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Various pregnancy complications, such as severe forms of preeclampsia or intrauterine growth restriction, are thought to arise from failures in the differentiation of human placental trophoblasts. Progenitors of the latter either develop into invasive extravillous trophoblasts, remodeling the uterine vasculature, or fuse into multinuclear syncytiotrophoblasts transporting oxygen and nutrients to the growing fetus. However, key regulatory factors controlling trophoblast self-renewal and differentiation have been poorly elucidated. Using primary cells, three-dimensional organoids, and CRISPR-Cas9 genome-edited JEG-3 clones, we herein show that YAP, the transcriptional coactivator of the Hippo signaling pathway, promotes maintenance of cytotrophoblast progenitors by different genomic mechanisms. Genetic or chemical manipulation of YAP in these cellular models revealed that it stimulates proliferation and expression of cell cycle regulators and stemness-associated genes, but inhibits cell fusion and production of syncytiotrophoblast (STB)-specific proteins, such as hCG and GDF15. Genome-wide comparisons of primary villous cytotrophoblasts overexpressing constitutively active YAP-5SA with YAP KO cells and syncytializing trophoblasts revealed common target genes involved in trophoblast stemness and differentiation. ChIP-qPCR unraveled that YAP-5SA overexpression increased binding of YAP–TEAD4 complexes to promoters of proliferation-associated genes such as CCNA and CDK6. Moreover, repressive YAP–TEAD4 complexes containing the histone methyltransferase EZH2 were detected in the genomic regions of the STB-specific CGB5 and CGB7 genes. In summary, YAP plays a pivotal role in the maintenance of the human placental trophoblast epithelium. Besides activating stemness factors, it also directly represses genes promoting trophoblast cell fusion.

While it is generally believed that the basic unit of territorial competitiveness is the firm, existing country level and regional competitiveness measures focus on the widely interpreted institutional aspects of competitiveness and neglect individual (firm) level characteristics. The theoretical concepts are also separated. One can find institutional and individual theories, but they are not related to each other. Popular competitiveness indices are based on institutional factors. Reflecting to this contradiction, we have created a new index that combines institutional aspects and individual competencies in a systemic way to measure regional competitiveness more correctly (highlights SME sector).

Ebben a tanulmányban bemutatjuk a kompetencia- és intézményi versenyképességi indexet (KIVI), amely a kisvállalati versenyképesség vizsgálatának új kompozit indikátora. A módszertan az egyéni vállalati kompetenciákat, valamint az intézményi és iparági tényezőket egyaránt magában foglalja, ezáltal alkalmas a kisvállalatok külső-belső működési környezetének komplex mérésére, valamint vállalatok és területi egységek értékelésére is. A versenyképességet városagglomerációs szinten mérjük, amelyet a területi különbségekből adódó eltérések vizsgálatára alkalmas, valós gazdasági térségnek tekintünk. Az intézményi és iparági változók kialakításánál a cégekre ható externális, agglomerációs tényezők 110 indikátorát használtunk fel, közülük számos saját fejlesztésű mutatót. A vállalati szintű adatokat a Kisvállalati Versenyképességi Index (KVI) módszertana alapján kalkuláltuk. A végső mintába 1283 kis- és középvállalat és 20 városagglomeráció került be. Míg az intézményi változók jól korrelálnak az agglomeráció fejlettségi szintjével, addig ilyen kapcsolat az egyéni tényezőkkel nincsen, ami azt jelenti, hogy a versenyképesség környezeti tényezői és az összesített vállalati egyéni kompetenciák nem feltétlenül mozognak azonos pályán. A KIVI alkalmazásának empirikus demonstrálása érdekében - az összesített adatok bemutatását követően - három városrégiót (Budapest, Pécs, Nyíregyháza) részletesen is elemzünk.

Background: An increasing number of studies suggest that diet plays an important role in regulating aging processes and modulates the development of the most important age-related diseases. Objective: The aim of this review is to provide an overview of the relationship between nutrition and critical age-associated diseases. Methods: A literature review was conducted to survey recent pre-clinical and clinical findings related to the role of nutritional factors in modulation of fundamental cellular and molecular mechanisms of aging and their role in prevention of the genesis of the diseases of aging. Results: Studies show that the development of cardiovascular and cerebrovascular diseases, neurodegenerative diseases, cognitive impairment and dementia can be slowed down or prevented by certain diets with anti-aging action. The protective effects of diets, at least in part, may be mediated by their beneficial macro- (protein, fat, carbohydrate) and micronutrient (vitamins, minerals) composition. Conclusions: Certain diets, such as the Mediterranean diet, may play a significant role in healthy aging by preventing the onset of certain diseases and by improving the aging process itself. This latter can be strengthened by incorporating fasting elements into the diet. As dietary recommendations change with age, this should be taken into consideration as well, when developing a diet tailored to the needs of elderly individuals. Future and ongoing clinical studies on complex anti-aging dietary interventions translating the results of preclinical investigations are expected to lead to novel nutritional guidelines for older adults in the near future.

This study investigated the presence and levels of five key mycotoxins—aflatoxins (AFs), deoxynivalenol (DON), fumonisin B1 (FB1), ochratoxin-A (OTA), and zearalenone (ZEN) and its metabolite alpha-zearalenol (α-ZOL)—in liver samples from 19 golden jackals (Canis aureus) in southern Hungary. Golden jackals, as apex predators with a diverse diet encompassing both plant and animal matter, can serve as valuable bioindicators of environmental mycotoxin contamination. Genetic analysis confirmed the canid samples as coming from golden jackals, excluding the possibility of domestic dogs or hybrid individuals. All samples tested positive for at least three mycotoxins, with multiple mycotoxins frequently co-occurring. DON was detected in 95% of the samples, followed by FB1 (79%) and ZEN (42%). ZOL, AFs, and OTA were present in all samples. Significant differences in mycotoxin concentrations were observed between age groups and sexes for some mycotoxins. Specifically, adult males exhibited higher ZEN concentrations, adult females had higher OTA levels, and females generally showed significantly higher DON concentrations than males. For all investigated individuals, we found significantly higher concentrations of ZEN, alpha-ZOL, and OTA in adult samples. Malondialdehyde (MDA), an indicator of oxidative stress, was also measured and correlated with mycotoxin levels. Pareto analysis suggested a correlation between MDA and OTA/ZEN. These findings highlight the exposure of golden jackals to a range of mycotoxins in their natural environments, potentially through both plant and animal food sources, and underscore the potential of these canids as sentinels for mycotoxin contamination in ecosystems.

Currently, an increasing amount of evidence supports the notion that vitamins C, D and E, carotenoids, and omega-3 fatty acids may protect against the progression of chronic respiratory diseases. Although chronic obstructive pulmonary disease (COPD) primarily affects the lung, it is often accompanied by extrapulmonary manifestations such as weight loss and malnutrition, skeletal muscle dysfunction, and an excess of harmful oxidants, which can lead to a decline in quality of life and possible death. Recently, the role of various vitamins, minerals, and antioxidants in mitigating the effects of environmental pollution and smoking has received significant attention. Therefore, this review evaluates the most relevant and up-to-date evidence on this topic. We conducted a literature review between 15 May 2018 and 15 May 2023, using the electronic database PubMed. Our search keywords included COPD, chronic obstructive pulmonary disease, FEV1, supplementation: vitamin A, vitamin D, vitamin E, vitamin C, vitamin B, omega-3, minerals, antioxidants, specific nutrient supplementations, clinical trials, and randomized controlled trials (RCTs). We focused on studies that measured the serum levels of vitamins, as these are a more objective measure than patient self-reports. Our findings suggest that the role of appropriate dietary supplements needs to be reconsidered for individuals who are predisposed to or at risk of these conditions.

Allele-specific expression (ASE) reflects the unequal expression of the parental alleles and can imply functional variants in cis-regulatory elements. The conventional ASE detection methods often depend on the presence of heterozygous variants in transcripts or sequencing a large number of individuals, both of which are often limited. In this study, we present a family-based strategy for detecting ASE and potential cis-regulatory elements utilizing both RNA-seq and whole-genome sequencing (WGS) from a pedigree. Using a rabbit family consisting of two divergent parents and their eight offspring, we identified 913 ASE genes by analyzing inheritance patterns of gene expression levels. Expression was classified into three levels—high, medium, and low—and used to define seven distinct expression groups across the family (e.g., H_L: high in the mother, low in the father, and intermediate in the offspring). Many ASE genes lacked heterozygous exonic variants, and inference was achieved via RNA read count patterns. We also pinpointed conserved transcription factor binding sites (TFBS) with sequence variants showing similar inherited genotypic patterns (e.g., AAxBB), suggesting their regulatory roles as eQTLs. Differential gene expression (DEG) analysis between the parents highlighted some candidate genes related to meat production and quality traits. Our findings show that the family-based method using RNA-seq and WGS data is promising for exploring ASE and mapping possible eQTLs.

Although their pathogenicity is most often unclear, some canine viruses have been found to infect carnivores other than dogs. This study relies on the surveillance of coronaviruses in 206 saliva and fecal samples of huntable, sympatric canid and mustelid species captured in Hungary, such as the native red fox ( Vulpes vulpes ), European badger ( Meles meles ), golden jackal ( Canis aureus ), and stone marten ( Martes foina ), as well as the recently settled alien raccoon dog ( Nyctereutes procyonoides ). Metagenomics‐based and direct sequence analysis were deployed to determine the genome sequence of coronaviruses identified in two specimens collected from red foxes. Near‐complete genome sequences of two canine coronaviruses (CCoVs) were obtained, together with the complete genome sequence of a canine circovirus (CanineCV) and the near‐complete genome sequence of a canine picodicistrovirus (CPDV) from one of the samples. These provided the first fox origin CCoV and CPDV sequence data, and the first recorded appearance of the CPDV in Europe. The results suggested that recombination is of great importance in the evolution of CCoV, CanineCV, and CPDV infecting dogs and wild‐living carnivores, including the red fox and golden jackal. These are widespread in Central and Southeast Europe, and have large ranges, facilitating transmission of the multihost canine pathogens.

Background West Nile virus (WNV) infections have become increasingly prevalent in certain European countries, including Hungary. Although most human infections do not cause severe symptoms, in approximately 1% of cases WNV infections can lead to severe WNV neuroinvasive disease (WNND) and death. The goal of our study was to assess the neurological status changes of WNV –infected patients admitted to inpatient care and to identify potential risk factors as underlying reasons for severe neurological outcome. Methods We conducted a retrospective chart review of 66 WNV-infected patients from four Hungarian medical centers. Patients’ neurological status at hospital admission and at two follow-up intervals (1st follow-up, within 60–90 days and 2nd follow-up, within 150–180 days, after hospital discharge) were assessed. All of the 66 patients in the initial sample had some type of neurological symptoms and 56 patients were diagnosed with WNND. The modified Rankin Scale (mRS) and the West Nile Virus Neurological Index (WNV-N Index), a scoring system designed for the purpose of this study, were used for neurological status assessment. Patients were dichotomized into two categories, “moderately severe” and “severe” based on their neurological status. Descriptive analysis for sample description, stratified analysis for calculation of odds ratio (OR) and logistic regression for continuous input variables, were performed. Results The average number of days between the onset of neurological symptoms and hospital admission (the neurological symptom interval) was 6.01 days. Complications during the hospital stay arose in almost a fifth of the patients (18.2%) and 5 patients died. Each day’s increase in the neurological symptom interval significantly increased the risk for developing a severe neurological status following hospital admission (0.799-fold and 0.688-fold, based on the WNV-N Index and mRS, respectively). Patients’ age, comorbidity, presence of complications and symptoms of malaise, and gait uncertainty were shown to be independent risk factors for severe neurological status. Conclusions Timely hospital admission of patients with neurological symptoms as well as risk assessment by clinicians - possibly with an optimal assessment tool for estimating neurological status- could improve the neurological outcome of WNV-infected patients.

The European rabbit exists in the wild and has several highly bred domesticated forms. There are well-separated wild European rabbit populations, and intensive breeding has resulted in various forms and utilizations. In this work, we aimed to carry out an extended WGS-based population genomics study on several wild European rabbit populations and selected breeds. Utilizing multiple methods, we showed that although domestic and wild populations were clearly separated, there was evidence of admixture between them in France and Hungary. The populations showed various levels of inbreeding, with one of the Hungarian subpopulations having excess runs of homozygosity. We identified numerous variants fixed in either domestic or wild animals, two of which were found to be fixed at different alleles in the two populations. Some putatively selected regions did not overlap with any known genes in the rabbit genome, suggesting some importance to these intergenic sites. The enrichment of selected regions in certain types of transcription factor binding sites suggests a possible role for these regulatory elements during domestication. In addition, the new high-coverage rabbit whole-genome sequences may provide helpful material for further population genetics analyses.