The aim of this study was to develop a positron emission tomography (PET) tracer based on the dual P-glycoprotein (P-gp) breast cancer resistance protein (BCRP) inhibitor tariquidar (1) to study the interaction of 1 with P-gp and BCRP in the blood-brain barrier (BBB) in vivo. Odesmethyl-1 was synthesized and reacted with [ 11 C]methyl triflate to afford [ 11 C]-1. Small-animal PET imaging of [ 11 C]-1 was performed in naïve rats, before and after administration of unlabeled 1 (15 mg/kg, n=3) or the dual P-gp/BCRP inhibitor elacridar (5 mg/kg, n=2), as well as in wildtype, Mdr1a/b (−/−) , Bcrp1 (−/−) and Mdr1a/b (−/−) Bcrp1 (−/−) mice (n=3). In vitro autoradiography was performed with [ 11 C]-1 using brain sections of all 4 mouse types, with and without coincubation with unlabeled 1 or elacridar (1 μM). In PET experiments in rats, administration of unlabeled 1 or elacridar increased brain activity uptake by a factor of 3-4, whereas blood activity levels remained unchanged. In Mdr1a/b (−/−) , Bcrp1 (−/−) and Mdr1a/b (−/−) Bcrp1 (−/−) mice, brain-toblood ratios of activity at 25 min after tracer injection were 3.4, 1.8 and 14.5 times higher, respectively, as compared to wild-type animals. Autoradiography showed approximately 50% less [ 11 C]-1 binding in transporter knockout mice compared to wild-type mice and significant displacement by unlabeled elacridar in wild-type and Mdr1a/b (−/−) mouse brains. Our data suggest that [ 11 C]-1 interacts specifically with P-gp and BCRP in the BBB. However, further investigations are needed to assess if [ 11 C]-1 behaves in vivo as a transported or a non-transported inhibitor.

Heterotrophic organisms rely on the ingestion of organic molecules or nutrients from the environment to sustain energy and biomass production. Non-motile, unicellular organisms have a limited ability to store nutrients or to take evasive action, and are therefore most directly dependent on the availability of nutrients in their immediate surrounding. Such organisms have evolved numerous developmental options in order to adapt to and to survive the permanently changing nutritional status of the environment. The phenotypical, physiological and molecular nature of nutrient-induced cellular adaptations has been most extensively studied in the yeast Saccharomyces cerevisiae. These studies have revealed a network of sensing mechanisms and of signalling pathways that generate and transmit the information on the nutritional status of the environment to the cellular machinery that implements specific developmental programmes. This review integrates our current knowledge on nutrient sensing and signalling in S. cerevisiae, and suggests how an integrated signalling network may lead to the establishment of a specific developmental programme, namely pseudohyphal differentiation and invasive growth.

F TIR spectroscopy is a nondestructive technique that provides structural information on molecular features of a large range of compounds. Its main advantages are speed, a high degree of automation, medium resolution, and cost-effectiveness. Recent improvements in instrumentation together with advances in fiber optics and chemometrics have provided an analytical tool that is suitable for routine qualitative analysis and process control in many industries.Although FTIR spectroscopy is widely applied in the food industry, acceptance of this technology in the grape and wine industry has been relatively slow and mainly

Similar to Alzheimer's disease (AD), dementia with Lewy bodies (DLB) is characterized by a profound degeneration of cortically-projecting cholinergic neurons of the basal forebrain (BF) and associated depletion of cortical cholinergic activity. We aimed to investigate subregional atrophy of the BF in DLB in vivo and compare it to the pattern of BF atrophy in AD. Structural MRI scans of 11 patients with DLB, 11 patients with Alzheimer's disease, and 22 healthy controls were analysed using a recently developed technique for automated BF morphometry based on high-dimensional image warping and cytoarchitectonic maps of BF cholinergic nuclei. For comparison, hippocampus volume was assessed within the same morphometric framework using recently published consensus criteria for the definition of hippocampus outlines on MRI. The DLB group demonstrated pronounced and subregion-specific atrophy of the BF which was comparable to BF atrophy in AD: volume of the nucleus basalis Meynert was significantly reduced by 20-25%, whereas rostral BF nuclei were only marginally affected. By contrast, hippocampus volume was markedly less affected in DLB compared to AD. Global cognition as determined by MMSE score was associated with BF volume in AD, but not in DLB, whereas visuoperceptual function as determined by the trail making test was associated with BF volume in DLB, but not in AD. DLB may be characterized by a more selective degeneration of the cholinergic BF compared to AD, which may be related to the differential cognitive profiles in both conditions.