INFLAMMASOMES AND GASDERMINS IN IMMUNE DEFENSE AND PATHOLOGY

Pyroptosis is a form of programmed cell death that effectively defends against intracellular pathogens by lysing an infected cell, thereby removing the pathogens’ replicative niche, and by releasing danger-associated molecular patterns and the pro-inflammatory cytokines interleukin (IL)-1b and IL-18, thereby promoting an immune response. However, when activated at the incorrect time or in excess, pyroptosis can cause significant pathology.Pyroptosis was traditionally considered to primarily occur in monocytes and macrophages and, as a result, most studies of pyroptosis to date utilized monocytes and macrophages. Recently, the role of pyroptosis in defending non-immune cells, most notably intestinal epithelial cells, has been appreciated. Furthermore, with the recent discovery that gasdermin D was the direct mediator of pyroptosis in macrophages and monocytes, we now know that there is an entire gasdermin family with similar pore-forming and lytic capabilities, each with a specific expression pattern in different tissue compartments. Consequently, it is essential to improve our understanding about how inflammasomes and various members of the gasdermin family trigger pyroptosis and interface with immune responses not just in macrophages, but also in other cell types and tissues as well.To explore this concept, we first compared the role of inflammasomes and gasdermin D in neutrophils versus macrophages during infection with the environmental pathogenBurkholderia thailandensis. Second, we completed the first steps for generating a cell-specific knockout line of gasdermin D. Third, we explored the gasdermin family by specifically focusing on the keratinocyte-specific gasdermin A, and by performing a molecular evolutionary analysis of the gasdermin family as a whole.Doctor of Philosoph

Brain Tumor Segmentation from MRI Data Using Ensemble Learning and Multi-Atlas

Atlases are frequently employed to assist medical image segmentation with prior information. This paper introduces a multi-atlas architecture that is trained to locally characterize the appearance (average intensity and standard deviation) of normal tissues in various observed and computed data channels of brain MRI records. The multiple atlas is then deployed to enhance the accuracy of an ensemble learning based brain tumor segmentation procedure that uses binary decision trees. The proposed method is validated using the low-grade tumor volumes of the BraTS 2016 train data set. The use of atlases improve the segmentation quality, causing a rise of up to 1.5% in average Dices scores

Veštaško razmnožavanje i reproduktivne osobine čikova (Misgurnus Fossilis)

U našem istraživanju je dvanaest ženki i osam mužjaka čikova veštački reprodukovano pre sezone mresta. Riba je uneta u laboratorijske tankove u rano proleće i ženke su tretirane sa 10 mg/kg telesne težine sa CP (ekstrakt hipofize šarana), dok su mužjaci hipofizirani sa 5mg/kg telesne težine radi izazivanja ovulacije i spermijacije. Ženke su ovulirale u narednih 18 do 24 časa i posle istiskivanja jaja su bila oplođena. Vrednosti pseudogonadosomatskog indeksa PGSIkod 4 ženke veoma su varirale (3.6 – 22.2%), stopa oplođenja je varirala od 30.34 do 93.81 % posle 24 časa od oplođenja. Tri dana po oplođenju larve su se izvalile (14.84-91.8%) i započele sa prvom egzogenom hranom šestog dana. Čikov se može razmnožavati kao i šaranske vrste u mrestilištima, jedina poteškoća je mala količina gameta. Veštačko razmnožavanje i uzgoj larvi može da pomogne u značajnom jačanju populacija, tako da bi bila moguća repopulacija već redukovanih populacijaii stvaranje novih staništakoji odgovaraju ovoj vrsti. Vijabilne larve iz interspecijske hibridizacije su se izlegle i na osnovu njihove morfologije mlađ nije ličila na hibride, što bi moglo da ukaže na sposobnost aseksualnog razmnožavanja. Genetička analiza nije pokazala genom mužjaka kod mlađi. F1R1 potomci su bili 50% tetraploidi (4n=100)i 50 % heksaploidi (6n=150). Ovo je prvi rezultat stvaranja heksaploida (broj hromozoma 150) čikova u laboratorijskim uslovima

Bulk composition of the Kaba meteorite by ICP OES and ICP MS

The Tenth Symposium on Polar Science/Poster presentations: [OA] Antarctic meteorites, Wed. 4 Dec. / Entrance Hall (1st floor), National Institute of Polar Researc

Poreklo i genetička struktura nekoliko mađarskih divljih i domestifikovanih populacija potočne pastrmke na osnovu PCR-RFLP i mikrosatelitskih markera

U Evropi je, na osnovu studija mitohondrijalne DNK, identifikovano pet evolutivnih linija potočne pastrmke (Salmo trutta m. fario L. 1758): Atlanska, Dunavska, Mediteranska, Jadranska i Mramorna. Mađarske linije bi teorijski trebalo da pripadaju Dunavskoj liniji na osnovu hidrogeografije zemlje, ipak, ovo nije potvrđeno genetičkim studijama. Korišćeni su molekularni markeri da bi se ispitalo genetička pozadina populacije potočne pastrmke u Mađarskoj. Istraživanja su uključila jedini matični nasad potočne pastrmke u Mađarskoj, kao i po jedna populacije u planinskim vencima Bükk, Aggtelek, Börzsöny i Visegrádi, po jedna populacija u svakom. Genetička analiza je do sada sprovedena na 533 individue, isečak peraja je uzorkovan sa svake ribe i PCR-RFLP (kontrolni region mitohondrijalne DNK, laktat dehidrogenaza i somatolaktin geni), kao i analiza mikrosatelitnih markeri (BFRO002, OMM1064, Ssa408uos, SsoSL417, SsoSL438) su bili korišćeni da bi se razlikovale Dunavska i Atlanska linija potočne pastrmke. Na osnovu genetičke analize mitohondrijalne DNK divljih populacija, udeo Dunavskog haplotipa je nizak (< 10 %), sa izuzetkom potoka Apátkúti u planinama Visegrádi, gde je nađena relativno visok udeo Dunavskog haplotipa (34%). 401 analizirani primerak matičnog jata farme je skoro u potpunosti Atlanski haplotip, što ukazuje na efekat osnivača. Iako su kasnije prikupljeni primerci iz obližnjeg potoka i pridodati matičnom jatu, njihov broj je bio ograničen jer su uglavnom svi bili mužjaci. Budući da je jedino matično jato u Mađarskoj, ribe sa ove farme se koriste za poribljavanje od strane ribolovaca, što može dovesti do značajnog uticaja na prirodne populacije. Na osnovu analize nuklearnih markera sve populacije su veoma heterogene. Veliki udeo (60-80%) Atlanskih alela primećen za ove markere na svim lokacijama gde je obavljano uzorkovanje ukazuje na efekat intenzivnog poribljavanja mađarskih salmonidnih regiona. Analize mikrosatelitskih markera su ukazale na visoku heterozigotnost i Hardy-Weinberg-ovu ravnotežu svih populacija

T cell immune response predicts survival in severely ill COVID-19 patients requiring venovenous extracorporeal membrane oxygenation support

IntroductionThere is a critical gap in understanding which SARS-CoV-2 patients would benefit most from venovenous extracorporeal membrane oxygenation (VV-ECMO) support. The potential role of a dysregulated immune response is still unclear in this patient population.ObjectivesTo assess the potential predictive value of SARS-CoV-2 specific cellular and humoral immune responses for survival in critically ill COVID-19 patients requiring VV-ECMO.MethodsWe conducted a prospective single-center observational study of unvaccinated patients requiring VV-ECMO support treated at the intensive care unit of Semmelweis University Heart and Vascular Center between March and December 2021. Peripheral blood samples were collected to measure the humoral and cellular immune statuses of the patients at the VV-ECMO cannulation. Patients were followed until hospital discharge.ResultsOverall, 35 COVID-19 patients (63% men, median age 37 years) on VV-ECMO support were included in our study. The time from COVID-19 verification to ECMO support was a median (IQR) of 10 (7-14) days. Of the patients, 9 (26%) were discharged alive and 26 (74%) died during their hospital stay. Immune tests confirmed ongoing SARS-CoV-2 infection in all the patients, showing an increased humoral immune response. SARS-CoV-2-specific cellular immune response was significantly higher among survivors compared to the deceased patients. A higher probability of survival was observed in patients with markers indicating a higher T cell response detected by both QuantiFeron (QF) and flow cytometry (Flow) assays. (Flow S1 CD8+ ≥ 0.15%, Flow S1 CD4+ ≥ 0.02%, QF CD4 ≥ 0.07, QF whole genome ≥ 0.59). In univariate Cox proportional hazard regression analysis BMI, right ventricular (RV) failure, QF whole genome T cell level, and Flow S1 CD8+ T cell level were associated with mortality, and we found that an increased T cell response showed a significant negative association with mortality, independent of BMI and RV failure.ConclusionEvaluation of SARS-CoV-2 specific T cell response before the cannulation can aid the risk stratification and evaluation of seriously ill COVID-19 patients undergoing VV-ECMO support by predicting survival, potentially changing our clinical practice in the future

Gajenje slatkovodnih riba u centralnoj i istočnoj Evropi: potrebe za istraživanjem i razvojem

Gajenje slatkovodinih riba ima veoma važnu ulogu za stabilizaciju biodiversiteta, resursa podzemnih voda, klime regiona kao i za snabdevenost hranom u Centralnoj i Istočnoj Evropi. Velika konkurencija cena ribe na međunarodnom tržištu i promene u navikama ishrane ljudi pojačavaju pritisak na mala i srednja preduzeća u Centralnoj i Istočnoj Evropi koja se bave gajenjem ribe i mogu da ugroze predeo oko uzgojnih jezera. Da bi povećali vrednost svih karika u lancu proizvodnje slatkovodnih riba, naučnici i proizvođači su identifikovali uobičajene i potencijalne izazove. Da bi se procenile potrebe sektora akvakulture u centralnoj i istočnoj Evropi, sprovedeni su polu strukturirani intervjui sa proizvođačima i prerađivačima ribe i udruženjima u Poljskoj i Češkoj, u okviru projekta SIAD i FP7 EU projekta TRAFOON. Takođe su održane radionice sa istraživačima u sektoru akvakulture duž svake karike lanca proizvodnje riba u Centralnoj i Istočnoj Evropi. Različite interesne strane su identifikovale nekoliko izazova koji ometaju razvoj slatkovodne akvakulture u Centralnoj i Istočnoj Evropi. Razvoj akvakulture zahteva postojanje harmonizovanog regulativnog/pravnog okvira. Razmena znanja bi imala pozitivan uticaj na razvoj uniformnih standarda za održivost, i pomogla bi stvaranju pravnih procedura za izdavanje dozvola i licenci. Potrebno je izvršiti ekonomsku procenu usluga koje ekosistem ribnjaka pruža. Poboljšana tehnoligija koja je povoljna po životnu sredinu i sistemi za upravljanje kvalitetom u proizvodnji i preradi su neophodni da bi se obezbedila ustaljenija ponuda proizvoda od ribe viskog kvaliteta. Potrošači treba da budu bolje informisani o funkciji koju slatkovodna akvakultura i njeni proizvodi imaju za životnu sredinu. Da bi došlo do održivog razvoja sektora akvakulture i da bi se izgradilo poverenje javnosti, veoma je važno podstaći društvene inovacije koje su primenljive na pojedinačni sektor ili pojedinačnu teritoriju. Da bi došlo do održivog razvoja sektora slatkovodne akvakulture potrebno je razviti strategije makro regionalnog razvoja koje su prilagođene određenim tržištima, uslovima životne sredine, ponašanju potrošača, kulturi i tradiciji i koje nude potencijal za razvoj izvan granica jedne zemlje. Razvoj i adaptacija ključnih tehnologija potrebni su da bi se stabilizovala konkurentna i održiva proizvodnja i prerada ribe u čijoj su proizvodnji resursi efikasno iskorišćeni

Genetic and environmental factors on heart rate, mean arterial pressure and carotid intima–media thickness: A longitudinal twin study

Background: Heart rate (HR), mean arterial pressure (MAP) and carotid intima–media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. Methods: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. Results: For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33–0.51) for HR, 0.34 (95% CI: 0.24–0.43) for MAP, and 0.23 (95% CI: 0.12–0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29–0.71) for HR, 0.56 (95% CI: 0.31–0.81) for MAP, and 0.36 (95% CI: 0.07–0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. Conclusions: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time

Pilot analysis of the usefulness of mortality risk score systems at resuscitated patients

Introduction: Sudden cardiac death is one of the most significant cardiovascular causes of death worldwide. Although there have been immense methodological and technical advances in the field of cardiopulmonary resuscitation and following intensive care in the last decade, currently there are only a few validated risk-stratification scoring systems for the quick and reliable estimation of the mortality risk of these patients at the time of admission to the intensive care unit. Objective: Our aim was to correlate the mortality prediction risk points calculated by CardShock Risk Score (CSRS) and modified (m) CSRS based on the admission data of the post-cardiac arrest syndrome (PCAS) patients. Methods: The medical records of 172 out-of-hospital resuscitated cardiac arrest patients, who were admitted at the Heart and Vascular Centre of Semmelweis University, were screened retrospectively. Out of the 172 selected patients, 123 were eligible for inclusion to calculate CSRS and mCSRS. Based on CSRS score, we generated three different groups of patients, with scores 1 to 3, 4 to 6, and 7+, respectively. Mortality data of the groups were compared by log-rank test. Results: Mean age of the patients was 63.6 years (69% male), the cause of sudden cardiac death was acut coronary syndrome in 80% of the cases. The early and late mortality was predicted by neurological status, serum lactate level, renal function, initial rhythm, and the need of catecholamines. Using mCSRS, a significant survival difference was proven in between the groups "1-3" vs "4-6" (p Conclusion: Compared to the CSRS, the mCSRS expanded with the 2 additional weighting points differentiates more specifically the low-moderate and high survival groups in the PCAS patient population treated in our institute.Peer reviewe