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  1. Article ; Online: Suicidal Phenotype of Proofreading-Deficient Herpes Simplex Virus 1 Polymerase Mutants.

    Brunialti, Marika / Höfler, Thomas / Nascimento, Mariana / Trimpert, Jakob

    Journal of virology

    2023  Volume 97, Issue 1, Page(s) e0135922

    Abstract: Herpes simplex virus 1 (HSV-1) encodes a family B DNA polymerase (Pol) capable of exonucleolytic proofreading whose functions have been extensively studied in the past. Early studies on ... ...

    Abstract Herpes simplex virus 1 (HSV-1) encodes a family B DNA polymerase (Pol) capable of exonucleolytic proofreading whose functions have been extensively studied in the past. Early studies on the
    MeSH term(s) DNA Replication/genetics ; Exonucleases/genetics ; Exonucleases/metabolism ; Herpesvirus 1, Human/enzymology ; Herpesvirus 1, Human/genetics ; Herpesvirus 1, Human/metabolism ; Mutation ; Phenotype
    Chemical Substances Exonucleases (EC 3.1.-) ; DNA polymerase, Simplexvirus (EC 3.1.11.-)
    Language English
    Publishing date 2023-01-04
    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.01359-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Open questions in the social lives of viruses.

    Leeks, Asher / Bono, Lisa M / Ampolini, Elizabeth A / Souza, Lucas S / Höfler, Thomas / Mattson, Courtney L / Dye, Anna E / Díaz-Muñoz, Samuel L

    Journal of evolutionary biology

    2023  Volume 36, Issue 11, Page(s) 1551–1567

    Abstract: Social interactions among viruses occur whenever multiple viral genomes infect the same cells, hosts, or populations of hosts. Viral social interactions range from cooperation to conflict, occur throughout the viral world, and affect every stage of the ... ...

    Abstract Social interactions among viruses occur whenever multiple viral genomes infect the same cells, hosts, or populations of hosts. Viral social interactions range from cooperation to conflict, occur throughout the viral world, and affect every stage of the viral lifecycle. The ubiquity of these social interactions means that they can determine the population dynamics, evolutionary trajectory, and clinical progression of viral infections. At the same time, social interactions in viruses raise new questions for evolutionary theory, providing opportunities to test and extend existing frameworks within social evolution. Many opportunities exist at this interface: Insights into the evolution of viral social interactions have immediate implications for our understanding of the fundamental biology and clinical manifestation of viral diseases. However, these opportunities are currently limited because evolutionary biologists only rarely study social evolution in viruses. Here, we bridge this gap by (1) summarizing the ways in which viruses can interact socially, including consequences for social evolution and evolvability; (2) outlining some open questions raised by viruses that could challenge concepts within social evolution theory; and (3) providing some illustrative examples, data sources, and conceptual questions, for studying the natural history of social viruses.
    MeSH term(s) Humans ; Biological Evolution ; Viruses/genetics ; Virus Diseases ; Genome, Viral ; Evolution, Molecular
    Language English
    Publishing date 2023-12-18
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1465318-7
    ISSN 1420-9101 ; 1010-061X
    ISSN (online) 1420-9101
    ISSN 1010-061X
    DOI 10.1111/jeb.14203
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  3. Article ; Online: σ

    Pennetzdorfer, Nina / Höfler, Thomas / Wölflingseder, Martina / Tutz, Sarah / Schild, Stefan / Reidl, Joachim

    Molecular microbiology

    2021  Volume 115, Issue 6, Page(s) 1244–1261

    Abstract: Bile resistance is essential for enteric pathogens, as exemplified by Vibrio cholerae, the causative agent of cholera. The outer membrane porin OmpU confers bacterial survival and colonization advantages in the presence of host-derived antimicrobial ... ...

    Abstract Bile resistance is essential for enteric pathogens, as exemplified by Vibrio cholerae, the causative agent of cholera. The outer membrane porin OmpU confers bacterial survival and colonization advantages in the presence of host-derived antimicrobial peptides as well as bile. Expression of ompU is controlled by the virulence regulator ToxR. rpoE knockouts are accompanied by suppressor mutations causing ompU downregulation. Therefore, OmpU constitutes an intersection of the ToxR regulon and the σ
    MeSH term(s) Adhesins, Bacterial/biosynthesis ; Adhesins, Bacterial/genetics ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Outer Membrane Proteins/metabolism ; Bacterial Proteins/metabolism ; DNA-Binding Proteins/metabolism ; Gene Deletion ; Gene Expression Regulation, Bacterial/genetics ; Porins/biosynthesis ; Porins/genetics ; Promoter Regions, Genetic/genetics ; Sigma Factor/genetics ; Transcription Factors/metabolism ; Vibrio cholerae/genetics ; Vibrio cholerae/metabolism
    Chemical Substances Adhesins, Bacterial ; Bacterial Outer Membrane Proteins ; Bacterial Proteins ; DNA-Binding Proteins ; OmpU protein, Vibrio cholerae ; Porins ; Sigma Factor ; Transcription Factors ; sporulation-specific sigma factors ; toxR protein, Vibrio cholerae
    Language English
    Publishing date 2021-01-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.14669
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2502: Show issues Location:
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  4. Article: Regulation of R1 Plasmid Transfer by H-NS, ArcA, TraJ, and DNA Sequence Elements.

    Bischof, Karin / Schiffer, Doris / Trunk, Sarah / Höfler, Thomas / Hopfer, Anja / Rechberger, Gerald / Koraimann, Günther

    Frontiers in microbiology

    2020  Volume 11, Page(s) 1254

    Abstract: In conjugative elements such as integrating conjugative elements (ICEs) or conjugative plasmids (CPs) transcription of DNA transfer genes is a prerequisite for cells to become transfer competent, i.e., capable of delivering plasmid DNA via bacterial ... ...

    Abstract In conjugative elements such as integrating conjugative elements (ICEs) or conjugative plasmids (CPs) transcription of DNA transfer genes is a prerequisite for cells to become transfer competent, i.e., capable of delivering plasmid DNA via bacterial conjugation into new host bacteria. In the large family of F-like plasmids belonging to the MobF
    Language English
    Publishing date 2020-06-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2020.01254
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Fast-forwarding evolution-Accelerated adaptation in a proofreading-deficient hypermutator herpesvirus.

    Xing, Na / Höfler, Thomas / Hearn, Cari J / Nascimento, Mariana / Camps Paradell, Georgina / McMahon, Dino P / Kunec, Dusan / Osterrieder, Nikolaus / Cheng, Hans H / Trimpert, Jakob

    Virus evolution

    2022  Volume 8, Issue 2, Page(s) veac099

    Abstract: Evolution relies on the availability of genetic diversity for fitness-based selection. However, most deoxyribonucleic acid (DNA) viruses employ DNA polymerases (Pol) capable of exonucleolytic proofreading to limit mutation rates during DNA replication. ... ...

    Abstract Evolution relies on the availability of genetic diversity for fitness-based selection. However, most deoxyribonucleic acid (DNA) viruses employ DNA polymerases (Pol) capable of exonucleolytic proofreading to limit mutation rates during DNA replication. The relative genetic stability produced by high-fidelity genome replication can make studying DNA virus adaptation and evolution an intensive endeavor, especially in slowly replicating viruses. Here, we present a proofreading-impaired Pol mutant (Y547S) of Marek's disease virus that exhibits a hypermutator phenotype while maintaining unimpaired growth
    Language English
    Publishing date 2022-10-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/veac099
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  6. Book: Teilvorhaben: Zellen und Stacks III

    Hoefler, Thomas
    Title variant ZeuS III ; sub-project: Cells and stacks III
    Institution Bayerische Motoren Werke Aktiengesellschaft, Antriebs- und Fahrwerkssysteme, Zukunftsantriebe, Hufelandstr. 8 a, 80937, Muenchen, DE
    Keywords Kosten ; Zuverlaessigkeit ; Zelle ; Fertigungstechnik ; Kostensenkung ; Energie ; Produktgestaltung ; Beschichtung ; Laborversuch ; Produktionstechnik ; Energiekosten ; Evaluation ; Pruefstand ; Kfz-Technik ; Kfz-Industrie ; Energietechnik ; Wirtschaftlichkeit ; Wirtschaftliche Aspekte
    Document type Book
    Remark project start: 01/01/2007 project end: 12/31/2010 grant ID: 0327766A
    Database Environmental research database (UFORDAT) of the German Federal Environment Agency (UBA)

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  7. Article ; Online: Host stimuli and operator binding sites controlling protein interactions between virulence master regulator ToxR and ToxS in Vibrio cholerae.

    Lembke, Mareike / Höfler, Thomas / Walter, Ada-Natsuko / Tutz, Sarah / Fengler, Vera / Schild, Stefan / Reidl, Joachim

    Molecular microbiology

    2020  Volume 114, Issue 2, Page(s) 262–278

    Abstract: Protein-protein interactions (PPIs) are key mechanisms in the maintenance of biological regulatory networks. Herein, we characterize PPIs within ToxR and its co-activator, ToxS, to understand the mechanisms of ToxR transcription factor activation. ToxR ... ...

    Abstract Protein-protein interactions (PPIs) are key mechanisms in the maintenance of biological regulatory networks. Herein, we characterize PPIs within ToxR and its co-activator, ToxS, to understand the mechanisms of ToxR transcription factor activation. ToxR is a key transcription activator that is supported by ToxS for virulence gene regulation in Vibrio cholerae. ToxR comprises a cytoplasmic DNA-binding domain that is linked by a transmembrane domain to a periplasmic signal receiver domain containing two cysteine residues. ToxR-ToxR and ToxR-ToxS PPIs were detected using an adenylate-cyclase-based bacterial two-hybrid system approach in Escherichia coli. We found that the ToxR-ToxR PPIs are significantly increased in response to ToxR operators, the co-activator ToxS and bile salts. We suggest that ToxS and bile salts promote the interaction between ToxR molecules that ultimately results in dimerization. Upon binding of operators, ToxR-ToxR PPIs are found at the highest frequency. Moreover, disulfide-bond-dependent interaction in the periplasm results in homodimer formation that is promoted by DNA binding. The formation of these homodimers and the associated transcriptional activity of ToxR were strongly dependent on the oxidoreductases DsbA/DsbC. These findings show that protein and non-protein partners, that either transiently or stably interact with ToxR, fine-tune ToxR PPIs, and its associated transcriptional activity in changing environments.
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Bile Acids and Salts/metabolism ; Binding Sites/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Escherichia coli/metabolism ; Gene Expression Regulation, Bacterial/genetics ; Host-Pathogen Interactions/physiology ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Protein Domains/genetics ; Protein Interaction Maps/physiology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Vibrio cholerae/metabolism ; Vibrio cholerae/pathogenicity ; Virulence/genetics ; Virulence Factors/genetics ; Virulence Factors/metabolism
    Chemical Substances Bacterial Proteins ; Bile Acids and Salts ; DNA-Binding Proteins ; Membrane Proteins ; Transcription Factors ; Virulence Factors ; toxR protein, Vibrio cholerae ; ToxS protein, Vibrio cholerae (135315-97-8)
    Language English
    Publishing date 2020-04-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.14510
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2502: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  8. Article ; Online: Neural Network-Assisted Humanization of COVID-19 Hamster scRNAseq Data Reveals Matching Severity States in Human Disease

    Friedrich, Vincent D / Pennitz, Peter / Wyler, Emanuel / Adler, Julia M / Postmus, Dylan / Alves, Luiz Gustavo Teixeira / Prigann, Julia / Pott, Fabian / Vladimirova, Daria / Hoefler, Thomas / Goekeri, Cengiz / Landthaler, Markus / Goffinet, Christine / Saliba, Antoine-Emmanuel / Scholz, Markus / Witzenrath, Martin / Trimpert, Jakob / Kirsten, Holger / Nouailles, Geraldine

    bioRxiv

    Abstract: Translating findings from animal models to human disease is essential for dissecting disease mechanisms, developing and testing precise therapeutic strategies. The coronavirus disease 2019 (COVID-19) pandemic has highlighted this need, particularly for ... ...

    Abstract Translating findings from animal models to human disease is essential for dissecting disease mechanisms, developing and testing precise therapeutic strategies. The coronavirus disease 2019 (COVID-19) pandemic has highlighted this need, particularly for models showing disease severity-dependent immune responses. Single-cell transcriptomics (scRNAseq) is well poised to reveal similarities and differences between species at the molecular and cellular level with unprecedented resolution. However, computational methods enabling detailed matching are still scarce. Here, we provide a structured scRNAseq-based approach that we applied to scRNAseq from blood leukocytes originating from humans and hamsters affected with moderate or severe COVID-19. Integration of COVID-19 patient data with two hamster models that develop moderate (Syrian hamster, Mesocricetus auratus) or severe (Roborovski hamster, Phodopus roborovskii) disease revealed that most cellular states are shared across species. A neural network-based analysis using variational autoencoders quantified the overall transcriptomic similarity across species and severity levels, showing highest similarity between neutrophils of Roborovski hamsters and severe COVID-19 patients, while Syrian hamsters better matched patients with moderate disease, particularly in classical monocytes. We further used transcriptome-wide differential expression analysis to identify which disease stages and cell types display strongest transcriptional changes. Consistently, hamster9s response to COVID-19 was most similar to humans in monocytes and neutrophils. Disease-linked pathways found in all species specifically related to interferon response or inhibition of viral replication. Analysis of candidate genes and signatures supported the results. Our structured neural network-supported workflow could be applied to other diseases, allowing better identification of suitable animal models with similar pathomechanisms across species.
    Keywords covid19
    Language English
    Publishing date 2024-01-12
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2024.01.11.574849
    Database COVID19

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  9. Article ; Online: Development of safe and highly protective live-attenuated SARS-CoV-2 vaccine candidates by genome recoding.

    Trimpert, Jakob / Dietert, Kristina / Firsching, Theresa C / Ebert, Nadine / Thi Nhu Thao, Tran / Vladimirova, Daria / Kaufer, Susanne / Labroussaa, Fabien / Abdelgawad, Azza / Conradie, Andelé / Höfler, Thomas / Adler, Julia M / Bertzbach, Luca D / Jores, Joerg / Gruber, Achim D / Thiel, Volker / Osterrieder, Nikolaus / Kunec, Dusan

    Cell reports

    2021  Volume 36, Issue 5, Page(s) 109493

    Abstract: Safe and effective vaccines are urgently needed to stop the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We construct a series of live attenuated vaccine candidates by large-scale recoding of the SARS-CoV-2 genome and ... ...

    Abstract Safe and effective vaccines are urgently needed to stop the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We construct a series of live attenuated vaccine candidates by large-scale recoding of the SARS-CoV-2 genome and assess their safety and efficacy in Syrian hamsters. Animals were vaccinated with a single dose of the respective recoded virus and challenged 21 days later. Two of the tested viruses do not cause clinical symptoms but are highly immunogenic and induce strong protective immunity. Attenuated viruses replicate efficiently in the upper but not in the lower airways, causing only mild pulmonary histopathology. After challenge, hamsters develop no signs of disease and rapidly clear challenge virus: at no time could infectious virus be recovered from the lungs of infected animals. The ease with which attenuated virus candidates can be produced and administered favors their further development as vaccines to combat the ongoing pandemic.
    MeSH term(s) Animals ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines ; Chlorocebus aethiops ; Gene Editing ; Genome, Viral ; Humans ; Immunity ; Mesocricetus ; Mutation ; Pandemics/prevention & control ; Respiratory System/pathology ; Respiratory System/virology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Vaccines, Attenuated ; Vero Cells ; Virus Replication
    Chemical Substances COVID-19 Vaccines ; Vaccines, Attenuated
    Language English
    Publishing date 2021-07-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.109493
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  10. Book ; Thesis: Synthese und supramolekulare Strukturen von Cycldextrinsulfonaten

    Höfler, Thomas

    1996  

    Author's details von Thomas Höfler
    Language German
    Size III, 142 S, graph. Darst
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Karlsruhe, 1996
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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