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  • 1
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    Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-12-04
    Description: Article Hereditary hypertrophic cardiomyopathy (HCM) is caused by mutations in cardiomyocyte genes, such as MYBPC3 . Here, the authors use virus-mediated gene therapy to correct Mycbpc3 mutations in 1-day-old mice and, by administering just a single dose, prevent development of HCM over a period of 34 weeks. Nature Communications doi: 10.1038/ncomms6515 Authors: Giulia Mearini, Doreen Stimpel, Birgit Geertz, Florian Weinberger, Elisabeth Krämer, Saskia Schlossarek, Julia Mourot-Filiatre, Andrea Stoehr, Alexander Dutsch, Paul J. M. Wijnker, Ingke Braren, Hugo A. Katus, Oliver J. Müller, Thomas Voit, Thomas Eschenhagen, Lucie Carrier
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Rescue of cardiomyopathy through U7snRNA-mediated exon skipping in Mybpc3-targeted knock-in mice (2013)
    Wiley-Blackwell
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    Publication Date: 2013-05-30
    Description: Exon skipping mediated by antisense oligoribonucleotides (AON) is a promising therapeutic approach for genetic disorders, but has not yet been evaluated for cardiac diseases. We investigated the feasibility and efficacy of viral-mediated AON transfer in a Mybpc3 -targeted knock-in (KI) mouse model of hypertrophic cardiomyopathy (HCM). KI mice carry a homozygous G〉A transition in exon 6, which results in three different aberrant mRNAs. We identified an alternative variant (Var-4) deleted of exons 5–6 in wild-type and KI mice. To enhance its expression and suppress aberrant mRNAs we designed AON-5 and AON-6 that mask splicing enhancer motifs in exons 5 and 6. AONs were inserted into modified U7 small nuclear RNA and packaged in adeno-associated virus (AAV-U7-AON-5+6). Transduction of cardiac myocytes or systemic administration of AAV-U7-AON-5+6 increased Var-4 mRNA/protein levels and reduced aberrant mRNAs. Injection of newborn KI mice abolished cardiac dysfunction and prevented left ventricular hypertrophy. Although the therapeutic effect was transient and therefore requires optimization to be maintained over an extended period, this proof-of-concept study paves the way towards a causal therapy of HCM. Exon skipping is a promising therapy for selected genetic diseases. Here, the authors show as a proof-of-principle that MYBPC3 mutation-induced cardiomyopathy can be rescued by AAV-U7-antisense oligoribonucleotides in the heart of neonatal mice.
    Print ISSN: 1757-4676
    Electronic ISSN: 1757-4684
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The European Molecular Biology Organization (EMBO).
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  • 3
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    Herbivore-induced defence response in the brown seaweed Fucus vesiculosus (Phaeophyceae): temporal pattern and gene expression (2014)
    TAYLOR & FRANCIS LTD
    In:  EPIC3European Journal of Phycology, TAYLOR & FRANCIS LTD, 49(3), pp. 356-369, ISSN: 0967-0262
    Details
    Publication Date: 2019-07-16
    Description: This study aimed to reveal the dynamics of inducible anti-herbivory traits in the brown seaweed Fucus vesiculosus, in response to grazing by the isopod Idotea baltica. As the molecular basis of defence induction in seaweeds is poorly understood, a transcriptomic approach was used to gain insight into cellular processes underlying defence induction and thus promote the mechanistic understanding of anti-herbivory responses in seaweeds. In a 27 day feeding-assayed induction experiment, temporal patterns of the induced anti-herbivory resistance of F. vesiculosus were assessed under laboratory conditions. Feeding assays were performed at three day intervals, using fresh and reconstituted food. Microarray hybridizations investigating the expression of genes 3 days before, as well as at the same time as, feeding assays revealed a decreased palatability of previously grazed F. vesiculosus pieces compared with non-grazed control pieces. Despite permanent exposure to grazers, F. vesiculosus palatability varied over time. Non-grazed F. vesiculosus pieces were significantly preferred to grazed pieces after 18 and again after 27 days of previous grazing, while their relative palatability for isopods was comparable at all other times during the experiment. Relative to controls, 562/402 genes were ≥ 1.5-fold up-/down-regulated in seaweed pieces that were grazed for 18 days, i.e. when induction of defences was detected in feeding assays. Massive reprogramming of the regulatory expression orchestra (translation, transcription) as well as up-regulation of genes involved in lipid and carbohydrate metabolism, intracellular trafficking, defence and stress response was found. At the same time, down-regulation of photosynthesis was observed in grazed seaweed pieces. This study suggests a high level of temporal variability in induced anti-herbivory traits of F. vesiculosus and reveals increased expression of genes with putative defensive functions in conjunction with the reallocation of resources from primary to secondary metabolism.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
    Format: application/pdf
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  • 4
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    Herbivore-induced defence response in the brown seaweed Fucus vesiculosus (Phaeophyceae): temporal pattern and gene expression (2014)
    TAYLOR & FRANCIS LTD
    In:  EPIC3European Journal of Phycology, TAYLOR & FRANCIS LTD, 49(3), pp. 356-369, ISSN: 0967-0262
    Details
    Publication Date: 2014-11-18
    Description: This study aimed to reveal the dynamics of inducible anti-herbivory traits in the brown seaweed Fucus vesiculosus, in response to grazing by the isopod Idotea baltica. As the molecular basis of defence induction in seaweeds is poorly understood, a transcriptomic approach was used to gain insight into cellular processes underlying defence induction and thus promote the mechanistic understanding of anti-herbivory responses in seaweeds. In a 27 day feeding-assayed induction experiment, temporal patterns of the induced anti-herbivory resistance of F. vesiculosus were assessed under laboratory conditions. Feeding assays were performed at three day intervals, using fresh and reconstituted food. Microarray hybridizations investigating the expression of genes 3 days before, as well as at the same time as, feeding assays revealed a decreased palatability of previously grazed F. vesiculosus pieces compared with non-grazed control pieces. Despite permanent exposure to grazers, F. vesiculosus palatability varied over time. Non-grazed F. vesiculosus pieces were significantly preferred to grazed pieces after 18 and again after 27 days of previous grazing, while their relative palatability for isopods was comparable at all other times during the experiment. Relative to controls, 562/402 genes were ≥ 1.5-fold up-/down-regulated in seaweed pieces that were grazed for 18 days, i.e. when induction of defences was detected in feeding assays. Massive reprogramming of the regulatory expression orchestra (translation, transcription) as well as up-regulation of genes involved in lipid and carbohydrate metabolism, intracellular trafficking, defence and stress response was found. At the same time, down-regulation of photosynthesis was observed in grazed seaweed pieces. This study suggests a high level of temporal variability in induced anti-herbivory traits of F. vesiculosus and reveals increased expression of genes with putative defensive functions in conjunction with the reallocation of resources from primary to secondary metabolism.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 5
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    DSM-5: a collection of psychiatrist views on the changes, controversies, and future directions (2013)
    BioMed Central
    Details
    Publication Date: 2013-09-13
    Description: The recent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association has led to much debate. For this forum article, we asked BMC Medicine Editorial Board members who are experts in the field of psychiatry to discuss their personal views on how the changes in DSM-5 might affect clinical practice in their specific areas of psychiatric medicine. This article discusses the influence the DSM-5 may have on the diagnosis and treatment of autism, trauma-related and stressor-related disorders, obsessive-compulsive and related disorders, mood disorders (including major depression and bipolar disorders), and schizophrenia spectrum disorders.
    Electronic ISSN: 1741-7015
    Topics: Medicine
    Published by BioMed Central
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  • 6
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    The Second Skin: Ecological Role of Epibiotic Biofilms on Marine Organisms (2012)
    Frontiers Media
    Details
    Publication Date: 2012-08-24
    Description: Martin Wahl, Franz Goecke, Antje Labes, Sergey Dobretsov and Florian Weinberger
    Electronic ISSN: 1664-302X
    Topics: Biology
    Published by Frontiers Media
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  • 7
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    Assessment of DNA synthesis in Islet-1+ cells in the adult murine heart (2014)
    Elsevier
    Details
    Publication Date: 2014-11-28
    Description: Publication date: Available online 24 November 2014 Source: Biochemical and Biophysical Research Communications Author(s): Florian Weinberger , Dennis Mehrkens , Jutta Starbatty , Philipp Nicol , Thomas Eschenhagen Rationale: Islet-1 positive (Islet-1 + ) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1 + cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ( 3 H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of 3 H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1 + cells. Whereas Islet − non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1 + cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
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