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Search Results: 1 - 10 of 142468 matches for " K. Ulrich Bayer "
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Improving a Natural CaMKII Inhibitor by Random and Rational Design
Steven J. Coultrap,K. Ulrich Bayer
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0025245
Abstract: CaM-KIIN has evolved to inhibit stimulated and autonomous activity of the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) efficiently, selectively, and potently (IC50 ~100 nM). The CN class of peptides, derived from the inhibitory region of CaM-KIIN, provides powerful new tools to study CaMKII functions. The goal of this study was to identify the residues required for CaMKII inhibition, and to assess if artificial mutations could further improve the potency achieved during evolution.
A Significant but Rather Mild Contribution of T286 Autophosphorylation to Ca2+/CaM-Stimulated CaMKII Activity
Steven J. Coultrap, Kelsey Barcomb, K. Ulrich Bayer
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037176
Abstract: Background Autophosphorylation of the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) at T286 generates partially Ca2+/CaM-independent “autonomous” activity, which is thought to be required for long-term potentiation (LTP), a form of synaptic plasticity thought to underlie learning and memory. A requirement for T286 autophosphorylation also for efficient Ca2+/CaM-stimulated CaMKII activity has been described, but remains controversial. Methodology/Principal Findings In order to determine the contribution of T286 autophosphorylation to Ca2+/CaM-stimulated CaMKII activity, the activity of CaMKII wild type and its phosphorylation-incompetent T286A mutant was compared. As the absolute activity can vary between individual kinase preparations, the activity was measured in six different extracts for each kinase (expressed in HEK-293 cells). Consistent with measurements on purified kinase (from a baculovirus/Sf9 cell expression system), CaMKII T286A showed a mildly but significantly reduced rate of Ca2+/CaM-stimulated phosphorylation for two different peptide substrates (to ~75–84% of wild type). Additional slower CaMKII autophosphorylation at T305/306 inhibits stimulation by Ca2+/CaM, but occurs only minimally for CaMKII wild type during CaM-stimulated activity assays. Thus, we tested if the T286A mutant may show more extensive inhibitory autophosphorylation, which could explain its reduced stimulated activity. By contrast, inhibitory autophosphorylation was instead found to be even further reduced for the T286A mutant under our assay conditions. On a side note, the phospho-T305 antibody showed some basal background immuno-reactivity also with non-phosphorylated CaMKII, as indicated by T305/306A mutants. Conclusions/Significance These results indicate that Ca2+/CaM-stimulated CaMKII activity is mildly (~1.2–1.3fold) further increased by additional T286 autophosphorylation, but that this autophosphorylation is not required for the major part of the stimulated activity. This indicates that the phenotype of CaMKII T286A mutant mice is indeed due to the lack of autonomous activity, as the T286A mutant showed no dramatic reduction in stimulated activity.
Camkii-Mediated Phosphorylation Regulates Distributions of Syngap-α1 and –α2 at the Postsynaptic Density
Yijung Yang, Jung-Hwa Tao-Cheng, K. Ulrich Bayer, Thomas S. Reese, Ayse Dosemeci
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0071795
Abstract: SynGAP, a protein abundant at the postsynaptic density (PSD) of glutamatergic neurons, is known to modulate synaptic strength by regulating the incorporation of AMPA receptors at the synapse. Two isoforms of SynGAP, α1 and α2, which differ in their C-termini, have opposing effects on synaptic strength. In the present study, antibodies specific for SynGAP-α1 and SynGAP-α2 are used to compare the distribution patterns of the two isoforms at the postsynaptic density (PSD) under basal and excitatory conditions. Western immunoblotting shows enrichment of both isoforms in PSD fractions isolated from adult rat brain. Immunogold electron microscopy of rat hippocampal neuronal cultures shows similar distribution of both isoforms at the PSD, with a high density of immunolabel within the PSD core under basal conditions. Application of NMDA promotes movement of SynGAP-α1 as well as SynGAP-α2 out of the PSD core. In isolated PSDs both isoforms of SynGAP can be phosphorylated upon activation of the endogenous CaMKII. Application of tatCN21, a cell-penetrating inhibitor of CaMKII, to hippocampal neuronal cultures blocks NMDA-induced redistribution of SynGAP-α1 and SynGAP-α2. Thus CaMKII activation promotes the removal of two distinct C-terminal SynGAP variants from the PSD.
CaMKII Binding to GluN2B Is Differentially Affected by Macromolecular Crowding Reagents
Dayton J. Goodell, Tatiana A. Eliseeva, Steven J. Coultrap, K. Ulrich Bayer
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096522
Abstract: Binding of the Ca2+/calmodulin(CaM)-dependent protein kinase II (CaMKII) to the NMDA-type glutamate receptor (NMDAR) subunit GluN2B controls long-term potentiation (LTP), a form of synaptic plasticity thought to underlie learning and memory. Regulation of this interaction is well-studied biochemically, but not under conditions that mimic the macromolecular crowding found within cells. Notably, previous molecular crowding experiments with lysozyme indicated an effect on the CaMKII holoenzyme conformation. Here, we found that the effect of molecular crowding on Ca2+/CaM-induced CaMKII binding to immobilized GluN2B in vitro depended on the specific crowding reagent. While binding was reduced by lysozyme, it was enhanced by BSA. The ATP content in the BSA preparation caused CaMKII autophosphorylation at T286 during the binding reaction; however, enhanced binding was also observed when autophosphorylation was blocked. Importantly, the positive regulation by nucleotide and BSA (as well as other macromolecular crowding reagents) did not alleviate the requirement for CaMKII stimulation to induce GluN2B binding. The differential effect of lysozyme (14 kDa) and BSA (66 kDa) was not due to size difference, as both dextran-10 and dextran-70 enhanced binding. By contrast, crowding with immunoglobulin G (IgG) reduced binding. Notably, lysozyme and IgG but not BSA directly bound to Ca2+/CaM in an overlay assay, suggesting a competition of lysozyme and IgG with the Ca2+/CaM-stimulus that induces CaMKII/GluN2B binding. However, lysozyme negatively regulated binding even when it was instead induced by CaMKII T286 phosphorylation. Alternative modes of competition would be with CaMKII or GluN2B, and the negative effects of lysozyme and IgG indeed also correlated with specific or non-specific binding to the immobilized GluN2B. Thus, the effect of any specific crowding reagent can differ, depending on its additional direct effects on CaMKII/GluN2B binding. However, the results of this study also indicate that, in principle, macromolecular crowding enhances CaMKII binding to GluN2B.
CaMKII Mediates Recruitment and Activation of the Deubiquitinase CYLD at the Postsynaptic Density
Soe Thein, Jung-Hwa Tao-Cheng, Yan Li, K. Ulrich Bayer, Thomas S. Reese, Ayse Dosemeci
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091312
Abstract: NMDA treatment of cultured hippocampal neurons causes recruitment of CYLD, as well as CaMKII, to the postsynaptic density (PSD), as shown by immunoelectron microscopy. Recruitment of CYLD, a deubiquitinase specific for K63-linked polyubiquitins, is blocked by pre-treatment with tatCN21, a CaMKII inhibitor, at a concentration that inhibits the translocation of CaMKII to the PSD. Furthermore, CaMKII co-immunoprecipitates with CYLD from solubilized PSD fractions, indicating an association between the proteins. Purified CaMKII phosphorylates CYLD on at least three residues (S-362, S-418, and S-772 on the human CYLD protein Q9NQC7-1) and promotes its deubiquitinase activity. Activation of CaMKII in isolated PSDs promotes phosphorylation of CYLD on the same residues and also enhances endogenous deubiquitinase activity specific for K63-linked polyubiquitins. Since K63-linked polyubiquitin conjugation to proteins inhibits their interaction with proteasomes, CaMKII-mediated recruitment and upregulation of CYLD is expected to remove K63-linked polyubiquitins and facilitate proteasomal degradation at the PSD.
A Functional Limit Theorem for Limit Order Books with State Dependent Price Dynamics
Christian Bayer,Ulrich Horst,Jinniao Qiu
Quantitative Finance , 2014,
Abstract: We consider a stochastic model for the dynamics of the two-sided limit order book (LOB). Our model is flexible enough to allow for a dependence of the price dynamics on volumes. For the joint dynamics of best bid and ask prices and the standing buy and sell volume densities, we derive a functional limit theorem, which states that our LOB model converges in distribution to a fully coupled SDE-SPDE system when the order arrival rates tend to infinity and the impact of an individual order arrival on the book as well as the tick size tends to zero. The SDE describes the bid/ask price dynamics while the SPDE describes the volume dynamics.
Cubature on Wiener space: pathwise convergence
Christian Bayer,Peter K. Friz
Quantitative Finance , 2013,
Abstract: Cubature on Wiener space [Lyons, T.; Victoir, N.; Proc. R. Soc. Lond. A 8 January 2004 vol. 460 no. 2041 169-198] provides a powerful alternative to Monte Carlo simulation for the integration of certain functionals on Wiener space. More specifically, and in the language of mathematical finance, cubature allows for fast computation of European option prices in generic diffusion models. We give a random walk interpretation of cubature and similar (e.g. the Ninomiya--Victoir) weak approximation schemes. By using rough path analysis, we are able to establish weak convergence for general path-dependent option prices.
Domain and Language Independent Feature Extraction for Statistical Text Categorization
Thomas Bayer,Ingrid Renz,Michael Stein,Ulrich Kressel
Computer Science , 1996,
Abstract: A generic system for text categorization is presented which uses a representative text corpus to adapt the processing steps: feature extraction, dimension reduction, and classification. Feature extraction automatically learns features from the corpus by reducing actual word forms using statistical information of the corpus and general linguistic knowledge. The dimension of feature vector is then reduced by linear transformation keeping the essential information. The classification principle is a minimum least square approach based on polynomials. The described system can be readily adapted to new domains or new languages. In application, the system is reliable, fast, and processes completely automatically. It is shown that the text categorizer works successfully both on text generated by document image analysis - DIA and on ground truth data.
Discursos ceremoniales tzotziles: una joya poco estudiada
K?hler, Ulrich;
Estudios de cultura maya , 2009,
Abstract: apart from verbal interchange in daily life and prayers directed to the gods there is another principal form of verbal expression among the tzotzil -and probably among the majority of maya peoples: ceremonial discourses. with the prayers they have in common a strict poetic form, but in contrast to them they are not sung. there exist both private and official ceremonial discourses. the latter are principally blessings for incoming new cargoholders and verbal exchange between different officials who organize a religious feast. of these official discourses several examples are presented, showing both their content and their poetic form of expression with many metaphors.
Models for Quarks and Elementary Particles --- Part IV: How Much Do We Know of This Universe?
Ulrich K. W. Neumann
Progress in Physics , 2008,
Abstract: Essential laws and principles of the natural sciences were discovered at the high aggregation levels of matter such as molecules, metal crystals, atoms and elementary particles. These principles reappear in these models in modified form at the fundamental level of the quarks. However, the following is probably true: since the principles apply at the fundamental level of the quarks they also have a continuing effect at the higher aggregation levels. In the manner of the law of mass action, eight processes for weak interaction are formulated, which are also called Weak Processes here. Rules for quark exchange of the reacting elementary particles are named and the quasi-Euclidian or complex spaces introduced in Part I associated with the respective particles. The weak processes are the gateway to the second strand of this universe which we practically do not know. The particles with complex space, e.g. the neutrino, form this second strand. According to the physical model of gravitation from Part III the particles of both strands have fields and are thus subject to the superposition, which results in the attraction by gravity of the particles of both strands. The weak processes (7) and (8) offer a fair chance for the elimination of highly radioactive waste.
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