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101.
Hellgren M Strömberg P Gallego O Martras S Farrés J Persson B Parés X Höög JO 《Cellular and molecular life sciences : CMLS》2007,64(4):498-505
The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2
(ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with
an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined Km values ranged from 0.05 to 0.3 μM and kcat values from 2.3 to 17.6 min−1, while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities
were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup.
This mutation increased the retinoid activity up to 100-fold. The Km values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic
retinol oxidation at physiological concentrations.
Received 12 October 2006; received after revision 6 December 2006; accepted 8 January 2007 相似文献
102.
Crnković-Mertens I Wagener N Semzow J Gröne EF Haferkamp A Hohenfellner M Butz K Hoppe-Seyler F 《Cellular and molecular life sciences : CMLS》2007,64(9):1137-1144
Cancer cells are typically characterized by apoptosis deficiency. In order to investigate a possible role for the anti-apoptotic
livin gene in renal cell cancer (RCC), we analyzed its expression in tumor tissue samples and in RCC-derived cell lines. In addition,
we studied the contribution of livin to the apoptotic resistance of RCC cells by RNA interference (RNAi). Livin gene expression was detected in a significant portion of RCC tumor tissue specimens (13/14, 92.9%) and tumor-derived cell
lines (12/15, 80.0%). Moreover, targeted inhibition of livin by RNAi markedly sensitized RCC cells towards proapoptotic stimuli, such as UV irradiation or the chemotherapeutic drugs
etoposide, 5-fluorouracil, and vinblastine. These effects were specific for livin expressing tumor cells. We conclude that livin can contribute significantly to the apoptosis resistance of RCC cells. Targeted inhibition of livin could represent a novel therapeutic strategy to increase the sensitivity of renal cancers towards pro-apoptotic agents.
Received 30 November 2006; received after revision 22 February 2007; accepted 20 March 2007 相似文献
103.
Receptor communication within the lymphocyte plasma membrane: a role for the thrombospondin family of matricellular proteins 总被引:1,自引:0,他引:1
Lymphocytes, the principal cells of the immune system, carry out immune surveillance throughout the body by their unique capacity
to constantly reposition themselves between a free-floating vascular state and a tissue state characterized by migration and
frequent adhesive interactions with endothelial cells and components of the extracellular matrix. Therefore, mechanisms co-ordinating
adhesion and migration with signals delivered through antigen recognition probably play a pivotal role for the regulation
of lymphocyte behaviour and function. Endogenous thrombospondin-1 (TSP-1) seems to be the hub in such a mechanism for autocrine
regulation of T cell adhesion and migration. TSP-1 functions as a mediator of cis interaction of vital receptors within the T lymphocyte plasma membrane, including integrins, low density lipoprotein receptor-related
protein, calreticulin and integrin-associated protein.
Received 1 June 2006; received after revision 28 June 2006; accepted 11 October 2006 相似文献
104.
Lindahl E Nyman U Melles E Sigmundsson K Ståhlberg M Wahren J Obrink B Shafqat J Joseph B Jörnvall H 《Cellular and molecular life sciences : CMLS》2007,64(4):479-486
Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is
internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide,
we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport
into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at
4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive
mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated
binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components
to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence
of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that
of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action.
Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006 相似文献
105.
Predicting Stock Return Volatility: Can We Benefit from Regression Models for Return Intervals?
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We study the performance of recently developed linear regression models for interval data when it comes to forecasting the uncertainty surrounding future stock returns. These interval data models use easy‐to‐compute daily return intervals during the modeling, estimation and forecasting stage. They have to stand up to comparable point‐data models of the well‐known capital asset pricing model type—which employ single daily returns based on successive closing prices and might allow for GARCH effects—in a comprehensive out‐of‐sample forecasting competition. The latter comprises roughly 1000 daily observations on all 30 stocks that constitute the DAX, Germany's main stock index, for a period covering both the calm market phase before and the more turbulent times during the recent financial crisis. The interval data models clearly outperform simple random walk benchmarks as well as the point‐data competitors in the great majority of cases. This result does not only hold when one‐day‐ahead forecasts of the conditional variance are considered, but is even more evident when the focus is on forecasting the width or the exact location of the next day's return interval. Regression models based on interval arithmetic thus prove to be a promising alternative to established point‐data volatility forecasting tools. Copyright ©2015 John Wiley & Sons, Ltd. 相似文献
106.
Christoph Wegener Christian von Spreckelsen Tobias Basse Hans‐Jörg von Mettenheim 《Journal of forecasting》2016,35(1):86-92
This paper discusses techniques that might be helpful in predicting interest rates and tries to evaluate a new hybrid forecasting approach. Results of examining government bond yields in Germany and France reported in this study indicate that a hybrid forecasting approach which combines techniques of cointegration analysis with neural network (NN) forecasting models can produce superior results to the use of NN forecasting models alone. The findings documented in this paper could be a consequence of the fact that examining differenced data under certain conditions will lead to a loss of information and that the inclusion of the error correction term from the cointegration model can help to cope with this problem. The paper also discusses some possibly interesting directions for further research. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
107.
108.
Thomas Görnitz 《Foundations of Science》2018,23(3):475-510
Our interest focusses on the idea, that consciousness is a powerful acting entity. Up to now there does not exist a scientific concept for this idea. This is not due to problems within the field of psychology or brain research, but rather in resisting theories of modern physics. That is, why we have to search for a solution in the field of physics. A solution can be found in a new understanding of the basics of physical theory. That could be given by abstract and absolute quantum bits of information (AQI bits). To avoid the popular misunderstanding of “information” as “meaningful” it was necessary to find a new word for the free-of-meaning AQI bits: the AQI bits establish a quantum pre-structure termed “Protyposis” (Greek: “pre-formation”), out of which real objects can be formed, starting from energetical and material elementary particles. The Protyposis AQI bits provide a pre-structure for all entities in natural sciences. They are the basic entities, whereof the physical nature of the brain, on the one hand, and the mental nature of consciousness, on the other hand, were formed during the cosmological and the following biological evolution. A deeper understanding of quantum structures may help to overcome the resistance against quantum theory in the field of brain research and consciousness. The key for an understanding is the concept of Protyposis, which means an abstract quantum information free of any definite meaning. With the AQI bits of the Protyposis, both, massless and massive quantum particles can be constructed. Even quantum information with special meanings, in example grammatically formulated thoughts, eventually could be explained. As long as the fundamental basis of quantum theory is misunderstood as being formed by a manifold of some small objects like atoms, quarks, or strings, the problem of understanding consciousness has no solution. If instead we understand quantum theory as based on truly simple quantum structures, there would be no longer fundamental problems for an understanding of consciousness. 相似文献
109.
Dominik C. Fuhrmann Ilka Wittig Stefan Dröse Tobias Schmid Nathalie Dehne Bernhard Brüne 《Cellular and molecular life sciences : CMLS》2018,75(16):3051-3067
Cell stress such as hypoxia elicits adaptive responses, also on the level of mitochondria, and in part is mediated by the hypoxia-inducible factor (HIF) 1α. Adaptation of mitochondria towards acute hypoxic conditions is reasonably well understood, while regulatory mechanisms, especially of respiratory chain assembly factors, under chronic hypoxia remains elusive. One of these assembly factors is transmembrane protein 126B (TMEM126B). This protein is part of the mitochondrial complex I assembly machinery. We identified changes in complex I abundance under chronic hypoxia, in association with impaired substrate-specific mitochondrial respiration. Complexome profiling of isolated mitochondria of the human leukemia monocytic cell line THP-1 revealed HIF-1α-dependent deficits in complex I assembly and mitochondrial complex I assembly complex (MCIA) abundance. Of all mitochondrial MCIA members, we proved a selective HIF-1-dependent decrease of TMEM126B under chronic hypoxia. Mechanistically, HIF-1α induces the E3-ubiquitin ligase F-box/WD repeat-containing protein 1A (β-TrCP1), which in turn facilitates the proteolytic degradation of TMEM126B. Attenuating a functional complex I assembly appears critical for cellular adaptation towards chronic hypoxia and is linked to destruction of the mitochondrial assembly factor TMEM126B. 相似文献