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

Visualization of Active Glucocerebrosidase in Rodent Brain with High Spatial Resolution following In Situ Labeling with Fluorescent Activity Based Probes

Bio-organic SynthesisMedical Biochemistr

Real-world fuel consumption of passenger cars

Since 2008 Travelcard Nederland BV and TNO collaborate to determine the real-world fuel consumption of modern vehicles. The difference between the official type-approval value and the actual fuel consumption has been reported over the years (Ligterink, 2010 and Ligterink, 2013 and Ligterink, 2014). The fact that both numbers do not coincide is not surprising, since the official typeapproval test for determining fuel consumption does not properly represent the real-world vehicle usage. However, the increasing gap between both numbers is remarkable. From year to year, the type-approval value decreases with new vehicle models. The real-world fuel consumption, on the other hand, is only slightly lower. Also for the same type-approval value the real-world fuel consumption is higher with newer vehicles

Dependence on technology, drivers, roads, and congestion of real-world vehicle fuel consumption

The Dutch national transport CO2 emissions are determined by summing individual cases: a particular vehicle, on a particular road and traffic situation. In this paper the different aspects and the relations among them, as used in emission predictions, are outlined. In particular the central role that the CO2 type-approval value (from the NEDC test) plays in the real-world CO2 emissions since 2000 is clarified. © The author(s) and/or their employer(s), 2012

Brommers in de stedelijke leefomgeving - Status rapport

Doel van dit rapport is de bij TNO beschikbare kennis over de uitlaatgasemissies

Elemental carbon as an indicator to monitor the effectiveness of traffic related measures on local air quality

Even when European standards on air quality are met, health effects occur near busy roads because of the increased exposure to tailpipe emissions. For a proper assessment of these effects, an additional indicator is available: elemental carbon (EC). This is a sensitive indicator for particulate matter from combustion emissions by road traffic. Currently, the concentrations of EC along busy roads are still significantly increased relative to the background, in contrast to PM10 and PM2.5. Therefore, the effectiveness of traffic measures on local air quality and associated health effects can be better assessed with EC than with PM mass. This paper discusses the relevance of EC as an indicator in the assessment of air quality and health. This is illustrated with two pilot studies in the Dutch cities of Arnhem and Helmond where traffic measures were evaluated with EC measurements. Also model calculations of the effect of 80 km/h speed limit zones on Dutch motorways on the health risks of local residents are presented. It is concluded that the assessment of EC through monitoring and/or modelling is a powerful policy instrument to analyse the impact of local traffic measures on air quality and health. Typically, people living close to busy road transport may live 1 to 6 months longer when measures like enhancing traffic flow, speed limiting and environmental zoning are implemented

Ecdysteroid hormones link the juvenile environment to alternative adult life histories in a seasonal insect

The conditional expression of alternative life strategies is a widespread feature of animal life and a pivotal adaptation to life in seasonal environments. To optimally match suites of traits to seasonally changing ecological opportunities, animals living in seasonal environments need mechanisms linking information on environmental quality to resource allocation decisions. The butterfly Bicyclus anynana expresses alternative adult life histories in the alternating wet and dry seasons of its habitat as endpoints of divergent developmental pathways triggered by seasonal variation in preadult temperature. Pupal ecdysteroid hormone titers are correlated with the seasonal environment, but whether they play a functional role in coordinating the coupling of adult traits in the alternative life histories is unknown. Here, we show that manipulating pupal ecdysteroid levels is sufficient to mimic in direction and magnitude the shifts in adult reproductive resource allocation normally induced by seasonal temperature. Crucially, this allocation shift is accompanied by changes in ecologically relevant traits, including timing of reproduction, life span, and starvation resistance. Together, our results support a functional role for ecdysteroids during development in mediating strategic reproductive investment decisions in response to predictive indicators of environmental quality. This study provides a physiological mechanism for adaptive developmental plasticity, allowing organisms to cope with variable environment