The improvement of the efficiency of logistics services in touristic industry at regional level

Green rural tourism is an effective instrument for workplaces creation and regional infrastructure development. The article explores the main types of rural tourism.          The peculiarities of tourist services on the territory of the „Kremenchuk Plavni” landscape park have been analyzed.  Some measures concerning the improvement of the efficiency of logistics services in touristic industry at regional level hav been proposed.Key words: rural green tourism, price strategy, rural tourism service, green tourism issue, the plant and animal world, logistics services, regional level

NEW TARGET GENES FOR TUMOR SUPPRESSORS p53 AND p73 IN REGENERATING LIVER

The p53-family of proteins regulates expression of target genes during tissue development and differentiation. Within the p53-family, p53 and p73 have hepatic-specific functions in development and tumor suppression. Despite a growing list of p53/p73 target genes, very few of these have been studied in vivo, and the knowledge regarding functions of p53 and p73 in normal tissues remains limited. p53+/-p73+/- mice develop hepatocellular carcinoma (HCC), whereas overexpression of p53 in human HCC leads to tumor regression. However, the mechanism of p53/p73 function in liver remains poorly characterized. Here, the model of mouse liver regeneration is used to identify new target genes for p53/p73 in normal quiescent vs. proliferating cells. In response to surgical removal of ~2/3 of liver mass (partial hepatectomy, PH), the remaining hepatocytes exit G0 of cell cycle and undergo proliferation to reestablish liver mass. The hypothesis tested in this work is that p53/p73 functions in cell cycle arrest, apoptosis and senescence are repressed during liver regeneration, and reactivated at the end of the regenerative response. Chromatin immunoprecipitation (ChIP), with a p73-antibody, was used to probe arrayed genomic sequences (ChIP-chip) and uncover 158 potential targets of p73-regulation in normal liver. Global microarray analysis of mRNA levels, at T=0-48h following PH, revealed sets of genes that change expression during regeneration. Eighteen p73-bound genes changed expression after PH. Four of these genes, Foxo3, Jak1, Pea15, and Tuba1 have p53 response elements (p53REs), identified in silico within the upstream regulatory region. Forkhead transcription factor Foxo3 is the most responsive gene among transcription factors with altered expression during regenerative, cellular proliferation. p53 and p73 bind a Foxo3 p53RE and maintain active expression in quiescent liver. During liver regeneration, binding of p53 and p73, recruitment of acetyltransferase p300, and an active chromatin structure of Foxo3 are disrupted, alongside loss of Foxo3 expression. These parameters of Foxo3 regulation are reestablished at completion of liver growth and regeneration, supporting a temporary suspension of p53 and p73 regulatory functions in normal cells during tissue regeneration

Influence of non-monetary information signals of the USA on the Ukrainian stock market volatility

The Ukrainian PFTS stock index volatility reaction as a whole and its constituent economic sectors (“Basic Materials”, “Financials”, “Industrials”, “Oil & Gas”, “Telecommunications”, “Utilities”) to seven non-monetary US information signals (“Consumer price index”, “Personal spending”, “Unemployment rate”, “Gross domestic product”, “Industrial production”, “Consumer confidence”, “Housing starts”) was carried out for the period 2000–2017 on the basis of closing stock quotations in the trading day format. To assess the “surprise” component direct influence nature of the USA selected non-monetary information signals on the PFTS stock index, an AR-GARCH econometric modelling device was used. The results achieved clearly indicate the presence of some PFTS stock index economic sectors heterogeneous reaction to the United States individual non-monetary information signals announcement. For example, such economic sectors as “Basic Materials”, “Financials”, and “Oil & Gas” volatility response to the US non-monetary information signal “Consumer price index” “surprise” components the opposite of the overall PFTS stock index reaction. It can also be concluded that the United States non-monetary information signals influence on the Ukrainian stock market volatility depends not only on the financial cycle phase and data frequency, but also on the PFTS stock index economic sector

Psycho-emotional states of future specialists in a socionomic area under lockdown and martial law: comparative analysis

The aim of the study is to perform comparative analysis of dominating psycho-emotional states of future specialists in a socionomic area under lockdown and martial law. A verification strategy is suggested for examining psycho-emotional states. The research used participant observation, valid and reliable psycho-diagnostic instruments, factor analysis, coefficients of empirical data reliability. It was established that in the comparison of the selected complex of psychological content parameters Group 1 (under lockdown) and Group 2 (under martial law) there are no significant differences. Two factor structures of the respondents’ psycho-emotional states were created: one of them – during the ongoing COVID-19 pandemic (59.91%) and the other – during the martial law (69.89%). It was found out that the obtained data on psycho-emotional states during the lockdown and the martial law are essentially different that did not allow determining or disproving significant differences by means of statistical coefficients. The study substantiated that the established empirical facts are characterized by scientific novelty which should be taken into consideration by organizers of educational and professional training for specialists in a socionomic area

Psychological well-being of children with special educational needs under martial law

Purpose is to examine psychological features of the impact of military actions on the emotional-volitional sphere of children with special educational needs; obtain scientific facts which will allow developing a system of support for parents and professionals working with such children. Two significant correlations were established: psychological well-being (PWB) with emotional state and mood (ES&M) (rs=-.289; р≤.01) and with the measurement “unchangeable” (U) (rs=.084; р≤.05). The study explains that significant differences in the emotional-volitional sphere have a negative effect on children’s psychological well-being. The second correlation signalizes the protection of children with special educational needs from psychological traumatic experience and creation of a favorable inclusive space. The research substantiates that psychological aid for sufferers of the war aggression is a permanent resource support, that can be provided for a long time. It has its favorable period and is capable of preventing serious complications

Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2

Gene duplication is a powerful driver of evolution. Newly duplicated genes acquire new roles that are relevant to fitness, or they will be lost over time. A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution.Institute for Diabetes, Obesity and Metabolism. Diabetes Research Center (Functional Genomics Core P30-DK19525

Interaction of the NRF2 and p63 transcription factors promotes keratinocyte proliferation in the epidermis

Epigenetic regulation of cell and tissue function requires the coordinated action of transcription factors. However, their combinatorial activities during regeneration remain largely unexplored. Here, we discover an unexpected interaction between the cytoprotective transcription factor NRF2 and p63-a key player in epithelial morphogenesis. Chromatin immunoprecipitation combined with sequencing and reporter assays identifies enhancers and promoters that are simultaneously activated by NRF2 and p63 in human keratinocytes. Modeling of p63 and NRF2 binding to nucleosomal DNA suggests their chromatin-assisted interaction. Pharmacological and genetic activation of NRF2 increases NRF2-p63 binding to enhancers and promotes keratinocyte proliferation, which involves the common NRF2-p63 target cyclin-dependent kinase 12. These results unravel a collaborative function of NRF2 and p63 in the control of epidermal renewal and suggest their combined activation as a strategy to promote repair of human skin and other stratified epithelia

Release of miR-29 Target Laminin C2 Improves Skin Repair

miRNAs are small noncoding RNAs that regulate mRNA targets in a cell-specific manner. miR-29 is expressed in murine and human skin, where it may regulate functions in skin repair. Cutaneous wound healing model in miR-29a/b1 gene knockout mice was used to identify miR-29 targets in the wound matrix, where angiogenesis and maturation of provisional granulation tissue was enhanced in response to genetic deletion of miR-29. Consistently, antisense-mediated inhibition of miR-29 promoted angiogenesis in vitro by autocrine and paracrine mechanisms. These processes are likely mediated by miR-29 target mRNAs released upon removal of miR-29 to improve cell–matrix adhesion. One of these, laminin (Lam)-c2 (also known as laminin γ2), was strongly up-regulated during skin repair in the wound matrix of knockout mice. Unexpectedly, Lamc2 was deposited in the basal membrane of endothelial cells in blood vessels forming in the granulation tissue of knockout mice. New blood vessels showed punctate interactions between Lamc2 and integrin α6 (Itga6) along the length of the proto-vessels, suggesting that greater levels of Lamc2 may contribute to the adhesion of endothelial cells, thus assisting angiogenesis within the wound. These findings may be of translational relevance, as LAMC2 was deposited at the leading edge in human wounds, where it formed a basal membrane for endothelial cells and assisted neovascularization. These results suggest a link between LAMC2, improved angiogenesis, and re-epithelialization

C6-ceramide synergistically potentiates the anti-tumor effects of histone deacetylase inhibitors via AKT dephosphorylation and α-tubulin hyperacetylation both in vitro and in vivo

Histone deacetylase inhibitors (HDACIs) have shown promising anti-tumor effects for a variety of malignancies, however, many tumors are reportedly resistant to them. In this study, we made a novel discovery that co-administration of HDACIs (Trichostatin A (TSA) and others) and exogenous cell-permeable short-chain ceramide (C6) results in striking increase in cancer cell death and apoptosis in multiple cancer cells. These events are associated with perturbations in diverse cell signaling pathways, including inactivation of Akt/mTOR and increase in α-tubulin acetylation (both in vivo and in vitro). TSA interacts in a highly synergistic manner with C6-ceramide to disrupt HDAC6/protein phosphatase 1 (PP1)/tubulin complex, to induce α-tubulin hyperacetylation, and to release and activate PP1, which then leads to AKT dephosphorylation and eventually causes cancer cell death. Interestingly, TSA itself results in short-term ceramide accumulation, which as a result of metabolic (glycosylation) removal, does not result in evident increase of cancer cell death. However, adding C6-ceramide led to a very pronounced increase in ceramide level and marked increase in cell death. Importantly, the effective synergistic anti-tumor activity of TSA plus C6-ceramide is also seen in in vivo mice xenograft pancreatic and ovarian cancer models, indicating that this regimen (HDACI plus C6-ceramide) may represent a more effective form of therapy against pancreatic and ovarian carcinoma