From Pure Art to Sheer Luxury: Magazines as Ornamental Constellations and the Emergence of Aesthetic Capitalism in the Early Twentieth Century

The concept of ‘ornamental constellations’ introduced in the following article highlights the structural relationships of decorative elements and miscellaneous content in magazines and the importance of the reader’s perspective for their interpretation. ‘Ornamental constellations’ are considered one of the most important media devices of emerging aesthetic capitalism, as they produce economies of attention and affect and establish a visual connection between the basic concept of a magazine, its individual contributions, and the readership addressed, thus promoting a specific aesthetic lifestyle. Their respective staging value is illustrated by analysing two complementary magazines and their constellation techniques: the elitist art magazine Blätter für die Kunst with its ‘strategic arrangement’ of literary and programmatic contributions and the creation of ‘resonances’ between them and the popular sports and society magazine Sport im Bild with its hybridizing flow of texts, images, and advertisements. Despite all the differences, it becomes clear that these are two quite compatible projects within the framework of an emerging aesthetic capitalism: whereas the Blätter für die Kunst staged and materialized the idea of pure art as an exclusive aesthetic lifestyle, the Sport im Bild made the desired aesthetic way of life also attainable by non-artists (with enough money) by associating it with the idea of an aesthetic capitalism

Resolving the Combinatorial Complexity of Smad Protein Complex Formation and Its Link to Gene Expression.

Upon stimulation of cells with transforming growth factor beta (TGF-beta), Smad proteins form trimeric complexes and activate a broad spectrum of target genes. It remains unresolved which of the possible Smad complexes are formed in cellular contexts and how these contribute to gene expression. By combining quantitative mass spectrometry with a computational selection strategy, we predict and provide experimental evidence for the three most relevant Smad complexes in the mouse hepatoma cell line Hepa1-6. Utilizing dynamic pathway modeling, we specify the contribution of each Smad complex to the expression of representative Smad target genes, and show that these contributions are conserved in human hepatoma cell lines and primary hepatocytes. We predict, based on gene expression data of patient samples, increased amounts of Smad2/3/4 proteins and Smad2 phosphorylation as hallmarks of hepatocellular carcinoma and experimentally verify this prediction. Our findings demonstrate that modeling approaches can disentangle the complexity of transcription factor complex formation and its impact on gene expression

Potential Therapeutic Effects of Long-Term Stem Cell Administration: Impact on the Gene Profile and Kidney Function of PKD/Mhm (Cy/+) Rats

Cystic kidney disease (CKD) is a heterogeneous group of genetic disorders and one of the most common causes of end-stage renal disease. Here, we investigate the potential effects of long-term human stem cell treatment on kidney function and the gene expression profile of PKD/Mhm (Cy/+) rats. Human adipose-derived stromal cells (ASC) and human skin-derived ABCB5+ stromal cells (2 × 106) were infused intravenously or intraperitoneally monthly, over 6 months. Additionally, ASC and ABCB5+-derived conditioned media were administrated intraperitoneally. The gene expression profile results showed a significant reprogramming of metabolism-related pathways along with downregulation of the cAMP, NF-kB and apoptosis pathways. During the experimental period, we measured the principal renal parameters as well as renal function using an innovative non-invasive transcutaneous device. All together, these analyses show a moderate amelioration of renal function in the ABCB5+ and ASC-treated groups. Additionally, ABCB5+ and ASC-derived conditioned media treatments lead to milder but still promising improvements. Even though further analyses have to be performed, the preliminary results obtained in this study can lay the foundations for a novel therapeutic approach with the application of cell-based therapy in CKD

Stem/Stromal Cells for Treatment of Kidney Injuries With Focus on Preclinical Models

Within the last years, the use of stem cells (embryonic, induced pluripotent stem cells, or hematopoietic stem cells), Progenitor cells (e.g., endothelial progenitor cells), and most intensely mesenchymal stromal cells (MSC) has emerged as a promising cell-based therapy for several diseases including nephropathy. For patients with end-stage renal disease (ESRD), dialysis or finally organ transplantation are the only therapeutic modalities available. Since ESRD is associated with a high healthcare expenditure, MSC therapy represents an innovative approach. In a variety of preclinical and clinical studies, MSC have shown to exert renoprotective properties, mediated mainly by paracrine effects, immunomodulation, regulation of inflammation, secretion of several trophic factors, and possibly differentiation to renal precursors. However, studies are highly diverse; thus, knowledge is still limited regarding the exact mode of action, source of MSC in comparison to other stem cell types, administration route and dose, tracking of cells and documentation of therapeutic efficacy by new imaging techniques and tissue visualization. The aim of this review is to provide a summary of published studies of stem cell therapy in acute and chronic kidney injury, diabetic nephropathy, polycystic kidney disease, and kidney transplantation. Preclinical studies with allogeneic or xenogeneic cell therapy were first addressed, followed by a summary of clinical trials carried out with autologous or allogeneic hMSC. Studies were analyzed with respect to source of cell type, mechanism of action etc

TSC22D4 is a molecular output of hepatic wasting metabolism

In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. Here, we show that tumour growth triggers hepatic metabolic dysfunction as part of the cancer cachectic phenotype, particularly by reduced hepatic very-low-density-lipoprotein (VLDL) secretion and hypobetalipoproteinemia. As a molecular cachexia output pathway, hepatic levels of the transcription factor transforming growth factor beta 1-stimulated clone (TSC) 22 D4 were increased in cancer cachexia. Mimicking high cachectic levels of TSC22D4 in healthy livers led to the inhibition of hepatic VLDL release and lipogenic genes, and diminished systemic VLDL levels under both normal and high fat dietary conditions. Liver-specific ablation of TSC22D4 triggered hypertriglyceridemia through the induction of hepatic VLDL secretion. Furthermore, hepatic TSC22D4 expression levels were correlated with the degree of body weight loss and VLDL hypo-secretion in cancer cachexia, and TSC22D4 deficiency rescued tumour cell-induced metabolic dysfunction in hepatocytes. Therefore, hepatic TSC22D4 activity may represent a molecular rationale for peripheral energy deprivation in subjects with metabolic wasting diseases, including cancer cachexi

microRNA-379 couples glucocorticoid hormones to dysfunctional lipid homeostasis

In mammals, glucocorticoids (GCs) and their intracellular receptor, the glucocorticoid receptor (GR), represent critical checkpoints in the endocrine control of energy homeostasis. Indeed, aberrant GC action is linked to severe metabolic stress conditions as seen in Cushing's syndrome, GC therapy and certain components of the Metabolic Syndrome, including obesity and insulin resistance. Here, we identify the hepatic induction of the mammalian conserved microRNA (miR)-379/410 genomic cluster as a key component of GC/GR-driven metabolic dysfunction. Particularly, miR-379 was up-regulated in mouse models of hyperglucocorticoidemia and obesity as well as human liver in a GC/GR-dependent manner. Hepatocyte-specific silencing of miR-379 substantially reduced circulating very-low-density lipoprotein (VLDL)-associated triglyceride (TG) levels in healthy mice and normalized aberrant lipid profiles in metabolically challenged animals, mediated through miR-379 effects on key receptors in hepatic TG re-uptake. As hepatic miR-379 levels were also correlated with GC and TG levels in human obese patients, the identification of a GC/GR-controlled miRNA cluster not only defines a novel layer of hormone-dependent metabolic control but also paves the way to alternative miRNA-based therapeutic approaches in metabolic dysfunctio

Erratum: ‘Corrigendum to “Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia” [Molecular Metabolism 5 (2) (2015) 67–78]’ (Molecular Metabolism (2016) 5(2) (67–78), (S2212877815002161), (10.1016/j.molmet.2015.11.004))

The authors regret that the original paper was published with an error in the supplementary data (Table 1). In order to identify tumor-secreted factors that contribute to cardiac atrophy under the condition of cancer cachexia, in the original study, we performed a differential secretome analysis comparing cell conditioned media from cachexia-inducing C26 colon carcinoma cells and non-cachexia-inducing MC38 colon carcinoma cells. Secreted proteins which were at least 2-fold more abundantly secreted from C26 cells were selected for further functional validation. Functional validation was performed by overexpressing candidate proteins in HEK293A cells and collecting the candidate-enriched cell conditioned media for assaying their atrophy-inducing potential on primary neonatal rat cardiomyocytes. In the context of subsequent studies focusing on different aspects of cancer-induced cachexia, we performed a differential transcriptomics analysis comparing RNAseq data from C26 and MC38 cells. While differential protein secretion does not necessarily need to be fully reflected by corresponding differences at the level of gene expression, we were still surprised about the lack of congruency between the corresponding regulation of gene expression and protein secretion. Surprisingly, for the overlap of genes and proteins being differentially regulated between C26 and MC38 cells (regardless of the direction of change), we found a significant negative correlation between differential gene expression and differential protein secretion (Corrigendum Figure 1 A). In order to elucidate the basis of this unexpected finding, we decided to repeat the differential secretome analysis in the same manner as it has been performed in the original study. Notably, the comparison between the secretome analyses (old vs new) revealed a remarkably strong negative correlation concerning the difference in protein secretion between C26 and MC38 cells (Corrigendum Figure 1B). Furthermore, when we then compared the new secretome analysis with the differences in the transcription between C26 and MC38 cells, there was a highly significant positive correlation (Corrigendum Figure 1C). The found consistency for the differences between the cell lines at distinct levels of regulation (transcription vs secretion) suggested that these datasets were correctly associated, in contrast to the previous comparison with the original differential secretome analysis. Taken together, these new analyses strongly indicate that in the original (old) secretome analysis, a swap in the sample allocation must have occurred, either during sample preparation, the subsequent proteomic or data analysis. Despite extensive evaluation of the respective experiment records, it was not possible to detect at which exact point in the course of the experimental work this mistake was made. Remarkably enough, the high-throughput functional validation of 109 candidates performed in the original study (original manuscript Figure 3C), using selected candidates now considered to be more abundantly secreted from non-cachexia-inducing MC38 instead of cachexia-inducing C26 cells, still revealed a set of candidates showing the expected atrophy effects upon treatment of primary cardiomyocytes with the respective candidate-enriched conditioned media. These effects were comparable to the effects of C26 conditioned medium on cardiomyocyte atrophy (original Figure 2A and B) and were therefore applied as primary selection criterion for putative cachexokines (mediators of cachexia). Additionally, further analysis selected a subset of 7 candidates which, similar to C26 conditioned medium, increased the fatty acid oxidation rate in neonatal rat cardiomyocytes treated with candidate-enriched medium (original Figure 4A). We speculate that the high-throughput functional analysis, albeit being based on an erroneous initial secretome analysis, contained a sufficient high number of protein candidates in order to contain protein factors which eventually turned out to be still relevant with respect to their capability to mediate a specific component of the cachexia phenotype (cardiomyocyte atrophy). This is exemplified by the main candidate Ataxin-10 (Atxn10), for which we could confirm elevated levels in different models of experimental cachexia, including C26 tumor-bearing mice but not in MC38 tumor-bearing mice (original Figure 5A–D). In a model pancreatic of cancer based on orthotopic cell implantation, circulating Atxn10 levels closely correlated with the degree of weight loss (Figure 5E and F). Finally, we found Atxn10 levels to be elevated in cancer patients with cachexia compared to weight-stable patients (Figure 5G). Therefore, we would like to emphasize that the majority of data provided in the publication is still correct. We apologize for any inconvenience that might have resulted from providing incorrect differential secretome data as supplemental material of the study and now provide the data of the new and correct differential secretome analysis (Corrigendum supplemental data)

Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia

Objectives: Cancer cachexia affects the majority of tumor patients and significantly contributes to high mortality rates in these subjects. Despite its clinical importance, the identity of tumor-borne signals and their impact on specific peripheral organ systems, particularly the heart, remain mostly unknown. Methods and results: By combining differential colon cancer cell secretome profiling with large-scale cardiomyocyte phenotyping, we identified a signature panel of seven "cachexokines", including Bridging integrator 1, Syntaxin 7, Multiple inositol-polyphosphate phosphatase 1, Glucosidase alpha acid, Chemokine ligand 2, Adamts like 4, and Ataxin-10, which were both sufficient and necessary to trigger cardiac atrophy and aberrant fatty acid metabolism in cardiomyocytes. As a prototypical example, engineered secretion of Ataxin-10 from non-cachexia-inducing cells was sufficient to induce cachexia phenotypes in cardiomyocytes, correlating with elevated Ataxin-10 serum levels in murine and human cancer cachexia models. Conclusions: As Ataxin-10 serum levels were also found to be elevated in human cachectic cancer patients, the identification of Ataxin-10 as part of a cachexokine cocktail now provides a rational approach towards personalized predictive, diagnostic and therapeutic measures in cancer cachexia