Blocking Metabotropic Glutamate Receptor Subtype 7 via the Venus Flytrap Domain Promotes a Chronic Stress-Resilient Phenotype in Mice.

Chronic psychosocial stress participates prominently in the etiology of various psychiatric conditions and comorbid somatic pathologies; however, suitable pharmacotherapy of these disorders is still of high medical need. During the last few decades, research on mGlu receptors advanced remarkably and much attention was given to the mGlu7 subtype. Here, genetic mGlu7 ablation, short-term pharmacological mGlu7 blockade, as well as siRNA-mediated knockdown of mGlu7 were shown to result in an acute anti-stress, antidepressant- and anxiolytic-like phenotype in mice. Moreover, we recently revealed a prominent stress-protective effect of genetic mGlu7 ablation also with respect to chronic psychosocial stress. In addition, we are able to demonstrate in the present study that the chronic pharmacological blockade of mGlu7 interferes with various chronic stress-induced alterations. For this, we used the chronic subordinate colony housing (CSC), a mouse model of chronic male subordination, in combination with chronic treatment with the mGlu7-selective orthosteric-like antagonist XAP044 (7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one). Interestingly, XAP044 dose-dependently ameliorates hypothalamic-pituitary-adrenal axis dysfunctions, thymus atrophy, as well as the CSC-induced increase in innate anxiety. Taken together, our findings provide further evidence for the role of mGlu7 in chronic psychosocial stress-induced alterations and suggests the pharmacological blockade of mGlu7 as a promising therapeutic approach for the treatment of chronic stress-related pathologies in men.

Dyskalemia: a management problem for students.

BACKGROUND: Although dyskalemia is common, its management can be problematic for students and general practitioners, especially when it occurs in patients with heart and renal failure. The basic academic knowledge of general medicine students, who have often not yet encountered clinical situations of dyskalemia, remains unclear in this regard. OBJECTIVES: The purpose of this study was to evaluate the knowledge and reflexive practices of general medicine students in regard to dyskalemia. METHODS: A cross-sectional survey, based on a self-questionnaire, of all of the students enrolled in general medicine studies at the Faculty of Medicine at the University of Nancy (France) at the end of their degree. The students were asked questions pertaining to specific clinical situations. The answers were compared to the information provided in the medical curriculum as well as to the relevant European guidelines. RESULTS: We collected 290 of the questionnaires (participation rate: 81.2%). The hyper- and hypokalemia thresholds considered pathological (3.5-5.0 mmol/L) were known by 78% and 67% of the students, respectively. The perception of danger in case of severe hypokalemia was underestimated by 62.7% of them. In most cases, the proposed management of hyperkalemia in heart and renal failure did not comply with the relevant guidelines. The students tended to favor permanent discontinuation of the administration of converting enzyme inhibitors (ACE) and/or mineralocorticoid receptor antagonists (MRA) without considering the need for their reintroduction (51.6%). Sodium polystyrene sulfate was frequently seen as an appropriate first-line treatment for hyperkalemia (45%). CONCLUSIONS: The knowledge and competence of general medicine students appear to be lacking for hyperkalemia in heart and renal failure, and they are long way from full compliance with the relevant European guidelines. Exposure to complex clinical situations as part of the medical curriculum, therefore, seems essential to improve the way dyskalemia is managed in France.

Substantial direct fitness gains of workers in a highly eusocial ant.

Hamilton's theory of inclusive fitness suggests that helpers in animal societies gain fitness indirectly by increasing the reproductive performance of a related beneficiary. Helpers in cooperatively breeding birds, mammals and primitively eusocial wasps may additionally obtain direct fitness through inheriting the nest or mating partner of the former reproductive. Here, we show that also workers of a highly eusocial ant may achieve considerable direct fitness by producing males in both queenless and queenright colonies. We investigated the reproductive success of workers of the ant Temnothorax crassispinus in nature and the laboratory by dissecting workers and determining the origin of males by microsatellite analysis. We show that workers are capable of activating their ovaries and successfully producing their sons independently of the presence of a queen. Genotypes revealed that at least one fifth of the males in natural queenright colonies were not offspring of the queen. Most worker-produced males could be assigned to workers that were unrelated to the queen, suggesting egg-laying by drifting workers.

Ant workers produce males in queenless parts of multi-nest colonies.

Workers of several social insects are capable of gaining direct fitness by laying unfertilized eggs, which then develop into males. However, under queenright conditions, direct reproduction of workers is usually prevented by queen-induced regulatory mechanisms. In nature, some ant colonies inhabit multiple nests sites (polydomy). This might allow workers to escape queen control and to reproduce. However, whether worker-produced brood survives after colony reunion in seasonally polydomous species remains unclear. In several species, worker-produced eggs and male-destined larvae are selectively destroyed in queenright colonies. Here, we test whether workers discriminate between queen- and worker-produced larvae during colony reunion. We examined the reproductive success of workers in queenless subcolonies of our study species Temnothorax crassispinus. Our results show that present brood did not inhibit worker reproduction but had a positive effect on worker lifespan. Larvae produced by workers were readily integrated into queenright subcolonies during colony reunion and these larvae successfully developed into adult males.