Characterization of the Sterol 24-C-Methyltransferase Genes Reveals a Network of Alternative Sterol Biosynthetic Pathways in Mucor lusitanicus

The fungal membrane contains ergosterol instead of cholesterol, which offers a specific point of attack for the defense against pathogenic fungi. Indeed, most antifungal agents target ergosterol or its biosynthesis

Dynamic transcriptional control of macrophage miRNA signature via inflammation responsive enhancers revealed using a combination of next generation sequencing-based approaches

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Introduction of a pharmacological neurovascular uncoupling model in rats based on results of mice

Our aim was to establish a pharmacologically induced neurovascular uncoupling (NVU) method in rats as a model of human cognitive decline. Pharmacologically induced NVU with subsequent neurological and cognitive defects was described in mice, but not in rats so far. We used 32 male Hannover Wistar rats. NVU was induced by intraperitoneal administration of a pharmacological “cocktail” consisting of N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MSPPOH, a specific inhibitor of epoxyeicosatrienoic acid-producing epoxidases, 5 mg kg−1), L-NG-nitroarginine methyl ester (L-NAME, a nitric oxide synthase inhibitor, 10 mg kg−1) and indomethacin (a nonselective inhibitor of cyclooxygenases, 1 mg kg−1) and injected twice daily for 8 consecutive days. Cognitive performance was tested in the Morris water-maze and fear-conditioning assays. We also monitored blood pressure. In a terminal operation a laser Doppler probe was used to detect changes in blood-flow (CBF) in the barrel cortex while the contralateral whisker pad was stimulated. Brain and small intestine tissue samples were collected post mortem and examined for prostaglandin E2 (PGE2) level. Animals treated with the “cocktail” showed no impairment in their performance in any of the cognitive tasks. They had higher blood pressure and showed cca. 50 decrease in CBF. Intestinal bleeding and ulcers were found in some animals with significantly decreased levels of PGE2 in the brain and small intestine. Although we could evoke NVU by the applied mixture of pharmacons, it also induced adverse side effects such as hypertension and intestinal malformations while the treatment did not cause cognitive impairment. Thus, further refinements are still required for the development of an applicable model

Three-component synthesis, utilization and biological activity of phosphinoyl-functionalized isoindolinones

A new method for the synthesis of 3-oxoisoindolin-1-ylphosphine oxides bearing same or different substituents on the phosphorus atom is described. The one-pot three-component reaction of 2-formylbenzoic acid, primary amines and achiral or P-stereogenic secondary phosphine oxides provided the target compounds under catalyst-free, mild conditions and for short reaction times. The deoxygenation of a 3-oxoisoindolin-1-ylphosphine oxide was also studied, and the phosphine obtained could be converted to a sulphide and to a platinum complex. The crystal structures of a selected phosphine oxide and the corresponding platinum species were investigated by X-ray diffraction analysis. The biological activity, such as in vitro cytotoxicity on different cell lines and antibacterial activity of the 3-oxoisoindolin-1-ylphosphine oxides was also investigated. Based on the IC50 values obtained, several derivatives showed moderate activity against the HL-60 cell line and two compounds containing 3,5-dimethylphenyl groups on the phosphorus atom showed promising activity against Bacillus subtilis bacteria

Systematic transcriptomic and phenotypic characterization of human and murine cardiac myocyte cell lines and primary cardiomyocytes reveals serious limitations and low resemblances to adult cardiac phenotype

Background Cardiac cell lines and primary cells are widely used in cardiovascular research. Despite increasing number of publications using these models, comparative characterization of these cell lines has not been performed, therefore, their limitations are undetermined. We aimed to compare cardiac cell lines to primary cardiomyocytes and to mature cardiac tissues in a systematic manner. Methods and results Cardiac cell lines (H9C2, AC16, HL-1) were differentiated with widely used protocols. Left ventricular tissue, neonatal primary cardiomyocytes, and human induced pluripotent stem cell-derived cardiomyocytes served as reference tissue or cells. RNA expression of cardiac markers (e.g. Tnnt2, Ryr2) was markedly lower in cell lines compared to references. Differentiation induced increase in cardiac- and decrease in embryonic markers however, the overall transcriptomic profile and annotation to relevant biological processes showed consistently less pronounced cardiac phenotype in all cell lines in comparison to the corresponding references. Immunocytochemistry confirmed low expressions of structural protein sarcomeric alpha-actinin, troponin I and caveolin-3 in cell lines. Susceptibility of cell lines to sI/R injury in terms of viability as well as mitochondrial polarization differed from the primary cells irrespective of their degree of differentiation. Conclusion Expression patterns of cardiomyocyte markers and whole transcriptomic profile, as well as response to sI/R, and to hypertrophic stimuli indicate low-to-moderate similarity of cell lines to primary cells/cardiac tissues regardless their differentiation. Low resemblance of cell lines to mature adult cardiac tissue limits their potential use. Low translational value should be taken into account while choosing a particular cell line to model cardiomyocytes

The genetic legacy of the Hunyadi descendants

The Hunyadi family is one of the most influential families in the history of Central Europe in the 14th–16th centuries. The family’s prestige was established by Johannes Hunyadi, a Turk-beater who rose to the position of governor of the Kingdom of Hungary. His second son, Matthias Hunyadi, became the elected ruler of the Kingdom of Hungary in 1458. The Hunyadi family had unknown origin. Moreover, Matthias failed to found a dynasty because of lacking a legitimate heir and his illegitimate son Johannes Corvinus was unable to obtain the crown. His grandson, Christophorus Corvinus, died in childhood, thus the direct male line of the family ended. In the framework of on interdisciplinary research, we have determined the whole genome sequences of Johannes Corvinus and Christophorus Corvinus by next-generation sequencing technology. Both of them carried the Y-chromosome haplogroup is E1b1b1a1b1a6a1c ~, which is widespread in Eurasia. The father-son relationship was verified using the classical STR method and whole genome data. Christophorus Corvinus belongs to the rare, sporadically occurring T2c1þ146 mitochondrial haplogroup, most frequent around the Mediterranean, while his father belongs to the T2b mitochondrial haplogroup, widespread in Eurasia, both are consistent with the known origin of the mothers. Archaeogenomic analysis indicated that the Corvinus had an ancient European genome composition. Based on the reported genetic data, it will be possible to identify all the other Hunyadi family member, whose only known grave site is known, but who are resting assorted with several other skeletons

Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection

Little is known about the role of the neuropeptide somatostatin (SST) in myocardial ischemia/reperfusion injury and cardioprotection. Here, we investigated the direct cardiocytoprotective effect of SST on ischemia/reperfusion injury in cardiomyocyte cultures, as well as the expression of SST and its receptors in pig and human heart tissues. SST induced a bell-shaped, concentration-dependent cardiocytoprotection in both adult rat primary cardiomyocytes and H9C2 cells subjected to simulated ischemia/ reperfusion injury. Furthermore, in a translational porcine closed-chest acute myocardial infarction model, ischemic preconditioning increased plasma SST-like immunoreactivity. Interestingly, SST expression was detectable at the protein, but not at the mRNA level in the pig left ventricles. SSTR1 and SSTR2, but not the other SST receptors, were detectable at the mRNA level by PCR and sequencing in the pig left ventricle. Moreover, remote ischemic conditioning upregulated SSTR1 mRNA. Similarly, SST expression was also detectable in healthy human interventricular septum samples at the protein level. Furthermore, SST-like immunoreactivity decreased in interventricular septum samples of patients with ischemic cardiomyopathy. SSTR1, SSTR2, and SSTR5 but not SST and the other SST receptors were detectable at the mRNA level by sequencing in healthy human left ventricles. In addition, in healthy human left ventricle samples, SSTR1 and SSTR2 mRNAs were expressed especially in vascular endothelial and some other cell types as detected by RNA Scope® in situ hybridization. This is the first demonstration that SST exerts a direct cardiocytoprotective effect against simulated ischemia/reperfusion injury. Moreover, SST is expressed in the heart tissue at the peptide level; however, it is likely to be of sensory neural origin since its mRNA is not detectable. SSTR1 and SSTR2 might be involved in the cardioprotective action of SST, but other mechanisms cannot be excluded

Általános nyelvészeti tanulmányok XXIX. - Kísérletes nyelvészet

Ez a kötet kísérletes nyelvészeti tanulmányokat tartalmaz, azaz olyan kutatások eredményeit ismerteti, amelyek egy tág értelemben vett „laboratóriumban" végzett kísérletek eredményein alapulnak. A kötet koncepciója szerint mind a legmodernebb technikai eszközrendszerekkel felszerelt kísérleti laboratóriumi struktúra, mind valamilyen speciális terep (óvoda, iskola, rehabilitációs intézet), mind pedig az internet, például a Facebook is szolgálhat kísérlet lefuttatásának kereteként. A nyelvészetben alkalmazott kísérletek módszertana természetesen követi a tudományos kísérletek általános paradigmáját és megőrzi annak lényeges jegyét: hogy megismételhető, objektív legyen. Amíg számos interdiszciplináris területen, így például a neurolingvisztikában és a pszicholingvisztikában, a tudományos kísérleteket a 19. század óta alkalmazzák, addig az olyan nyelvészeti témákban, mint a nyelvtan készítése, a nyelvleírás, viszonylag újabb fejlemény a kísérletes módszertan alkalmazása. Ezt sok minden motiválta, többek között a kurrens nyelvészeti modellek, elméletek és variánsaik versengései és ennek kapcsán olyan objektív bizonyítékok keresése, amelyek csak kísérleti helyzetekben állíthatók elő. Kötetünk tanulmányait négy tematikus egység szerint csoportosítottuk: 1. Nyelvleírási kérdések, 2. Nyelvelsajátítás, 3. A mesterségesnyelvtan-elsajátítási paradigma alkalmazásai, 4. Nyelvi zavarok. A szerzők között nemcsak a terület jelentős ismertségű személyiségei, hanem külföldről korábban hazatért, vagy más országokban dolgozó és az itthoniakkal szoros kapcsolatokat fenntartó, sőt Magyarországon működő külföldi kutatók is megtalálhatók, példázva a magyarországi nyelvészet nemzetközi beágyazottságát. Nyolc tanulmány esetében a szerzők mellékeltek a kísérleteik hátteréhez, például az adatbázisokhoz, vagy a keretként szolgáló kutatási projekthez és kutatócsoporthoz elvezető internetes linkeket, melyeket QR-kódok formájában adunk meg. A QR-kódok okostelefonnal azonnal aktív linkekre fordíthatók