6 research outputs found

    Early phase of plasticity-related gene regulation and SRF dependent transcription in the hippocampus

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    Hippocampal organotypic cultures are a highly reliable in vitro model for studying neuroplasticity: in this paper, we analyze the early phase of the transcriptional response induced by a 20 \ub5M gabazine treatment (GabT), a GABA-Ar antagonist, by using Affymetrix oligonucleotide microarray, RT-PCR based time-course and chromatin-immuno-precipitation. The transcriptome profiling revealed that the pool of genes up-regulated by GabT, besides being strongly related to the regulation of growth and synaptic transmission, is also endowed with neuro-protective and pro-survival properties. By using RT-PCR, we quantified a time-course of the transient expression for 33 of the highest up-regulated genes, with an average sampling rate of 10 minutes and covering the time interval [10 3690] minutes. The cluster analysis of the time-course disclosed the existence of three different dynamical patterns, one of which proved, in a statistical analysis based on results from previous works, to be significantly related with SRF-dependent regulation (p-value<0.05). The chromatin immunoprecipitation (chip) assay confirmed the rich presence of working CArG boxes in the genes belonging to the latter dynamical pattern and therefore validated the statistical analysis. Furthermore, an in silico analysis of the promoters revealed the presence of additional conserved CArG boxes upstream of the genes Nr4a1 and Rgs2. The chip assay confirmed a significant SRF signal in the Nr4a1 CArG box but not in the Rgs2 CArG box

    Genome-wide significant association with seven novel multiple sclerosis risk loci

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    Objective A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5x10(-8)) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03x10(-12)), CD28 (rs6435203, p=1.35x10(-9)), LPP (rs4686953, p=3.35x10(-8)), ETS1 (rs3809006, p=7.74x10(-9)), DLEU1 (rs806349, p=8.14x10(-12)), LPIN3 (rs6072343, p=7.16x10(-12)) and IFNGR2 (rs9808753, p=4.40x10(-10)). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases

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    Not AvailableThe increasing demand for crop production, given worldwide increases in the human population, puts pressure on moving natural resources towards sus-tainable development. This creates a big challenge for the upcoming generation. If improvement is not successful, there exists the unfortunate consequence that global food production may soon become insufficient to feed all of the world’s people. It is therefore essential that agricultural productivity be significantly increased in a more sustainable and environmentally friendly approach. Plant-beneficiary rhizo-bacteria (PBR) naturally activate microorganisms found in the soil. Because they are inexpensive, effective, and environmentally friendly, PBR are gaining impor-tance for use in crop production by restoring the soil’s natural fertility and protect-ing it against drought and soil diseases, thereby stimulating plant growth. PBR decrease the use of chemical fertilisers, pesticides, and artificial growth regulators; the intensive use of these inputs has led to severe health and environmental hazards, such as soil erosion, water contamination, pesticide poisoning, decreased ground-water table, water logging, surface crusting and depletion of biodiversity. The use of PBR has been proven to be an environmentally sound way of increasing crop yields by facilitating plant growth through either a direct or indirect mechanism with the aim of sustaining soil health over the long term. (7) (PDF) Towards Plant-Beneficiary Rhizobacteria and Agricultural Sustainability. Available from: https://www.researchgate.net/publication/325854138_Towards_Plant-Beneficiary_Rhizobacteria_and_Agricultural_Sustainability [accessed Nov 19 2018].Not Availabl

    Brain imaging genetics in ADHD and beyond – Mapping pathways from gene to disorder at different levels of complexity

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