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排序方式: 共有397条查询结果,搜索用时 15 毫秒
1.
Jennifer C. Sasaki Ashley Allemang Steven M. Bryce Laura Custer Kerry L. Dearfield Yasmin Dietz Azeddine Elhajouji Patricia A. Escobar Albert J. Fornace Jr Roland Froetschl Sheila Galloway Ulrike Hemmann Giel Hendriks Heng-Hong Li Mirjam Luijten Gladys Ouedraogo Lauren Peel Stefan Pfuhler Daniel J. Roberts Véronique Thybaud Jan van Benthem Carole L. Yauk Maik Schuler 《Environmental and molecular mutagenesis》2020,61(1):114-134
In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc. 相似文献
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Characterization of a functional promoter polymorphism of the human tryptophan hydroxylase 2 gene in serotonergic raphe neurons. 总被引:2,自引:0,他引:2
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Application of mycobacterial proteomics to vaccine design: improved protection by Mycobacterium bovis BCG prime-Rv3407 DNA boost vaccination against tuberculosis 总被引:4,自引:0,他引:4
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Mollenkopf HJ Grode L Mattow J Stein M Mann P Knapp B Ulmer J Kaufmann SH 《Infection and immunity》2004,72(11):6471-6479
Information from comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guerin (BCG) principally allows prediction of potential vaccine candidates. Thirty-six M. tuberculosis DNA vaccine candidates identified by comparative proteome analysis were evaluated in the mouse model for protection against low-dose aerosol M. tuberculosis infection. We identified the DNA vaccine candidate Rv3407 as a protective antigen and analyzed putative major histocompatibility complex class I epitopes by computational predictions and gamma interferon Elispot assays. Importantly, we discovered that the DNA vaccine Rv3407 improved the efficacy of BCG vaccination in a heterologous prime-boost vaccination protocol. Our data demonstrate the rationale of a combination of proteomics, epitope prediction, and broad screening of putative antigens for identification of novel DNA vaccine candidates. Furthermore, our experiments show that heterologous prime-boost vaccination with a defined antigen boost "on top" of a BCG primer provides superior protection against tuberculosis over vaccination with BCG alone. 相似文献
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Die Anaesthesiologie - 相似文献
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Devon L. Drey Eric C. O'Quinn Tamilarasan Subramani Kristina Lilova Gianguido Baldinozzi Igor M. Gussev Antonio F. Fuentes Joerg C. Neuefeind Michelle Everett David Sprouster Alexandra Navrotsky Rodney C. Ewing Maik Lang 《RSC advances》2020,10(57):34632
Pyrochlore (A2B2O7) is an important, isometric structure-type because of its large variety of compositions and structural derivatives that are generally related to different disordering mechanisms at various spatial scales. The disordering is key to understanding variations in properties, such as magnetic behavior or ionic conduction. Neutron and X-ray total scattering methods were used to investigate the degree of structural disorder in the Ho2Ti2−xZrxO7 (x = 0.0–2.0, Δx = 0.25) solid solution series as a function of the Zr-content, x. Ordered pyrochlores (Fdm) disorder to defect fluorite (Fmm) via cation and anion disordering. Total scattering experiments with sensitivity to the cation and anion sublattices provide unique insight into the underlying atomic processes. Using simultaneous Rietveld refinement (long-range structure) and small-box refinement PDF analysis (short-range structure), we show that the series undergoes a rapid transformation from pyrochlore to defect fluorite at x ≈ 1.2, while the short-range structure exhibits a linear increase in a local weberite-type phase, C2221, over the entire composition range. Enthalpies of formation from the oxides determined using high temperature oxide melt solution calorimetry support the structural data and provide insight into the effect of local ordering on the energetics of disorder. The measured enthalpies of mixing are negative and are fit by a regular solution parameter of W = −31.8 ± 3.7 kJ mol−1. However, the extensive short-range ordering determined from the structural analysis strongly suggests that the entropies of mixing must be far less positive than implied by the random mixing of a regular solution. We propose a local disordering scheme involving the pyrochlore 48f to 8a site oxygen Frenkel defect that creates 7-coordinated Zr sites contained within local weberite-type coherent nanodomains. Thus, the solid solution is best described as a mixture of two phases, with the weberite-type nanodomains triggering the long-range structural transformation to defect fluorite after accumulation above a critical concentration (50% Ti replaced by Zr).Combined neutron and X-ray total scattering with calorimetric measurements of the solid solution series Ho2Ti2−xZrxO7 reveals a complex order–disorder transition across short, intermediate, and long length scales induced by chemical substitution. 相似文献
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Ralf E. Harskamp MD Wichert J. Kuijt MD Peter Damman MD PhD Marcel A. Beijk MD PhD Maik J. Grundeken MD Pier Woudstra MD Jan G. Tijssen PhD Robbert J. de Winter MD PhD 《Catheterization and cardiovascular interventions》2014,83(2):203-209
Objectives : To describe clinical outcome after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) due to graft failure. Background : Limited data are available on outcome after PCI for graft failure‐induced ACS in the drug‐eluting stent (DES) era. Methods : Patients were identified who underwent PCI either with DES or BMS for ACS due to graft failure between January 2003 and December 2008. Follow‐up was performed at 1 year and April 2011. The primary endpoint was the composite of death, myocardial infarction (MI), or target vessel revascularization (TVR). Kaplan–Meier estimates were calculated at 1 and 5‐year follow‐up. Predictors were identified by backward selection in Cox proportional hazards models. Results : A total of 92 patients underwent PCI, of which 77 were treated with bare metal stents (BMS) and 15 with DES. Patient and procedural characteristics were similar in both groups. Mean follow‐up was 3.2 years. Five‐year composite event rate was 65.9% after BMS vs. 43.4% after DES implantation (P = 0.17). Individual endpoints were comparable in both groups. Recurrence of angina, hospitalization, and repeat interventions were similar. After multivariable adjustment, the use of DES was not associated with a significant reduction in the primary endpoint (HR = 0.44, 0.18–1.04, p = 0.06). Conclusion : In patients presenting with ACS due to acute graft failure, long‐term outcomes remain poor. In a nonrandomized comparison with BMS, DES use was not associated with significant improved long‐term clinical outcomes. © 2012 Wiley Periodicals, Inc. 相似文献
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Gijs Kooij Kathrin Kopplin Rosel Blasig Marchel Stuiver Nathalie Koning Gera Goverse Susanne M. A. van der Pol Bert van het Hof Maik Gollasch Joost A. R. Drexhage Arie Reijerkerk Iwan C. Meij Reina Mebius Thomas E. Willnow Dominik Müller Ingolf E. Blasig Helga E. de Vries 《Acta neuropathologica》2014,128(2):267-277
Multiple sclerosis (MS) is a chronic neuro-inflammatory disorder, which is marked by the invasion of the central nervous system by monocyte-derived macrophages and autoreactive T cells across the brain vasculature. Data from experimental animal models recently implied that the passage of leukocytes across the brain vasculature is preceded by their traversal across the blood–cerebrospinal fluid barrier (BCSFB) of the choroid plexus. The correlation between the presence of leukocytes in the CSF of patients suffering from MS and the number of inflammatory lesions as detected by magnetic resonance imaging suggests that inflammation at the choroid plexus contributes to the disease, although in a yet unknown fashion. We here provide first insights into the involvement of the choroid plexus in the onset and severity of the disease and in particular address the role of the tight junction protein claudin-3 (CLDN3) in this process. Detailed analysis of human post-mortem brain tissue revealed a selective loss of CLDN3 at the choroid plexus in MS patients compared to control tissues. Importantly, mice that lack CLDN3 have an impaired BCSFB and experience a more rapid onset and exacerbated clinical signs of experimental autoimmune encephalomyelitis, which coincides with enhanced levels of infiltrated leukocytes in their CSF. Together, this study highlights a profound role for the choroid plexus in the pathogenesis of multiple sclerosis, and implies that CLDN3 may be regarded as a crucial and novel determinant of BCSFB integrity. 相似文献
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