Biology subjects

Swartz, M. E.

Publications and source records attributed to Swartz, M. E..

3 recordsLinked to original sources

bioRxiv2026

Inverse-scattering of absorptive samples via beam propagation

Inverse-scattering methods enable label-free, quantitative visualization of a samples three-dimensional (3D) refractive index (RI), providing intrinsic and volumetric morphological contrast without exogenous labels. This is achieved by developing computational frameworks that reconstruct the samples 3D RI from a series of scattering measurements acquired under different data-capture conditions. Recent advances have demonstrated successful 3D RI reconstructions in multiple-scattering samples using angle-varying illuminations; however, these studies have primarily focused on non-absorptive samples. Here, we extend the multi-slice beam propagation (MSBP) inverse-scattering framework to reconstruct complex-valued RI, encompassing both the samples conventional RI (real part) and absorptivity (imaginary part). We show that reconstructing complex-valued RI makes the inverse problem ill-posed under angle-varying illumination alone, and that incorporating measurement diversity from both angle-varying illumination and sample defocus is necessary to ensure stable and accurate convergence. Experimental demonstrations were conducted on 1) dyed microsphere samples to characterize accuracy of reconstructed RI and absorptivity; and 2) diverse absorptive scattering samples to demonstrate biological utility. These results represent an important step for label-free volumetric imaging in biological tissue, which typically exhibits both scattering and absorption.

bioengineering↗

bioRxiv2025

Inverse-scattering in biological samples via beam-propagation

Multiple scattering limits optical imaging in thick biological samples by scrambling sample-specific information. Physics-based inverse-scattering methods aim to computationally recover this information, often using non-convex optimization to reconstruct the scatter-corrected sample. However, this non-convexity can lead to inaccurate reconstructions, especially in highly scattering samples. Here, we show that various implementation strategies for even the same inverse-scattering method significantly affect reconstruction quality. We demonstrate this using multi-slice beam propagation (MSBP), a relatively simple nonconvex inverse-scattering method that reconstructs a scattering samples 3D refractive-index (RI). By systematically conducting MSBP-based inverse-scattering on both phantoms and biological samples, we showed that an amplitude-only cost function in the inverse-solver, combined with angular and defocus diversity in the scattering measurements, enabled high-quality, fully-volumetric RI imaging. This approach achieved subcellular resolution and label-free 3D contrast across diverse, multiple-scattering samples. These results lay the groundwork for robust use of inverse-scattering techniques to achieve biologically interpretable 3D imaging in increasingly thick, multicellular samples, introducing a new paradigm for deep-tissue computational imaging.

bioengineering↗

bioRxiv2025

Re-visiting the potential impact of doxycycline post-exposure prophylaxis (doxy-PEP) on the selection of doxycycline resistance in Neisseria commensals

Doxycycline post-exposure prophylaxis (doxy-PEP) is a preventative strategy demonstrated to reduce bacterial sexually transmitted infections in high-risk populations. However, the impact of doxy-PEP on antibiotic resistance acquisition in key members of our microbiomes, is as of yet unclear. For example, commensal Neisseria are known reservoirs of resistance for gonococci through horizontal gene transfer (HGT), and are more likely to experience bystander selection due to doxy-PEP as they are universally carried. Thus, the consequences of doxycycline selection on commensal Neisseria will be critical to investigate to understand possible resistance mechanisms that may be transferred to an important human pathogen. Here, we use in vitro antibiotic gradients to evolve four Neisseria commensals (N. cinerea, N. canis, N. elongata, and N. subflava, n=4 per species) across a 20-day time course; and use whole genome sequencing to nominate derived mutations. After selection, 12 of 16 replicates evolved doxycycline resistance (> 1 g/mL). Across resistant lineages: An A46T substitution in the repressor of the Mtr efflux pump (MtrR) and a V57M substitution in the 30 ribosomal protein S10 were clearly associated with elevated MICs. Additional mutations in ribosomal components also emerged in strains with high MICs (i.e., 16S rRNA G1057C, RplX A14T). We find the MtrR 46T, RpsJ 57M, and RplX 14T circulating in natural commensal populations. Furthermore, in vitro co-evolution of N. gonorrhoeae with Neisseria commensals demonstrated rapid transfer of the pConj plasmid to N. subflava and N. cinerea, and pbla to N. cinerea. Finally, collection of novel commensals from human hosts reveals 46% of isolates carrying doxycycline resistance; and doxycycline resistance was significantly greater in participants self-reporting doxycycline use in the past 6 months. High-level doxycycline resistance (> 8 g/mL) was always associated with carriage of the ribosomal protection protein (tetM) and pConj. Ultimately, characterizing the contemporary prevalence of doxycycline resistance, and underlying resistance mechanisms, in commensal communities may help us to predict the long-term impact of doxy-PEP on Neisseria, and the likelihood of transferring particular genotypes across species boundaries.

microbiology↗