The elementary obstruction and the Weil restriction

In this text we investigate the good behaviour of the elementary obstruction, introduced by Colliot-Thelene and Sansuc. This is an obstruction to the existence of a rational points on certain algebraic varieties. Assuming some conditions on the Picard group, we prove that the elementary obstruction behaves well under the Weil restriction of a variety.Comment: 9 pages, revised version for publicatio

Dietary advanced glycation endproducts (AGEs) increase their concentration in plasma and tissues, result in inflammation and modulate gut microbial composition in mice; evidence for reversibility

Scope: Dietary advanced glycation endproducts (AGEs) are associated with negative biological effects, possibly due to accumulation in plasma and tissues and through modulation of inflammation and gut microbiota. Whether these biological consequences are reversible by limiting dietary AGE intake is unknown. Methods and results: Young healthy C57BL/6 mice were fed a standard chow (n = 10) or a baked chow high AGE-diet (n = 10) (~1.8–6.9 fold increased protein-bound Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl) lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)) for 10 weeks or a switch diet with baked chow for 5 weeks followed by 5 weeks of standard chow (n = 10). We assessed accumulation of AGEs in plasma, kidney, and liver and measured inflammatory markers and gut microbial composition. After 10 weeks of baked chow, a substantial panel of AGEs were increased in plasma, liver, and kidney. These increases were normalized after the switch diet. The inflammatory z-score increased after the baked chow diet. Gut microbial composition differed significantly between groups, with enriched Dubosiella spp. dominating these alterations. Conclusion: A high AGE-diet led to an increase of AGEs in plasma, kidney, and liver and to more inflammation and modification of the gut microbiota. These effects were reversed or discontinued by a diet lower in AGEs.Peer reviewe

Methylglyoxal-Derived Advanced Glycation Endproducts Accumulate in Multiple Sclerosis Lesions

Multiple sclerosis (MS) is a demyelinating autoimmune disease in which innate and adaptive immune cells infiltrate the central nervous system (CNS) and damage the myelin sheaths surrounding the axons. Upon activation, infiltrated macrophages, CNS-resident microglia, and astrocytes switch their metabolism toward glycolysis, resulting in the formation of α-dicarbonyls, such as methylglyoxal (MGO) and glyoxal (GO). These potent glycating agents lead to the formation of advanced glycation endproducts (AGEs) after reaction with amino acids. We hypothesize that AGE levels are increased in MS lesions due to the inflammatory activation of macrophages and astrocytes. First, we measured tissue levels of AGEs in brain samples of MS patients and controls. Analysis of MS patient and non-demented control (NDC) specimens showed a significant increase in protein-bound Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), the major AGE, compared to white matter of NDCs (107 ± 11 vs. 154 ± 21, p < 0.05). In addition, immunohistochemistry revealed that MGO-derived AGEs were specifically present in astrocytes, whereas the receptor for AGEs, RAGE, was detected on microglia/macrophages. Moreover, in cerebrospinal fluid from MS patients, α-dicarbonyls and free AGEs correlated with their respective levels in the plasma, whereas this was not observed for protein-bound AGEs. Taken together, our data show that MG-H1 is produced by astrocytes. This suggests that AGEs secreted by astrocytes have paracrine effects on RAGE-positive macrophages/microglia and thereby contribute to the pathology of MS

LDL Receptor Knock-Out Mice Are a Physiological Model Particularly Vulnerable to Study the Onset of Inflammation in Non-Alcoholic Fatty Liver Disease

Non-alcoholic steatohepatitis (NASH) involves steatosis combined with inflammation, which can progress into fibrosis and cirrhosis. Exploring the molecular mechanisms of NASH is highly dependent on the availability of animal models. Currently, the most commonly used animal models for NASH imitate particularly late stages of human disease. Thus, there is a need for an animal model that can be used for investigating the factors that potentiate the inflammatory response within NASH. We have previously shown that 7-day high-fat-high-cholesterol (HFC) feeding induces steatosis and inflammation in both APOE2ki and Ldlr(-/-) mice. However, it is not known whether the early inflammatory response observed in these mice will sustain over time and lead to liver damage. We hypothesized that the inflammatory response in both models is sufficient to induce liver damage over time.APOE2ki and Ldlr(-/-) mice were fed a chow or HFC diet for 3 months. C57Bl6/J mice were used as control.Surprisingly, hepatic inflammation was abolished in APOE2ki mice, while it was sustained in Ldlr(-/-) mice. In addition, increased apoptosis and hepatic fibrosis was only demonstrated in Ldlr(-/-) mice. Finally, bone-marrow-derived-macrophages of Ldlr(-/-) mice showed an increased inflammatory response after oxidized LDL (oxLDL) loading compared to APOE2ki mice.Ldlr(-/-) mice, but not APOE2ki mice, developed sustained hepatic inflammation and liver damage upon long term HFC feeding due to increased sensitivity for oxLDL uptake. Therefore, the Ldlr(-/-) mice are a promising physiological model particularly vulnerable for investigating the onset of hepatic inflammation in non-alcoholic steatohepatitis

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Werner Wouters Stadsarcheologie in Vlaanderen. Een korte inleiding.Marie Christine Laleman Het geheugen van een stad: drie decennia Gentse stadsarcheologie. [A citys memory: three decades of city archeology in Ghent.]Gent speelde met de officiële oprichting in 1975 van een Dienst Archeologie en Historische Monumenten in België een pioniersrol.Figuren als Firmin De Smidt, Adelbert Van de Walle en Siegfried De Laet hadden weliswaar het pad gebaand, maar na de stadsarcheologische verkenning van de buitentuin van de Sint-Pietersabdij zou niets meer zijn zoals het was.Joan Vandenhoute en Patrick Raveschot, pioniers van het eerste uur, kunnen het niet meer navertellen, maar met Marie Christine Laleman wordt het verleden meer dan ooit een gesprekspartner voor de toekomst.Bieke Hillewaert Archeologie in Brugge. Van Stedelijke naar intergemeentelijke dienst. [Achaeology in Bruges. From urban to inter-municipal service.]De belangrijke archeologische verzameling van de Brugse Stedelijke Musea vormde de achtergrond voor de oprichting in 1977 van een eigen Stedelijke Archeologische Dienst. Nog maar pas in 2004 ging deze op in Raakvlak, een interlokale vereniging - tussen polders en zandstreek - voor archeologie in Brugge en Ommeland. Vanuit de nieuwe vestiging in de Pakhuizen aan de Komvest legt Bieke Hillewaert de link tussen de Société Archéologique de Bruges en de Lokale Archeologische Advieskaart, met duidelijke klemtoon op het bodemonderzoek.Bart Robberechts, Liesbeth Troubleyn, Raf Ribbens en Frank Kinnaer Mechelen en de stedelijke dienst Archeologie. [Mechelen and the municipal archaeology sevice.]Heel wat water vloeide door Zenne en Dijle sinds de vroegste graafwerken in de Mechelse Sint-Romboutskathedraal, nauwelijks een eeuw terug, en het recente archeologisch onderzoek van de Grote Markt, Veemarkt en het Minderbroederklooster.In het zog van een lange traditie aan archeologische verenigingen en voor een alerte bevolking werd in 2004 het onwaarschijnlijke bewaarheid: de oprichting van een stedelijke dienst Archeologie zonder eigen stadsarcheoloog: een uitdaging waar Bart Robberechts, Liesbeth Troubleyn, Raf Ribbens en Frank Kinnaer intussen met succes vaste vorm aan gaven.Johan Veeckman en Tim Bellens Stadsarcheologie in Antwerpen. [City archaeology in Antwerp.]Na een blitse start in 1952, in de schaduw van het Steen, belandde het stadsarcheologisch onderzoek in de Scheldestad voor lange jaren in de spreekwoordelijke steeg.De ruim 400 publicaties wijzen immers ook tegelijk op de keerzijde van de medaille: archeologie gelieerd met museale werking en niet met ruimtelijke ordening.Sinds 1995 vonden archeologie en monumentenzorg elkaar in de huidige Stadsontwikkeling. Johan Veeckman en Tim Bellens juichen de evolutie met recente resultaten toe.Hubert Heymans en Anja Neskens Stadsarcheologie in Maaseik. [City archaeology in Maaseik.]Hiertoe gestimuleerd door lokale privé-sponsoring en de creatie van een eerste archeologisch museum nam de stad Maaseik reeds in 1984 de moedige beslissing tot aanstelling van een stadsarcheoloog annex conservator.Beperkte middelen beperkten ook de interventies tot noodopgravingen, occasioneel tot ruimer onderzoek. Wat kaarslicht en een Agnus Dei zoal vermogen verneemt de lezer met Hubert Heymans en Anja Neskens hierbij uit eerste bron.Summar

Internalization of Modified Lipids by CD36 and SR-A Leads to Hepatic Inflammation and Lysosomal Cholesterol Storage in Kupffer Cells

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis and inflammation, which can further progress into fibrosis and cirrhosis. Recently, we demonstrated that combined deletion of the two main scavenger receptors, CD36 and macrophage scavenger receptor 1 (MSR1), which are important for modified cholesterol-rich lipoprotein uptake, reduced NASH. The individual contributions of these receptors to NASH and the intracellular mechanisms by which they contribute to inflammation have not been established. We hypothesize that CD36 and MSR1 contribute independently to the onset of inflammation in NASH, by affecting intracellular cholesterol distribution inside Kupffer cells (KCs).Ldlr(-/-) mice were transplanted with wild-type (Wt), Cd36(-/-) or Msr1(-/-) bone marrow and fed a Western diet for 3 months. Cd36(-/-)- and Msr1(-/-)- transplanted (tp) mice showed a similar reduction in hepatic inflammation compared to Wt-tp mice. While the total amount of cholesterol inside KCs was similar in all groups, KCs of Cd36(-/-)- and Msr1(-/-)-tp mice showed increased cytoplasmic cholesterol accumulation, while Wt-tp mice showed increased lysosomal cholesterol accumulation.CD36 and MSR1 contribute similarly and independently to the progression of inflammation in NASH. One possible explanation for the inflammatory response related to expression of these receptors could be abnormal cholesterol trafficking in KCs. These data provide a new basis for prevention and treatment of NASH