Publications

What is a Publication?
1579 Publications visible to you, out of a total of 1579

Abstract

Not specified

Authors: Taein Kwon, Bugra Tekin, Jan Stühmer, Federica Bogo, Marc Pollefeys

Date Published: 2021

Publication Type: InProceedings

Abstract (Expand)

The multimeric plasma glycoprotein (GP) von Willebrand factor (VWF) is best known for recruiting platelets to sites of injury during primary hemostasis. Generally, mutations in the VWF gene lead to loss of hemostatic activity and thus the bleeding disorder von Willebrand disease. By employing cone and platelet aggregometry and microfluidic assays, we uncovered a platelet GPIIb/IIIa-dependent prothrombotic gain of function (GOF) for variant p.Pro2555Arg, located in the C4 domain, leading to an increase in platelet aggregate size. We performed complementary biophysical and structural investigations using circular dichroism spectra, small-angle X-ray scattering, nuclear magnetic resonance spectroscopy, molecular dynamics simulations on the single C4 domain, and dimeric wild-type and p.Pro2555Arg constructs. C4-p.Pro2555Arg retained the overall structural conformation with minor populations of alternative conformations exhibiting increased hinge flexibility and slow conformational exchange. The dimeric protein becomes disordered and more flexible. Our data suggest that the GOF does not affect the binding affinity of the C4 domain for GPIIb/IIIa. Instead, the increased VWF dimer flexibility enhances temporal accessibility of platelet-binding sites. Using an interdisciplinary approach, we revealed that p.Pro2555Arg is the first VWF variant, which increases platelet aggregate size and shows a shear-dependent function of the VWF stem region, which can become hyperactive through mutations. Prothrombotic GOF variants of VWF are a novel concept of a VWF-associated pathomechanism of thromboembolic events, which is of general interest to vascular health but not yet considered in diagnostics. Thus, awareness should be raised for the risk they pose. Furthermore, our data implicate the C4 domain as a novel antithrombotic drug target. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Authors: Volker Huck, Po-Chia Chen, Emma-Ruoqi Xu, Alexander Tischer, Ulrike Klemm, Camilo Aponte-Santamaría, Christian Mess, Tobias Obser, Fabian Kutzki, Gesa König, Cécile V. Denis, Frauke Gräter, Matthias Wilmanns, Matthew Auton, Stefan W Schneider, Reinhard Schneppenheim, Janosch Hennig, Maria A. Brehm

Date Published: 31st Dec 2020

Publication Type: Journal

Abstract

Not specified

Authors: Saskia Haupt, Nils Gleim, Aysel Ahadova, Hendrik Bläker, Magnus von Knebel Doeberitz, Matthias Kloor, Vincent Heuveline

Date Published: 29th Dec 2020

Publication Type: Unpublished

Abstract

Not specified

Authors: Ariane Nunes-Alves, Angelica Mazzolari, Kenneth M. Merz

Date Published: 28th Dec 2020

Publication Type: Journal

Abstract (Expand)

We present time-resolved ultraviolet-pump x-ray probe Auger spectra of 2-thiouracil. An ultraviolet induced shift towards higher kinetic energies is observed in the sulfur 2p Auger decay. The difference Auger spectra of pumped and unpumped molecules exhibit ultrafast dynamics in the shift amplitude, in which three phases can be recognized. In the first 100 fs, a shift towards higher kinetic energies is observed, followed by a 400 fs shift back to lower kinetic energies and a 1 ps shift again to higher kinetic energies. We use a simple Coulomb-model, aided by quantum chemical calculations of potential energy states, to deduce a C–S bond expansion within the first 100 fs. The bond elongation triggers internal conversion from the photoexcited S2 to the S1 state. Based on timescales, the subsequent dynamics can be interpreted in terms of S1 nuclear relaxation and S1-triplet internal conversion.

Authors: F Lever, D Mayer, D Picconi, J Metje, S Alisauskas, F Calegari, S Düsterer, C Ehlert, R Feifel, M Niebuhr, B Manschwetus, M Kuhlmann, T Mazza, M S Robinson, R J Squibb, A Trabattoni, M Wallner, P Saalfrank, T J A Wolf, M Gühr

Date Published: 17th Dec 2020

Publication Type: Journal

Abstract

Not specified

Authors: Benoit Morel, Pierre Barbera, Lucas Czech, Ben Bettisworth, Lukas Hübner, Sarah Lutteropp, Dora Serdari, Evangelia-Georgia Kostaki, Ioannis Mamais, Alexey M Kozlov, Pavlos Pavlidis, Dimitrios Paraskevis, Alexandros Stamatakis

Date Published: 15th Dec 2020

Publication Type: Journal

Abstract (Expand)

The recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell sequencing technology. Thousands—or even millions—of cells analyzed in a single experiment amount to a data revolution in single-cell biology and pose unique data science problems. Here, we outline eleven challenges that will be central to bringing this emerging field of single-cell data science forward. For each challenge, we highlight motivating research questions, review prior work, and formulate open problems. This compendium is for established researchers, newcomers, and students alike, highlighting interesting and rewarding problems for the coming years.

Authors: David Lähnemann, Johannes Köster, Ewa Szczurek, Davis J. McCarthy, Stephanie C. Hicks, Mark D. Robinson, Catalina A. Vallejos, Kieran R. Campbell, Niko Beerenwinkel, Ahmed Mahfouz, Luca Pinello, Pavel Skums, Alexandros Stamatakis, Camille Stephan-Otto Attolini, Samuel Aparicio, Jasmijn Baaijens, Marleen Balvert, Buys de Barbanson, Antonio Cappuccio, Giacomo Corleone, Bas E. Dutilh, Maria Florescu, Victor Guryev, Rens Holmer, Katharina Jahn, Thamar Jessurun Lobo, Emma M. Keizer, Indu Khatri, Szymon M. Kielbasa, Jan O. Korbel, Alexey M. Kozlov, Tzu-Hao Kuo, Boudewijn P.F. Lelieveldt, Ion I. Mandoiu, John C. Marioni, Tobias Marschall, Felix Mölder, Amir Niknejad, Lukasz Raczkowski, Marcel Reinders, Jeroen de Ridder, Antoine-Emmanuel Saliba, Antonios Somarakis, Oliver Stegle, Fabian J. Theis, Huan Yang, Alex Zelikovsky, Alice C. McHardy, Benjamin J. Raphael, Sohrab P. Shah, Alexander Schönhuth

Date Published: 1st Dec 2020

Publication Type: Journal

Powered by
(v.1.14.2)
Copyright © 2008 - 2023 The University of Manchester and HITS gGmbH