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991.
Chisato Morita Ryuichi Sumioka Masanobu Nakata Nobuo Okahashi Satoshi Wada Takashi Yamashiro Mikako Hayashi Shigeyuki Hamada Tomoko Sumitomo Shigetada Kawabata 《PloS one》2014,9(8)
Streptococcus sanguinis, a member of the commensal mitis group of streptococci, is a primary colonizer of the tooth surface, and has been implicated in infectious complications including bacteremia and infective endocarditis. During disease progression, S. sanguinis may utilize various cell surface molecules to evade the host immune system to survive in blood. In the present study, we discovered a novel cell surface nuclease with a cell-wall anchor domain, termed SWAN (streptococcal wall-anchored nuclease), and investigated its contribution to bacterial resistance against the bacteriocidal activity of neutrophil extracellular traps (NETs). Recombinant SWAN protein (rSWAN) digested multiple forms of DNA including NET DNA and human RNA, which required both Mg2+ and Ca2+ for optimum activity. Furthermore, DNase activity of S. sanguinis was detected around growing colonies on agar plates containing DNA. In-frame deletion of the swan gene mostly reduced that activity. These findings indicated that SWAN is a major nuclease displayed on the surface, which was further confirmed by immuno-detection of SWAN in the cell wall fraction. The sensitivity of S. sanguinis to NET killing was reduced by swan gene deletion. Moreover, heterologous expression of the swan gene rendered a Lactococcus lactis strain more resistant to NET killing. Our results suggest that the SWAN nuclease on the bacterial surface contributes to survival in the potential situation of S. sanguinis encountering NETs during the course of disease progression. 相似文献
992.
Heather Keith David B. Lindenmayer Brendan G. Mackey David Blair Lauren Carter Lachlan McBurney Sachiko Okada Tomoko Konishi-Nagano 《PloS one》2014,9(9)
Carbon stock change due to forest management and disturbance must be accounted for in UNFCCC national inventory reports and for signatories to the Kyoto Protocol. Impacts of disturbance on greenhouse gas (GHG) inventories are important for many countries with large forest estates prone to wildfires. Our objective was to measure changes in carbon stocks due to short-term combustion and to simulate longer-term carbon stock dynamics resulting from redistribution among biomass components following wildfire. We studied the impacts of a wildfire in 2009 that burnt temperate forest of tall, wet eucalypts in south-eastern Australia. Biomass combusted ranged from 40 to 58 tC ha−1, which represented 6–7% and 9–14% in low- and high-severity fire, respectively, of the pre-fire total biomass carbon stock. Pre-fire total stock ranged from 400 to 1040 tC ha−1 depending on forest age and disturbance history. An estimated 3.9 TgC was emitted from the 2009 fire within the forest region, representing 8.5% of total biomass carbon stock across the landscape. Carbon losses from combustion were large over hours to days during the wildfire, but from an ecosystem dynamics perspective, the proportion of total carbon stock combusted was relatively small. Furthermore, more than half the stock losses from combustion were derived from biomass components with short lifetimes. Most biomass remained on-site, although redistributed from living to dead components. Decomposition of these components and new regeneration constituted the greatest changes in carbon stocks over ensuing decades. A critical issue for carbon accounting policy arises because the timeframes of ecological processes of carbon stock change are longer than the periods for reporting GHG inventories for national emissions reductions targets. Carbon accounts should be comprehensive of all stock changes, but reporting against targets should be based on human-induced changes in carbon stocks to incentivise mitigation activities. 相似文献
993.
Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction in bovine aortic endothelial cells 总被引:6,自引:0,他引:6
Sendo T Sumimura T Itoh Y Goromaru T Aki K Yano T Oike M Ito Y Mori S Nishibori M Oishi R 《Cellular signalling》2003,15(8):773-781
We report here a direct modulation by mast cell tryptase of endothelial barrier function through activation of proteinase-activated receptor-2 (PAR-2). In cultured bovine aortic endothelial cells (BAECs), tryptase, trypsin and PAR-2 activating peptide impaired the barrier function as determined by the permeability of protein-conjugated Evans blue. The tryptase-induced barrier dysfunction was completely blocked by U73122, and partially reversed by xestospongin C, calphostin C or Y27632. The intracellular Ca(2+) was elevated by tryptase. It was notable that ioxaglate, a contrast material that degranulates mast cells, markedly increased the permeability when applied to BAECs in combination with mast cells, an action that was blocked by nafamostat, a potent tryptase inhibitor. Immunofluorescence analysis showed that actin stress fibre formation and disruption of VE-cadherin were observed after exposure to tryptase or ioxaglate in combination with mast cells. Therefore, it is suggested that mast cell tryptase impairs endothelial barrier function through activation of endothelial PAR-2 in a manner dependent on the phospholipase C activity. 相似文献
994.
DNA mismatch repair (MMR) is integral to the maintenance of genomic stability and more recently has been demonstrated to affect apoptosis and cell cycle arrest in response to a variety of adducts induced by exogenous agents. Comparing Msh2-null and wildtype mouse embryonic fibroblasts (MEFs), both primary and transformed, we show that Msh2 deficiency results in increased survival post-UVB, and that UVB-induced apoptosis is significantly reduced in Msh2-deficient cells. Furthermore, p53 phosphorylation at serine 15 is delayed or diminished in Msh2-deficient cells, suggesting that Msh2 may act upstream of p53 in a post-UVB apoptosis or growth arrest response pathway. Taken together, these data suggest that MMR heterodimers containing Msh2 may function as a sensor of UVB-induced DNA damage and influence the initiation of UVB-induced apoptosis, thus implicating MMR in protecting against UV-induced tumorigenesis. 相似文献
995.
996.
Tomoko Naganuma Mii Tanaka Shiori Tezuka Sam M.J.G. Steyaert Kahoko Tochigi Akino Inagaki Hiroaki Myojo Koji Yamazaki Shinsuke Koike 《Ecology and evolution》2021,11(14):9182
Previous studies on the mating system of the Asian black bear (Ursus thibetanus) have been limited to observations of captive populations and estimations of multiple paternities. Hence, the mating system of wild bears remains poorly understood. Animal‐borne camera systems (i.e., cameras mounted on animals) provide novel tools to study the behavior of elusive animals. Here, we used an animal‐borne video system to record the activities of wild bears during the mating season. Video camera collars were attached to four adult Asian black bears (male “A” and “B,” and female “A” and “B”) captured in Tokyo, central Japan, in May and June 2018. The collars were retrieved in July 2018, after which the video data were downloaded and analyzed in terms of bear activity and mating behavior. All the bears were found to interact with other uniquely identifiable bears for some of the time (range 9–22 days) during the deployment period (range 36–45 days), and multiple mating in males was documented. Both males and females exhibited different behaviors on social days (i.e., days when the bear interacted with conspecifics) compared with solitary days (i.e., days with no observed interactions with conspecifics). Compared with solitary days, the bears spent a lower proportion of time on foraging activities and higher proportion of time on resting activities on social days. Our results suggest that Asian black bears have a polygamous mating system, as both sexes consort and potentially mate with multiple partners during a given mating season. Furthermore, bears appeared to reduce their foraging activities on social days and engaged more in social interactions. 相似文献
997.
Germline mutations of the Liver Kinase b1 (LKB1/STK11) tumor suppressor gene have been linked to Peutz-Jeghers Syndrome (PJS), an autosomal-dominant, cancer-prone disorder in which patients develop neoplasms in several organs, including the oviduct, ovary, and cervix. We have conditionally deleted Lkb1 in Müllerian duct mesenchyme-derived cells of the female reproductive tract and observed expansion of the stromal compartment and hyperplasia and/or neoplasia of adjacent epithelial cells throughout the reproductive tract with paratubal cysts and adenomyomas in oviducts and, eventually, endometrial cancer. Examination of the proliferation marker phospho-histone H3 and mammalian Target Of Rapamycin Complex 1 (mTORC1) pathway members revealed increased proliferation and mTORC1 activation in stromal cells of both the oviduct and uterus. Treatment with rapamycin, an inhibitor of mTORC1 activity, decreased tumor burden in adult Lkb1 mutant mice. Deletion of the genes for Tuberous Sclerosis 1 (Tsc1) or Tsc2, regulators of mTORC1 that are downstream of LKB1 signaling, in the oviductal and uterine stroma phenocopies some of the defects observed in Lkb1 mutant mice, confirming that dysregulated mTORC1 activation in the Lkb1-deleted stroma contributes to the phenotype. Loss of PTEN, an upstream regulator of mTORC1 signaling, along with Lkb1 deletion significantly increased tumor burden in uteri and induced tumorigenesis in the cervix and vagina. These studies show that LKB1/TSC1/TSC2/mTORC1 signaling in mesenchymal cells is important for the maintenance of epithelial integrity and suppression of carcinogenesis in adjacent epithelial cells. Because similar changes in the stromal population are also observed in human oviductal/ovarian adenoma and endometrial adenocarcinoma patients, we predict that dysregulated mTORC1 activity by upstream mechanisms similar to those described in these model systems contributes to the pathogenesis of these human diseases. 相似文献
998.
Okada Y Shimane K Kochi Y Tahira T Suzuki A Higasa K Takahashi A Horita T Atsumi T Ishii T Okamoto A Fujio K Hirakata M Amano H Kondo Y Ito S Takada K Mimori A Saito K Kamachi M Kawaguchi Y Ikari K Mohammed OW Matsuda K Terao C Ohmura K Myouzen K Hosono N Tsunoda T Nishimoto N Mimori T Matsuda F Tanaka Y Sumida T Yamanaka H Takasaki Y Koike T Horiuchi T Hayashi K Kubo M Kamatani N Yamada R Nakamura Y Yamamoto K 《PLoS genetics》2012,8(1):e1002455
999.
N Sato N Suzuki A Sasaki E Aizawa T Obayashi M Kanazawa T Mizuno M Kano M Aoki S Fukudo 《PloS one》2012,7(9):e42450
Background
Corticotropin-releasing hormone (CRH) acts mainly via the CRH receptor 1 (CRH-R1) and plays a crucial role in the stress-induced pathophysiology of irritable bowel syndrome (IBS). Several studies have demonstrated that variants of the CRH-R1 gene carry a potential risk for depression, but evidence for an association between CRH-R1 genotypes and IBS is lacking. We tested the hypothesis that genetic polymorphisms and haplotypes of CRH-R1 moderate the IBS phenotype and negative emotion in IBS patients.Methods
A total of 103 patients with IBS and 142 healthy controls participated in the study. Three single-nucleotide polymorphisms of the CRH-R1 gene (rs7209436, rs242924, and rs110402) were genotyped. Subjects'' emotional states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-rating Depression Scale.Results
The TT genotype of rs7209436 (P = 0.01) and rs242924 (P = 0.02) was significantly more common in patients with IBS than in controls. Total sample analysis showed significant association between bowel pattern (normal, diarrhea, constipation, or mixed symptoms) and the T allele of rs7209436 (P = 0.008), T allele of rs242924 (P = 0.019), A allele of rs110402 (P = 0.047), and TAT haplocopies (P = 0.048). Negative emotion was not associated with the examined CRH-R1 SNPs.Conclusion
These findings suggest that genetic polymorphisms and the CRH-R1 haplotypes moderate IBS and related bowel patterns. There was no clear association between CRH-R1 genotypes and negative emotion accompanying IBS. Further studies on the CRH system are therefore warranted. 相似文献1000.
Satoshi Sekiguchi Kiminori Kimura Tomoko Chiyo Takahiro Ohtsuki Yoshimi Tobita Yuko Tokunaga Fumihiko Yasui Kyoko Tsukiyama-Kohara Takaji Wakita Toshiyuki Tanaka Masayuki Miyasaka Kyosuke Mizuno Yukiko Hayashi Tsunekazu Hishima Kouji Matsushima Michinori Kohara 《PloS one》2012,7(12)
Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains. The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. We also demonstrated that the onset of chronic hepatitis in CN2-29(+/−)/MxCre(+/−) mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor) TNF-α and (interleukin) IL-6. Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine. 相似文献