers anticipate how Dall's sheep populations will respond to changes in local environmental conditions. Our results also highlight the utility of multiple remotely sensed environmental conditions for ungulate management, especially passive microwave products that provide valuable information on winter icing events. © 2020 The Wildlife Society. 相似文献
64.
IL-28 elicits antitumor responses against murine fibrosarcoma 总被引:3,自引:0,他引:3
Numasaki M Tagawa M Iwata F Suzuki T Nakamura A Okada M Iwakura Y Aiba S Yamaya M 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(8):5086-5098
IL-28 is a recently described antiviral cytokine. In this study, we investigated the biological effects of IL-28 on tumor growth to evaluate its antitumor activity. IL-28 or retroviral transduction of the IL-28 gene into MCA205 cells did not affect in vitro growth, whereas in vivo growth of MCA205IL-28 was markedly suppressed along with survival advantages when compared with that of controls. When the metastatic ability of IL-28-secreting MCA205 cells was compared with that of controls, the expression of IL-28 resulted in a potent inhibition of metastases formation in the lungs. IL-28-mediated suppression of tumor growth was mostly abolished in irradiated mice, indicating that irradiation-sensitive cells, presumably immune cells, are primarily involved in the IL-28-induced suppression of tumor growth. In vivo cell depletion experiments displayed that polymorphonuclear neutrophils, NK cells, and CD8 T cells, but not CD4 T cells, play an equal role in the IL-28-mediated inhibition of in vivo tumor growth. Consistent with these findings, inoculation of MCA205IL-28 into mice evoked enhanced IFN-gamma production and cytotoxic T cell activity in spleen cells. Antitumor action of IL-28 is partially dependent on IFN-gamma and is independent of IL-12, IL-17, and IL-23. IL-28 increased the total number of splenic NK cells in SCID mice and enhanced IL-12-induced IFN-gamma production in vivo and expanded spleen cells in C57BL/6 mice. Moreover, IL-12 augmented IL-28-mediated antitumor activity in the presence or absence of IFN-gamma. These findings indicate that IL-28 has bioactivities that induce innate and adaptive immune responses against tumors. 相似文献
65.
Nobuhiko Watanabe Hiroshi Nakagawa Shuji Kitajima Enqi Liu Masatoshi Morimoto Teruo Watanabe Jianglin Fan 《Experimental Animals》2005,54(4):353-357
In the present study, embryo transfer was performed using frozen-thawed embryos to establish a SPF colony of human apolipoprotein (a) (apo(a)) transgenic rabbits. Apo(a) transgenic rabbits were kept under conventional condition and were infected with Bordetella bronchiseptica. Embryos at the morula stage were collected and stored in liquid nitrogen. After thawing, the in vitro survival rate was 84.6%, and 125 morphologically normal embryos were transferred to 6 SPF recipient rabbits. Four rabbits became pregnant and 23 live pups were born. PCR and Western blot analyses revealed that 9 of 23 pups were transgenic and expressed apo(a) protein. Microbiological tests showed all rabbits were free from infections. We succeeded in establishing a SPF colony of apo(a) transgenic rabbits. These rabbits are now maintained under a barrier system and are available for medical research. 相似文献
66.
Summary The basic problems of applying solvent extraction to ethanol fermentation were investigated. The selection of solvents was based on the selectivity ratio, which was expressed as the ratio of the ethanol distribution coefficient to the water distribution coefficient. Solvents with high selectivity ratios of more than 50 were found mainly among the alcohols and esters. However, most of these solvents were toxic to ethanol-producing microorganisms. We tried to make a barrier to solvent molecules beneath the surface of gel beads immobilizing the cells as a protection against solvent toxicity. Porapack Q was found to be an effective barrier, and the ethanol production rate of immobilized cells protected with Porapack Q did not change event after the production of eight batches in medium saturated with sec-octanol, which was the most toxic solvent used in our experiments. 相似文献
67.
Koizumi J Kojima T Kamekura R Kurose M Harimaya A Murata M Osanai M Chiba H Himi T Sawada N 《The Journal of membrane biology》2007,218(1-3):1-7
The epithelium of upper respiratory tissues such as nasal mucosa forms a continuous barrier to a wide variety of exogenous
antigens. The epithelial barrier function is regulated in large part by the intercellular junctions, referred to as gap and
tight junctions. However, changes of gap and tight junctions during differentiation of human nasal epithelial (HNE) cells
are still unclear. In the present study, to investigate changes of gap and tight junctions during differentiation of HNE cells
in vitro, we used primary human HNE cells cocultured with primary human nasal fibroblast (HNF) cells in a noncontact system. In HNE
cells cocultured with HNF cells for 2 weeks, numerous elongated cilia-like structures were observed compared to those without
HNF cells. In the coculture, downregulation of Cx26 and upregulation of Cx30.3 and Cx31 were observed together with extensive
gap junctional intercellular communication. Furthermore, expression of the tight junction proteins claudin-1, claudin-4, occludin
and ZO-2 was increased. These results suggest that switching in expression of connexins and induction of tight junction proteins
may be closely associated with differentiation of HNE cells in
vitro and that differentiation of HNE cells requires unknown soluble factors secreted from HNF cells. 相似文献
68.
69.
Saya Kuribayashi Yoshihiro Sakoda Takeshi Kawasaki Tomohisa Tanaka Naoki Yamamoto Masatoshi Okamatsu Norikazu Isoda Yoshimi Tsuda Yuji Sunden Takashi Umemura Noriko Nakajima Hideki Hasegawa Hiroshi Kida 《PloS one》2013,8(7)
Highly pathogenic avian influenza viruses (HPAIVs) cause lethal infection in chickens. Severe cases of HPAIV infections have been also reported in mammals, including humans. In both mammals and birds, the relationship between host cytokine response to the infection with HPAIVs and lethal outcome has not been well understood. In the present study, the highly pathogenic avian influenza viruses A/turkey/Italy/4580/1999 (H7N1) (Ty/Italy) and A/chicken/Netherlands/2586/2003 (H7N7) (Ck/NL) and the low pathogenic avian influenza virus (LPAIV) A/chicken/Ibaraki/1/2005 (H5N2) (Ck/Ibaraki) were intranasally inoculated into chickens. Ty/Italy replicated more extensively than Ck/NL in systemic tissues of the chickens, especially in the brain, and induced excessive mRNA expression of inflammatory and antiviral cytokines (IFN-γ, IL-1β, IL-6, and IFN-α) in proportion to its proliferation. Using in situ hybridization, IL-6 mRNA was detected mainly in microglial nodules in the brain of the chickens infected with Ty/Italy. Capillary leakage assessed by Evans blue staining was observed in multiple organs, especially in the brains of the chickens infected with Ty/Italy, and was not observed in those infected with Ck/NL. In contrast, LPAIV caused only local infection in the chickens, with neither apparent cytokine expression nor capillary leakage in any tissue of the chickens. The present results indicate that an excessive cytokine response is induced by rapid and extensive proliferation of HPAIV and causes fatal multiple organ failure in chickens. 相似文献
70.
Nicotine enhances neovascularization and promotes tumor growth 总被引:7,自引:0,他引:7
Solid tumors require vascularization for their growth. Bone marrow-derived endothelial progenitor cells participate in tumor angiogenesis. Here, we show that nicotine markedly accelerated growth of colon cancer cells inoculated subcutaneously in mice but had no effect on proliferation of carcinoma cells in vitro. We found that the tumor growth was associated with increased vascularization of the tumor and that bone marrow-derived cells contributed to the formation of the new blood vessels. Our findings show that nicotine promotes tumor growth, at least in part, by stimulating tumor-associated neovascularization. 相似文献