Celiac disease patient IgA antibodies induce endothelial adhesion and cell polarization defects via extracellular transglutaminase 2

We have recently found that celiac disease patient serum-derived autoantibodies targeted against transglutaminase 2 interfere with several steps of angiogenesis, including endothelial sprouting and migration, though the mechanism involved remained to be fully characterized. This study now investigated the processes underlying the antiangiogenic effects exerted by celiac disease patient antibodies on endothelial cells, with particular regard to the adhesion, migration, and polarization signaling pathway. We observed that celiac IgA reduced endothelial cell numbers by affecting adhesion without increasing apoptosis. Endothelial cells in the presence of celiac IgA showed weak attachment, a high susceptibility to detach from fibronectin, and a disorganized extracellular matrix due to a reduction of protein cross-links. Furthermore, celiac patient IgA led to secretion of active transglutaminase 2 from endothelial cells into the culture supernatants. Additionally, cell surface transglutaminase 2 mediated integrin clustering in the presence of celiac IgA was coupled to augmented expression of ß1-integrin. We also observed that celiac patient IgA-treated endothelial cells had migratory defects and a less polarized phenotype when compared to control groups, and this was associated with the RhoA signaling pathway. These biological effects mediated by celiac IgA on endothelial cells were partially influenced but not completely abolished by R281, an irreversible extracellular transglutaminase 2 enzymatic activity inhibitor. Taken together, our results imply that celiac patient IgA antibodies disturb the extracellular protein cross-linking function of transglutaminase 2, thus altering cell-extracellular matrix interactions and thereby affecting endothelial cell adhesion, polarization, and motility. © 2013 Springer Basel.

Thioredoxin is involved in endothelial cell extracellular transglutaminase 2 activation mediated by celiac disease patient IgA

Purpose: To investigate the role of thioredoxin (TRX), a novel regulator of extracellular transglutaminase 2 (TG2), in celiac patients IgA (CD IgA) mediated TG2 enzymatic activation. Methods: TG2 enzymatic activity was evaluated in endothelial cells (HUVECs) under different experimental conditions by ELISA and Western blotting. Extracellular TG2 expression was studied by ELISA and immunofluorescence. TRX was analysed by Western blotting and ELISA. Serum immunoglobulins class A from healthy subjects (H IgA) were used as controls. Extracellular TG2 enzymatic activity was inhibited by R281. PX12, a TRX inhibitor, was also employed in the present study. Results: We have found that in HUVECs CD IgA is able to induce the activation of extracellular TG2 in a dose-dependent manner. Particularly, we noted that the extracellular modulation of TG2 activity mediated by CD IgA occurred only under reducing conditions, also needed to maintain antibody binding. Furthermore, CD IgA-treated HUVECs were characterized by a slightly augmented TG2 surface expression which was independent from extracellular TG2 activation. We also observed that HUVECs cultured in the presence of CD IgA evinced decreased TRX surface expression, coupled with increased secretion of the protein into the culture medium. Intriguingly, inhibition of TRX after CD IgA treatment was able to overcome most of the CD IgA-mediated effects including the TG2 extracellular transamidase activity. Conclusions: Altogether our findings suggest that in endothelial cells CD IgA mediate the constitutive activation of extracellular TG2 by a mechanism involving the redox sensor protein TRX. © 2013 Nadalutti et al.

Are transglutaminase 2 inhibitors able to reduce gliadin-induced toxicity related to celiac disease? A proof-of-concept study

Purpose Celiac disease is an autoimmune-mediated enteropathy characterized by adaptive and innate immune responses to dietary gluten in wheat, rye and barley in genetically susceptible individuals. Gluten-derived gliadin peptides are deamidated by transglutaminase 2 (TG2), leading to an immune response in the small-intestinal mucosa. TG2 inhibitors have therefore been suggested as putative drugs for celiac disease. In this proof-of-concept study we investigated whether two TG2 inhibitors, cell-impermeable R281 and cell-permeable R283, can prevent the toxic effects of gliadin in vitro and ex vivo. Methods Intestinal epithelial Caco-2 cells were treated with peptic-tryptic-digested gliadin (PT-gliadin) with or without TG2 inhibitors and thereafter direct toxic effects (transepithelial resistance, cytoskeletal rearrangement, junction protein expression and phoshorylation of extracellular-signal-regulated kinase 1/2) were determined. In an organ culture of celiacpatient- derived small-intestinal biopsies we measured secretion of TG2-autoantibodies into the culture medium and the densities of CD25- and interleukin (IL) 15-positive cells, forkhead box P3 (FOXP3)-positive regulatory Tcells (Tregs) and Ki-67- positive proliferating crypt cells. Results Both TG2 inhibitors evinced protective effects against gliadin-induced detrimental effects in Caco-2 cells but the cellimpermeableR281seemedslightlymorepotent. Inaddition,TG2 inhibitor R281 modified the gluten-induced increase in CD25- and IL15-positive cells,Tregs and crypt cell proliferation, but had no effect on antibody secretion in celiac-patient-derived biopsies. Conclusions Our results suggest that TG2 inhibitors are able to reduce certain gliadin-induced effects related to responses in vitro and ex vivo. © Springer Science+Business Media, LLC 2012.

Application of calorimetric method for loss measurement of a SynRM drive system

Synchronous reluctance motors (SynRMs) are gaining in popularity in industrial drives due to their permanent magnet-free, competitive performance, and robust features. This paper studies the power losses in a 90-kW converter-fed SynRM drive by a calorimetric method in comparison of the traditional input-output method. After the converter and the motor were measured simultaneously in separate chambers, the converter was installed inside the large-size chamber next to the motor and the total drive system losses were obtained using one chamber. The uncertainty of both measurement methods is analyzed and discussed.

The Europeanisation of foreign aid policy. Slovenia and Latvia 1998–2010

Book review: The Europeanisation of Foreign Aid Policy. Slovenia and Latvia 1998–2010 PETERIS TIMOFEJEVS HENRIKSSON Umeå, Umeå University Department of Political Science, 2013. (Statsvetenskapliga institutionens skriftserie/Research Report 2013:5) ISBN 978-91-7459-716-5.

Enhanced Volatile Organic Compounds emissions and organic aerosol mass increase the oligomer content of atmospheric aerosols

Secondary organic aerosol (SOA) accounts for a dominant fraction of the submicron atmospheric particle mass, but knowledge of the formation, composition and climate effects of SOA is incomplete and limits our understanding of overall aerosol effects in the atmosphere. Organic oligomers were discovered as dominant components in SOA over a decade ago in laboratory experiments and have since been proposed to play a dominant role in many aerosol processes. However, it remains unclear whether oligomers are relevant under ambient atmospheric conditions because they are often not clearly observed in field samples. Here we resolve this long-standing discrepancy by showing that elevated SOA mass is one of the key drivers of oligomer formation in the ambient atmosphere and laboratory experiments. We show for the first time that a specific organic compound class in aerosols, oligomers, is strongly correlated with cloud condensation nuclei (CCN) activities of SOA particles. These findings might have important implications for future climate scenarios where increased temperatures cause higher biogenic volatile organic compound (VOC) emissions, which in turn lead to higher SOA mass formation and significant changes in SOA composition. Such processes would need to be considered in climate models for a realistic representation of future aerosol-climate-biosphere feedbacks.

EUSAAR size distribution analysis database

Two years of harmonized aerosol number size distribution data from 24 European field monitoring sites have been analysed. The results give a comprehensive overview of the European near surface aerosol particle number concentrations and number size distributions between 30 and 500 nm of dry particle diameter. Spatial and temporal distribution of aerosols in the particle sizes most important for climate applications are presented. We also analyse the annual, weekly and diurnal cycles of the aerosol number concentrations, provide log-normal fitting parameters for median number size distributions, and give guidance notes for data users. Emphasis is placed on the usability of results within the aerosol modelling community. We also show that the aerosol number concentrations of Aitken and accumulation mode particles (with 100 nm dry diameter as a cut-off between modes) are related, although there is significant variation in the ratios of the modal number concentrations. Different aerosol and station types are distinguished from this data and this methodology has potential for further categorization of stations aerosol number size distribution types. The European submicron aerosol was divided into characteristic types: Central European aerosol, characterized by single mode median size distributions, unimodal number concentration histograms and low variability in CCN-sized aerosol number concentrations; Nordic aerosol with low number concentrations, although showing pronounced seasonal variation of especially Aitken mode particles; Mountain sites (altitude over 1000 m a.s.l.) with a strong seasonal cycle in aerosol number concentrations, high variability, and very low median number concentrations. Southern and Western European regions had fewer stations, which decreases the regional coverage of these results. Aerosol number concentrations over the Britain and Ireland had very high variance and there are indications of mixed air masses from several source regions; the Mediterranean aerosol exhibit high seasonality, and a strong accumulation mode in the summer. The greatest concentrations were observed at the Ispra station in Northern Italy with high accumulation mode number concentrations in the winter. The aerosol number concentrations at the Arctic station Zeppelin in Ny-Ålesund in Svalbard have also a strong seasonal cycle, with greater concentrations of accumulation mode particles in winter, and dominating summer Aitken mode indicating more recently formed particles. Observed particles did not show any statistically significant regional work-week or weekday related variation in number concentrations studied. Analysis products are made for open-access to the research community, available in a freely accessible internet site. The results give to the modelling community a reliable, easy-to-use and freely available comparison dataset of aerosol size distributions.

Valtatien 13 parantaminen välillä Lappeenranta–Nuijamaa : Hanke-esite

Valtatien 13 osuus Lappeenrannasta Nuijamaalle kuuluu Euroopan komission päättämään Suomen kattavaan liikenneverkkoon TEN-T. Tieosuus on maan toiseksi tärkein kansainvälisen liikenteen yhteys kuljetuksille ja henkilöliikenteelle. Valtatie 13 kulkee maan poikki länsirannikolta Kokkolasta Lappeenrantaan ja siitä edelleen Nuijamaan rajanylityspaikan kautta Venäjän puolelle Viipuriin. Valtatie 13 palvelee osaltaan myös paikallista liikkumista Nuijamaan kylätaajaman ja Lappeenrannan välillä. Erityisesti Mustolan alueelle ja myös osittain Nuijamaan raja-aseman läheisyyteen suunnitellut ja jo osittain toteutuneet maankäytön kaupalliset palvelut lisäävät voimakkaasti kasvaessaan myös seudullista liikennettä suunnitteluosuudella. Nuijamaan raja-asema on ollut Suomen itärajan toiseksi vilkkain tieliikenteen rajanylityspaikka. Rajanylityspaikan kautta kulki vuonna 2015 noin miljoona ajoneuvoa ja 2,4 miljoonaa matkustajaa. Venäjän ja Suomen valtioiden välisen liikenteen kasvu on ollut voimakkainta Kaakkois-Suomessa ja sille on edelleen perusteltuja kasvuodotuksia, vaikka viime aikoina liikenne on merkittävästi vähentynyt. Myös tavaraliikenteellä on potentiaalia lisääntyä viimeaikaisesta. Suunnittelualueeseen kuuluu valtatien 13 (16,6 km) lisäksi valtatien 6 länsipuolinen valtatien 13 jatke Karjalantie (mt 3821) (1,2 km). Yleissuunnitelmassa on selvitetty valtatien 13 puutteet ja ongelmat, palvelutasotavoitteet, valtatien 13 ja muiden väylien periaateratkaisut tilantarpeineen, suhde ympäröivään maankäyttöön, vaikutukset sekä mahdollisuudet vaiheittain toteuttamiseksi. Päätavoitteena on ollut selvittää valtatien 13 ja muiden väylien kehittämisen periaatteet niin, että palvelutasopuutteet saadaan poistettua ja valtatie 13 vastaa sille asetettuja vaatimuksia liikenteen sujuvuuden ja turvallisuuden kannalta. Osana suunnitelmaa on esitetty toimenpiteet meluhaittojen torjumiseksi ja ympäristövaikutusten lieventämiseksi. Valtatie 13 parannetaan nykyisellä paikallaan korkealuokkaiseksi nelikaistaiseksi valtatieksi tarvittavine tie-, katu- ja liittymäjärjestelyineen. Vastakkaiset ajosuunnat on erotettu toisistaan rakenteellisesti ja kaikki valtatien liittymät ovat eritasoliittymiä.

The Virtual International Stroke Trials Archive

Background and Purpose - Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. Methods - Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. Results - ”Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on 15 000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 6912 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. Conclusions - This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning. (Stroke. 2007;38:1905-1910.)

Telmisartan to prevent recurrent stroke and cardiovascular events

Background Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin–angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin–angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. Methods In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. Results The median interval from stroke to randomization was 15 days. During a mean followup of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P = 0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P = 0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P = 0.10). Conclusions Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Background Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens — aspirin plus extendedrelease dipyridamole (ASA–ERDP) versus clopidogrel. Methods In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. Results A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). Conclusions The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

Gräs från våtmark som additiv i bränslepellets : Effekter på pelletskvalitet och energiförbrukning

Because of global warming the energy production development has progressed towards more renewable energy sources. Biomass has great potential in this matter and pellet is already a big market that has increased seven times the past decade. A periodically strained woodchip resource market and statements of short supply in the future has got actors exploring opportunities with other commodities. Grasses such as Canary grass has shown great potential in this matter and in this study a wetland grass is tested as an additive, 0,5, 1,0, 1,5, and 1,9%, with spruce woodchips. The test production series was performed at a production unit located at the department of environmental and energy system at Karlstad University, Karlstad. Quality was controlled accordingly to the European standard and parameters such as energy consumption, moisture content, mechanical durability and bulk density was tested. For comparison, a sample with only spruce wood chips was produced, and a sample containing 1% of a commonly used additive, potato starch. The results showed that a decrease in energy consumption with 14% when 2% wetland grass was added, part of the decline may be due to the increased production flow compared with the reference sample. The positive effects on decrease in energy consumption, that 1% potato starch results in, is equal to reults from 1% wetlandgrass. This indicates lubricating properties in wetlandgrass. This is attributed to that herbaceous plants have a high content of extracts such as waxes and that they cause less friction in the press. Tests also showed that pellet with wetland grass did not qualify the European standard in terms of mechanical durability. Extracts can form a weak boundary layer in the pellet and cause this. A possible trend shows a better mechanical durability with more grass in pellets. The presence of different size of particles can be a reason. Moisture content qualifies according to the European standard but is below optimum 8%. This despite to relatively high moisture content in the mixer. Higher moisture content in the press would certainly result in a generally higher quality. Suggestions for future studies are to produce pellets with greater distribution on the wetland grass added, to easier interpret a connection. Also examine the extracts behavior with different moisture content. For a sustainable development accordingly renewable energy it is important to ensure the future commodity market for pellets. Further studies should be performed to help the development of alternative raw materials in conjunction with pellet production.

Patientutbildningens betydelse för livskvalitèn hos patienter med hjärtsvikt : En litteratur studie

Introduktion: Runt 250 000 personer i Sverige är drabbade av hjärtsvikt. Det finns olika grader av hjärtsvikt som påverkar patienters dagliga liv på olika nivåer vilket kan påverka patienters livskvalité. Livskvalité är ett brett begrepp som är multidimensionellt. Patientutbildning är en del av sjuksköterskans profession och syftar till att hjälpa patienter förbättra sin egen hälsa. Syfte: Syftet med litteraturstudien var att belysa patientutbildningens betydelse för livskvalitén hos patienter med hjärtsvikt. Metod: Under litteraturstudien har Polit och Beck (2016) niostegsmodell använts. Till litteratursökningen användes databaserna Cinahl och PubMed. Databassökningen resulterade i 10 artiklar samt två artiklar som söktes manuellt. Artiklarna granskades kritiskt och utgjorde därefter materialet för litteraturstudiens resultat. Resultat: Det slutgiltiga resultatet delades in i två huvudteman vilka var En förändrad tillvaro och Kunskap och trygghet med totalt fem underteman. Slutsats: Litteraturstudien påvisar att patientutbildning kan påverka patienter med hjärtsvikt då livskvalitén generellt har förbättrats för de patienter som erhållit patientutbildning. Litteraturstudien visar att patientutbildning kan ge en förändrad fysisk funktion, socialt och emotionellt stöd, förmåga att utföra egenvård samt ge kunskap, förståelse och kontroll över tillståndet.

NGL-projekt vid Högskolan Dalarna : 1. Anneli Fjordevik intervjuas av Charlotte Lindgren

NGL-projekt vid Högskolan Dalarna inom språkavdelningen som handlar om informella internetbaserade lärmiljöer.

NGL-projekt vid Högskolan Dalarna : 2. Olga Mattsson intervjuas av Charlotte Lindgren

NGL-projekt vid Högskolan Dalarna inom språkavdelningen som handlar om webbaserade digitala prov.