The Paleocene-Eocene Flagstaff Formation in the Sixmile Canyon area of the Wasatch Plateau, Central Utah

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Neural origins of human sickness in interoceptive responses to inflammation

BACKGROUND: Inflammation is associated with psychological, emotional, and behavioral disturbance, known as sickness behavior. Inflammatory cytokines are implicated in coordinating this central motivational reorientation accompanying peripheral immunologic responses to pathogens. Studies in rodents suggest an afferent interoceptive neural mechanism, although comparable data in humans are lacking. METHODS: In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Profile of Mood State questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed a high-demand color word Stroop task during functional magnetic resonance imaging. Blood samples were performed at baseline and immediately after scanning. RESULTS: Typhoid but not placebo injection produced a robust inflammatory response indexed by increased circulating interleukin-6 accompanied by a significant increase in fatigue, confusion, and impaired concentration at 3 hours. Performance of the Stroop task under inflammation activated brain regions encoding representations of internal bodily state. Spatial and temporal characteristics of this response are consistent with interoceptive information flow via afferent autonomic fibers. During performance of this task, activity within interoceptive brain regions also predicted individual differences in inflammation-associated but not placebo-associated fatigue and confusion. Maintenance of cognitive performance, despite inflammation-associated fatigue, led to recruitment of additional prefrontal cortical regions. CONCLUSIONS: These findings suggest that peripheral infection selectively influences central nervous system function to generate core symptoms of sickness and reorient basic motivational states. PMID:19409533[PubMed - indexed for MEDLINE] PMCID: PMC2885492Free PMC Articl

Vascular Architecture of the Lactating and Non-Lactating Teat of the Bitch: A Scanning Electron- and Light Microscope Study

Tissues from fourteen mammary glands of eight bitches were prepared for scanning electron microscopy of vascular corrosion casts and for histology to study the vasculature of the lactating and non-lactating teats. The densely-meshed mammary dermal capillary network formed ridges and troughs. The teat ducts were vascularized by a relatively densely-meshed capillary network which drained into veins longitudinally oriented to the ducts. Between eight and fifteen teat duct openings were seen on the tip of the teat, that were sometimes divided by a septum. The inner vascularization of the teat showed that the main papillary arteries divided into undulating secondary papillary arteries which presented numerous semi-constrictions and loops. Their structure may help during erection of the teat. Arteriovenous anastomoses found at different points may participate in blood flow maintenance during suckling, heat regulation and teat erection. Veins freely anastomosed and ran longitudinally to the axis of the teat. They exhibited numerous bicuspid valves. In non-lactating teats, vessels showed the same main architecture and characteristics mentioned above, although these were considerably less marked. The structure of the vascular elements in the teat of the bitch could favor blood flow during suckling and suggest that vessels adapt to the physiological situation

Error management theory and the adaptive significance of transgenerational maternal-stress effects on offspring phenotype

It is well established that circulating maternal stress hormones (glucocorticoids, GCs) can alter offspring phenotype. There is also a growing body of empirical work, within ecology and evolution, indicating that maternal GCs link the environment experienced by the mother during gestation with changes in offspring phenotype. These changes are considered to be adaptive if the maternal environment matches the offspring\u27s environment and maladaptive if it does not. While these ideas are conceptually sound, we lack a testable framework that can be used to investigate the fitness costs and benefits of altered offspring phenotypes across relevant future environments. We present error management theory as the foundation for a framework that can be used to assess the adaptive potential of maternal stress hormones on offspring phenotype across relevant postnatal scenarios. To encourage rigorous testing of our framework, we provide field-testable hypotheses regarding the potential adaptive role of maternal stress across a diverse array of taxa and life histories, as well as suggestions regarding how our framework might provide insight into past, present, and future research. This perspective provides an informed lens through which to design and interpret experiments on the effects of maternal stress, provides a framework for predicting and testing variation in maternal stress across and within taxa, and also highlights how rapid environmental change that induces maternal stress may lead to evolutionary traps

Error management theory and the adaptive significance of transgenerational maternal‐stress effects on offspring phenotype

It is well established that circulating maternal stress hormones (glucocorticoids, GCs) can alter offspring phenotype. There is also a growing body of empirical work, within ecology and evolution, indicating that maternal GCs link the environment experienced by the mother during gestation with changes in offspring phenotype. These changes are considered to be adaptive if the maternal environment matches the offspring’s environment and maladaptive if it does not. While these ideas are conceptually sound, we lack a testable framework that can be used to investigate the fitness costs and benefits of altered offspring phenotypes across relevant future environments. We present error management theory as the foundation for a framework that can be used to assess the adaptive potential of maternal stress hormones on offspring phenotype across relevant postnatal scenarios. To encourage rigorous testing of our framework, we provide field‐testable hypotheses regarding the potential adaptive role of maternal stress across a diverse array of taxa and life histories, as well as suggestions regarding how our framework might provide insight into past, present, and future research. This perspective provides an informed lens through which to design and interpret experiments on the effects of maternal stress, provides a framework for predicting and testing variation in maternal stress across and within taxa, and also highlights how rapid environmental change that induces maternal stress may lead to evolutionary traps.This article provides a quantitative framework as a means of generating field‐testable hypotheses regarding the adaptive potential of maternal stress under different scenario combinations. By providing a mechanistic basis for examining the adaptive potential of maternal stress effects, our overall aim is not only to provide a means for explaining patterns and testing new hypotheses, but to catalyze the study of maternal stress effects under this framework across a diversity of species, life histories, and environments.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145404/1/ece34074_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145404/2/ece34074.pd

Error management theory and the adaptive significance of transgenerational maternal-stress effects on offspring phenotype

It is well established that circulating maternal stress hormones (glucocorticoids, GCs) can alter offspring phenotype. There is also a growing body of empirical work, within ecology and evolution, indicating that maternal GCs link the environment experienced by the mother during gestation with changes in offspring phenotype. These changes are considered to be adaptive if the maternal environment matches the offspring\u27s environment and maladaptive if it does not. While these ideas are conceptually sound, we lack a testable framework that can be used to investigate the fitness costs and benefits of altered offspring phenotypes across relevant future environments. We present error management theory as the foundation for a framework that can be used to assess the adaptive potential of maternal stress hormones on offspring phenotype across relevant postnatal scenarios. To encourage rigorous testing of our framework, we provide field-testable hypotheses regarding the potential adaptive role of maternal stress across a diverse array of taxa and life histories, as well as suggestions regarding how our framework might provide insight into past, present, and future research. This perspective provides an informed lens through which to design and interpret experiments on the effects of maternal stress, provides a framework for predicting and testing variation in maternal stress across and within taxa, and also highlights how rapid environmental change that induces maternal stress may lead to evolutionary traps

Chronic Restraint Stress Impairs Voluntary Wheel Running but Has No Effect on Food-Motivated Behavior in Mice

Chronic restraint stress is known to cause significant alterations of mitochondrial biology. However, its effects on effort-based behavior and the sensitivity of these effects to treatments that restore mitochondrial function have not been assessed. Based on the hypothesis that the behavioral consequences of this stressor should be more severe for an energy demanding activity than for an energy procuring activity, we compared the effects of chronic restraint stress on the performance of male mice trained to use a running wheel or to nose poke for a food reward in an operant conditioning cage. In accordance with our hypothesis, we observed that exposure of mice to 2-hour daily restraint sessions for 14 to 16 days during the light phase of the cycle reliably decreased voluntary wheel running but had no effect on working for food in a fixed ratio 10 schedule of food reinforcement or in a progressive ratio schedule of food reinforcement. This dissociation between the two types of behavioral activities could reflect an adaptive response to the constraint imposed by chronic restraint stress on mitochondria function and its negative consequences on energy metabolism. To determine whether it is the case, we administered mesenchymal stem cells intranasally to chronically restrained mice to repair the putative mitochondrial dysfunction induced by chronic restraint stress. This intervention had no effect on wheel running deficits. Assessment of mitochondrial gene expression in the brain of mice submitted to chronic restraint stress revealed an increase in the expression of genes involved in mitochondrial biology that showed habituation with repetition of daily sessions of restraint stress. These original findings can be interpreted to indicate that chronic restraint stress induces behavioral and mitochondrial adjustments that contribute to metabolic adaptation to this stressor and maintain metabolic flexibility

Equipped for Life in the Boreal Forest: The Role of the Stress Axis in Mammals

The hypothalamic-pituitary-adrenal axis (stress axis) plays a central role in equipping mammals to succeed in the challenging environment of the boreal forest. Over the last 20 years, we have tackled a broad range of topics to understand how the stress axis functions in four key herbivore species. The central challenge for snowshoe hares is coping with their predators, whereas for the others, it is primarily coping with each other (especially during reproduction) and with their physical environment. Hares are severely stressed by their predators during the population decline. The predator threat causes major changes in the stress axis of hares and reduces their reproduction; in addition, acting through maternal programming, it is the most plausible explanation for the extended period of low numbers following the population decline. Arctic ground squirrel males have an intense breeding season for two to three weeks in early spring, after which many of them die. The functioning of their stress axis changes markedly and is key in meeting their energy demands during this period. In contrast, red-backed vole males, though also short-lived, breed repeatedly only in the summer of their life, and their stress axis shows no change in function. However, their reproductive effort negatively affects their long-term survival. Territorial red squirrels experience marked interannual fluctuations in their major food source (white spruce seed), resulting in major fluctuations in their densities and consequently in the intensity of territorial competition. Changes in the densities of red squirrels also alter maternal stress hormone levels, inducing adaptive plasticity in offspring postnatal growth rates that prepares offspring for the environment they will encounter at independence. To survive winter, red squirrels need to defend their territories year-round, and the basis of this defense appears to be adrenal dehydroepiandrosterone, which has the benefits, but not the costs, of gonadal steroids. Arctic ground squirrels survive winter by hibernating in deeply frozen ground. Unlike all other hibernators, they have evolved a unique adaptation: high levels of adrenal androgens in summer to accumulate protein reserves that they then burn in winter. With a rapidly changing climate, the stress axis will play a key role in permitting northern animals to adapt, but the linkages between the changes in the abiotic and biotic components of the boreal forest and the phenotypic plasticity in the stress response of its inhabitants are not well understood for these or any other herbivore species.L’axe hypothalamo-hypophyso-surrénalien (l’axe du stress) joue un rôle central pour aider les mammifères à réussir dans l’environnement difficile de la forêt boréale. Ces 20 dernières années, nous nous sommes penchés sur une vaste gamme de sujets afin de comprendre comment fonctionne l’axe du stress chez quatre grandes espèces herbivores. Pour le lièvre d’Amérique, le défi central consiste à faire face à ses prédateurs, tandis que pour les autres espèces, ce défi consiste à se faire face mutuellement (surtout pendant la reproduction) de même qu’à faire face à leur environnement physique. Les lièvres subissent beaucoup de stress de la part de leurs prédateurs pendant la diminution de la population. La menace des prédateurs est la cause de changements majeurs sur l’axe du stress des lièvres, ce qui a pour effet de réduire leur reproduction. De plus, en raison de leur programmation maternelle, il s’agit de l’explication la plus plausible justifiant la période prolongée de leur faible nombre suivant la diminution de la population. Le spermophile arctique mâle a une période de reproduction intense pendant deux à trois semaines au début du printemps et après cela, un grand nombre d’entre eux meurent. Le fonctionnement de son axe de stress change de façon marquée, ce qui est essentiel à sa demande en énergie pendant cette période. Par contraste, le campagnol à dos roux mâle, même s’il ne vit également pas longtemps, se reproduit à répétition seulement pendant l’été de sa vie, et le fonctionnement de son axe de stress ne montre aucun changement. Cependant, ses efforts de reproduction ont des incidences négatives sur sa survie à long terme. Pour sa part, la principale source d’alimentation (les graines d’épinette blanche) de l’écureuil roux territorial connaît des fluctuations interannuelles marquées, ce qui se traduit par une fluctuation majeure en matière de densité de cette espèce animale et, par conséquent, en matière d’intensité de la concurrence pour le territoire. Les changements de densité d’écureuils roux exercent également une influence sur les taux d’hormone maternelle de stress, ce qui donne lieu à une plasticité adaptative des taux de croissance postnatale de la progéniture qui prépare la progéniture pour faire face à l’environnement dans lequel ils évolueront au stade de l’indépendance. Pour survivre à l’hiver, l’écureuil roux doit défendre son territoire à l’année et pour y parvenir, il se sert de la déhydroépiandrostérone surrénalienne, qui comporte les avantages des stéroïdes gonades, sans les coûts. Le spermophile arctique survit à l’hiver en hibernant dans le sol gelé en profondeur. Contrairement à tous les autres hibernateurs, il s’est développé une adaptation unique en son genre, soit des taux élevés d’androgènes surrénaliens en été qui lui permettent d’accumuler les réserves de protéines qu’il brûle ensuite pendant l’hiver. À la lumière du changement climatique rapide, l’axe de stress jouera un rôle-clé pour permettre aux animaux du Nord de s’adapter, mais les liens entre les changements des composantes abiotiques et biotiques de la forêt boréale et la plasticité phénotypique de la réaction de stress de ses habitants ne sont pas bien compris dans le cas de ces espèces herbivores ou de toute autre espèce herbivore

Social effects of territorial neighbours on the timing of spring breeding in North American red squirrels

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordOrganisms can affect one another’s phenotypes when they socially interact. Indirect genetic effects occur when an individual’s phenotype is affected by genes expressed in another individual. These heritable effects can enhance or reduce adaptive potential, thereby accelerating or reversing evolutionary change. Quantifying these social effects is therefore crucial for our understanding of evolution, yet estimates of indirect genetic effects in wild animals are limited to dyadic interactions. We estimated indirect phenotypic and genetic effects, and their covariance with direct effects, for the date of spring breeding in North American red squirrels (Tamiasciurus hudsonicus) living in an array of territories of varying spatial proximity. Additionally, we estimated indirect effects and the strength of selection at low and high population densities. Social effects of neighbours on the date of spring breeding were different from zero at high population densities but not at low population densities. Indirect phenotypic effects accounted for a larger amount of variation in the date of breeding than differences attributable to the among-individual variance, suggesting social interactions are important for determining breeding dates. The genetic component to these indirect effects was however not statistically significant. We therefore showcase a powerful and flexible method that will allow researchers working in organisms with a range of social systems to estimate indirect phenotypic and genetic effects, and demonstrate the degree to which social interactions can influence phenotypes, even in a solitary species

Resolution of Cisplatin-Induced Fatigue Does Not Require Endogenous Interleukin-10 in Male MiceB

Based on previous results showing a pivotal role of endogenous interleukin-10 (IL-10) in the recovery from cisplatin-induced peripheral neuropathy, the present experiments were carried out to determine whether this cytokine plays any role in the recovery from cisplatin-induced fatigue in male mice. Fatigue was measured by decreased voluntary wheel running in mice trained to run in a wheel in response to cisplatin. Mice were treated with a monoclonal neutralizing antibody (IL-10na) administered intranasally during the recovery period to neutralize endogenous IL-10. In the first experiment, mice were treated with cisplatin (2.83 mg/kg/day) for five days and IL-10na (12 μg/day for three days) five days later. In the second experiment, they were treated with cisplatin (2.3 mg/kg/day for 5 days twice at a five-day interval) and IL10na (12 μg/day for three days) immediately after the last injection of cisplatin. In both experiments, cisplatin decreased body weight and reduced voluntary wheel running. However, IL-10na did not impair recovery from these effects. These results show that the recovery from the cisplatin-induced decrease in wheel running does not require endogenous IL-10 in contrast to the recovery from cisplatin-induced peripheral neuropathy