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    Ancestral and developmental cold alter brown adipose tissue function and adult thermal acclimation in Peromyscus

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    Small, non-hibernating endotherms increase their thermogenic capacity to survive seasonal cold, through adult phenotypic flexibility. In mammals, this response is primarily driven by remodeling of brown adipose tissue (BAT), which matures postnatally in altricial species. In many regions, ambient temperatures can vary dramatically throughout the breeding season. We used second-generation lab-born Peromyscus leucopus, cold exposed during two critical developmental windows, to test the hypothesis that adult phenotypic flexibility to cold is influenced by rearing temperature. We found that cold exposure during the postnatal period (14 °C, birth to 30 days) accelerated BAT maturation and permanently remodeled this tissue. As adults, these mice had increased BAT activity and thermogenic capacity relative to controls. However, they also had a blunted acclimation response when subsequently cold exposed as adults (5 °C for 6 weeks). Mice born to cold-exposed mothers (14 °C, entire pregnancy) also showed limited capacity for flexibility as adults, demonstrating that maternal cold stress programs the offspring thermal acclimation response. In contrast, for P. maniculatus adapted to the cold high alpine, BAT maturation rate was unaffected by rearing temperature. However, both postnatal and prenatal cold exposure limited the thermal acclimation response in these cold specialists. Our results suggest a complex interaction between developmental and adult environment, influenced strongly by ancestry, drives thermogenic capacity in the wild

    Effects of Tongue Strength Training on Mealtime Function in Long-Term Care

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    Purpose The primary aim of this study was to determine the feasibility and effectiveness of an 8-week tongue-strengthening intervention protocol for seniors with mild to moderately severe cognitive impairment in the long-term care setting. Outcome measures of interest included tongue strength, mealtime duration, and food intake. Method In this pre–post group study of treatment outcomes, data were collected from 7 adults (aged 84–99 years). Participants were observed across a series of mealtimes to determine mealtime duration and intake before and after 16 treatment sessions. During therapy, participants performed isometric strength exercises and tongue pressure accuracy tasks using the Iowa Oral Performance Instrument (model number 2.1, IOPI Medical). Differences in tongue strength as a function of treatment were explored between the first 3 and final 3 sessions using univariate repeated-measures analysis of variance. Single-subject methods were used to explore baseline and posttreatment data for measures of mealtime function. Results Anterior and posterior tongue strength increased significantly with therapy. There were no changes in mealtime function. Conclusions This study shows proof of concept that some older adults with cognitive impairment are able to participate in a tongue-strengthening intervention and achieve improvements in tongue strength. Failure to find evidence of associated changes of mealtime function suggests that mealtime measures may not be directly sensitive to changes in tongue strength. </jats:sec

    Evolved Mechanisms of Aerobic Performance and Hypoxia Resistance in High-Altitude Natives

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    Comparative physiology studies of high-altitude species provide an exceptional opportunity to understand naturally evolved mechanisms of hypoxia resistance. Aerobic capacity (VO2max) is a critical performance trait under positive selection in some high-altitude taxa, and several high-altitude natives have evolved to resist the depressive effects of hypoxia on VO2max. This is associated with enhanced flux capacity through the O2transport cascade and attenuation of the maladaptive responses to chronic hypoxia that can impair O2transport. Some highlanders exhibit elevated rates of carbohydrate oxidation during exercise, taking advantage of its high ATP yield per mole of O2. Certain highland native animals have also evolved more oxidative muscles and can sustain high rates of lipid oxidation to support thermogenesis. The underlying mechanisms include regulatory adjustments of metabolic pathways and to gene expression networks. Therefore, the evolution of hypoxia resistance in high-altitude natives involves integrated functional changes in the pathways for O2and substrate delivery and utilization by mitochondria.</jats:p

    Changes in gut microbiota during development of compulsive checking and locomotor sensitization induced by chronic treatment with the dopamine agonist quinpirole

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    Long-term treatment of rats with the D2/D3 dopamine agonist quinpirole induces compulsive checking (proposed as animal model of obsessive-compulsive disorder) and locomotor sensitization. The mechanisms by which long-term use of quinpirole produces those behavioral transformations are not known. Here we examined whether changes in gut microbiota play a role in these behavioral phenomena, by monitoring the development of compulsive checking and locomotor sensitization at the same time as measuring the response of gut microbiota to chronic quinpirole injections. Two groups of rats received nine injections of saline (n=16) or quinpirole (n=15; 0.25 mg/kg), at weekly intervals for the first 5 weeks and then two injections per week until the end of treatment. After each injection, rats were placed on a large open field for 55 min, and their behavior was video recorded for subsequent analysis. Fecal matter was collected after each trial and frozen for bacterial community profiling of the 16S rRNA gene, using paired-end reads of the V3 region. The results indicated that the induction of locomotor sensitization and compulsive checking was accompanied by changes in several communities of bacteria belonging to the order Clostridiales (class Clostridia, phylum Firmicutes), and predominantly in Lachnospiraceae and Ruminococcaceae families of bacteria. It is suggested that changes in these microbes may serve to support the energy use requirements of compulsive checking and obsessive-compulsive disorder

    Evolved changes in phenotype across skeletal muscles in deer mice native to high altitude

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    The cold and hypoxic conditions at high altitude necessitate high metabolic O2 demands to support thermogenesis while hypoxia reduces O2 availability. Skeletal muscles play key roles in thermogenesis, but our appreciation of muscle plasticity and adaptation at high altitude has been hindered by past emphasis on only a small number of muscles. We examined this issue in deer mice (Peromyscus maniculatus). Mice derived from both high-Altitude and low-Altitude populations were born and raised in captivity and then acclimated as adults to normoxia or hypobaric hypoxia (12 kPa O2 for 6 8 wk). Maximal activities of citrate synthase (CS), cytochrome c oxidase (COX), b-hydroxyacyl-CoA dehydrogenase (HOAD), hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) were measured in 20 muscles involved in shivering, locomotion, body posture, ventilation, and mastication. Principal components analysis revealed an overall difference in muscle phenotype between populations but no effect of hypoxia acclimation. High-Altitude mice had greater activities of mitochondrial enzymes and/or lower activities of PK or LDH across many (but not all) respiratory, limb, core and mastication muscles compared with low-Altitude mice. In contrast, chronic hypoxia had very few effects across muscles. Further examination of CS in the gastrocnemius showed that population differences in enzyme activity stemmed from differences in protein abundance and mRNA expression but not from population differences in CS amino acid sequence. Overall, our results suggest that evolved increases in oxidative capacity across many skeletal muscles, at least partially driven by differences in transcriptional regulation, may contribute to high-Altitude adaptation in deer mice

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