Inflammation Aggravates Disease Severity in Marfan Syndrome Patients

BACKGROUND: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-beta and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-beta and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-beta were found especially in MFS patients with aortic root dilatation (124 pg/ml), when compared to MFS patients with normal aorta (10 pg/ml; p = 8x10(-6), 95% CI: 70-159 pg/ml). Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR) = 0%), ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC) = 1.8; 1.4; 1.5, FDR = 0%) and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%). Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF) in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02) and increased number of CD8+ T-cells (p = 0.003) in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients

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

Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals

peer-reviewedH.D.D., A.J.C., P.J.B. and B.J.H. would like to acknowledge the Dairy Futures Cooperative Research Centre for funding. H.P. and R.F. acknowledge funding from the German Federal Ministry of Education and Research (BMBF) within the AgroClustEr ‘Synbreed—Synergistic Plant and Animal Breeding’ (grant 0315527B). H.P., R.F., R.E. and K.-U.G. acknowledge the Arbeitsgemeinschaft Süddeutscher Rinderzüchter, the Arbeitsgemeinschaft Österreichischer Fleckviehzüchter and ZuchtData EDV Dienstleistungen for providing genotype data. A. Bagnato acknowledges the European Union (EU) Collaborative Project LowInputBreeds (grant agreement 222623) for providing Brown Swiss genotypes. Braunvieh Schweiz is acknowledged for providing Brown Swiss phenotypes. H.P. and R.F. acknowledge the German Holstein Association (DHV) and the Confederación de Asociaciones de Frisona Española (CONCAFE) for sharing genotype data. H.P. was financially supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft (DFG) (grant PA 2789/1-1). D.B. and D.C.P. acknowledge funding from the Research Stimulus Fund (11/S/112) and Science Foundation Ireland (14/IA/2576). M.S. and F.S.S. acknowledge the Canadian Dairy Network (CDN) for providing the Holstein genotypes. P.S. acknowledges funding from the Genome Canada project entitled ‘Whole Genome Selection through Genome Wide Imputation in Beef Cattle’ and acknowledges WestGrid and Compute/Calcul Canada for providing computing resources. J.F.T. was supported by the National Institute of Food and Agriculture, US Department of Agriculture, under awards 2013-68004-20364 and 2015-67015-23183. A. Bagnato, F.P., M.D. and J.W. acknowledge EU Collaborative Project Quantomics (grant 516 agreement 222664) for providing Brown Swiss and Finnish Ayrshire sequences and genotypes. A.C.B. and R.F.V. acknowledge funding from the public–private partnership ‘Breed4Food’ (code BO-22.04-011- 001-ASG-LR) and EU FP7 IRSES SEQSEL (grant 317697). A.C.B. and R.F.V. acknowledge CRV (Arnhem, the Netherlands) for providing data on Dutch and New Zealand Holstein and Jersey bulls.Stature is affected by many polymorphisms of small effect in humans1. In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10−8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP–seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The life-cycle energy consumption of zero-energy houses

Taking the building sector’s huge impact on the environment into consideration, the European Union aims at ‘nearly zero-energy’ buildings by 2021, imposing strict requirements for the (non-renewable) operational energy consumption. The life cycle energy consumption of these nearly zero-energy buildings is an aspect of growing interest, encompassing both the life cycle embodied energy and end-of-life energy in building products, and the operational energy use throughout the building service life. Moreover, in Belgium zero-energy houses have to meet the passive house requirements in order to enjoy tax benefits. This contribution examines the life cycle energy consumption for various scenarios of zero-energy houses by means of Life Cycle Energy Analysis, thus examining whether passive house requirements are useful from the perspective of life cycle energy consumption. For the various zero-energy house scenarios, an analysis is provided of the contribution of the different components, such as building construction materials and building services, to the total life cycle energy consumption. Results reveal that a zero-energy house roughly consumes 2 to 4 times less non-renewable life cycle energy than a typical Belgian passive house, and 3 to 5 times less than a house following current standard building practice. Secondly, the results demonstrate that there is no clear distinction in favor of either passive or standard zero-energy house scenarios. In essence, the lower embodied energy in building services in the passive house scenarios counterbalances the higher building construction embodied energy and vice versa for the standard house. As a conclusion, passive house requirements are not considered an essential criterion for zero-energy houses from a life cycle energy point of view. The research however reveals that the choice of building construction materials and of building services types are the determining factors influencing life cycle energy consumption. Large energy savings up to 30 kWh/year/m² can be obtained through a proficient choice of building materials and building services for zero-energy houses. Regarding the embodied energy in building constructions, a timber frame house and massive brick house can be equally energy efficient. Looking at the embodied energy in building services, the embodied energy in wood pellets and in photovoltaic panels reveal to be of major importance

Life cycle energy use of a zero-energy house

Taking the building sector’s huge impact on the environment into consideration, the European Union aims at ‘nearly zero-energy’ houses by 2021 through strict requirements for the (non-renewable) operational energy use. Although it is not included in current calculation methods, the life cycle energy use of buildings is an aspect of growing interest, encompassing both the operational energy use throughout the building service life and the life cycle embodied energy and end-of-life energy in building materials. This contribution examines the life cycle energy use of a zero-energy case study house by means of a life cycle energy assessment and contains a parameter analysis of its different components, such as the building construction and building services. The results show that, during its entire lifecycle, a zero-energy house uses 2 to 4 times less non-renewable energy than a passive house with identical floor plan and 3 to 5 times less than a house built according to standard building practice in Belgium. Secondly, the embodied energy in a zero-energy house with a passive building envelope proves to be equal to that in a zero-energy house with a standard building envelope. Thus, passive house requirements are not considered an essential criterion for zero-energy houses from life cycle energy point of view. On the other hand, the study reveals that the choice of building construction materials and building services are determining factors for the life cycle energy use, resulting in energy savings up to 35 kWh/year/m² for zero-energy houses

Life cycle energy analysis of a zero-energy house

Most zero-energy concepts focus on a reduction of the non-renewable operational energy use in buildings rather than taking the reduction of their life cycle energy use as a starting point. Nevertheless, the life cycle embodied and end-of-life energy will become more important, especially in buildings with low operational energy. Therefore, the life cycle energy use of a Belgian zero-energy reference house is examined by means of life cycle energy assessment. The influence of design decisions and regulations on the building construction type, the building services, and the performance of the building envelope are investigated. In terms of thermal performance of the building, the results show that the life cycle embodied energy in zero-energy houses with passive or standard thermal performance was not substantially different. From a life cycle energy perspective, passive house requirements are not essential criteria for zero-energy houses in Belgium. On the other hand, large life cycle energy savings were obtained through a proficient selection of all building construction materials and services. For the life cycle embodied energy in building constructions, the best timber frame and masonry houses were equally efficient. Wood pellets and photovoltaic panels were decisive factors in the life cycle embodied energy of building services