Biology subjects

Olsen, M.

Publications and source records attributed to Olsen, M..

5 recordsLinked to original sources

bioRxiv2026

Safety and Feasibility of Infusing Ex Vivo Expanded Allogeneic Canine Natural Killer Cells for the Treatment of Metastatic Solid Tumors

BackgroundCompanion canines need advances in therapeutic options for solid tumor malignancies. Prior studies established feasibility of autologous natural killer (NK) cell infusions in canines with solid tumors; however, autologous products are limited by dysfunctional immunity and a manufacturing process that delays care. Allogeneic NK cells offer the possibility of "off-the-shelf" therapy to be administered from healthy donors. MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from healthy canine donors via density gradient separation. NK cells were expanded with recombinant human IL-2 and canine IL-21 with the addition of K562 feeder cells transfected with CD137 ligand and membrane bound human IL-15. Additional experiments included IL-12 in the expansions. In vitro potency was assessed via co-culture with the D17-mKate2 canine osteosarcoma cell line. Three canines were enrolled in a phase 1 trial infusing ex vivo expanded allogeneic NK cells after lymphodepletion. ResultsFlow cytometric analysis confirmed successful expansion of canine NK cells with up to 50% of cells demonstrating NKp46+ after 14 days of expansion. Residual T cell numbers varied based on donor. The addition of IL-12 led to increased NK cell expansion. Incucyte demonstrated potency with increasing osteosarcoma cell death at higher effector to target ratios. Three canines with metastatic/refractory solid tumors were successfully lymphodepleted and infused with allogeneic NK cell products. The canines tolerated the infusions well. ConclusionsCanine allogeneic NK cells were successfully expanded and activated ex vivo, demonstrated potency in vitro, and safety in vivo. Further studies will optimize the NK cell product and escalate dosing to reach the maximal tolerable dose.

cancer biology↗

bioRxiv2025

Neuropixels Opto: Combining high-resolution electrophysiology and optogenetics

High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations, and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 70 m wide, 1 cm long shank, allowing spatially addressable optogenetic stimulation with blue and red light. In mouse cortex, Neuropixels Opto probes delivered high-quality recordings together with spatially addressable optogenetics, differentially activating or silencing neurons at distinct cortical depths. In mouse striatum and other deep structures, Neuropixels Opto probes delivered efficient optotagging, facilitating the identification of two cell types in parallel. Neuropixels Opto probes represent an unprecedented tool for recording, identifying, and manipulating neuronal populations.

neuroscience↗

bioRxiv2024

The NPxY motifs in the β integrin regulate serotonin response and mechanosensation in C. elegans

BackgroundIntegrin is an {beta} heterodimeric receptor to the extracellular matrix; its binding to the matrix recruits focal adhesions to two NPxY motifs, the tyrosine phosphorylation sites in the cytoplasmic domain. Studies found that replacing tyrosines (Y) with phenylalanines (F) in the motif of {beta}1 integrin displayed little developmental or behavioral defects. However, the tyrosine-to-alanine (A) caused embryonic lethality. ResultsHere we report novel functions of the NPxY motifs in C. elegans pat-3 {beta} integrin. The membrane-proximal non-phosphorylation pat-3(Y792F) mutation caused hypersensitive egg laying in serotonin, which is more prominent than the membrane-distal NPxY804. The double non-phosphorylatable pat-3(YYFF) mutant exhibited serotonin hypersensitivity and defective egg retention. The phosphomimetic NPxY, pat-3(Y804E), mutant displayed a reduced egg laying in response to serotonin and fluoxetine, suggesting that the NPxY phosphorylation is associated with vulval contraction and serotonin sensitivity. Additionally, pat-3(Y792A), pat-3(Y792F), pat-3(Y804E), and pat-3(YYFF) mutants exhibited mechanosensation defects, demonstrating that NPxY phosphorylation regulates sensory neuron activity. Further revealed that exogenous serotonin reduced mechanosensation, while blocking serotonin secretion rescued the mechanosensation of pat-3 NPxY mutants, suggesting that integrin NPxY modulates serotonin levels in C. elegans. ConclusionOur results underscore the functional importance of pat-3 NPxY motifs in muscle and neurons, potentially linking integrin NPxY motifs to neurotransmitter response and mechanosensory functions.

cell biology↗

bioRxiv2024

Protamine Protects Against Vancomycin Induced Kidney Injury

IntroductionVancomycin causes kidney injury by accumulating in the proximal tubule, likely mediated by megalin uptake. Protamine is a putative megalin inhibitor that shares binding sites with heparin and is approved for heparin overdose in patients. MethodsWe employed a well characterized Sprague Dawley rat model to assess kidney injury and function in animals that received vancomycin, protamine alone, or vancomycin plus protamine over 5 days. Urinary KIM-1 was used as the primary measure for kidney injury while iohexol clearance was calculated to assess kidney function. Animals had samples drawn pre-treatment to serve as their own controls. Additionally, since protamine is not a known nephrotoxin, the protamine group also served as a control. Cellular inhibition studies were performed to assess the ability of protamine to inhibit OAT1, OAT3, and OCT2. ResultsRats that received vancomycin had significantly increased urinary KIM-1 on day 2 (24.9 ng/24h, 95% CI 1.87 to 48.0) compared to the protamine alone group. By day 4, animals that received protamine with vancomycin had urinary KIM-1 amounts that were elevated compared to protamine alone (KIM-1 29.0 ng/24h, 95% CI 5.0 to 53.0). No statistically significant differences were identified for iohexol clearance changes between drug groups or when comparing clearance change from baseline (P>0.05). No substantial inhibition of OAT1, OAT3, or OCT2 was observed with protamine. IC50 values for protamine were 1e-4 M for OAT1 and OAT3 and 4.3e-5 M for OCT2. ConclusionProtamine, when added to vancomycin therapy, delays vancomycin induced kidney injury as defined by urinary KIM-1 in the rat model by one to three days. Protamine putatively acts through blockade of megalin and does not appear to have significant inhibition on OAT1, OAT3, or OCT2. Since protamine is an approved FDA medication, it has clinical potential as a therapeutic to reduce vancomycin related kidney injury; however, greater utility may be found by pursuing compounds with fewer adverse event liabilities.

pharmacology and toxicology↗

bioRxiv2019

SHARQnet - Sophisticated Harmonic Artifact Reduction in Quantitative Susceptibility Mapping using a Deep Convolutional Neural Network

Quantitative susceptibility mapping (QSM) reveals pathological changes in widespread diseases such as Parkinsons disease, Multiple Sclerosis, or hepatic iron overload. QSM requires multiple processing steps after the acquisition of magnetic resonance imaging (MRI) phase measurements such as unwrapping, background field removal and the solution of an ill-posed field-to-source-inversion. Current techniques utilize iterative optimization procedures to solve the inversion and background field correction, which are computationally expensive and lead to suboptimal or over-regularized solutions requiring a careful choice of parameters that make a clinical application of QSM challenging. We have previously demonstrated that a deep convolutional neural network can invert the magnetic dipole kernel with a very efficient feed forward multiplication not requiring iterative optimization or the choice of regularization parameters. In this work, we extended this approach to remove background fields in QSM. The prototype method, called SHARQnet, was trained on simulated background fields and tested on 3T and 7T brain datasets. We show that SHARQnet outperforms current background field removal procedures and generalizes to a wide range of input data without requiring any parameter adjustments. In summary, we demonstrate that the solution of ill-posed problems in QSM can be achieved by learning the underlying physics causing the artifacts and removing them in an efficient and reliable manner and thereby will help to bring QSM towards clinical applications.

neuroscience↗