Minor Role of Plasminogen in Complement Activation on Cell Surfaces

Atypical hemolytic uremic syndrome (aHUS) is a rare, but severe thrombotic microangiopathy. In roughly two thirds of the patients, mutations in complement genes lead to uncontrolled activation of the complement system against self cells. Recently, aHUS patients were described with deficiency of the fibrinolytic protein plasminogen. This zymogen and its protease form plasmin have both been shown to interact with complement proteins in the fluid phase. In this work we studied the potential of plasminogen to restrict complement propagation. In hemolytic assays, plasminogen inhibited complement activation, but only when it had been exogenously activated to plasmin and when it was used at disproportionately high concentrations compared to serum. Addition of only the zymogen plasminogen into serum did not hinder complement-mediated lysis of erythrocytes. Plasminogen could not restrict deposition of complement activation products on endothelial cells either, as was shown with flow cytometry. With platelets, a very weak inhibitory effect on deposition of C3 fragments was observed, but it was considered too weak to be significant for disease pathogenesis. Thus it was concluded that plasminogen is not an important regulator of complement on self cells. Instead, addition of plasminogen was shown to clearly hinder platelet aggregation in serum. This was attributed to plasmin causing disintegration of formed platelet aggregates. We propose that reduced proteolytic activity of plasmin on structures of growing thrombi, rather than on complement activation fragments, explains the association of plasminogen deficiency with aHUS. This adds to the emerging view that factors unrelated to the complement system can also be central to aHUS pathogenesis and suggests that future research on the mechanism of the disease should expand beyond complement dysregulation.Peer reviewe

Green areas around homes reduce atopic sensitization in children

Peer reviewe

Effects on mitochondrial transcription of manipulating mTERF protein levels in cultured human HEK293 cells

Peer reviewe

Defect detection in textile fabric images using subband domain subspace analysis

In this work, a new model that combines the concepts of wavelet transformation and subspace analysis tools, like Independent Component Analysis, Topographic Independent Component Analysis, and Independent Subspace Analysis, is developed for the purpose of defect detection in textile images. In previous works, it has been shown that reduction of the textural components of the textile image by preprocessing has increased the performance of the system. Based on this observation, in present work, the aforementioned subspace analysis tools are aimed to be applied on the sub-band images. The feature vector of a sub-window of a test image is compared with that of the defect-free image in order to make a decision. This decision is based on a Euclidean distance classifier. The performance increase that results using wavelet transformation prior to subspace analysis has been discussed in detail. While all the subspace analysis methods has been found to lead to the same detection performances, as a further step, independent subspace analysis is used to classify the detected defects according to their directionalities

Winter Time Concentrations and Size Distribution of Bioaerosols in Different Residential Settings in the UK

The total concentration and size distribution of bioaerosols in three different types of housing (single room in shared accommodation [type I], single bedroom flat in three-storey building [type II] and two- or threebedroom detached houses [type III]) was assessed during the winter. This research was an extension of a previous study carried out in the summer. The measurement campaign was undertaken in winter 2008 and 30 houses were sampled. Samples were taken from kitchens, living rooms, corridors (only in housing type I) and outdoors with an Anderson 6 stage viable impactor. In housing type I, the total geometric mean concentration was highest in the corridor for both bacteria and fungi (3,171 and 1,281 CFU/m3, respectively). In type II residences, both culturable bacteria and fungi were greatest in the living rooms (3,487 and 833 CFU/m3, respectively). The living rooms in type III residences had largest number of culturable bacteria (1,361 CFU/m3) while fungi were highest in kitchens (280 CFU/m3). The concentrations of culturable bacteria and fungi were greater in mouldy houses than non-mouldy houses. A considerable variation was seen in the size distribution of culturable bacteria in type I residences compared to types II and III. For all housing types more than half of culturable bacterial and fungal aerosol were respirable (<4.7 μm) and so have the potential to penetrate into lower respiratory system. Considerable variation in concentration and size distribution within different housing types in the same geographical region highlights the impact of differences in design, construction, use and management of residential built environment on bioaerosols levels and consequent varied risk of population exposure to airborne biological agents. © Springer Science+Business Media B.V. 2012

Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis

Background. Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. Aim:To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. Patients: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. Methods: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. Results: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (< 2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. Conclusion: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance. Copyright (c) 2006 S. Karger AG, Basel

Astrophysical components separation of COBE-DMR 4yr data with FastICA

We present an application of the fast Independent Component Analysis method to the COBE-DMR 4yr data. Although the signal-to-noise ratio in the COBE-DMR data is typically $\sim 1$, the approach is able to extract the CMB signal with high confidence when working at high galactic latitudes. The reconstructed CMB map shows the expected frequency scaling of the CMB. We fit the resulting CMB component for the rms quadrupole normalisation Qrms and primordial spectral index n and find results in excellent agreement with those derived from the minimum-noise combination of the 90 and 53 GHz DMR channels without galactic emission correction. Including additional channels (priors) such as the Haslam map of radio emission at 408 MHz and the DIRBE 140um map of galactic infra-red emission, the FastICA algorithm is able to both detect galactic foreground emission and separate it from the dominant CMB signal. Fitting the resulting CMB component for Qrms and n we find good agreement with the results from Gorski et al.(1996) in which the galactic emission has been taken into account by subtracting that part of the DMR signal observed to be correlated with these galactic template maps. We further investigate the ability of FastICA to evaluate the extent of foreground contamination in the COBE-DMR data. We include an all-sky Halpha survey (Dickinson, Davies & Davis 2003) to determine a reliable free-free template. In particular we find that, after subtraction of the thermal dust emission predicted by the Finkbeiner, Davis & Schlegel (1999) model 7, this component is the dominant foreground emission at 31.5 GHz. This indicates the presence of an anomalous dust correlated component which is well fitted by a power law spectral shape $\nu^{-\beta}$ with $\beta \sim 2.5$ in agreement with Banday et al. (2003).Comment: Submitted to MNRA

Analysis of Linear Antibody Epitopes on Factor H and CFHR1 Using Sera of Patients with Autoimmune Atypical Hemolytic Uremic Syndrome

Introduction: In autoimmune atypical hemolytic uremic syndrome (aHUS), the complement regulator factor H (FH) is blocked by FH autoantibodies, while 90% of the patients carry a homozygous deletion of its homolog complement FH-related protein 1 (CFHR1). The functional consequence of FH-blockade is widely established; however, the molecular basis of autoantibody binding and the role of CFHR1 deficiency in disease pathogenesis are still unknown. We performed epitope mapping of FH to provide structural insight in the autoantibody recruitment on FH and potentially CFHR1. Methods: Eight anti-FH positive aHUS patients were enrolled in this study. With overlapping synthetic FH and CFHR1 peptides, we located the amino acids (aa) involved in binding of acute and convalescence stage autoantibodies. We confirmed the location of the mapped epitopes using recombinant FH domains 19-20 that carried single-aa substitutions at the suspected antibody binding sites in three of our patients. Location of the linear epitopes and the introduced point mutations was visualized using crystal structures of the corresponding domains of FH and CFHR1. Results: We identified three linear epitopes on FH (aa1157-1171; aa1177-1191; and aa1207-1226) and one on CFHR1 (aa276-290) that are recognized both in the acute and convalescence stages of aHUS. We observed a similar extent of autoantibody binding to the aHUS-specific epitope aa1177-1191 on FH and aa276-290 on CFHR1, despite seven of our patients being deficient for CFHR1. Epitope mapping with the domain constructs validated the location of the linear epitopes on FH with a distinct autoantibody binding motif within aa1183-1198 in line with published observations. Summary: According to the results, the linear epitopes we identified are located close to each other on the crystal structure of FH domains 19-20. This tertiary configuration contains the amino acids reported to be involved in C3b and sialic acid binding on the regulator, which may explain the functional deficiency of FH in the presence of auto antibodies. The data we provide identify the exact structures involved in autoantibody recruitment on FH and confirm the presence of an autoantibody binding epitope on CFHR1.Peer reviewe