Novel brain expressed RNA identified at the MIR137 schizophrenia-associated locus

AbstractGenome-wide association studies (GWAS) have identified a locus on chromosome 1p21.3 to be highly associated with schizophrenia. A microRNA, MIR137, within this locus has been proposed as the gene causally associated with schizophrenia, due to its known role as a regulator of neuronal development and function. However, the involvement of other genes within this region, including DPYD (dihydropyrimidine dehydrogenase), is also plausible. In this communication, we describe a previously uncharacterised, brain-expressed RNA, EU358092, within the schizophrenia-associated region at 1p21.3. As we observed for MIR137, EU358092 expression was modulated in response to psychoactive drug treatment in the human SH-SY5Y neuroblastoma cell line. Bioinformatic analysis of publically available CNS expression data indicates that MIR137 and EU358092 are often co-expressed in vivo. A potential regulatory domain for expression of EU358092 is identified by bioinformatic analysis and its regulatory function is confirmed by reporter gene assays. These data suggest a potentially important role for EU358092 in the aetiology of schizophrenia, either individually or in combination with other genes at this locus

Holocene geochemical footprint from Semiarid alpine wetlands in southern Spain

Here we provide the geochemical dataset that our research group has collected after 10 years of investigation in the Sierra Nevada National Park in southern Spain. These data come from Holocene sedimentary records from four alpine sites (ranging from ∼2500 to ∼3000 masl): two peatlands and two shallow lakes. Different kinds of organic and inorganic analyses have been conducted. The organic matter in the bulk sediment was characterised using elemental measurements and isotope-ratio mass spectrometry (EA-IRMS). Leaf waxes in the sediment were investigated by means of chromatography with flame-ionization detection and mass spectrometry (GC-FID, GC-MS). Major, minor and trace elements of the sediments were analysed with atomic absorption (AAS), inductively coupled plasma mass spectrometry (ICP-MS), as well as X-ray scanning fluorescence. These data can be reused by environmental researchers and soil and land managers of the Sierra Nevada National Park and similar regions to identify the effect of natural climate change, overprinted by human impact, as well as to project new management policies in similar protected areas.Universidad de Granada. Departamento de Estratigrafía y PaleontologíaJunta de Andalucía: Grupos de investigación RNM190 y RNM309Junta de Andalucía: Proyecto P11-RNM-7332España, Ministerio de Economía y Competitividad: Proyecto CGL2013-47038-RRamón y Cajal Fellowship: RYC-2015-18966Small Research Grant by the Carnegie Trust for the Universities of ScotlandMarie Curie Intra-European Fellowship of the 7th Framework Programme for Research, Technological Development and Demonstration of the European Commission: NAOSIPUK. Grant Number: PIEF-GA-2012-62302

Fiber optic Raman spectroscopy for the evaluation of disease state in Duchenne muscular dystrophy:An assessment using the mdx model and human muscle

INTRODUCTION/AIMS: Raman spectroscopy is an emerging technique for the evaluation of muscle disease. In this study we evaluate the ability of in vivo intramuscular Raman spectroscopy to detect the effects of voluntary running in the mdx model of Duchenne muscular dystrophy (DMD). We also compare mdx data with muscle spectra from human DMD patients. METHODS: Thirty 90‐day‐old mdx mice were randomly allocated to an exercised group (48‐hour access to a running wheel) and an unexercised group (n = 15 per group). In vivo Raman spectra were collected from both gastrocnemius muscles and histopathological assessment subsequently performed. Raman data were analyzed using principal component analysis–fed linear discriminant analysis (PCA‐LDA). Exercised and unexercised mdx muscle spectra were compared with human DMD samples using cosine similarity. RESULTS: Exercised mice ran an average of 6.5 km over 48 hours, which induced a significant increase in muscle necrosis (P = .03). PCA‐LDA scores were significantly different between the exercised and unexercised groups (P < .0001) and correlated significantly with distance run (P = .01). Raman spectra from exercised mice more closely resembled human spectra than those from unexercised mice. DISCUSSION: Raman spectroscopy provides a readout of the biochemical alterations in muscle in both the mdx mouse and human DMD muscle

Guidance for the assessment of risks to bees from the use of plant protection products applied as seed coating and soil applications – conclusions of the ICPBR dedicated working group

contribution to session IRegulatory issuesBackground: Soil or seed applied plant protection products (PPPs) aim at bringing the amount of active substance involved to the only parts of the plant that have to be protected. Despite a reduced exposure of non target organisms by this way, an exposure of honey bees through residues in pollen and/or nectar may not be excluded for substances that migrate towards the upper plant parts. Directive 91/414/EEC, related guidance documents and literature data were reviewed and discussed by a working group of the ICPBR (International Commission for Plant-Bee Relationships) with the aim to provide adequate guidance to proceed in a risk assessment in such cases.Results: The review and expert knowledge collected within ecotoxicology, entomology and plant residue area allowed to identify the key parameters that trigger a risk assessment as well as basic hypotheses to consider in deciding for the experimentations required (laboratory, semi-field and field tests). A stepwise, tiered approach is proposed, which has been checked for its ability to discriminate substances that may pose a risk to bees from substances of low concern. Conclusion: The present scheme is proposed to update the current EPPO risk assessment scheme with a special issue on systemic PPPs.Keywords: risk assessment, honey bees, soil or seed treatments, systemic

Label-free fibre optic Raman spectroscopy with bounded simplex-structured matrix factorization for the serial study of serum in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease in urgent need of disease biomarkers for the assessment of promising therapeutic candidates in clinical trials. Raman spectroscopy is an attractive technique for identifying disease related molecular changes due to its simplicity. Here, we describe a fibre optic fluid cell for undertaking spontaneous Raman spectroscopy studies of human biofluids that is suitable for use away from a standard laboratory setting. Using this system, we examined serum obtained from patients with ALS at their first presentation to our centre (n = 66) and 4 months later (n = 27). We analysed Raman spectra using bounded simplex-structured matrix factorization (BSSMF), a generalisation of non-negative matrix factorisation which uses the distribution of the original data to limit the factorisation modes (spectral patterns). Biomarkers associated with ALS disease such as measures of symptom severity, respiratory function and inflammatory/immune pathways (C3/C-reactive protein) correlated with baseline Raman modes. Between visit spectral changes were highly significant (p = 0.0002) and were related to protein structure. Comparison of Raman data with established ALS biomarkers as a trial outcome measure demonstrated a reduction in required sample size with BSSMF Raman. Our portable, simple to use fibre optic system allied to BSSMF shows promise in the quantification of disease-related changes in ALS over short timescales

Environmental risk assessment scheme for plant protection products - Chapter 10: Honeybees – Proposed scheme

contribution to session I Regulatory issue

Peribiliary glands are key in regeneration of the human biliary epithelium after severe bile duct injury

Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking. We, therefore, developed a novel ex vivo model using precision-cut slices of extrahepatic human bile ducts obtained from discarded donor livers, providing an intact anatomical organization of cell structures, to study spatiotemporal differentiation and migration of PBG cells after severe biliary injury. Post-ischemic bile duct slices were incubated in oxygenated culture medium for up to a week. At baseline, severe tissue injury was evident with loss of luminal epithelial lining and mural stroma necrosis. In contrast, PBG remained relatively well preserved and different reactions of PBG were noted, including PBG dilatation, cell proliferation and maturation. Proliferation of PBG cells increased after 24 h of oxygenated incubation, reaching a peak after 72 h. Proliferation of PBG cells was paralleled by a reduction in PBG apoptosis and differentiation from a primitive and pluripotent (Nanog+/Sox9+) to a mature (CFTR+/secretin receptor+) and activated phenotype (increased expression of HIF-1α, Glut-1, and VEGF-A). Migration of proliferating PBG cells in our ex vivo model was unorganized, but resulted in generation of epithelial monolayers at stromal surfaces. CONCLUSION: Human PBG contain biliary progenitor cells and are able to respond to bile duct epithelial loss with proliferation, differentiation, and maturation to restore epithelial integrity. The ex vivo spatiotemporal behaviour of human PBG cells provides evidence for a pivotal role of PBG in biliary regeneration after severe injury. This article is protected by copyright. All rights reserved