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  1. Book ; Thesis: Rhadinovirus vector-mediated transgene expression and regulation

    Toptan, Tuna

    2010  

    Author's details vorgelegt von Tuna Toptan
    Subject code 616.9
    Language English
    Size VI, 91 Bl. : Ill., graph. Darst., 30 cm
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Heidelberg, Univ., Diss., 2010
    HBZ-ID HT016704044
    Database Catalogue ZB MED Medicine, Health

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  2. Article ; Online: The Relapse Phenomenon in Mild COVID Treated With Nirmatrelvir/Ritonavir in an Immunocompetent Patient.

    Hoehl, Sebastian / Toptan, Tuna / Rabenau, Holger F / Ciesek, Sandra

    Deutsches Arzteblatt international

    2022  Volume 119, Issue 37, Page(s) 619–620

    Language English
    Publishing date 2022-12-12
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2406159-1
    ISSN 1866-0452 ; 1866-0452
    ISSN (online) 1866-0452
    ISSN 1866-0452
    DOI 10.3238/arztebl.m2022.0267
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Application of Herpesvirus Saimiri as an Alternative Gene Therapy Vector

    Tuna Toptan

    Arsiv Kaynak Tarama Dergisi, Vol 25, Iss 1, Pp 41-

    2016  Volume 51

    Abstract: Herpesvirus saimiri is the prototype rhadinovirus and is closely related to human Kaposi's sarcoma-associated herpesvirus. Herpesvirus saimiri strains of subgroup C transduce a broad spectrum of cancer cells and primary cells including human T ... ...

    Abstract Herpesvirus saimiri is the prototype rhadinovirus and is closely related to human Kaposi's sarcoma-associated herpesvirus. Herpesvirus saimiri strains of subgroup C transduce a broad spectrum of cancer cells and primary cells including human T lymphocytes very efficiently and enable stable transgene expression. Herpesvirus saimiri as a gene therapy vector is favorable because of its large packaging capacity, extensive cell tropism, and long-termed persistence as non-integrating episomes and thus exhibits numerous advantages over commonly used viral vectors. In order to use Herpesvirus saimiri as a secure and versatile gene therapy vehicle, it should be easily manipulated and modified. The recent advances in molecular cloning of large genomic fragments such as virus genomes as bacterial artificial chromosomes facilitated the functional studies and manipulation of herpesviruses using the recombination system of bacteria. Among these, red-recombination based and ldquo;en passant and rdquo; mutagenesis method enables seamless genome modification such as deletion, insertion and point mutation very easily and efficiently. [Archives Medical Review Journal 2016; 25(1.000): 41-51]
    Keywords Herpesvirus saimiri ; viral vectors ; gene therapy ; recombination ; bacterial artificial chromosome ; Medicine ; R ; Medicine (General) ; R5-920
    Language Turkish
    Publishing date 2016-03-01T00:00:00Z
    Publisher Cukurova University Faculty of Medicine
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Pediatrics and COVID-19.

    Toptan, Tuna / Ciesek, Sandra / Hoehl, Sebastian

    Advances in experimental medicine and biology

    2021  Volume 1318, Page(s) 197–208

    Abstract: Viral respiratory tract infections are prevalent in children. They have substantial effects on childhood morbidity throughout the world, especially in developing countries. In this chapter, we describe the preliminary characteristics of pediatric COVID- ... ...

    Abstract Viral respiratory tract infections are prevalent in children. They have substantial effects on childhood morbidity throughout the world, especially in developing countries. In this chapter, we describe the preliminary characteristics of pediatric COVID-19 and discover that severe and critical disease in children is rare. Many children remain asymptomatic. The reason why severity increases with progressing age and largely spares children is not yet known. In the search for possible explanations, we explore key differences between the pediatric and adult immune responses to new pathogens, and in host factors, such as ACE2 abundance.
    MeSH term(s) Adult ; COVID-19 ; Child ; Humans ; Pediatrics ; Peptidyl-Dipeptidase A ; SARS-CoV-2
    Chemical Substances Peptidyl-Dipeptidase A (EC 3.4.15.1)
    Language English
    Publishing date 2021-05-10
    Publishing country United States
    Document type Journal Article
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-030-63761-3_12
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Low But Recoverable Markers of Humoral Immune Response to BNT162b2 in Elderly LTCF Residents Five to Seven Months After Two-Dose Vaccination.

    Delbrück, Marla / Hoehl, Sebastian / Toptan, Tuna / Schenk, Barbara / Grikscheit, Katharina / Metzler, Melinda / Herrmann, Eva / Ciesek, Sandra

    Frontiers in aging

    2022  Volume 3, Page(s) 883724

    Abstract: The immune response is known to wane after vaccination with BNT162b2, but the role of age, morbidity and body composition is not well understood. We conducted a cross-sectional study in long-term care facilities (LTCFs) for the elderly. All study ... ...

    Abstract The immune response is known to wane after vaccination with BNT162b2, but the role of age, morbidity and body composition is not well understood. We conducted a cross-sectional study in long-term care facilities (LTCFs) for the elderly. All study participants had completed two-dose vaccination with BNT162b2 five to 7 months before sample collection. In 298 residents (median age 86 years, range 75-101), anti-SARS-CoV-2 rector binding IgG antibody (anti-RBD-IgG) concentrations were low and inversely correlated with age (mean 51.60 BAU/ml). We compared the results to Health Care Workers (HCW) aged 18-70 years (
    Language English
    Publishing date 2022-04-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 3076785-4
    ISSN 2673-6217 ; 2673-6217
    ISSN (online) 2673-6217
    ISSN 2673-6217
    DOI 10.3389/fragi.2022.883724
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Widespread keratosis pilaris-like eruption in an immunocompromised child.

    Frigerio, Alice / Toptan, Tuna / Chang, Yuan / Abbott, James / Cipriano, Sarah D / Bowen, Anneli R

    JAAD case reports

    2019  Volume 5, Issue 4, Page(s) 352–354

    Language English
    Publishing date 2019-04-05
    Publishing country United States
    Document type Case Reports
    ZDB-ID 2834220-3
    ISSN 2352-5126
    ISSN 2352-5126
    DOI 10.1016/j.jdcr.2019.02.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: High-Frequency Self-Testing by Schoolteachers for Sars-Cov-2 Using a Rapid Antigen Test–Results of the Safe School Hesse study.

    Hoehl, Sebastian / Schenk, Barbara / Rudych, Olga / Göttig, Stephan / Foppa, Ivo / Kohmer, Niko / Karaca, Onur / Toptan, Tuna / Ciesek, Sandra

    Deutsches Arzteblatt international

    2021  Volume 118, Issue 14, Page(s) 252–253

    MeSH term(s) COVID-19 ; COVID-19 Testing ; Humans ; SARS-CoV-2 ; Self-Testing ; Sensitivity and Specificity
    Language English
    Publishing date 2021-06-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2406159-1
    ISSN 1866-0452 ; 1866-0452
    ISSN (online) 1866-0452
    ISSN 1866-0452
    DOI 10.3238/arztebl.m2021.0187
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Molecular Analyses of Clinical Isolates and Recombinant SARS-CoV-2 Carrying B.1 and B.1.617.2 Spike Mutations Suggest a Potential Role of Non-Spike Mutations in Infection Kinetics.

    Veleanu, Andrei / Kelch, Maximilian A / Ye, Chengjin / Flohr, Melanie / Wilhelm, Alexander / Widera, Marek / Martinez-Sobrido, Luis / Ciesek, Sandra / Toptan, Tuna

    Viruses

    2022  Volume 14, Issue 9

    Abstract: Some of the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are less susceptible to neutralization with post-vaccine sera and monoclonal antibodies targeting the viral spike glycoprotein. This raises concerns of disease ... ...

    Abstract Some of the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are less susceptible to neutralization with post-vaccine sera and monoclonal antibodies targeting the viral spike glycoprotein. This raises concerns of disease control, transmissibility, and severity. Numerous substitutions have been identified to increase viral fitness within the nucleocapsid and nonstructural proteins, in addition to spike mutations. Therefore, we sought to generate infectious viruses carrying only the variant-specific spike mutations in an identical backbone to evaluate the impact of spike and non-spike mutations in the virus life cycle. We used en passant mutagenesis to generate recombinant viruses carrying spike mutations of B.1 and B.1.617.2 variants using SARS-CoV-2- bacterial artificial chromosome (BAC). Neutralization assays using clinical sera yielded comparable results between recombinant viruses and corresponding clinical isolates. Non-spike mutations for both variants neither seemed to effect neutralization efficiencies with monoclonal antibodies nor the response to treatment with inhibitors. However, live-cell imaging and microscopy revealed differences, such as persisting syncytia and pronounced cytopathic effect formation, as well as their progression between BAC-derived viruses and clinical isolates in human lung epithelial cell lines and primary bronchial epithelial cells. Complementary RNA analyses further suggested a potential role of non-spike mutations in infection kinetics.
    MeSH term(s) Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Glycoproteins/genetics ; Humans ; Mutation ; RNA, Complementary ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Glycoproteins ; RNA, Complementary ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-09-12
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14092017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Comparison of the Ct-values for genomic and subgenomic SARS-CoV-2 RNA reveals limited predictive value for the presence of replication competent virus.

    Roesmann, Fabian / Jakobsche, Irene / Pallas, Christiane / Wilhelm, Alexander / Raffel, Johanna / Kohmer, Niko / Toptan, Tuna / Berger, Annemarie / Goetsch, Udo / Ciesek, Sandra / Widera, Marek

    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology

    2023  Volume 165, Page(s) 105499

    Abstract: SARS-CoV-2 is the causative agent of the acute respiratory disease COVID-19. In addition to the full length positive-sensed, single-stranded genomic RNA (gRNA), viral subgenomic RNAs (sgRNAs) that are required for expression of the 3' region of the ... ...

    Abstract SARS-CoV-2 is the causative agent of the acute respiratory disease COVID-19. In addition to the full length positive-sensed, single-stranded genomic RNA (gRNA), viral subgenomic RNAs (sgRNAs) that are required for expression of the 3' region of the genome are synthesized in virus-infected cells. However, whether these sgRNA-species might be used as a measure of active virus replication and to predict infectivity is still under debate. The commonly used methods to monitor and quantitate SARS-CoV-2 infections are based on RT-qPCR analysis and the detection of gRNA. The infectivity of a sample obtained from nasopharyngeal or throat swabs is associated with the viral load and inversely correlates with Ct-values, however, a cut-off value predicting the infectivity highly depends on the performance of the assay. Furthermore, gRNA derived Ct-values result from nucleic acid detection and do not necessarily correspond to active replicating virus. We established a multiplex RT-qPCR assay on the cobas 6800 omni utility channel concomitantly detecting SARS-CoV-2 gRNA
    MeSH term(s) Humans ; RNA, Viral/genetics ; SARS-CoV-2/genetics ; COVID-19/diagnosis ; Subgenomic RNA ; Genomics ; Virus Replication
    Chemical Substances RNA, Viral ; Subgenomic RNA
    Language English
    Publishing date 2023-05-29
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1446080-4
    ISSN 1873-5967 ; 1386-6532
    ISSN (online) 1873-5967
    ISSN 1386-6532
    DOI 10.1016/j.jcv.2023.105499
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Machine learning on large scale perturbation screens for SARS-CoV-2 host factors identifies β-catenin/CBP inhibitor PRI-724 as a potent antiviral.

    Kelch, Maximilian A / Vera-Guapi, Antonella / Beder, Thomas / Oswald, Marcus / Hiemisch, Alicia / Beil, Nina / Wajda, Piotr / Ciesek, Sandra / Erfle, Holger / Toptan, Tuna / Koenig, Rainer

    Frontiers in microbiology

    2023  Volume 14, Page(s) 1193320

    Abstract: Expanding antiviral treatment options against SARS-CoV-2 remains crucial as the virus evolves under selection pressure which already led to the emergence of several drug resistant strains. Broad spectrum host-directed antivirals (HDA) are promising ... ...

    Abstract Expanding antiviral treatment options against SARS-CoV-2 remains crucial as the virus evolves under selection pressure which already led to the emergence of several drug resistant strains. Broad spectrum host-directed antivirals (HDA) are promising therapeutic options, however the robust identification of relevant host factors by CRISPR/Cas9 or RNA interference screens remains challenging due to low consistency in the resulting hits. To address this issue, we employed machine learning, based on experimental data from several knockout screens and a drug screen. We trained classifiers using genes essential for virus life cycle obtained from the knockout screens. The machines based their predictions on features describing cellular localization, protein domains, annotated gene sets from Gene Ontology, gene and protein sequences, and experimental data from proteomics, phospho-proteomics, protein interaction and transcriptomic profiles of SARS-CoV-2 infected cells. The models reached a remarkable performance suggesting patterns of intrinsic data consistency. The predicted HDF were enriched in sets of genes particularly encoding development, morphogenesis, and neural processes. Focusing on development and morphogenesis-associated gene sets, we found β-catenin to be central and selected PRI-724, a canonical β-catenin/CBP disruptor, as a potential HDA. PRI-724 limited infection with SARS-CoV-2 variants, SARS-CoV-1, MERS-CoV and IAV in different cell line models. We detected a concentration-dependent reduction in cytopathic effects, viral RNA replication, and infectious virus production in SARS-CoV-2 and SARS-CoV-1-infected cells. Independent of virus infection, PRI-724 treatment caused cell cycle deregulation which substantiates its potential as a broad spectrum antiviral. Our proposed machine learning concept supports focusing and accelerating the discovery of host dependency factors and identification of potential host-directed antivirals.
    Language English
    Publishing date 2023-06-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2023.1193320
    Database MEDical Literature Analysis and Retrieval System OnLINE

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