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Alexander Dietrich

Bio: Alexander Dietrich is an academic researcher from Ludwig Maximilian University of Munich. The author has contributed to research in topics: Transient receptor potential channel & TRPC. The author has an hindex of 49, co-authored 120 publications receiving 7689 citations. Previous affiliations of Alexander Dietrich include University of Ulm & University of Marburg.


Papers
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Journal ArticleDOI
TL;DR: These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotsic syndrome.
Abstract: Nephrotic syndrome, a malfunction of the kidney glomerular filter, leads to proteinuria, edema and, in steroid-resistant nephrotic syndrome, end-stage kidney disease. Using positional cloning, we identified mutations in the phospholipase C epsilon gene (PLCE1) as causing early-onset nephrotic syndrome with end-stage kidney disease. Kidney histology of affected individuals showed diffuse mesangial sclerosis (DMS). Using immunofluorescence, we found PLCepsilon1 expression in developing and mature glomerular podocytes and showed that DMS represents an arrest of normal glomerular development. We identified IQ motif-containing GTPase-activating protein 1 as a new interaction partner of PLCepsilon1. Two siblings with a missense mutation in an exon encoding the PLCepsilon1 catalytic domain showed histology characteristic of focal segmental glomerulosclerosis. Notably, two other affected individuals responded to therapy, making this the first report of a molecular cause of nephrotic syndrome that may resolve after therapy. These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotic syndrome.

505 citations

Journal ArticleDOI
TL;DR: It is implied that constitutively active TRPC3-type channels, which are up-regulated in TRPC6-deficient smooth muscle cells, are not able to functionally replace TRPC 6, which has distinct nonredundant roles in the control of vascular smooth muscle tone.
Abstract: Among the TRPC subfamily of TRP (classical transient receptor potential) channels, TRPC3, -6, and -7 are gated by signal transduction pathways that activate C-type phospholipases as well as by direct exposure to diacylglycerols. Since TRPC6 is highly expressed in pulmonary and vascular smooth muscle cells, it represents a likely molecular candidate for receptor-operated cation entry. To define the physiological role of TRPC6, we have developed a TRPC6-deficient mouse model. These mice showed an elevated blood pressure and enhanced agonist-induced contractility of isolated aortic rings as well as cerebral arteries. Smooth muscle cells of TRPC6-deficient mice have higher basal cation entry, increased TRPC-carried cation currents, and more depolarized membrane potentials. This higher basal cation entry, however, was completely abolished by the expression of a TRPC3-specific small interference RNA in primary TRPC6(-)(/)(-) smooth muscle cells. Along these lines, the expression of TRPC3 in wild-type cells resulted in increased basal activity, while TRPC6 expression in TRPC6(-/-) smooth muscle cells reduced basal cation influx. These findings imply that constitutively active TRPC3-type channels, which are up-regulated in TRPC6-deficient smooth muscle cells, are not able to functionally replace TRPC6. Thus, TRPC6 has distinct nonredundant roles in the control of vascular smooth muscle tone.

485 citations

Journal ArticleDOI
14 Aug 2008-Neuron
TL;DR: Taken together, the results establish TRPC3 as a new type of postsynaptic channel that mediates mGluR-dependent synaptic transmission in cerebellar Purkinje cells and is crucial for motor coordination.

376 citations

Journal ArticleDOI
TL;DR: It is concluded that store depletion-activated Ca2+ entry occurs through channels that have TRPs as one of their normal structural components, and that these channels are directly activated by IP3Rs.
Abstract: Homologues of Drosophilia transient receptor potential (TRP) have been proposed to be unitary subunits of plasma membrane ion channels that are activated as a consequence of active or passive depletion of Ca2+ stores. In agreement with this hypothesis, cells expressing TRPs display novel Ca2+-permeable cation channels that can be activated by the inositol 1,4,5-trisphosphate receptor (IP3R) protein. Expression of TRPs alters cells in many ways, including up-regulation of IP3Rs not coded for by TRP genes, and proof that TRP forms channels of these and other cells is still missing. Here, we document physical interaction of TRP and IP3R by coimmunoprecipitation and glutathione S-transferase-pulldown experiments and identify two regions of IP3R, F2q and F2g, that interact with one region of TRP, C7. These interacting regions were expressed in cells with an unmodified complement of TRPs and IP3Rs to study their effect on agonist- as well as store depletion-induced Ca2+ entry and to test for a role of their respective binding partners in Ca2+ entry. C7 and an F2q-containing fragment of IP3R decreased both forms of Ca2+ entry. In contrast, F2g enhanced the two forms of Ca2+ entry. We conclude that store depletion-activated Ca2+ entry occurs through channels that have TRPs as one of their normal structural components, and that these channels are directly activated by IP3Rs. IP3Rs, therefore, have the dual role of releasing Ca2+ from stores and activating Ca2+ influx in response to either increasing IP3 or decreasing luminal Ca2+.

363 citations

Journal ArticleDOI
Christopher J. Milne, Thomas Schietinger, M. Aiba, Arturo Alarcon, J. Alex, Alexander Anghel, Vladimir Arsov, Carl Beard, Paul Beaud, Simona Bettoni, M. Bopp, H. Brands, Manuel Brönnimann, Ingo Brunnenkant, Marco Calvi, A. Citterio, Paolo Craievich, Marta Csatari Divall, Mark Dällenbach, Michael D’Amico, Andreas Dax, Yunpei Deng, Alexander Dietrich, Roberto Dinapoli, Edwin Divall, Sladana Dordevic, Simon Ebner, Christian Erny, Hansrudolf Fitze, Uwe Flechsig, Rolf Follath, F. Frei, Florian Gärtner, Romain Ganter, Terence Garvey, Zheqiao Geng, I. Gorgisyan, C. Gough, A. Hauff, Christoph P. Hauri, Nicole Hiller, Tadej Humar, Stephan Hunziker, Gerhard Ingold, Rasmus Ischebeck, Markus Janousch, Pavle Juranić, M. Jurcevic, Maik Kaiser, Babak Kalantari, Roger Kalt, B. Keil, Christoph Kittel, Gregor Knopp, W. Koprek, Henrik T. Lemke, Thomas Lippuner, Daniel Llorente Sancho, Florian Löhl, C. Lopez-Cuenca, Fabian Märki, F. Marcellini, G. Marinkovic, Isabelle Martiel, Ralf Menzel, Aldo Mozzanica, Karol Nass, Gian Luca Orlandi, Cigdem Ozkan Loch, Ezequiel Panepucci, Martin Paraliev, Bruce D. Patterson, Bill Pedrini, Marco Pedrozzi, Patrick Pollet, Claude Pradervand, Eduard Prat, Peter Radi, Jean-Yves Raguin, S. Redford, Jens Rehanek, Julien Réhault, Sven Reiche, Matthias Ringele, J. Rittmann, Leonid Rivkin, Albert Romann, Marie Ruat, C. Ruder, Leonardo Sala, Lionel Schebacher, T. Schilcher, Volker Schlott, Thomas J. Schmidt, Bernd Schmitt, Xintian Shi, M. Stadler, L. Stingelin, Werner Sturzenegger, Jakub Szlachetko, D. Thattil, D. Treyer, A. Trisorio, Wolfgang Tron, S. Vetter, Carlo Vicario, Didier Voulot, Meitian Wang, Thierry Zamofing, Christof Zellweger, R. Zennaro, Elke Zimoch, Rafael Abela, Luc Patthey, Hans-Heinrich Braun 
TL;DR: The SwissFEL X-ray Free Electron Laser (XFEL) facility as discussed by the authors started construction at the Paul Scherrer Institute (Villigen, Switzerland) in 2013 and will be ready to accept its first users in 2018 on the Aramis hard Xray branch.
Abstract: The SwissFEL X-ray Free Electron Laser (XFEL) facility started construction at the Paul Scherrer Institute (Villigen, Switzerland) in 2013 and will be ready to accept its first users in 2018 on the Aramis hard X-ray branch. In the following sections we will summarize the various aspects of the project, including the design of the soft and hard X-ray branches of the accelerator, the results of SwissFEL performance simulations, details of the photon beamlines and experimental stations, and our first commissioning results.

295 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: The universality of calcium as an intracellular messenger depends on its enormous versatility, which is exploited to control processes as diverse as fertilization, proliferation, development, learning and memory, contraction and secretion.
Abstract: The universality of calcium as an intracellular messenger depends on its enormous versatility. Cells have a calcium signalling toolkit with many components that can be mixed and matched to create a wide range of spatial and temporal signals. This versatility is exploited to control processes as diverse as fertilization, proliferation, development, learning and memory, contraction and secretion, and must be accomplished within the context of calcium being highly toxic. Exceeding its normal spatial and temporal boundaries can result in cell death through both necrosis and apoptosis.

5,369 citations

Journal ArticleDOI
TL;DR: This review presents the best characterized of these biochemical pathways that control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division.
Abstract: Approximately one percent of the human genome encodes proteins that either regulate or are regulated by direct interaction with members of the Rho family of small GTPases. Through a series of complex biochemical networks, these highly conserved molecular switches control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division. In the first part of this review, we present the best characterized of these biochemical pathways; in the second part, we attempt to integrate these molecular details into a biological context.

2,876 citations

Journal ArticleDOI
TL;DR: The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.
Abstract: Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.

2,813 citations

Journal ArticleDOI
21 Feb 1992-Cell
TL;DR: Using positional cloning strategies, this work has identified a CTG triplet repeat that undergoes expansion in myotonic dystrophy patients and PCR analysis of the interval containing this repeat indicates that unaffected individuals have been 5 and 27 copies.

2,606 citations