Publications by authors named "L J Willmore"
Article Synopsis
- Some individuals react differently to chronic stress, with some being more susceptible while others display resilience.
- This study focuses on the lateral habenula (LHb), which is involved in signaling negative outcomes, to see how its activity differs between susceptible and resilient mice during stress.
- Findings reveal that susceptible mice exhibit increased LHb activity during stress, particularly when near aggressors, leading to long-lasting effects on brain activity and behavior that promote further susceptibility.
Article Synopsis
- - The study investigates how different mice respond to chronic stress, focusing on the lateral habenula (LHb), which is linked to negative learning signals.
- - Researchers found that susceptible mice show greater LHb activity when near aggressive mice after experiencing social defeat stress, contributing to their susceptibility.
- - The increased LHb activity during stress leads to widespread changes in brain function in susceptible mice, resulting in lasting impacts on their behavior and neural responses.
The introduction of AlphaFold 2 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design. Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein-ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein-nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody-antigen prediction accuracy compared with AlphaFold-Multimer v.
View Article and Find Full Text PDFProtein tyrosine phosphatase SHP2 mediates RAS-driven MAPK signaling and has emerged in recent years as a target of interest in oncology, both for treating with a single agent and in combination with a KRAS inhibitor. We were drawn to the pharmacological potential of SHP2 inhibition, especially following the initial observation that drug-like compounds could bind an allosteric site and enforce a closed, inactive state of the enzyme. Here, we describe the identification and characterization of (formerly RLY-1971), a SHP2 inhibitor currently in clinical trials in combination with KRAS G12C inhibitor divarasib (GDC-6036) for the treatment of solid tumors driven by a KRAS G12C mutation.
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