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  • 1
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  Molecular Psychiatry Vol. 26, No. 10 ( 2021-10), p. 5790-5796
    In: Molecular Psychiatry, Springer Science and Business Media LLC, Vol. 26, No. 10 ( 2021-10), p. 5790-5796
    Abstract: Alzheimerʼs disease (AD) is a neurodegenerative disorder of unknown cause with complex genetic and environmental traits. While AD is extremely prevalent in human elderly, it hardly occurs in non-primate mammals and even non-human-primates develop only an incomplete form of the disease. This specificity of AD to human clearly implies a phylogenetic aspect. Still, the evolutionary dimension of AD pathomechanism remains difficult to prove and has not been established so far. To analyze the evolutionary age and dynamics of AD-associated-genes, we established the AD-associated genome-wide RNA-profile comprising both protein-coding and non-protein-coding transcripts. We than applied a systematic analysis on the conservation of splice-sites as a measure of gene-structure based on multiple alignments across vertebrates of homologs of AD-associated-genes. Here, we show that nearly all AD-associated-genes are evolutionarily old and did not originate later in evolution than not-AD-associated-genes. However, the gene-structures of loci, that exhibit AD-associated changes in their expression, evolve faster than the genome at large. While protein-coding-loci exhibit an enhanced rate of small changes in gene structure, non-coding loci show even much larger changes. The accelerated evolution of AD-associated-genes indicates a more rapid functional adaptation of these genes. In particular AD-associated non-coding-genes play an important, as yet largely unexplored, role in AD. This phylogenetic trait indicates that recent adaptive evolution of human brain is causally involved in basic principles of neurodegeneration. It highlights the necessity for a paradigmatic change of our disease-concepts and to reconsider the appropriateness of current animal-models to develop disease-modifying strategies that can be translated to human.
    Type of Medium: Online Resource
    ISSN: 1359-4184 , 1476-5578
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1502531-7
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  • 2
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-01-11)
    Abstract: Scientific Reports 6: Article number: 34589; published online: 07 October 2016; updated: 11 January 2017 In this Article, Ivo Grosse is incorrectly affiliated to “Department of Soil Ecology, UFZ - Helmholtz Centre for Environmental Research, Theodor-Lieser-Str. 4, 06120, Halle/Saale, Germany”. The correct affiliations for Ivo Grosse are listed below:
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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  • 3
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-07-04)
    Abstract: Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2553671-0
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  • 4
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2016-10-07)
    Abstract: The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases ( DUSP genes) and of PPP1R15A , which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2615211-3
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2017
    In:  Journal of Biotechnology Vol. 261 ( 2017-11), p. 97-104
    In: Journal of Biotechnology, Elsevier BV, Vol. 261 ( 2017-11), p. 97-104
    Type of Medium: Online Resource
    ISSN: 0168-1656
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2016476-2
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2020
    In:  Theory in Biosciences Vol. 139, No. 4 ( 2020-12), p. 349-359
    In: Theory in Biosciences, Springer Science and Business Media LLC, Vol. 139, No. 4 ( 2020-12), p. 349-359
    Abstract: Many small nucleolar RNAs and many of the hairpin precursors of miRNAs are processed from long non-protein-coding host genes. In contrast to their highly conserved and heavily structured payload, the host genes feature poorly conserved sequences. Nevertheless, there is mounting evidence that the host genes have biological functions beyond their primary task of carrying a ncRNA as payload. So far, no connections between the function of the host genes and the function of their payloads have been reported. Here we investigate whether there is evidence for an association of host gene function or mechanisms with the type of payload. To assess this hypothesis we test whether the miRNA host genes (MIRHGs), snoRNA host genes (SNHGs), and other lncRNA host genes can be distinguished based on sequence and/or structure features unrelated to their payload. A positive answer would imply a functional and mechanistic correlation between host genes and their payload, provided the classification does not depend on the presence and type of the payload. A negative answer would indicate that to the extent that secondary functions are acquired, they are not strongly constrained by the prior, primary function of the payload. We find that the three classes can be distinguished reliably when the classifier is allowed to extract features from the payloads. They become virtually indistinguishable, however, as soon as only sequence and structure of parts of the host gene distal from the snoRNAs or miRNA payload is used for classification. This indicates that the functions of MIRHGs and SNHGs are largely independent of the functions of their payloads. Furthermore, there is no evidence that the MIRHGs and SNHGs form coherent classes of long non-coding RNAs distinguished by features other than their payloads.
    Type of Medium: Online Resource
    ISSN: 1431-7613 , 1611-7530
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2020743-8
    detail.hit.zdb_id: 1376847-5
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  Algorithms for Molecular Biology Vol. 16, No. 1 ( 2021-12)
    In: Algorithms for Molecular Biology, Springer Science and Business Media LLC, Vol. 16, No. 1 ( 2021-12)
    Abstract: Advances in genome sequencing over the last years have lead to a fundamental paradigm shift in the field. With steadily decreasing sequencing costs, genome projects are no longer limited by the cost of raw sequencing data, but rather by computational problems associated with genome assembly. There is an urgent demand for more efficient and and more accurate methods is particular with regard to the highly complex and often very large genomes of animals and plants. Most recently, “hybrid” methods that integrate short and long read data have been devised to address this need. Results is such a hybrid genome assembler. It has been designed specificially with an emphasis on utilizing low-coverage short and long reads. starts from a bipartite overlap graph between long reads and restrictively filtered short-read unitigs. This graph is translated into a long-read overlap graph G . Instead of the more conventional approach of removing tips, bubbles, and other local features, stepwisely extracts subgraphs whose global properties approach a disjoint union of paths. First, a consistently oriented subgraph is extracted, which in a second step is reduced to a directed acyclic graph. In the next step, properties of proper interval graphs are used to extract contigs as maximum weight paths. These path are translated into genomic sequences only in the final step. A prototype implementation of , entirely written in python, not only yields significantly more accurate assemblies of the yeast and fruit fly genomes compared to state-of-the-art pipelines but also requires much less computational effort. Conclusions is new low-cost genome assembler that copes well with large genomes and low coverage. It is based on a novel approach for reducing the overlap graph to a collection of paths, thus opening new avenues for future improvements. Availability The prototype is available at https://github.com/TGatter/LazyB .
    Type of Medium: Online Resource
    ISSN: 1748-7188
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2224970-9
    SSG: 12
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  • 8
    In: Non-Coding RNA, MDPI AG, Vol. 7, No. 2 ( 2021-05-28), p. 32-
    Abstract: Dictyostelium discoideum is a social amoeba, which on starvation develops from a single-cell state to a multicellular fruiting body. This developmental process is accompanied by massive changes in gene expression, which also affect non-coding RNAs. Here, we investigate how tRNAs as key regulators of the translation process are affected by this transition. To this end, we used LOTTE-seq to sequence the tRNA pool of D. discoideum at different developmental time points and analyzed both tRNA composition and tRNA modification patterns. We developed a workflow for the specific detection of modifications from reverse transcriptase signatures in chemically untreated RNA-seq data at single-nucleotide resolution. It avoids the comparison of treated and untreated RNA-seq data using reverse transcription arrest patterns at nucleotides in the neighborhood of a putative modification site as internal control. We find that nucleotide modification sites in D. discoideum tRNAs largely conform to the modification patterns observed throughout the eukaroytes. However, there are also previously undescribed modification sites. We observe substantial dynamic changes of both expression levels and modification patterns of certain tRNA types during fruiting body development. Beyond the specific application to D. discoideum our results demonstrate that the developmental variability of tRNA expression and modification can be traced efficiently with LOTTE-seq.
    Type of Medium: Online Resource
    ISSN: 2311-553X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2813993-8
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  • 9
    In: Molecular Systems Biology, EMBO, Vol. 12, No. 5 ( 2016-05)
    Abstract: image A time‐resolved quantitative analysis of TTP binding sites, mRNA abundance, and mRNA stability in mouse macrophages generates a transcriptome‐wide atlas of cis ‐acting elements controlling mRNA decay in inflammation. A genome‐wide, high‐resolution, and time‐resolved analysis of TTP binding sites is performed in immunostimulated macrophages. “ TTP atlas”, a functionally annotated collection of mapped TTP binding sites relating TTP binding to transcriptome‐wide differential mRNA decay rates and differential mRNA expression in WT and TTP ‐deficient macrophages, is generated ( http://ttp-atlas.univie.ac.at ). Transcriptome‐wide analysis of mRNA stability and mRNA expression identifies a TTP ‐driven switch initiating resolution of inflammation and indicates a limited co‐regulation of inflammatory mRNA decay by TTP and HuR.
    Type of Medium: Online Resource
    ISSN: 1744-4292 , 1744-4292
    Language: English
    Publisher: EMBO
    Publication Date: 2016
    detail.hit.zdb_id: 2193510-5
    SSG: 12
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  • 10
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-4-15)
    Abstract: CRISPR-Cas constitutes an adaptive prokaryotic defence system against invasive nucleic acids like viruses and plasmids. Beyond their role in immunity, CRISPR-Cas systems have been shown to closely interact with components of cellular DNA repair pathways, either by regulating their expression or via direct protein-protein contact and enzymatic activity. The integrase Cas1 is usually involved in the adaptation phase of CRISPR-Cas immunity but an additional role in cellular DNA repair pathways has been proposed previously. Here, we analysed the capacity of an archaeal Cas1 from Haloferax volcanii to act upon DNA damage induced by oxidative stress and found that a deletion of the cas1 gene led to reduced survival rates following stress induction. In addition, our results indicate that Cas1 is directly involved in DNA repair as the enzymatically active site of the protein is crucial for growth under oxidative conditions. Based on biochemical assays, we propose a mechanism by which Cas1 plays a similar function to DNA repair protein Fen1 by cleaving branched intermediate structures. The present study broadens our understanding of the functional link between CRISPR-Cas immunity and DNA repair by demonstrating that Cas1 and Fen1 display equivalent roles during archaeal DNA damage repair.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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