Delta and theta activity during slow-wave sleep are associated with declarative but not with non-declarative learning in children with sleep-disordered breathing

info:eu-repo/semantics/publishe

Employment status and health related quality of life among Hodgkin-lymphoma survivors'- results based on data from a major treatment center in Hungary

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Kynurenic Acid and Its Analog SZR104 Exhibit Strong Antiinflammatory Effects and Alter the Intracellular Distribution and Methylation Patterns of H3 Histones in Immunochallenged Microglia-Enriched Cultures of Newborn Rat Brains

Kynurenic acid (KYNA) is implicated in antiinflammatory processes in the brain through several cellular and molecular targets, among which microglia-related mechanisms are of paramount importance. In this study, we describe the effects of KYNA and one of its analogs, the brain-penetrable SZR104 (N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-hydroxyquinoline-2-carboxamide), on the intracellular distribution and methylation patterns of histone H3 in immunochallenged microglia cultures. Microglia-enriched secondary cultures made from newborn rat forebrains were immunochallenged with lipopolysaccharide (LPS). The protein levels of selected inflammatory markers C-X-C motif chemokine ligand 10 (CXCL10) and C-C motif chemokine receptor 1 (CCR1), histone H3, and posttranslational modifications of histone H3 lys methylation sites (H3K9me3 and H3K36me2, marks typically associated with opposite effects on gene expression) were analyzed using quantitative fluorescent immunocytochemistry and western blots in control or LPS-treated cultures with or without KYNA or SZR104. KYNA and SZR104 reduced levels of the inflammatory marker proteins CXCL10 and CCR1 after LPS-treatment. Moreover, KYNA and SZR104 favorably affected histone methylation patterns as H3K9me3 and H3K36me2 immunoreactivities, and histone H3 protein levels returned toward control values after LPS treatment. The cytoplasmic translocation of H3K9me3 from the nucleus indicated inflammatory distress, a process that could be inhibited by KYNA and SZR104. Thus, KYNA signaling and metabolism, and especially brain-penetrable KYNA analogs such as SZR104, could be key targets in the pathway that connects chromatin structure and epigenetic mechanisms with functional consequences that affect neuroinflammation and perhaps neurodegeneration

Structure and Function of Enterocyte in Intrauterine Growth Retarded Pig Neonates

The intestine of intrauterine growth retarded (IUGR) neonates showed different morphology compared to neonates born with normal body weight (NBW). The aim of the present study was to investigate the ultrastructure and proteomic profile of the gut epithelium in IUGR pig neonates with special attention to the digestive and absorptive function. Intestine tissue samples were investigated in 7-day-old IUGR and NBW littermate piglets using histometry, immunofluorescence, scanning electron microscopy (SEM), and mass spectrometry analysis. IUGR piglets have shown reduced mucosa and muscularis thickness and an enhanced number of foetal type enterocytes (FTE). SEM studies have shown the lack of the characteristic large-size vacuole in IUGR’s enterocytes. Delayed removal of FTE in IUGR neonates was probably due to the inhibited apoptosis in the apical part of villi and increased apoptosis and reduced mitosis in the crypt region. In the expression of proteins in the intestinal mucosa such as hexokinase I, histones, and prelamin A/C, carbamoyl phosphate was reduced in IUGR neonates. Finally, IUGR intestines showed higher expression of HSPA9 and HSPA5 as apoptosis markers. The data indicate modifications of gut mucosa in IUGRs that may result in slower gut mucosa maturation and reduced utilisation of nutrient as compared to NBW pig neonates

Perception, understanding, and action: attitudes of climate change in the Hungarian population

This study is based on a non-representative, national level survey sample whose main purpose is to interpret the general population’s understanding of climate change. The study also provides an examination of correlations between climate change concerns and the taking of individual action as well as the relationship between pro-environmental thinking and climate change scepticism. Our results show a moderate correlation between the general population’s concerns and the professional views on the subject, known in the literature as the New Environmental Paradigm scale and Scepticism scale, but a significantly weaker correlation when it comes to taking action against climate change. Factors relating to the respondents, such as residence settlement type, education level, gender, age, personal and social values, or casual attributions in relation to climate change heavily influence this weaker correlation. Most respondents assessed climate change as a current (urgent), but geographically remote phenomenon. This is a clear indication of problems associated with cognitive conceptualization and the localization of climate change in communication. The target audience must be taken into account when designing climate change communications because interpretations of climate change can vary widely and cover a broad range attitudes ranging from concern about to issue all the way to climate change scepticism. This also applies to views concerning responsibility for climate change with some believing it is a political responsibility and others believing it is a scientific responsibility

CHARACTERIZATION OF Pseudomonas syringae pv. morsprunorum ORIGINATING FROM SWEET CHERRY AND PLUM IN SERBIA

Pseudomonas strains originating from symptomatic (bacterial spot) leaf tissues of sweet cherry (Topola, Šumadija) and plum (Krušedol Selo, Srem) were isolated during 2016 and 2020, respectively. Based on the findings yielded by classical microbiological methods, LOPAT (+---+), GATTa (--++) and pathogenicity tests performed on detached fruitlets (sweet and sour cherry) and pods (bean pods), all strains were confirmed to belong to P. syringae pv. morsprunorum. The detection of cfl gene allowed strains that belong to race 1 to be identified. The DNA fingerprinting patterns obtained with four rep-PCR (BOX and ERIC), RAPD-PCR (M13), and IS50-PCR (IS50) methods revealed that the seven tested sweet cherry and plum P. s. pv. morsprunorum strains, as well as comparative KBNS71 and the reference strain CFBP 2119, were genetically heterogeneous. Conversely, MLSA based on the four-gene-based scheme (gapA, gltA, gyrB, and rpoD) indicated genetic homogeneity among all tested Serbian sweet cherry and plum strains, as well as P. s. pv. morsprunorum race 1 strains from the NCBI. Although the MLSA findings indicate that the sweet cherry and plum strains used in this study are 100% identical, as they might have different virulence genes, genome sequencing should be performed to eventually find the strain sub-clades based on the host

Calmodulin as Ca2+-Dependent Interactor of FTO Dioxygenase

FTO is an N(6)-methyladenosine demethylase removing methyl groups from nucleic acids. Several studies indicate the creation of FTO complexes with other proteins. Here, we looked for regulatory proteins recognizing parts of the FTO dioxygenase region. In the Calmodulin (CaM) Target Database, we found the FTO C-domain potentially binding CaM, and we proved this finding experimentally. The interaction was Ca(2+)-dependent but independent on FTO phosphorylation. We found that FTO–CaM interaction essentially influences calcium-binding loops in CaM, indicating the presence of two peptide populations—exchanging as CaM alone and differently, suggesting that only one part of CaM interacts with FTO, and the other one reminds free. The modeling of FTO–CaM interaction showed its stable structure when the half of the CaM molecule saturated with Ca(2+) interacts with the FTO C-domain, whereas the other part is disconnected. The presented data indicate calmodulin as a new FTO interactor and support engagement of the FTO protein in calcium signaling pathways

Cross-sectional comparison of health care delivery and reimbursement between segregated and nonsegregated communities in Hungary

IntroductionSpatially segregated, socio-economically deprived communities in Europe are at risk of being neglected in terms of health care. In Hungary, poor monitoring systems and poor knowledge on the health status of people in these segregated areas prevent the development of well-informed effective interventions for these vulnerable communities.AimsWe used data available from National Health Insurance Fund Management to better describe health care performance in segregated communities and to develop more robust monitoring systems.MethodsA cross-sectional study using 2020 health care data was conducted on each general medical practice (GMP) in Hungary providing care to both segregated and nonsegregated (complementary) adult patients. Segregated areas were mapped and ascertained by a governmental decree that defines them as within settlement clusters of adults with low level of education and income. Age, sex, and eligibility for exemption certificate standardized indicators for health care delivery, reimbursement, and premature mortality were computed for segregated and nonsegregated groups of adults and aggregated at the country level. The ratio of segregation and nonsegregation specific indicators (relative risk, RR) was computed with the corresponding 95% confidence intervals (95% CI).ResultsBroad variations between GMPs were detected for each indicator. Segregated groups had a significantly higher rate of health care service use than complementary groups (RR = 1.22, 95% CI: 1.219;1.223) while suffering from significantly reduced health care reimbursement (RR = 0.940, 95% CI: 0.929;0.951). The risk of premature mortality was significantly higher among segregated patients (RR = 1.184, 95% CI: 1.087;1.289). Altogether, living in a segregated area led to an increase in visits to health care services by 18.1% with 6.6% less health spending.ConclusionAdults living in segregated areas use health care services more frequently than those living in nonsegregated areas; however, the amount of health care reimbursement they receive is significantly lower, suggesting lower quality of care. The health status of segregated adults is remarkably lower, as evidenced by their higher premature mortality rate. These findings demonstrate the need for intervention in this vulnerable group. Because our study reveals serious variation across GMPs, segregation-specific monitoring is necessary to support programs sensitive to local issues and establish necessary benchmarks

ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy

The nine identified human homologues of E. coli AlkB 2-oxoglutarate (2OG) and Fe(II)-dependent dioxygenase, ALKBH1-8 and FTO, display different substrate specificities and diverse biological functions. Here we discovered the combined overexpression of members of the ALKBH family in head and neck squamous cell carcinomas (HNSCC). We found direct correlation of ALKBH3 and FTO expression with primary HNSCC tumor size. We observed unidentified thus far cytoplasmic localization of ALKBH2 and 5 in HNSCC, suggesting abnormal role(s) of ALKBH proteins in cancer. Further, high expression of ALKBHs was observed not only in HNSCC, but also in several cancerous cell lines and silencing ALKBH expression in HeLa cancer cells resulted in dramatically decreased survival. considering the discovered impact of high expression of ALKBH proteins on HNSCC development, we screened for ALKBH blockers among newly synthetized anthraquinone derivatives and demonstrated their potential to support standard anticancer therapy

New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project

In the European regulatory context, rodent in vivo studies are the predominant source of neurotoxicity information. Although they form a cornerstone of neurotoxicological assessments, they are costly and the topic of ethical debate. While the public expects chemicals and products to be safe for the developing and mature nervous systems, considerable numbers of chemicals in commerce have not, or only to a limited extent, been assessed for their potential to cause neurotoxicity. As such, there is a societal push toward the replacement of animal models with in vitro or alternative methods. New approach methods (NAMs) can contribute to the regulatory knowledge base, increase chemical safety, and modernize chemical hazard and risk assessment. Provided they reach an acceptable level of regulatory relevance and reliability, NAMs may be considered as replacements for specific in vivo studies. The European Partnership for the Assessment of Risks from Chemicals (PARC) addresses challenges to the development and implementation of NAMs in chemical risk assessment. In collaboration with regulatory agencies, Project 5.2.1e (Neurotoxicity) aims to develop and evaluate NAMs for developmental neurotoxicity (DNT) and adult neurotoxicity (ANT) and to understand the applicability domain of specific NAMs for the detection of endocrine disruption and epigenetic perturbation. To speed up assay time and reduce costs, we identify early indicators of later-onset effects. Ultimately, we will assemble second-generation developmental neurotoxicity and first-generation adult neurotoxicity test batteries, both of which aim to provide regulatory hazard and risk assessors and industry stakeholders with robust, speedy, lower-cost, and informative next-generation hazard and risk assessment tools