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Introduction. The article examines the current philosophical debates about the relationship between secular and religious worldviews. The article outlines recent forms of postsecularization as the continued existence of religious communities in a continually secularizing environment, identifying its main dimensions: the deinstitutionalization of the religious lifestyle, the individualization of faith, and the development of new social forms in the religious fi eld. Theoretical analysis. The central premise of the study is that existing approaches are not only controversial, but have their limitations to describing perspectives of secular-religious dialogue in a constructive way. On the basis of the discursive approach rational-discursive and relativistic-conventional strategies of secular-religious dialogue are identified and discussed. In this context, J. Habermas suggests that religion and secular worldviews have to learn from each other, and religion has to be “translated” into the rational language of secular culture, neutralizing its most dangerous components. At the same time, J.Milbank fi nds the essentialization of secular reason problematic. In conclusion, perspectives of secular-religious dialogue in the context of Russian culture are discussed. The essence of this model consists in the search for a compromise between the extremes of dogmatic faith and secular reason.

The article defines the contemporary social myth as a value-laden phenomenon with the potential and significance, but which is used in different ways by actors – an indwelling by a myth, a creator of a myth and a critic of a myth. The process of myth-making is considered as launching the so-called work on myth, which includes both the activity of myth-makers and the functioning of the myth in the masses. The appeal to the project function of the social myth and the consideration of the degree of awareness of the myth by individual groups actualize the question of the myth as a factor in constructing images of the future. Taking into account the ideas of R. Barthes and C. Bottici, the author concludes that the myth already contains significant images that allow the future to become more concrete. Using the example of the state as the main generator of myths for a wide audience, it is suggested that all the trajectories of creating potential images of the future are confined to the myth of the hero. Conclusions are drawn about the demand for such images of the future, which are built around the figure of a leader correlated with a mythological hero, that the scale of the state is a suitable level for reasoning about the spread and limits of the influence of modern myth-making, and that the constructive potential of the myth is involved in creating images of the future.

Proteomic studies have identified moesin (MSN), a protein containing a four-point-one, ezrin, radixin, moesin (FERM) domain, and the receptor CD44 as hub proteins found within a coexpression module strongly linked to Alzheimers disease (AD) traits and microglia. These proteins are more abundant in Alzheimers patient brains, and their levels are positively correlated with cognitive decline, amyloid plaque deposition, and neurofibrillary tangle burden. The MSN FERM domain interacts with the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) and the cytoplasmic tail of CD44. Inhibiting the MSN-CD44 interaction may help limit AD-associated neuronal damage. Here, we investigated the feasibility of developing inhibitors that target this protein-protein interaction. We have employed structural, mutational, and phage-display studies to examine how CD44 binds to the FERM domain of MSN. Interestingly, we have identified an allosteric site located close to the PIP2 binding pocket that influences CD44 binding. These findings suggest a mechanism in which PIP2 binding to the FERM domain stimulates CD44 binding through an allosteric effect, leading to the formation of a neighboring pocket capable of accommodating a receptor tail. Furthermore, high-throughput screening of a chemical library identified two compounds that disrupt the MSN-CD44 interaction. One compound series was further optimized for biochemical activity, specificity, and solubility. Our results suggest that the FERM domain holds potential as a drug development target. Small molecule preliminary leads generated from this study could serve as a foundation for additional medicinal chemistry efforts with the goal of controlling microglial activity in AD by modifying the MSN-CD44 interaction.

The present article addressed the issue of university teachers' working experience in the field of class-oriented online teaching English in higher educational institutions. The central aim of this study was a detailed description of the system for assessing reading skills utilized in English proficiency tests (CAE (C1), TOEFL, IELTS), as well as a comprehensive analysis of testing results. As a part of a thorough investigation, the article detailed three major reading modes and tasks most commonly used in such tests (scan-reading, skim-reading, and in-depth reading). Besides, in order to obtain reliable conclusions about the reasonability of the test tasks, the study took into account the tests' duration, the number and types of tasks, as well as the length of reading passages proposed. The research population comprised 622 second-year students from all faculties of the National Research University "Higher School of Economics" (Nizhny Novgorod Campus, Russia) with English proficiency levels from B1 to C1+. All data required for the study were collected from the outcomes of international English exams (CAE (C1), TOEFL, IELTS), conducted in the form of testing in 2013, 2014, and 2015. The results of this examination showed that 97% of students involved successfully solved multiple choice tasks, 96% demonstrated an understanding of the dependence between headings and text fragments, and 95% succeeded in gap-filling tasks. Provided that research participants were engaged in active work on English reading comprehension improvement throughout the examination period, 95% of students have mastered their reading skills.

Despite widespread utilization of immunotherapy, treating immune-cold tumors remains a challenge. Multiomic analyses and experimental validation identified the OTUD4/CD73 proteolytic axis as a promising target in treating immune-suppressive triple negative breast cancer (TNBC). Mechanistically, deubiquitylation of CD73 by OTUD4 counteracted its ubiquitylation by TRIM21, resulting in CD73 stabilization inhibiting tumor immune responses. We further demonstrated the importance of TGF-[beta] signaling for orchestrating the OTUD4/CD73 proteolytic axis within tumor cells. Spatial transcriptomics profiling discovered spatially resolved features of interacting malignant and immune cells pertaining to expression levels of OTUD4 and CD73. In addition, ST80, a newly developed inhibitor, specifically disrupted proteolytic interaction between CD73 and OTUD4, leading to reinvigoration of cytotoxic [CD8.sup.+] T cell activities. In preclinical models of TNBC, ST80 treatment sensitized refractory tumors to anti-PD-LI therapy. Collectively, our findings uncover what we believe to be a novel strategy for targeting the immunosuppressive OTUD4/CD73 proteolytic axis in treating immune-suppressive breast cancers with the inhibitor ST80., Introduction Despite the widespread utilization of immunotherapy, the poor clinical response by immune-suppressive tumors is an emerging challenge in use of current immune checkpoint inhibitors. Triple negative breast cancers (TNBCs) [...]

Non-coding RNA expression has shown to have cell type-specificity. The regulatory characteristics of these molecules are impacted by changes in their expression levels. We performed next-generation sequencing and examined small RNA-seq data obtained from 6 different types of blood cells separated by fluorescence-activated cell sorting of severe COVID−19 patients and healthy control donors. In addition to examining the behavior of piRNA in the blood cells of severe SARS-CoV−2 infected patients, our aim was to present a distinct piRNA differential expression portrait for each separate cell type. We observed that depending on the type of cell, different sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, and neutrophils) have altering piRNA expression patterns. After analyzing the expression of piRNAs in each set of sorted cells from patients with severe COVID−19, we observed 3 significantly elevated piRNAs - piR−33,123, piR−34,765, piR−43,768 and 9 downregulated piRNAs in erythrocytes. In lymphocytes, all 19 piRNAs were upregulated. Monocytes were presented with a larger amount of statistically significant piRNA, 5 upregulated (piR−49039 piR−31623, piR−37213, piR−44721, piR−44720) and 35 downregulated. It has been previously shown that piR−31,623 has been associated with respiratory syncytial virus infection, and taking in account the major role of piRNA in transposon silencing, we presume that the differential expression patterns which we observed could be a signal of indirect antiviral activity or a specific antiviral cell state. Additionally, in lymphocytes, all 19 piRNAs were upregulated. [ABSTRACT FROM AUTHOR]

Motivation Software is vital for the advancement of biology and medicine. Impact evaluations of scientific software have primarily emphasized traditional citation metrics of associated papers, despite these metrics inadequately capturing the dynamic picture of impact and despite challenges with improper citation. Results To understand how software developers evaluate their tools, we conducted a survey of participants in the Informatics Technology for Cancer Research (ITCR) program funded by the National Cancer Institute (NCI). We found that although developers realize the value of more extensive metric collection, they find a lack of funding and time hindering. We also investigated software among this community for how often infrastructure that supports more nontraditional metrics were implemented and how this impacted rates of papers describing usage of the software. We found that infrastructure such as social media presence, more in-depth documentation, the presence of software health metrics, and clear information on how to contact developers seemed to be associated with increased mention rates. Analysing more diverse metrics can enable developers to better understand user engagement, justify continued funding, identify novel use cases, pinpoint improvement areas, and ultimately amplify their software's impact. Challenges are associated, including distorted or misleading metrics, as well as ethical and security concerns. More attention to nuances involved in capturing impact across the spectrum of biomedical software is needed. For funders and developers, we outline guidance based on experience from our community. By considering how we evaluate software, we can empower developers to create tools that more effectively accelerate biological and medical research progress. Availability and implementation More information about the analysis, as well as access to data and code is available at https://github.com/fhdsl/ITCR_Metrics_manuscript_website. [ABSTRACT FROM AUTHOR]

The research is devoted to the study of the functional role structure of the interaction of the company's top management. The subject area of the study includes projects of digital transformation of business processes. The functional role status of IT directors for such positions as CIO, CDO, CDTO, CTO, CA was investigated. The analysis of the most frequently used models of interaction of IT directors was carried out and the optimal model was determined. The study was conducted using the Delphi expert assessment and the hierarchy analysis method. For the established optimal model related to the integration type of management, the organisational features of its application are described. Solutions are proposed to improve the quality of functional-role interaction of IT directors, which consider personal effectiveness, interaction style, ability to adopt technologies. The results of the study inform scientists about new data in the field of organisational behaviour for companies implementing digital initiatives. Practitioners can use the results of our research to adapt their organisational structure in such a way as to reduce the risks of the human factor during the implementation of the digital transformation strategy. [ABSTRACT FROM AUTHOR]