Volgograd Institute of Business

The Metaproteomics Initiative was officially launched in 2021 to strengthen collaboration, promote knowledge exchange, and support and lead standardization efforts within the growing metaproteomics community. Over the past five years, the Initiative has developed into a structured, global network of researchers. It has launched community-driven benchmark studies, helped shape emerging metadata and reporting standards, developed practical guidance and training materials, organized international symposia, and fostered connections across the microbiome research landscape (https://metaproteomics.org/). We outline the Initiative's organization, activities, achievements, and ongoing efforts, and reflect on how sustained, community-led coordination has shaped the development of metaproteomics as a field. We further position the Grand Metaproteome Challenges as a next step toward coordinated, community-scale biological research, aimed at advancing functional microbiome studies across clinical, industrial, and environmental application domains, and invite engagement from the wider microbiome and omics communities.

Abstract Intra-tumour heterogeneity (ITH) and cellular plasticity contribute to therapy resistance. Single-cell transcriptomics is the gold standard for assessing ITH, but this approach remains costly and slow. Here, we show that distinct melanoma transcriptomic states exhibit unique cellular morphologies, and introduce ORIGAMI, a scalable flow cytometry assay leveraging cell surface area (S) and volume (V) measurements to resolve melanoma cell state diversity and to track therapy-induced transitions. MAPK- and CDK4/6-targeted therapies induce predictable shifts in cell geometry: drug-tolerant persister cancer cells increase cell surface area along a de-differentiation trajectory and/or increase volume while acquiring senescent-like features. Using ORIGAMI-guided screening, we identified brefeldin A (BFA) and other ER-Golgi modulators as agents that reduce surface area, promote differentiation, and sensitize melanoma cells to targeted therapies. Therapy-induced high-volume cells exhibit lysosomal scaling and increased sensitivity to nigericin, a natural polyether related to the lysosomal iron sequestering compounds and ferroptosis inducers salinomycin and narasin. Nigericin and BFA combined with MEK- and CDK4/6-inhibitors are highly potent in vitro across cell states and genotypes, and significantly extend survival in NRAS-mutant melanoma patient-derived xenografts without overt toxicity. Moreover, this combination induces hallmarks of immunogenic cell death and enhances anti–PD-1 efficacy in immunotherapy-refractory preclinical models. Beyond melanoma, the combination shows broad anti-tumour activity across a large panel of cancer lines derived from varied tissues. These findings establish a generalizable, geometry-based framework to monitor ITH, anticipate plasticity, and inform genotype-agnostic combination strategies that negate non-genetic adaptive resistance while potentiating immunotherapy.

исследуется репрезентация феномена прекарности в публикациях российских СМИ. Характеризуется функционирование обозначающих структурные элементы (субъектов, процесса, признака, состояния) феномена прекарности лексических единиц, их семантика, синтагматика, контекстуальные коннотации; реализация деонтического подтекста, случаи эвфимизации, акцентируемые посредством смещения коммуникативного фокуса аспекты рассматриваемого феномена. Определяются закономерности репрезентации феномена прекарности в исследуемом материале.

Subject. This article focuses on the Russian Federation subjects' budgets and financial stability using the original dynamic approach. Objectives. The article aims to conduct an analysis of the regional regulatory tools impact on the risks to the financial stability of budgets in Russia. Methods. For the study, we used the methods of analysis, synthesis, deduction, induction, and grouping, as well as index, coefficient, and correlation-regression analyses. Results. The article analyzes the impact of the regulatory factors of regional administrations on the financial stability indicators according to the author-proposed criteria. Conclusions. The proposed criteria allow for a more adequate conclusion about financial stability, to highlight problems in the management of regional finances, and develop recommendations for their resolution.

New information on the distribution of an alien species in the Ural River, the European bitterling (Rhodeus amarus), is provided. Individuals of this fish species have been recorded only in a few localities along a 200-km section of the river between the mouths of the Kolpachka and Alimbet rivers, which is apparently due to its relatively recent introduction. The appearance of the species may be related to its occurrence in pond farms, in which it was accidentally introduced together with fish stocks for farming. An argument in favor of this is the current distribution of the bitterling, which coincided with that of the Stone moroko (Pseudorasbora parva), another recently identified invasive species in the Ural River. The study and analysis of the main diagnostic taxonomic features confirm the naturalization of the European bitterling in the Ural River, and the dynamics of the settlement of representatives of the genus Rhodeus in areas adjacent to the Ural basin was characterized. The phytoplankton in the feeding habitats of the bitterling, mainly microalgae, was also characterized. In total, 90 species were noted in the food spectrum of the species, the most important among which were representatives of the diatom Navicula spp. and Amphora spp. Judging by the selectivity index, the European bitterling prefers mostly representatives of the Amphora spp., Synedra spp., and Cymbella spp. Low values of this indicator are characteristic of taxa of Cryptomonas spp., Oscillatoria spp., Cosmarium spp., and Closterium spp. The main biomass of algae consumed is made up of benthic and plankto-benthic species. As bivalves of the Unionidae family serve as a spawning substrate for the European bitterling, the wide distribution of these bivalves in the Ural basin has also been characterized, as their occurrence opens up the prospects for further dispersal of this species.

Mlade djevojke, adolescentice u razdoblju puberteta izložene su brojnim izazovima, a jedan od njih je zasigurno maloljetna i neželjena trudnoća, na koju djevojke u toj razvojnoj dobi najčešće nisu spremne. Cilj rada je osvijestiti važnost edukacije, podrške i sustavnih promjena u rješavanju problema maloljetne i neželjene trudnoće. Maloljetna trudnoća se odnosi na trudnoću u kojoj trudnica nije punoljetna, što može varirati ovisno o državi, no obično podrazumijeva 18 godina. Neadekvatan, odnosno nedovoljno prisutan seksualni odgoj u školama postavlja se kao značajan problem kod maloljetne i neželjene trudnoće. Također, nedostupnost kontracepcije, što zbog financijskih razloga što zbog stigmatizacije, značajno pridonosi ovoj problematici. Nadalje, u društvima gdje su teme seksualnog zdravlja tabuizirane, očekivana je nedovoljna briga o reproduktivnom zdravlju žene. Važno je izbjeći svaki oblik stigmatizacije neželjene ili maloljetne trudnoće, kako osoba ne bi osjećala sram i dodatno narušila psihičko zdravlje. Naglasak prvenstveno treba biti na prevenciji, promociji seksualnog, zdravstvenog odgoja u školama, dostupnosti kontracepcije, te edukaciji mladih ljudi. Kada do neželjene, odnosno maloljetne trudnoće ipak dođe, ključna i prijeko potrebna je emocionalna, psihološka pomoć majci, koja se nosi sa složenom, novonastalom situacijom, te brojnim izazovima i emocijama u mladoj dobi.

Abstract Positive selection of thymocytes is essential for laying the foundations of the mammalian immune system that include the T cell repertoire, self-tolerance, and prevention of autoimmunity. Themis, the archetypal member of a metazoan protein family featuring distinctive CABIT domains, crucially regulates thymocyte positive selection by linking signalling by the T cell receptor (TCR) to the linker of activation of TCR (LAT). Intriguingly, Themis has been proposed to function via a constitutive complex with the multifunctional adaptor Grb2. Although poised to represent a paradigm shift in our understanding of TCR signalling, the structural and mechanistic basis of such an assembly has remained enigmatic. Here, we present the cryo-EM structure of Themis in complex with Grb2, which reveals how the tandem CABIT domains of Themis engulf the C-terminal SH3 domain of Grb2 (Grb2SH3C) to enable its latching onto the proline rich sequence of Themis. The remaining two domains of Grb2 adopt at least three conformational poses set to interact with other binding partners such as Sos1. Structural insights from unbound Themis unmask the pronounced flexibility of the CABIT domains of Themis, which becomes ordered upon binding to Grb2 to create a binding hotspot for their constitutive complex. Indeed, Themis variants that abrogate interactions with Grb2 also fail to activate the tyrosine phosphatase SHP-1 after TCR stimulation, analogous to the functional phenotype of Themis-deficient cells. Collectively, our study draws the blueprint of the Themis-Grb2 complex as a dynamic structural hub in T cell development.

Complementary and alternative medicine (CAM) is increasingly present in oncology, challenging the boundaries of conventional practice and raising important bioethical issues. This cross-sectional study investigated perceptions of the therapeutic value of CAM among 832 participants: 411 oncology patients and 421 healthcare professionals at a Croatian university hospital. Using validated CHBQ and IMAQ instruments, the results showed that patients’ expectations were significantly higher than those of physicians (p<0.001), particularly regarding psychophysical well-being (72.1%), immune system support (89.8%), and reduction of side effects (82.9%). Nurses occupied a middle position. These discrepancies reflect empirical differences and deeper ethical tensions between clinical authority and patient autonomy. CAM is a space where patients assert agency, seek meaning, and strive for holistic healing beyond biomedical reductionism. The findings underscore the need for ethical integration of evidence-based CAM into oncology care, supported by improved education and respectful dialogue. Supporting informed decision-making requires bridging epistemological gaps while respecting patients’ values.