Biology subjects

Carlson, B.

Publications and source records attributed to Carlson, B..

11 recordsLinked to original sources

bioRxiv2026

IOP-independent treatment for neurodegeneration in glaucoma using optimized ROS-scavenging microparticles for sustained release of erythropoietin

Glaucoma is a slow-progressing neurodegenerative disease of the optic projection to the brain and a leading cause of blindness worldwide. Current treatments are targeted towards lowering intraocular pressure (IOP), the only known, modifiable risk factor; however, this strategy is ineffective in many patients. An early hallmark of glaucomatous neurodegeneration is increased reactive oxygen species (ROS), representing an alternative opportunity for intervention to halt or slow disease progression. In this work, we optimize a ROS-scavenging copolymer, poly(propylene sulfide-co-ethylene sulfide) (PPSES), for formulation of size-controlled, stabilized, antioxidant microparticles (MPs) for sustained release of the protein erythropoietin (EPO). EPO promotes biological antioxidant defense via activation of NRF2-mediated transcription of antioxidant genes. This MP system overcomes the short half-life of EPO and leverages the combined benefits of bioactive EPO with long-lasting, inherently antioxidant PPSES MPs. The lead EPO-MP formulation preserves neurons in both mouse and non-human primate models of glaucoma through suppression of oxidative stress and optic nerve degeneration. EPO-loaded PPSES MPs represent a translationally relevant therapy for long-term management of glaucoma independent of IOP.

bioengineering↗

bioRxiv2025

Flexible Methods for Species Distribution Modeling with Small Samples

O_LISpecies distribution models (SDMs) are used for understanding where species live or could potentially live and are a key resource for ecological research and conservation decision-making. However, current SDM methods often perform poorly for rare or inadequately sampled species, which includes most species on earth as well as most of those of the greatest conservation concern. C_LIO_LIHere, we evaluate the performance of three recently developed modeling approaches specifically designed for data-deficient situations: 1) plug-and-play modeling, 2) density-ratio modeling, and 3) environmental-range modeling. We compare the performance of these methods with Maxent, a widely used method. We compare model performance across sample sizes as well as comparisons limited to only data-poor species. We also ask to what extent model cross-validation performance on training data was correlated with model performance on independent, presence-absence data. C_LIO_LIWe show that, across all species, one or more of the plug-and-play, density-ratio, or environmental-range algorithms outperformed Maxent in 72% of cases, with three of the algorithms having AUC distributions not significantly different from Maxents. For data-poor species (those with 20 or fewer occurrences), 24 of the algorithms considered had AUC distributions that were not significantly different from Maxent. However, despite these comparable AUC scores, we found that the algorithm outputs (when thresholded to predict presence vs absence) spanned a wide gradient of sensitivity vs. specificity. Specificity and prediction accuracy assessed on training data were strongly correlated with specificity and prediction accuracy assessed on independent presence-absence data, however AUC and sensitivity had weak correlations. We found that only for 16% of species was the model that performed best on the training data the best performing model when evaluated on independent, presence-absence data. Finally, we show how ensembles of models that span the sensitivity-specificity gradient can represent model disagreement in poorly sampled species and improve model predictions. C_LIO_LIThis work supports plug-and-play, density-ratio, and environmental-range modeling as useful alternatives to Maxent, particularly for data-deficient species. While our work suggests that identifying the best model for a given species is challenging, we argue that incorporating the predictions of multiple models provides a useful way forward. C_LI Data/Code for peer reviewAnonymized data and code underlying this work are publicly available at: https://anonymous.4open.science/r/Flexible_Methods_for_Small_Sample_Size_Distribution_Modeling

ecology↗

bioRxiv2025

Tension-Induced Stiffening of Cytoskeletal Components Regulates Cardiomyocyte Contractility

Cardiomyocytes continuously experience mechanical stimuli that regulate their contractile behavior and contribute to overall heart function. Despite the importance of mechanotransduction in cardiac physiology, the mechanisms by which cardiomyocytes integrate external mechanical cues, such as stretch and environmental stiffness, remain poorly understood. In this study, we present a combined theoretical and experimental framework to investigate how strain-induced cytoskeletal stiffening modulates cardiomyocyte contractility and force generation. Our study elucidates that regulating the mechanical tension cardiomyocytes experience in tissue--whether by modulating environmental stiffness, external stretching, or cardiac fibroblast activation--can effectively tune their contractility, with cytoskeletal strain stiffening playing a central role in this mechanotransductive response.

biophysics↗

bioRxiv2025

An ex vivo and in vitro investigation of extracellular vesicle interactions with B cells of Macaca nemestrina and humans

AbstractExtracellular vesicles may modify recipient cell behavior through multiple mechanisms, including interacting with the cell surface or internal membrane components and delivering luminal cargo to the cytoplasm. Here, we use a previously established ex vivo approach to investigate the cellular fate of EVs spiked into whole blood samples from nonhuman primate (NHP) and human donors and contrast these findings with results from in vitro assays. We report that EVs are internalized by NHP and human B cells while also associating to some degree with other PBMCs. EVs exhibit greater association with B cells in ex vivo whole blood compared to isolated B cells, suggesting that blood components may promote EV interactions or that cell isolation factors may inhibit this association. Cellular uptake of EVs involves clathrin-dependent endocytosis and may be aided by other pathways, including direct EV-cell membrane fusion. Overall, our data suggest that EV association, including uptake, by B cells occurs in at least two primate species. These findings highlight the potential to develop new strategies to either enhance or inhibit EV tropism toward B cells. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/637883v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@bd28e3org.highwire.dtl.DTLVardef@c76b28org.highwire.dtl.DTLVardef@4c2e44org.highwire.dtl.DTLVardef@1719771_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2024

Scaling ecological niches from individuals to populations and beyond

The niche is a key concept that unifies ecology and evolutionary biology. However, empirical and theoretical treatments of the niche are mostly performed at the species level, neglecting individuals as important units of ecological and evolutionary processes. So far, a formal mathematical link between individual-level niches and higher organismal-level niches has been lacking, hampering the unification of ecological theories and more accurate forecasts of biodiversity change. To fill in this gap, we propose a bottom-up approach to derive population and higher organismal-level niches from individual niches. We demonstrate the power of our framework by showing that 1) the statistical properties of higher organismal-level niches (e.g. niche breadth, skewness etc.) can be partitioned into individual contributions; 2) the species-level niche shifts can be estimated by tracing the responses of individuals. Our method paves the way for a unifying niche theory and enables mechanistic assessments of organism-environment relationships across organismal scales.

ecology↗

bioRxiv2024

Exploring the adhesion properties of extracellular vesicles for functional assays

The "stickiness" of extracellular vesicles (EVs) can pose challenges for EV processing and storage, but adhesive properties may also be exploited to immobilize EVs directly on surfaces for various measurement techniques, including super-resolution microscopy. Direct adhesion to surfaces may allow examination of broader populations of EVs than molecular affinity approaches, which can also involve specialized, expensive affinity reagents. Here, we report on the interaction of EVs with borosilicate glass and quartz coverslips and on the effects of pre-coating coverslips with poly-L-lysine (PLL), a reagent commonly used to facilitate interactions between negatively charged surfaces of cells and amorphous surfaces. Additionally, we compared two mounting media conditions for super-resolution microscopy (SRM) imaging and used immobilized EVs for a B-cell interaction test. Our findings suggest that borosilicate glass coverslips immobilize EVs better than quartz glass coverslips. We also found that PLL is not strictly required for EV retention but contributes to the uniform distribution of EVs on borosilicate glass coverslips. Overall, these findings suggest that standard lab materials like borosilicate glass coverslips, with or without PLL, can be effectively used for the immobilization of EVs in specific imaging techniques.

cell biology↗

bioRxiv2023

An ex vivo model of interactions between extracellular vesicles and peripheral mononuclear blood cells in whole blood

Extracellular vesicles (EVs) can be loaded with therapeutic cargo and engineered for retention by specific body sites; therefore, they have great potential for targeted delivery of biomolecules to treat diseases. However, the pharmacokinetics and biodistribution of EVs in large animals remain relatively unknown, especially in primates. We recently reported that when cell culture-derived EVs are administered intravenously to Macaca nemestrina (pig-tailed macaques), they differentially associate with specific subsets of peripheral blood mononuclear cells (PBMCs). More than 60% of CD20+ B cells were observed to associate with EVs for up to 1 hr post-intravenous administration. To investigate these associations further, we developed an ex vivo model of whole blood collected from healthy pig-tailed macaques. Using this ex vivo system, we found that labeled EVs preferentially associate with B cells in whole blood at levels similar to those detected in vivo. This study demonstrates that ex vivo blood can be used to study EV-blood cell interactions.

immunology↗

bioRxiv2022

A ubiquitous spectrolaminar motif of local field potential power across the primate cortex

The mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity exists across the cortex. Here, we report such a motif in the power of local field potentials (LFP). We implanted multicontact laminar probes in five macaque monkeys and recorded activity across layers in 14 cortical areas at various hierarchical processing stages in all cortical lobes. The anatomical laminar locations of recordings were histologically identified via electrolytic lesions. In all areas, we found a common spectrolaminar pattern characterized by an increasing deep-to-superficial layer gradient of gamma frequency LFP power peaking in layers 2/3, and an increasing superficial-to-deep gradient of alpha-beta power peaking in layers 5/6. Our results show an electrophysiological dissociation between superficial and deep layers that is preserved across the cortex, suggesting a ubiquitous layer and frequency-based mechanism for cortical computation.

neuroscience↗

bioRxiv2021

Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina

Extracellular vesicles (EVs) have great potential as novel drug carriers for the treatment of various diseases. These lipid bilayer vesicles are naturally abundant in mammalian tissues and circulation, can be loaded with therapeutic small molecule drugs, (si)RNA, proteins and CRISPR/Cas9, and may be engineered for retention by specific tissues. However, many questions remain on the optimal dosing, administration route, and pharmacokinetics of EVs. Previous studies have addressed biodistribution and pharmacokinetics in rodents, but little evidence is available from larger animals. Here, we investigated the pharmacokinetics and biodistribution of Expi293F-derived EVs labelled with a highly sensitive nanoluciferase reporter (palmGRET) in a non-human primate model (Macaca nemestrina), comparing intravenous (IV) and intranasal (IN) administration over a 125-fold dose range. We report that EVs administered IV had markedly longer circulation times in plasma than previously reported in mice, and were detectable in cerebrospinal fluid (CSF) after 30-60 minutes. Already after one minute following IV administration, we observed EV uptake by PBMCs, most notably B-cells. EVs were detected in liver and spleen within one hour of IV administration. None of the IN doses resulted in readily detectable EV levels in plasma, CSF, or organs, suggesting that IN delivery of EVs in large animals including humans may require reconsideration or pretreatment approaches. Furthermore, EV circulation times strongly decreased after repeated IV administration, possibly due to immune responses and with clear implications for xenogeneic EV-based therapeutics. We hope that our findings from this baseline study in macaques will help to inform future research and therapeutic development of EVs.

pharmacology and toxicology↗

bioRxiv2018

The role of gene flow in rapid and repeated evolution of cave related traits in Mexican tetra, Astyanax mexicanus

Understanding the molecular basis of repeated evolved phenotypes can yield key insights into the evolutionary process. Quantifying the amount of gene flow between populations is especially important in interpreting mechanisms of repeated phenotypic evolution, and genomic analyses have revealed that admixture is more common between diverging lineages than previously thought. In this study, we resequenced and analyzed nearly 50 whole genomes of the Mexican tetra from three blind cave populations, two surface populations, and outgroup samples. We confirmed that cave populations are polyphyletic and two Astyanax mexicanus lineages are present in our dataset. The two lineages likely diverged [~]257k generations ago, which, assuming 1 generation per year, is substantially younger than previous mitochondrial estimates of 5-7mya. Divergence of cave populations from their phylogenetically closest surface population likely occurred between [~]161k - 191k generations ago. The favored demographic model for most population pairs accounts for divergence with secondary contact and heterogeneous gene flow across the genome, and we rigorously identified abundant gene flow between cave and surface fish, between caves, and between separate lineages of cave and surface fish. Therefore, the evolution of cave-related traits occurred more rapidly than previously thought, and trogolomorphic traits are maintained despite substantial gene flow with surface populations. After incorporating these new demographic estimates, our models support that selection may drive the evolution of cave-derived traits, as opposed to the classic hypothesis of disuse and drift. Finally, we show that a key QTL is enriched for genomic regions with very low divergence between caves, suggesting that regions important for cave phenotypes may be transferred between caves via gene flow. In sum, our study shows that shared evolutionary history via gene flow must be considered in studies of independent, repeated trait evolution.

evolutionary biology↗

bioRxiv2017

Microevolutionary processes underlying macroevolutionary patterns of electric signal diversity in mormyrid fish

The mormyrid fish species Paramormyrops kingsleyae emits an electric organ discharge (EOD) with a dual role in communication and electrolocation. Populations of P. kingsleyae have either biphasic or triphasic EODs, a feature which characterizes interspecific signal diversity among the Paramormyrops genus. We quantified variation in EODs of 327 P. kingsleyae from 9 populations throughout Gabon and compared it to genetic variation estimated from 5 neutral microsatellite loci. We found no correlation between electric signal and genetic distances, suggesting that EOD divergence between populations of P. kingsleyae cannot be explained by drift alone. An alternative hypothesis is that EOD differences are a cue for assortative mating, which would require P. kingsleyae be capable of differentiating between divergent EOD waveforms. Using a habituation-dishabituation assay, we found that P. kingsleyae can discriminate between triphasic and biphasic EOD types. Nonetheless, patterns of genetic and electric organ morphology divergence provide evidence for hybridization between signal types. Although reproductive isolation with respect to signal type is not absolute, our results suggest that EOD variation in P. kingsleaye has the potential to serve as a cue for assortative mating and point to selective forces rather than drift as important drivers of signal evolution.

evolutionary biology↗