Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal-PFC connectivity. Altered hippocampal-PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1-PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity

High intake of sugars and starch, low number of meals and low roughage intake are associated with equine gastric ulcer syndrome in a Belgian cohort

Equine gastric ulcer syndrome (EGUS) is a pathological condition affecting the glandular and squamous regions of the stomach. It is characterized by non-specific clinical signs, behavioural changes or can also be found without any overt clinical manifestations. Nutritional factors such as intermittent feeding, high sugars and starch intake, large amounts of straw as forage and prolonged time without access to forage have all been associated with an increased risk of equine squamous gastric disease (ESGD). The aim of this study was to investigate which nutritional practices are commonly seen in clinical ESGD cases in Belgium. Medical records of 27 horses referred to the equine nutritional service at Ghent University (2013-2018) due to equine gastric ulcer lesions were reviewed. Twenty-one healthy horses referred for dietary evaluation during the same period were selected as control cases (CC). Dietary evaluation was performed on an individual basis. Forage/concentrate ratio on dry matter basis, forage content in the diet, total dietary sugars and starch intake per day and per meal were analysed. Retrospective descriptive and statistical analyses were performed. Significantly, higher amounts of forage intake (%DM per BW) in the CC vs. ESGD group were noted (p <= .05) with average values of 1.39 (SD +/- 0.27) and 1.27 (SD +/- 0.70) respectively. There were no significant differences for sugars and starch intake in g/kg BW/day (p = .18). However, the sugars and starch intake per meal (g/kg BW/meal) in the CC group (average value 1.06, SD +/- 0.56) was significantly (p < .001) lower than in the EGUS group (average value 1.85 SD +/- 0.78). Forage intake below the recommended absolute minimum value as well as high sugars and starch intake were most commonly associated with EGUS in the present case series. An adequate diet formulation taking into account these main nutritional factors is therefore essential to avoid gastric problems in horses

Live Imaging of Xwnt5A-ROR2 Complexes

Secreted molecules of the Wnt family regulate key decisions in embryogenesis and adult tissue homeostasis by activating a complex network of Wnt signaling pathways. Although the different branches of Wnt signaling have been studied for more than 25 years, fluorophore tagged constructs for live cell imaging of Wnt molecules activating the Wnt/β-catenin pathway have become available only recently. We have generated a fluorophore tagged Wnt construct of the Xenopus Wnt5a protein (Xwnt5A) with the enhanced green fluorescent protein (EGFP), Xwnt5A-EGFP. This construct activates non-canonical Wnt pathways in an endocytosis dependent manner and is capable of compensating for the loss of endogenous Xwnt5A in Xenopus embryos. Strikingly, non-canonical Wnt pathway activation was restricted to short-range signaling while an inhibitory effect was observed in transwell cell cultures taken as long-range signaling model sytem. We used our Xwnt5A-EGFP construct to analyze in vivo binding of Wnt5A to its co-receptor ROR2 on the microscopic and on the molecular level. On the microscopic level, Xwnt5A-EGFP clusters in the membrane and recruits ROR2-mCherry to these clusters. Applying dual-colour dual-focus line-scanning fluorescence correlation spectroscopy on dorsal marginal zone explants, we identified membrane tethered Xwnt5A-EGFP molecules binding to ROR2-mCherry molecules. Our data favour a model, in which membrane-tethered Wnt-5A recruits ROR2 to form large ligand/receptor clusters and signals in an endocytosis-dependent manner

La chirurgie vaginale prothétique peut-elle être proposée aux patientes âgées de plus de 75 ans ?

International audiencePrevalence of pelvic organ prolapse will increase with the aging of the population. Concerning the treatment of pelvic organ prolapse, transvaginal route is often preferred for elderly women. However few data are available concerning transvaginal mesh surgery in this population. The aim of this study was to compare efficiency and complications of transvaginal mesh surgery between women aged over 75 and younger women.La chirurgie par voie vaginale est souvent privilégiée pour le traitement du prolapsus chez les patientes âgées. Cependant peu de données existent sur les résultats de la chirurgie prothétique dans cette population. L’objectif de cette étude était donc d’évaluer l’efficacité ainsi que les complications de la chirurgie vaginale prothétique chez les patientes âgées de plus de 75 ans par rapport aux patientes plus jeunes