Pro-inflammatory TNF-α and IFN-γ Promote Tumor Growth and Metastasis via Induction of MACC1

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Early stage CRC patients have a good prognosis. If distant metastasis occurs, the 5-year survival drops below 10%. Despite treatment success over the last decades, treatment options for metastatic disease are still limited. Therefore, novel targets are needed to foster therapy of advanced stage CRC patients and hinder progression of early stage patients into metastasis. A novel target is the crucial oncogene Metastasis-Associated in Colon Cancer 1 (MACC1) involved in molecular pathogenesis of CRC metastasis. MACC1 induces cell proliferation and motility, supports cellular survival and rewires metabolism resulting in increased metastasis in vivo. MACC1 is a prognostic biomarker not only for CRC but for more than 20 solid cancer entities. Inflammation plays a pivotal role in tumorigenesis, tumor progression and metastasis. For CRC, inflammatory bowel disease and ulcerative colitis are important inflammation associated risk factors. Certain cytokines, such as TNF-α and IFN-γ, are key factors in determining the contribution of the inflammatory process to CRC. Knowledge of the connection between inflammation and MACC1 driven tumors remains unclear. Gene expression analysis of CRC cells after cytokine stimulation was analyzed by qRT-PCR and Western blot. Cellular motility was assessed by Boyden chamber assays. MACC1 promoter activity after stimulation with pro-inflammatory cytokines was measured using promoter-luciferase constructs. To investigate signal transduction from receptor to effector molecules, blocking experiments using neutralizing antibodies and knockdown experiments were performed. Following TNF-α stimulation, MACC1 and c-Jun expression were significantly increased at the mRNA and protein level. Knockdown of c-Jun reduced MACC1 inducibility following TNF-α stimulation. TNF-α promoted MACC1-induced cell migration that was reverted following MACC1 knockdown. Moreover, MACC1 and c-Jun expression were downregulated by blocking TNFR1, but not TNFR2. Knock down of the NF-κB subunit, p65, reduced basal MACC1 and c-Jun mRNA expression levels. Adalimumab, a clinically approved monoclonal anti-TNF-α antibody, hindered MACC1 induction. The present study highlights that TNF-α regulates the induction of MACC1 via the NF-κB subunit p65 and the transcription factor c-Jun in CRC cells. This finding unravels a novel signaling pathway upstream of MACC1 and provides a potential therapeutic target for the treatment of CRC patients with an associated inflammation

Ansätze zur Reduktion der Nebenkosten im sozialen Wohnungsbau am Beispiel des Vorhabens "PassivhausSozialPlus" in Darmstadt

ANSÄTZE ZUR REDUKTION DER NEBENKOSTEN IM SOZIALEN WOHNUNGSBAU AM BEISPIEL DES VORHABENS "PASSIVHAUSSOZIALPLUS" IN DARMSTADT Ansätze zur Reduktion der Nebenkosten im sozialen Wohnungsbau am Beispiel des Vorhabens "PassivhausSozialPlus" in Darmstadt / Großklos, Marc (Rights reserved) ( -

The predictive value of depression in the years after heart transplantation for mortality during long-term follow-up

Objective Current understanding of the prognostic impact of depression on mortality after heart transplantation (HTx) is limited. We examined whether depression after HTx is a predictor of mortality during extended follow-up. Subsequently, we explored whether different symptom dimensions of depression could be identified and whether they were differentially associated with mortality. Methods Survival analyses were performed in a sample of 141 HTx recipients assessed for depression, measured by self-report of depressive symptoms (Beck Depression Inventory – version 1A [BDI-1A]), at median 5.0 years after HTx, and followed thereafter for survival status for up to 18.6 years. We used uni- and multivariate Cox proportional hazard models to examine the association of clinically significant depression (BDI-1A total score ≥10), as well as the cognitive-affective and the somatic subscales of the BDI-1A (resulting from principal component analysis) with mortality. In the multivariate analyses, we adjusted for relevant sociodemographic and clinical variables. Results Clinically significant depression was a significant predictor of mortality (hazard ratio = 2.088; 95% confidence interval = 1.366–3.192; p = .001). Clinically significant depression also was an independent predictor of mortality in the multivariate analysis (hazard ratio = 1.982; 95% confidence interval = 1.220–3.217; p = .006). The somatic subscale, but not the cognitive-affective subscale, was significantly associated with increased mortality in univariate analyses, whereas neither of the two subscales was an independent predictor of mortality in the multivariate analysis. Conclusions Depression measured by self-report after HTx is associated with increased mortality during extended follow-up. Clinical utility and predictive validity of specific depression components require further study.acceptedVersio

Scenario Analyses Concerning Energy Efficiency and Climate Protection in Regional and National Residential Building Stocks. Examples from Nine European Countries. - EPISCOPE Synthesis Report No. 3

This report documents methodological aspects and selected results of the scenario analyses to assess refurbishment as well as energy saving processes and project future energy consumption.. It covers scenario calculations conducted for regional residential building stocks in Salzburg/Austria, the Comunidat Valenciana/Spain, the Piedmont Region/Italy, the national non-profit housing stock in the Netherlands as well as the national residential building stocks in Germany, England, Greece, Norway, and Slovenia. Thereby, the objective of the scenario analysis is not a prediction of future energy demand in the respective building stock. Rather, the objective is to show the potential future impact of predefined assumptions. This may help respective key actors and policy makers to decide on strategies and policies for transforming building stocks towards carbon dioxide neutrality

Lost in Transformation? Chancen und Herausforderungen für inklusiven Unterricht im Angesicht der digitalen Transformation

Ausgehend von den entwickelten Qualitätsmerkmalen und Gelingensbedingungen für inklusiven Unterricht diskutiert der Beitrag anhand von 14 Merkmalen die Frage, welche Chancen und Herausforderungen aktuelle Digitalisierungsprozesse für die Gestaltung inklusiven Unterrichts eröffnen können. Mit der Vorstellung von Gelingensbedingungen verfolgt der Beitrag das Ziel, eine Strukturierungshilfe zur Diskussion zu stellen, um im Kontext der komplexen Entwicklungs- und Transformationsprozesse nicht die Orientierung zu verlieren. Diese Gelingensbedingungen sind das (Zwischen-)Ergebnis der interdisziplinären Werkstatt Digitalisierung in inklusiven Settings als Bestandteil des QLB-Projektes BRIDGES an der Universität Vechta. Im Rahmen des Beitrages werden die gemeinsam entwickelten Merkmale vorgestellt und die fachspezifischen Perspektiven der beteiligten Bildungswissenschaften und Fachdidaktiken exemplarisch dargelegt. (DIPF/Orig.

Tracking of Energy Performance Indicators in Residential Building Stocks – Different Approaches and Common Results - EPISCOPE Synthesis Report No. 4

A central task of IEE EPISCOPE project was to carry out energy balance calculations and scenario analysis for national, regional or local residential building stocks against the background of energy saving and climate protection targets. The EPISCOPE Synthesis Report No. 4 documents the individual approaches of collecting information for the investigated residential building stocks as a foundation for building stock models and scenario calculations. Issues related to the availability of data and data quality are discussed, and concepts for a continuous monitoring (a regular data collection) are presented as a basis for a future tracking of energy performance in the observed building stocks

1207 Use of energy profile indicators to determine the expected range of heating energy consumption

A small set of query variables designed to collect information about the energy-related features of residential buildings is presented. These “energy profile indicators” include information about those visible characteristics of a building which have a notable impact on its energy performance and are simple to assess. The queries are an interesting source for a rough energy performance calculation for single buildings as well as for housing portfolios or housing stocks.A method has been developed to transform the energy profile indicators into input data for a physical calculation model. It consists of procedures to estimate the envelope area, U-values, and efficiency values of the heat supply system. To all model input variables an uncertainty is assigned. If information from a query is not available, the model input is set to a state representing the average building stock and the uncertainty of this quantity is adjusted to a value reflecting the variance in the stock. The resulting uncertainty of the calculated energy use is determined.Examples of the application of the method are given to show the influence of different unknown quantities including occupant behaviour. Experiences on the coherence with metered consumption are reported

Sexualität, Identität und Begehren im Kontext kultureller Zweigeschlechtlichkeit

Stein-Hilbers M, Soine S, Wrede B. Sexualität, Identität und Begehren im Kontext kultureller Zweigeschlechtlichkeit. In: Schmerl C, Soine S, Stein-Hilbers M, Wrede B, eds. Sexuelle Szenen. Inszenierungen von Geschlecht und Sexualität in modernen Gesellschaften. Opladen: Leske und Budrich; 2000: 9-24