Wild bank voles (Clethrionomys glareolus) kept in the laboratory under barren housing conditions develop high incidences of type 1 diabetes mellitus due to beta cell-specific lysis in association ...with the appearance of GAD65, IA-2, and insulin autoantibodies. Wild-caught and immediately analyzed voles show no histological signs of diabetes, and the disease may therefore be induced by circumstances related to the housing of the animals in captivity. We tested the possibility that postnatal stress by either maternal separation or water immersion at different intervals would induce diabetes in adult bank voles. We found that low-frequent stress during the first 21 days of life increases, whereas high-frequent stress markedly reduces, the incidence of type 1 diabetes in adulthood. These results differentiate the role of early-experienced stress on subsequent type 1 diabetes development and emphasize that the bank vole may serve as a useful new animal model for the disease.
Wild bank voles (Clethrionomys glareolus) may develop diabetes in laboratory captivity. The aim of this study was to test whether bank voles develop type 1 diabetes in association with Ljungan virus. ...Two groups of bank voles were analyzed for diabetes, pancreas histology, autoantibodies to glutamic acid decarboxylase (GAD65), IA-2, and insulin by standardized radioligand-binding assays as well as antibodies to in vitro transcribed and translated Ljungan virus antigens. Group A represented 101 trapped bank voles, which were screened for diabetes when euthanized within 24 hours of capture. Group B represented 67 bank voles, which were trapped and kept in the laboratory for 1 month before being euthanized. Group A bank voles did not have diabetes. Bank voles in group B (22/67; 33%) developed diabetes due to specific lysis of pancreatic islet beta cells. Compared to nondiabetic group B bank voles, diabetic animals had increased levels of GAD65 (P < .0001), IA-2 (P < .0001), and insulin (P = .03) autoantibodies. Affected islets stained positive for Ljungan virus, a novel picorna virus isolated from bank voles. Ljungan virus inoculation of nondiabetic wild bank voles induced beta-cell lysis. Compared to group A bank voles, Ljungan virus antibodies were increased in both nondiabetic (P < .0001) and diabetic (P = .0015) group B bank voles. Levels of Ljungan virus antibodies were also increased in young age at onset of newly diagnosed type 1 diabetes in children (P < .01). These findings support the hypothesis that the development of type 1 diabetes in captured wild bank voles is associated with Ljungan virus. It is speculated that bank voles may have a possible zoonotic role as a reservoir and vector for virus that may contribute to the incidence of type 1 diabetes in humans.
Wild bank voles ( Clethrionomys glareolus ) may develop diabetes in laboratory captivity. The aim of this study was to test whether bank voles develop type 1 diabetes in association with Ljungan ...virus. Two groups of bank voles were analyzed for diabetes, pancreas histology, autoantibodies to glutamic acid decarboxylase (GAD65), IA‐2, and insulin by standardized radioligand‐binding assays as well as antibodies to in vitro transcribed and translated Ljungan virus antigens. Group A represented 101 trapped bank voles, which were screened for diabetes when euthanized within 24 hours of capture. Group B represented 67 bank voles, which were trapped and kept in the laboratory for 1 month before being euthanized. Group A bank voles did not have diabetes. Bank voles in group B (22/67; 33%) developed diabetes due to specific lysis of pancreatic islet beta cells. Compared to nondiabetic group B bank voles, diabetic animals had increased levels of GAD65 ( P < .0001), IA‐2 ( P < .0001), and insulin ( P = .03) autoantibodies. Affected islets stained positive for Ljungan virus, a novel picorna virus isolated from bank voles. Ljungan virus inoculation of nondiabetic wild bank voles induced beta‐cell lysis. Compared to group A bank voles, Ljungan virus antibodies were increased in both nondiabetic ( P < .0001) and diabetic ( P = .0015) group B bank voles. Levels of Ljungan virus antibodies were also increased in young age at onset of newly diagnosed type 1 diabetes in children ( P < .01). These findings support the hypothesis that the development of type 1 diabetes in captured wild bank voles is associated with Ljungan virus. It is speculated that bank voles may have a possible zoonotic role as a reservoir and vector for virus that may contribute to the incidence of type 1 diabetes in humans.
When caged in groups of three and fed ad libitum, dominant male mice survived longer than subordinate group members which again lived longer than males caged in groups of nine, among whom no rank ...order was established. In groups of nine the social structure was not affected when the food supply was reduced to the lowest level not affecting survival, but in groups of three, food reduction made the survival of both dominant and subordinate animals drop to a level matching that of groups of nine. After challenge with a small dose of Moloney virus, leukemia developed among ad libitum fed subordinate mice in groups of three and members of groups of nine, but not among the dominant animals. Food restriction enhanced the leukemia incidence, but dominant animals continued to go free. We conclude that subordinance and also lack of social hierarchy result in a higher incidence of virus induced leukemia, that severe food restriction does the same, and that the effect of social order on leukemia development prevails even under feeding conditions that nearly abolish group-related differences in survival.
During the last decade, the study of fluctuating asymmetry (FA) in relation to different fitness aspects has become a popular issue in evolutionary biology. FA is suggested to be important as an ...index of selective advantage in both sexual and natural selection. Evidence for these hypotheses is obtained from field studies in which FA is found to be negatively correlated with various fitness components. In this paper, we demonstrate that the apparent significance of FA may depend on assumptions of linearity between size of a trait and FA, and between trait size and fitness. By means of numerical examples, we show that even small, and probably common, deviations from the assumed linearity can bias the statistical analyses to such an extent that it casts serious doubt on the validity of the postulated causal relationship between FA and fitness. We recommend reanalyses of existing data and emphatically suggest that the underlying statistical assumptions are critically evaluated in future studies of FA, especially concerning linear relationships between the variables.
Ninety-six pigs, half females and half castrated males from 12 litters, were housed in 24 groups of four litter mates. From an age of 115 days half of the groups were subjected to chronic stress for ...33 days consisting of a schedule of unpredictable, inescapable electroshocks, and half served as controls. Behavior and performance were measured on all animals in the group, hormone data on one female in each group, and data on ulceration on the castrates. Behaviorally, the pigs did not habituate to 31 days of stress treatment. One to 2 days of stress treatment produced a behavioral activation that after 9 to 10 days was restricted to the time period of potential stress treatment. After 30 to 31 days it was replaced by passive behavior. In the beginning as well as after 30 to 31 days of intermittent stress, time spent sitting was increased. In addition, 6 days of intermittent stress reduced the baseline mean of plasma ACTH. After 33 days of stress the baseline mean of plasma ACTH was normalized, but the time course of diurnal secretion of ACTH was shifted. No effects of the chronic intermittent stress on basic levels of plasma cortisol, performance, or gastric ulceration were evident. In conclusion, the effect of intermittent stress depends on the number of days of intermittent stress treatment and it does not inevitably include changes in the basic levels of cortisol. Thus, assessment of stress must be based on a wide range of variables describing the process.
Ninetysix pigs, half females and half castrated males from 12 litters, were housed in 24 groups of 4 litter mates (2 females, 2 castrates). The pigs were weaned at 4 weeks of age and from the age of ...115 days half of the groups were subjected to a schedule of unpredictable, inescapable electroshocks for 33 days, and half served as control. The adrenocortical reactivity to ACTH stimulation and to an emotional stressor (the procedure associated with initiation of blood collection) was measured in females, whereas the behavioural and pituitary-adrenocortical reactivity to an open field test was measured in castrates, as was the behavioural reactivity in a social test. Intermittent stress increased adrenocortical reactivity to ACTH stimulation significantly. This effect was present within the first week of intermittent stress (p < 0.06), but no difference was found after 4-5 weeks of stress. In contrast, the adrenocortical reactivity to additional emotional stressors was unaffected by stress after one week of intermittent stress, but increased after 4-5 weeks. In the open field test, centre location increased after one week of intermittent stress, whereas exploration decreased and walking and ambulation increased after 4-5 weeks of stress. In addition, 4-5 weeks of intermittent stress decreased aggressiveness in a social test. In conclusion, the change in reactivity to an additional acute stressor during intermittent stress appeared in different variables and contexts at different times during the course of intermittent stress. Thus, assessment of stress based on changed reactivity has to include several distinct measures of behavioural and hormonal reactivity.
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