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1539 Publications visible to you, out of a total of 1539

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Date Published: 1st Aug 2023

Publication Type: Journal

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The VHT Roadmap is due – in its final version – by the end of the EDITH Coordination and Support Action (i.e., September 2024). The present document is the first draft of the Roadmap, This preliminaryy version of the Roadmap was planned in EDITH’s Grant Agreement as an initial contribution to the internal decision-making process of the European Commission. It has the declared purpose of allowing the Commission to start specifying already at an early stage by what steps the goal of pursuing the development of a VHT-based healthcare will be likely to trigger an effective engagement of Europe’s researchers, clinicians, industries, and regulators. This interim version is therefore meant to highlight what is currently the envisioned structure of what will be in a year time the final roadmap and its main contents, leaving open the possibility that these contents can still be subject to both substantial and formal changes, in response to suggestions coming from both the European Commission and from different sectors of the broadening community of practice that the EDITH CSA is addressing. In consideration of these double-edge purposes, this preliminary draft aims to capture the main concepts and the overall approach of the VHT Roadmap, while also identifying relevant challenges (from the perspective of research, infrastructure, and other specific aspects) that need to be addressed in the remaining year of the EDITH CSA (and beyond) and which will require further analysis, with the support of the whole VHT Community. For the technology, standards, regulatory, and legal aspects, the draft provides an overview of the state of the art and an analysis of VHT-specific needs, without determining as yet any conclusive choice. Given the evolving nature of this document, the submitted text will again be made publicly available for further comments and feedback, in view of possibly including valuable inputs in a next version. For general discussions, we encourage everyone to use the slack channel on the In silico World Community of Practice (ISW_CoP: https://insilico.world/community/join-the-community-of-practice-channels/). Critical remarks are welcome, as well as additional contributions, but also comments highlighting what sections are particularly appreciated will definitely help. if you would like to stay updated on EDITH's progress, you can enter your details via the contact form on the website: https://www.edith-csa.eu/contact/

Author: Gerhard Mayer, Martin Golebiewski

Date Published: 31st Jul 2023

Publication Type: Misc

Abstract

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Authors: Zheng-Wei Liu, Friedrich K. Röpke, Zhanwen Han

Date Published: 26th Jul 2023

Publication Type: Journal

Abstract (Expand)

The talin-vinculin axis is a key mechanosensing component of cellular focal adhesions. How talin and vinculin respond to forces and regulate one another remains unclear. By combining single molecule magnetic tweezer experiments, Molecular Dynamics simulations, actin bundling assays, and adhesion assembly experiments in live cells, we here discover a two-ways allosteric network within vinculin as a regulator of the talin-vinculin interaction. We directly observe a maturation process of vinculin upon talin binding which reinforces the binding to talin at a rate of 0.03 s−1. This allosteric transition can compete with force-induced dissociation of vinculin from talin only at 7-10 pN. Mimicking the allosteric activation by mutation yields a vinculin molecule that bundles actin and localizes to focal adhesions in a force-independent manner. Hence, the allosteric switch confines talin-vinculin interactions and focal adhesion build-up to intermediate force levels. The ‘allosteric vinculin mutant’ is a valuable molecular tool to further dissect the mechanical and biochemical signalling circuits at focal adhesions and elsewhere.

Authors: Florian Franz, Rafael Tapia-Rojo, Sabina Winograd-Katz, Rajaa Boujemaa-Paterski, Wenhong Li, Tamar Unger, Shira Albeck, Camilo Aponte-Santamaría, Sergi Garcia-Manyes, Ohad Medalia, Benjamin Geiger, Frauke Gräter

Date Published: 18th Jul 2023

Publication Type: Journal

Abstract

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Authors: Wei Liu, Yi Fan, Michael Strube

Date Published: 14th Jul 2023

Publication Type: InProceedings

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Authors: Chloé Braud, Christian Hardmeier, Junyi Jessy Li, Sharid Loaciga, Michael Strube, Amir Zeldes

Date Published: 13th Jul 2023

Publication Type: Proceedings

Abstract (Expand)

Abstract Motivation Simulating Multiple Sequence Alignments (MSAs) using probabilistic models of sequence evolution plays an important role in the evaluation of phylogenetic inference tools, and isluation of phylogenetic inference tools, and is crucial to the development of novel learning-based approaches for phylogenetic reconstruction, for instance, neural networks. These models and the resulting simulated data need to be as realistic as possible to be indicative of the performance of the developed tools on empirical data and to ensure that neural networks trained on simulations perform well on empirical data. Over the years, numerous models of evolution have been published with the goal to represent as faithfully as possible the sequence evolution process and thus simulate empirical-like data. In this study, we simulated DNA and protein MSAs under increasingly complex models of evolution with and without insertion/deletion (indel) events using a state-of-the-art sequence simulator. We assessed their realism by quantifying how accurately supervised learning methods are able to predict whether a given MSA is simulated or empirical. Results Our results show that we can distinguish between empirical and simulated MSAs with high accuracy using two distinct and independently developed classification approaches across all tested models of sequence evolution. Our findings suggest that the current state-of-the-art models fail to accurately replicate several aspects of empirical MSAs, including site-wise rates as well as amino acid and nucleotide composition. Data and Code Availability All simulated and empirical MSAs, as well as all analysis results, are available at https://cme.h-its.org/exelixis/material/simulation_study.tar.gz . All scripts required to reproduce our results are available at https://github.com/tschuelia/SimulationStudy and https://github.com/JohannaTrost/seqsharp . Contact julia.haag@h-its.org

Authors: Johanna Trost, Julia Haag, Dimitri Höhler, Laurent Jacob, Alexandros Stamatakis, Bastien Boussau

Date Published: 12th Jul 2023

Publication Type: Journal

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