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Search Results: 1 - 10 of 968 matches for " Clemens Steegborn "
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Sirt5 Deacylation Activities Show Differential Sensitivities to Nicotinamide Inhibition
Frank Fischer, Melanie Gertz, Benjamin Suenkel, Mahadevan Lakshminarasimhan, Mike Schutkowski, Clemens Steegborn
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045098
Abstract: Sirtuins are protein deacylases regulating metabolism and aging processes, and the seven human isoforms are considered attractive therapeutic targets. Sirtuins transfer acyl groups from lysine sidechains to ADP-ribose, formed from the cosubstrate NAD+ by release of nicotinamide, which in turn is assumed to be a general Sirtuin inhibitor. Studies on Sirtuin regulation have been hampered, however, by shortcomings of available assays. Here, we describe a mass spectrometry–based, quantitative deacylation assay not requiring any substrate labeling. Using this assay, we show that the deacetylation activity of human Sirt5 features an unusual insensitivity to nicotinamide inhibition. In contrast, we find similar values for Sirt5 and Sirt3 for the intrinsic NAD+ affinity as well as the apparent NAD+ affinity in presence of peptide. Structure comparison and mutagenesis identify an Arg neighboring to the Sirt5 nicotinamide binding pocket as a mediator of nicotinamide resistance, and statistical sequence analyses along with testing further Sirtuins reveal a network of coevolved residues likely defining a nicotinamide-insensitive Sirtuin deacetylase family. The same Arg was recently reported to render Sirt5 a preferential desuccinylase, and we find that this Sirt5 activity is highly sensitive to nicotinamide inhibition. Analysis of Sirt5 structures and activity data suggest that an Arg/succinate interaction is the molecular basis of the differential nicotinamide sensitivities of the two Sirt5 activities. Our results thus indicate a Sirtuin subfamily with nicotinamide-insensitive deacetylase activity and suggest that the molecular features determining nicotinamide sensitivity overlap with those dominating deacylation specificity, possibly suggesting that other subfamily members might also prefer other acylations than acetylations.
A Molecular Mechanism for Direct Sirtuin Activation by Resveratrol
Melanie Gertz, Giang Thi Tuyet Nguyen, Frank Fischer, Benjamin Suenkel, Christine Schlicker, Benjamin Fr?nzel, Jana Tomaschewski, Firouzeh Aladini, Christian Becker, Dirk Wolters, Clemens Steegborn
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049761
Abstract: Sirtuins are protein deacetylases regulating metabolism, stress responses, and aging processes, and they were suggested to mediate the lifespan extending effect of a low calorie diet. Sirtuin activation by the polyphenol resveratrol can mimic such lifespan extending effects and alleviate metabolic diseases. The mechanism of Sirtuin stimulation is unknown, hindering the development of improved activators. Here we show that resveratrol inhibits human Sirt3 and stimulates Sirt5, in addition to Sirt1, against fluorophore-labeled peptide substrates but also against peptides and proteins lacking the non-physiological fluorophore modification. We further present crystal structures of Sirt3 and Sirt5 in complex with fluorogenic substrate peptide and modulator. The compound acts as a top cover, closing the Sirtuin’s polypeptide binding pocket and influencing details of peptide binding by directly interacting with this substrate. Our results provide a mechanism for the direct activation of Sirtuins by small molecules and suggest that activators have to be tailored to a specific Sirtuin/substrate pair.
CO2 Acts as a Signalling Molecule in Populations of the Fungal Pathogen Candida albicans
Rebecca A. Hall,Luisa De Sordi,Donna M. MacCallum,Hüsnü Topal,Rebecca Eaton,James W. Bloor,Gary K. Robinson,Lonny R. Levin,Jochen Buck,Yue Wang,Neil A. R. Gow,Clemens Steegborn,Fritz A. Mühlschlegel
PLOS Pathogens , 2010, DOI: 10.1371/journal.ppat.1001193
Abstract: When colonising host-niches or non-animated medical devices, individual cells of the fungal pathogen Candida albicans expand into significant biomasses. Here we show that within such biomasses, fungal metabolically generated CO2 acts as a communication molecule promoting the switch from yeast to filamentous growth essential for C. albicans pathology. We find that CO2-mediated intra-colony signalling involves the adenylyl cyclase protein (Cyr1p), a multi-sensor recently found to coordinate fungal responses to serum and bacterial peptidoglycan. We further identify Lys 1373 as essential for CO2/bicarbonate regulation of Cyr1p. Disruption of the CO2/bicarbonate receptor-site interferes selectively with C. albicans filamentation within fungal biomasses. Comparisons between the Drosophila melanogaster infection model and the mouse model of disseminated candidiasis, suggest that metabolic CO2 sensing may be important for initial colonisation and epithelial invasion. Our results reveal the existence of a gaseous Candida signalling pathway and its molecular mechanism and provide insights into an evolutionary conserved CO2-signalling system.
Inelastic J/psi Photoproduction
M. Kraemer,J. Zunft,J. Steegborn,P. M. Zerwas
Physics , 1994, DOI: 10.1016/0370-2693(95)00155-E
Abstract: Inelastic photoproduction of $J/\psi$ particles at high energies is one of the processes to determine the gluon distribution in the nucleon. We have calculated the QCD radiative corrections to the color-singlet model of this reaction. They are large at moderate photon energies, but decrease with increasing energies. The cross section and the $J/\psi$ energy spectrum are compared with the available fixed-target photoproduction data and predictions are given for the HERA energy range.
Fragmentation production of doubly heavy baryons
M. A. Doncheski,J. Steegborn,M. L. Stong
Physics , 1995, DOI: 10.1103/PhysRevD.53.1247
Abstract: Baryons with a single heavy quark are being studied experimentally at present. Baryons with two units of heavy flavor will be abundantly produced not only at future colliders, but also at existing facilities. In this paper we study the production via heavy quark fragmentation of baryons containing two heavy quarks at the Tevatron, the LHC, HERA, and the NLC. The production rate is woefully small at HERA and at the NLC, but significant at $pp$ and $p\bar{p}$ machines. We present distributions in various kinematical variables in addition to the integrated cross sections at hadron colliders.
Computational Precision of the Power Function for Conditional Tests of Assumptions of the Rasch Model  [PDF]
Clemens Draxler, Jan Philipp Nolte
Open Journal of Statistics (OJS) , 2018, DOI: 10.4236/ojs.2018.86058
Abstract: Draxler and Zessin [1] derived the power function for a class of conditional tests of assumptions of a psychometric model known as the Rasch model and suggested an MCMC approach developed by Verhelst [2] for the numerical approximation of the power of the tests. In this contribution, the precision of the Verhelst approach is investigated and compared with an exact sampling procedure proposed by Miller and Harrison [3] for which the discrete probability distribution to be sampled from is exactly known. Results show no substantial differences between the two numerical procedures and quite accurate power computations. Regarding the question of computing time the Verhelst approach will have to be considered much more efficient.
Polysilane Dendrimers
Clemens Krempner
Polymers , 2012, DOI: 10.3390/polym4010408
Abstract: The synthesis, structure and electronic properties of polysilane dendrimers, a relatively new class of highly branched and silicon-rich molecular architectures is reviewed. After a detailed discussion of main synthetic strategies to well-defined single-core and double-core polysilane dendrimers, important structural and conformational features determined by single crystal X-ray crystallography and 29Si-NMR spectroscopy are presented. The last part highlights the most interesting photochemical properties of polysilane dendrimers such as UV absorption and emission behavior, which are compared with those of linear and branched polysilanes.
Application of in vivo microscopy: evaluating the immune response in living animals
Clemens Scheinecker
Arthritis Research & Therapy , 2005, DOI: 10.1186/ar1843
Abstract: Until recently, the only method of demonstrating antigen processing and peptide–major histocompatibility complex (pMHC) formation by antigen-presenting cells (APCs) in vivo was to measure antigen-specific T cell activation in vitro [1,2]. Although these T cell-based assay systems are very sensitive, their drawbacks are variations in the stimulatory capacity of different APC populations and the unknown activation state of the responder T cells.Flow cytometry and tissue section imaging have been valuable methods for the investigation of antigen presentation in vivo. In particular, the use of pMHC-specific antibodies allows the detection of small numbers of molecules per cell, thereby permitting the analysis of antigen-specific T cell activation [3-5].The ability of a cell to move on any substrate must represent a combination between adhesion and the ability to extend processes. However, this obviously depends strongly on the nature of the surface; results on lymphocyte motility and interactions with APCs obtained from studies in vitro have consequently given drastically different results depending on the experimental system used [6-8]. In contrast, studies in vitro have provided valuable information about the signaling cascade that leads to lymphocyte activation, thereby describing the intricate choreography of key signaling molecules that participate in the formation of the immunological synapse at the T cell–APC interface [9,10]. Nevertheless, chemokine gradients, signals from the local nervous system and circulating hormones as well as integrin interactions with components of the extracellular matrix are lacking in cell culture systems. Finally, this methodology does not allow the observation of the movement and interaction of APCs with lymphocytes within organized lymphoid tissues in real time over short intervals.This has led several laboratories to develop imaging methods with high resolution to be able to perform spatiotemporal analysis of cell–cell interaction
Golden nugget: Graz, Austri
Clemens Luser
ARQ , 2006,
Abstract:
Des divisions aux alternances
Eric Clemens
Topologik : Rivista Internazionale di Scienze Filosofiche, Pedagogiche e Sociali , 2012,
Abstract: - From the divisions to the alternations - Society, action and common good give sense to democracy. Society is in fact a set of unmitigated divisions (horizontal and vertical, material and symbolic). Democratic action, since the discourse’s conflicts, doesn’t change the human beings, but things between they, in the alternation of power’s institutions for our only good in common: the body. With this aim, the Basic Income Earth Network is necessary.
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