Decarbonisation of transport: options and challenges

This EASAC report reviews options for reducing greenhouse gas (GHG) emissions from European transport. It argues for stronger policies to bridge the gap between the GHG emission reductions that will be delivered by current policies and the levels needed to limit global warming to less than 2°C or even 1.5°C (Paris Agreement). The report focusses on road transport because, in the EU, this contributes 72% of transport GHG emissions. EASAC recommends a combination of transitional measures for the next 10-15 years and sustainable measures for the long term, based on a three level policy framework: avoid and contain demand for transport services; shift passengers and freight to transport modes with lower emissions (trains, buses and ships); and improve performance through vehicle design, more efficient powertrains and replacing fossil fuels with sustainable energy carriers including low-carbon electricity, hydrogen and synthetic fuels. Opportunities for the EU to strengthen its industrial competitiveness and create high quality jobs are also discussed

The role of multixenobiotic transporters in predatory marine molluscs as counter-defense mechanisms against dietary allelochemicals

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 152 (2010): 288-300, doi:10.1016/j.cbpc.2010.05.003.Multixenobiotic transporters have been extensively studied for their ability to modulate the disposition and toxicity of pharmacological agents, yet their influence in regulating the levels of dietary toxins within marine consumers has only recently been explored. This study presents functional and molecular evidence for multixenobiotic transporter-mediated efflux activity and expression in the generalist gastropod Cyphoma gibbosum, and the specialist nudibranch Tritonia hamnerorum, obligate predators of chemically defended gorgonian corals. Immunochemical analysis revealed that proteins with homology to permeability glycoprotein (P-gp) were highly expressed in T. hamnerorum whole animal homogenates and localized to the apical tips of the gut epithelium, a location consistent with a role in protection against ingested prey toxins. In vivo dye assays with specific inhibitors of efflux transporters demonstrated the activity of P-gp and multidrug resistance-associated protein (MRP) families of ABC transporters in T. hamnerorum. In addition, we identified eight partial cDNA sequences encoding two ABCB and two ABCC proteins from each molluscan species. Digestive gland transcripts of C. gibbosum MRP-1, which have homology to vertebrate glutathione-conjugate transporters, were constitutively expressed regardless of gorgonian diet. This constitutive expression may reflect the ubiquitous presence of high affinity substrates for C. gibbosum glutathione transferases in gorgonian tissues likely necessitating export by MRPs. Our results suggest that differences in multixenobiotic transporter expression patterns and activity in molluscan predators may stem from the divergent foraging strategies of each consumer.Financial support was provided by the Ocean Life Institute Tropical Research Initiative Grant (WHOI) to KEW and MEH; the Robert H. Cole Endowed Ocean Ventures Fund (WHOI) to KEW; the National Undersea Research Center – Program Development Proposal (CMRC-03PRMN0103A) to KEW; and the National Science Foundation (Graduate Research Fellowship to KEW and DEB-0919064 to EES)

Decarbonisation of transport: options and challenges

This EASAC report reviews options for reducing greenhouse gas (GHG) emissions from European transport. It argues for stronger policies to bridge the gap between the GHG emission reductions that will be delivered by current policies and the levels needed to limit global warming to less than 2\xc2\xb0C or even 1.5\xc2\xb0C (Paris Agreement). The report focusses on road transport because, in the EU, this contributes 72% of transport GHG emissions. EASAC recommends a combination of transitional measures for the next 10-15 years and sustainable measures for the long term, based on a three level policy framework: avoid and contain demand for transport services; shift passengers and freight to transport modes with lower emissions (trains, buses and ships); and improve performance through vehicle design, more efficient powertrains and replacing fossil fuels with sustainable energy carriers including low-carbon electricity, hydrogen and synthetic fuels. Opportunities for the EU to strengthen its industrial competitiveness and create high quality jobs are also discussed

High-grade glioma in very young children: a rare and particular patient population

In the past years, pediatric high-grade gliomas (HGG) have been the focus of several research articles and reviews, given the recent discoveries on the genetic and molecular levels pointing out a clinico-biological uniqueness of the pediatric population compared to their adult counterparts with HGG. On the other hand, there are only scarce data about HGG in very young children (below 3 years of age at diagnosis) due to their relatively low incidence. However, the few available data suggest further distinction of this very rare subgroup from older children and adults at several levels including their molecular and biological characteristics, their treatment management, as well as their outcome. This review summarizes and discusses the current available knowledge on the epidemiological, neuropathological, genetic and molecular data of this subpopulation. We discuss these findings and differences compared to older patients suffering from the same histologic disease. In addition, we highlight the particular clinical and neuro-radiological findings in this specific subgroup of patients as well as their current management approaches and treatment outcomes

Occurrence of high‐grade glioma in Noonan syndrome: Report of two cases

Noonan syndrome (NS) is an autosomal dominant disorder commonly caused by PTPN11 germline mutations. Patients are characterized by short stature, congenital heart defects, facial dysmorphism, and increased risk of malignancies including brain tumors. Commonly associated brain tumors are dysembryoplastic neuroepithelial tumor and low-grade glioma. We report two cases of anaplastic astrocytoma with PTPN11-related NS. We conducted a systematic search of medical databases looking for other reported cases of high-grade glioma associated with NS and identified 24 cases of brain tumors, all of which were low-grade glial or glioneuronal tumors except for one case of medulloblastoma

La prison du Pied-du-Courant

Background & Aims: We have specified the features of progressive familial intrahepatic cholestasis type 3 and investigated in 31 patients whether a defect of the multidrug resistance 3 gene (MDR3) underlies this phenotype. Methods: MDR3 sequencing liver MDR3 immunohistochemistry, and biliary phospholipid dosage were performed, Results: Liver histology showed a pattern of biliary cirrhosis with patency of the biliary tree. Age at presentation ranged from the neonatal period to early adulthood. Sequence analysis revealed 16 different mutations in 17 patients. Mutations were identified on both alleles in 12 patients and only on 1 allele in 5, Four mutations lead to a frame shift, 2 are nonsense, and 10 are missense, An additional missense mutation probably representing a polymorphism was found in 5 patients, MDR3 mutations were associated with abnormal MDRB canalicular staining and a low proportion of biliary phospholipids, Gallstones or episodes of cholestasis of pregnancy were found in patients or parents. Children with missense mutations had a less severe disease and more often a beneficial effect of ursodeoxycholic acid therapy. Conclusions: At least one third of the patients with a progressive familial intrahepatic cholestasis type 3 phenotype have a proven defect of MDR3, This gene defect should also be considered in adult liver diseases

Prediction of altered 3 '-UTR miRNA-binding sites from RNA-seq data: the swine leukocyte antigen complex (SLA) as a model region

The SLA (swine leukocyte antigen, MHC: SLA) genes are the most important determinants of immune, infectious disease and vaccine response in pigs; several genetic associations with immunity and swine production traits have been reported. However, most of the current knowledge on SLA is limited to gene coding regions. MicroRNAs (miRNAs) are small molecules that post-transcriptionally regulate the expression of a large number of protein-coding genes in metazoans, and are suggested to play important roles in fine-tuning immune mechanisms and disease responses. Polymorphisms in either miRNAs or their gene targets may have a significant impact on gene expression by abolishing, weakening or creating miRNA target sites, possibly leading to phenotypic variation. We explored the impact of variants in the 3′-UTR miRNA target sites of genes within the whole SLA region. The combined predictions by TargetScan, PACMIT and TargetSpy, based on different biological parameters, empowered the identification of miRNA target sites and the discovery of polymorphic miRNA target sites (poly-miRTSs). Predictions for three SLA genes characterized by a different range of sequence variation provided proof of principle for the analysis of poly-miRTSs from a total of 144 M RNA-Seq reads collected from different porcine tissues. Twenty-four novel SNPs were predicted to affect miRNA-binding sites in 19 genes of the SLA region. Seven of these genes (SLA-1, SLA-6, SLA-DQA, SLA-DQB1, SLA-DOA, SLA-DOB and TAP1) are linked to antigen processing and presentation functions, which is reminiscent of associations with disease traits reported for altered miRNA binding to MHC genes in humans. An inverse correlation in expression levels was demonstrated between miRNAs and co-expressed SLA targets by exploiting a published dataset (RNA-Seq and small RNA-Seq) of three porcine tissues. Our results support the resource value of RNA-Seq collections to identify SNPs that may lead to altered miRNA regulation patterns