Functional rescue of the glomerulosclerosis phenotype in Mpv17 mice by transgenesis with the human Mpv17 homologue

The germ line insertion of a defective retrovirus into the Mpv17 gene of mice is associated with a recessive phenotype. Mice homozygous for the integration develop glomerulosclerosis at a young age. The phenotype resembles human glomerulosclerosis in its physiological parameters as well as in histology. A human homologue of the Mpv17 gene has been identified, isolated and analyzed. We here show that this gene, which has a role in the production of reactive oxygen species, can rescue the phenotype of Mpv17 deficient mice when introduced by transgenesis. This provides formal proof for the hypothesis that the phenotype is caused by the loss of function of the Mpv17 gene. It also provides evidence for the functional conservation of the Mpv17 gene in mammals and points to a potential role of this gene in human kidney disease

CIK Cells and HDAC Inhibitors in Multiple Myeloma

Multiple myeloma is the second most common hematological malignancy. Despite all the progress made in treating multiple myeloma, it still remains an incurable disease. Patients are left with a median survival of 4-5 years. The combined treatment of multiple myeloma with histone deacetylase inhibitors and cytokine-induced killer cells provides a promising targeted treatment option for patients. This study investigated the impact of a combined treatment compared to treatment with histone deacetylase inhibitors. The experiments revealed that a treatment with histone deacetylase (HDAC) inhibitors could reduce cell viability to 59% for KMS 18 cell line and 46% for the U-266 cell line. The combined treatment led to a decrease of cell viability to 33% for KMS 18 and 27% for the U-266 cell line, thus showing a significantly better efficacy than the single treatment

A monoclonal antibody raised against bacterially expressed MPV17 sequences shows peroxisomal, endosomal and lysosomal localisation in U2OS cells

Recessive mutations in the MPV17 gene cause mitochondrial DNA depletion syndrome, a fatal infantile genetic liver disease in humans. Loss of function in mice leads to glomerulosclerosis and sensineural deafness accompanied with mitochondrial DNA depletion. Mutations in the yeast homolog Sym1, and in the zebra fish homolog tra cause interesting, but not obviously related phenotypes, although the human gene can complement the yeast Sym1 mutation. The MPV17 protein is a hydrophobic membrane protein of 176 amino acids and unknown function. Initially localised in murine peroxisomes, it was later reported to be a mitochondrial inner membrane protein in humans and in yeast. To resolve this contradiction we tested two new mouse monoclonal antibodies directed against the human MPV17 protein in Western blots and immunohistochemistry on human U2OS cells. One of these monoclonal antibodies showed specific reactivity to a protein of 20 kD absent in MPV17 negative mouse cells. Immunofluorescence studies revealed colocalisation with peroxisomal, endosomal and lysosomal markers, but not with mitochondria. This data reveal a novel connection between a possible peroxisomal/endosomal/lysosomal function and mitochondrial DNA depletion

A monoclonal antibody raised against bacterially expressed MPV17 sequences shows peroxisomal, endosomal and lysosomal localisation in U2OS cells

Recessive mutations in the MPV17 gene cause mitochondrial DNA depletion syndrome, a fatal infantile genetic liver disease in humans. Loss of function in mice leads to glomerulosclerosis and sensineural deafness accompanied with mitochondrial DNA depletion. Mutations in the yeast homolog Sym1, and in the zebra fish homolog tra cause interesting, but not obviously related phenotypes, although the human gene can complement the yeast Sym1 mutation. The MPV17 protein is a hydrophobic membrane protein of 176 amino acids and unknown function. Initially localised in murine peroxisomes, it was later reported to be a mitochondrial inner membrane protein in humans and in yeast. To resolve this contradiction we tested two new mouse monoclonal antibodies directed against the human MPV17 protein in Western blots and immunohistochemistry on human U2OS cells. One of these monoclonal antibodies showed specific reactivity to a protein of 20 kD absent in MPV17 negative mouse cells. Immunofluorescence studies revealed colocalisation with peroxisomal, endosomal and lysosomal markers, but not with mitochondria. This data reveal a novel connection between a possible peroxisomal/endosomal/lysosomal function and mitochondrial DNA depletion

Die Textualität der Kultur. Gegenstände, Methoden, Probleme der kultur- und literaturwissenschaftlichen Forschung

Im Zuge des sogenannten "cultural turn", der die traditionellen Geisteswissenschaften als Kulturwissenschaften neu bestimmte, sah sich auch die Literaturwissenschaft mit ganz neuen Ansprüchen konfrontiert: Statt sich wie bisher mit literarischen Werken oder Texten des täglichen Gebrauchs zu befassen, sollte sie plötzlich mittels interdisziplinärer Ansätze kulturelle Phänomene aller Art wie Rituale, politische Machtstrukturen oder gesellschaftliche Konstellationen analysieren und erklären. Eine Möglichkeit, das Verhältnis von Text und kulturellem Kontext zu denken, bildet die Vorstellung der Textualität der Kultur, die von Stephen Greenblatt, Louis Montrose und anderen Vertretern des New Historicism unter Bezugnahme auf den Kulturbegriff des Ethnologen Clifford Geertz entwickelt wurde. Geertz versteht Kultur als ein „Netzwerk von bedeutungstragenden Verknüpfungen“ (Geertz 1973), dem ein semiotischer, also ein textueller Charakter eigen ist. Dieses analytische Modell eröffnet die Möglichkeit eines bruchlosen Übergangs zwischen dem Text und dem ihn umgebenden Kontext – eines Übergangs, der in beide Richtungen funktioniert und zudem als "dynamisch" vorgestellt wird: Nicht nur wird der Text als Produkt kultureller Einflüsse angesehen und in einen bereits existierenden Kontext eingeordnet, auch dieser Kontext selbst ist als Zeichengewebe charakterisiert durch seine latenten Bedeutungspotentialen, die erst in der entsprechenden Lektüre aktualisiert und damit realisiert werden. Diese Auffassung von der Textualität der Kultur und der Kulturalität von Texten bildet die gemeinsame methodische Annahme der im vorliegenden Tagungsband versammelten Beiträge.After the "cultural turn" of the 1990s redefined the traditional humanities under the label “Cultural Studies”, literary studies were confronted with new challenges. Suddenly, instead of concentrating mainly on literary works or texts fromeveryday life, they were expected to analyse and explain cultural phenomena such as rituals, structures of power or social constellations, using interdisciplinary methods. One possibility for conceptualizing the relationship between text and context is the notion of the "textuality of culture". This idea was coined by Stephen Greenblatt, Louis Montrose, and other scholars of "the New Historicism," referring to a concept of culture first developed by the ethnologist Clifford Geertz. To Geertz, culture is a “web of significance” of a semiotic and textual nature (Geertz 1973). Assuming a dynamic rather than a static relationship, this analytical model allows for fluent interactions between text and context: No longer is a text just considered to be a product of cultural influences set within a given context. Instead, this context, being a web of signs, was understood to be itself "textual", creating unfulfilled potentials of meaning. Only by being ‘read’ and actualized, are these cultural meanings solidified andthus made real. These notions of the "culturality of texts" and the "textuality of culture" constitute the common methodological assumptions of all the articles assembled in this volume

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives