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41.
Karina Weinhold Udo Krause-Buchholz Gerhard Rödel Michael Kasper Kathrin Barth 《Cellular and molecular life sciences : CMLS》2010,67(15):2631-2642
P2X4 and P2X7 receptors are ATP-gated ion channels that are co-expressed in alveolar epithelial type I cells. Both receptors
are localized to the plasma membrane and partly associated with lipid rafts. Here we report on our study in an alveolar epithelial
cell line of the molecular organization of P2X7R and P2X4R receptors and the effect of their knockdown. Native gel electrophoresis
reveals three P2X7R complexes of ~430, ~580 and ~760 kDa. The latter two correspond exactly in size to signals of Cav-1, the
structural protein of caveolae. Interestingly knockdown of P2rx7 affects protein levels, the intracellular distribution and the supramolecular organization of Cav-1 as well as of P2X4R,
which is mainly detected in a complex of ~430 kDa. Our data suggest upregulation of P2X4R as a compensatory mechanism of P2X7R
depletion. 相似文献
42.
Michael Hofreiter Torsten Schöneberg 《Cellular and molecular life sciences : CMLS》2010,67(15):2591-2603
Variation in pigmentation is one of the most conspicuous phenotypic traits in vertebrates. Although mammals show less variation
in body pigmentation than other vertebrate groups, the genetics of colour determination and variation is best understood for
them. More than 150 genes have been identified that influence pigmentation, and in many cases, the cause for variation in
pigmentation has been identified down to the underlying nucleotide changes. These studies show that while some genes are often
responsible for deviating pigmentation, similar or almost identical phenotypes even in the same species may be due to mutations
in different genes. In this review we will first discuss the current knowledge about the genes and their functions underlying
the biochemical pathways that determine pigmentation and then give examples where the mutations responsible for colour variation
have been determined. Finally, we will discuss potential evolutionary causes for and consequences of differences in pigmentation
between individuals. 相似文献
43.
Michael R. Yeaman 《Cellular and molecular life sciences : CMLS》2010,67(4):525-544
Platelets interact with bacterial pathogens through a wide array of cellular and molecular mechanisms. The consequences of
this interaction may significantly influence the balance between infection and immunity. On the one hand, recent data indicate
that certain bacteria may be capable of exploiting these interactions to gain a virulence advantage. Indeed, certain bacterial
pathogens appear to have evolved specific ways in which to subvert activated platelets. Hence, it is conceivable that some
bacterial pathogens exploit platelet responses. On the other hand, platelets are now known to possess unambiguous structures
and functions of host defense effector cells. Recent discoveries emphasize critical features enabling such functions, including
expression of toll-like receptors that detect hallmark signals of bacterial infection, an array of microbicidal peptides,
as well as other host defense molecules and functions. These concepts are consistent with increased risk and severity of bacterial
infection as correlates of clinical abnormalities in platelet quantity and quality. In these respects, the molecular and cellular
roles of platelets in host defense against bacterial pathogens are explored with attention on advances in platelet immunobiology. 相似文献
44.
Michael Bartholomew 《Annals of science》2013,70(6):525-535
This article ventures a reappraisal of Huxley's role in the Darwinian debates. First, the views on life-history held by Huxley before 1859 are identified. Next, the disharmony between these views and the view put forward by Darwin in the Origin of species (1859) is discussed. Huxley's defence of the Origin is then reviewed in an effort to show that, despite his fervour on Darwin's behalf, his advocacy of the case for natural selection was not particularly compelling, and that his own scientific work took no revolutionary new direction after 1859. 相似文献
45.
Linda Reinhard Henning Tidow Michael J. Clausen Poul Nissen 《Cellular and molecular life sciences : CMLS》2013,70(2):205-222
The Na+,K+-ATPase, or sodium pump, is well known for its role in ion transport across the plasma membrane of animal cells. It carries out the transport of Na+ ions out of the cell and of K+ ions into the cell and thus maintains electrolyte and fluid balance. In addition to the fundamental ion-pumping function of the Na+,K+-ATPase, recent work has suggested additional roles for Na+,K+-ATPase in signal transduction and biomembrane structure. Several signaling pathways have been found to involve Na+,K+-ATPase, which serves as a docking station for a fast-growing number of protein interaction partners. In this review, we focus on Na+,K+-ATPase as a signal transducer, but also briefly discuss other Na+,K+-ATPase protein–protein interactions, providing a comprehensive overview of the diverse signaling functions ascribed to this well-known enzyme. 相似文献
46.
Vivek S. Peche Tad A. Holak Bhagyashri D. Burgute Kosmas Kosmas Sushant P. Kale F. Thomas Wunderlich Fatiha Elhamine Robert Stehle Gabriele Pfitzer Klaus Nohroudi Klaus Addicks Florian Stöckigt Jan W. Schrickel Julia Gallinger Michael Schleicher Angelika A. Noegel 《Cellular and molecular life sciences : CMLS》2013,70(3):527-543
Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects. 相似文献
47.
John T. Heiker Nora Klöting Peter Kovacs E. Bartholomeus Kuettner Norbert Sträter Stephan Schultz Matthias Kern Michael Stumvoll Matthias Blüher Annette G. Beck-Sickinger 《Cellular and molecular life sciences : CMLS》2013,70(14):2569-2583
The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin–hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic β-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance. 相似文献
48.
Irina Tikhonenko Valentin Magidson Ralph Gräf Alexey Khodjakov Michael P. Koonce 《Cellular and molecular life sciences : CMLS》2013,70(7):1285-1296
The M-type kinesin isoform, Kif9, has recently been implicated in maintaining a physical connection between the centrosome and nucleus in Dictyostelium discoideum. However, the mechanism by which Kif9 functions to link these two organelles remains obscure. Here we demonstrate that the Kif9 protein is localized to the nuclear envelope and is concentrated in the region underlying the centrosome point of attachment. Nuclear anchorage appears mediated through a specialized transmembrane domain located in the carboxyl terminus. Kif9 interacts with microtubules in in vitro binding assays and effects an endwise depolymerization of the polymer. These results suggest a model whereby Kif9 is anchored to the nucleus and generates a pulling force that reels the centrosome up against the nucleus. This is a novel activity for a kinesin motor, one important for progression of cells into mitosis and to ensure centrosome-nuclear parity in a multinuclear environment. 相似文献
49.
John D. Norton is responsible for a number of influential views in contemporary philosophy of science. This paper will discuss two of them. The material theory of induction claims that inductive arguments are ultimately justified by their material features, not their formal features. Thus, while a deductive argument can be valid irrespective of the content of the propositions that make up the argument, an inductive argument about, say, apples, will be justified (or not) depending on facts about apples. The argument view of thought experiments claims that thought experiments are arguments, and that they function epistemically however arguments do. These two views have generated a great deal of discussion, although there hasn't been much written about their combination. I argue that despite some interesting harmonies, there is a serious tension between them. I consider several options for easing this tension, before suggesting a set of changes to the argument view that I take to be consistent with Norton's fundamental philosophical commitments, and which retain what seems intuitively correct about the argument view. These changes require that we move away from a unitary epistemology of thought experiments and towards a more pluralist position. 相似文献
50.