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  1. AU="Nils Hartmann"
  2. AU="Simionescu, Maya"
  3. AU="Feng, Yicheng"
  4. AU="Roger Le Grand"
  5. AU="Tesfalidet, Solomon"
  6. AU="Geladari, Eleni"
  7. AU="Pallabi Mustafi"
  8. AU=Mountfort Katrina
  9. AU="Horne, Patrick"
  10. AU="Mhurchu, Cliona Ni"
  11. AU="Yatoo, Ali Mohd"
  12. AU="Zhang, Zhiru"
  13. AU="Hadie Adams"
  14. AU="Gaskin, Thomas R"
  15. AU="Guo, Chong"
  16. AU="Guocan Wang"
  17. AU="Catherine Crenn-Hebert"
  18. AU="Alistar, Cristina F"
  19. AU="Makhani, Sarah S"
  20. AU="Tayyeb Pourfallah"
  21. AU="Mauad, Thais"

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  1. Artikel ; Online: Systems Analysis Reveals Ageing-Related Perturbations in Retinoids and Sex Hormones in Alzheimer’s and Parkinson’s Diseases

    Simon Lam / Nils Hartmann / Rui Benfeitas / Cheng Zhang / Muhammad Arif / Hasan Turkez / Mathias Uhlén / Christoph Englert / Robert Knight / Adil Mardinoglu

    Biomedicines, Vol 9, Iss 1310, p

    2021  Band 1310

    Abstract: Neurodegenerative diseases, including Alzheimer’s (AD) and Parkinson’s diseases (PD), are complex heterogeneous diseases with highly variable patient responses to treatment. Due to the growing evidence for ageing-related clinical and pathological ... ...

    Abstract Neurodegenerative diseases, including Alzheimer’s (AD) and Parkinson’s diseases (PD), are complex heterogeneous diseases with highly variable patient responses to treatment. Due to the growing evidence for ageing-related clinical and pathological commonalities between AD and PD, these diseases have recently been studied in tandem. In this study, we analysed transcriptomic data from AD and PD patients, and stratified these patients into three subclasses with distinct gene expression and metabolic profiles. Through integrating transcriptomic data with a genome-scale metabolic model and validating our findings by network exploration and co-analysis using a zebrafish ageing model, we identified retinoids as a key ageing-related feature in all subclasses of AD and PD. We also demonstrated that the dysregulation of androgen metabolism by three different independent mechanisms is a source of heterogeneity in AD and PD. Taken together, our work highlights the need for stratification of AD/PD patients and development of personalised and precision medicine approaches based on the detailed characterisation of these subclasses.
    Schlagwörter neurodegeneration ; Alzheimer’s ; Parkinson’s ; ageing ; systems biology ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-09-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Deletion of Cd44 Inhibits Metastasis Formation of Liver Cancer in Nf2 -Mutant Mice

    Monserrat Gerardo-Ramírez / Vanessa Giam / Diana Becker / Marco Groth / Nils Hartmann / Helen Morrison / Helen L. May-Simera / Markus P. Radsak / Jens U. Marquardt / Peter R. Galle / Peter Herrlich / Beate K. Straub / Monika Hartmann

    Cells, Vol 12, Iss 1257, p

    2023  Band 1257

    Abstract: Primary liver cancer is the third leading cause of cancer-related death worldwide. An increasing body of evidence suggests that the Hippo tumor suppressor pathway plays a critical role in restricting cell proliferation and determining cell fate during ... ...

    Abstract Primary liver cancer is the third leading cause of cancer-related death worldwide. An increasing body of evidence suggests that the Hippo tumor suppressor pathway plays a critical role in restricting cell proliferation and determining cell fate during physiological and pathological processes in the liver. Merlin (Moesin-Ezrin-Radixin-like protein) encoded by the NF2 (neurofibromatosis type 2) gene is an upstream regulator of the Hippo signaling pathway. Targeting of Merlin to the plasma membrane seems to be crucial for its major tumor-suppressive functions; this is facilitated by interactions with membrane-associated proteins, including CD44 (cluster of differentiation 44). Mutations within the CD44-binding domain of Merlin have been reported in many human cancers. This study evaluated the relative contribution of CD44- and Merlin-dependent processes to the development and progression of liver tumors. To this end, mice with a liver-specific deletion of the Nf2 gene were crossed with Cd44 -knockout mice and subjected to extensive histological, biochemical and molecular analyses. In addition, cells were isolated from mutant livers and analyzed by in vitro assays. Deletion of Nf2 in the liver led to substantial liver enlargement and generation of hepatocellular carcinomas (HCCs), intrahepatic cholangiocarcinomas (iCCAs), as well as mixed hepatocellular cholangiocarcinomas. Whilst deletion of Cd44 had no influence on liver size or primary liver tumor development, it significantly inhibited metastasis formation in Nf2 -mutant mice. CD44 upregulates expression of integrin β2 and promotes transendothelial migration of liver cancer cells, which may facilitate metastatic spreading. Overall, our results suggest that CD44 may be a promising target for intervening with metastatic spreading of liver cancer.
    Schlagwörter CD44 ; Merlin ; NF2 ; liver cancer ; HCC ; ICAM-1 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2023-04-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: CD44 Contributes to the Regulation of MDR1 Protein and Doxorubicin Chemoresistance in Osteosarcoma

    Monserrat Gerardo-Ramírez / Friederike L. Keggenhoff / Vanessa Giam / Diana Becker / Marco Groth / Nils Hartmann / Beate K. Straub / Helen Morrison / Peter R. Galle / Jens U. Marquardt / Peter Herrlich / Monika Hartmann

    International Journal of Molecular Sciences, Vol 23, Iss 8616, p

    2022  Band 8616

    Abstract: Osteosarcoma is the most common type of pediatric bone tumor. Despite great advances in chemotherapy during the past decades, the survival rates of osteosarcoma patients remain unsatisfactory. Drug resistance is one of the main reasons, leading to ... ...

    Abstract Osteosarcoma is the most common type of pediatric bone tumor. Despite great advances in chemotherapy during the past decades, the survival rates of osteosarcoma patients remain unsatisfactory. Drug resistance is one of the main reasons, leading to treatment failure and poor prognosis. Previous reports correlated expression of cluster of differentiation 44 (CD44) with drug resistance and poor survival of osteosarcoma patients, however the underlying mechanisms are poorly defined. Here, we investigated the role of CD44 in the regulation of drug chemoresistance, using osteosarcoma cells isolated from mice carrying a mutation of the tumor suppressor neurofibromatosis type 2 ( Nf2 ) gene. CD44 expression was knocked-down in the cells using CRISPR/Cas9 approach. Subsequently, CD44 isoforms and mutants were re-introduced to investigate CD44-dependent processes. Sensitivity to doxorubicin was analyzed in the osteosarcoma cells with modified CD44 expression by immunoblot, colony formation- and WST-1 assay. To dissect the molecular alterations induced by deletion of Cd44 , RNA sequencing was performed on Cd44 -positive and Cd44 -negative primary osteosarcoma tissues isolated from Nf2 -mutant mice. Subsequently, expression of candidate genes was evaluated by quantitative reverse transcription PCR (qRT-PCR). Our results indicate that CD44 increases the resistance of osteosarcoma cells to doxorubicin by up-regulating the levels of multidrug resistance (MDR) 1 protein expression, and suggest the role of proteolytically released CD44 intracellular domain, and hyaluronan interactions in this process. Moreover, high throughput sequencing analysis identified differential regulation of several apoptosis-related genes in Cd44 -positive and -negative primary osteosarcomas, including p53 apoptosis effector related to PMP-22 ( Perp ). Deletion of Cd44 in osteosarcoma cells led to doxorubicin-dependent p53 activation and a profound increase in Perp mRNA expression. Overall, our results suggest that CD44 might be an important regulator ...
    Schlagwörter CD44 ; MDR1 ; bone tumors ; osteosarcoma ; hyaluronic acid ; proteolytic cleavage ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 570 ; 610
    Sprache Englisch
    Erscheinungsdatum 2022-08-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients

    Anna Haupts / Anne Vogel / Sebastian Foersch / Monika Hartmann / Annett Maderer / Nicolas Wachter / Tobias Huber / Werner Kneist / Wilfried Roth / Hauke Lang / Markus Moehler / Nils Hartmann

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Band 17

    Abstract: Abstract The current standard for molecular profiling of colorectal cancer (CRC) is using resected or biopsied tissue specimens. However, they are limited regarding sampling frequency, representation of tumor heterogeneity, and sampling can expose ... ...

    Abstract Abstract The current standard for molecular profiling of colorectal cancer (CRC) is using resected or biopsied tissue specimens. However, they are limited regarding sampling frequency, representation of tumor heterogeneity, and sampling can expose patients to adverse side effects. The analysis of cell-free DNA (cfDNA) from blood plasma, which is part of a liquid biopsy, is minimally invasive and in principle enables detection of all tumor-specific mutations. Here, we analyzed cfDNA originating from nucleus and mitochondria and investigated their characteristics and mutation status in a cohort of 18 CRC patients and 10 healthy controls using targeted next-generation sequencing (NGS) and digital PCR. Longitudinal analyses of nuclear cfDNA level and size during chemotherapy revealed a decreasing cfDNA content and a shift from short to long fragments, indicating an appropriate therapy response, while shortened cfDNAs and increased cfDNA content corresponded with tumor recurrence. Comparative NGS analysis of nuclear tissue and plasma DNA demonstrated a good patient-level concordance and cfDNA revealed additional variants in three of the cases. Analysis of mitochondrial cfDNA surprisingly revealed a higher plasma copy number in healthy subjects than in CRC patients. These results highlight the potential clinical utility of liquid biopsies in routine diagnostics and surveillance of CRC patients as complementation to tissue biopsies or as an attractive alternative in cases where tissue biopsies are risky or the quantity/quality does not allow testing.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-08-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Substrate-mediated effects in photothermal patterning of alkanethiol self-assembled monolayers with microfocused continuous-wave lasers

    Anja Schröter / Mark Kalus / Nils Hartmann

    Beilstein Journal of Nanotechnology, Vol 3, Iss 1, Pp 65-

    2012  Band 74

    Abstract: In recent years, self-assembled monolayers (SAMs) have been demonstrated to provide promising new approaches to nonlinear laser processing. Most notably, because of their ultrathin nature, indirect excitation mechanisms can be exploited in order to ... ...

    Abstract In recent years, self-assembled monolayers (SAMs) have been demonstrated to provide promising new approaches to nonlinear laser processing. Most notably, because of their ultrathin nature, indirect excitation mechanisms can be exploited in order to fabricate subwavelength structures. In photothermal processing, for example, microfocused lasers are used to locally heat the substrate surface and initiate desorption or decomposition of the coating. Because of the strongly temperature-dependent desorption kinetics, the overall process is highly nonlinear in the applied laser power. For this reason, subwavelength patterning is feasible employing ordinary continuous-wave lasers. The lateral resolution, generally, depends on both the type of the organic monolayer and the nature of the substrate. In previous studies we reported on photothermal patterning of distinct types of SAMs on Si supports. In this contribution, a systematic study on the impact of the substrate is presented. Alkanethiol SAMs on Au-coated glass and silicon substrates were patterned by using a microfocused laser beam at a wavelength of 532 nm. Temperature calculations and thermokinetic simulations were carried out in order to clarify the processes that determine the performance of the patterning technique. Because of the strongly temperature-dependent thermal conductivity of Si, surface-temperature profiles on Au/Si substrates are very narrow ensuring a particularly high lateral resolution. At a 1/e spot diameter of 2 µm, fabrication of subwavelength structures with diameters of 300–400 nm is feasible. Rapid heat dissipation, though, requires high laser powers. In contrast, patterning of SAMs on Au/glass substrates is strongly affected by the largely distinct heat conduction within the Au film and in the glass support. This results in broad surface temperature profiles. Hence, minimum structure sizes are larger when compared with respective values on Au/Si substrates. The required laser powers, though, are more than one order of magnitude lower. ...
    Schlagwörter femtosecond lasers ; nonlinear laser processing ; self-assembled monolayers ; subwavelength patterning ; ultrathin resists ; Technology ; T ; Chemical technology ; TP1-1185 ; Science ; Q ; Physics ; QC1-999
    Thema/Rubrik (Code) 620
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Beilstein-Institut
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Publisher Correction

    Peer Aramillo Irizar / Sascha Schäuble / Daniela Esser / Marco Groth / Christiane Frahm / Steffen Priebe / Mario Baumgart / Nils Hartmann / Shiva Marthandan / Uwe Menzel / Jule Müller / Silvio Schmidt / Volker Ast / Amke Caliebe / Rainer König / Michael Krawczak / Michael Ristow / Stefan Schuster / Alessandro Cellerino /
    Stephan Diekmann / Christoph Englert / Peter Hemmerich / Jürgen Sühnel / Reinhard Guthke / Otto W. Witte / Matthias Platzer / Eytan Ruppin / Christoph Kaleta

    Nature Communications, Vol 10, Iss 1, Pp 1-

    Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly

    2019  Band 1

    Abstract: The original version of this Article contained an error in the spelling of the author Jule Müller, which was incorrectly given as Julia Müller. Additionally, in Fig. 4a, the blue-red colour scale for fold change in ageing/disease regulation included a ... ...

    Abstract The original version of this Article contained an error in the spelling of the author Jule Müller, which was incorrectly given as Julia Müller. Additionally, in Fig. 4a, the blue-red colour scale for fold change in ageing/disease regulation included a blue stripe in place of a red stripe at the right-hand end of the scale. These errors have been corrected in both the PDF and HTML versions of the Article.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2019-05-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Publisher Correction

    Peer Aramillo Irizar / Sascha Schäuble / Daniela Esser / Marco Groth / Christiane Frahm / Steffen Priebe / Mario Baumgart / Nils Hartmann / Shiva Marthandan / Uwe Menzel / Jule Müller / Silvio Schmidt / Volker Ast / Amke Caliebe / Rainer König / Michael Krawczak / Michael Ristow / Stefan Schuster / Alessandro Cellerino /
    Stephan Diekmann / Christoph Englert / Peter Hemmerich / Jürgen Sühnel / Reinhard Guthke / Otto W. Witte / Matthias Platzer / Eytan Ruppin / Christoph Kaleta

    Nature Communications, Vol 10, Iss 1, Pp 1-

    Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly

    2019  Band 1

    Abstract: The original version of this Article contained an error in the spelling of the author Jule Müller, which was incorrectly given as Julia Müller. Additionally, in Fig. 4a, the blue-red colour scale for fold change in ageing/disease regulation included a ... ...

    Abstract The original version of this Article contained an error in the spelling of the author Jule Müller, which was incorrectly given as Julia Müller. Additionally, in Fig. 4a, the blue-red colour scale for fold change in ageing/disease regulation included a blue stripe in place of a red stripe at the right-hand end of the scale. These errors have been corrected in both the PDF and HTML versions of the Article.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2019-05-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly

    Peer Aramillo Irizar / Sascha Schäuble / Daniela Esser / Marco Groth / Christiane Frahm / Steffen Priebe / Mario Baumgart / Nils Hartmann / Shiva Marthandan / Uwe Menzel / Jule Müller / Silvio Schmidt / Volker Ast / Amke Caliebe / Rainer König / Michael Krawczak / Michael Ristow / Stefan Schuster / Alessandro Cellerino /
    Stephan Diekmann / Christoph Englert / Peter Hemmerich / Jürgen Sühnel / Reinhard Guthke / Otto W. Witte / Matthias Platzer / Eytan Ruppin / Christoph Kaleta

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Band 11

    Abstract: Ageing is associated with a pronounced shift in mortality from cancer to degenerative diseases. Here, the authors show that in concordance with this shift, conserved transcriptional alterations during ageing across four vertebrates align with ... ...

    Abstract Ageing is associated with a pronounced shift in mortality from cancer to degenerative diseases. Here, the authors show that in concordance with this shift, conserved transcriptional alterations during ageing across four vertebrates align with degenerative diseases but are opposite to those in cancer.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2018-01-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel: High tandem repeat content in the genome of the short-lived annual fish Nothobranchius furzeri: a new vertebrate model for aging research

    Reichwald, Kathrin / Alessandro Cellerino / Chris Lauber / Christoph Englert / Gernot Glöckner / Indrajit Nanda / Jeanette Kirschner / Karol Szafranski / Manfred Schartl / Markus B Schilhabel / Matthias Platzer / Michael Schmid / Nils Hartmann / Stefan Taudien / Susanne Schories / Ulrike Gausmann

    Genome biology. 2009 Feb., v. 10, no. 2

    2009  

    Abstract: BACKGROUND: The annual fish Nothobranchius furzeri is the vertebrate with the shortest known life span in captivity. Fish of the GRZ strain live only three to four months under optimal laboratory conditions, show explosive growth, early sexual maturation ...

    Abstract BACKGROUND: The annual fish Nothobranchius furzeri is the vertebrate with the shortest known life span in captivity. Fish of the GRZ strain live only three to four months under optimal laboratory conditions, show explosive growth, early sexual maturation and age-dependent physiological and behavioral decline, and express aging related biomarkers. Treatment with resveratrol and low temperature significantly extends the maximum life span. These features make N. furzeri a promising new vertebrate model for age research. RESULTS: To contribute to establishing N. furzeri as a new model organism, we provide a first insight into its genome and a comparison to medaka, stickleback, tetraodon and zebrafish. The N. furzeri genome contains 19 chromosomes (2n = 38). Its genome of between 1.6 and 1.9 Gb is the largest among the analyzed fish species and has, at 45%, the highest repeat content. Remarkably, tandem repeats comprise 21%, which is 4-12 times more than in the other four fish species. In addition, G+C-rich tandem repeats preferentially localize to centromeric regions. Phylogenetic analysis based on coding sequences identifies medaka as the closest relative. Genotyping of an initial set of 27 markers and multi-locus fingerprinting of one microsatellite provides the first molecular evidence that the GRZ strain is highly inbred. CONCLUSIONS: Our work presents a first basis for systematic genomic and genetic analyses aimed at understanding the mechanisms of life span determination in N. furzeri.
    Schlagwörter biomarkers ; captive animals ; chromosomes ; Danio rerio ; decline ; fish ; genome ; genotyping ; longevity ; microsatellite repeats ; models ; Nothobranchius furzeri ; phylogeny ; resveratrol ; sexual maturity ; tandem repeat sequences ; temperature
    Sprache Englisch
    Erscheinungsverlauf 2009-02
    Umfang p. 2166.
    Erscheinungsort Springer-Verlag
    Dokumenttyp Artikel
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/gb-2009-10-2-r16
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  10. Artikel: Insights into Sex Chromosome Evolution and Aging from the Genome of a Short-Lived Fish

    Reichwald, Kathrin / Andreas Petzold / Philipp Koch / Bryan R. Downie / Nils Hartmann / Stefan Pietsch / Mario Baumgart / Domitille Chalopin / Marius Felder / Martin Bens / Arne Sahm / Karol Szafranski / Stefan Taudien / Marco Groth / Ivan Arisi / Anja Weise / Samarth S. Bhatt / Virag Sharma / Johann M. Kraus /
    Florian Schmid / Steffen Priebe / Thomas Liehr / Matthias Görlach / Manuel E. Than / Michael Hiller / Hans A. Kestler / Jean-Nicolas Volff / Manfred Schartl / Alessandro Cellerino / Christoph Englert / Matthias Platzer

    Cell. 2015 Dec. 03, v. 163

    2015  

    Abstract: The killifish Nothobranchius furzeri is the shortest-lived vertebrate that can be bred in the laboratory. Its rapid growth, early sexual maturation, fast aging, and arrested embryonic development (diapause) make it an attractive model organism in ... ...

    Abstract The killifish Nothobranchius furzeri is the shortest-lived vertebrate that can be bred in the laboratory. Its rapid growth, early sexual maturation, fast aging, and arrested embryonic development (diapause) make it an attractive model organism in biomedical research. Here, we report a draft sequence of its genome that allowed us to uncover an intra-species Y chromosome polymorphism representing—in real time—different stages of sex chromosome formation that display features of early mammalian XY evolution “in action.” Our data suggest that gdf6Y, encoding a TGF-β family growth factor, is the master sex-determining gene in N. furzeri. Moreover, we observed genomic clustering of aging-related genes, identified genes under positive selection, and revealed significant similarities of gene expression profiles between diapause and aging, particularly for genes controlling cell cycle and translation. The annotated genome sequence is provided as an online resource (http://www.nothobranchius.info/NFINgb).
    Schlagwörter Nothobranchius furzeri ; Y chromosome ; biomedical research ; cell cycle ; diapause ; embryogenesis ; evolution ; fish ; gene expression ; genes ; mammals ; nucleotide sequences ; sexual maturity ; transforming growth factor beta ; translation (genetics)
    Sprache Englisch
    Erscheinungsverlauf 2015-1203
    Umfang p. 1527-1538.
    Erscheinungsort Elsevier Inc.
    Dokumenttyp Artikel
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2015.10.071
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