Long-term implantation of acoustic transmitters induces chronic inflammatory cytokine expression in adult rainbow trout (Oncorhynchus mykiss)

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.vetimm.2018.10.003 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Telemetry transmitters are frequently used in studies of wild fish migration and behavior. Although the effects of surgically implanted transmitters on survival, tag retention, healing and growth have been studied, there has been little research regarding the potential immune response induced by these transmitters. In the current study, mature rainbow trout received either surgical implantation of an acoustic transmitter or a sham surgical procedure. These fish were then sampled over a 10-week period so that pro-inflammatory cytokine expression in the spleen, peritoneal cavity lymphocytes and muscle at the surgical site could be analyzed. There were no significant differences in transcript expression for the spleen and muscle tissue between fish that had a transmitter and those that received the surgical procedure alone. However, transmitter presence significantly increased the expression of IL-6, IL-1β and TNFα in the peritoneal cells at 10 weeks indicating that tagged fish may be coping with chronic inflammation. Furthermore, tagged male fish had a higher inflammatory response in 10-week peritoneal lavage samples when compared to their tagged mature female counterparts, providing some evidence that mature female rainbow trout may have suppressed immune function when sexually mature. Externally, fish appeared to heal at similar rates regardless of the presence or absence of the transmitter, but the tag itself was prone to encapsulation and adhesion to the body wall and/or surgical site. This suggests that fish tagged with large intraperitoneal implants may not behave similarly to their wild counterparts. This research could aid in the development of improved telemetry tags that are more biocompatible, economical and better able to track fish behavior/movement.Canada Research Council Research ChairNSERC Discovery Grant [217529

Long-term implantation of acoustic transmitters induces chronic inflammatory cytokine expression in adult rainbow trout (Oncorhynchus mykiss)

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.vetimm.2018.10.003 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Telemetry transmitters are frequently used in studies of wild fish migration and behavior. Although the effects of surgically implanted transmitters on survival, tag retention, healing and growth have been studied, there has been little research regarding the potential immune response induced by these transmitters. In the current study, mature rainbow trout received either surgical implantation of an acoustic transmitter or a sham surgical procedure. These fish were then sampled over a 10-week period so that pro-inflammatory cytokine expression in the spleen, peritoneal cavity lymphocytes and muscle at the surgical site could be analyzed. There were no significant differences in transcript expression for the spleen and muscle tissue between fish that had a transmitter and those that received the surgical procedure alone. However, transmitter presence significantly increased the expression of IL-6, IL-1β and TNFα in the peritoneal cells at 10 weeks indicating that tagged fish may be coping with chronic inflammation. Furthermore, tagged male fish had a higher inflammatory response in 10-week peritoneal lavage samples when compared to their tagged mature female counterparts, providing some evidence that mature female rainbow trout may have suppressed immune function when sexually mature. Externally, fish appeared to heal at similar rates regardless of the presence or absence of the transmitter, but the tag itself was prone to encapsulation and adhesion to the body wall and/or surgical site. This suggests that fish tagged with large intraperitoneal implants may not behave similarly to their wild counterparts. This research could aid in the development of improved telemetry tags that are more biocompatible, economical and better able to track fish behavior/movement.Canada Research Council Research ChairNSERC Discovery Grant [217529

Developing a New Agritech Product to Increase and Enhance the Uptake of Vitamin D and Other Vitamins and Minerals in Mushrooms

This study aimed to test and refine a new method of mushroom vitamin and mineral enrichment with the use of novel ‘during-growth’ and ‘water-on’ liquid supplements. Through experimental trials, different formulations and dosages, as produced by NutriGain Ltd, were compared along with untreated and UV treated mushrooms, all in commercial conditions, through collaboration with Drinkwater Mushrooms Ltd. This aimed to assess the product in its suitability for providing nutritionally relevant content of Vitamin D, as well as the Bvitamins; B1, B2, B6 and B12, and Selenium. Vitamin D is the most important target of enrichment due to the possibility in replacing the current energyintensive and high associated carbon emitting method of UV enrichment, which comes with many issues such as limited application (only brown mushrooms) and slowed packaging for application after growth. This has great potential benefits and opportunities for novel food products and public health by increasing levels of vitamins to combat deficiencies which are becoming more common in the UK and globally, especially vitamin D deficiencies. The experiment involved commercial growth trials using white button mushrooms conducted at Drinkwater Mushrooms Ltd., with applications of product produced by NutriGain and analysis of vitamins and mineral content at Lancaster Environment Centre using HPLC and ICP-OES methods. A dosage rate in vitamin D of around 125-150 mg/m2 in a calcium-based formulation of the liquid supplement was identified to yield higher vitamin D contents than other formulations tested, such as potassium-based, and was successful in matching UV-produced levels of vitamin D, without discolouration of white mushrooms. Enrichment with the novel MycroNutrient product gave a significant improvement compared to untreated samples, at levels of around 30 µg/g DW, whilst also providing nutritionally relevant levels of B-vitamins. All at a predicted annual carbon emission reduction of 99% in the process alone through the replacement of the UV method for this new treatment being applied to all mushrooms, both white and brown

Assessment of female reproductive status by male longtailed macaques, Macaca fascicularis, under natural conditions

Recent theories on primate sexual selection have paid increasing attention to the importance of reproductive strategies of females living in multimale groups. However, the extent to which females are able effectively to conceal or advertise the time of ovulation as part of these strategies remains unclear. Few studies have investigated the ability of males to discern female reproductive status under natural conditions, and none has taken into account differences in male rank, and thus ability to gain access to females or cues. We tested male assessment of a female's fertile phase under natural conditions in longtailed macaques. We used timing of mate guarding by dominant males and the response of subordinate males towards the repeated playback of a female copulation call to measure male interest in females throughout the ovarian cycle. Relating the degree of male interest to female reproductive status, as determined noninvasively by faecal hormone analysis, we found that interest in females shown by both dominant and subordinate males was strongest during and around the fertile phase. Our results also indicate that males were better able to recognize the fertile period in conception than in nonconception cycles. Furthermore, our finding of a strong positive relation between male interest and female oestrogen levels in all cycles indicates that at least some of the cues used by males to assess female reproductive status are oestrogen related

Sestrins are evolutionarily conserved mediators of exercise benefits.

Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the metabolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism. Among the various targets modulated by Sestrin in response to exercise, AKT and PGC1α are critical for the Sestrin effects in extending endurance. These results indicate that Sestrin is a key integrating factor that drives the benefits of chronic exercise to metabolism and physical endurance

Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer

© 2021, The Author(s). Low-coverage whole-genome sequencing (LC-WGS) can provide insight into oncogenic molecular changes. Serum extracellular vesicles (EV) represent a novel liquid biopsy source of tumoral DNA. This study compared copy number alteration (CNA) profiles generated from LC-WGS of formalin-fixed paraffin-embedded (FFPE) tumoral DNA and EV-DNA obtained from cancer patients. Patients with squamous cell carcinoma of the base of tongue (n = 3) and cutaneous squamous cell carcinoma (n = 2) were included. LC-WGS (0.5-1X coverage) was performed on FFPE-DNA and serum EV-DNA. Similarity between CNA profiles was analysed using QDNAseq. FFPE samples had a mean CNA of 31 (range 17–50) over 1.9 × 109 (range 1.0–2.6 × 109) bp in length, and EV samples had a mean CNA value of 17 (range 7–19) over 7.6 × 108 (range 2.9–15 × 108) bp in length. A mean of 8 (range 0–21) CNA over 5.9 × 108 (range 1.6–14 × 108) bp in length was found to overlap between EV and FFPE-derived samples per patient. Although the mean correlation efficient between samples was r = 0.34 (range − .08 to 0.99), this was not statistically significant (p \u3e 0.05). Regions of highest deletion and duplication in FFPE samples were not well reflected in the EV-DNA. Selected CNA regions in EV-associated DNA were reflective of the primary tumor, however appreciation of global CNA and areas of most significant change was lost. The utility of LC-WGS of EV-derived DNA is likely limited to molecular alterations of known interest

The Impact of Enhanced and Non-Enhanced Biochars on the Catabolism of 14C-Phenanthrene in Soil

Biochar is a by-product from the pyrolysis of biomass and has a great potential in soil amendment due to its carbon and nutrient-rich properties. The aim of this study was to investigate the impact of increasing amounts (0, 0.01, 0.1, 0.2, 0.5 and 1.0%) of two types of biochar (so-called enhanced and non-enhanced) to soil on the biodegradation of 14C-phenanthrene. Enhanced biochar contains inoculants which are designed to potentially stimulate microbial activity and promote biological function in soil. After 100 d of incubation, the addition of 0.5% and 1% enhanced (EbioC) and non-enhanced biochars (NEbioC) led to longer lag phases, reduced rates and extents of 14C-phenanthrene in amended soil. However, in soils amended with 0.01%, 0.1% and 0.2% amendments, extents of mineralisation of 14C-phenanthrene increased and were found to be higher in the EBioC- as compared to the NEbioC-amended soils. Increasing soil-phenanthrene contact time also increased 14C-phenanthrene mineralisation in soil which had received smaller amounts of EBioC. Application of both EbioC and NEbioC also enriched the soil microbial populations during the incubation. However, it was found that phenanthrene-degrading microbial populations declined as soil contact time increased; this was particularly true for soils receiving larger amounts of due to reduction in the mobile/bioaccessible fraction of the phenanthrene in soil. The findings revealed the importance of the type and amount of biochar that may be added to soil to stimulate or enhance organic contaminant biodegradation

Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood-brain barrier dysfunction module.

Blood vessels in the CNS form a specialized and critical structure, the blood-brain barrier (BBB). We present a resource to understand the molecular mechanisms that regulate BBB function in health and dysfunction during disease. Using endothelial cell enrichment and RNA sequencing, we analyzed the gene expression of endothelial cells in mice, comparing brain endothelial cells with peripheral endothelial cells. We also assessed the regulation of CNS endothelial gene expression in models of stroke, multiple sclerosis, traumatic brain injury and seizure, each having profound BBB disruption. We found that although each is caused by a distinct trigger, they exhibit strikingly similar endothelial gene expression changes during BBB disruption, comprising a core BBB dysfunction module that shifts the CNS endothelial cells into a peripheral endothelial cell-like state. The identification of a common pathway for BBB dysfunction suggests that targeting therapeutic agents to limit it may be effective across multiple neurological disorders

MRI Relaxometry for Quantitative Analysis of USPIO Uptake in Cerebral Small Vessel Disease

A protocol for evaluating ultrasmall superparamagnetic particles of iron oxide (USPIO) uptake and elimination in cerebral small vessel disease patients was developed and piloted. B1-insensitive R1 measurement was evaluated in vitro. Twelve participants with history of minor stroke were scanned at 3-T MRI including structural imaging, and R1 and R2* mapping. Participants were scanned (i) before and (ii) after USPIO (ferumoxytol) infusion, and again at (iii) 24–30 h and (iv) one month. Absolute and blood-normalised changes in R1 and R2* were measured in white matter (WM), deep grey matter (GM), white matter hyperintensity (WMH) and stroke lesion regions. R1 measurements were accurate across a wide range of values. R1 (p < 0.05) and R2* (p < 0.01) mapping detected increases in relaxation rate in all tissues immediately post-USPIO and at 24–30 h. R2* returned to baseline at one month. Blood-normalised R1 and R2* changes post-infusion and at 24–30 h were similar, and were greater in GM versus WM (p < 0.001). Narrower distributions were seen with R2* than for R1 mapping. R1 and R2* changes were correlated at 24–30 h (p < 0.01). MRI relaxometry permits quantitative evaluation of USPIO uptake; R2* appears to be more sensitive to USPIO than R1. Our data are explained by intravascular uptake alone, yielding estimates of cerebral blood volume, and did not support parenchymal uptake. Ferumoxytol appears to be eliminated at 1 month. The approach should be valuable in future studies to quantify both blood-pool USPIO and parenchymal uptake associated with inflammatory cells or blood-brain barrier leak

Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes.

BACKGROUND: Evidence from several recent metabolomic studies suggests that increased concentrations of triacylglycerols with shorter (14-16 carbon atoms), saturated fatty acids are associated with insulin resistance and the risk of type 2 diabetes. Although causality cannot be inferred from association studies, patients in whom the primary cause of insulin resistance can be genetically defined offer unique opportunities to address this challenge. METHODS: We compared metabolite profiles in patients with congenital lipodystrophy or loss-of-function insulin resistance (INSR gene) mutations with healthy controls. RESULTS: The absence of significant differences in triacylglycerol species in the INSR group suggest that changes previously observed in epidemiological studies are not purely a consequence of insulin resistance. The presence of triacylglycerols with lower carbon numbers and high saturation in patients with lipodystrophy suggests that these metabolite changes may be associated with primary adipose tissue dysfunction. The observed pattern of triacylglycerol species is indicative of increased de novo lipogenesis in the liver. To test this we investigated the distribution of these triacylglycerols in lipoprotein fractions using size exclusion chromatography prior to mass spectrometry. This associated these triacylglycerols with very low-density lipoprotein particles, and hence release of triacylglycerols into the blood from the liver. To test further the hepatic origin of these triacylglycerols we induced de novo lipogenesis in the mouse, comparing ob/ob and wild-type mice on a chow or high fat diet, confirming that de novo lipogenesis induced an increase in relatively shorter, more saturated fatty acids. CONCLUSIONS: Overall, these studies highlight hepatic de novo lipogenesis in the pathogenesis of metabolic dyslipidaemia in states where energy intake exceeds the capacity of adipose tissue