A5009468541- Genetic Mapping and Diversity in Plants and Animals
- Genetic and phenotypic traits in livestock
- Genetic Associations and Epidemiology
- Neurotransmitter Receptor Influence on Behavior
- HIV Research and Treatment
- Adipose Tissue and Metabolism
- RNA and protein synthesis mechanisms
- Stress Responses and Cortisol
- Nicotinic Acetylcholine Receptors Study
- Decision-Making and Behavioral Economics
- Receptor Mechanisms and Signaling
- Neuroendocrine regulation and behavior
- Peroxisome Proliferator-Activated Receptors
- Biochemical Analysis and Sensing Techniques
- DNA and Nucleic Acid Chemistry
- Regulation of Appetite and Obesity
- CRISPR and Genetic Engineering
- Gene expression and cancer classification
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetics and Plant Breeding
- Mental Health Research Topics
- interferon and immune responses
- Smoking Behavior and Cessation
- Gut microbiota and health
- HIV-related health complications and treatments
University of California, San Diego
2017-2025
Resonance Research (United States)
2024
The Ohio State University
2024
Medical University of South Carolina
2024
Università di Camerino
2024
Wake Forest University
2023
University at Buffalo, State University of New York
2022
Rancho BioSciences (United States)
2021
University of Chicago
2016
University of Rochester
2010-2015
Obesity is influenced by genetic and environmental factors. Despite the success of human genome-wide association studies, specific genes that confer obesity remain largely unknown. The objective this study was to use outbred rats identify loci underlying related morphometric metabolic traits.
The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold increases contiguity 290-fold compared with its predecessor. Gene annotations are now more complete, improving mapping precision genomic, transcriptomic, proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains substrains using mRatBN7.2. defined...
Inhibition of mixed lineage kinase 3 (MLK3) is a potential strategy for treatment Parkinson's disease and HIV-1 associated neurocognitive disorders (HAND), requiring an inhibitor that can achieve significant brain concentration levels. We report here URMC-099 (1) orally bioavailable (F = 41%), potent (IC50 14 nM) MLK3 with excellent exposure in mouse PK models minimal interference key human CYP450 enzymes or hERG channels. The compound inhibits LPS-induced TNFα release microglial cells,...
BackgroundMultiple factors contribute to the etiology of addiction, including genetics, sex, and a number addiction-related behavioral traits. One trait where individuals assign incentive salience food stimuli ("sign-trackers", ST) are more impulsive compared those that do not ("goal-trackers", GT), as well sensitive drugs drug stimuli. Furthermore, this GT/ST phenotype predicts differences in other measures. Recent studies have implicated gut microbiota key regulator brain behavior, shown...
Heterogeneous Stock (HS) rats are a genetically diverse outbred rat population that is widely used for studying genetics of behavioral and physiological traits. Mapping Quantitative Trait Loci (QTL) associated with transcriptional changes would help to identify mechanisms underlying these We generated genotype transcriptome data five brain regions from 88 HS rats. identified 21 392 cis-QTLs expression splicing across all validated their effects using allele specific data. 80 cases where...
Addiction vulnerability is associated with the tendency to attribute incentive salience reward predictive cues. Both addiction and attribution of are influenced by environmental genetic factors. To characterize contributions attribution, we performed a genome-wide association study (GWAS) in cohort 1596 heterogeneous stock (HS) rats. Rats underwent Pavlovian conditioned approach task that characterized responses food-associated stimuli ("cues"). Responses ranged from cue-directed...
Common genetic factors likely contribute to multiple psychiatric diseases including mood and substance use disorders. Certain stable, heritable traits reflecting temperament, termed externalizing or internalizing, play a large role in modulating vulnerability these To model tendencies, we selectively bred rats for high low exploration novel environment [bred High Responders (bHR) vs. Low (bLR)]. identify genes underlying the response selection, phenotyped genotyped 538 from an F2 cross...
Human immunodeficiency virus-associated neurological disease (HAND) still causes significant morbidity, despite success reducing viral loads with combination antiretroviral therapy. The dopamine (DA) system is particularly vulnerable in HAND. We hypothesize that early, “reversible” DAergic synaptic dysfunction occurs long before neuron loss. As such, aging human virus (HIV)-infected individuals may be to other age-related neurodegenerative diseases like Parkinson's (PD), underscoring the...
Abstract Sensitivity to cocaine and its associated stimuli (“cues”) are important factors in the development maintenance of addiction. Rodent studies suggest that this sensitivity is related, part, propensity attribute incentive salience food cues, which, turn, contributes self-administration, cue-induced relapse drug-seeking. Whereas each these traits has established links drug use, relatedness between individual themselves not been well characterized preclinical models. To end, a cue was...
Many personality traits are influenced by genetic factors. Rodents models provide an efficient system for analyzing contribution to these traits. Using 1,246 adolescent heterogeneous stock (HS) male and female rats, we conducted a genome-wide association study (GWAS) of behaviors measured in open field, including locomotion, novel object interaction, social interaction. We identified 30 significant quantitative trait loci (QTL). multiple criteria, the presence high impact genomic variants...
Abstract Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host maladaptive behavioral traits associated with range neuropsychiatric disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This dysregulation is influenced by genetic factors. For example, enrichment produces beneficial neurobehavioral effects animal models such The present study determined on measures related regulation...
Abstract Both emotional and social traits interact with genetic factors to influence smoking behavior. We previously established a socially acquired nicotine intravenous self-administration model where learning of nicotine-associated odor cue reversed conditioned flavor aversion promoted intake. In this study, we first phenotyped ~800 adolescent heterogeneous stock rats in open field, novel object interaction, elevated plus maze, marble burying behaviors. These were then on...
Opioid misuse is a prominent public health concern, although patterns of use may confer different vulnerability to relapse. Continuous-access (ContA) self-administration has traditionally been used in preclinical models study drug-motivated behaviors and produces robust escalation intake tolerance development. Alternatively, studies using intermittent access (IntA), where occurs discrete drug-available periods, suggest that overall be dissociable from subsequent increases motivation (i.e.,...
Abstract The increased prevalence of opioid use disorder (OUD) makes it imperative to disentangle the biological mechanisms contributing individual differences in OUD vulnerability. shows strong heritability, however genetic variants vulnerability remain poorly defined. We performed a genome-wide association study using over 850 male and female heterogeneous stock (HS) rats identify genes underlying behaviors associated with such as nociception, well heroin-taking, extinction seeking...
The intestinal microbiome influences health and disease. Its composition is affected by host genetics environmental exposures. Understanding genetic effects critical but challenging in humans, due to the difficulty of detecting, mapping interpreting them. To address this, we analysed four cohorts outbred laboratory rats exposed distinct controlled environments. We found that polygenic were consistent across identified three replicated microbiome-associated loci. One involved a...
Genome-wide association studies ( GWAS ) have implicated specific alleles and genes as risk factors for numerous complex traits. However, translating results into biologically therapeutically meaningful discoveries remains extremely challenging. Most identify noncoding regions of the genome, suggesting that differences in gene regulation are major driver trait variability. To better integrate with regulatory polymorphisms, we previously developed PrediXcan (also known “transcriptome-wide...
Background Transposable elements constitute a significant portion of eukaryotic genomes, yet their role in chromatin organization remains poorly understood. Methods This study aimed to computationally investigate the density patterns transposons around contact points identified from public Micro-C conformation data human cell culture. The peak various transposable families and subfamilies were studied within 100kb window centered on points. analysis was focused most abundant transposons,...
A secreted glycoprotein (GP) with apparent molecular mass of 90 kDa produced by cultured embryonic cells Drosophila melanogaster was isolated and partially characterized. GP is enriched Ser + Thr Pro residues that constitute up to 30% the total number amino acids. An abundant carbohydrate moiety (40% mass) mainly represented vertebrate mucin‐type O‐linked disaccharide units Gal(β1–3)‐GalNAc, occupying about a half rendering molecule high resistance protease action. few N ‐glycans are also...
A vexing observation in genome-wide association studies (GWASs) is that parallel analyses different species may not identify orthologous genes. Here, we demonstrate cross-species translation of GWASs can be greatly improved by an analysis co-localization within molecular networks. Using body mass index (BMI) as example, show the genes associated with BMI humans lack significant agreement those identified rats. However, networks interconnecting these substantial overlap, highlighting common...
Human Immunodeficiency Virus-1 (HIV-1)-associated neurocognitive disorder (HAND) is likely neuroinflammatory in origin, believed to be triggered by inflammatory and oxidative stress responses cytokines HIV protein gene products such as the transactivator of transcription (Tat). Here we demonstrate increased messenger RNA for nuclear factor-kappa B (NF-κB) family member, factor RelB, brain doxycycline-induced Tat transgenic mice, RelB synthesis Tat-exposed microglial cells. Since genetic...