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  1. Article ; Online: WT1 in Adipose Tissue

    Karin M. Kirschner / Holger Scholz

    Frontiers in Cell and Developmental Biology, Vol

    From Development to Adult Physiology

    2022  Volume 10

    Abstract: Much of the fascination of the Wilms tumor protein (WT1) emanates from its unique roles in development and disease. Ubiquitous Wt1 deletion in adult mice causes multiple organ failure including a reduction of body fat. WT1 is expressed in fat cell ... ...

    Abstract Much of the fascination of the Wilms tumor protein (WT1) emanates from its unique roles in development and disease. Ubiquitous Wt1 deletion in adult mice causes multiple organ failure including a reduction of body fat. WT1 is expressed in fat cell progenitors in visceral white adipose tissue (WAT) but detected neither in energy storing subcutaneous WAT nor in heat producing brown adipose tissue (BAT). Our recent findings indicate that WT1 represses thermogenic genes and maintains the white adipose identity of visceral fat. Wt1 heterozygosity in mice is associated with molecular and morphological signs of browning including elevated levels of uncoupling protein 1 (UCP1) in epididymal WAT. Compared to their wild-type littermates, Wt1 heterozygous mice exhibit significantly improved whole-body glucose tolerance and alleviated hepatic steatosis under high-fat diet. Partial protection of heterozygous Wt1 knockout mice against metabolic dysfunction is presumably related to browning of their epididymal WAT. In the light of recent advancements, this article reviews the role of WT1 in the development of visceral WAT and its supposed function as a regulator of white adipose identity.
    Keywords white adipocyte ; brown adipocyte differentiation ; thermogenesis ; uncoupling protein (UCP) ; WAT browning ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Phenotypic and genotypic discrimination of Francisella tularensis ssp. holarctica clades

    Kristin Köppen / Kerstin Rydzewski / Joerg Doellinger / Kerstin Myrtennäs / Mats Forsman / Sandra Appelt / Holger Scholz / Klaus Heuner

    International Journal of Medical Microbiology, Vol 313, Iss 4, Pp 151583- (2023)

    2023  

    Abstract: Francisella tularensis is the causative agent of tularemia, a zoonotic disease with a wide host range. F. tularensis ssp. holarctica (Fth) is of clinical relevance for European countries, including Germany. Whole genome sequencing methods, including ... ...

    Abstract Francisella tularensis is the causative agent of tularemia, a zoonotic disease with a wide host range. F. tularensis ssp. holarctica (Fth) is of clinical relevance for European countries, including Germany. Whole genome sequencing methods, including canonical Single Nucleotide Polymorphism (canSNP) typing and whole genome SNP typing, have revealed that European Fth strains belong to a few monophyletic populations. The majority of German Fth isolates belong to two basal phylogenetic clades B.6 (biovar I) and B.12 (biovar II). Strains of B.6 and B.12 seem to differ in their pathogenicity, and it has been shown that strains of biovar II are resistant against erythromycin. In this study, we present data corroborating our previous data demonstrating that basal clade B.12 can be divided into clades B.71 and B.72. By applying phylogenetic whole genome analysis as well as proteome analysis, we could verify that strains of these two clades are distinct from one another. This was confirmed by measuring the intensity of backscatter light on bacteria grown in liquid media. Strains belonging to clades B.6, B.71 or B.72 showed clade-specific backscatter growth curves. Furthermore, we present the whole genome sequence of strain A-1341, as a reference genome of clade B.71, and whole proteomes comparison of Fth strains belonging to clades B.6, B.71 and B.72. Further research is necessary to investigate phenotypes and putative differences in pathogenicity of the investigated different clades of Fth to better understand the relationship between observed phenotypes, pathogenicity and distribution of Fth strains.
    Keywords Francisella ; Phylogenetic clade B.71 ; B.12 ; B.6 ; Proteomics ; Mass spectrometry ; Microbiology ; QR1-502 ; Other systems of medicine ; RZ201-999
    Subject code 572
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Ex vivo cultures combined with vivo-morpholino induced gene knockdown provide a system to assess the role of WT1 and GATA4 during gonad differentiation.

    Lucas J Rudigier / Christof Dame / Holger Scholz / Karin M Kirschner

    PLoS ONE, Vol 12, Iss 4, p e

    2017  Volume 0176296

    Abstract: Gonad morphogenesis relies on the correct spatiotemporal expression of a number of genes that together fulfill the differentiation of the bipotential gonad into testes or ovaries. As such, the transcription factors WT1 and GATA4 are pivotal for proper ... ...

    Abstract Gonad morphogenesis relies on the correct spatiotemporal expression of a number of genes that together fulfill the differentiation of the bipotential gonad into testes or ovaries. As such, the transcription factors WT1 and GATA4 are pivotal for proper gonadal development. Here we address the contributions of GATA4 and WT1 to the sex differentiation phase in testes and ovaries. We applied an ex vivo technique for cultivating gonads in hanging droplets of media that were supplemented with vivo-morpholinos to knockdown WT1 and GATA4 either alone or in combination at the same developmental stage. We show that WT1 is equally important for both, the initial establishment and the maintenance of the sex-specific gene expression signature in testes and ovaries. We further identified Foxl2 as a novel putative downstream target gene of WT1. Moreover, knockdown of WT1 reduced mRNA levels of several molecular components of the hedgehog signaling pathway in XY gonads, whereas Gata4 vivo-morpholino treatment increased transcripts of Dhh and Ptch1 in embryonic testes. The data suggest that for its proper function, WT1 relies on the correct expression of the GATA4 protein. Furthermore, GATA4 down-regulates several ovarian promoting genes in testes, such as Ctnnb1, Fst, and Bmp2, suggesting that this repression is required for maintaining the male phenotype. In conclusion, this study provides novel insights into the role of WT1 and GATA4 during the sex differentiation phase and represents an approach that can be applied to assess other proteins with as yet unknown functions during gonadal development.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: The Wilms tumor protein WT1 stimulates transcription of the gene encoding insulin-like growth factor binding protein 5 (IGFBP5)

    Müller, Miriam / Anja Bondke Persson / Holger Scholz / Karin M. Kirschner / Katharina Krueger

    Gene. 2017 July 01, v. 619

    2017  

    Abstract: Insulin-like growth factor (IGF) binding proteins (IGFBPs) constitute a family of six secreted proteins that regulate the signaling of insulin-like growth factors (IGFs). IGFBP5 is the most conserved family member in vertebrates and the major IGF binding ...

    Abstract Insulin-like growth factor (IGF) binding proteins (IGFBPs) constitute a family of six secreted proteins that regulate the signaling of insulin-like growth factors (IGFs). IGFBP5 is the most conserved family member in vertebrates and the major IGF binding protein in bone. IGFBP5 is required for normal development of the musculoskeletal system, and various types of cancer frequently express high levels of IGFP5. Here we identify the gene encoding IGFBP5 as a novel downstream target of the Wilms tumor protein WT1. IGFBP5 and WT1 are expressed in an overlapping pattern in the condensing metanephric mesenchyme of embryonic murine kidneys. Down-regulation of WT1 by transfection with antisense vivo-morpholino significantly decreased Igfbp5 transcripts in murine embryonic kidney explants. Likewise, silencing of Wt1 in a mouse mesonephros-derived cell line reduced Igfbp5 mRNA levels by approximately 80%. Conversely, induction of the WT1(−KTS) isoform, whose role as transcriptional regulator has been firmly established, significantly increased IGFBP5 mRNA and protein levels in osteosarcoma cells. IGFBP5 expression was not significantly changed by WT1(+KTS) protein, which exhibits lower DNA binding affinity than the WT1(−KTS) isoform and has a presumed role in post-transcriptional gene regulation. Luciferase reporter constructs harboring 0.8 and 1.6 kilobases of the murine Igfbp5 promoter, respectively, were stimulated approximately 5-fold by co-transfection of WT1(−KTS). The WT1(+KTS) variant had no significant effect on IGFBP5 promoter activity. Binding of WT1(−KTS), but not of WT1(+KTS) protein, to the IGFBP5 promoter in human osteosarcoma cells was proven by chromatin immunoprecipitation (ChIP) and confirmed by electrophoretic mobility shift assay. These findings demonstrate that WT1 activates transcription of the IGFBP5 gene with possible implications for kidney development and bone (patho)physiology.
    Keywords binding capacity ; chromatin ; DNA ; explants ; gel electrophoresis ; gene expression regulation ; genes ; humans ; insulin-like growth factor binding proteins ; kidneys ; luciferase ; messenger RNA ; mice ; musculoskeletal system ; osteosarcoma ; precipitin tests ; protein secretion ; somatomedins ; transcription (genetics) ; transcription factors ; transfection
    Language English
    Dates of publication 2017-0701
    Size p. 21-29.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2017.03.037
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 79/715: Show issues

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  5. Article ; Online: Can we make human plague history? A call to action

    Nils Christian Stenseth / Minoarisoa Rajerison / Maherisoa Ratsitorahina / Javier Pizarro-Cerdá / Christian Demeure / Steve Belmain / Holger Scholz / Romain Girod / Joseph Hinnebusch / Ines Vigan-Womas / Eric Bertherat / Yazdan Yazadanpanah / Guia Carrara / Jane Deuve / Eric D'ortenzio / Jose Oswaldo Cabanillas Angulo

    BMJ Global Health, Vol 4, Iss

    2019  Volume 6

    Keywords Medicine (General) ; R5-920 ; Infectious and parasitic diseases ; RC109-216
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Detection of Babesia venatorum, Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis in Ixodes persulcatus ticks from Mongolia

    Karnath, Carolin / Anna Obiegala / Battsetseg Jigjav / Damdindorj Tserennorov / Daniel Kiefer / Henri Derschum / Holger Scholz / Martin Pfeffer / Nyamdorj Tsogbadrakh / Otgonbataar Dashdavaa / Sandra Essbauer / Stephanie Speck

    Ticks and tick-borne diseases. 2016 Mar., v. 7, no. 2

    2016  

    Abstract: Information about the prevalence and geographical distribution of tick-borne pathogens Anaplasma phagocytophilum, Candidatus Neoehrlichia mikurensis, and Babesia spp. is still rare in Mongolia. We tested 275 Ixodes persulcatus ticks for A. ... ...

    Abstract Information about the prevalence and geographical distribution of tick-borne pathogens Anaplasma phagocytophilum, Candidatus Neoehrlichia mikurensis, and Babesia spp. is still rare in Mongolia. We tested 275 Ixodes persulcatus ticks for A. phagocytophilum, Cand. N. mikurensis and Babesia spp. and 125 Dermacentor nuttalli ticks especially for Babesia spp. using different PCR methods. Ticks were collected from three provinces (Selenge, Arkhangai, Khentii) in Mongolia. DNA of A. phagocytophilum, Cand. N. mikurensis and Babesia spp. were found with a prevalence of 6.2%, 1.5% and 3.3% in each case in I. persulcatus ticks. This is the first time Cand. N. mikurensis was found in ticks from Mongolia. Sequence analysis of Babesia spp.-positive amplicons showed exclusively B. venatorum, which had also not been mentioned in Mongolia before. On the contrary, all D. nuttalli ticks tested negatively for Babesia spp. This study demonstrates that all three zoonotic pathogens are present in I. persulcatus ticks in Mongolia, and justify the need for further investigations of a more detailed genetic characterization of these pathogens.
    Keywords Anaplasma phagocytophilum ; Babesia ; Dermacentor ; DNA ; geographical distribution ; Ixodes persulcatus ; pathogens ; polymerase chain reaction ; sequence analysis ; tick-borne diseases ; ticks ; Mongolia
    Language English
    Dates of publication 2016-03
    Size p. 357-360.
    Publishing place Elsevier GmbH
    Document type Article
    ZDB-ID 2541872-5
    ISSN 1877-9603 ; 1877-959X
    ISSN (online) 1877-9603
    ISSN 1877-959X
    DOI 10.1016/j.ttbdis.2015.12.007
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  7. Article: Analysis of the genetic distribution among members of Clostridium botulinum group I using a novel multilocus sequence typing (MLST) assay

    Olsen, Jaran S / Anette K. Trømborg / Florigio Lista / Holger Scholz / Ingjerd Thrane / Janet M. Blatny / Silvia Fillo / Tone Aarskaug / Vincent Ramisse

    Journal of microbiological methods. 2014 Jan., v. 96

    2014  

    Abstract: Clostridium botulinum is the etiological agent of botulism. Due to food-borne poisoning and the potential use of the extremely toxic botulinum neurotoxin (BoNT) from C. botulinum in bioterror or biocrime related actions, reliable high resolution typing ... ...

    Abstract Clostridium botulinum is the etiological agent of botulism. Due to food-borne poisoning and the potential use of the extremely toxic botulinum neurotoxin (BoNT) from C. botulinum in bioterror or biocrime related actions, reliable high resolution typing methods for discriminating C. botulinum strains are needed. Partial sequencing of the adk, atpH, gyrB, proC, rpoD and spo0A genes from 51 various C. botulinum/sporogenes isolates was performed, resulting in 37 different sequence types (STs). Analysis of the sequence data revealed a genetic distribution in five larger clusters with a loose correlation to the BoNT serotypes. The developed MLST assay had a slightly lower resolution ability when compared to the MLVA (multilocus variable number of tandem repeat analysis), but the two methods resulted in similar subclusters of the strains possessing the BoNT serotypes A, B and F. The current work presents the development of a novel MLST assay useful for genotyping C. botulinum related to basic phylogenetic research and trace-back analysis in microbial forensic studies.
    Keywords botulinum toxin ; botulism ; Clostridium botulinum ; etiological agents ; forensic sciences ; genes ; multilocus sequence typing ; multiple-locus variable number tandem-repeat analysis ; phylogeny ; serotypes ; toxicity
    Language English
    Dates of publication 2014-01
    Size p. 84-91.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 604916-3
    ISSN 1872-8359 ; 0167-7012
    ISSN (online) 1872-8359
    ISSN 0167-7012
    DOI 10.1016/j.mimet.2013.11.003
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1849: Show issues Location:
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  8. Article ; Online: Natural Burkholderia mallei Infection in Dromedary, Bahrain

    Ulrich Wernery / Renate Wernery / Marina Joseph / Fajer Al-Salloom / Bobby Johnson / Joerg Kinne / Shanti Jose / Sherry Jose / Britta Tappendorf / Heidie Hornstra / Holger Scholz

    Emerging Infectious Diseases, Vol 17, Iss 7, Pp 1277-

    2011  Volume 1279

    Abstract: We confirm a natural infection of dromedaries with glanders. Multilocus variable number tandem repeat analysis of a Burkholderia mallei strain isolated from a diseased dromedary in Bahrain revealed close genetic proximity to strain Dubai 7, which caused ... ...

    Abstract We confirm a natural infection of dromedaries with glanders. Multilocus variable number tandem repeat analysis of a Burkholderia mallei strain isolated from a diseased dromedary in Bahrain revealed close genetic proximity to strain Dubai 7, which caused an outbreak of glanders in horses in the United Arab Emirates in 2004.
    Keywords bacteria ; Burkholderia mallei ; glanders ; Bahrain ; camel ; dromedary ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Language English
    Publishing date 2011-07-01T00:00:00Z
    Publisher Centers for Disease Control and Prevention
    Document type Article ; Online
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