Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Helminth fauna of Mus musculus Linnaeus, 1758 from the suburban area of Belgrade, Serbia

The helminth fauna of the house mouse (Mus musculus Linnaeus, 1758) was studied on the basis of 429 host individuals from the suburban area of Belgrade. Eleven helminth species were recorded: three cestode species - Catenotaenia pusilla, Rodentolepis fraterna, and Cysticercus (= Strobilocercus) fasciolaris [larval stage of Taenia taeniaeformis (Batsch, 1821)]; and eight nematode species - Heligmosomoides polygyrus, Syphacia sp., Aspiculuris tetraptera, Syphacia obvelata, Heterakis spumosa, Trichuris muris, Mastophorus muris, and Gongylonema sp. Within the general helminth fauna, H. polygyrus was found to be the most prevalent species (39.2%) and caused the highest infection intensity. Prevalences of A. tetraptera, C. pusilla, and S. obvelata ranged from 12.8% to 6.1%, while the remaining species showed prevalences ranging from 4.9% (for Syphacia sp.) to 0.2% (for Gongylonema sp.). All the species found in males were also present in females, with the exceptions of M. muris and Gongylonema sp. No significant differences were found between males and females regarding prevalence (P%), mean infection intensity (MI), or mean abundance (MA).Helmintofauna kućnog miša (Mus musculus) istraživana je kod 429 jedinki izlovljenih sa suburbanog područja Beograda (selo Jabuka, 15 km severoistočno od Beograda), a prisustvo 3 vrste pantljičara (Cestoda) i 8 vrsta valjkastih crva (Nematoda) utvrđeno je u 262 jedinke (61.1%). Od pantljičara su bile prisutne Catenotaena pusilla, Rodentolepis fraterna i larveni stadijum Taenia taeniaeformis - Cysticercus (= Strobilocercus) fasciolaris, a od valjkastih crva Helygmosomoides polygirus, Syphacia sp., S. obvelata, Aspiculuris tetraptera, Heterakis spumosa, Trichuris muris, Mastophorus muris i Gongylonema sp. Dominantna vrsta bila je H. polygyrus sa prevalencom od 39,2% i prouzrokovala je najviši intenzitet infekcije. Za A. tetraptera, C. pusilla i S. obvelata prevalence su iznosile od 12,8 do 6,1%, a za ostale vrste helminata od 4,9 (za Syphacia sp.) do 0,2% (za Gongylonema sp.). Sve vrste nađene u mužjacima kućnog miša bile su nađene i u ženkama, izuzimajući M. muris i Gongylonema sp. Nisu nađene statistički značajne razlike između mužjaka i ženki kućnog miša u pogledu prevalence (P%) i srednjih vrednosti intenziteta infekcije (MI) i abundancije (MA).Projekat ministarstva br. 14303

Basic indices of spleen immune activity in natural populations of Norway rats (Rattus norvegicus berkenhout, 1769) in Serbia

Basic parameters of spleen immune activity (spleen weight, histomorphology of splenic compartments, and mitogen-induced splenocyte proliferative capacity in vitro) were evaluated in adult individuals of wild Norway rats from urban habitats and compared to the same data obtained in laboratory rat strains. A wider range of relative spleen mass and differential histomorphological characteristics, together with differences in the level and pattern of responsiveness of splenocytes to exogenous stimulation, were noted in spleens of wild Norway rats. Evidence of both enhanced and low-level immune-relevant spleen activity in wild rats demonstrates the complexity of changes in spleen immune activity in rats from natural populations.Ispitivani su osnovni parametri imunske aktivnosti u slezini (masa slezine, histomorfologija i sposobnost ćelija slezine da profilerišu u odgovoru na mitogen u in vitro uslovima) kod adultnih jedinki sivog pacova iz urbanih staništa i poređeni sa podacima dobijenim kod laboratorijskih sojeva pacova. Kod jedinki iz prirodnih populacija je zapažen veći opseg relativnih masa slezine, različite histomorfološke karakteristike i razlike u nivou i načinu odgovara ćelija slezine na egzogenu stimulaciju u poređenju sa jedinkama laboratorijskih sojeva. Ovi podaci ukazuju na kompleksne promene u imunskoj aktivnosti slezine kod jedinki iz prirodnih populacija.Projekat ministarstva br. 14303

Numerical simulation of thermo-fluid properties and optimization of hot water storage tank in biomass heating systems

Za potrebe zagrevanja 1 ha plastenika na poljoprivrednom dobru u Padinskoj Skeli, koje se nalazi u okviru PKB korporacije, izgrađen je grejni sistem sa kotlom na biomasu, u kome se toplota dobija sagorevanjem balirane sojine slame. Zbog nestacionarnih efekata zagrevanja pojavila se potreba za uključivanjem akumulatora toplote u sistem grejanja. Ovaj rad ima za cilj numeričku i eksperimentalnu studiju izvršenu sa ciljem optimizacije akumulatora toplote u predmetnom grejnom sistemu, kao i optimizaciju celokupnog grejnog sistema. U akumulatoru toplote kapaciteta 100 m3, u kome se skladišti zagrejana voda, izvršena su merenja u 256 tačaka, kako u stacionarnom tako i u nestacionarnom režimu rada kotla. Analiza optimizacije je izvršena numeričkom simulacijom koja je obuhvatala i stacionarne i nestacionarne režime. Dobijeni rezultati pokazuju dobro poklapanje rezultata dobijenih eksperimentom i numeričkom simulacijom.A 1.5 MW combustion facility burning large bales of soy straw has been built for the purpose of heating 1 ha of vegetable greenhouses located within the complex of Agricultural Plant PKB in Padinska Skela, Serbia. The paper addresses numerical and experimental study of temperature distribution in a cylindrical, 100 m3 (8 m high, 4 m in diameter) hot water storage tank. The water tank optimization, as well as optimization of the heating facility as a whole, were identified as the main goals of the study performed. Water temperature was measured by a temperature probe inserted in the tank. Measurements were conducted in 256 measurement points, both under steady and unsteady water flow conditions. Water tank optimization analysis was carried out utilizing both steady and unsteady state numerical simulation. The results obtained indicated good agreement between the experimental and computational data acquired

Granulocyte-stimulating activity of the anticoagulant warfarin in rats

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Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study.

INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA

Validation of Atmospheric Boundary Layer Turbulence Model By On-Site Measurements

Modeling atmosperic boundary layer with standard linear models does not sufficiently reproduce wind conditions in complex terrain, especially on leeward sides of terrain slopes More complex models. based on Reynolds averaged Navier-Stokes equations and two-equation kappa-epsilon turbulence models for neutral conditions in atmospheric boundary written in general curvilinear non-orthogonal co-ordinate system, have been evaluated In order to quantify the differences and level of accuracy of different turbulence models, investigation has been performed using standard kappa-epsilon model without additional production terms and kappa-epsilon turbulence models with modified set of model coefficients The sets of full conservation equations are numerically solved by computational fluid dynamics technique. Numerical calculations of turbulence models are compared to the reference experimental data of Askervein hill measurement

Anthropometrische, kraft-, ausdauer-und flexibilitätsmerkmale männlicher elite-eiskletterer und sportkletterer

Objective: Purpose of this study was to compare elite male ice climbers and sport climbers for their anthropometry, muscular strength, endurance, and flexibility. Although there is a certain overlap between these two activities, sport climbing, which recently became an Olympic discipline, has been studied significantly more than the ice climbing. Hence, the second aim was to indirectly determine whether sport climbing training processes and nutrition can be beneficial for the ice climbing athletes. › Methods: 23 male ice climbers of the Ice Climbing World Cup 2010 in Saas Fee (Switzerland) who all reached the final round were compared to 23 elite male sport climbers, which refers to “on sight” climbing grade of VII+/6b (UIAA/French) or higher. Measurements included anthropometry, three different tests for flexibility, two for strength and two for endurance. › Results: Ice climbers have more fat in the trunk region (Fat%-T), have significantly less handgrip strength in both hands, as well as strength to mass ratio (SMR) of the dominant hand. In the test “foot raise”, ice climbers showed significantly less flexibility. › Conclusion: Results indicate that ice climbers have not only higher body fat percentage, probably as an adaption to cold environment but also lower strength and flexibility than sport climbers. With such data, we can conclude that sport climbing training protocols for development of strength, endurance and flexibility can be potentially beneficial to ice climbers.Ziel: Ziel dieser Studie war es, männliche Elite-Eisk letterer und Sportk letterer hinsichtlich ihrer Anthropometrie, Muskelkraft, Ausdauer und Flexibilität zu vergleichen. Das zweite Ziel war zu bestimmen, ob Trainingsprozesse und Ernährung auf der Grundlage von Untersuchungen an Sportk letterern auch für Eiskletterer von Vorteil sein können.›Methoden: 23 männliche Eisk letterer des Ice Climbing World Cup 2010 in Saas Fee (Schweiz), die alle in die Finalrunde kamen, w urden mit 23 männlichen Elite-Sportkletterern verglichen, die „on sight“ einen K lettergrad von V II+/6b (UIA A/French) oder hö-her aufw iesen. Die Messungen umfassten die Anthropometrie, drei verschiedene Tests für Flexibilität, zwei für K raft und zwei für Ausdauer.›Ergebnisse: Eisk letterer haben mehr Fett im Rumpf bereich (Fat%-T), signifikant weniger Handgriff kraft in beiden Händen sowie Kraft-zu-Masse-Verhältnis (SMR) der dominanten Hand. Eiskletterer zeigten deutlich weniger Flexibilität imHüftbereich.›Schlussfolgerung: Die Ergebnisse zeigen, dass Eisk letterer nicht nur einen höheren Körperfettanteil haben, wahrscheinlich als Anpassung an eine kalte Umgebung, sondern auch eine gerin-gere Kraft und Flexibilität als Sportkletterer. Sportkletter-Trai-ningsprotokolle können zur Entw ick lung von Kraft, Ausdauer und Flexibilität für Eisk letterer potenziell von Vorteil sein