Biology subjects

Jimenez, K.

Publications and source records attributed to Jimenez, K..

3 recordsLinked to original sources

bioRxiv2025

Application of machine learning to discriminate photoreceptor cell species in xenotransplanted chimeric retinas

Photoreceptor transplantation is being studied to improve visual function in retinal diseases causing blindness, such as age-related macular degeneration, hereditary eye diseases, and traumatic retinopathy, among others. Preclinical studies often involve the delivery of exogenous human photoreceptor cells into the retinas of animal models. In such experiments, a key readout is the differential frequency of donor cell somatic integration versus artificial labeling secondary to material transfer of cytosolic or nuclear labels from donor to recipient cells. For this analysis, the ability to recognize photoreceptor nuclei as being of donor (human) versus animal is key, but purely immunohistology discrimination can be challenging because of antigenic species overlap or intercellular antigen transfer. To address this challenge, we sought to develop and validate a computational technique to discriminate between photoreceptor cells of different animal species based on machine learning of nuclear morphology. Here, we aimed to evaluate the feasibility of using computer-assisted detection of separate nuclei and employing random forest classification to automate the species differentiation, among DAPI-stained photoreceptors after xeno-transplantation of human photoreceptors into the retinas of mice and pigs. Our models were trained on single-species samples and validated with mixed-species samples. We then transplanted human embryonic stem cell-derived retinal organoid cells into rodent and pig retinal degeneration models. The random forest model accurately determined cell identity post-xenotransplantation, validated by histological assessment using an anti-human nuclear antibody. Our results support the potential efficacy of employing machine learning image analysis and classification techniques that may promote experimental rigor, minimize observer bias, and enable high throughput semi-automated workflows for transplantation outcomes analysis. The methodological framework reported here may enable a more nuanced and precise analysis of the behavior of transplanted photoreceptors for the purposes of human retinal regeneration.

neuroscience↗

bioRxiv2024

Unexpected levels of antibiotic resistance in marine bacterial communities not solely explained by urban river discharge

Driven by anthropogenic pressures, antibiotic resistance has become more prevalent within urban bacterial communities over recent decades. In general, resistance is expected to spread from highly impacted areas into surrounding environments as the spatial patterns of resistance reflect the balance between the ability of dispersal and horizontal gene transfer to spread resistance, and the effects of dilution or selection driven by other environmental or ecological factors that change along these gradients. However, the strength and scale of this effect is less clear, especially in coastal environments. We investigated antibiotic resistance of bacterial communities along a transect from a freshwater site in the Los Angeles River (surrounded by high-density urban development) out into the San Pedro Basin in the Pacific Ocean. We determined the minimum concentration of twelve different antibiotics needed to inhibit the growth of bacterial communities across eight sites. We also examined community composition and the prevalence of known genes related to antibiotic resistance from anthropogenic sources in each sample using 16S rRNA sequencing and qPCR. In contrast to our expectations, marine bacteria communities displayed higher resistance than the freshwater LA River community. Rather than the presence of known resistance genes or proximity to urban impacts, patterns of resistance were more strongly associated with the higher species diversity found in marine communities. These unexpected results open new opportunities to determine why marine bacterial communities possess high resistance and the repercussions for potentially pathogenic bacteria and their impacts on the health of humans and wildlife.

microbiology↗

bioRxiv2022

Non-synaptic alterations in striatal excitability and cholinergic modulation in a SAPAP3 mouse model of compulsive motor behavior

Deletion of the OCD-associated gene SAP90/PSD-95-associated protein 3 (Sapap3), which encodes a postsynaptic anchoring protein at corticostriatal synapses, causes OCD-like motor behaviors in mice. While corticostriatal synaptic dysfunction is central to this phenotype, the striatum efficiently adapts to pathological changes, often in ways that expand upon the original circuit impairment. Here we show that SAPAP3 deletion causes non-synaptic and pathwayspecific alterations in dorsolateral striatum circuit function. While somatic excitability was elevated in striatal projection neurons (SPNs), dendritic excitability was exclusively enhanced in direct pathway SPNs. Layered on top of this, cholinergic modulation was altered in opposing ways: striatal cholinergic interneuron density and evoked acetylcholine release were elevated, while basal muscarinic modulation of SPNs was reduced. These data describe how SAPAP3 deletion alters the striatal landscape upon which impaired corticostriatal inputs will act, offering a basis for how pathological synaptic integration and unbalanced striatal output underlying OCD-like behaviors may be shaped.

neuroscience↗