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  1. Article ; Online: Proteome Profiling of

    Birhanu, Alemayehu Godana / Gómez-Muñoz, Marta / Kalayou, Shewit / Riaz, Tahira / Lutter, Timo / Yimer, Solomon Abebe / Abebe, Markos / Tønjum, Tone

    ACS omega

    2022  Volume 7, Issue 4, Page(s) 3470–3482

    Abstract: Reactive nitrogen species (RNS) are secreted by human cells in response to infection ... ...

    Abstract Reactive nitrogen species (RNS) are secreted by human cells in response to infection by
    Language English
    Publishing date 2022-01-14
    Publishing country United States
    Document type Journal Article
    ISSN 2470-1343
    ISSN (online) 2470-1343
    DOI 10.1021/acsomega.1c05923
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Lineage-Specific Proteomic Signatures in the

    Yimer, Solomon Abebe / Kalayou, Shewit / Homberset, Håvard / Birhanu, Alemayehu Godana / Riaz, Tahira / Zegeye, Ephrem Debebe / Lutter, Timo / Abebe, Markos / Holm-Hansen, Carol / Aseffa, Abraham / Tønjum, Tone

    Frontiers in microbiology

    2020  Volume 11, Page(s) 550760

    Abstract: Despite the discovery of the tubercle bacillus more than 130 years ago, its physiology and the mechanisms of virulence are still not fully understood. A comprehensive analysis of the proteomes of members of the human- ... ...

    Abstract Despite the discovery of the tubercle bacillus more than 130 years ago, its physiology and the mechanisms of virulence are still not fully understood. A comprehensive analysis of the proteomes of members of the human-adapted
    Language English
    Publishing date 2020-09-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2020.550760
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Constitutive nuclear localization of an alternatively spliced sirtuin-2 isoform.

    Rack, Johannes G M / VanLinden, Magali R / Lutter, Timo / Aasland, Rein / Ziegler, Mathias

    Journal of molecular biology

    2014  Volume 426, Issue 8, Page(s) 1677–1691

    Abstract: Sirtuin-2 (SIRT2), the cytoplasmic member of the sirtuin family, has been implicated in the deacetylation of nuclear proteins. Although the enzyme has been reported to be located to the nucleus during G2/M phase, its spectrum of targets suggests ... ...

    Abstract Sirtuin-2 (SIRT2), the cytoplasmic member of the sirtuin family, has been implicated in the deacetylation of nuclear proteins. Although the enzyme has been reported to be located to the nucleus during G2/M phase, its spectrum of targets suggests functions in the nucleus throughout the cell cycle. While a nucleocytoplasmic shuttling mechanism has been proposed for SIRT2, recent studies have indicated the presence of a constitutively nuclear isoform. Here we report the identification of a novel splice variant (isoform 5) of SIRT2 that lacks a nuclear export signal and encodes a predominantly nuclear isoform. This novel isoform 5 fails to show deacetylase activity using several assays, both in vitro and in vivo, and we are led to conclude that this isoform is catalytically inactive. Nevertheless, it retains the ability to interact with p300, a known interaction partner. Moreover, changes in intrinsic tryptophan fluorescence upon denaturation indicate that the protein is properly folded. These data, together with computational analyses, confirm the structural integrity of the catalytic domain. Our results suggest an activity-independent nuclear function of the novel isoform.
    MeSH term(s) 5' Untranslated Regions ; Alternative Splicing ; Catalytic Domain/genetics ; Cell Nucleus/enzymology ; HEK293 Cells ; HeLa Cells ; Humans ; Models, Molecular ; Nuclear Export Signals ; Protein Conformation ; Protein Folding ; Protein Isoforms/chemistry ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Protein Structure, Tertiary ; RNA Precursors/genetics ; RNA Precursors/metabolism ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Sirtuin 2/chemistry ; Sirtuin 2/genetics ; Sirtuin 2/metabolism ; Static Electricity
    Chemical Substances 5' Untranslated Regions ; Nuclear Export Signals ; Protein Isoforms ; RNA Precursors ; Recombinant Proteins ; SIRT2 protein, human (EC 3.5.1.-) ; Sirtuin 2 (EC 3.5.1.-)
    Language English
    Publishing date 2014-04-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2013.10.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 867: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: High Prevalence of Infectious Adeno-associated Virus (AAV) in Human Peripheral Blood Mononuclear Cells Indicative of T Lymphocytes as Sites of AAV Persistence.

    Hüser, Daniela / Khalid, Dina / Lutter, Timo / Hammer, Eva-Maria / Weger, Stefan / Heßler, Melanie / Kalus, Ulrich / Tauchmann, Yvonne / Hensel-Wiegel, Karin / Lassner, Dirk / Heilbronn, Regine

    Journal of virology

    2017  Volume 91, Issue 4

    Abstract: Seroepidemiology shows that infections with adeno-associated virus (AAV) are widespread, but diverse AAV serotypes isolated from humans or nonhuman primates have so far not been proven to be causes of human disease. In view of the increasing success of ... ...

    Abstract Seroepidemiology shows that infections with adeno-associated virus (AAV) are widespread, but diverse AAV serotypes isolated from humans or nonhuman primates have so far not been proven to be causes of human disease. In view of the increasing success of AAV-derived vectors in human gene therapy, definition of the in vivo sites of wild-type AAV persistence and the clinical consequences of its reactivation is becoming increasingly urgent. Here, we identify the presumed cell type for AAV persistence in the human host by highly sensitive AAV PCRs developed for the full spectrum of human AAV serotypes. In genomic-DNA samples from leukocytes of 243 healthy blood donors, 34% were found to be AAV positive, predominantly AAV type 2 (AAV2) (77%), AAV5 (19%), and additional serotypes. Roughly 11% of the blood donors had mixed AAV infections. AAV prevalence was dramatically increased in immunosuppressed patients, 76% of whom were AAV positive. Of these, at least 45% displayed mixed infections. Follow-up of single blood donors over 2 years allowed repeated detection of the initial and/or additional AAV serotypes, suggestive of fluctuating, persistent infection. Leukocyte separation revealed that AAV resided in CD3
    Importance: Adeno-associated virus is viewed as apathogenic and replication defective, requiring coinfection with adenovirus or herpesvirus for productive infection. In vivo persistence of a defective virus requires latency in specialized cell types to escape the host immune response until viral spread becomes possible. Reactivation from latency can be induced by diverse stimuli, including infections, typically induced upon host immunosuppression. We show for the first time that infectious AAV is highly prevalent in human leukocytes, specifically T lymphocytes, and that AAV is strongly amplified upon immunosuppression, along with reactivation of latent human herpesviruses. In the absence of an animal model to study the AAV life cycle, our findings in the human host will advance the understanding of AAV latency, reactivation, and in vivo pathogenesis.
    MeSH term(s) DNA, Viral ; Dependovirus/classification ; Dependovirus/physiology ; Humans ; Immunocompromised Host ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/virology ; Parvoviridae Infections/epidemiology ; Parvoviridae Infections/virology ; Polymerase Chain Reaction ; Prevalence ; Seroepidemiologic Studies ; T-Lymphocytes/immunology ; T-Lymphocytes/virology ; Virus Activation ; Virus Latency
    Chemical Substances DNA, Viral
    Language English
    Publishing date 2017-01-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.02137-16
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 609: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: The PHD finger of p300 influences its ability to acetylate histone and non-histone targets.

    Rack, Johannes G M / Lutter, Timo / Kjæreng Bjerga, Gro Elin / Guder, Corina / Ehrhardt, Christine / Värv, Signe / Ziegler, Mathias / Aasland, Rein

    Journal of molecular biology

    2014  Volume 426, Issue 24, Page(s) 3960–3972

    Abstract: In enzymes that regulate chromatin structure, the combinatorial occurrence of modules that alter and recognise histone modifications is a recurrent feature. In this study, we explored the functional relationship between the acetyltransferase domain and ... ...

    Abstract In enzymes that regulate chromatin structure, the combinatorial occurrence of modules that alter and recognise histone modifications is a recurrent feature. In this study, we explored the functional relationship between the acetyltransferase domain and the adjacent bromodomain/PHD finger (bromo/PHD) region of the transcriptional coactivator p300. We found that the bromo/PHD region of p300 can bind to the acetylated catalytic domain in vitro and augment the catalytic activity of the enzyme. Deletion of the PHD finger, but not the bromodomain, impaired the ability of the enzyme to acetylate histones in vivo, whilst it enhanced p300 self-acetylation. A point mutation in the p300 PHD finger that is related to the Rubinstein-Taybi syndrome resulted in increased self-acetylation but retained the ability to acetylate histones. Hence, the PHD finger appears to negatively regulate self-acetylation. Furthermore, our data suggest that the PHD finger has a role in the recruitment of p300 to chromatin.
    MeSH term(s) Acetylation ; Binding Sites/genetics ; Biocatalysis ; E1A-Associated p300 Protein/chemistry ; E1A-Associated p300 Protein/genetics ; E1A-Associated p300 Protein/metabolism ; HEK293 Cells ; HeLa Cells ; Histones/metabolism ; Humans ; Immunoblotting ; Immunohistochemistry ; Microscopy, Fluorescence ; Models, Molecular ; Point Mutation ; Protein Binding ; Protein Structure, Tertiary
    Chemical Substances Histones ; E1A-Associated p300 Protein (EC 2.3.1.48) ; EP300 protein, human (EC 2.3.1.48)
    Language English
    Publishing date 2014-12-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2014.08.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 867: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Integration preferences of wildtype AAV-2 for consensus rep-binding sites at numerous loci in the human genome.

    Hüser, Daniela / Gogol-Döring, Andreas / Lutter, Timo / Weger, Stefan / Winter, Kerstin / Hammer, Eva-Maria / Cathomen, Toni / Reinert, Knut / Heilbronn, Regine

    PLoS pathogens

    2010  Volume 6, Issue 7, Page(s) e1000985

    Abstract: Adeno-associated virus type 2 (AAV) is known to establish latency by preferential integration in human chromosome 19q13.42. The AAV non-structural protein Rep appears to target a site called AAVS1 by simultaneously binding to Rep-binding sites (RBS) ... ...

    Abstract Adeno-associated virus type 2 (AAV) is known to establish latency by preferential integration in human chromosome 19q13.42. The AAV non-structural protein Rep appears to target a site called AAVS1 by simultaneously binding to Rep-binding sites (RBS) present on the AAV genome and within AAVS1. In the absence of Rep, as is the case with AAV vectors, chromosomal integration is rare and random. For a genome-wide survey of wildtype AAV integration a linker-selection-mediated (LSM)-PCR strategy was designed to retrieve AAV-chromosomal junctions. DNA sequence determination revealed wildtype AAV integration sites scattered over the entire human genome. The bioinformatic analysis of these integration sites compared to those of rep-deficient AAV vectors revealed a highly significant overrepresentation of integration events near to consensus RBS. Integration hotspots included AAVS1 with 10% of total events. Novel hotspots near consensus RBS were identified on chromosome 5p13.3 denoted AAVS2 and on chromsome 3p24.3 denoted AAVS3. AAVS2 displayed seven independent junctions clustered within only 14 bp of a consensus RBS which proved to bind Rep in vitro similar to the RBS in AAVS3. Expression of Rep in the presence of rep-deficient AAV vectors shifted targeting preferences from random integration back to the neighbourhood of consensus RBS at hotspots and numerous additional sites in the human genome. In summary, targeted AAV integration is not as specific for AAVS1 as previously assumed. Rather, Rep targets AAV to integrate into open chromatin regions in the reach of various, consensus RBS homologues in the human genome.
    MeSH term(s) Base Sequence ; Binding Sites ; Chromosomes, Human ; Computational Biology ; DNA-Binding Proteins/metabolism ; Dependovirus/genetics ; Genome, Human ; Genome, Viral ; Humans ; Viral Proteins/metabolism ; Virus Integration ; Virus Latency/genetics
    Chemical Substances DNA-Binding Proteins ; Viral Proteins ; rep proteins, Adeno-associated virus 2 (137750-19-7)
    Language English
    Publishing date 2010-07-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1000985
    Database MEDical Literature Analysis and Retrieval System OnLINE

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