Biology subjects

Kang, I.

Publications and source records attributed to Kang, I..

At least 19 recordsLinked to original sources

bioRxiv2026

ANNet: A first-principles neural network for forward and inverse dynamics

Biological and robotic systems must solve two related computations to move: inverse dynamics, which determines the forces or torques needed to produce a desired movement, and forward dynamics, which maps applied forces to motion. Although these computations are coupled by the same equations of motion, they are usually estimated or implemented as distinct inverse and forward mappings, in both model-based and data-driven formulations. This separation can obscure the shared structure that constrains both problems. Here, we present ANNet, a physics-informed neural network that places both computations on a common learned representation by learning a single scalar quantity from classical mechanics--Appell acceleration energy. The network maps kinematic state and candidate accelerations to this scalar function, and inverse dynamics is obtained by differentiating the learned energy function with respect to acceleration to recover joint torques. Forward dynamics is then calculated without retraining by embedding the same learned energy landscape in an optimization objective whose unconstrained minimum satisfies the Gibbs- Appell equation. The resulting accelerations are integrated forward in time. We evaluate ANNet on a double pendulum paradigm. In trials unseen by the network during training, inverse and optimization-based forward simulations are real-time accurate. Our results provide a first-principles route for using a single learned representation to support both prediction and control. SignificanceRobots and animals must solve two problems to move: computing the forces or torques needed for a desired motion (inverse dynamics) and determining the motion produced by applied forces (forward dynamics), which are usually modeled separately. We show that both problems can be expressed using a single scalar function from classical mechanics, Appell acceleration energy. A neural network trained so that the derivative of this learned function matches reference joint torques performs inverse dynamics. The same network then computes forward dynamics by minimizing an objective built from the learned energy landscape, without retraining. This framework provides a unified representation for prediction and control in both neuroscience and robotics.

neuroscience↗

bioRxiv2026

Cultivation and genomic characterization of the first representative of the globally distributed marine UBA868 group

Members of the UBA868 group within the order Arenicellales are globally distributed marine Gammaproteobacteria predicted to participate in sulfur and carbon cycling, yet their physiology and ecological roles remain unknown due to the absence of cultured representatives. Here, we report the isolation and characterization of the first heterotrophic representative of the previously uncultured UBA868 group. Using dilution-to-extinction cultivation, we obtained four isolates from the Yellow Sea whose high-quality genomes represent a single UBA868 species. One strain, IMCC57338, maintained in axenic culture, exhibited small coccoid morphology and slow growth (doubling time [~]2.9 days), consistent with an oligotrophic lifestyle. Genome analysis revealed a predominantly aerobic chemoorganoheterotrophic lifestyle with a streamlined central carbon metabolism, including a complete glyoxylate shunt and limited carbohydrate utilization capacity, suggesting adaptation to low-nutrient conditions. The genome also encodes pathways for methylated amine oxidation coupled to formaldehyde assimilation via the serine cycle, indicating a capacity for methylotrophy. Genes encoding sulfur oxidation (Sox) and reverse dissimilatory sulfite reductase (rDsr) pathways further suggest a capacity for sulfur-based chemolithoheterotrophy. Global metagenomic and metatranscriptomic read recruitment showed that the species represented by IMCC57338 is widely distributed across ocean basins and pelagic depth layers, with higher abundance and transcriptional activity in mesopelagic waters. Our findings provide the first physiological and genomic insights into the UBA868 group and suggest that members of this lineage contribute to the cycling of organic carbon, C1 compounds, and sulfur in marine ecosystems.

microbiology↗

bioRxiv2026

Fall risk-aware adaptation explains suboptimal locomotor performance

AO_SCPLOWBSTRACTC_SCPLOWHuman locomotion requires balancing multiple biological objectives, such as metabolic energy efficiency, stability, and symmetry. While models based on optimization successfully predict how humans walk in familiar settings, they fail to explain why individuals adopt inefficient movement patterns in novel environments, even after extensive practice. Here, we show that such suboptimality in a novel environment arises from a fundamental prioritization of safety. We find that individuals do not simply fail to reach an optimal solution; instead, they navigate an environment-dependent risk landscape by mitigating the statistical probability of falling. We find that this risk-averse strategy is explained by adjusting internal learning parameters: specifically, the learning rate and the tradeoff between metabolic cost and symmetry, in a manner that lowers fall risk. To quantify this process, we developed an inverse adaptation modeling framework; this approach works backwards from locomotor performance data to mathematically infer the underlying internal learning parameters and how they vary with fall risk. Our analysis reveals that the observed motor performance is explained by a global probabilistic fall risk rather than a local step-based measure of instability. Ultimately, these findings reveal that fall risk-aware adaptation explains suboptimal locomotor behavior, providing a new data-driven framework to understand the drivers of motor performance.

neuroscience↗

bioRxiv2026

Generation and characterization of human iPSC-derived NPC1I1061T/I10161T i3Neurons as a model for NPC1 disease

Niemann-Pick disease, type C is an autosomal recessive, fatal, neurodegenerative disorder caused by pathological variants in NPC1 or NPC2. Dysfunction of either NPC1 or NPC2 results in impaired intracellular cholesterol transport and subsequent storage of unesterified cholesterol in endolysosomal compartments. Earlier cell-based studies utilized patient fibroblasts to study this disease; however, neuronal cells allow for investigation of the neurodegenerative aspect of NPC1. Expression of neurogenin in induced pluripotent stem cells leads to the generation of i3Neurons (integrated, isogenic, and inducible), allowing for rapid, synchronized growth of homogenous neurons. In this study, we report the development and characterization of a human iPSC-derived NPC1I1061T/I1061Ti3Neuronal model system. NPC1I1061Tis a missense variant resulting in a misfolded protein targeted for proteasomal degradation in the ER. NPC1I1061T/I1061T i3Neurons phenocopied the cellular pathological features of NPC1 disease including endolysosomal cholesterol accumulation, lysosomal morphological changes, and response to the proteostasis modulator, mo56HC. The NPC1 phenotype was alleviated by 2-hydroxypropyl-{beta}-cyclodextrin treatment, a drug demonstrating efficacy both in vitro and in vivo. This NPC1I1061T/I1061T i3Neuronal cell line can facilitate future high-throughput drug and genomic screens, particularly those aimed at identifying proteostasis regulators that improve the expression/stability of the mutant NPC1 protein.

neuroscience↗

bioRxiv2026

In vivo aberration measurement and correction for ultrafast FACED two-photon fluorescence microscopy of the brain

Ultrafast two-photon fluorescence microscopy (2PFM) based on free-space angular-chirp-enhanced delay (FACED) enables megahertz line scanning and kilohertz frame rates for in vivo brain imaging. However, optical aberrations from the imaging system and brain tissue degrade spatial resolution, signal, and contrast at depth. Here we integrate adaptive optics (AO) with FACED 2PFM to achieve synapse-resolving ultrafast imaging in the living mouse brain. Because FACED generates a one-dimensional array of temporally delayed, spatially separated excitation foci at 1 gigahertz, we developed a focus-averaging, frequency-multiplexed aberration measurement method that simultaneously measures and corrects the average aberration across all FACED foci using a segmented deformable mirror. We validated the accuracy of our method in correcting both system and artificial aberrations. When applied to in vivo morphological imaging of the mouse brain, AO enhances resolution, signal, contrast of dendritic shafts, spines, and boutons. Functionally, AO improves cerebral blood flow imaging by increasing plasma signal and kymograph contrast over large fields of view; when used for glutamate imaging, it amplifies transient amplitudes and reveals visually evoked glutamate release that were undetectable without correction. Together, these results establish AO-FACED 2PFM as a powerful approach that combines ultrafast imaging with high spatial resolution for structural and functional imaging in the living mouse brain.

neuroscience↗

bioRxiv2026

Identification of Lupus Immune Complex-Driven Pathogenic Pro-inflammatory Monocytes and Macrophages in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE or lupus) is an autoimmune disease characterized by anti-nuclear antibody (ANA) production and inflammation, though the mechanisms by which ANAs induce inflammation and tissue injury are incompletely understood. Here, we identified distinct subsets of mononuclear phagocytes (MPs), including monocytes (Mo) and macrophages (M{Phi}), driven by lupus immune complex (IC), comprised of ANAs and their target antigens. scRNA-seq of human Mo incubated with U1-snRNP (snRNP) lupus IC revealed expansion of distinct pro-inflammatory Mo subsets with upregulation of inflammatory genes including those encoding cytokines, NLRP3, and transcription factors. These transcriptomic changes strongly correlated with protein expression, as determined by proteomic analysis. Mo developed similar pro-inflammatory transcriptomic changes in response to other lupus ICs containing anti-dsDNA and Ro60 antibodies. Interrogation of scRNA-seq datasets from the skin, kidney, and peripheral blood of lupus patients revealed the presence and expansion of pro-inflammatory Mo and M{Phi} populations exhibiting transcriptomic signatures similar to those observed in lupus IC-stimulated Mo. Some of these cells expressing the snRNP IC gene signature exhibited low expression of the type I IFN signature, suggesting that lupus IC and type I IFN signaling may independently affect Mo subsets. In lupus nephritis, infiltration of CD68+ M{Phi} expressing NLRP3 was associated with treatment outcomes. Inhibiting activation of the transcription factor ETS2, a master regulator of Mo/M{Phi}-driven inflammation, attenuated lupus IC-induced activation of pro-inflammatory Mo. Collectively, these findings provide novel insights into the role of lupus IC-driven pro-inflammatory MPs in the pathogenesis of SLE and highlight their relevance as therapeutic targets. Significance StatementSystemic lupus erythematosus (SLE or lupus) is a multi-systemic autoimmune inflammatory disease characterized by anti-nuclear antibody (ANA) production. Lupus immune complex (IC), consisting of ANAs and their target antigens, likely play a critical role in the pathogenesis of lupus through activation of mononuclear phagocytes (MPs), including monocytes (Mo) and macrophages (M{Phi}), which can produce an array of inflammatory molecules. Using transcriptomic and proteomic analyses, our study identified distinct pro-inflammatory Mo populations driven by lupus IC, along with expansion of similar pro-inflammatory Mo and M{Phi} subsets in the skin, kidneys, and peripheral blood of lupus patients. These findings provide novel insights into the pathogenic role of lupus IC-driven pro-inflammatory MPs and support a scientific rationale for therapeutically targeting these cells. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=155 HEIGHT=200 SRC="FIGDIR/small/700902v2_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@1839430org.highwire.dtl.DTLVardef@175dd1dorg.highwire.dtl.DTLVardef@107b54forg.highwire.dtl.DTLVardef@11096b0_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2026

Cross-cohort analysis reveals conserved gut virome signatures and phage-encoded auxiliary functions in ulcerative colitis

While gut bacteriome dysbiosis is a well-established hallmark of ulcerative colitis (UC), the ecological and functional remodeling of the gut virome conserved across diverse populations remains unclear. Here, by constructing a cross-cohort atlas of the UC-associated fecal virome, we show that viral reorganization closely parallels bacterial dysbiosis, with enrichment of phages targeting disease-associated bacterial taxa. We identified a conserved set of UC-associated viral signatures that robustly distinguished UC from healthy controls using machine-learning-based classification across independent cohorts. Functional profiling further revealed that phages enriched in UC carried higher densities of auxiliary metabolic genes (AMGs) related to virulence and antibiotic resistance than phages depleted in UC, with immune evasion and glycopeptide resistance genes particularly overrepresented. Together, our cross-cohort approach highlights the value of the gut virome-based diagnostic framework for UC and suggests that phage-encoded AMGs may contribute to shaping the gut ecosystem under inflammatory conditions.

microbiology↗

bioRxiv2025

Parallel frequency-multiplexed aberration measurement for widefield fluorescence microscopy

Widefield fluorescence microscopy is widely used for imaging at subcellular resolution, but its performance in complex samples is degraded by optical aberrations. Because aberrations can vary spatially across the field of view (FOV), accurate aberration measurement and correction at multiple FOV locations are essential for achieving high-quality imaging over large areas. Here, we introduce parallel frequency-multiplexed aberration measurement (PFAM) to perform massively parallel aberration measurements across an extended FOV. We validated PFAM using fluorescent beads and demonstrated simultaneous measurement and effective correction of spatially varying aberrations at 125 FOV locations. To address the challenges of wavefront sensing in complex samples, we further developed PFAM-SIFT by integrating structured illumination, thereby achieving robust aberration measurement in both brain slices and the mouse brain in vivo. Together, PFAM and PFAM-SIFT provide accurate and scalable wavefront sensing solutions for widefield imaging, enabling simultaneous aberration measurement of spatially varying aberrations in complex biological samples.

biophysics↗

bioRxiv2024

Synthesis of USC-093 and comparison with its promoiety enantiomer USC-093D against adenovirus in vitro and in a Syrian hamster model

Adenovirus infections of immunocompromised humans are a significant source of morbidity and mortality. At present, no drug has been approved by FDA for the treatment of adenovirus infections. A current treatment of such infections is off-label use of an antiviral acyclic nucleotide phosphonate, cidofovir (CDV, (S)-HPMPC), which requires i.v. administration and has dose-limiting kidney toxicity. We recently reported that USC-093, a homoserinamide analogue of the tyrosinamide (S)- HPMPA prodrug USC-087, was orally effective at a 10 mg/kg against disseminated human adenovirus infection (HAdV-C6) in a Syrian hamster model, although their efficacy was marginal after respiratory infection. Neither prodrug manifested GI toxicity. Unlike USC-087, USC-093 showed no significant nephrotoxicity at the effective dose. Here, we describe in detail the synthesis of USC-093 and also its D-homoserinamide analogue, USC-093D, in four steps (20-40% overall yield) starting from Boc-protected L-homoserine or D-homoserine lactone, respectively. The two stereoisomeric prodrugs had EC50 30-70 nM vs. Ad5 or 1-6 nM vs. Ad6 in HFF cells, with USC-093D giving the lower values. The prodrugs were 30-59x more potent vs. Ad5 and 82-332x more potent than Ad6 relative to the positive control, CDV. To ascertain whether D-chirality in the promoiety could enhance the performance of the prodrug in vivo, USC-093D and USC-093 were compared in the Syrian hamster model (treated from day 1 q.d at an experimentally determined maximum tolerated oral dose of 20 mg/kg)). In this study, the hamsters were instilled i.n. with vehicle or 4X1010 PFU/kg of HAdV-C6 to promote lung infection. Oral valganciclovir (VGCV) at 200 mg/kg b.i.d. was used as the positive control. The body weights were recorded daily, and at 3 days post challenge, gross pathological observation was performed. Lung samples were collected, and the virus burden was determined by TCID50 assay. The results show that altering homoserine stereochemistry did not markedly improve the efficacy of the orally administered prodrug, consistent with the premise that its mechanism of transport is likely not dependent on stereoselective pathways, such as hPEPT1-mediated uptake.

biochemistry↗

bioRxiv2024

Adaptive optical correction in in vivo two-photon fluorescence microscopy with neural fields

Adaptive optics (AO) restore ideal imaging performance in complex samples by measuring and correcting optical aberrations, but often require custom-built microscopes with carefully aligned wavefront sensing/shaping devices and can be susceptible to sample motion. Here we describe NeAT, a computational framework using neural fields for AO two-photon fluorescence microscopy. NeAT estimates wavefront aberration and recovers sample structure from a 3D image stack without requiring external datasets for training. Incorporating motion correction in learning and correcting conjugation errors commonly found in commercial microscopes, NeAT is designed for deployment in biological laboratories for in vivo imaging. We validate NeATs performance using a custom-built microscope with a wavefront sensor under varying signal-to-noise ratios, aberration, and motion conditions. With a commercial microscope, we demonstrate real-time aberration correction for in vivo morphological and functional imaging in the living mouse brain, with NeAT improving signal and accuracy of glutamate and calcium imaging of synapses and neurons.

neuroscience↗

bioRxiv2023

Syncytia Formation Promotes Virus Resistance to Interferon and Neutralizing Antibodies

SARS-CoV-2, like many viruses, generates syncytia but the role of syncytia formation in viral evolution remains unknown. Using SARS-CoV-2 and SARS-CoV-2 Spike (S) replacement vesicular stomatitis (VSV), we show that S-mediated syncytia impair the antiviral effects of interferons in cultured cells, human lung cell cultures, and hACE2 transgenic mice. Amino acid substitutions that modulate syncytia formation in Delta- and Omicron-encoded S have parallel effects on viral interferon resistance. S-mediated syncytia compromise antibody-mediated virus neutralization in cultured cells. We recapitulate interferon and neutralizing antibody resistance in syncytia generated by the orthoreovirus p14 fusion-associated small transmembrane (FAST) protein in VSV, influenza virus, and seasonal coronavirus OC43 infections. These findings explain selection of SARS-CoV-2 fusogenic variants in humans and, more generally, the evolution of fusogenic viruses driven by adaptive and innate immunity.

microbiology↗

bioRxiv2023

Optical segmentation-based compressed readout of neuronal voltage dynamics

Functional imaging of biological dynamics generally begins with acquiring time-series images, followed by quantifying spatially averaged intensity traces for the regions of interest (ROIs). The conventional pipeline discards a substantial portion of the acquired data when quantifying intensity traces, indicative of inefficient data acquisition. Here we propose a conceptually novel acquisition pipeline that assigns each ROI to a single pixel in the detector, enabling optimally compressed acquisition of the intensity traces. As a proof-of-principle, we implemented a detection module composed of a pair of spatial light modulators and a microlens array, which segments the original image into multiple subimages by introducing distinct angular shifts to each ROI. Each subimage exclusively encodes the signal for the corresponding ROI, facilitating the compressed readout of its intensity trace using a single pixel. This spatial compression allowed for maximizing the temporal information without compromising the spatial information on ROIs. Harnessing our novel approach, we demonstrate the recording of circuit-scale neuronal voltage dynamics at over 5 kHz sampling rate, revealing the individual action potential waveforms within subcellular structures, as well as their submillisecond-scale temporal delays.

neuroscience↗

bioRxiv2023

Cultivation of SAR202 Bacteria from the Ocean

Here we report the first successful cultivation of SAR202 bacteria, a superorder in the phylum Chloroflexota, which have long been at the top of "most wanted" lists of uncultivated microbial life. It has been proposed that ancient expansions of catabolic enzyme paralogs in SAR202 broadened the spectrum of organic compounds they could oxidize, leading to transformations of the Earths carbon cycle. We cultured the cells from surface seawater using dilution-to-extinction culturing. Their growth was very slow (0.18-0.24 day-1) and was inhibited by exposure to light. The genomes, of ca. 3.08 Mbp, encoded archaella, archaeal motility structures, and multiple sets of paralogs, including 80 genes in enolase superfamily and 44 genes in NAD(P)-dependent dehydrogenase family. We propose that these paralogs participate in multiple parallel pathways of non-phosphorylative sugar and sugar acid catabolism, and demonstrate that, as predicted by this scheme, the sugars -fucose and -rhamnose and their lactone and acid forms are utilized by these cells.

microbiology↗

bioRxiv2022

Altered CD8+ T cell associated aging gene signature in the peripheral blood of patients with Alzheimer's disease.

INTRODUCTIONEffector memory (EM) CD8+ T cells have been associated with poor cognition in Alzheimers disease (AD). Our lab recently discovered an age-associated gene expression signature of IL-7 receptor alpha (IL-7R)low EM CD8+ T cells. We hypothesized that individuals with AD have altered levels of this IL-7Rlow aging gene expression. METHODSForty genes associated with IL-7Rlow EM CD8+ T cells, AD, or memory, were analyzed in peripheral blood of participants with normal cognition, mild cognitive impairment, and dementia by qPCR. RESULTSOf the eight genes that were found to be differentially expressed based on clinical diagnosis, 5 genes (62.5%) were IL-7Rlow aging genes. Principal component analysis revealed 3 clusters of participants with dementia which had distinct expression levels of IL-7Rlow aging genes and cognitive function. DISCUSSIONOur findings support the possible relationship of the IL-7Rlow EM CD8+ T cell aging signature with cognition in individuals with dementia due to AD.

immunology↗

bioRxiv2022

Activity in primate visual cortex is minimally driven by spontaneous movements

Organisms process sensory information in the context of their own moving bodies, an idea referred to as embodiment. This idea is important for developmental neuroscience, and increasingly plays a role in robotics and systems neuroscience. The mechanisms that support such embodiment are unknown, but a manifestation could be the observation in mice of brain-wide neuromodulation, including in the primary visual cortex, driven by task-irrelevant spontaneous body movements. Here we tested this hypothesis in macaque monkeys, a primate model for human vision, by simultaneously recording visual cortex activity and facial and body movements. Activity in the visual cortex (V1, V2, V3/V3A) was associated with the animals own movements, but this modulation was largely explained by the impact of the movements on the retinal image. These results suggest that embodiment in primate vision may be realized by input provided by the eyes themselves.

neuroscience↗

bioRxiv2021

Pattern and component responses of primate MT neurons recorded with multi-contact electrodes, stimulated with 1D and 2D noise patterns.

Direction selective neurons in primary visual cortex (area V1) are affected by the aperture problem, i.e., they are only sensitive to motion orthogonal to their preferred orientation. A solution to this problem first emerges in the middle temporal (MT) area, where a subset of neurons (called pattern cells) combine motion information across multiple orientations and directions, becoming sensitive to pattern motion direction. These cells are expected to play a prominent role in subsequent neural processing, but they are intermixed with cells that behave like V1 cells (component cells), and others that do not clearly fall in either group. The picture is further complicated by the finding that cells that behave like pattern cells with one type of pattern, might behave like component cells for another. We recorded from macaque MT neurons using multi-contact electrodes while presenting both type I and unikinetic plaids, in which the components were 1D noise patterns. We found that the indices that have been used in the past to classify neurons as pattern or component cells work poorly when the properties of the stimulus are not optimized for the cell being recorded, as is always the case with multi-contact arrays. We thus propose alternative measures, which considerably ameliorate the problem, and allow us to gain insights in the signals carried by individual MT neurons. We conclude that arranging cells along a component-to-pattern continuum is an oversimplification, and that the signals carried by individual cells only make sense when embodied in larger populations.

neuroscience↗

bioRxiv2021

No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination

The impact of coronavirus disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated two of the most widely propagated claims to determine 1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities, and 2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from vaccinated murine pregnancies exhibit high circulating levels of anti-Spike and anti-RBD antibodies to SARS-CoV-2 consistent with maternal antibody status, indicating transplacental transfer. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.

immunology↗

bioRxiv2021

Comparison of neuromuscular junction dynamics following ischemic and aged skeletal muscle

Both aging and neuromuscular diseases lead to significant changes in the morphology and functionality of the neuromuscular synapse. Skeletal muscles display a remarkable regenerative capacity, however, are still susceptible to diseases of aging and peripheral nerve perturbations. In this study, we assessed how neuromuscular synapses differ in aged and injured skeletal muscle using an improved neuromuscular junction (NMJ) staining and imaging method. We found that both aged and ischemic skeletal muscle display Wallerian degeneration of the presynaptic motor axons and fragmentation of postsynaptic acetylcholine receptors (AChRs). Quantifiable measurements of various metrics of the NMJs provide a more concrete idea of the dynamics that are occurring in the muscle microenvironment. We questioned whether neuronal degradation precedes myofiber atrophy or vice versa. Previously, it was shown that a cellular crosstalk exists among the motor neurons, myofibers, vasculature, and mitochondria within the muscle microdomain. It is apparent that lack of blood flow to motor neurons in ischemic skeletal muscle disrupts the structure of NMJs, however it is unclear if the aging condition experiences similar dynamics. We demonstrated that both aged and ischemic skeletal muscle demonstrate similar patterns of degeneration, characterized by a smaller percentage overlap of presynaptic and postsynaptic sides, greater fragmentation of AChRs, and a smaller area of AChR clusters. Together, these results reveal high resolution, precise parallels between the aged and ischemic NMJs. Impact StatementThe goal of this study was to assess changes in presynaptic motor neurons and postsynaptic acetylcholine receptors following an ischemic injury model and compare this with an aging model. This was accomplished by characterizing key components of NMJ morphology, including overlap and size of the receptors. There is currently limited research investigating the cellular communication between skeletal muscle fibers and motor neurons. Additionally, there is limited work comparing neuromuscular remodeling in aged and young models. With the substantial prevalence of neuromuscular disorders, especially in the aging population, it is essential to understand nerve-muscle interactions in order to promote increased mobility and improved quality of life in both injury and aging models.

neuroscience↗