AQuaRef: Machine learning accelerated quantum refinement of protein structures.

Cryo-EM and X-ray crystallography provide crucial experimental data for obtaining atomic-detail models of biomacromolecules. Refining these models relies on library-based stereochemical restraints, which, in addition to being limited to known chemical entities, do not include meaningful noncovalent interactions relying solely on nonbonded repulsions. Quantum mechanical (QM) calculations could alleviate these issues but are too expensive for large molecules.

Likelihood-based interactive local docking into cryo-EM maps in ChimeraX.

The interpretation of cryo-EM maps often includes the docking of known or predicted structures of the components, which is particularly useful when the map resolution is worse than 4 Å. Although it can be effective to search the entire map to find the best placement of a component, the process can be slow when the maps are large. However, frequently there is a well-founded hypothesis about where particular components are located.

The Phenix-AlphaFold webservice: Enabling AlphaFold predictions for use in Phenix.

Advances in machine learning have enabled sufficiently accurate predictions of protein structure to be used in macromolecular structure determination with crystallography and cryo-electron microscopy data. The Phenix software suite has AlphaFold predictions integrated into an automated pipeline that can start with an amino acid sequence and data, and automatically perform model-building and refinement to return a protein model fitted into the data. Due to the steep technical requirements of running AlphaFold efficiently, we have implemented a Phenix-AlphaFold webservice that enables all Phenix users to run AlphaFold predictions remotely from the Phenix GUI starting with the official 1.

Rethinking diagnosis-based service models for childhood neurodevelopmental disabilities in Canada: a question of equity.

Neurodevelopmental disability in children covers a vast array of congenital and acquired long-term conditions associated with brain or neuromuscular impairments that impact function. While some presentations of neurodevelopmental disability align with diagnostic labels, many do not, leaving children whose conditions don't fit neatly under diagnostic labels struggling to access services or families and professionals feeling pressured to assign a diagnostic label in order to access services. In this paper, we (1) discuss the evidence showing that there is often a mismatch between a child's neurodevelopmental diagnosis, or lack of diagnosis, and function, (2) comment on the inequities exacerbated by diagnosis-based approaches for services, and (3) highlight the potential benefits of using a function and participation-based approach for providing services to children with neurodevelopmental disabilities.

Decreased β-catenin Protein in Lungs From Human Congenital Diaphragmatic Hernia Archival Pathology Specimens: A Case-control Study.

Background: Lung hypoplasia contributes to congenital diaphragmatic hernia (CDH) associated morbidity and mortality. Changes in lung wingless-type MMTV integration site family member (Wnt)-signalling and its downstream effector beta-catenin (CTNNB1), which acts as a transcription coactivator, exist in animal CDH models but are not well characterized in humans. We aim to identify changes to Wnt-signalling gene expression in human CDH lungs and hypothesize that pathway expression will be lower than controls.