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181.
Michiaki Yamashita Yumiko Yamashita Tamami Suzuki Yoko Kani Nanami Mizusawa Shintaro Imamura Kenji Takemoto Tatsuro Hara Md. Anwar Hossain Takeshi Yabu Ken Touhata 《Marine biotechnology (New York, N.Y.)》2013,15(5):559-570
The selenium (Se)-containing antioxidant selenoneine (2-selenyl-N α,N α,N α-trimethyl-l-histidine) has recently been discovered to be the predominant form of organic Se in tuna blood. Although dietary intake of fish Se has been suggested to reduce methylmercury (MeHg) toxicity, the molecular mechanism of MeHg detoxification by Se has not yet been determined. Here, we report evidence that selenoneine accelerates the excretion and demethylation of MeHg, mediated by a selenoneine-specific transporter, organic cations/carnitine transporter-1 (OCTN1). Selenoneine was incorporated into human embryonic kidney HEK293 cells transiently overexpressing OCTN1 and zebrafish blood cells by OCTN1. The K m for selenoneine uptake was 13.0 μM in OCTN1-overexpressing HEK293 cells and 9.5 μM in zebrafish blood cells, indicating high affinity of OCTN1 for selenoneine in human and zebrafish cells. When such OCTN1-expressing cells and embryos were exposed to MeHg–cysteine (MeHgCys), MeHg accumulation was decreased and the excretion and demethylation of MeHg were enhanced by selenoneine. In addition, exosomal secretion vesicles were detected in the culture water of embryos that had been microinjected with MeHgCys, suggesting that these may be responsible for MeHg excretion and demethylation. In contrast, OCTN1-deficient embryos accumulated MeHg, and MeHg excretion and demethylation were decreased. Furthermore, Hg accumulation was decreased in OCTN1-overexpressing HEK293 cells, but not in mock vector-transfected cells, indicating that selenoneine and OCTN1 can regulate MeHg detoxification in human cells. Thus, the selenoneine-mediated OCTN1 system regulates secretory lysosomal vesicle formation and MeHg demethylation. 相似文献
182.
Dispersal is a key process in population and evolutionary ecology. Individual decisions are affected by fitness consequences of dispersal, but these are difficult to measure in wild populations. A long‐term dataset on a geographically closed bird population, the Mauritius kestrel, offers a rare opportunity to explore fitness consequences. Females dispersed further when the availability of local breeding sites was limited, whereas male dispersal correlated with phenotypic traits. Female but not male fitness was lower when they dispersed longer distances compared to settling close to home. These results suggest a cost of dispersal in females. We found evidence of both short‐ and long‐term fitness consequences of natal dispersal in females, including reduced fecundity in early life and more rapid aging in later life. Taken together, our results indicate that dispersal in early life might shape life history strategies in wild populations. 相似文献
183.
Ken Chen Nicholas E Navin Yong Wang Heather K Schmidt John W Wallis Beifang Niu Xian Fan Hao Zhao Michael D McLellan Katherine A Hoadley Elaine R Mardis Timothy J Ley Charles M Perou Richard K Wilson Li Ding 《Genome biology》2013,14(8):R87
Producing gene fusions through genomic structural rearrangements is a major mechanism for tumor evolution. Therefore, accurately detecting gene fusions and the originating rearrangements is of great importance for personalized cancer diagnosis and targeted therapy. We present a tool, BreakTrans, that systematically maps predicted gene fusions to structural rearrangements. Thus, BreakTrans not only validates both types of predictions, but also provides mechanistic interpretations. BreakTrans effectively validates known fusions and discovers novel events in a breast cancer cell line. Applying BreakTrans to 43 breast cancer samples in The Cancer Genome Atlas identifies 90 genomically validated gene fusions. BreakTrans is available at http://bioinformatics.mdanderson.org/main/BreakTrans 相似文献
184.
Luc Friboulet Sophie Postel-Vinay Tony Sourisseau Julien Adam Annabelle Stoclin Florence Ponsonnailles Nicolas Dorvault Frédéric Commo Patrick Saulnier Sophie Salome-Desmoulez Géraldine Pottier Fabrice André Guido Kroemer Jean Charles Soria Ken André Olaussen 《Cell cycle (Georgetown, Tex.)》2013,12(20):3298-3306
ERCC1 (excision repair cross-complementation group 1) plays essential roles in the removal of DNA intrastrand crosslinks by nucleotide excision repair, and that of DNA interstrand crosslinks by the Fanconi anemia (FA) pathway and homology-directed repair processes (HDR). The function of ERCC1 thus impacts on the DNA damage response (DDR), particularly in anticancer therapy when DNA damaging agents are employed. ERCC1 expression has been proposed as a predictive biomarker of the response to platinum-based therapy. However, the assessment of ERCC1 expression in clinical samples is complicated by the existence of 4 functionally distinct protein isoforms, which differently impact on DDR. Here, we explored the functional competence of each ERCC1 protein isoform and obtained evidence that the 202 isoform is the sole one endowed with ERCC1 activity in DNA repair pathways. The ERCC1 isoform 202 interacts with RPA, XPA, and XPF, and XPF stability requires expression of the ERCC1 202 isoform (but none of the 3 others). ERCC1-deficient non-small cell lung cancer cells show abnormal mitosis, a phenotype reminiscent of the FA phenotype that can be rescued by isoform 202 only. Finally, we could not observe any dominant-negative interaction between ERCC1 isoforms. These data suggest that the selective assessment of the ERCC1 isoform 202 in clinical samples should accurately reflect the DDR-related activity of the gene and hence constitute a useful biomarker for customizing anticancer therapies. 相似文献
185.
Siu Wai Tsang Hongjie Zhang Chengyuan Lin Haitao Xiao Michael Wong Hongcai Shang Zhi-Jun Yang Aiping Lu Ken Kin-Lam Yung Zhaoxiang Bian 《PloS one》2013,8(12)
Pancreatic fibrosis, a prominent histopathological feature of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma, is essentially a dynamic process that leads to irreversible scarring of parenchymal tissues of the pancreas. Though the exact mechanisms of its initiation and development are poorly understood, recent studies suggested that the activation of pancreatic stellate cells (PSCs) plays a critical role in eliciting such active course of fibrogenesis. Anthraquinone compounds possess anti-inflammatory bioactivities whereas its natural derivative rhein has been shown to effectively reduce tissue edema and free-radical production in rat models of inflammatory conditions. Apart from its anti-inflammatory properties, rhein actually exerts strong anti-fibrotic effects in our current in-vivo and in-vitro experiments. In the mouse model of cerulein-induced CP, prolonged administration of rhein at 50 mg/kg/day significantly decreased immunoreactivities of the principal fibrotic activators alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-β) on pancreatic sections implicating the activation of PSCs, which is the central tread to fibrogenesis, was attenuated. Consequently, the overwhelmed deposition of extracellular matrix proteins fibronectin 1 (FN1) and type I collagen (COL I-α1) in exocrine parenchyma was found accordingly reduced. In addition, the expression levels of sonic hedgehog (SHH), which plays important roles in molecular modulation of various fibrotic processes, and its immediate effector GLI1 in pancreatic tissues were positively correlated to the degree of cerulein-induced fibrosis. Such up-regulation of SHH signaling was restrained in rhein-treated CP mice. In cultured PSCs, we demonstrated that the expression levels of TGF-β-stimulated fibrogenic markers including α-SMA, FN1 and COL I-α1 as well as SHH were all notably suppressed by the application of rhein at 10 μM. The present study firstly reported that rhein attenuates PSC activation and suppresses SHH/GLI1 signaling in pancreatic fibrosis. With strong anti-fibrotic effects provided, rhein can be a potential remedy for fibrotic and/or PSC-related pathologies in the pancreas. 相似文献
186.
Crystal Y. Q. Du Roy C. Y. Choi Ken Y. Z. Zheng Tina T. X. Dong David T. W. Lau Karl W. K. Tsim 《PloS one》2013,8(11)
Yu Ping Feng San (YPFS), a Chinese herbal decoction, is composed of Astragali Radix (AR; Huangqi), Atractylodis Macrocephalae Rhizoma (AMR; Baizhu) and Saposhnikoviae Radix (SR; Fangfeng) in a weight ratio of 1∶2∶1. Clinically, YPFS has been widely used to regulate immune functions; however, the action mechanism of it is not known. Here, we addressed this issue by providing detail analyses of chemical and biological properties of YPFS. By using rapid resolution liquid chromatography coupled with mass spectrometry, fifteen chemicals deriving from different herbs of YPFS were determined, and which served as a control for the standardization of the herbal extract of YPFS. In general, the amounts of chosen chemical markers were higher in a preparation of YPFS as compared to that of single herb or two-herb compositions. In order to reveal the immune functions of YPFS, the standardized extract was applied onto cultured murine macrophages. The treatment of YPFS stimulated the mRNA and protein expressions of pro-inflammatory cytokines via activation of NF-κB by enhancing IκBα degradation. In contrast, the application of YPFS suppressed the expressions of pro-inflammatory cytokines significantly in the lipopolysaccharide (LPS)-induced chronic inflammation model. In addition, YPFS could up regulate the phagocytic activity in cultured macrophages. These results therefore supported the bi-directional immune-modulatory roles of YPFS in regulating the releases of cytokines from macrophages. 相似文献
187.
Purpose
To assess the time course of optical quality and intraocular scattering in relation to visual acuity after femtosecond lenticule extraction (FLEx) for the correction of myopia.Methods
This study evaluated 36 eyes of 36 patients with spherical equivalents of −4.38±1.53 D [mean ± standard deviation] who underwent FLEx. Before surgery, and 1 week and 1, 3 and 6 months after surgery, we assessed the modulation transfer function (MTF) cutoff frequency, Strehl ratio, objective scattering index (OSI), and OQAS values (OVs), using a double-pass instrument. We also investigated the relationship of the OSI with corrected distance visual acuity (CDVA) preoperatively and postoperatively.Results
The mean changes in MTF cutoff frequency, Strehl ratio, OSI, OV100%, OV20%, and OV9% preoperatively and 6 months postoperatively were −5.51±15.01, −0.03±0.07, 0.35±0.83, −0.17±0.48, −0.14±0.38, and −0.09±0.22, respectively. We found no significant preoperative correlation between the OSI and logMAR CDVA (Spearman rank correlation coefficient r = 0.068, p = 0.69), and modest, but significant correlations 1 week and 1, 3, and 6 months postoperatively (r = 0.572, r = 0.562, r = 0.542, r = 0.540, p<0.001, respectively).Conclusions
FLEx induced a transient decrease in optical quality in association with an increase in intraocular scattering in the early postoperative period, possibly due to mild interface haze formation, but gradually recovered with time. It is suggested that this transient degradation in optical quality related to an increase in the intraocular scattering may result in a slight delay of CDVA recovery in the early postoperative period. 相似文献188.
Norval J. C. Strachan Ovidiu Rotariu Marion MacRae Samuel K. Sheppard Alison Smith-Palmer John Cowden Martin C. J. Maiden Ken J. Forbes 《PloS one》2013,8(11)
A framework of general factors for infectious disease emergence was made operational for Campylobacter utilising explanatory variables including time series and risk factor data. These variables were generated using a combination of empirical epidemiology, case-case and case-control studies, time series analysis, and microbial sub-typing (source attribution, diversity, genetic distance) to unravel the changing/emerging aetiology of human campylobacteriosis. The study focused on Scotland between 1990–2012 where there was a 75% increase in reported cases that included >300% increase in the elderly and 50% decrease in young children. During this period there were three phases 1990–2000 a 75% rise and a 20% fall to 2006, followed by a 19% resurgence. The rise coincided with expansions in the poultry industry, consumption of chicken, and a shift from rural to urban cases. The post-2000 fall occurred across all groups apart from the elderly and coincided with a drop of the prevalence of Campylobacter in chicken and a higher proportion of rural cases. The increase in the elderly was associated with uptake of proton pump inhibitors. During the resurgence the increase was predominantly in adults and the elderly, again there was increasing use of PPIs and high prevalences in chicken and ruminants. Cases associated with foreign travel during the study also increased from 9% to a peak of 16% in 2006 before falling to an estimated 10% in 2011, predominantly in adults and older children. During all three periods source attribution, genetic distance, and diversity measurements placed human isolates most similar to those in chickens. A combination of emergence factors generic for infectious diseases were responsible for the Campylobacter epidemic. It was possible to use these to obtain a putative explanation for the changes in human disease and the potential to make an informed view of how incidence rates may change in the future. 相似文献
189.
Shotaro Sasaki Masaki Kobayashi Yuya Futagi Jiro Ogura Hiroaki Yamaguchi Natsuko Takahashi Ken Iseki 《PloS one》2013,8(7)