Twist: A Regulator of Epithelial-Mesenchymal Transition in Lung Fibrosis

BACKGROUND: Several studies have implicated viral infection as an important factor in the pathogenesis of IPF and related fibrotic lung disorders. Viruses are thought to cause epithelial cell injury and promote epithelial-mesenchymal transition (EMT), a process whereby differentiated epithelial cells undergo transition to a mesenchymal phenotype, and considered a source of fibroblasts in the setting of lung injury. We have demonstrated an association between the epithelial injury caused by chronic herpes virus infection with the murine gamma-herpes virus, MHV68, and lung fibrosis. We hypothesize that EMT in this model of virus-induced pulmonary fibrosis is driven by the expression of the transcription factor Twist. METHODS/FINDINGS: In vitro MHV68 infection of murine lung epithelial cells induced expression of Twist, and mesenchymal markers. Stable overexpression of Twist promoted EMT in MLE15 lung epithelial cells. Transient knockdown expression of Twist resulted in preservation of epithelial phenotype after in vitro MHV68 infection. In concordance, high expression of Twist was found in lung epithelial cells of MHV68 infected mice, but not in mock infected mice. Alveolar epithelial cells from lung tissue of idiopathic pulmonary fibrosis (IPF) patients were strongly positive for Twist. These cells demonstrated features of EMT with low expression of E-cadherin and upregulation of the mesenchymal marker N-cadherin. Finally, IPF tissue with high Twist protein levels was also positive for the herpesvirus, EBV. CONCLUSIONS/SIGNIFICANCE: We conclude that Twist contributes to EMT in the model of virus-induced pulmonary fibrosis. We speculate that in some IPF cases, gamma-herpes virus infection with EBV might be a source of injury precipitating EMT through the expression of Twist

Study of the value orientations and soft skills in modern senior high school students (in the context of the doctrine of sustainable development)

The concept of sustainable development involves maintaining the stability of social systems through the development of human capital. The formation of values and universal skills of the youth population is an important component of human capital. The article studies the problem of the universal readiness of school leavers for academic activity and professional labor that is expressed by the degree of formation of value orientations, which are the basis for non-specialized soft skills. The level of development of soft skills of senior high school students in modern comprehensive schools, that ensures the behavioral characteristics of self-organization and work ethics, depends on the values they share, which were studied using the survey method. The randomized survey of senior high school students in Rostov region (N = 4037, 59.3% of girls), carried out in 2019, was aimed at identification of the elements of social collectivism - social egoism in the minds of young people and normative - deviant components of behavior motivation. The studied value orientations of young people were re-duced to social-cognitive elements and attitudes. The authors proceeded from the fact that evident social collectivism - social egoism is directly associated with manifestations of normative / deviant behavior. As a result of processing of the data obtained, a quantitative analysis and explication of the development of value orientations and soft skills in the field of work and organizational ethics of the modern contingent of secondary school students was represented, what made it possible to formulate the preferential directions of pedagogic work

The Interrelationship between Coping Strategies and Socio-Psychological Competency of University Students’ Personality

In contemporary society characterized by socio-economic and political instability, the problem of studying the factors and mechanisms that contribute to the constructive resolution of life difficulties and counteracting their negative consequences is very important. This paper contains the results of an empirical study of the characteristics and relationships of students’ coping behavior with different levels of their socio-psychological competency. The research methods comprised the following: theoretical analysis, empirical research (testing), qualitative analysis of the obtained data, mathematical and statistical data processing (SPSS Statistics, Excel). The characteristics of indicators of socio-psychological competency were determined with the use of the technique for assessing socio-communicative competency, as well as a questionnaire that reveals the possibility of using socio-psychological skills by a person in difficult life situations. To study coping behavior, the following were used: “The ways of coping questionnaire” and “The youth coping scale”. The validity and reliability of the research results was ensured by the initial methodological positions, the use of tested tools, representativeness of the research sample, as well as mathematical processing of data with the help of software package for statistical analysis. The conclusions have been drawn that the basis of constructive mechanisms to overcome difficult life situations is a high level of formation of professional skills and abilities, introversion, motivation to achieve success, high intellectual development, moral standards, a high level of development of communication skills. It is these mechanisms that make it possible to resolve problem situations and tasks at work in a productive way. Their absence or a low level of development contributes to the dominance of situational methods of overcoming difficult life situations that impede professional formation and personal development

Digital model of psychophysiological support for university students

The paper presents a digital model of psychophysiological support for students, organized at various sites of the university. The digital model of psychophysiological support includes a set of procedures and activities aimed at ensuring the impact and support of health indicators, biological functions of homeostasis, and the psychophysiological well-being of students. Among the components of the digital model is the innovative project “Online Curator”, which contains a step-by-step description of the sequence of pedagogical actions of curators of student groups, which are based on the constantly updated information resource “Electronic methodological library”. Pedagogical actions are carried out by curators based on the results of annual monitoring and identification of risk groups among the students. Typical problems of students identified during testing in 2021 were problems of the emotional and personal sphere; communication problems; intrapersonal problems and difficulties of adaptation. The resource “Electronic methodological library” described in the paper is an original bank of methodological information designed to improve the psychological and pedagogical competence of curators and to directly organize a variety of extracurricular work with students. The inclusion of the curator’s figure in collective and individual activities for the psychological support of students using IS resources allows him to effectively carry out socializing, preventive, regulatory functions, providing effective support for the psychological well-being of students

Ising Universality in Three Dimensions: A Monte Carlo Study

We investigate three Ising models on the simple cubic lattice by means of Monte Carlo methods and finite-size scaling. These models are the spin-1/2 Ising model with nearest-neighbor interactions, a spin-1/2 model with nearest-neighbor and third-neighbor interactions, and a spin-1 model with nearest-neighbor interactions. The results are in accurate agreement with the hypothesis of universality. Analysis of the finite-size scaling behavior reveals corrections beyond those caused by the leading irrelevant scaling field. We find that the correction-to-scaling amplitudes are strongly dependent on the introduction of further-neighbor interactions or a third spin state. In a spin-1 Ising model, these corrections appear to be very small. This is very helpful for the determination of the universal constants of the Ising model. The renormalization exponents of the Ising model are determined as y_t = 1.587 (2), y_h = 2.4815 (15) and y_i = -0.82 (6). The universal ratio Q = ^2/ is equal to 0.6233 (4) for periodic systems with cubic symmetry. The critical point of the nearest-neighbor spin-1/2 model is K_c=0.2216546 (10).Comment: 25 pages, uuencoded compressed PostScript file (to appear in Journal of Physics A

Echinococcus granulosus cyst fluid enhances epithelial - mesenchymal transition

Aims Cystic Echinococcosis is characterised by fluid filled hydatid cysts in the liver and lungs. The cysts are surrounded by a host fibrous layer (the pericyst) which acts to isolate the parasite from surrounding tissues. Previous studies in liver cysts have indicated that the parasite may be stimulating fibrosis. The aim of this study was to investigate whether Hydatid Cyst Fluid (HCF) could influence the potential for fibrosis to occur in lung tissue by stimulating epithelial to mesenchymal transition (EMT) in a human lung epithelial cell line. Methods and Results An adenocarcinoma-derived alveolar basal epithelial cell line (A549) was used as a model for human alveolar epithelial cells (AEC II). These were cultured in vitro with HCF (UK sheep origin). Assays to investigate cell proliferation, cell migration and expression of cytoskeletal markers showed that HCF could stimulate changes indicative of EMT, including enhanced cell proliferation and migration; increased expression of mesenchymal cytoskeletal markers (fibronectin and vimentin) accompanied by a down regulation of an epithelial marker (E-cadherin). Conclusions Molecules within hydatid cyst fluid are capable of inducing phenotypic changes in A549 cells indicating that the parasite has the potential to modify lung epithelial cells which could contribute to fibrotic reactions

Human Herpesvirus 8 Interferon Regulatory Factor-Mediated BH3-Only Protein Inhibition via Bid BH3-B Mimicry

Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of host cells. For HHV-8, viral interferon regulatory factor-1 (vIRF-1) contributes to this process in part via inhibitory interactions with BH3-only protein (BOP) Bim, recently identified as an interaction partner of vIRF-1. Here we recognize that the Bim-binding domain (BBD) of vIRF-1 resembles a region (BH3-B) of Bid, another BOP, which interacts intramolecularly with the functional BH3 domain of Bid to inhibit it pro-apoptotic activity. Indeed, vIRF-1 was found to target Bid in addition to Bim and to interact, via its BBD region, with the BH3 domain of each. In functional assays, BBD could substitute for BH3-B in the context of Bid, to suppress Bid-induced apoptosis in a BH3-binding-dependent manner, and vIRF-1 was able to protect transfected cells from apoptosis induced by Bid. While vIRF-1 can mediate nuclear sequestration of Bim, this was not the case for Bid, and inhibition of Bid and Bim by vIRF-1 could occur independently of nuclear localization of the viral protein. Consistent with this finding, direct BBD-dependent inactivation by vIRF-1 of Bid-induced mitochondrial permeabilization was demonstrable in vitro and isolated BBD sequences were also active in this assay. In addition to Bim and Bid BH3 domains, BH3s of BOPs Bik, Bmf, Hrk, and Noxa also were found to bind BBD, while those of both pro- and anti-apoptotic multi-BH domain Bcl-2 proteins were not. Finally, the significance of Bid to virus replication was demonstrated via Bid-depletion in HHV-8 infected cells, which enhanced virus production. Together, our data demonstrate and characterize BH3 targeting and associated inhibition of BOP pro-apoptotic activity by vIRF-1 via Bid BH3-B mimicry, identifying a novel mechanism of viral evasion from host cell defenses