Biology subjects

Martinez, A. R.

Publications and source records attributed to Martinez, A. R..

4 recordsLinked to original sources

bioRxiv2025

Genome-wide association study of cocaine self-administration behavior in Heterogeneous Stock rats

BackgroundCocaine use disorder (CUD) is a major public health crisis with detrimental individual and societal effects. The specific genes mediating CUD remain largely unknown. MethodsWe conducted a genome-wide association study (GWAS) using outbred N/NIH Heterogeneous Stock (HS; n = 836, female = 415, male = 421) rats. We examined multiple CUD-related phenotypes that captured acquisition of self-administration, escalation of intake, and compulsive-like responding. ResultsConsistent with the existing literature, these traits were phenotypically and genetically correlated and exhibited modest heritability (h2 = 0.07 - 0.16). We identified six genome-wide significant associations. One locus on chromosome 19 was associated with the variable time between cocaine infusions (post infusion interval) and contains several carboxylesterase genes that are orthologous to the human CES1 gene; notably, carboxylesterases metabolize cocaine. Three non-synonymous coding variants in the genes Ces1c and Ces1d were in perfect linkage disequilibrium with this locus, suggesting that one or more of them might be the causal SNP. The other 5 loci also contained promising coding and expression variants, including Trak2, a gene previously associated with CUD in human GWAS and Slc10a7, Plcl1, and Satb2 which have been associated with alcohol and tobacco use disorder. ConclusionsThis is the largest genetic study of cocaine self-administration ever conducted in any species. Our results replicate previous loci associated with CUD in humans and provide several novel biological insights including the potential of pharmacological strategies targeting carboxylesterases for the treatment of CUD.

genetics↗

bioRxiv2025

A Preclinical Alcohol BioBank: Samples from Behaviorally Characterized HS Rats for AUD Research

Alcohol use disorder (AUD) imposes a significant global health burden, yet effective treatments remain limited due to the scarcity of well-characterized biological sample repositories. To address this gap, we established the UCSD Alcohol BioBank, a comprehensive resource containing thousands of samples from over 700 genetically diverse heterogeneous stock (HS) rats. Modeled after successful cocaine and oxycodone biobanks, this repository utilizes the chronic intermittent ethanol vapor exposure (CIE) model, paired with oral self-administration, to characterize AUD-like behaviors, including ethanol consumption, preference, motivation, and withdrawal symptoms such as allodynia and anxiety-like behavior. Longitudinal samples (blood, urine, and feces) are collected before, during, and after ethanol exposure, while terminal samples (brain, heart, liver, kidneys, cecum, reproductive organs, adrenal glands, peripheral blood mononuclear cells) are obtained at intoxication, acute withdrawal, protracted abstinence, or from naive controls. Samples are preserved via snap-freezing or paraformaldehyde fixation to support diverse applications, including genomics, transcriptomics, proteomics, and neuroanatomy. The genetic diversity of HS rats enables genome-wide association studies (GWAS) to identify AUD-related genetic variants. Freely available to non-profit organizations at www.alcoholbiobank.org, with genetic and behavioral data deposited in public repositories, the Alcohol BioBank facilitates collaborative research to uncover biomarkers and develop novel therapies for AUD, addressing a critical need in addiction science.

animal behavior and cognition↗

bioRxiv2024

1-Aminocyclopropane-1-carboxylic acid oxidase determines the fate of ethylene biosynthesis in a tissue-specific way to fine-tune development and stress resilience

Ethylene is involved in several developmental processes and responses towards (a)biotic stress. In seed plants, ethylene is produced from its precursor 1-aminocyclopropane-1-carboxylic acid (ACC) by the enzyme ACC-oxidase (ACO). Despite its key role in ethylene synthesis, the ACO gene family has not yet been fully characterized. We investigated the five ACO members of Arabidopsis thaliana and revealed a tissue-and developmentally specific expression pattern. Furthermore, the five ACO enzymes each have a different capacity to produce ethylene. Combined, this allows for a precise spatial and temporal regulation of ethylene synthesis. At the sub-cellular level, we uncovered that ACOs reside in the cytosol, where ethylene is likely synthesized, but surprisingly also in the nucleus. Using reverse genetics of single and higher order aco mutants we revealed a high degree of gene redundancy and minimal phenotypes. A lack of ethylene synthesis by knocking out all five ACOs did not impair normal vegetative and generative development but did influence processes associated with high rates of ethylene production such as petal abscission. This suggests that ethylene is not a prime regulator of development, but more a moderator. We also showed that the inability to synthesize ethylene impairs some abiotic (nutrient deficiency and metal toxicity) and biotic (Botrytis cinerea) stress responses, similar as plants insensitive towards ethylene, corroborating the role of ethylene in mediating stress responses. In conclusion, the ACO gene family enables plants to fine-tune their ethylene synthesis rates, but a lack their off is not crucial for normal development and stress survival.

plant biology↗

bioRxiv2018

Development of a GFP Fluorescent Bacterial Biosensor for the Detection and Quantification of Silver and Copper Ions

Ionic silver is known to be an effective antimicrobial agent widely used in the cleaning and medical industries, however, there are several concerns regarding the release of silver pollutants into the environment. Presented here are two engineered bacterial biosensors for the detection and quantification of silver. The biosensors contain a silver resistance operon and a GFP gene that is strictly regulated through silver activated regulatory regions that control expression of the sil operons. The two biosensors are responsive to a wide range of silver ion concentrations, and a correlation between silver and GFP signal is seen at select concentration ranges. The biosensors were shown to detect silver ions released from silver nanoparticles, and have the potential to become a method for monitoring ion release rates of different nanoparticles. Interestingly, the close homology of the silver resistance and copper resistance genes allowed for the biosensor to also be responsive to copper ions, implying that copper ions activate silver resistance. Further development of this biosensor could lead to commercial applications for environmental monitoring.\n\nImportanceIonic silver is known to have many harmful environmental effects. Silver pollutants have been found in various environmental settings such as natural waterways and tailings from mining operations, raising concern. In addition, persistent exposure to silver in medical and environmental settings has led to the development of silver resistant bacteria, many of which are also resistant to a wide range of antibiotics. Some of these have the potential to develop into human pathogens. It then becomes important to have standardized methods for detecting and monitoring silver concentrations in various environments so that appropriate measures can be taken to prevent further silver ion release. This research shows that bacterial biosensors engineered to detect and quantify silver ions can be developed as effective alternatives to traditional analytical techniques. Further development of such biosensors could result in a commercial system for short and long term environmental monitoring, which is important as products containing silver and other heavy metals become increasingly popular.

synthetic biology↗