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This research focuses on studying the avian populations in the floodplains of the Kara Yertis and Yertis River in the Pavlodar region, Kazakhstan. There are notable gaps in our understanding of the avifauna in these areas, highlighting the need for continued ornithological research. The primary goal is to address these limitations, with a focus on the Zaysan depression in the East Kazakhstan region and the Pavlodar region. Global climate change and anthropogenic impacts, such as hydroelectric power stations and reservoir construction, are identified as potential contributors to environmental changes in the region. One significant impact is the potential shift in the timing of spring nesting due to climate change, affecting different bird species in varying ways. To investigate these dynamics, field studies were conducted in May and June of 2023, covering seven sites along the Kara Yertis and Yertis River in the Pavlodar region. The study adhered to standardized protocols, taking into account the phenological aspects of bird life cycles. The density of bird species was estimated using route accounting on permanent inventory plots. The study identified a total of 127 bird species across 16 orders in the two model areas. This included species listed in the Red Book, highlighting the importance of conservation efforts. In the Irtysh River of the Pavlodar region with a high humidity level, compared with the Kara Yertis, there were fewer anthropogenic impacts and more bird species (103 species). This study shows that, taking into account climate change and anthropogenic impacts, it is necessary to constantly monitor this region and develop conservation and adaptation strategies. [ABSTRACT FROM AUTHOR]

This article provides an overview of the history of the question of the unfinished novel «The Mystery of Edwin Drood» by Charles Dickens, the critical reviews of the novel, and attempts to complete it. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on hospital outcomes of percutaneous coronary interventions (PCI) in patients with acute coronary syndrome (ACS)., Materials and Methods: A cohort prospective study of the COPD effect on mortality and coronary microvascular obstruction (CMVO, no-reflow) development after PCI in ACS was carried out. 626 patients admitted in 2019-2020 were included, 418 (67%) - men, 208 (33%) - women. Median age - 63 [56; 70] years. Myocardial infarction with ST elevation identified in 308 patients (49%), CMVO - in 59 (9%) patients (criteria: blood flow <3 grade according to TIMI flow grade; perfusion <2 points according to Myocardial blush grade; ST segment resolution <70%). 13 (2.1%) patients died. Based on the questionnaire "Chronic Airways Diseases, A Guide for Primary Care Physicians, 2005", 2 groups of patients were identified: 197 (31%) with COPD (≥17 points) and 429 (69%) without COPD (<17 points). Groups were compared on unbalanced data (÷ 2 Pearson, Fisher exact test). The propensity score was calculated, and a two-way logistic regression analysis was performed. The data were balanced by the Kernel "weighting" method, logistic regression analysis was carried out using "weighting" coefficients. Results as odds ratio (OR) and 95% confidence interval., Results: The conducted research allowed us to obtain the following results, depending on the type of analysis: 1) analysis of unbalanced data in patients with COPD: OR death 3.60 (1.16-11.12); p =0.03; OR CMVO 0.65 (0.35-1.22); p =0,18; 2) two-way analysis with propensity score: OR death 3.86 (1.09-13.74); p =0.04; OR CMVO 0.61 (0.31-1.19); p =0.15; 3) regression analysis with "weight" coefficients: OR death 12.49 (2.27-68.84); p =0.004; OR CMVO 0.63 (0.30-1.33); p =0.22., Conclusion: The presence of COPD in patients with ACS undergoing PCI increases mortality and does not affect the incidence of CMVO.

In the modern theory of compressed concrete elements, the most attention is paid to longitudinal deformations, whereas transverse ones are rarely considered and just within Poisson's coefficient limits (i.e., elastic concrete behavior in the transverse direction). However, transverse deformations significantly develop beyond the limits corresponding to Poisson's coefficient, where they lead to longitudinal crack initiation and development. In-depth experimental and numerical investigations of transverse deformations in the inelastic stage showed that it is necessary to consider crack propagation. The present study proposes simultaneous consideration of longitudinal and transverse deformations, as well as the appearance of cracks and their widths and depths. This allowed us to obtain a complete compressed concrete element behavior pattern at all performance stages in two types of limit states (based on longitudinal and transverse deformations). Consequently, new ultimate limit states by the depth and width of cracks caused by transverse deformations are proposed to be included in modern design practices and codes.

Importance: Alphavirus replicons are being developed as self-amplifying RNAs aimed at improving the efficacy of mRNA vaccines. These replicons are convenient for genetic manipulations and can express heterologous genetic information more efficiently and for a longer time than standard mRNAs. However, replicons mimic many aspects of viral replication in terms of induction of innate immune response, modification of cellular transcription and translation, and expression of nonstructural viral genes. Moreover, all replicons used in this study demonstrated expression of heterologous genes in cell- and replicon's origin-specific modes. Thus, many aspects of the interactions between replicons and the host remain insufficiently investigated, and further studies are needed to understand the biology of the replicons and their applicability for designing a new generation of mRNA vaccines. On the other hand, our data show that replicons are very flexible expression systems, and additional modifications may have strong positive impacts on protein expression., Competing Interests: The authors declare no conflict of interest.

Importance: Our study highlights the mechanisms behind the cell's resistance to stress granule (SG) formation after infection with Old World alphaviruses. Shortly after infection, the replication of these viruses hinders the cell's ability to form SGs, even when exposed to chemical inducers such as sodium arsenite. This resistance is primarily attributed to virus-induced transcriptional and translational shutoffs, rather than interactions between the viral nsP3 and the key components of SGs, G3BP1/2, or the ADP-ribosylhydrolase activity of nsP3 macro domain. While interactions between G3BPs and nsP3 are essential for the formation of viral replication complexes, their role in regulating SG development appears to be small, if any. Cells harboring replicating viruses or replicons with lower abilities to inhibit transcription and/or translation, but expressing wild-type nsP3, retain the ability for SG development. Understanding these mechanisms of regulation of SG formation contributes to our knowledge of viral replication and the intricate relationships between alphaviruses and host cells., Competing Interests: The authors declare no conflict of interest.

Replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strongly affects cellular metabolism and results in rapid development of the cytopathic effect (CPE). The hallmarks of virus-induced modifications are inhibition of translation of cellular mRNAs and redirection of the cellular translational machinery to the synthesis of virus-specific proteins. The multifunctional nonstructural protein 1 (nsp1) of SARS-CoV-2 is a major virulence factor and a key contributor to the development of translational shutoff. In this study, we applied a wide range of virological and structural approaches to further analyze nsp1 functions. The expression of this protein alone was found to be sufficient to cause CPE. However, we selected several nsp1 mutants exhibiting noncytopathic phenotypes. The attenuating mutations were detected in three clusters, located in the C-terminal helices, in one of the loops of the structured domain and in the junction of the disordered and structured fragment of nsp1. NMR-based analysis of the wild type nsp1 and its mutants did not confirm the existence of a stable β5-strand that was proposed by the X-ray structure. In solution, this protein appears to be present in a dynamic conformation, which is required for its functions in CPE development and viral replication. The NMR data also suggest a dynamic interaction between the N-terminal and C-terminal domains. The identified nsp1 mutations make this protein noncytotoxic and incapable of inducing translational shutoff, but they do not result in deleterious effects on viral cytopathogenicity. IMPORTANCE The nsp1 of SARS-CoV-2 is a multifunctional protein that modifies the intracellular environment for the needs of viral replication. It is responsible for the development of translational shutoff, and its expression alone is sufficient to cause a cytopathic effect (CPE). In this study, we selected a wide range of nsp1 mutants exhibiting noncytopathic phenotypes. The attenuating mutations, clustered in three different fragments of nsp1, were extensively characterized via virological and structural methods. Our data strongly suggest interactions between the nsp1 domains, which are required for the protein's functions in CPE development. Most of the mutations made nsp1 noncytotoxic and incapable of inducing translational shutoff. Most of them did not affect the viability of the viruses, but they did decrease the rates of replication in cells competent in type I IFN induction and signaling. These mutations, and their combinations, in particular, can be used for the development of SARS-CoV-2 variants with attenuated phenotypes.

The theoretical stress-strain model for compressed composite cement materials' behavior without empirical coefficients was proposed by Iskhakov in 2018. This model includes the following main parameters describing concrete behavior: stresses and strains corresponding to the border between the elastic and non-elastic behavior stages of a concrete specimen, ultimate elastic strains, and stresses and strains at the end of the post-peak region. Particular attention is focused on the descending branch of the stress-strain diagram, as well as on the analysis of concrete elastic and plastic potentials. These potentials are important for assessing the dynamic response of the concrete element section, as well as for concrete creep analysis. The present research is aimed at experimental verification of the above-mentioned theoretical model. The obtained experimental results are in good agreement with the theoretical ones, which confirms the model's accuracy and enables a significant reduction in the empirical coefficients number in compressed reinforced concrete elements design. This, in turn, represents the scientific novelty of this study.

Circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the human population leads to further viral evolution. The new variants that arise during this evolution are more infectious. Our data suggest that newer variants have shifted from utilizing both cathepsin/endosome- and TMPRSS2-mediated entry mechanisms to rely on a TMPRSS2-dependent entry pathway. Accordingly, only the early lineages of SARS-CoV-2 are capable of infecting and forming syncytia in Vero/ACE2 cells which lack TMPRSS2 expression. The presence of an intact multibasic furin cleavage site (FCS) in the S protein was a key requirement for cell-to-cell fusion. Deletion of FCS makes SARS-CoV-2 more infectious in vitro but renders it incapable of syncytium formation. Cell-to-cell fusion likely represents an alternative means of virus spread and is resistant to the presence of high levels of neutralizing monoclonal antibodies (MAbs) and immune sera in the media. In this study, we also noted that cells infected with SARS-CoV-2 with an intact FCS or alphavirus replicon expressing S protein (VEErep/S) released high levels of free S1 subunit. The released S1 is capable of activating the TLR4 receptor and inducing a pro-inflammatory response. Thus, S1 activation of TLR4 may be an important contributor to SARS-CoV-2-induced COVID-19 disease and needs to be considered in the design of COVID mRNA vaccines. Lastly, a VEErep/S-replicon was shown to produce large amounts of infectious, syncytium-forming pseudoviruses and thus could represent alternative experimental system for screening inhibitors of virus entry and syncytium formation. IMPORTANCE The results of this study demonstrate that the late lineages of SARS-CoV-2 evolved to more efficient use of the TMPRSS2-mediated entry pathway and gradually lost an ability to employ the cathepsins/endosome-mediated entry. The acquisition of a furin cleavage site (FCS) by SARS-CoV-2-specific S protein made the virus a potent producer of syncytia. Their formation is also determined by expression of ACE2 and TMPRSS2 and is resistant to neutralizing human MAbs and immune sera. Syncytium formation appears to be an alternative means of infection spread following the development of an adaptive immune response. Cells infected with SARS-CoV-2 with an intact FCS secrete high levels of the S1 subunit. The released S1 demonstrates an ability to activate the TLR4 receptor and induce pro-inflammatory cytokines, which represent a hallmark of SARS-CoV-2 pathogenesis. Alphavirus replicons encoding SARS-CoV-2 S protein cause spreading, syncytium-forming infection, and they can be applied as an experimental tool for studying the mechanism of syncytium formation.

Structural characterization of the SARS-CoV-2 full length nsp1 protein will be an essential tool for developing new target-directed antiviral drugs against SARS-CoV-2 and for further understanding of intra- and intermolecular interactions of this protein. As a first step in the NMR studies of the protein, we report the 1H, 13C and 15N resonance backbone assignment as well as the Cβ of the apo form of the full-lengthSARS-CoV-2 nsp1 including the folded domain together with the flaking N- and C- terminal intrinsically disordered fragments. The 19.8 kD protein was characterized by high-resolution NMR. Validation of assignment have been done by using two different mutants, H81P and K129E/D48E as well as by amino acid specific experiments. According to the obtained assignment, the secondary structure of the folded domain in solution was almost identical to its previously published X-ray structure as well as another published secondary structure obtained by NMR, but some discrepancies have been detected. In the solution SARS-CoV-2 nsp1 exhibited disordered, flexible N- and C-termini with different dynamic characteristics. The short peptide in the beginning of the disordered C-terminal domain adopted two different conformations distinguishable on the NMR time scale. We propose that the disordered and folded nsp1 domains are not fully independent units but are rather involved in intramolecular interactions. Studies of the structure and dynamics of the SARS-CoV-2 mutant in solution are on-going and will provide important insights into the molecular mechanisms underlying these interactions., Competing Interests: The authors have declared that no competing interests exist.

A chimeric Eilat/ Chikungunya virus (EILV/CHIKV) was previously reported to replicate only in mosquito cells but capable of inducing robust adaptive immunity in animals. Here, we initially selected C7/10 cells to optimize the production of the chimeric virus. A two-step procedure produced highly purified virus stocks, which was shown to not cause hypersensitive reactions in a mouse sensitization study. We further optimized the dose and characterized the kinetics of EILV/CHIKV-induced immunity. A single dose of 10 8 PFU was sufficient for induction of high levels of CHIKV-specific IgM and IgG antibodies, memory B cell and CD8 + T cell responses. Compared to the live-attenuated CHIKV vaccine 181/25, EILV/CHIKV induced similar levels of CHIKV-specific memory B cells, but higher CD8 + T cell responses at day 28. It also induced stronger CD8 + , but lower CD4 + T cell responses than another live-attenuated CHIKV strain (CHIKV/IRES) at day 55 post-vaccination. Lastly, the purified EILV/CHIKV triggered antiviral cytokine responses and activation of antigen presenting cell (APC)s in vivo, but did not induce APCs alone upon in vitro exposure. Overall, our results demonstrate that the EILV/CHIKV vaccine candidate is safe, inexpensive to produce and a potent inducer of both innate and adaptive immunity in mice.