Biology subjects

Dixon, B.

Publications and source records attributed to Dixon, B..

6 recordsLinked to original sources

bioRxiv2026

Transcriptional regulation of the rainbow trout spleen corticotropin-releasing factor system in response to inflammatory challenges: roles of NF-kB and cortisol

The corticotropin-releasing factor (CRF) system bidirectionally interacts with cytokines and other immune-related components in mammals. However, the nature of these interactions remains poorly characterized in other vertebrates, including teleost fishes. To gain insight into the relationship between immune responses and the CRF system in teleosts, we explored how CRF system components were transcriptionally regulated in immune organs of rainbow trout (Oncorhynchus mykiss). We first characterized the CRF system in the spleen and head kidney--two primary immune organs in teleosts--and found that many CRF system components were present in both tissues, but splenic expression was consistently greater. Changes in the abundance of splenic CRF system components following vaccination (which transiently stimulated inflammatory responses and cytokine production) indicated contrasting and time-dependent regulation of CRF receptor 1 (CRFR1; suppression) and CRFR2 (stimulation) activities in response to an inflammatory challenge. Using spleen explant cultures, we then evaluated whether these effects were mediated by either of nuclear factor kappa B (NF-{kappa}B; a pro-inflammatory transcription factor) or cortisol (an anti-inflammatory hormone). At baseline, cultured spleens increased cytokine production and exhibited transcriptional changes in CRF system components comparable to those observed following vaccination. Cortisol treatment and NF-{kappa}B inhibition both attenuated the rise in cytokine transcription; however, cortisol treatment generally affected transcripts influencing CRFR1 activity, while NF-{kappa}B inhibition reduced CRFR2 activity. Overall, our data provide novel insight into CRF system regulation in the spleen and suggest that cortisol and inflammatory cytokines differentially regulate CRFR1 and CRFR2 activity within this organ.

physiology↗

bioRxiv2025

Optical Brain Pulse Monitoring for Detection of Large Vessel Occlusion Stroke in a Sheep Model

Early stroke detection and treatment are critical for improving patient outcomes. Optical brain pulse monitoring (OBPM) uses red and infrared light to capture brain pulse waveforms reflecting arteriole-to-venous pressure levels driving microvascular blood flow. This study assessed OBPMs potential to detect middle cerebral artery occlusion (MCAo) and reperfusion in a clinically relevant sheep model. Stroke was induced in 11 Merino wethers via 4-hour occlusion of the right MCA, followed by 6 hours of reperfusion. OBPM recordings were taken at baseline, MCAo, early and late reperfusion. The OBPM brain pulse waveform classes were classified based on the presence of arterial or central venous circulation wave features. Magnetic resonance imaging assessed infarct volume at 2 hours post-reperfusion. Invasive brain tissue oxygen and intracranial pressures were also monitored. The OBPM brain pulse waveform classes changed during MCAo and reperfusion (p <0.0001). MCAo was associated brain pulses with venous circulation features (p = 0.0007). Reperfusion was associated with the return of arterial circulation features (p = 0.001). Early reperfusion was also associated with an increase in the brain pulse amplitude (p < 0.05) and the respiratory wave amplitude (p < 0.05). OBPM may aid in early stroke detection and reperfusion assessment following intervention.

physiology↗

bioRxiv2024

Development of multi-species qPCR assays for a stress transcriptional profiling (STP) Chip to assess the resilience of salmonids to changing environments

Ecologically and socio-economically important salmonid fishes in Canada are threatened by diverse environmental stressors. However, predicting species responses to environmental change requires understanding the underlying molecular mechanisms governing environmental stress tolerance. Developing advanced molecular genetic tools will provide opportunities to predict how salmonid fishes will respond to environmental stressors and assess their adaptive potential and vulnerability into the future. Here, we developed a panel of Taqman quantitative PCR (qPCR) assays designed to measure mRNA transcript abundance at selected candidate loci for use across salmonids. We designed and applied those assays for use in a high-throughput nanofluidic OpenArray Stress Transcriptional Profiling Chip (STP-Chip) capable of 2688 simultaneous qPCR at multiple gene loci (112 targets for 12 samples in duplicate). Using the nanofluidic STP-Chip, we tested these 112 multi-species qPCR assays using gill, liver and muscle tissue from eight species of salmonids across four genera. Of the selected 112 assays, 69 assays showed amplification in gill, 64 in liver, and 67 in muscle across all eight salmonid species. The percentage of assays that showed amplification across three tissues varied between genera: In general, Salmo, Oncorhynchus, and Salvelinus species showed a higher success rate than Coregonus species. Stress, circadian rhythm, apoptosis, growth-metabolism, and detoxification-relevant assays showed high success rates for amplification across all salmonid species for all three tissues. In contrast, neural plasticity, appetite regulation, osmoregulation, immune function, endocrine disruption, and hypoxia-relevant assays showed low success. Not surprisingly, we observed tissue-specific variation among qPCR amplification patterns. There were significant differences in mRNA transcript abundance among species across the four genera, but we did not see variation between species from the same genus. These qPCR assays can be used to design custom STP-Chips that can be used for quantifying stress in salmonid fish, improving health through more accurate diagnostic tests for disease, and monitoring adaptation to accelerated climate change regionally and globally.

genomics↗

bioRxiv2022

A 1D Model Characterizing the Role of Spatiotemporal Contraction Distributions on Lymph Transport

BackgroundLymphedema is a condition in which the two primary functions of the lymphatic system, immunity and lymph transport, are compromised. Computational models of lymphatic function to characterize lymph transport have proved useful in quantifying changes in lymph transport in health and disease; however, much is unknown regarding the regulation of contractions throughout a lymphatic network. The purpose of this paper is to study the role of pacemaking cells and contractile wave propagation on lymph transport using a 1-D mathematical model. MethodA 1D fluid-solid modeling framework with constitutive relationships were employed to characterize the interaction between the contracting vessel wall and the lymph flow during contractions. The time-space distribution of contraction waves along the length of a three-lymphangion chain, was determined by prescribing the location of pacemaking cells and parameters that govern the contractile wave propagation, with the total contractile response at each location determined as the summation of the local electrical signals. ResultsSpatiotemporal changes in radius and lymphangion ejection fraction from our illustrative simulations mimic well values reported in isolated lymphatics from the wild-type (WT) and Smmhc-CreERT2;Cx45fx/fx knock-out (KO) reported in the literature. The flow rate is 5.43 and 2.45 L/hr in the WT and the KO (average) models, respectively. The average and the peak WSS in the WT model are 0.08 and 4 dyn/cm2 and -0.03 and 0.87 dyn/cm2 in the KO (average) models, respectively. ConclusionsThe factors that govern the timing of lymphatic contractions remain largely unknown; but these factors likely play a central role in health and disease. This modeling framework captures well lymphatic contractile wave propagations and how it relates to lymph transport and may motivate novel assays and experimental endpoints to evaluate subtle changes in lymphatic pumping function in the development and progression of lymphedema.

bioengineering↗

bioRxiv2021

Commercial vaccines do not confer protection against two genetic strains of Piscirickettsia salmonis, LF-89-like and EM-90-like, in Atlantic salmon.

In Atlantic salmon, vaccines have failed to control and prevent Piscirickettsiosis, for reasons that remain elusive. In this study, we report the efficacy of a commercial vaccine developed with the Piscirickettsia salmonis isolate AL100005 against other two isolates which are considered highly and ubiquitously prevalent in Chile: LF-89-like and EM-90-like. Two cohabitation trials were performed to mimic real-life conditions and vaccine performance: 1) post smolt fish were challenged with a single infection of LF-89-like, 2) adults were coinfected with EM-90-like and a low coinfection of sea lice. In the first trial, the vaccine delayed smolt mortalities by two days; however, unvaccinated and vaccinated fish did not show significant differences in survival (unvaccinated: 60.3%, vaccinated: 56.7%; p = 0.28). In the second trial, mortality started three days later for vaccinated fish than unvaccinated fish. However, unvaccinated and vaccinated fish did not show significant differences in survival (unvaccinated: 64.6%, vaccinated: 60.2%, p= 0.58). Thus, we found no evidence that the evaluated vaccines confer effective protection against of LF-89-like or EM-90-like with estimated relative survival proportions (RPSs) of -9% and -12%, respectively. More studies are necessary to evaluate whether pathogen heterogeneity is a key determinant of the vaccine efficacy against P. salmonis.

immunology↗

bioRxiv2018

MinION re-sequencing of Giardia genomes and de novo assembly of a new Giardia isolate

BackgroundGenomes of the parasite Giardia duodenalis are relatively small for eukaryotic genomes, yet there are only six publicly available. Difficulties in assembling the tetraploid G. duodenalis genome from short read sequencing data likely contribute to this lack of genomic information. We sequenced three isolates of G. duodenalis (AWB, BGS, and beaver) on the Oxford Nanopore Technologies MinION whose long reads have the potential to address genomic areas that are problematic for short reads.\n\nResultsUsing a hybrid approach that combines MinION long reads and Illumina short reads to take advantage of the continuity of the long reads and the accuracy of the short reads we generated reference quality genomes for each isolate. The genomes for two of the isolates were evaluated against the available reference genomes for comparison. The third genome for which there is no previous data was then assembled. The long reads were used to find structural variants in each isolate to examine heterozygosity. Consistent with previous findings based on SNPs, Giardia BGS was found to be considerably more heterozygous than the other isolates that are from Assemblage A. We also find an enrichment of variant-specific surface proteins in some of the structural variant regions.\n\nConclusionsOur results show that the MinION can be used to generate reference quality genomes in Giardia and further be used to identify structural variant regions that are an important source of genetic variation not previously examined in these parasites.

genomics↗