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51.
52.
Structural maintenance of chromosomes protein C-terminal domains bind preferentially to DNA with secondary structure 总被引:1,自引:0,他引:1
AT Akhmedov C Frei M Tsai-Pflugfelder B Kemper SM Gasser R Jessberger 《Canadian Metallurgical Quarterly》1998,273(37):24088-24094
Structural maintenance of chromosomes (SMC) proteins interact with DNA in chromosome condensation, sister chromatid cohesion, DNA recombination, and gene dosage compensation. How individual SMC proteins and their functional domains bind DNA has not been described. We demonstrate the ability of the C-terminal domains of Saccharomyces cerevisiae SMC1 and SMC2 proteins, representing two major subfamilies with different functions, to bind DNA in an ATP-independent manner. Three levels of DNA binding specificity were observed: 1) a >100-fold preference for double-stranded versus single-stranded DNA; 2) a high affinity for DNA fragments able to form secondary structures and for synthetic cruciform DNA molecules; and 3) a strong preference for AT-rich DNA fragments of particular types. These include fragments from the scaffold-associated regions, and an alternating poly(dA-dT)-poly(dT-dA) synthetic polymer, as opposed to a variety of other polymers. Reannealing of complementary DNA strands is also promoted primarily by the C-terminal domains. Consistent with their in vitro DNA binding activity, we show that overexpression of the SMC C termini increases plasmid loss without altering viability or cell cycle progression. 相似文献
53.
A temperature-sensitive mutant of Moloney murine leukemia virus defective in an early function and injected into newborn mice produced lower limb paralysis. Susceptible mice were inbred strains CFW/D, CBA/H, C3H/Bi/Ka, and outbred NIH Swiss stock. Inbred W/Fu rats and C57BL/Ka mice did not develop the paralysis, though the latter were infected with virus; the sera from these mice produced paralysis in susceptible CFW mice. 相似文献
54.
R Schiffmann NK Dwyer IA Lubensky M Tsokos VE Sutliff JS Latimer KP Frei RO Brady NW Barton EJ Blanchette-Mackie E Goldin 《Canadian Metallurgical Quarterly》1998,95(3):1207-1212
Mucolipidosis type IV is an autosomal recessive lysosomal storage disease of unknown etiology that causes severe neurological and ophthalmological abnormalities. In an attempt to obtain insight into the nature of the metabolic abnormality in this disorder, we prospectively evaluated 15 consecutive patients, aged 2 to 23 years, over a period of 22 months. The finding of iron deficiency in some of the patients led us to the discovery that all patients but one had markedly elevated blood gastrin levels. None had vitamin B12 deficiency. Gastroscopy in three patients showed normal gross appearance of the mucosa in two patients, 4 and 7 years old, and mucosal atrophy in a 22-year-old. Parietal cells were present in normal numbers and contained large cytoplasmic inclusions that were confirmed immunohistochemically to be lysosomal in nature. Other gastric epithelial cells appeared normal. Parietal cells contained very few tubulovesicular membranes, suggesting cellular activation, whereas apical canaliculi appeared relatively nonactivated. Both subunits of the parietal cell H+/K+-ATPase were present, and both partially colocalized with f-actin at the apical membrane. We conclude that patients with mucolipidosis type IV are constitutively achlorhydric and have partially activated parietal cells. We hypothesize that the defective protein in this disease is closely associated with the final stages of parietal cell activation and is critical for a specific type of cellular vacuolar trafficking between the cytoplasm and the apical membrane domain. 相似文献
55.
Vuong H.-H. Xie Y.-H. Frei M.R. Hobler G. Pelaz L. Rafferty C.S. 《Electron Devices, IEEE Transactions on》2000,47(7):1401-1405
We report experimental results demonstrating the use of transient enhanced diffusion (TED) caused by silicon implant for “tuning” boron out-diffusion. The effect was measured as a function of the silicon implant dose and anneal temperature, and a range of boron junction depth movement from almost none up to 81 nm was observed with increasing TED at 750°C. The diffused profiles could be approximated by using a modified solubility limit model to describe the enhanced boron diffusion and clustering. However, by using a more sophisticated continuum model based on atomistic calculations, excellent agreement with the measured profiles could he obtained. In addition, the fit to the measured data yields the fraction of boron present in BI2 precursor clusters after silicon implant as a function of the silicon implant dose. Two possible applications of the TED “tuning” are discussed, with device simulations which show that the effect is sufficiently large to tune the base width of a bipolar device from being depleted to that suitable for a high performance device 相似文献
56.
Marie Stiborová Věra ?erná Michaela Moserová Iveta Mrízová Volker M. Arlt Eva Frei 《International journal of molecular sciences》2015,16(1):284-306
Ellipticine is a DNA-damaging agent acting as a prodrug whose pharmacological efficiencies and genotoxic side effects are dictated by activation with cytochrome P450 (CYP). Over the last decade we have gained extensive experience in using pure enzymes and various animal models that helped to identify CYPs metabolizing ellipticine. In this review we focus on comparison between the in vitro and in vivo studies and show a necessity of both approaches to obtain valid information on CYP enzymes contributing to ellipticine metabolism. Discrepancies were found between the CYP enzymes activating ellipticine to 13-hydroxy- and 12-hydroxyellipticine generating covalent DNA adducts and those detoxifying this drug to 9-hydroxy- and 7-hydroellipticine in vitro and in vivo. In vivo, formation of ellipticine-DNA adducts is dependent not only on expression levels of CYP3A, catalyzing ellipticine activation in vitro, but also on those of CYP1A that oxidize ellipticine in vitro mainly to the detoxification products. The finding showing that cytochrome b5 alters the ratio of ellipticine metabolites generated by CYP1A1/2 and 3A4 explained this paradox. Whereas the detoxification of ellipticine by CYP1A and 3A is either decreased or not changed by cytochrome b5, activation leading to ellipticine-DNA adducts increased considerably. We show that (I) the pharmacological effects of ellipticine mediated by covalent ellipticine-derived DNA adducts are dictated by expression levels of CYP1A, 3A and cytochrome b5, and its own potency to induce these enzymes in tumor tissues, (II) animal models, where levels of CYPs are either knocked out or induced are appropriate to identify CYPs metabolizing ellipticine in vivo, and (III) extrapolation from in vitro data to the situation in vivo is not always possible, confirming the need for these animal models. 相似文献
57.
M. Khl M. Heck S. Brunold U. Frei B. Carlsson K. Mller 《Solar Energy Materials & Solar Cells》2004,84(1-4):275
New solar absorber coatings are developed and used in advanced collector designs with improved efficiency. The operation temperature and stagnation temperature as the main durability load for the absorbers were increasing during the past due to these innovations. Especially the highly selective new coatings have to suffer by these stronger loads. The service life estimation procedures developed in the framework of research activities of the IEA Solar Heating and Cooling Programme (Task 10 and Working Group Materials in Solar–Thermal Collectors) were based on load profiles for less-advanced absorbers and collectors and did not take into account the impact of the optical properties of the absorber coatings on the stagnation temperature of the collectors, which is the main reason for temperature degradation. A new procedure was developed, which allows testing depending on the optical properties (Solar absorptance and thermal emittance) of the absorbers. 相似文献
58.
JR Jauchem MR Frei KL Ryan JH Merritt MR Murphy 《Canadian Metallurgical Quarterly》1999,46(1):117-120
OBJECTIVE: This report describes the radiologic findings and discusses the clinical consequences of acute traumatic aortic tear occurring with an aberrant right subclavian artery. CONCLUSION: Identification of an aberrant right subclavian artery with acute traumatic aortic tear must be emphasized to reduce iatrogenic morbidity and mortality. 相似文献
59.
60.
MP Zanni D Mauri-Hellweg C Brander T Wendland B Schnyder E Frei S von Greyerz A Bircher WJ Pichler 《Canadian Metallurgical Quarterly》1997,158(3):1139-1148
To investigate the cellular immune response to the drug lidocaine, we generated T cell lines and clones from the peripheral blood of four patients with proven allergy to lidocaine. The patients had contact dermatitis after topical application of lidocaine, and local swelling or generalized erythema exudativum multiforme after submucosal/subcutaneous injection of lidocaine. Two of three lidocaine-specific T cell lines were oligoclonal and one even became monoclonal, while the simultaneously analyzed immune response to tetanus toxoid was polyclonal. The lidocaine-specific T cell lines cross-reacted to mepivacaine, but not to other local anesthetics (bupivacaine, procaine, oxybuprocaine, and tetracaine). The majority of reactive T cells belonged to the CD4 cell lineage and were MHC class II restricted, but cloning also revealed some MHC class I-restricted CD8+ clones. A total of 2 of 56 lidocaine-specific T cell clones were CD4-CD8- and expressed TCR-gammadelta. The majority of 13 analyzed CD4 clones produced a rather polarized cytokine pattern, with a dominance of Th2-like cytokines showing a high IL-5 production. In addition, three CD4+ and all CD8+ (n = 7) clones secreted high IFN-gamma and low levels of IL-5/IL-4 (Th1-like). The data illustrate that a drug that sensitizes via the skin elicits a heterogeneous T cell response. The high IL-5 production and the participation of specific CD4+CD8+ and even gammadelta+ T cells appear to be distinguishing features of this hapten-specific immune response. 相似文献