The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory Enhancers and Limits Activation of Alternatively Polarized Macrophages

The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300, and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation, and chromatin accessibility. The repressor function of STAT6 is HDAC3 dependent on a subset of IL-4-repressed genes. In addition, STAT6-repressed enhancers show extensive overlap with the NF-kappaB p65 cistrome and exhibit decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes. As a consequence, macrophages exhibit diminished inflammasome activation, decreased IL-1beta production, and pyroptosis. Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli

Elasto-mechanical properties of living cells

The possibility to directly measure the elasticity of living cell has emerged only in the last few decades. In the present study the elastic properties of two cell lines were followed. Both types are widely used as cell barrier models (e.g. blood-brain barrier). During time resolved measurement of the living cell elasticity a continuous quasi-periodic oscillation of the elastic modulus was observed. Fast Fourier transformation of the signals revealed that a very limited number of three to five Fourier terms fitted the signal in the case of human cerebral endothelial cells. In the case of canine kidney epithelial cells more than 8 Fourier terms did not result a good fit. Calculating the correlation between nucleus and periphery of the signals revealed a higher correlation factor for the endothelial cells compared to the epithelial cells

Subacute effects of a food flavour on fish model

Dóra Bencsik1,2, Balázs P Szabó1, Gyöngyi Gazsi2, Béla Urbányi2, Béla Szende3, Gergely Rácz3, Antal Véha1, Zsolt Csenk

Absztrakt automaták és formális nyelvek = Abstract Automata and Formal Languages

Monográfiában foglaltuk össze a véges automata hálózatok elméletének alapvető eredményeit . Megadtuk a Leticsevszkij kritérium nélküli automata-hálózatok egy új jellemzését. Megadtunk bizonyos szimbólum osztályokkal ellátott többszalagos automatákat. Megadtuk és vizsgáltuk a kutatásaink során felfedezett automataelméleti elvű új titkosítási rendszert. Új bizonyítást adtunk a Lyndon-Schützenberger tételre és a Shyr-Yu tételre. Általánosítottuk a szavak primitivitásának, illetve periodicitásának fogalmát, s megadtuk, hogy melyek azok a Marcus nyelvtanok, amelyek az adott típusú szavakból álló nyelveket képesek generálni. Sikerült találni egy iterációs lemmát azon környezetfüggetlen nyelvekre, melyek nem lineárisak. A contextuális sztringnyelvek általánosításaként bevezettük és vizsgáltuk a hypergráf contextuális nyelvek és nyelvtanok fogalmát. Automaták segítségével jellemeztük az uniómentes nyelveket. Leírtuk a különféle logikai kalkulusok és valamely levezetési rendszer szabályai szerint megadott levezetések kapcsolatait, s a különféle kalkulusok normalizálhatósági tulajdonságait. Új elvű számítási kutatásainkban az intervallum-értékű számításokat, mint új számítási modellt írtuk le. Digitális geometriai kutatásainkban digitális távolság alapján értelmezett szakaszokat, köröket, hiperbolákat és parabolákat vizsgáltunk. | We summarized in monograph the fundamental results of theory of finite automata networks. We gave a new characterization of automata-networks having no Letichevsky criteria. We gave multi-tape automata supplied by certain symbol classes. We gave and investigated a novel cryptosystem based on automata theory discovered during our research.. We gave a new proof of Lyndon-Schützenberger Theorem and Shyr-Yu Theorem. We generalized the concept of primitivity and periodicity of words and we give the Marcus gramars which are able to generate languages consisting of given type words. It succeed in finding an iteration lemma for non-linear context-free languages. As a generalization of contextual string languages, we introduced and investigated the concept of hypergraph contextual grammars and languages. We characterized the union-free languages by automata. We described the connections of derivations given by various logical calculi and certain derivation system, moreover the normalizable properties of various calculi. In our new computation principle researches we described the intervallum-value computations as new computation model In our digital geometric researches we investigated the sessions, circles, hyperbolas and parabolas defined by a digital distance

De-adhesion dynamics of melanoma cells from brain endothelial layer

Metastasis formation is a complex and not entirely understood process. The poorest prognosis and the most feared complications are associated to brain metastases. Melanoma derived brain metastases show the highest prevalence. Due to the lack of classical lymphatic drainage, in the process of brain metastases formation the haematogenous route is of primordial importance. The first and crucial step in this multistep process is the establishment of firm adhesion between the blood travelling melanoma cells and the tightly connected layer of the endothelium, which is the fundamental structure of the blood-brain barrier. This study compares the de-adhesion properties and dynamics of three melanoma cells types (WM35, A2058 and A375) to a confluent layer of brain micro-capillary endothelial cells. Cell type dependent adhesion characteristics are presented, pointing towards the existence of metastatic potential related nanomechanical aspects. Apparent mechanical properties such as elasticity, maximal adhesion force, number, size and distance of individual rupture events showed altered values pointing towards cell type dependent aspects. Our results underline the importance of mechanical details in case of intercellular interactions. Nevertheless, it suggests that in adequate circumstances elastic and adhesive characterizations might be used as biomarkers

Selective production of imines and benzimidazoles by cooperative bismuth(III)/transition metal ion catalysis

Cooperative Bi(III)/Co(II) and Bi(III)/Mn(II) heterogeneous catalysts have been developed enabling efficient oxidative annulations for preparing both cross-coupled imines and benzimidazoles under ambient conditions in an atom-economic and time-efficient manner, involving ambient air as oxidant and without the need of any other additives. This is the first synergistic Lewis acid/transition metal catalyzed annulation which is potentiated by the interfaces between the building blocks of the catalysts. To achieve our goals, a useful fabrication process has been developed to heterogenize the transition metal ions via strong interactions on well-known Sillèn-type bismuth subcarbonate (bismutite). Their reusability, activity and selectivity as well as water-tolerance have made them potential competitors to effective heterogeneous/homogeneous catalysts reported previously

The applicability of 10 ml cryotubes for sperm cryopreservation in a Hungarian carp landrace (Cyprinus carpio carpio morpha accuminatus)

In our study, the comparison of 5 ml straw and 10 ml cryotube during sperm cryopreservation in a Hungarian carp landrace (Cyprinus carpio carpio morpha accuminatus) was carried out. Three different dilution ratios (1:1, 1:4 and 1:9) were also tested using the cryotube. A significantly higher pMOT was recorded using the cryotube in comparison with the straw. VCL and STR were similar in both groups. Cryopreservation had a negative effect on pMOT and VCl using the cryotube and also the straw where, STR was not reduced significantly. An increasing tendency was observed using higher dilution of sperm during cryopreservation; however, significant difference was not recorded between the three groups. VCL and STR were similar in all groups. Cryotube was applicable for the sperm cryopreservation of the Hungarian carp landrace. However, the standardization for the freezing method specified for this volume is recommended. The different dilution ratios needed be tested also during fertilization

Direct mapping of melanoma cell – endothelial cell interactions

The most life-threatening aspect of cancer is metastasis; cancer patient mortality is mainly due to metastasis. Among all metastases, presence of brain metastasis is one with the poorest prognosis; the median survival time can be counted in months. Therefore, prevention or decreasing their incidence would be highly desired both by patients and physicians. Since the central nervous system (CNS) lacks classical lymphatic circulation, metastatic cells invading the CNS must breach the blood-brain barrier. The key step in this process is the establishment of firm adhesion between the cancer cell and the cerebral endothelial layer. Using the atomic force microscope, a high resolution force-spectrograph, our aim was to explore the connections among the cell morphology, cellular mechanics and biological function in the process of transendothelial migration of metastatic cancer cells. By immobilization of a melanoma cell to an atomic force microscope’s cantilever, intercellular adhesion was directly measured at quasi-physiological conditions. Hereby we present our latest results using this melanoma -decorated probe. Binding characteristics to a confluent layer of brain endothelial cells was directly measured by means of single cell force spectroscopy. Adhesion dynamics and strength was characterized and we present data about spatial distribution of elasticity and detachment strength. These results highlight the importance of cellular mechanics in brain metastasis formation and emphasize the enormous potential towards exploration of intercellular dynamics related processes

Obstruktív koszorúér-betegség nélkül kialakuló heveny szívizominfarktus (MINOCA) – gyakoriság és prognózis = Myocardial infarction without obstructive coronary artery disease (MINOCA) – prevalence and prognosis

Absztrakt: Bevezetés: A szignifikáns koszorúér-obstrukció nélkül kialakuló heveny szívinfarktus (MINOCA) gyakoriságával és prognózisával kapcsolatos adatok ellentmondóak. Célkitűzés: A MINOCA gyakoriságának és a betegek prognózisának vizsgálata nagy esetszámú, válogatás nélküli beteganyagban. Módszer: A Nemzeti Szívinfarktus Regiszter adatbázisában 45 223 akut myocardialis infarctus miatt kezelt beteg található, akiknél a kórházi felvételre 2014. január 1. és 2018. június 30. között került sor, és a kezelés során koronarográfia történt. A kórházi kezelésre 22 469 betegnél (49,7%) ST-elevációval járó (STEMI), míg 22 754 (50,3%) esetben nem ST-elevációval járó infarktus (NSTEMI) miatt került sor. A MINOCA-csoportba 2003 beteget soroltunk, akiknél a koronarográfia nem igazolt obstruktív koszorúér-betegséget, és kórelőzményükben nem volt szívinfarktus, szívelégtelenség, percutan coronariaintervenció, illetve revascularisatiós műtét. A koronarográfia 43 220 betegnél igazolt szignifikáns koszorúér-betegséget, akiket a MICAD-csoportba soroltunk. Vizsgáltuk a betegek klinikai adatait, a halálozást és a reinfarktust. A túlélést a Kaplan–Meier-módszer szerint vizsgáltuk, és Cox proporcionális hazárd modellel elemeztük. Eredmények: AMI-ban a MINOCA gyakorisága 4,4%. Eltérő gyakoriságot találtunk STEMI, illetve NSTEMI esetén (2,0% vs. 6,8%). A MINOCA-csoport betegei fiatalabbak voltak (64,0 ± 14,4 vs. 65,5 ± 12,2 év), és magasabb volt a nők előfordulási aránya (55,7 vs. 36,5%). A MICAD-betegek között gyakoribb volt a hypertonia (79,1% vs. 73,7%), a cukorbetegség (33,0% vs. 21,2%) és a perifériás érbetegség (12% vs. 8%). Az egy éven belüli reinfarktust, valamint a halálozást – minden vizsgált időpontban – a MICAD-csoportban találtuk magasabbnak. Következtetés: A MINOCA-csoporton belül a STEMI-, illetve NSTEMI-diagnózissal kezelt férfiak halálozása nem különbözött, ezzel szemben a nők esetén a STEMI-típusú infarktus esetén (MINOCA–STEMI) a nők halálozása lényegesen magasabb volt. Orv Hetil. 2019; 160(45): 1791–1797. | Abstract: Introduction: There are conflicting data on the prevalence and prognosis of AMI patients with non-obstructive coronary artery disease (MINOCA). Aim: We studied the prevalence and prognosis of MINOCA patients. Method: In the Hungarian Myocardial Infarction Registry (HUMIR) 45,223 patients (pts) with acute myocardial infarction (AMI) were found who were treated between Jan 1, 2014, and June 30, 2018, and coronary arteriography was performed. ST-elevation myocardial infarction was diagnosed in 22,469 pts (49.7%). Patients without obstructive coronary artery disease who had no previous myocardial infarction, heart failure, PCI and CABG procedure were selected to the MINOCA group (n = 2003). Patients with obstructive coronary artery disease belonged to the MICAD group (n = 43,220). We investigated clinical characteristics of the patients, overall survival and reinfarction. Survival curves were estimated with the Kaplan–Meier method and were modeled with the Cox proportional hazards model. Results: The proportion of MINOCA pts among all myocardial infarction was by 4.4% higher in the STEMI pts compared to the NSTEMI group (2.0% vs. 6.8%). The MINOCA pts were younger (age 64.0 ± 14.4 vs. 65.5 ± 12.2 years), and the proportion of women was higher (55.7% vs. 36.5%). Hypertension, diabetes mellitus and peripheral artery disease were more common in the MICAD group (79.1% vs. 73.7%, 33.0% vs. 21.2%, and 12% vs. 8%). The mortality was higher among the MICAD pts. In the MINOCA group, the mortality of men did not differ between STEMI and NSTEMI, as opposed to women: women with STEMI had higher mortality than women with NSTEMI. The risk of reinfarction was higher in the MICAD group, especially in NSTEMI, the risk in the MINOCA group was lower, and there was no substantial difference between types. Conclusion: In this real word, retrospective, observational study, we found a significant difference in the prevalence of MINOCA pts according to different types of myocardial infarction. In the MINOCA group, the mortality of women with STEMI was substantially higher. Orv Hetil. 2019; 160(45): 1791–1797

Selective production of imines and benzimidazoles by cooperative bismuth(III)/transition metal ion catalysis

Cooperative Bi(III)/Co(II) and Bi(III)/Mn(II) heterogeneous catalysts have been developed enabling efficient oxidative annulations for preparing both cross-coupled imines and benzimidazoles under ambient conditions in an atom-economic and time-efficient manner, involving ambient air as oxidant and without the need of any other additives. This is the first synergistic Lewis acid/transition metal catalyzed annulation which is potentiated by the interfaces between the building blocks of the catalysts. To achieve our goals, a useful fabrication process has been developed to heterogenize the transition metal ions via strong interactions on well-known Sillèn-type bismuth subcarbonate (bismutite). Their reusability, activity and selectivity as well as water-tolerance have made them potential competitors to effective heterogeneous/homogeneous catalysts reported previously