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11.
The growth and function of organs such as pancreatic islets adapt to meet physiological challenges and maintain metabolic balance, but the mechanisms controlling these facultative responses are unclear. Diabetes in patients treated with calcineurin inhibitors such as cyclosporin A indicates that calcineurin/nuclear factor of activated T-cells (NFAT) signalling might control adaptive islet responses, but the roles of this pathway in beta-cells in vivo are not understood. Here we show that mice with a beta-cell-specific deletion of the calcineurin phosphatase regulatory subunit, calcineurin b1 (Cnb1), develop age-dependent diabetes characterized by decreased beta-cell proliferation and mass, reduced pancreatic insulin content and hypoinsulinaemia. Moreover, beta-cells lacking Cnb1 have a reduced expression of established regulators of beta-cell proliferation. Conditional expression of active NFATc1 in Cnb1-deficient beta-cells rescues these defects and prevents diabetes. In normal adult beta-cells, conditional NFAT activation promotes the expression of cell-cycle regulators and increases beta-cell proliferation and mass, resulting in hyperinsulinaemia. Conditional NFAT activation also induces the expression of genes critical for beta-cell endocrine function, including all six genes mutated in hereditary forms of monogenic type 2 diabetes. Thus, calcineurin/NFAT signalling regulates multiple factors that control growth and hallmark beta-cell functions, revealing unique models for the pathogenesis and therapy of diabetes. 相似文献
12.
In late 2001, the Object Management Group issued a Request for Proposal to develop a testing profile for UML 2.0. In June 2003, the work on the UML 2.0 Testing Profile was finally adopted by the OMG. Since March 2004, it has become an official standard of the OMG. The UML 2.0 Testing Profile provides support for UML based model-driven testing. This paper introduces a methodology on how to use the testing profile in order to modify and extend an existing UML design model for test issues. The application of the methodology will be explained by applying it to an existing UML Model for a Bluetooth device. 相似文献
13.
Hubert Bader Klaus Dorn Bernd Hupfer Helmut Ringsdorf 《Cellular and molecular life sciences : CMLS》1991,47(1):A15-A23
Posters
Membrane biology and signal transduction 相似文献14.
Helmut Lütkepohl 《Journal of forecasting》1986,5(2):85-95
If interest centres on forecasting a temporally aggregated multiple time series and the generation process of the disaggregate series is a known vector ARMA (autoregressive moving average) process then forecasting the disaggregate series and temporally aggregating the forecasts is at least as efficient, under a mean squared error measure, as forecasting the aggregated series directly. Necessary and sufficient conditions for equality of the two forecasts are given. In practice the data generation process is usually unknown and has to be determined from the available data. Using asymptotic theory it is shown that also in this case aggregated forecasts from the disaggregate process will usually be superior to forecasts obtained from the aggregated process. 相似文献
15.
Helmut Metzner 《Cellular and molecular life sciences : CMLS》1980,36(11):1275-1278
16.
Lateralization of brain functions, once believed to be a human characteristic, has now been found to be widespread among vertebrates. In birds, asymmetries of visual functions are well studied, with each hemisphere being specialized for different tasks. Here we report lateralized functions of the birds' visual system associated with magnetoperception, resulting in an extreme asymmetry of sensing the direction of the magnetic field. We found that captive migrants tested in cages with the magnetic field as the only available orientation cue were well oriented in their appropriate migratory direction when using their right eye only, but failed to show a significant directional preference when using their left eye. This implies that magnetoreception for compass orientation, assumed to take place in the eyes alongside the visual processes, is strongly lateralized, with a marked dominance of the right eye/left brain hemisphere. 相似文献
17.
This paper argues that essential features of Feyerabend's philosophy, namely his radicalization of critical rationalism and his turn to relativism, could be understood better in the light of his engagement with early Greek thought. In contrast to his earlier, Popperian views he came to see the Homeric worldview as a genuine alternative, which was not falsified by the Presocratics. Unlike socio–psychological and externalist accounts my reading of his published and unpublished material suggests that his alternative reconstruction of the ancient beginnings of the Western scientific tradition motivate and justify his moderate Protagorean relativism. 相似文献
18.
van den Bogaart G Meyenberg K Risselada HJ Amin H Willig KI Hubrich BE Dier M Hell SW Grubmüller H Diederichsen U Jahn R 《Nature》2011,479(7374):552-555
Neuronal exocytosis is catalysed by the SNAP receptor protein syntaxin-1A, which is clustered in the plasma membrane at sites where synaptic vesicles undergo exocytosis. However, how syntaxin-1A is sequestered is unknown. Here we show that syntaxin clustering is mediated by electrostatic interactions with the strongly anionic lipid phosphatidylinositol-4,5-bisphosphate (PIP2). Using super-resolution stimulated-emission depletion microscopy on the plasma membranes of PC12 cells, we found that PIP2 is the dominant inner-leaflet lipid in microdomains about 73 nanometres in size. This high accumulation of PIP2 was required for syntaxin-1A sequestering, as destruction of PIP2 by the phosphatase synaptojanin-1 reduced syntaxin-1A clustering. Furthermore, co-reconstitution of PIP2 and the carboxy-terminal part of syntaxin-1A in artificial giant unilamellar vesicles resulted in segregation of PIP2 and syntaxin-1A into distinct domains even when cholesterol was absent. Our results demonstrate that electrostatic protein-lipid interactions can result in the formation of microdomains independently of cholesterol or lipid phases. 相似文献
19.
Lin JS Anaclet C Sergeeva OA Haas HL 《Cellular and molecular life sciences : CMLS》2011,68(15):2499-2512
Wakefulness and consciousness depend on perturbation of the cortical soliloquy. Ascending activation of the cerebral cortex
is characteristic for both waking and paradoxical (REM) sleep. These evolutionary conserved activating systems build a network
in the brainstem, midbrain, and diencephalon that contains the neurotransmitters and neuromodulators glutamate, histamine,
acetylcholine, the catecholamines, serotonin, and some neuropeptides orchestrating the different behavioral states. Inhibition
of these waking systems by GABAergic neurons allows sleep. Over the past decades, a prominent role became evident for the
histaminergic and the orexinergic neurons as a hypothalamic waking center. 相似文献
20.
Helmut Schwegler 《Foundations of Science》2001,6(4):241-253
The way physics and other parts of science work can be explained in the framework of radical constructivism. However, this constructivist view itself shows that a uniquily accepted epistemology, constructivism or any other, would not be an advantage for the developmentof science. Unlike physics some parts of science successfully use constructivist concepts inside their theories. Because this is the case particularly in learning theory, constructivist ideas can help to improve physics teaching. 相似文献