Doppler-echokardiographische Verlaufsuntersuchungen von Herzdilatation und Herzhypertrophie an zwei Beispielen transgener Mausmodelle mit einer herzspezifischen Überexpression von Proteinphosphatase 2A und Guanylyl Cyklase-A Knockout

In Myokardbiopsien von Patienten mit terminaler Herzinsuffizienz wurden erhöhte Aktivitätsstufen von Proteinphosphatasen festgestellt. Zur Analyse der Bedeutung von Proteinphosphatase 2A (PP2A) für die Ausbildung von Herzerkrankungen führten wir Doppler-echokardiographische Untersuchungen an einem transgenen Mausmodell mit einer herzspezfischen Überexpression von PP2A durch. Die Mäuse entwickelten eine kardiale Dilatation und eine reduzierte Herzkontraktilität. Störungen in der Phosphataseexprimierung können eine Herzinsuffizienz auslösen. Die Entwicklung einer Herzinsuffizienz wird durch Mediatoren gesteuert. Das atriale natriuretische Peptid (ANP) wirkt durch Senkung von Vor- und Nachlast kardioprotektiv. Über Bindung des ANP-Rezeptors wird die Guanylyl Cyclase-A (GC-A) aktiviert. Zur Analyse einer gezielten ANP/GC-A Dysfunktion führten wir Doppler-echokardiographische Untersuchungen an transgenen GC-A Knockout Mäusen durch. Diese wiesen Herzdilatation und –hypertrophie auf

Global survey on durability variation – on the effect of the reference species

Climate change due to anthropogenic emissions is the largest environmental challenge of ourtime. Forest-based value chains play an important role in reducing the accumulation of CO2 in the atmosphere. Maximizing the use of wood to tackle climate change requires improved understanding of the service life of timber products. This information can best be obtained from field testing and while there is an abundance of field performance data from sites all over the world, most of the data are not available in a form that can be utilised for service life models. The IRG Durability Database aims to improve the usability of existing performance data and create added value for durability research and service life prediction. The present paper takes the first steps in comparing global field test performance data from the IRG Durability Database for non-durable reference species. Data were obtained from six species above ground and ground contact field tests from 36 sites around the world. For each dataset, decay rates and service life (where applicable) were calculated. Datasets were then grouped together based on test method and species. Decay rate was faster and more uniform in ground contact than above ground. Inground contact, beech decayed most rapidly, followed by Norway spruce and Scots pines apwood. All appeared to be suitable for use as reference species, however slow-grown spruce should be avoided. There were no statistically significant correlations between ground contact decay rate and the Scheffer Climate Index (SCI). In above ground tests, differences in decay ratewere largely related to differences in moisture dynamics. Species with the greatest absorption and retention of water decayed most rapidly. Test methods that absorbed and retained the most moisture (e.g. painted L-joints) resulted in more rapid decay. Above ground decay rate and SCI were significantly correlated in two data sets that had a wide range of SCI values. Correlations were not significant when only European test sites were included. Estimating decay rate from field testing results in highly variable data. Comparing data from global test sites is made more difficult by the absence of common field testing standards

The Role of CXCL13 and CXCL9 in Early Breast Cancer

Background: Chemokines, cytokines in the immune microenvironment of tumors, may be associated with patient outcome. We assessed the impact of CXCL13 and CXCL9 on disease-free (DFS) and overall survival (OS), in an attempt to retrospectively evaluate both T and B cell function in the microenvironment of primary tumors from patients with breast cancer. Materials and Methods: Formalin-fixed paraffin-embedded tissue blocks from patients with intermediate/high-risk, early breast cancer, treated with sequential adjuvant epirubicin, paclitaxel, and cyclophosphamide methotrexate fluorouracil within a randomized trial, were tested for CXCL13 and CXCL9 messenger RNA expression; 557 patients with adequate tissue were eligible for the analysis. Results: CXCL13 was correlated with CXCL9 (rho = 0.52; P < .001). High-expressing CXL13 and CXCL9 tumors had higher Ki67 and tumor infiltrating lymphocyte density (P-values < .001). High CXCL9 expression was an unfavorable prognosticator for OS among all patients (hazard ratio [HR], 1.73; P = .021), whereas it showed favorable significance for both DFS and OS in patients with triple negative disease (HR, 0.29; P = .027 and HR, 0.32; P = .045). High CXCL13 conferred longer DFS and OS among patients with luminal-human epidermal growth factor receptor 2 disease (HR, 0.31; P = .013 and HR, 0.25; P = .005). Patients with low CXCL13 and high CXCL9 expression had shorter DFS and OS compared with those with high expression of both chemokines (HR, 1.63; P = .006 and HR, 1.61; P = .016). Conclusions: Both biomarkers were associated with poor prognosis characteristics and with tumor infiltrating lymphocyte density. High CXCL9 conferred an improved prognosis in the triple negative subtype, whereas high CXCL13 was associated with improved outcome in the luminal-human epidermal growth factor receptor 2 subtype. Chemokines can be associated with breast cancer subtype and outcome. These data should be evaluated prospectively. © 2019 Elsevier Inc. Chemokines are of increasing interest in breast cancer. A total of 557 tissue samples from patients with early breast cancer treated in the context of a prospective adjuvant chemotherapy trial were tested for CXCL13 and CXCL9 expression, and the results were associated with outcome and other markers. CXCL13 was associated with triple positive disease and CXCL9 with triple negative disease, both conferring improved outcome. © 2019 Elsevier Inc