Physical and optical aerosol properties at the Dutch North Sea coast based on AERONET observations

International audienceSun photometer measurements at the AERONET station at the North Sea coast in The Hague (The Netherlands) provide a climatology of optical and physical aerosol properties for the area. Results are presented from the period January 2002 to July 2003. For the analysis and interpretation these data are coupled to chemical aerosol data from a nearby station of the Dutch National Air Quality Network. This network provides PM10 and black carbon concentrations. Meteorological conditions and air mass trajectories are also used. Due to the location close to the coast, the results are strongly dependent on wind direction, i.e. air mass trajectory. In general the aerosol optical properties are governed by industrial aerosol emitted form various industrial, agricultural and urban areas surrounding the site in almost all directions over land. For maritime air masses industrial aerosols are transported from over the North Sea, whereas very clean air is transported from the NW in clean polar air masses from the North Atlantic. In the winter the effect of the production of sea salt aerosol at high wind speeds is visible in the optical and physical aerosol data. In these cases fine and coarse mode radii are similar to those reported in the literature for marine aerosol. Relations are derived between the Ångström coefficients with both the fine/coarse mode fraction and the ratio of black carbon and PM10

Physical and optical aerosol properties at the Dutch North Sea coast

International audienceSun photometer measurements at the AERONET station at the North Sea coast in The Hague (The Netherlands) provide a climatology of optical and physical aerosol properties for the area. Results are presented from the period January 2002 to July 2003. For the analysis and interpretation these data are coupled to chemical aerosol data from a nearby station of the Dutch National Air Quality Network. This network provides PM10 and black carbon concentrations. Meteorological conditions and air mass trajectories are also used. Due to the location close to the coast, the results are strongly dependent on wind direction, i.e.~air mass trajectory. In general the aerosol optical properties are governed by industrial aerosol emitted form various industrial, agricultural and urban areas surrounding the site in almost all directions over land. For maritime air masses industrial aerosols are transported from over the North Sea, whereas very clean air is transported from the NW in clean polar air masses from the North Atlantic. In the winter the effect of the production of sea salt aerosol at high wind speeds is visible in the optical and physical aerosol data. In these cases fine and coarse mode radii are similar to those reported in the literature for marine aerosol. Relations are derived between the Ångström coefficients with both the fine/coarse mode fraction and the ratio of black carbon and PM10

Next-generation sequencing for diagnosis of thoracic aortic aneurysms and dissections: diagnostic yield, novel mutations and genotype phenotype correlations

Additional file 1. Complementary data on primer sequences, SKI amplification and survival analyses

Analysis of necroptotic proteins in failing human hearts

BACKGROUND: Cell loss and subsequent deterioration of contractile function are hallmarks of chronic heart failure (HF). While apoptosis has been investigated as a participant in the progression of HF, it is unlikely that it accounts for the total amount of non-functional tissue. In addition, there is evidence for the presence of necrotic cardiomyocytes in HF. Therefore, the objective of this study was to investigate the necroptotic proteins regulating necroptosis, a form of programmed necrosis, and thereby assess its potential role in human end-stage HF. METHODS: Left ventricular samples of healthy controls (C) and patients with end-stage HF due to myocardial infarction (CAD) or dilated cardiomyopathy (DCM) were studied. Immunoblotting for necroptotic and apoptotic markers was performed. Triton X-114 fractionated samples were analyzed to study differences in subcellular localization. RESULTS: Elevated expression of RIP1 (receptor-interacting protein), pSer227-RIP3 and its total levels were observed in HF groups compared to controls. On the other hand, caspase-8 expression, a proapoptotic protease negatively regulating necroptosis, was downregulated suggesting activation of necroptosis signaling. Total mixed-lineage kinase domain-like protein (MLKL) expression did not differ among the groups; however, active cytotoxic forms of MLKL were present in all HF samples while they were expressed at almost undetectable levels in controls. Interestingly, pThr357-MLKL unlike pSer358-MLKL, was higher in DCM than CAD. In HF, the subcellular localization of both RIP3 and pThr357-MLKL was consistent with activation of necroptosis signaling. Expression of main apoptotic markers has not indicated importance of apoptosis. CONCLUSIONS: This is the first evidence showing that human HF of CAD or DCM etiology is positive for markers of necroptosis which may be involved in the development of HF

Posttranslational modifications of calcium/calmodulin-dependent protein kinase IIdelta and its downstream signaling in human failing hearts

BACKGROUND: In human failing hearts (HF) of different origin (coronary artery disease-CAD, dilated-DCM, restrictive and hypertrophic cardiomyopathy-OTHER), we investigated the active forms of Ca2+/calmodulin-dependent protein kinase IIdelta (p-Thr287-CaMKIIdelta, oxMet281/282-CaMKIIdelta) and their role in phenotypes of the disease. METHODS AND RESULTS: Although basic diagnostic and clinical markers indicating the attenuated cardiac contractility and remodeling were comparable in HF groups, CaMKIIdelta-mediated axis was different. P-Thr287-CaMKIIdelta was unaltered in CAD group, whereas it was upregulated in non-ischemic cardiomyopathic groups. No correlation between the upregulated p-Thr287-CaMKIIdelta and QT interval prolongation was detected. Unlike in DCM, oxMet281/282-CaMKIIdelta did not differ among HF groups. Independently of CaMKIIdelta phosphorylation/oxidation, activation of its downstreams-phospholamban and cardiac myosin binding protein-C was significantly downregulated supporting both diminished cardiac lusitropy and inotropy in all hearts. Content of sarcoplasmic reticulum Ca2+-ATPase 2a in all HF was unchanged. Protein phosphatase1beta was upregulated in CAD and DCM only, while 2A did not differ among groups. CONCLUSION: This is the first demonstration that the posttranslational activation of CaMKIIdelta differs in HF depending on etiology. Lower levels of downstream molecular targets of CaMKIIdelta do not correlate with either activation of CaMKIIdelta or the expression of major protein phosphatases in the HF. Thus, it is unlikely that these mechanisms exclusively underlie failing of the heart

Regulation of proteasome assembly and activity in health and disease

The proteasome degrades most cellular proteins in a controlled and tightly regulated manner and thereby controls many processes, including cell cycle, transcription, signalling, trafficking and protein quality control. Proteasomal degradation is vital in all cells and organisms, and dysfunction or failure of proteasomal degradation is associated with diverse human diseases, including cancer and neurodegeneration. Target selection is an important and well-established way to control protein degradation. In addition, mounting evidence indicates that cells adjust proteasome-mediated degradation to their needs by regulating proteasome abundance through the coordinated expression of proteasome subunits and assembly chaperones. Central to the regulation of proteasome assembly is TOR complex 1 (TORC1), which is the master regulator of cell growth and stress. This Review discusses how proteasome assembly and the regulation of proteasomal degradation are integrated with cellular physiology, including the interplay between the proteasome and autophagy pathways. Understanding these mechanisms has potential implications for disease therapy, as the misregulation of proteasome function contributes to human diseases such as cancer and neurodegeneration.</p

Alternative Splicing of NOX4 in the Failing Human Heart

Increased oxidative stress is a major contributor to the development and progression of heart failure, however, our knowledge on the role of the distinct NADPH oxidase (NOX) isoenzymes, especially on NOX4 is controversial. Therefore, we aimed to characterize NOX4 expression in human samples from healthy and failing hearts. Explanted human heart samples (left and right ventricular, and septal regions) were obtained from patients suffering from heart failure of ischemic or dilated origin. Control samples were obtained from donor hearts that were not used for transplantation. Deep RNA sequencing of the cardiac transcriptome indicated extensive alternative splicing of the NOX4 gene in heart failure as compared to samples from healthy donor hearts. Long distance PCR analysis with a universal 5'-3' end primer pair, allowing amplification of different splice variants, confirmed the presence of the splice variants. To assess translation of the alternatively spliced transcripts we determined protein expression of NOX4 by using a specific antibody recognizing a conserved region in all variants. Western blot analysis showed up-regulation of the full-length NOX4 in ischemic cardiomyopathy samples and confirmed presence of shorter isoforms both in control and failing samples with disease-associated expression pattern. We describe here for the first time that NOX4 undergoes extensive alternative splicing in human hearts which gives rise to the expression of different enzyme isoforms. The full length NOX4 is significantly upregulated in ischemic cardiomyopathy suggesting a role for NOX4 in ROS production during heart failure

Novel Interactions between Actin and the Proteasome Revealed by Complex Haploinsufficiency

Saccharomyces cerevisiae has been a powerful model for uncovering the landscape of binary gene interactions through whole-genome screening. Complex heterozygous interactions are potentially important to human genetic disease as loss-of-function alleles are common in human genomes. We have been using complex haploinsufficiency (CHI) screening with the actin gene to identify genes related to actin function and as a model to determine the prevalence of CHI interactions in eukaryotic genomes. Previous CHI screening between actin and null alleles for non-essential genes uncovered ∼240 deleterious CHI interactions. In this report, we have extended CHI screening to null alleles for essential genes by mating a query strain to sporulations of heterozygous knock-out strains. Using an act1Δ query, knock-outs of 60 essential genes were found to be CHI with actin. Enriched in this collection were functional categories found in the previous screen against non-essential genes, including genes involved in cytoskeleton function and chaperone complexes that fold actin and tubulin. Novel to this screen was the identification of genes for components of the TFIID transcription complex and for the proteasome. We investigated a potential role for the proteasome in regulating the actin cytoskeleton and found that the proteasome physically associates with actin filaments in vitro and that some conditional mutations in proteasome genes have gross defects in actin organization. Whole-genome screening with actin as a query has confirmed that CHI interactions are important phenotypic drivers. Furthermore, CHI screening is another genetic tool to uncover novel functional connections. Here we report a previously unappreciated role for the proteasome in affecting actin organization and function