Biology subjects

Moon, B.

Publications and source records attributed to Moon, B..

5 recordsLinked to original sources

bioRxiv2024

HIV broadly neutralizing antibody escapability drives the therapeutic efficacy of vectored immunotherapy

Broadly neutralizing antibodies (bNAbs) have shown promise for prevention and treatment of HIV. Potency and breadth measured in vitro are often used as predictors of clinical potential; however, human studies demonstrate that clinical efficacy of bNAbs can be undermined by both pre-existing and de novo resistance. Here we find that HIV-infected humanized mice receiving bNAbs delivered via AAV as Vectored ImmunoTherapy (VIT) can be used to identify antibody escape paths, which are largely conserved for each bNAb. Path selection, and consequent therapeutic success, is driven by the fitness cost and resistance benefit of emerging mutations. Applying this framework, we independently modulated bNAb resistance or the fitness cost of escape mutants, resulting in enhanced efficacy of VIT. This escape path analysis successfully explains the therapeutic efficacy of bNAbs, and enables a tractable means of quantifying and comparing the potential for viral escape from therapeutics in vivo. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/603156v4_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@180c86borg.highwire.dtl.DTLVardef@1e6108dorg.highwire.dtl.DTLVardef@148bac7org.highwire.dtl.DTLVardef@1de93ca_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Molecular tension authenticates apoptotic cells being phagocytosed.

Profound cytoskeletal reorganization and plasma membrane deformation in phagocytes is indispensable for phagocytosis of massive apoptotic cells, but whether these dynamics accompany a mechanical signal modulating signaling during efferocytosis remains largely unexplored. Here, we report that tension between phosphatidylserine (PS) and PS receptors (PSR) generated at the phagocytic synapse serves as a signal to determine whether PS-exposing cells should be phagocytosed. Mechanistically, increased membrane tension of phagocytes via Rac1-dependent actin polymerization and membrane stiffness of apoptotic cells caused tension between PS and PSRs, leading to phosphoinositide 3-kinase recruitment to PSRs, which resulted in Rac1 inactivation and myosin II phosphorylation required for phagocytic cup closure. Our observations imply that tension between PS and PSRs acts as a mechanical fail-safe to prevent removal of all PS-exposing cells for the integrity of efferocytosis. One-Sentence SummaryTension between phosphatidylserine and its receptors acts as a final decision-maker determining phagocytosis of apoptotic cells.

cell biology↗

bioRxiv2024

High refresh rate display for natural monocular viewing in AOSLO psychophysics experiments

By combining an external display operating at 360 frames per second with an Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) for human foveal imaging, we demonstrate color stimulus delivery at high spatial and temporal resolution in AOSLO psychophysics experiments. A custom pupil relay enables viewing of the stimulus through a 3-mm effective pupil diameter and provides refractive error correction from -8 to +4 diopters. Performance of the assembled and aligned pupil relay was validated by measuring the wavefront error across the field of view and correction range, and the as-built Strehl ratio was 0.64 or better. High-acuity stimuli were rendered on the external display and imaged through the pupil relay to demonstrate that spatial frequencies up to 54 cycles per degree, corresponding to 20/11 visual acuity, are resolved. The completed external display was then used to render fixation markers across the field of view of the monitor, and a continuous retinal montage spanning 9.4 by 5.4 degrees of visual angle was acquired with the AOSLO. We conducted eye-tracking experiments during free-viewing and high-acuity tasks with polychromatic images presented on the external display. Sub-arcminute eye position uncertainty was achieved, enabling precise localization of the line of sight on the monitor while simultaneously imaging the fine structure of the human central fovea. This high refresh rate display overcomes the temporal, spectral, and field of view limitations of AOSLO-based stimulus presentation, enabling natural monocular viewing of stimuli in psychophysics experiments conducted with AOSLO.

bioengineering↗

bioRxiv2023

Dynamics of Collagen Oxidation and Cross Linking in Regenerating and Irreversibly Infarcted Myocardium

In mammalian hearts myocardial infarction produces a permanent collagen-rich scar. Conversely, in zebrafish a collagen-rich scar forms but is completely resorbed as the myocardium regenerates. The formation of cross-links in collagen hinders its degradation but cross-linking has not been well characterized in zebrafish hearts. Here, a library of fluorescent probes to quantify collagen oxidation, the first step in collagen cross-link (CCL) formation, was developed. Myocardial injury in mice or zebrafish resulted in similar dynamics of collagen oxidation in the myocardium in the first month after injury. However, during this time, mature CCLs such as pyridinoline and deoxypyridinoline developed in the murine infarcts but not in the zebrafish hearts. High levels of newly oxidized collagen were still seen in murine scars with mature CCLs. These data suggest that fibrogenesis remains dynamic, even in mature scars, and that the absence of mature CCLs in zebrafish hearts may facilitate their ability to regenerate.

biochemistry↗

bioRxiv2022

Alignment, calibration, and validation of an adaptive optics scanning laser ophthalmoscope optimized for resolving human cones in the central fovea

Advances in adaptive optics scanning laser ophthalmoscope (AOSLO) technology have enabled cones in the human fovea to be reliably resolved, providing new insight into human foveal anatomy, visual perception, and retinal degenerative diseases. These high-resolution ophthalmoscopes require careful alignment of each optical subsystem to ensure diffraction-limited imaging performance, which is necessary for resolving the smallest foveal cones. This paper presents a systematic and rigorous methodology for building, aligning, calibrating, and testing an AOSLO designed for imaging the cone mosaic of the central fovea in humans with cellular resolution. This methodology uses a two-stage alignment procedure and thorough system testing to achieve diffraction-limited performance. Results from retinal imaging of healthy human subjects show that the system can resolve cones at the very center of the fovea, the region where the cones are smallest and most densely packed.

bioengineering↗