Biology subjects

Bartsch, A.

Publications and source records attributed to Bartsch, A..

4 recordsLinked to original sources

bioRxiv2023

Internally-consistent and fully-unbiased multimodal MRI brain template construction from UK Biobank: Oxford-MM

Anatomical MRI templates of the brain are essential to group-level analyses and image processing pipelines, as they provide a reference space for spatial normalisation. While it has become common for studies to acquire multimodal MRI data, many templates are still limited to one type of modality, usually either scalar or tensor-based. Aligning each modality in isolation does not take full advantage of the available complementary information, such as strong contrast between tissue types in structural images, or axonal organisation in the white matter in diffusion tensor images. Most existing strategies for multimodal template construction either do not use all modalities of interest to inform the template construction process, or do not use them in a unified framework. Here, we present multimodal, cross-sectional templates constructed from UK Biobank data: the OMM-1 template, and age-dependent templates for each year of life between 45 to 81. All templates are fully unbiased to represent the average shape of the populations they were constructed from, and internally consistent through jointly informing the template construction process with T1, T2-FLAIR and DTI data. The OMM-1 template was constructed with a multi-resolution, iterative approach using 240 individuals in the 50-55 year age range. The age-dependent templates were estimated using a Gaussian Process, which describes the change in average brain shape with age in 37,330 individuals. All templates show excellent contrast and alignment within and between modalities. The global brain shape and size is not preconditioned on existing templates, although maximal possible compatibility with MNI-152 space was maintained through rigid alignment. We showed benefits in registration accuracy across two datasets (UK Biobank and HCP), when using the OMM-1 as the template compared with FSLs MNI-152 template, and found that the use of age-dependent templates further improved accuracy to a small but detectable extent. All templates are publicly available and can be used as a new reference space for uni- or multimodal spatial alignment.

neuroscience↗

bioRxiv2023

MMORF - FSL's MultiMOdal Registration Framework

We present MMORF--FSLs MultiMOdal Registration Framework--a newly released nonlinear image registration tool designed primarily for application to MRI images of the brain. MMORF is capable of simultaneously optimising both displacement and rotational transformations within a single registration framework by leveraging rich information from multiple scalar and tensor modalities. The regularisation employed in MMORF promotes local rigidity in the deformation, and we have previously demonstrated how this effectively controls both shape and size distortion, and leads to more biologically plausible warps. The performance of MMORF is benchmarked against three established nonlinear registration methods--FNIRT, ANTs and DR-TAMAS--across four domains: FreeSurfer label overlap, DTI similarity, task-fMRI cluster mass, and distortion. Results show that MMORF performs as well as or better than all other methods across every domain--both in terms of accuracy and levels of distortion. MMORF is available as part of FSL, and its inputs and outputs are fully compatible with existing workflows. We believe that MMORF will be a valuable tool for the neuroimaging community, regardless of the domain of any downstream analysis, providing state-of-the-art registration performance that integrates into the rich and widely adopted suite of analysis tools in FSL.

neuroscience↗

bioRxiv2020

An antibiotic-resistance conferring mutation in a neisserial porin: Structure, ion flux, and ampicillin binding

Gram-negative bacteria cause the majority of highly drug-resistant bacterial infections. To cross the outer membrane of the complex Gram-negative cell envelope, antibiotics permeate through porins, trimeric channel proteins that enable the exchange of small polar molecules. Mutations in porins contribute to the development of drug-resistant phenotypes. In this work, we show that a single point mutation in the porin PorB from Neisseria meningitidis, the causative agent of bacterial meningitis, can strongly affect the binding and permeation of beta-lactam antibiotics. Using X-ray crystallography, high-resolution electrophysiology, atomistic biomolecular simulation, and liposome swelling experiments, we demonstrate differences in drug binding affinity, ion selectivity and drug permeability of PorB. Our work further reveals distinct interactions between the transversal electric field in the porin eyelet and the zwitterionic drugs, which manifest themselves under applied electric fields in electrophysiology and are altered by the mutation. These observations may apply more broadly to drug-porin interactions in other channels. Our results improve the molecular understanding of porin-based drug-resistance in Gram-negative bacteria.

biophysics↗

bioRxiv2018

High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB

The permeation of most antibiotics through the outer membrane of Gram-negative bacteria occurs through porin channels. To design drugs with increased activity against Gram-negative bacteria in the face of the antibiotic resistance crisis, the strict constraints on the physicochemical properties of the permeants imposed by these channels must be better understood. Here we show that a combination of high-resolution electrophysiology, new noise-filtering analysis protocols and atomistic biomolecular simulations reveals weak binding events between the {beta}-lactam antibiotic ampicillin and the porin PorB from the pathogenic bacterium Neisseria meningitidis. In particular, an asymmetry often seen in the electrophysiological characteristics of ligand-bound channels is utilised to characterise the binding site and molecular interactions in detail, based on the principles of electro-osmotic flow through the channel. Our results provide a rationale for the determinants that govern the binding and permeation of zwitterionic antibiotics in anion-selective porin channels.

biophysics↗