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61.
Novel mutants of NAB corepressors enhance activation by Egr transactivators. 总被引:1,自引:0,他引:1 下载免费PDF全文
J Svaren B R Sevetson T Golda J J Stanton A H Swirnoff J Milbrandt 《The EMBO journal》1998,17(20):6010-6019
62.
Salmonella/microsome soft-agar overlay ('Ames' test) plates were prepared using the previously published 'York' method. Plates treated with either added 3-methylcholanthrene (3MC) or 3,3'-dichlorobenzidine (DCB) and Aroclor-induced rat-liver S9 were stored at 4 degrees after preparation and removed at time intervals thereafter for incubation at 37 degrees. The number of 3MC-induced mutants in TA100 fell within 24 h of storage by 50% but then remained at this level until 96 h. Storage for a total of 336 h still showed some residual mono-oxygenase activity. On the other hand the ability to convert DCB to a mutagen for TA98 appeared to increase with storage, reaching a peak by 96 h. After this time the number of induced mutants fell until by 336 h the numbers were approximately equal to those plates which had not been stored in the cold. 相似文献
63.
64.
Fiona Fouhy Jennifer Deane Mary C. Rea órla O’Sullivan R. Paul Ross Grace O’Callaghan Barry J. Plant Catherine Stanton 《PloS one》2015,10(3)
Background
High-throughput sequencing has enabled detailed insights into complex microbial environments, including the human gut microbiota. The accuracy of the sequencing data however, is reliant upon appropriate storage of the samples prior to DNA extraction. The aim of this study was to conduct the first MiSeq sequencing investigation into the effects of faecal storage on the microbiota, compared to fresh samples. Culture-based analysis was also completed.Methods
Seven faecal samples were collected from healthy adults. Samples were separated into fresh (DNA extracted immediately), snap frozen on dry ice and frozen for 7 days at -80°C prior to DNA extraction or samples frozen at -80°C for 7 days before DNA extraction. Sequencing was completed on the Illumina MiSeq platform. Culturing of total aerobes, anaerobes and bifidobacteria was also completed.Results
No significant differences at phylum or family levels between the treatment groups occurred. At genus level only Faecalibacterium and Leuconostoc were significantly different in the fresh samples compared to the snap frozen group (p = 0.0298; p = 0.0330 respectively). Diversity analysis indicated that samples clustered based on the individual donor, rather than by storage group. No significant differences occurred in the culture-based analysis between the fresh, snap or -80°C frozen samples.Conclusions
Using the MiSeq platform coupled with culture-based analysis, this study highlighted that limited significant changes in microbiota occur following rapid freezing of faecal samples prior to DNA extraction. Thus, rapid freezing of samples prior to DNA extraction and culturing, preserves the integrity of the microbiota. 相似文献65.
Zhiwei Feng Stanton Kochanek David Close LiRong Wang Ajay Srinivasan Abdulrahman A. Almehizia Prema Iyer Xiang-Qun Xie Paul A. Johnston Barry Gold 《Journal of chemical biology》2015,8(3):79-93
Apurinic/apyrimidinic endonuclease-1/redox effector factor-1 (APE-1) is a critical component of base excision repair that excises abasic lesions created enzymatically by the action of DNA glycosylases on modified bases and non-enzymatically by hydrolytic depurination/depyrimidination of nucleobases. Many anticancer drugs generate DNA adducts that are processed by base excision repair, and tumor resistance is frequently associated with enhanced APE-1 expression. Accordingly, APE-1 is a potential therapeutic target to treat cancer. Using computational approaches and the high resolution structure of APE-1, we developed a 5-point pharmacophore model for APE-1 small molecule inhibitors. One of the nM APE-1 inhibitors (AJAY-4) that was identified based on this model exhibited an overall median growth inhibition (GI50) of 4.19 μM in the NCI-60 cell line panel. The mechanism of action is shown to be related to the buildup of abasic sites that cause PARP activation and PARP cleavage, and the activation of caspase-3 and caspase-7, which is consistent with cell death by apoptosis. In a drug combination growth inhibition screen conducted in 10 randomly selected NCI-60 cell lines and with 20 clinically used non-genotoxic anticancer drugs, a synergy was flagged in the SK-MEL-5 melanoma cell line exposed to combinations of vemurafenib, which targets melanoma cells with V600E mutated BRAF, and AJAY-4, our most potent APE-1 inhibitor. The synergy between AJAY-4 and vemurafenib was not observed in cell lines expressing wild-type B-Raf protein. This synergistic combination may provide a solution to the resistance that develops in tumors treated with B-Raf-targeting drugs.
Electronic supplementary material
The online version of this article (doi:10.1007/s12154-015-0131-7) contains supplementary material, which is available to authorized users. 相似文献66.
Lesley Cottrell Carrie Rishel Christa Lilly Scott Cottrell Aaron Metzger Halima Ahmadi Bo Wang Xiaoming Li Bonita Stanton 《PloS one》2015,10(5)
In this study, we examined how adolescents compare monitoring efforts by their parents to those of a "good parent" standard and assessed the impact of these comparisons on adolescent self-disclosure and risk behavior and their perceptions of their parents'' monitoring knowledge. Survey responses from 519 adolescents (12–17 years) at baseline of a larger, longitudinal study examining parental monitoring and adolescent risk were examined. Adolescents’ “good parent comparisons” differed greatly by monitoring areas (e.g., telephone use, health, money); however, between 5.5% and 25.8% of adolescents believed their parents needed to monitor their activities more than they currently were monitoring. Alternatively, between 8.5% and 23.8% of adolescents believed their parents needed to monitor their activities less often. These perceptions significantly distinguished adolescents in terms of their level of disclosure, perceived monitoring knowledge, and risk involvement. Adolescents who viewed their parents as needing to monitor more were less likely to disclose information to their parents (p<.001), less likely to perceive their parents as having greater monitoring knowledge (p<.001), and more likely to be involved in a risk behaviors (p<.001) than adolescents who perceived their parents needed no change. Adolescent disclosure to a parent is a powerful predictor of adolescent risk and poor health outcomes. These findings demonstrate that adolescents'' comparisons of their parents'' monitoring efforts can predict differences in adolescent disclosure and future risk. Obtaining adolescent "good parent" comparisons may successfully identify intervention opportunities with the adolescent and parent by noting the areas of need and direction of monitoring improvement. 相似文献
67.
Rathika Krishnasamy Nicole M. Isbel Carmel M. Hawley Elaine M. Pascoe Matthew Burrage Rodel Leano Brian A. Haluska Thomas H. Marwick Tony Stanton 《PloS one》2015,10(5)
BackgroundEchocardiographic global longitudinal strain (GLS) is increasingly recognised as a more effective technique than conventional ejection fraction (EF) in detecting subtle changes in left ventricular (LV) function. This study investigated the prognostic value of GLS over EF in patients with advanced Chronic Kidney Disease (CKD).MethodsThe study included 183 patients (57% male, 63% on dialysis) with CKD stage 4, 5 and 5Dialysis (D). 112 (61%) of patients died in a follow up of 7.8 ± 4.4 years and 41% of deaths were due to cardiovascular (CV) disease. GLS was calculated using 2-dimensional speckle tracking and EF was measured using Simpson’s biplane method. Cox proportional hazard models were used to assess the association of measures of LV function and all- cause and CV mortality.ResultsThe mean GLS at baseline was -13.6 ± 4.3% and EF was 45 ± 11%. GLS was a significant predictor of all-cause [Hazard Ratio (HR) 1.09 95%; Confidence Interval (CI) 1.02–1.16; p = 0.01] and CV mortality (HR 1.16 95%; CI 1.04–1.30; p = 0.008) following adjustment for relevant clinical variables including LV mass index (LVMI) and EF. GLS also had greater predictive power for both all- cause and CV mortality compared to EF. Impaired GLS (>-16%) was associated with a 5.6-fold increased unadjusted risk of CV mortality in patients with preserved EF.ConclusionsIn this cohort of patients with advanced CKD, GLS is a more sensitive predictor of overall and CV mortality compared to EF. Studies of larger populations in CKD are required to confirm that GLS provides additive prognostic value in patients with preserved EF. 相似文献
68.
Background
In 1996 Massachusetts proposed regulations that would require tobacco companies to disclose information about the ingredients in their products on a by-brand basis. This paper examines the strategies employed by Philip Morris to stop these regulations from being implemented.Methods and Finding
We used previously secret tobacco industry documents and published literature to examine the activities of the tobacco companies after the regulations were proposed. Philip Morris hired a public relations firm to establish a coalition that was instructed to oppose the regulations by linking them to other industrial sectors (the slippery slope) and stating they would damage the state''s economy. Philip Morris also retained a polling firm to test the popularity of specific arguments against ingredient disclosure and developed a strategic plan for opposing similar regulations in Vermont.Conclusion
Tobacco companies have historically used third parties to form coalitions to oppose ingredient disclosure regulations. These coalitions have had success preventing regulations from being implemented after they are initially proposed by creating the appearance of local opposition. With countries around the world currently implementing ingredient disclosure regulations in the WHO Framework Convention on Tobacco, governments and regulatory agencies should be aware of the political strategies that the tobacco companies have used to create the impression of popular opposition to these measures. 相似文献69.
Anzhelika G. Vorobyeva Michael Stanton Aurélien Godinat Kjetil B. Lund Grigory G. Karateev Kevin P. Francis Elizabeth Allen Juri G. Gelovani Emmet McCormack Mark Tangney Elena A. Dubikovskaya 《PloS one》2015,10(6)
Bacterial nitroreductases (NTRs) have been widely utilized in the development of novel antibiotics, degradation of pollutants, and gene-directed enzyme prodrug therapy (GDEPT) of cancer that reached clinical trials. In case of GDEPT, since NTR is not naturally present in mammalian cells, the prodrug is activated selectively in NTR-transformed cancer cells, allowing high efficiency treatment of tumors. Currently, no bioluminescent probes exist for sensitive, non-invasive imaging of NTR expression. We therefore developed a "NTR caged luciferin" (NCL) probe that is selectively reduced by NTR, producing light proportional to the NTR activity. Here we report successful application of this probe for imaging of NTR in vitro, in bacteria and cancer cells, as well as in vivo in mouse models of bacterial infection and NTR-expressing tumor xenografts. This novel tool should significantly accelerate the development of cancer therapy approaches based on GDEPT and other fields where NTR expression is important. 相似文献
70.
A raster-based method for determining complex view factor patterns is presented (HURES model). The model uses Johnson and Watson’s view factor analysis method for fisheye lens photographs. The entire sphere is divided into 13 different view factors: open sky; sunny and shaded building walls, vegetation (trees) and ground surfaces above and below 1.2 m from the ground surface. The HURES model gave reasonable view factor results in tests at two urban study sites on summer days: downtown Nanaimo, B.C., Canada and Changwon, Republic of Korea. HURES gave better estimates of open sky view factors determined from fisheye lens photographs than did ENVI-met 3.1 and RayMan Pro. However, all three models underestimated sky view factor. For view factor analysis in outdoor urban areas, the 10° interval of rotation angle at 100 m distance of annuli will be suitable settings for three-dimensional computer simulations. The HURES model can be used for the rapid determination of complex view factor patterns which facilitates the analysis of their effects. Examples of how differing view factor patterns can affect human thermal sensation indices are given. The greater proportion of sunny view factors increased the computed predicted mean vote (PMV) by 1.3 on the sunny side of the street compared with the shady side during mid-morning in downtown Nanaimo. In another example, effects of differing amounts of open sky, sunny ground, sunny buildings and vegetation combined to produce only slight differences in PMV and two other human thermal sensation indices, PET and UTCI. 相似文献