Wfs1 Is Expressed In Dopaminoceptive Regions Of The Amniote Brain And Modulates Levels Of D1-Like Receptors

During amniote evolution, the construction of the forebrain has diverged across different lineages, and accompanying the structural changes, functional diversification of the homologous brain regions has occurred. This can be assessed by studying the expression patterns of marker genes that are relevant in particular functional circuits. In all vertebrates, the dopaminergic system is responsible for the behavioral responses to environmental stimuli. Here we show that the brain regions that receive dopaminergic input through dopamine receptor D1 are relatively conserved, but with some important variations between three evolutionarily distant vertebrate lines–house mouse (Mus musculus), domestic chick (Gallus gallus domesticus) / common quail (Coturnix coturnix) and red-eared slider turtle (Trachemys scripta). Moreover, we find that in almost all instances, those brain regions expressing D1-like dopamine receptor genes also express Wfs1. Wfs1 has been studied primarily in the pancreas, where it regulates the endoplasmic reticulum (ER) stress response, cellular Ca2+ homeostasis, and insulin production and secretion. Using radioligand binding assays in wild type and Wfs1-/- mouse brains, we show that the number of binding sites of D1-like dopamine receptors is increased in the hippocampus of the mutant mice. We propose that the functional link between Wfs1 and D1-like dopamine receptors is evolutionarily conserved and plays an important role in adjusting behavioral reactions to environmental stimuli

Effect of chronic valproic Acid treatment on hepatic gene expression profile in wfs1 knockout mouse

Valproic acid (VPA) is a widely used anticonvulsant and mood-stabilizing drug whose use is often associated with drug-induced weight gain. Treatment with VPA has been shown to upregulate Wfs1 expression in vitro. Aim of the present study was to compare the effect of chronic VPA treatment in wild type (WT) and Wfs1 knockout (KO) mice on hepatic gene expression profile. Wild type, Wfs1 heterozygous, and homozygous mice were treated with VPA for three months (300?mg/kg i.p. daily) and gene expression profiles in liver were evaluated using Affymetrix Mouse GeneChip 1.0?ST array. We identified 42 genes affected by Wfs1 genotype, 10 genes regulated by VPA treatment, and 9 genes whose regulation by VPA was dependent on genotype. Among the genes that were regulated differentially by VPA depending on genotype was peroxisome proliferator-activated receptor delta (Ppard), whose expression was upregulated in response to VPA treatment in WT, but not in Wfs1 KO mice. Thus, regulation of Ppard by VPA is dependent on Wfs1 genotype

Controlling complexity: the clinical relevance of mouse complex genetics.

Experimental animal models are essential to obtain basic knowledge of the underlying biological mechanisms in human diseases. Here, we review major contributions to biomedical research and discoveries that were obtained in the mouse model by using forward genetics approaches and that provided key insights into the biology of human diseases and paved the way for the development of novel therapeutic approaches

Changes in climate, catchment vegetation and hydrogeology as the causes of dramatic lake-level fluctuations in the Kurtna Lake District, NE Estonia

Numerous lakes in the world serve as sensitive indicators of climate change. Water levels for lakes Ahnejärv and Martiska, two vulnerable oligotrophic closed-basin lakes on sandy plains in northeastern Estonia, fell more than 3 m in 1946–1987 and rose up to 2 m by 2009. Earlier studies indicated that changes in rates of groundwater abstraction were primarily responsible for the changes, but scientifically sound explanations for water-level fluctuations were still lacking. Despite the inconsistent water-level dataset, we were able to assess the importance of changing climate, catchment vegetation and hydrogeology in water-level fluctuations in these lakes. Our results from water-balance simulations indicate that before the initiation of ground­water abstraction in 1972 a change in the vegetation composition on the catchments triggered the lake-level decrease. The water-level rise in 1990–2009 was caused, in addition to the reduction of groundwater abstraction rates, by increased precipitation and decreased evaporation. The results stress that climate, catchment vegetation and hydrogeology must all be considered while evaluating the causes of modern water-level changes in lakes

Work-in-progress: Soft-skills development for higher education engineering and economic students using HERA collaborative serious games

This paper presents the objectives and developments in the scope of the HERA project, an Erasmus + initiative whose purpose is to address the interdisciplinary soft skill needs in the fields of engineering and economics. HERA deploys active learning to expose Higher Education students to complex challenges, the solution to which requires the integration of interdisciplinary knowledge in engineering and economics in a manner that emulates real-world problem-solving processes. The article describes the HERA serious game environment and proposes the game dynamics, scenarios and challenges, showing how they can be used to achieve the project goals. © 2020 IEEE

Limbic system associated membrane protein (LSAMP) and wolframin (WFS1) as the potential targets for influencing emotional disorders

Invited Lectur

Students and Teachers’ Need for Sustainable Education: Lessons from the Pandemic

The COVID-19 pandemic challenged the sustainability of higher education as millions of students were forced out of school, shifting to online learning instead of in-class education. In the Erasmus+ project, Virtual Presence in Higher Education Hybrid Learning Delivery (VIE), we were concerned with the level of readiness and the ability of higher-education students and teachers to face this changing situation. This paper reports the results of a survey which assessed the experiences that students and teachers had during the pandemic and, in particular, the development of soft skills through active learning methodologies. The project results show that there are still some unmet needs, but existing digital technologies, tools, and platforms already provide valuable solutions both for students and teachers that ensure a continuation of high-quality learning experiences. © 2022 by the authors

Wfs1 mutation makes mice sensitive to insulin-like effect of acute valproic acid and resistant to streptozocin

Valproic acid (VLP) is a widely used anticonvulsant and mood-stabilizing drug that relieves the endoplasmic reticulum (ER) stress response, a pathogenetic process related to diabetes. The aim of the present study was to evaluate whether acute valproic acid is able to interfere with glucose intolerance in two different diabetes models: The first model was a Wfs1 mutant mouse with an elevated ER stress response and the second model a streptozocin-induced diabetic mouse. VLP (300 mg/kg, i.p.) was administered to Wfs1 knockout (KO) mice and glucose tolerance test was performed 15 min later. VLP did not have an effect on the course of the glucose tolerance test in wild-type mice, while it did normalize the glucose intolerance in Wfs1 knockout mice. Acute valproic acid also lowered the blood glucose levels in streptozocin-treated mice and potentiated the effect of insulin in these mice. Thus, acute valproic acid is effective in lowering blood glucose levels possibly by potentiating insulin action in both Wfs1 KO mice and in streptozocin-induced type 1 diabetic mice

A Virtual Environment to Support Digital Education Readiness and Creative Skills

The VIE (Virtual presence in higher education hybrid learning environments) is an Erasmus+ project which was approved in the extraordinary call during the COVID pandemic to support digital education readiness and collaborative skills. This project is aimed to design and implement a highly interactive digital collaborative learning platform. VIE envisions a digital work environment through which students will design solutions to learning challenges through brainstorming and synthesizing by building on each other's ideas. The VIE solution will simulate the way that students work together in a classroom towards design solution by taking notes on a common blackboard that all can see and update at the same time. The service functionality will include: avatar presence through which participants will be able to recognize their team members in the digital environment; sharing of ideas in the form of building blocks that all can see, review, edit, and combine simultaneously towards building a larger solution from smaller contributions; and project organization that allows the effective management and prioritization of tasks in a visual and engaging manner. Interaction will be supported through both desktop and mobile devices for maximizing access flexibility. © 2021 IEEE