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41.
The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts 总被引:14,自引:0,他引:14
Hartmann D de Strooper B Serneels L Craessaerts K Herreman A Annaert W Umans L Lübke T Lena Illert A von Figura K Saftig P 《Human molecular genetics》2002,11(21):2615-2624
The metalloprotease ADAM 10 is an important APP alpha-secretase candidate, but in vivo proof of this is lacking. Furthermore, invertebrate models point towards a key role of the ADAM 10 orthologues Kuzbanian and sup-17 in Notch signalling. In the mouse, this function is, however, currently attributed to ADAM 17/TACE, while the role of ADAM 10 remains unknown. We have created ADAM 10-deficient mice. They die at day 9.5 of embryogenesis with multiple defects of the developing central nervous system, somites, and cardiovascular system. In situ hybridization revealed a reduced expression of the Notch target gene hes-5 in the neural tube and an increased expression of the Notch ligand dll-1, supporting an important role for ADAM 10 in Notch signalling in the vertebrates as well. Since the early lethality precluded the establishment of primary neuronal cultures, APPs alpha generation was analyzed in embryonic fibroblasts and found to be preserved in 15 out of 17 independently generated ADAM 10-deficient fibroblast cell lines, albeit at a quantitatively more variable level than in controls, whereas a severe reduction was found in only two cases. The variability was not due to differences in genetic background or to variable expression of the alternative alpha-secretase candidates ADAM 9 and ADAM 17. These results indicate, therefore, either a regulation between ADAMs on the post-translational level or that other, not yet known, proteases are able to compensate for ADAM 10 deficiency. Thus, the observed variability, together with recent reports on tissue-specific expression patterns of ADAMs 9, 10 and 17, points to the existence of tissue-specific 'teams' of different proteases exerting alpha-secretase activity. 相似文献
42.
Markus F. Neurath Ivan Fuss Manolis Pasparakis Lena Alexopoulou Sylva Haralambous Karl-Hermann Meyer zum Büschenfelde Warren Strober George Kollias 《European journal of immunology》1997,27(7):1743-1750
Antibodies to tumor necrosis factor (TNF)-α have been recently proposed as effective treatment for patients with Crohn's disease. Here, we analyze the functional role of TNF-α in a mouse model of chronic intestinal inflammation induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that mimics some characteristics of Crohn's disease in humans. Macrophage-enriched lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis produced 10–30-fold higher levels of TNF-α mRNA and protein than cells from control mice. When mice with chronic colitis were treated by intraperitoneal injection of antibodies to TNF-α, an improvement of both the clinical and histopathologic signs of disease was found. Isolated macrophage-enriched LP cells from anti-TNF-α-treated mice produced strikingly less pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant role of TNF-α in the mouse TNBS-induced colitis model was further underlined by the finding that striking colonic inflammation and lethal pancolitis was induced in TNF-α-transgenic mice upon TNBS treatment. Conversely, no significant TNBS-induced colitis could be induced in mice in which the TNF-α gene had been inactivated by homologous recombination. Complementation of TNF-α function in TNF?/? mice by the expression of a mouse TNF-α transgene was sufficient to reverse this effect. Taken together, the data provide direct evidence for a predominant role of TNF-α in a mouse model of chronic intestinal inflammation and encourage further clinical trials with antibodies to TNF-α for the treatment of patients with Crohn's disease. 相似文献
43.
Observations on skin reflectance were made on 309 endogamous Indian families, for constitutive (medial upper arm) and facultative skin colour (forehead) to investigate which of the two colours is under a rigid control of genetic action. An assessment of data by coefficient of correlation "r" show that facultative colour is inherited more strictly than the constitutive colour.
Received 4 July, accepted 3 October 1983 相似文献
Received 4 July, accepted 3 October 1983 相似文献
44.
Marius Schwabenland Henrike Salié Jovan Tanevski Saskia Killmer Marilyn Salvat Lago Alexandra Emilia Schlaak Lena Mayer Jakob Matschke Klaus Püschel Antonia Fitzek Benjamin Ondruschka Henrik E. Mei Tobias Boettler Christoph Neumann-Haefelin Maike Hofmann Angele Breithaupt Nafiye Genc Christine Stadelmann Bertram Bengsch 《Immunity》2021,54(7):1594-1610.e11
45.
Vural Alperen Carobbio Andrea Luigi Camillo Ferrari Marco Rampinelli Vittorio Schreiber Alberto Mattavelli Davide Doglietto Francesco Buffoli Barbara Rodella Luigi Fabrizio Taboni Stefano Tomasoni Michele Gualtieri Tommaso Deganello Alberto Hirtler Lena Nicolai Piero 《Neurosurgical review》2021,44(5):2857-2878
Neurosurgical Review - Transorbital endoscopic approaches are increasing in popularity as they provide corridors to reach various areas of the ventral skull base through the orbit. They can be used... 相似文献
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49.
Lena Thyrell Olle Sangfelt Boris Zhivotovsky Katja Pokrovskaja Yisong Wang Stefan Einhorn Dan Grandér 《Journal of interferon & cytokine research》2005,25(2):63-72
Interferons (IFNs) exert antitumor effects in several human malignancies, but their mechanism of action is unclear. There is a great variability in sensitivity to IFN treatment depending on both tumor type and the individual patient. The reason for this variable sensitivity is not known. The fact that several IFN-induced anticellular effects are exerted through modulation of proto-oncogenes and tumor suppressor genes may indicate that the malignant genotype may be decisive in the cell's sensitivity to IFN. To determine if a deregulated oncogene could alter the cellular response to IFN, a mouse lymphoma cell line (J3D) was stably transfected with the viral human papillomavirus-16 (HPV-16) E7 oncogene. The E7-transfected cells and their respective mock-transfected sister clones were treated with IFN-alpha and examined for possible IFN-induced anticellular effects. We found that the E7-transfected clones were greatly sensitized to IFN-alpha-induced apoptosis compared with their mock-transfected counterparts. Induction of apoptosis in the transfected cells correlated with the ability of IFN to activate parts of the proapoptotic machinery specifically in these cells, including activation of caspases and the proapoptotic protein Bak. In summary, our data suggest that transfection of malignant cells with the E7 oncogene can sensitize them to IFN-alpha-induced apoptosis. This demonstrates that an oncogenic event may alter the cellular sensitivity to IFN and might also have implications for treatment of HPV-related diseases with IFN. 相似文献
50.
Jenny Englert Lena Witzdam Dominik Söder Manuela Garay-Sarmiento Anton Joseph Anna M. Wagner Cesar Rodriguez-Emmenegger 《Macromolecular chemistry and physics.》2023,224(24):2300306
The immobilization of vesicles has been conceptualized as a method to functionalize biointerfaces. However, the preservation of their integrity post immobilization remains a considerable challenge. Interfacial interactions can cause vesicle rupture upon close surface contact and non-specific protein adsorption impairing surface functions. To date, immobilization of vesicles has relied solely on either entrapment or prior modification of vesicles, both of which require laborious preparation and limit their applications. This work develops a bioinspired strategy to pin vesicles without prior modification while preserving their intact shape. This work introduces antifouling diblock copolymers and ultrathin surface-attached hydrogels containing a brush-like interface consisting of a bottle brush copolymer of N-(2-hydroxypropyl) methacrylamide (HPMA) and N-(3-methacrylamidopropyl)-N,N-dimethyldodecan-1-aminiumiodide (C12+). The presence of positive charges generates an attractive force that pulls vesicles toward the surface. At the surface, the amphiphilic properties of the combs facilitate their insertion into the membrane, mimicking the harpooning mechanism observed in antimicrobial peptides. Importantly, the antifouling poly(HPMA) backdrop serves to safeguard the vesicles by preventing deformation and breakage. Using a combination of thermodynamic analysis, surface plasmon resonance, and confocal laser scanning microscopy, this work demonstrates the efficiency of this biomimetic system to capture vesicles while maintaining an antifouling interface necessary for bioapplications. 相似文献