Biology subjects

Schneider, J. E.

Publications and source records attributed to Schneider, J. E..

5 recordsLinked to original sources

bioRxiv2026

The RND family efflux pump FemT contributes to lipid homeostasis in Staphylococcus aureus

The RND efflux pump FemT encoded by SAUSA300_2213 of Staphylococcus aureus USA300 is co-transcribed with femX which has an essential role in synthesizing the Lipid II precursor of peptidoglycan. Anticipating that this arrangement reflects a critical accessory role for femT, we constructed USA300{Delta}femT to assess its function. Although growth of USA300{Delta}femT in tryptic soy broth (TSB) was not impaired, transcriptomic data revealed a mild cellular stress response, accompanied by reduced expression of ohyA and crt genes involved in fatty acid metabolism and carotenoid lipid synthesis respectively. Accordingly, USA300{Delta}femT exhibited impaired growth on exposure to saturated and unsaturated fatty acids, and exposure to subinhibitory 50 {micro}M palmitic acid promoted accumulation of reactive oxygen species, reduced respiratory activity, and altered membrane function and morphology. The transcriptome of cells grown under this condition revealed strongly attenuated expression of ohyA and crt, and several genes required for oxidative and anaerobic respiration, concomitant with strongly enhanced expression of several stress response pathways. Cellular metabolites were also profoundly altered. Finally, lipidomic analysis of USA300{Delta}femT exposed to oleic acid revealed increased incorporation of oleic acid into phosphatidylglycerol, accompanied by a significant reduction in undecaprenol C55 lipid carrier, and respiratory quinones MK-7 and MK-8. Our data are consistent with a role for FemT in maintaining cellular lipid homeostasis by promoting efflux of isoprenoid and carotenoid lipids that are prone to oxidative damage, including C55 and menaquinones that undergo cyclic reactions in peptidoglycan synthesis and electron transport.

microbiology↗

bioRxiv2025

ZOnally magnified Oblique Multi-slice (ZOOM) for cardiac diffusion weighted imaging in vivo

PurposeCardiac diffusion weighted imaging (cDWI) commonly utilizes 2D-selective RF-pulses (such as ZOOMit) to avoid aliasing artifacts when reducing the field of view (FOV). These RF-pulses, which may require parallel transmit capability, typically take several 10s of milliseconds, prolonging the echo time (TE) of the imaging sequence. Conversely, slice selection using ZOnally-magnified Oblique Multi-slice (ZOOM) (i.e. tilting the excitation relative to the refocusing RF-pulse) is an alternative for reducing FOV while shortening TE. We hypothesized that ZOOM, with appropriate choices for the RF-pulse tilt angle and thickness, can be reliably used as an alternative to ZOOMit for cardiac Diffusion Tensor Imaging (cDTI). MethodsWe scanned phantoms using full FOV and ZOOM with various parameters chosen from a 2-dimensional grid of angles and thicknesses. We identified a subset of 5 ZOOM parameters for in vivo cDTI experiments. We performed cDTI on healthy volunteers on a Siemens Prisma (6 subjects) and a Connectom (6 subjects) MR system using the 5 identified ZOOM settings, as well as ZOOMit (Prisma only) and no ZOOM (Connectom only). We compared mean diffusivity (MD), fractional anisotropy (FA), and secondary eigenvector angle (|E2A|) between scans. ResultsAverage MD, and standard deviation of MD and FA, were significantly reduced by ZOOM compared to no ZOOM on Connectom. We found no significant differences in any averaged diffusion measures between ZOOMit and ZOOM on Prisma. ConclusionCombining ZOOM with cardiac diffusion weighted imaging allows for TE to be considerably shortened (from 79ms to 67ms) while reducing FOV to avoid aliasing artifacts.

biophysics↗

bioRxiv2025

Robust constrained weighted least squares for in vivo human cardiac diffusion kurtosis imaging

SummaryRobust estimation with convexity constraints significantly improves signal fitting for in vivo human cardiac diffusion kurtosis imaging. PurposeCardiac diffusion tensor imaging (cDTI) is an emerging technique to investigate the microstructure of heart tissue. At sufficiently high b-values, additional information on microstructure can be observed, but the data require a representation beyond DTI such as diffusion kurtosis imaging (DKI). cDTI is highly prone to image corruption, which researchers usually attempt to handle with shot-rejection. However, this can be handled more generally with robust estimation techniques. Recent work has also demonstrated the need to perform constrained fitting for DKI, as fitted parameters can otherwise violate necessary constraints on the signal behaviour, causing significant errors in estimated measures. MethodsWe developed robust constrained weighted least squares (RCWLS) by combining robust estimation with convexity constraints specifically for DKI. Using in vivo cardiac DKI data from 11 healthy volunteers collected with a Connectom scanner, we tested various combinations of fitting techniques, with/without robustness and with/without constraints. ResultsRCWLS was the only tested technique that convincingly showed radial kurtosis to be larger than axial kurtosis for all subjects, something that is expected in myocardium due to increased restrictions to diffusion in the plane perpendicular to the primary myocyte direction. RCWLS also showed the best correction of corrupted regions in diffusion parameter maps for individual subjects. ConclusionFitting techniques utilizing both robust estimation and constraints are essential to facilitate applicability of in vivo cardiac DKI.

physiology↗

bioRxiv2025

Cardiac diffusion kurtosis imaging in the human heart in vivo using 300mT/m gradients

PurposeDiffusion tensor imaging (DTI) is commonly used in cardiac diffusion magnetic resonance imaging (dMRI). However, the tissues microstructure (cells, membranes, etc.) restricts the movement of the water molecules, making the spin displacements deviate from Gaussian behaviour. This effect may be observed with diffusion kurtosis imaging (DKI) using sufficiently high b-values (b > 450 s/mm2), which are presently outside the realm of routine cardiac dMRI due to the limited gradient strength of clinical scanners. The Connectom scanner with Gmax = 300 mT/m enables high b-values at echo times (TE) similar to DTI on standard clinical scanners, therefore facilitating cardiac DKI in humans. MethodsCardiac-gated, second-order motion-compensated dMRI was performed with bmax = 1350 s/mm2 in 10 healthy volunteers on a 3T MRI scanner with Gmax = 300 mT/m. The signal was fitted to a cumulant expansion up to and including the kurtosis term and diffusion metrics such as fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) were calculated. ResultsWe demonstrate deviation of the signal from monoexponential decay for b-values > 450 s/mm2 (MK = 0.32 {+/-} 0.03). Radial kurtosis (RK = 0.35 {+/-} 0.04) was observed slightly larger than axial kurtosis (AK = 0.27 {+/-} 0.02), and the difference is statistically significant (RK - AK = 0.08 {+/-} 0.04, p = 2e - 4). ConclusionThis work demonstrates the feasibility of quantifying kurtosis effect in the human heart in vivo (at an echo time shorter than typical TEs reported for cardiac DTI), using high-performance gradient systems (which are 4-8 times stronger than on standard clinical scanners). Our work lays the foundation for exploring new biomarkers in cardiac dMRI beyond DTI.

biophysics↗

bioRxiv2019

Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis.

Developmental defects affecting the heart and aortic arch arteries are a key phenotype observed in DiGeorge syndrome patients and are caused by a microdeletion on chromosome 22q11. Heterozygosity of TBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key component for the arch artery defects. Pax9 is expressed in the pharyngeal endoderm and is downregulated in Tbx1 mutant mice. We show here that Pax9 deficient mice are born with complex cardiovascular malformations affecting the outflow tract and aortic arch arteries with failure of the 3rd and 4th pharyngeal arch arteries to form correctly. Transcriptome analysis indicated that Pax9 and Tbx1 may function together, and mice double heterozygous for Tbx1/Pax9 presented with a significantly increased incidence of interrupted aortic arch when compared to Tbx1 heterozygous mice. Using a novel Pax9Cre allele we demonstrated that the site of this Tbx1-Pax9 genetic interaction is in the pharyngeal endoderm, therefore revealing that a Tbx1/Pax9-controlled signalling mechanism emanating from the pharyngeal endoderm is required for critical tissue interactions during normal morphogenesis of the pharyngeal arch artery system.\n\nSummary statementPax9 is required for outflow tract and aortic arch development, and functions together with Tbx1 in the pharyngeal endoderm for 4th arch artery formation.

developmental biology↗