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Doucette, J.

Publications and source records attributed to Doucette, J..

3 recordsLinked to original sources

Microbiome derived acidity protects against microbial invasion in Drosophila

Microbial invasions underlie host-microbe interactions that result in microbial pathogenesis and probiotic colonization. While these processes are of broad interest, there are still gaps in our understanding of the barriers to entry and how some microbes overcome them. In this study, we explore the effects of the microbiome on invasions of foreign microbes in Drosophila melanogaster. We demonstrate that gut microbes Lactiplantibacillus plantarum and Acetobacter tropicalis improve survival during invasion of a lethal gut pathogen and lead to a reduction in microbial burden. Using a novel multi-organism interactions assay, we report that L. plantarum inhibits the growth of three invasive Gram-negative bacteria, while A. tropicalis prevents this inhibition. A series of in vitro and in vivo experiments revealed that inhibition by L. plantarum is linked to its ability to acidify both internal and external environments, including culture media, fly food, and the gut itself, while A. tropicalis diminishes the inhibition by quenching acids. We propose that acid produced by the microbiome serves as an important gatekeeper to microbial invasions, as only microbes capable of tolerating acidic environments can colonize the host. The methods described herein will add to the growing breadth of tools to study microbe-microbe interactions in broad contexts.

microbiology↗

Myelin water imaging depends on white matter fiber orientation in the human brain

The multiexponential T2 decay of the magnetic resonance imaging (MRI) signal from cerebral white matter can be separated into short components sensitive to myelin water and long components related to intra- and extracellular water. In this study we investigated to what degree the myelin water fraction (MWF) depends on the angle between white matter fibers and the main magnetic filed. Maps of MWF were acquired using multi echo CPMG and GRASE sequences. The CPMG sequence was acquired with a TR of 1073 ms, 1500 ms and 2000 ms. The fiber orientation was mapped with diffusion tensor imaging. By angle-wise pooling the voxels across the brains white matter, an orientation dependent MWF curve was generated. We found that MWF varied between 25% and 35% across different fiber orientations. The orientation dependency of the MWF is characterized by a dipole-dipole interaction model. Furthermore, the selection of the TR influences the orientation dependent and global white matter MWF. White matter fiber orientation induces a strong systematic bias on the estimation of MWF. This finding has important implications for future research and the interpretation of MWI results in previously published studies.

biophysics↗

The role of diffusion and perivascular spaces in dynamic susceptibility contrast MRI

We investigated the effects of brain tissue orientation, diffusion, and perivascular spaces on dynamic susceptibility contrast MRI. A 3D numerical model of a white matter voxel was created that consists of an isotropic capillary bed and anisotropic vessels that run in parallel with white matter tracts and are surrounded by perivascular spaces. The signal within the voxel was simulated by solving the Bloch-Torrey equation. Experimental perfusion data were acquired with a gradient echo dynamic susceptibility contrast scan. White matter fibre orientation was mapped with diffusion tensor imaging. Our numerical model of the contrast agent induced increase in R2*, as a function of tissue orientation, was fit to dynamic susceptibility contrast MRI data from thirteen subjects by minimizing the bias-corrected Akaike information criterion. White matter blood volume fraction in both the isotropic and the anisotropic vessels was determined as a free parameter, and results were analyzed as a function of diffusivity and perivascular space size. Total white matter blood volume was found to be 2.57%, with one third of the blood residing in blood vessels that run parallel with white matter tracts. Gradient echo dynamic susceptibility contrast MRI strongly depended on white matter tissue orientation and, according to the numerical simulations, this effect is amplified by diffusion and perivascular spaces.

biophysics↗