22 research outputs found

    Microarray-Based Sketches of the HERV Transcriptome Landscape

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    Human endogenous retroviruses (HERVs) are spread throughout the genome and their long terminal repeats (LTRs) constitute a wide collection of putative regulatory sequences. Phylogenetic similarities and the profusion of integration sites, two inherent characteristics of transposable elements, make it difficult to study individual locus expression in a large-scale approach, and historically apart from some placental and testis-regulated elements, it was generally accepted that HERVs are silent due to epigenetic control. Herein, we have introduced a generic method aiming to optimally characterize individual loci associated with 25-mer probes by minimizing cross-hybridization risks. We therefore set up a microarray dedicated to a collection of 5,573 HERVs that can reasonably be assigned to a unique genomic position. We obtained a first view of the HERV transcriptome by using a composite panel of 40 normal and 39 tumor samples. The experiment showed that almost one third of the HERV repertoire is indeed transcribed. The HERV transcriptome follows tropism rules, is sensitive to the state of differentiation and, unexpectedly, seems not to correlate with the age of the HERV families. The probeset definition within the U3 and U5 regions was used to assign a function to some LTRs (i.e. promoter or polyA) and revealed that (i) autonomous active LTRs are broadly subjected to operational determinism (ii) the cellular gene density is substantially higher in the surrounding environment of active LTRs compared to silent LTRs and (iii) the configuration of neighboring cellular genes differs between active and silent LTRs, showing an approximately 8 kb zone upstream of promoter LTRs characterized by a drastic reduction in sense cellular genes. These gathered observations are discussed in terms of virus/host adaptive strategies, and together with the methods and tools developed for this purpose, this work paves the way for further HERV transcriptome projects

    HIV infection and HERV expression: a review

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    The human genome contains multiple copies of retrovirus genomes known as endogenous retroviruses (ERVs) that have entered the germ-line at some point in evolution. Several of these proviruses have retained (partial) coding capacity, so that a number of viral proteins or even virus particles are expressed under various conditions. Human ERVs (HERVs) belong to the beta-, gamma-, or spuma- retrovirus groups. Endogenous delta- and lenti- viruses are notably absent in humans, although endogenous lentivirus genomes have been found in lower primates. Exogenous retroviruses that currently form a health threat to humans intriguingly belong to those absent groups. The best studied of the two infectious human retroviruses is the lentivirus human immunodeficiency virus (HIV) which has an overwhelming influence on its host by infecting cells of the immune system. One HIV-induced change is the induction of HERV transcription, often leading to induced HERV protein expression. This review will discuss the potential HIV-HERV interactions

    Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins

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    Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. Methods For brain and spinal cord tissue samples from ALS patients and controls, we identified transcribed HML-2 loci by generating and mapping HML-2-specific cDNA sequences. We predicted expression of HML-2 env gene-derived proteins based on the observed cDNA sequences. Furthermore, we determined overall HML-2 transcript levels by RT-qPCR and investigated presence of HML-2 Env protein in ALS and control tissue samples by Western blotting. Results We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Conclusions Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease

    Transposable elements in the mammalian embryo: pioneers surviving through stealth and service

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    Controlled synthesis and catalytic properties of supported In Pd intermetallic compounds

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    DTA/TG/MS measurements were used to investigate the temperature-dependent and successive phase formation of different intermetallic In-Pd compounds by controlled reduction of PdO/In2\O3 with hydrogen. Reduction procedures were developed to obtain supported intermetallic InPd and In3Pd2 particles by reactive metal-support interaction (RMSI) without detectable amounts of other compounds. In7Pd3 could only be obtained in admixture with elemental indium due to the direct reduction of the In2O3 support at temperatures above 350 degrees C. All materials exhibit catalytic activity for methanol steam reforming and exhibit high CO2 selectivities up to 98%. Long-term measurements proved the superior stability of the In-Pd/In2O3 materials in comparison with Cu-based systems over 100 h times on stream with high selectivity. (C) 2016 Elsevier Inc. All rights reserved

    Ga Pd Ga2O3 Catalysts The Role of Gallia Polymorphs, Intermetallic Compounds, and Pretreatment Conditions on Selectivity and Stability in Different Reactions

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    A series of gallia-supported Pd-Ga catalysts that consist of metallic nanoparticles on three porous polymorphs of Ga2O3 (α-, β-, and γ-Ga2O3) were synthesized by a controlled co-precipitation of Pd and Ga. The effects of formation of Ga-Pd intermetallic compounds (IMCs) were studied in four catalytic reactions: methanol steam reforming, hydrogenation of acetylene, and methanol synthesis by CO and CO2 hydrogenation reactions. The IMC Pd2Ga forms upon reduction of α- and β-Ga2O3-supported materials in hydrogen at temperatures of 250 and 310 °C, respectively. At higher temperatures, Ga-enrichment of the intermetallic particles is observed, leading to formation of Pd5Ga3 before the support itself is reduced at temperatures above 565 °C. In the case of Ga-Pd/γ-Ga2O3, no information about the metal particles could be obtained owing to their very small size and high dispersion; however, the catalytic results suggest that the IMC Pd2Ga also forms in this sample. Pd2Ga/gallia samples show a stable selectivity towards ethylene in acetylene hydrogenation (≈75 %), which is higher than for a monometallic Pd reference catalyst. An even higher selectivity of 80 % was observed for Pd5Ga3 supported on α-Ga2O3. In methanol steam reforming, the Ga-Pd/Gallia catalysts showed, in contrast to Pd/Al2O3, selectivity towards CO2 of up to 40 %. However, higher selectivities, which have been reported for Pd2Ga in literature, could not be reproduced in this study, which might be a result of particle size effects. The initially higher selectivity of the Pd5Ga3-containing samples was not stable, suggesting superior catalytic properties for this IMC, but that re-oxidation of Ga species and formation of Pd2Ga occurs under reaction conditions. In methanol synthesis, CO hydrogenation did not occur, but a considerable methanol yield from a CO2/H2 feed was observed for Pd2Ga/α-Ga2O3
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