Biology subjects

Gill, T.

Publications and source records attributed to Gill, T..

6 recordsLinked to original sources

bioRxiv2026

Seizures and tauopathy following neurotrauma are mediated by prion protein and metabotropic glutamate receptor 5

Traumatic brain injury (TBI) is one of the world's leading causes of death and disability and a major risk factor for dementias. The primary dementia associated with TBI is chronic traumatic encephalopathy (CTE), a neurodegenerative disease classified as a tauopathy, in which toxic tau molecules lead to disease pathologies and degeneration. The processes that lead to tauopathy and subsequent dementia after TBI remain unclear. Here, we built upon the finding that seizures after TBI may be a mechanism leading to tauopathy, by dissecting the functions of the metabotropic glutamate receptor 5 - cellular prion protein (mGluR5-PrPC) pathway. We delivered TBI to larval in a blast paradigm, and quantified aggregation of Tau via a genetically-encoded Tau-GFP fusion reporter. Zebrafish larvae lacking prp2 (homolog of mammalian cellular Prion Protein, PrPC) displayed a 168% increase in post-traumatic seizures activity after TBI. An mGluR5 agonist (CHPG) reduced post-traumatic seizures, whereas an mGluR5 antagonist (MPEP) increased post-traumatic seizures. Moreover, agonizing mGluR5 reduced tau aggregation and antagonizing mGluR5 increased tau burden. Larvae seizing from convulsants, rather than TBI, were treated with CHPG/MPEP and provided a similar pattern of outcomes, suggesting seizures may be a factor needed for mGluR5 activity to influence tau aggregation. The PrPC-mGluR5 pathway is proposed as one candidate pathomechanism linking TBI to subsequent seizures and tauopathy, and thus it warrants investigation as a target for prophylactic interventions.

neuroscience↗

bioRxiv2024

Personality assessment of synanthropic rhesus macaques: implications and challenges

"What makes animals thrive in human-dominated environments?" is a question that has been extensively researched transcending disciplines, but findings remain inconclusive. Consistent inter-individual differences or personalities can potentially explain the functional significance of habitat-specific traits and their variations that help animals successfully coexist with humans. Rhesus macaques (Macaca mulatta) are the most successful non-human primate in the Anthropocene, living in diverse climatic and environmental conditions. Studying the personalities of synanthropic rhesus macaques can provide insights into the biological traits that facilitate their success in human-dominated environments. We employed a multi-method bottom-up approach of behavioral observations and novelty experiments, standardized for assessing captive non-human primates, to evaluate the personalities of synanthropic adult rhesus macaques (N=52). To our surprise, novelty experiments encountered significant challenges, limiting their effectiveness. However, behavioral observations in the form of focal sampling revealed two repeatable traits: sociability and cautiousness. We found an effect of sex on sociability, where males were more sociable than females. In an additional analysis, we found that individuals who obtained food through contact provisioning had higher cautiousness scores than individuals who obtained food through non-contact provisioning. We discuss how the observed personality traits and their variations potentially offer adaptive advantages in human-dominated environments, where rhesus macaques face both benefits, such as anthropogenic subsidies and reduced predation, and costs, like exposure to anthropogenic stressors. We also emphasize that protocols designed for captive conditions may not be directly applicable to free-living animals. Thus, the study underscores the need to reconsider experimental designs to obtain comparable empirical evidence between captive and non-captive populations to enhance the ecological validity of personality assessments. Nevertheless, empirically identifying traits using observations in synanthropic species like rhesus macaques can still provide valuable insights into the mechanisms that enable certain animals to thrive amidst a rapid expansion of anthropogenic activities. Research highlightsStudying personalities of synanthropic animals can shed light on the biological traits that help them thrive in human-dominated environments. A bottom-up multi-method approach, standardized for assessing captive NHP personalities, was employed to study a population of synanthropic rhesus macaques. Behavioral observations captured two repeatable traits, namely sociability and cautiousness, where comparatively more cautious individuals obtained food through contact provisioning. Novelty experiments faced significant challenges.

animal behavior and cognition↗

bioRxiv2024

A larval zebrafish model of TBI: Optimizing the dose of neurotrauma for discovery of treatments and aetiology

Traumatic brain injuries (TBI) are diverse with heterogeneous injury pathologies, which creates challenges for the clinical treatment and prevention of secondary pathologies such as post-traumatic epilepsy and subsequent dementias. To develop pharmacological strategies that treat TBI and prevent complications, animal models must capture the spectrum of TBI severity to better understand pathophysiological events that occur during and after injury. To address such issues, we improved upon our recent larval zebrafish TBI paradigm emphasizing titrating to different injury levels. We observed coordination between an increase in injury level and clinically relevant injury phenotypes including post-traumatic seizures (PTS) and tau aggregation. This preclinical TBI model is simple to implement, allows dosing of injury levels to model diverse pathologies, and can be scaled to medium- or high-throughput screening.

neuroscience↗

bioRxiv2021

Axial spondyloarthritis patients have altered mucosal IgA response to oral and fecal microbiota

ObjectiveTo investigate whether axial spondyloarthritis (AxSpA) patients have an altered immunoglobulin A (IgA) response in the gut and oral microbial communities. MethodsWe performed 16S rRNA gene (16S) sequencing on IgA positive (IgA+) and IgA negative (IgA-) fractions (IgA-SEQ) from feces (n=17 AxSpA; n=14 healthy) and saliva (n=17 AxSpA; n=12 healthy), as well as on IgA-unsorted fecal and salivary samples. PICRUSt2 was used to predict microbial metabolic potential in AxSpA patients and healthy controls (HCs). ResultsIgA-SEQ revealed enrichment of several microbes in the fecal (Akkermansia, Ruminococcaceae, Lachnospira) and salivary (Prevotellaceae, Actinobacillus) microbiome in AxSpA patients as compared with HCs. Fecal microbiome from AxSpA patients showed a trend towards increased alpha diversity of the IgA+ fraction and decreased diversity in the IgA- fraction in comparison with HCs, while the salivary microbiome exhibits a significant decrease in alpha diversity in both IgA+ and IgA- fractions. Increased IgA coating of Clostridiales Family XIII correlated with disease severity. Inferred metagenomic analysis suggests perturbation of metabolites and metabolic pathways for inflammation (oxidative phosphorylation, glutathione metabolism) and metabolism (propanoate and butanoate metabolism) in AxSpA patients. ConclusionsAnalyses of fecal and salivary microbes from AxSpA patients reveal distinct populations of immunoreactive microbes using novel IgA-SEQ approach, which were not captured by comparing their relative abundance with HCs. Predictive metagenomic analysis revealed perturbation of metabolites/metabolic pathways in AxSpA patients. Future studies on these immunoreactive microbes may lead to better understanding of the functional role of IgA in maintaining microbial structure and human health.

immunology↗

bioRxiv2020

BBrowser: Making single-cell data easily accessible

BioTurings BBrowser is a software solution that helps scientists effectively analyze single-cell omics data. It combines big data with big computation and modern data visualization to create a unique platform where scientists can interact and obtain important biological insights from the massive amounts of single-cell data. BBrowser has three main components: a curated single-cell database, a big-data analytics layer, and a data visualization module. BBrowser is available for download at: https://bioturing.com/bbrowser/download.

bioinformatics↗

bioRxiv2019

Draft genome assemblies using sequencing reads from Oxford Nanopore Technology and Illumina platforms for four species of North American killifish from the Fundulus genus

Draft de novo reference genome assemblies were obtained from four North American killifish species (Fundulus xenicus, Fundulus catenatus, Fundulus nottii, and Fundulus olivaceus) using sequence reads from Illumina and Oxford Nanopore Technologies PromethION platforms. For each species, the PromethION platform was used to generate 30-45x sequence coverage, and the Illumina platform was used to generate 50-160x sequence coverage. Contig N50 values ranged from 0.4 Mb to 2.7 Mb, and BUSCO scores were consistently above 90% complete using the Eukaryota database. Draft assemblies and raw sequencing data are available for public use. We encourage use and re-use of these data for assembly benchmarking and external analyses.

genomics↗