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  1. Buch ; Online ; Dissertation / Habilitation: Molekulare Analysen zur Funktion von SPOC1 (PHF13) in der epigenetischen Regulation der Spermatogenese mit Hilfe eines Spoc1-/- -Mausmodells

    Nelkenbrecher, Claudia [Verfasser] / Winterpacht, Andreas [Akademischer Betreuer]

    2014  

    Verfasserangabe Claudia Nelkenbrecher. Gutachter: Andreas Winterpacht
    Schlagwörter Medizin, Gesundheit ; Medicine, Health
    Thema/Rubrik (Code) sg610
    Sprache Deutsch
    Verlag Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
    Erscheinungsort Erlangen
    Dokumenttyp Buch ; Online ; Dissertation / Habilitation
    Datenquelle Digitale Dissertationen im Internet

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  2. Artikel ; Online: CHROMAgar™ LIN-R as an efficient screening tool to assess the prevalence of linezolid-resistant enterococci in German hospital patients-a multicentre study approach, 2021-2022.

    Bender, Jennifer K / Baufeld, Elsa / Becker, Karsten / Claus, Heike / Dudakova, Anna / Dörre, Achim / Fila, Nikoletta / Fleige, Carola / Hamprecht, Axel / Hoffmann, Armin / Hogardt, Michael / Kaasch, Achim J / Kola, Axel / Kriebel, Nancy / Layer-Nicolaou, Franziska / Marschal, Matthias / Molitor, Ernst / Mutters, Nico T / Liese, Jan /
    Nelkenbrecher, Claudia / Neumann, Bernd / Rohde, Holger / Steinmann, Jörg / Sörensen, Michael / Thelen, Philipp / Weig, Michael / Zautner, Andreas E / Werner, Guido

    The Journal of antimicrobial chemotherapy

    2023  Band 78, Heft 9, Seite(n) 2185–2191

    Abstract: Background: In recent years, an increasing number of linezolid-resistant enterococci (LRE) was recognized at the German National Reference Centre (NRC) for Enterococci. National guidelines on infection prevention recommend screening for LRE in ... ...

    Abstract Background: In recent years, an increasing number of linezolid-resistant enterococci (LRE) was recognized at the German National Reference Centre (NRC) for Enterococci. National guidelines on infection prevention recommend screening for LRE in epidemiologically linked hospital settings without referring to a reliable and rapid diagnostic method. Since 2020, CHROMAgar™ provide a chromogenic linezolid screening agar, LIN-R, suitable to simultaneously screen for linezolid-resistant staphylococci and enterococci.
    Objectives: To assess the applicability of CHROMAgar™ LIN-R in clinical settings for detecting LRE directly from patient material and to infer prevalence rates of LRE amongst German hospital patients.
    Methods: During the 3-month trial period, clinical samples were plated on CHROMAgar™ LIN-R. Antimicrobial susceptibility testing was performed using VITEK2 or disc diffusion. At the NRC, linezolid resistance was determined by broth microdilution, multiplex-PCR for cfr/optrA/poxtA and by a restriction-based assay for 23S rDNA mutations.
    Results: The 12 participating study sites used 13 963 CHROMAgar™ LIN-R plates during the study period. Of 442 presumptive LRE, 192 were confirmed by phenotypic methods. Of these, 161 were received by the NRC and 121 (75%) were verified as LRE. Most of LR-E. faecium 53/81 (65%) exhibited a 23S rRNA gene mutation as the sole resistance-mediating mechanism, whereas optrA constituted the dominant resistance trait in LR-E. faecalis [39/40 (98%)]. Prevalence of LRE across sites was estimated as 1% (ranging 0.18%-3.7% between sites).
    Conclusions: CHROMAgar™ LIN-R represents a simple and efficient LRE screening tool in hospital settings. A high proportion of false-positive results demands validation of linezolid resistance by a reference method.
    Mesh-Begriff(e) Humans ; Linezolid/pharmacology ; Anti-Bacterial Agents/pharmacology ; Prevalence ; Drug Resistance, Bacterial/genetics ; Enterococcus/genetics ; Hospitals ; Gram-Positive Bacterial Infections/epidemiology ; Enterococcus faecium/genetics ; Microbial Sensitivity Tests ; Enterococcus faecalis
    Chemische Substanzen Linezolid (ISQ9I6J12J) ; Anti-Bacterial Agents
    Sprache Englisch
    Erscheinungsdatum 2023-07-15
    Erscheinungsland England
    Dokumenttyp Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 191709-2
    ISSN 1460-2091 ; 0305-7453
    ISSN (online) 1460-2091
    ISSN 0305-7453
    DOI 10.1093/jac/dkad218
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: C4ORF48, a gene from the Wolf-Hirschhorn syndrome critical region, encodes a putative neuropeptide and is expressed during neocortex and cerebellar development.

    Endele, Sabine / Nelkenbrecher, Claudia / Bördlein, Annegret / Schlickum, Stefanie / Winterpacht, Andreas

    Neurogenetics

    2011  Band 12, Heft 2, Seite(n) 155–163

    Abstract: In order to identify novel genes involved in mental retardation/intellectual disability, we focused on a microdeletion reported in a patient with a mild form of Wolf-Hirschhorn syndrome. This patient presented with attention-deficit hyperactivity ... ...

    Abstract In order to identify novel genes involved in mental retardation/intellectual disability, we focused on a microdeletion reported in a patient with a mild form of Wolf-Hirschhorn syndrome. This patient presented with attention-deficit hyperactivity disorder, some learning and fine motor deficits as well as facial abnormalities. The deleted region included three genes. Here, we report the first characterization of one of these genes, C4ORF48. C4ORF48 encodes a short (139 aa) evolutionarily conserved protein with a predicted signal peptide and two potential dibasic convertase cleavage sites. In mice, we demonstrated expression of the corresponding protein exclusively in brain tissue using an anti-mouse C4Orf48 polyclonal antibody. Detailed RNA in situ hybridization experiments revealed expression of C4Orf48 in different zones during cortical and cerebellar development, as well as in almost all cortical and subcortical regions of the adult mouse brain. Based on the present data, we propose that C4Orf48 probably encodes a novel neuropeptide, which, if hemizygously deleted, may be involved in the observed intellectual and fine motor disabilities and thus in the overall neurological aspects of Wolf-Hirschhorn syndrome.
    Mesh-Begriff(e) Amino Acid Sequence ; Animals ; Animals, Newborn ; COS Cells ; Cerebellum/embryology ; Cerebellum/metabolism ; Chlorocebus aethiops ; Embryo, Mammalian ; Gene Expression Regulation, Developmental ; Genetic Loci ; Humans ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Neocortex/embryology ; Neocortex/metabolism ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neuropeptides/genetics ; Neuropeptides/metabolism ; Proteins/genetics ; Proteins/physiology ; Sequence Homology, Amino Acid ; Wolf-Hirschhorn Syndrome/genetics
    Chemische Substanzen C4ORF48 protein, human ; Nerve Tissue Proteins ; Neuropeptides ; Proteins
    Sprache Englisch
    Erscheinungsdatum 2011-02-02
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1339887-8
    ISSN 1364-6753 ; 1364-6745
    ISSN (online) 1364-6753
    ISSN 1364-6745
    DOI 10.1007/s10048-011-0275-8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: SPOC1 (PHF13) is required for spermatogonial stem cell differentiation and sustained spermatogenesis.

    Bördlein, Annegret / Scherthan, Harry / Nelkenbrecher, Claudia / Molter, Tina / Bösl, Michael R / Dippold, Christine / Birke, Kerstin / Kinkley, Sarah / Staege, Hannah / Will, Hans / Winterpacht, Andreas

    Journal of cell science

    2011  Band 124, Heft Pt 18, Seite(n) 3137–3148

    Abstract: SPOC1 (PHF13) is a recently identified protein that has been shown to dynamically associate with somatic chromatin, to modulate chromatin compaction and to be important for proper cell division. Here, we report on the expression of SPOC1 in promyelocytic ...

    Abstract SPOC1 (PHF13) is a recently identified protein that has been shown to dynamically associate with somatic chromatin, to modulate chromatin compaction and to be important for proper cell division. Here, we report on the expression of SPOC1 in promyelocytic leukaemia zinc finger (PLZF)-positive undifferentiated spermatogonial stem cells (SSCs) of the mouse testis. To investigate further the biological function of SPOC1 in germ cells we generated Spoc1 mutant mice from a gene-trap embryonic stem cell clone. Postpubertal homozygous Spoc1(-/-) animals displayed a pronounced progressive loss of germ cells from an initially normal germ epithelium of the testis tubules leading to testis hypoplasia. This loss first affected non-SSC stages of germ cells and then, at a later time point, the undifferentiated spermatogonia. Remarkably, successive loss of all germ cells (at >20 weeks of age) was preceded by a transient increase in the number of undifferentiated A(aligned) (A(al)) spermatogonia in younger mice (at >10 weeks of age). The number of primary Spoc1(-/-) gonocytes, the proliferation of germ cells, and the initiation and progression of meiosis was normal, but we noted a significantly elevated level of apoptosis in the Spoc1(-/-) testis. Taken together, the data argue that SPOC1 is indispensable for stem cell differentiation in the testis and for sustained spermatogenesis.
    Mesh-Begriff(e) Adult Stem Cells/metabolism ; Adult Stem Cells/pathology ; Animals ; Apoptosis/genetics ; Cell Differentiation/genetics ; Cell Survival/genetics ; Chromatin Assembly and Disassembly ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Humans ; Male ; Mice ; Mice, Knockout ; Mutation/genetics ; Spermatogenesis/genetics ; Spermatogonia/metabolism ; Spermatogonia/pathology ; Testis/metabolism ; Testis/pathology ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemische Substanzen DNA-Binding Proteins ; PHF13 protein, human ; Transcription Factors
    Sprache Englisch
    Erscheinungsdatum 2011-09-15
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.085936
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Frequent inactivation of cysteine dioxygenase type 1 contributes to survival of breast cancer cells and resistance to anthracyclines.

    Jeschke, Jana / O'Hagan, Heather M / Zhang, Wei / Vatapalli, Rajita / Calmon, Marilia Freitas / Danilova, Ludmila / Nelkenbrecher, Claudia / Van Neste, Leander / Bijsmans, Ingrid T G W / Van Engeland, Manon / Gabrielson, Edward / Schuebel, Kornel E / Winterpacht, Andreas / Baylin, Stephen B / Herman, James G / Ahuja, Nita

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2013  Band 19, Heft 12, Seite(n) 3201–3211

    Abstract: Purpose: Genome-wide DNA methylation analyses have identified hundreds of candidate DNA-hypermethylated genes in cancer. Comprehensive functional analyses provide an understanding of the biologic significance of this vast amount of DNA methylation data ... ...

    Abstract Purpose: Genome-wide DNA methylation analyses have identified hundreds of candidate DNA-hypermethylated genes in cancer. Comprehensive functional analyses provide an understanding of the biologic significance of this vast amount of DNA methylation data that may allow the determination of key epigenetic events associated with tumorigenesis.
    Experimental design: To study mechanisms of cysteine dioxygenase type 1 (CDO1) inactivation and its functional significance in breast cancer in a comprehensive manner, we screened for DNA methylation and gene mutations in primary breast cancers and analyzed growth, survival, and reactive oxygen species (ROS) production in breast cancer cells with restored CDO1 function in the context of anthracycline treatment.
    Results: DNA methylation-associated silencing of CDO1 in breast cancer is frequent (60%), cancer specific, and correlates with disease progression and outcome. CDO1 function can alternatively be silenced by repressive chromatin, and we describe protein-damaging missense mutations in 7% of tumors without DNA methylation. Restoration of CDO1 function in breast cancer cells increases levels of ROS and leads to reduced viability and growth, as well as sensitization to anthracycline treatment. Priming with 5-azacytidine of breast cancer cells with epigenetically silenced CDO1 resulted in restored expression and increased sensitivity to anthracyclines.
    Conclusion: We report that silencing of CDO1 is a critical epigenetic event that contributes to the survival of oxidative-stressed breast cancer cells through increased detoxification of ROS and thus leads to the resistance to ROS-generating chemotherapeutics including anthracyclines. Our study shows the importance of CDO1 inactivation in breast cancer and its clinical potential as a biomarker and therapeutic target to overcome resistance to anthracyclines.
    Mesh-Begriff(e) Anthracyclines/administration & dosage ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cysteine Dioxygenase/antagonists & inhibitors ; Cysteine Dioxygenase/genetics ; DNA Methylation/genetics ; Drug Resistance, Neoplasm/genetics ; Drug Resistance, Neoplasm/immunology ; Female ; Gene Silencing ; Humans ; Reactive Oxygen Species/metabolism
    Chemische Substanzen Anthracyclines ; Reactive Oxygen Species ; Cysteine Dioxygenase (EC 1.13.11.20)
    Sprache Englisch
    Erscheinungsdatum 2013-04-29
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-12-3751
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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