Protein markers for insulin-producing beta cells with higher glucose sensitivity

Background and Methodology: Pancreatic beta cells show intercellular differences in their metabolic glucose sensitivity and associated activation of insulin production. To identify protein markers for these variations in functional glucose sensitivity, rat beta cell subpopulations were flow-sorted for their level of glucose-induced NAD(P) H and their proteomes were quantified by label-free data independent alternate scanning LC-MS. Beta cell-selective proteins were also identified through comparison with rat brain and liver tissue and with purified islet alpha cells, after geometrical normalization using 6 stably expressed reference proteins. Principal Findings: All tissues combined, 943 proteins were reliably quantified. In beta cells, 93 out of 467 quantifiable proteins were uniquely detected in this cell type; several other proteins presented a high molar abundance in beta cells. The proteome of the beta cell subpopulation with high metabolic and biosynthetic responsiveness to 7.5 mM glucose was characterized by (i) an on average 50% higher expression of protein biosynthesis regulators such as 40S and 60S ribosomal constituents, NADPH-dependent protein folding factors and translation elongation factors; (ii) 50% higher levels of enzymes involved in glycolysis and in the cytosolic arm of the malate/aspartate-NADH-shuttle. No differences were noticed in mitochondrial enzymes of the Krebs cycle, beta-oxidation or respiratory chain. Conclusions: Quantification of subtle variations in the proteome using alternate scanning LC-MS shows that beta cell metabolic glucose responsiveness is mostly associated with higher levels of glycolytic but not of mitochondrial enzymes

Incarceratie van dunne darm doorheen het foramen omentale (epiploïcum) : een retrospectieve studie bij 100 paarden

A retrospective study was performed on 100 horses with incarceration of the small intestine through the omental (epiploic) foramen at the Faculty of Veterinary Medicine of Ghent University in Belgium during the period 1994-2001. Preoperative euthanasia was done in 10 horses for different reasons and an explorative laparotomy was performed in 90. Of these ninety horses, 1 died spontaneously during surgical intervention, 10 underwent euthanasia because of the extent of the lesions or a fatal hemorrhage, and surgery was completed on the other 79. A second intervention was necessary in 11 of these 79 horses. Simple reduction and reposition of the small intestine was possible in 35 of them, and a resection followed by an intestinal anastomosis was required in the other 44. Forty-four (49%) of the original 90 horses in which surgery was accomplished were discharged from the clinic. Six of these 44 were re-operated. The survival rate in the group of horses that under-went simple reduction was 60% and in the group that underwent resection and anastomosis it was 52%. After discharge from the clinic, 9 of the original 44 horses were lost for follow-up, and the remaining 3 5 survived for at least 9 months. During the follow-up period (I to 7 years), 16 horses had one or more bouts of colic, for which reason 5 of them (14%) underwent euthanasia. In this study the mean age of the horses with incarceration of the small intestine through the omental foramen was 9.46 years. Geldings, males and riding horses were clearly more represented. During surgical intervention a medio-lateral incarceration was observed in 98% of the horses. A negative correlation was observed between the survival rate and the length of the incarcerated intestinal segment, on the one hand, and between the survival rate and the distance to the clinic (duration after onset of symptoms) on the other

Ryanodine receptors are targeted by anti-apoptotic Bcl-X-L involving its BH4 domain and Lys87 from its BH3 domain

Anti-apoptotic B-cell lymphoma 2 (Bcl-2) family members target several intracellular Ca2+-transport systems. Bcl-2, via its N-terminal Bcl-2 homology (BH) 4 domain, inhibits both inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs), while Bcl-X-L, likely independently of its BH4 domain, sensitizes IP3Rs. It remains elusive whether Bcl-XL can also target and modulate RyRs. Here, Bcl-X-L co-immunoprecipitated with RyR3 expressed in HEK293 cells. Mammalian protein-protein interaction trap (MAPPIT) and surface plasmon resonance (SPR) showed that Bcl-XL bound to the central domain of RyR3 via its BH4 domain, although to a lesser extent compared to the BH4 domain of Bcl-2. Consistent with the ability of the BH4 domain of Bcl-X-L to bind to RyRs, loading the BH4-Bcl-X-L peptide into RyR3-overexpressing HEK293 cells or in rat hippocampal neurons suppressed RyR-mediated Ca2+ release. In silico superposition of the 3D-structures of Bcl-2 and Bcl-XL indicated that Lys87 of the BH3 domain of Bcl-XL could be important for interacting with RyRs. In contrast to Bcl-X-L, the Bcl-X-L(K87D) mutant displayed lower binding affinity for RyR3 and a reduced inhibition of RyR-mediated Ca2+ release. These data suggest that Bcl-X-L binds to RyR channels via its BH4 domain, but also its BH3 domain, more specific Lys87, contributes to the interaction

Delen van de Brouwersbuis in het stadspark van Antwerpen. Eindverslag van een toevalsvondst

Na de melding van een toevalsvondst in het stadspark van Antwerpen werd door het agentschap Onroerend Erfgoed de aangetroffen bakstenen constructie gedocumenteerd en opgegraven. Door de nauwkeurige studie van de opbouw van de constructie en het consulteren van en het confronteren van de gegevens met meerdere historische bronnen kon dit vrij gelegde deel toegeschreven worden aan de zgn. Brouwersbuis