Dietary Lipids Affect the Onset of Hibernation in the Garden Dormouse (Eliomys quercinus): Implications for Cardiac Function

Dietary lipids strongly influence patterns of hibernation in heterotherms. Increased dietary uptake of n-6 polyunsaturated fatty acids (PUFAs), particularly of linoleic acid (LA, C18:2 n-6), enables animals to reach lower body temperatures (Tb), lengthens torpor bout duration, and results in lower energy expenditure during hibernation. Conversely, dietary n-3 PUFA impacts negatively on hibernation performance. PUFA in surrounding phospholipids (PLs) presumably modulate the temperature-dependent activity of the sarcoplasmic reticulum (SR) Ca2+ ATPase 2 (SERCA2) and thus determine the threshold Tb still allowing proper heart function during torpor. We tested the effect of diets enriched with 10% of either corn oil (“CO,” high n-6 PUFA, e.g., LA) or menhaden oil [“MO,” long-chain n-3 PUFA, e.g., docosahexaenoic acid (DHA)] on hibernation performance and SERCA2 activity levels during torpor in garden dormice, an insectivorous, fat-storing hibernator. Prior to hibernation, individuals fed the MO diet showed an almost nine-times higher DHA levels and 30% lower LA proportions in white adipose tissue (WAT), reflecting the fatty acid composition of SR membranes, compared to CO-diet fed animals. When fed the MO diet, dormice significantly delayed their mean onset of hibernation by almost 4 days (range: 0–12 days), compared with CO-diet fed animals. Hibernation onset correlated positively with WAT-DHA levels and negatively with WAT-LA proportions prior to hibernation. Subsequently, hibernating patterns were similar between the two dietary groups, despite a significant difference in WAT-LA but not in WAT-DHA levels in mid-hibernation. SR-PL fatty acid composition and SERCA2 activity were identical in torpid individuals from the two dietary groups in mid-hibernation. In line with our previous findings on Syrian hamsters, a granivorous, food-storing hibernator, SERCA2 activity correlated positively with LA and negatively with DHA levels of SR-PL in torpid dormice, although SERCA2 activity was about three-times higher in garden dormice than in Syrian hamsters at similar PL-DHA proportions. Similarly, minimal Tb during torpor decreased as SERCA2 activity increased. We conclude that: (1) fatty acid composition of SR membranes modulates cardiac SERCA2 activity, hence determining the minimum Tb tolerated by hibernators, and (2) high DHA levels prevent hibernators from entering into torpor, but the critical levels differ substantially between species

Investigation of cardiorespiratory effects of the selective 5-HT4 agonist BIMU-8 in etorphine-immobilised goats (Capra aegagrus hircus) in a randomized, blinded and controlled trial

BACKGROUND : Opioid-induced respiratory compromise remains a significant challenge in etorphine-immobilised wildlife. Serotonergic agonists offer a potential avenue for preventing or treating opioid-induced respiratory compromise. We therefore aimed to determine whether the selective 5- hydroxytryptamine receptor 4 (5-HT4) agonist, BIMU-8, reverses opioidinduced respiratory compromise in etorphine-immobilised goats. METHODS : Seven healthy adult goats were immobilised with etorphine, then treated with BIMU-8 or sterile water 5 minutes later in a randomised, prospective cross-over study. Cardiorespiratory variables were measured at 1-minute intervals from 4 minutes before etorphine to 15 minutes after its administration. Arterial blood gas analyses were also performed before and after etorphine administration and the respective treatments. RESULTS : Intravenous injection of BIMU-8 attenuated etorphine-induced respiratory compromise, as indicated by improvements, compared to baseline and between treatments, in respiratory rate (ƒR), peripheral arterial blood oxygen saturation (SpO2), partial pressure of arterial oxygen (PaO2) and the alveolar-arterial oxygen partial pressure gradient (P(A-a)O2). BIMU-8 caused an increase in heart rate and a temporary decrease in arterial blood pressure. Mild movements and slight muscle spasm occurred but BIMU-8 did not reverse immobilisation. CONCLUSION : Our results indicate that BIMU-8 may be a potential drug candidate for the treatment, or prevention, of etorphine-induced respiratory compromise in immobilised ungulateshttps://bvajournals.onlinelibrary.wiley.com/journal/20427670dm2022Centre for Veterinary Wildlife StudiesParaclinical Science

Validation experiment females

Validation experiment females, biological validatio

Glucocorticoid data field Glis glis females

field data, Glis glis females, glucocorticoids, animal parameters and environmental factor

Data from: The insensitive dormouse: reproduction skipping is not caused by chronic stress in Glis glis

Entire populations of edible dormice (Glis glis) can skip reproduction in years without mast seeding of deciduous trees (particularly beech or oak seed), because juveniles require high caloric seeds for growth and fattening prior to hibernation. We hypothesized that, in mast failure years, female dormice may be forced to spend larger amounts of time foraging for low-quality food, which should increase their exposure to predators, mainly owls. This may lead to chronic stress, i.e., long-term increased secretion of Glucocorticoids (GC), which can have inhibitory effects on reproductive function in both female and male mammals. We monitored reproduction in free-living female dormice over three years with varying levels of food availability, and performed a supplemental feeding experiment. To measure stress hormone levels, we determined fecal GC metabolite (GCM) concentrations collected during the day, which reflect hormone secretion rates in the previous nocturnal activity phase. We found that year-to-year differences in beech mast significantly affected fecal GCM levels and reproduction. However, contrary to our hypothesis, GCM levels were lowest in a non-mast year without reproduction, and significantly elevated in full-mast and intermediate years, as well as under supplemental feeding. Variation in owl density in our study area had no influence on GCM levels. Consequently, we conclude that down-regulation of gonads and reproduction skipping in mast-failure years in this species is not caused by chronic stress. Thus, in edible dormice, delayed reproduction apparently is profitable in response to the absence of energy-rich food in non-mast years, but not in response to chronic stress

Circulating Tumor DNA as a Marker for Treatment Response in Metastatic Melanoma Patients Using Next-Generation Sequencing—A Prospective Feasibility Study

We prospectively performed a longitudinal analysis of circulating tumor DNA (ctDNA) from 149 plasma samples and CT scans in Stage III and IV metastatic melanoma patients (n = 20) treated with targeted agents or immunotherapy using two custom next-generation sequencing (NGS) Ion AmpliSeq™ HD panels including 60 and 81 amplicons in 18 genes, respectively. Concordance of matching cancer-associated mutations in tissue and plasma was 73.3%. Mutant allele frequency (MAF) levels showed a range from 0.04% to 28.7%, well detectable with NGS technologies utilizing single molecule tagging like the AmpliSeq™ HD workflow. Median followup time of the tissue and/or plasma positive cohort (n = 15) was 24.6 months and median progression-free survival (PFS) was 7.8 months. Higher MAF ≥ 1% at baseline was not significantly associated with a risk of progression (Odds Ratio = 0.15; p = 0.155). Although a trend could be seen, MAF levels did not differ significantly over time between patients with and without a PFS event (p = 0.745). Depending on the cell-free DNA amount, NGS achieved a sensitivity down to 0.1% MAF and allowed for parallel analysis of multiple mutations and previously unknown mutations. Our study indicates that NGS gene panels could be useful for monitoring disease burden during therapy with ctDNA in melanoma patients