Dimerization of visinin-like protein 1 is regulated by oxidative stress and calcium and is a pathological hallmark of amyotrophic lateral sclerosis

AbstractRedox control of proteins that form disulfide bonds upon oxidative challenge is an emerging topic in the physiological and pathophysiological regulation of protein function. We have investigated the role of the neuronal calcium sensor protein visinin-like protein 1 (VILIP-1) as a novel redox sensor in a cellular system. We have found oxidative stress to trigger dimerization of VILIP-1 within a cellular environment and identified thioredoxin reductase as responsible for facilitating the remonomerization of the dimeric protein. Dimerization is modulated by calcium and not dependent on the myristoylation of VILIP-1. Furthermore, we show by site-directed mutagenesis that dimerization is exclusively mediated by Cys187. As a functional consequence, VILIP-1 dimerization modulates the sensitivity of cells to an oxidative challenge. We have investigated whether dimerization of VILIP-1 occurs in two different animal models of amyotrophic lateral sclerosis (ALS) and detected soluble VILIP-1 dimers to be significantly enriched in the spinal cord from phenotypic disease onset onwards. Moreover, VILIP-1 is part of the ALS-specific protein aggregates. We show for the first time that the C-terminus of VILIP-1, containing Cys187, might represent a novel redox-sensitive motif and that VILIP-1 dimerization and aggregation are hallmarks of ALS. This suggests that VILIP-1 dimers play a functional role in integrating the cytosolic calcium concentration and the oxidative status of the cell. Furthermore, a loss of VILIP-1 function owing to protein aggregation in ALS could be relevant in the pathophysiology of the disease

Sammenhenger mellom pris, tilskudd og produsert mengde i norsk husdyrproduksjon

To prosjekter angående sammenheng mellom pris, tilskudd og produsert mengde i noen husdyrproduksjoner ligger bak denne rapporten. Arbeidet med prosjektene har gått parallelt, og det har vært et tett samarbeid mellom prosjektmedarbeiderne. En brukergruppe sammensatt av nøkkelpersoner fra næring og offentlig forvaltning har bidratt underveis. Den ene delen er en deskriptiv analyse av utvikling av priser, tilskudd og produksjon i perioden 1998-2018. Den andre delen er empiriske analyser for storfe, fordelt på ammeku og melkeku, samt sau/lam og gris. Rapporten gir en kompakt og samlet oversikt over utviklingen i pris, tilskudd og produsert mengde i norsk husdyrproduksjon de siste 20 årene...publishedVersio