Geometrically Reduced Modelling of Pulsatile Flow in Perivascular Networks

Flow of cerebrospinal fluid in perivascular spaces is a key mechanism underlying brain transport and clearance. In this paper, we present a mathematical and numerical formalism for reduced models of pulsatile viscous fluid flow in networks of generalized annular cylinders. We apply this framework to study cerebrospinal fluid flow in perivascular spaces induced by pressure differences, cardiac pulse wave-induced vascular wall motion and vasomotion. The reduced models provide approximations of the cross-section average pressure and cross-section flux, both defined over the topologically one-dimensional centerlines of the network geometry. Comparing the full and reduced model predictions, we find that the reduced models capture pulsatile flow characteristics and provide accurate pressure and flux predictions across the range of idealized and image-based scenarios investigated—at a fraction of the computational cost of the corresponding full models. The framework presented thus provides a robust and effective computational approach for large scale in-silico studies of pulsatile perivascular fluid flow and transport.publishedVersio

The mechanisms behind perivascular fluid flow

Flow of cerebrospinal fluid (CSF) in perivascular spaces (PVS) is one of the key concepts involved in theories concerning clearance from the brain. Experimental studies have demonstrated both net and oscillatory movement of microspheres in PVS (Mestre et al. (2018), Bedussi et al. (2018)). The oscillatory particle movement has a clear cardiac component, while the mechanisms involved in net movement remain disputed. Using computational fluid dynamics, we computed the CSF velocity and pressure in a PVS surrounding a cerebral artery subject to different forces, representing arterial wall expansion, systemic CSF pressure changes and rigid motions of the artery. The arterial wall expansion generated velocity amplitudes of 60–260 μ m/s, which is in the upper range of previously observed values. In the absence of a static pressure gradient, predicted net flow velocities were small (<0.5 μ m/s), though reaching up to 7 μ m/s for non-physiological PVS lengths. In realistic geometries, a static systemic pressure increase of physiologically plausible magnitude was sufficient to induce net flow velocities of 20–30 μ m/s. Moreover, rigid motions of the artery added to the complexity of flow patterns in the PVS. Our study demonstrates that the combination of arterial wall expansion, rigid motions and a static CSF pressure gradient generates net and oscillatory PVS flow, quantitatively comparable with experimental findings. The static CSF pressure gradient required for net flow is small, suggesting that its origin is yet to be determined

Mycobacterial resistance to zinc poisoning requires assembly of P-ATPase-containing membrane metal efflux platforms

International audienceThe human pathogen Mycobacterium tuberculosis requires a P-1B-ATPase metal exporter, CtpC (Rv3270), for resistance to zinc poisoning. Here, we show that zinc resistance also depends on a chaperone-like protein, PacL1 (Rv3269). PacL1 contains a transmembrane domain, a cytoplasmic region with glutamine/alanine repeats and a C-terminal metal-binding motif (MBM). PacL1 binds Zn2+, but the MBM is required only at high zinc concentrations. PacL1 co-localizes with CtpC in dynamic foci in the mycobacterial plasma membrane, and the two proteins form high molecular weight complexes. Foci formation does not require flotillin nor the PacL1 MBM. However, deletion of the PacL1 Glu/Ala repeats leads to loss of CtpC and sensitivity to zinc. Genes pacL1 and ctpC appear to be in the same operon, and homologous gene pairs are found in the genomes of other bacteria. Furthermore, PacL1 colocalizes and functions redundantly with other PacL orthologs in M. tuberculosis. Overall, our results indicate that PacL proteins may act as scaffolds that assemble P-ATPase-containing metal efflux platforms mediating bacterial resistance to metal poisoning.The human pathogen Mycobacterium tuberculosis requires a metal exporter, CtpC, for resistance to zinc poisoning. Here, the authors show that zinc resistance also depends on a chaperone-like protein that binds zinc ions, forms high-molecular-weight complexes with CtpC in the cytoplasmic membrane, and is required for CtpC function

A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

International audienc

firedrakeproject/ufl: The Unified Form Language

<p>This release is specifically created to document the version of ufl used in a particular set of experiments using Firedrake. Please do not cite this as a general source for Firedrake or any of its dependencies. Instead, refer to https://www.firedrakeproject.org/citing.html</p&gt