Ste20-Related Proline/Alanine-Rich Kinase (SPAK) Regulated Transcriptionally by Hyperosmolarity Is Involved in Intestinal Barrier Function

The Ste20-related protein proline/alanine-rich kinase (SPAK) plays important roles in cellular functions such as cell differentiation and regulation of chloride transport, but its roles in pathogenesis of intestinal inflammation remain largely unknown. Here we report significantly increased SPAK expression levels in hyperosmotic environments, such as mucosal biopsy samples from patients with Crohn's disease, as well as colon tissues of C57BL/6 mice and Caco2-BBE cells treated with hyperosmotic medium. NF-κB and Sp1-binding sites in the SPAK TATA-less promoter are essential for SPAK mRNA transcription. Hyperosmolarity increases the ability of NF-κB and Sp1 to bind to their binding sites. Knock-down of either NF-κB or Sp1 by siRNA reduces the hyperosmolarity-induced SPAK expression levels. Furthermore, expression of NF-κB, but not Sp1, was upregulated by hyperosmolarity in vivo and in vitro. Nuclear run-on assays showed that hyperosmolarity increases SPAK expression levels at the transcriptional level, without affecting SPAK mRNA stability. Knockdown of SPAK expression by siRNA or overexpression of SPAK in cells and transgenic mice shows that SPAK is involved in intestinal permeability in vitro and in vivo. Together, our data suggest that SPAK, the transcription of which is regulated by hyperosmolarity, plays an important role in epithelial barrier function

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Nonlinearity and Topology

The interplay of nonlinearity and topology results in many novel and emergent properties across a number of physical systems such as chiral magnets, nematic liquid crystals, Bose-Einstein condensates, photonics, high energy physics, etc. It also results in a wide variety of topological defects such as solitons, vortices, skyrmions, merons, hopfions, monopoles to name just a few. Interaction among and collision of these nontrivial defects itself is a topic of great interest. Curvature and underlying geometry also affect the shape, interaction and behavior of these defects. Such properties can be studied using techniques such as, e.g. the Bogomolnyi decomposition. Some applications of this interplay, e.g. in nonreciprocal photonics as well as topological materials such as Dirac and Weyl semimetals, are also elucidated

Thrombosis in vasculitis: from pathogenesis to treatment

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients

Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

Landslide risk assessment and management by decision analytical procedure for Derekoy, Konya, Turkey

The Derekoy landslide threatening the town of Derekoy, Konya, Turkey is investigated in order to assess and manage the associated risk. Derekoy town, located 12 km west of Konya city center, which is the second largest city in central Anatolia, has been extending due to the demand for new settlement places in Konya for the last decade. As most of the town is situated on the slopes of Meram river valley, on which the slope movements are observed, the risk of landslide has been increasing due to these new settlements. In this study, the landslide risk in Derekoy is assessed by following the so-called decision analytical procedure. The risk is defined by multiplication of hazard and consequences of the hazard. The hazard, which is the probability of slope failure, is computed by using the first-order second-moment (FOSM) method. The possible consequences of a landslide in Derekoy are analyzed and their costs are assessed relative to each other. A decision tree for choosing among the possible alternatives for reducing the risk is constructed in order to manage the risk

An accuracy assessment methodology for the remotely sensed discontinuities: a case study in Andesite Quarry area, Turkey

The discontinuities play an important role in both the design and development stages of many geotechnical engineering projects. Therefore, semi-automatic detection of discontinuities based on remote sensing will save a considerable amount of time and cost. Accuracy of the semi-automatically detected discontinuities is also as important as the detection process, since the results directly reflect the uncertainty in the geotechnical problem. The current paper presents an accuracy assessment methodology for semi-automatically detected discontinuities from remotely sensed images. Semi-automatic lineament analysis is performed by using high-resolution satellite imagery for identification of rock discontinuities at the Andesite quarry area in Golbas1 Ankara, Turkey. A highresolution data IKONOS Precision Plus with 1m resolution orthorectified image has been used in the present study. The accuracy assessment methodology is developed based on a comparison of manually extracted lineaments using directional filtering and semi-automatically detected lineaments with LINE module of PCI Geomatica 8.2 and manual intervention. The proposed accuracy assessment methodology considers the accuracy based on location and length of the lineaments. In this respect, it has two dimensions. For the algorithm of the developed methodology, a software called LINECOMP, is coded in Java environment. The LINECOMP is composed of three modules. These are: LINE ADDRESS for identification of pixel addresses of lineaments; which is used for locational accuracy assessment; LINE COMPARE for comparing two lineament maps with respect to lineament pixels, which is used for length-based accuracy; and LINE CLASSIFICATION for classifying the assessed accuracy with respect to the amount of location and length matching. The performance of the proposed accuracy assessment method is also verified by the field studies carried out in the study area

AC losses and determination of some superconducting parameters of Ag2O added Bi2223 superconductors

WOS: 000237060100008The effects of Ag2O addition on electromagnetic properties in a Bi2223 superconductor have been investigated by means of AC susceptibility measurements and theoretical analysis. Intergranular critical current density was found to be decreased with increased amount of Ag2O addition (0, 15, 30 wt.%). The effective volume fractions of the grains were estimated as a function of Ag2O amount. The field and temperature dependence of the intergranular critical current density for each sample has been accounted by the function J(cm) (T) = (J(0)/B-n) (1 - T/T-cm)(P), where alpha(0) denotes the pinning strength parameter at T = 0. The field exponent n, temperature exponent p, and maximum intergranular loss peaks, which are determined from the comparison of the experimental and calculated curves, increased with increasing amount of Ag2O addition. Experimental isothermal hysteresis losses as a function of field amplitude are also seen to adequately be reproduced by model calculation using the same fitting parameters as for AC susceptibility chi(n)(T) data. (c) 2006 Elsevier B.V. All rights reserved