Gpnmb is a potential marker for the visceral pathology in Niemann-Pick type C disease

Impaired function of NPC1 or NPC2 lysosomal proteins leads to the intracellular accumulation of unesterified cholesterol, the primary defect underlying Niemann-Pick type C (NPC) disease. In addition, glycosphingolipids (GSLs) accumulate in lysosomes as well. Intralysosomal lipid accumulation triggers the activation of a set of genes, including potential biomarkers. Transcript levels of Gpnmb have been shown to be elevated in various tissues of an NPC mouse model. We speculated that Gpnmb could serve as a marker for visceral lipid accumulation in NPC disease. We report that Gpnmb expression is increased at protein level in macrophages in the viscera of Npc1nih/nih mice. Interestingly, soluble Gpnmb was also found to be increased in murine and NPC patient plasma. Exposure of RAW264.7 macrophages to the NPC-phenotype-inducing drug U18666A also upregulated Gpnmb expression. Inhibition of GSL synthesis with the glucosylceramide synthase (GCS) inhibitor N-butyl-1-deoxynojirimycin prevented U18666A-induced Gpnmb induction and secretion. In summary, we show that Gpnmb is upregulated in NPC mice and patients, most likely due to GSL accumulation

Populatieomvang van ganzen en Smienten en verspreiding binnen Nederland : ontwikkeling in populatieomvang op relevant flyway niveau en verdeling over Nederland, met name binnen en buiten opvanggebieden - Seizoen 2005/2006

Het Beleidskader Faunabeheer richt zich op de opvang van ganzen en Smienten in foerageergebieden. Met behulp van flankerende verjaging worden de beleidskadersoorten geconcentreerd in foerageergebieden. Ter evaluatie van het opvangbeleid is gekeken of er een negatieve invloed bestaat op de aantallen overwinteraars, en daarnaast of deze te concentreren zijn in foerageergebieden. Uitspraken over de internationale aantalsontwikkeling zijn gezien de onvolledigheid van IWC gegevens niet mogelijk. Landelijke trends van Smient, Kolgans en Grauwe gans zijn respectievelijk; stabiel, matige toename en sterke toename. In het seizoen 2005/2006 werd 44% van de ganzen en 13% van de Smienten opgevangen, daarnaast verbleven achtereenvolgens nog eens 20% en 45% in natuurgebieden. Hoewel het percentage overwinteraars dat zich binnen de foerageergebieden bevond hoger was dan in het voorgaande seizoen, is het verschil niet significant. Onderzoek van Alterra met SOVO

Ecologische gegevens van vogels voor Standaard Gegevensformulieren Vogelrichtlijngebieden

In dit rapport wordt verslag gedaan van de ecologische beoordeling van Vogelrichtlijngebieden voor de vogels voor de Standaard Gegevensformulieren. Na een beschrijving van de gevolgde werkwijze om de populatie, behoudsstatus, isolatie en algemene beoordeling te bepalen, worden in tabelvorm per soort voor alle relevante Vogelrichtlijngebieden de beoordelingen gepresenteer

Aortic microcalcification is associated with elastin fragmentation in Marfan syndrome

Marfan syndrome (MFS) is a connective tissue disorder in which aortic rupture is the major cause of death. MFS patients with an aortic diameter below the advised limit for prophylactic surgery (<5 cm) may unexpectedly experience an aortic dissection or rupture, despite yearly monitoring. Hence, there is a clear need for improved prognostic markers to predict such aortic events. We hypothesize that elastin fragments play a causal role in aortic calcification in MFS, and that microcalcification serves as a marker for aortic disease severity. To address this hypothesis, we analysed MFS patient and mouse aortas. MFS patient aortic tissue showed enhanced microcalcification in areas with extensive elastic lamina fragmentation in the media. A causal relationship between medial injury and microcalcification was revealed by studies in vascular smooth muscle cells (SMCs); elastin peptides were shown to increase the activity of the calcification marker alkaline phosphatase (ALP) and reduce the expression of the calcification inhibitor matrix GLA protein in human SMCs. In murine Fbn1C1039G/+ MFS aortic SMCs, Alpl mRNA and activity were upregulated as compared with wild-type SMCs. The elastin peptide-induced ALP activity was prevented by incubation with lactose or a neuraminidase inhibitor, which inhibit the elastin receptor complex, and a mitogen-activated protein kinase kinase-1/2 inhibitor, indicating downstream involvement of extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation. Histological analyses in MFS mice revealed macrocalcification in the aortic root, whereas the ascending aorta contained microcalcification, as identified with the near-infrared fluorescent bisphosphonate probe OsteoSense-800. Significantly, microcalcification correlated strongly with aortic diameter, distensibility, elastin breaks, and phosphorylated ERK1/2. In conclusion, microcalcification co-localizes with aortic elastin degradation in MFS aortas of humans and mice, where elastin-derived peptides induce a calcification process in SMCs via the elastin receptor complex and ERK1/2 activation. We propose microcalcification as a novel imaging marker to monitor local elastin degradation a

Broedsucces van kustbroedvogels in de Waddenzee in 2009 en 2010

Sinds 2005 worden in de Waddenzee jaarlijks gegevens verzameld over het broedsucces van een aantal karakteristieke kustbroedvogels. Hiervoor worden tien vogelsoorten gevolgd die representatief worden geacht voor specifieke habitats en voedselgroepen. Het reproductiemeetnet Waddenzee wordt uitgevoerd als een ‘early warning systeem’ om het reproducerend vermogen van de vogelpopulaties in de Waddenzee te volgen en de achterliggende processen van populatieveranderingen te doorgronden en fungeert als een wezenlijke aanvulling op de monitoring van aantallen en aantalsveranderingen. Het onderzoek wordt uitgevoerd in het kader van trilaterale afspraken met Duitsland en Denemarken (TMAP). De resultaten uit 2009 en 2010 laten zien dat veel soorten kustbroedvogels op dit moment een relatief laag broedsucces hebben. Vooral voor Eider, Scholekster, Kluut, Visdief en Noordse Stern geldt dat er te weinig jongen vliegvlug worden om de populatie op peil te houden. De slechte broedresultaten worden veroorzaakt door verschillende factoren. Eén daarvan is overstromingen als gevolg van hoog water gedurende het broedseizoen. Ook worden in de nestfase veel broedvogels slachtoffer van predatie van legsels, met name door Vos en Bruine Rat. Daarnaast speelt een te geringe voedselbeschikbaarheid een ro

Температурное поле в кристалле иттрий-алюминиевого граната при двухстадийном выращивании

Установлено существование оптимального значения теплопроводности, при котором достигается наиболее равномерное распределение модуля температурного градиента на фронте кристаллизации

Impact of obesity on taste receptor expression in extra-oral tissues: emphasis on hypothalamus and brainstem OPEN

Sweet perception promotes food intake, whereas that of bitterness is inhibitory. Surprisingly, the expression of sweet G protein-coupled taste receptor (GPCTR) subunits (T1R2 and T1R3) and bitter GPCTRs (T2R116, T2R118, T2R138 and T2R104), as well as the α-subunits of the associated signalling complex (αGustducin, Gα14 and αTransducin), in oral and extra-oral tissues from lean and obese mice, remains poorly characterized. We focused on the impact of obesity on taste receptor expression in brain areas involved in energy homeostasis, namely the hypothalamus and brainstem. We demonstrate that many of the GPCTRs and α-subunits are co-expressed in these tissues and that obesity decreases expression of T1R3, T2R116, Gα14, αTrans and TRPM5. In vitro high levels of glucose caused a prominent down-regulation of T1R2 and Gα14 expression in cultured hypothalamic neuronal cells, leptin caused a transient down-regulation of T1R2 and T1R3 expression. Intriguingly, expression differences were also observed in other extra-oral tissues of lean and obese mice, most strikingly in the duodenum where obesity reduced the expression of most bitter and sweet receptors. In conclusion, obesity influences components of sweet and bitter taste sensing in the duodenum as well as regions of the mouse brain involved in energy homeostasis, including hypothalamus and brainstem. Taste perception is an important aspect in the control of food intake. Taste is mainly sensed by taste receptor containing cells located in the taste buds distributed in the different gustatory epitheliums in the tongue, palate, larynx and epiglottis. The sensing of sweet, umami and bitter taste is mediated by two G protein-coupled taste receptor (GPCTR) families: the T1R family, which is mainly involved in the sensing of sweet and umami taste-like signalling molecules and the T2R family, involved in the sensing of bitter taste-like signalling molecules 1 . The T1R family consists of three different GPCTRs that generate at least two heterodimeric receptors: T1R1+T1R3 associated with umami taste sensing and T1R2+T1R3 associated with sweet taste sensing 1,2 . In mice the T2R family consists of at least 36 distinct taste receptor members, which individually sense bitter taste like molecules 3 . The human T2R16 selectively recognizes β-glucopyranosides 4 , while the human T2R38 recognizes phenylthiocarbamide (PTC) 5 . The functional importance of the latter two human receptors was demonstrated by the finding that overexpression of either receptor in mice increases food avoidance 6 . Although the T1R and T2R receptor families drive different taste perceptions, they share similar downstream G protein-coupled signalling pathways. In particular, the taste specific α-subunit of the G protein α-gustducin (αGust) is coupled to both receptor families and has been described as critical for sweet and bitter taste responses 7 . Nevertheless, αGust knockout animals still preserve a moderate sensitivity to some bitter compounds and to sweet compounds in higher mM concentration