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Russian armed forces launched a large-scale invasion of Ukraine on February 24, 2022. [...]the conflict threatens to become the worst humanitarian crisis since World War II. Russian attacks had led to power and water shortages in many parts of Ukraine, resulting in frequent blackouts and posing a significant risk to nuclear power plant operations. [...]the current situation in Ukraine faces a serious, complex, and continuing CBRNE (chemical, biological, radiological, nuclear, and high-yield explosives) disaster [1]. [...]this report was formulated from a communication between former colleagues in Ukraine and Japan, on the assessment of the actual situation of the mental health services provision in Ukraine under the threat of CBRNE hazard posed by the 2022 Russian invasion.

Open systems can only exist by self-organization as pulsing structures exchanging matter and energy with the outer world. This review is an attempt to reveal the organizational principles of the heterochromatin supra-intra-chromosomal network in terms of nonlinear thermodynamics. The accessibility of the linear information of the genetic code is regulated by constitutive heterochromatin (CHR) creating the positional information in a system of coordinates. These features include scale-free splitting-fusing of CHR with the boundary constraints of the nucleolus and nuclear envelope. The analysis of both the literature and our own data suggests a radial-concentric network as the main structural organization principle of CHR regulating transcriptional pulsing. The dynamic CHR network is likely created together with nucleolus-associated chromatin domains, while the alveoli of this network, including springy splicing speckles, are the pulsing transcription hubs. CHR contributes to this regulation due to the silencing position variegation effect, stickiness, and flexible rigidity determined by the positioning of nucleosomes. The whole system acts in concert with the elastic nuclear actomyosin network which also emerges by self-organization during the transcriptional pulsing process. We hypothesize that the the transcriptional pulsing, in turn, adjusts its frequency/amplitudes specified by topologically associating domains to the replication timing code that determines epigenetic differentiation memory.

Here, we review the role of the circadian clock (CC) in the resistance of cancer cells to genotoxic treatments in relation to whole-genome duplication (WGD) and telomere-length regulation. The CC drives the normal cell cycle, tissue differentiation, and reciprocally regulates telomere elongation. However, it is deregulated in embryonic stem cells (ESCs), the early embryo, and cancer. Here, we review the DNA damage response of cancer cells and a similar impact on the cell cycle to that found in ESCs—overcoming G1/S, adapting DNA damage checkpoints, tolerating DNA damage, coupling telomere erosion to accelerated cell senescence, and favouring transition by mitotic slippage into the ploidy cycle (reversible polyploidy). Polyploidy decelerates the CC. We report an intriguing positive correlation between cancer WGD and the deregulation of the CC assessed by bioinformatics on 11 primary cancer datasets (rho = 0.83; p < 0.01). As previously shown, the cancer cells undergoing mitotic slippage cast off telomere fragments with TERT, restore the telomeres by ALT-recombination, and return their depolyploidised offspring to telomerase-dependent regulation. By reversing this polyploidy and the CC “death loop”, the mitotic cycle and Hayflick limit count are thus again renewed. Our review and proposed mechanism support a life-cycle concept of cancer and highlight the perspective of cancer treatment by differentiation.

Near-triploid human tumors are frequently resistant to radio/chemotherapy through mechanisms that are unclear. We recently reported a tight association of male tumor triploidy with XXY karyotypes based on a meta-analysis of 15 tumor cohorts extracted from the Mitelman database. Here we provide a conceptual framework of the digyny-like origin of this karyotype based on the germline features of malignant tumors and adaptive capacity of digyny, which supports survival in adverse conditions. Studying how the recombinatorial reproduction via diploidy can be executed in primary cancer samples and HeLa cells after DNA damage, we report the first evidence that diploid and triploid cell sub-populations constitutively coexist and inter-change genomes via endoreduplicated polyploid cells generated through genotoxic challenge. We show that irradiated triploid HeLa cells can enter tripolar mitosis producing three diploid sub-subnuclei by segregation and pairwise fusions of whole genomes. Considering the upregulation of meiotic genes in tumors, we propose that the reconstructed diploid sub-cells can initiate pseudo-meiosis producing two “gametes” (diploid “maternal” and haploid “paternal”) followed by digynic-like reconstitution of a triploid stemline that returns to mitotic cycling. This process ensures tumor survival and growth by (1) DNA repair and genetic variation, (2) protection against recessive lethal mutations using the third genome.

Unicellular green alga represents not only a convenient model for its biochemical and physiological studies but also a sensitive system to test the effects of various environmental factors. Algae cells of two strains, SA-3 strain (exsymbiotic from Paramecium bursaria) and Chlorella vulgaris c-27, were asynchronously cultured in the presence of 0.01% Aerosil A-300. Aerosil effects on algae were monitored at logarithmic and stationary phases of their growth by flow cytometry and microscopic counting of algal numbers. The growth patterns of algae were evaluated by their forward light scatter versus fluorescence of endogenous chlorophyll (FL3-height) signal distributions. Although aerosil itself did not cause any direct effects on algal morphology, it affected the growth patterns and the numbers of algae of both strains. Their growth patterns were remarkably altered in the late logarithmic phase cultures (6-day cultures). However, a significant increase of cell numbers was found in the stationary phase cultures (9- and 12-day cultures). While C. vulgaris c-27 demonstrated an increase of cell numbers by approximately 11% in the 9- and 12-day cultures, the amounts of SA-3 cells in the 9- and 12-days cultures were increased by 16% and 35%, respectively. Our study shows aerosil in its colloidal form stimulates proliferation of algae mainly via an acceleration of their life cycles. The stimulatory effect of silica on the growth of algae, the mechanism of which remains to be clarified, might have a practical (e.g., ecological) interest for regulation of algal expansion.Key words: aerosil, cloned algae, growth, forward light scatter, chlorophyll fluorescence.

The Circadian Clock (CC) drives the normal cell cycle and reciprocally regulates telomere elongation. However, it can be deregulated in cancer, embryonic stem cells (ESC), and the early embryo. Here, its role in the resistance of cancer cells to genotoxic treatments was assessed in relation to whole-genome duplication (WGD) and telomere regulation. We first evaluated the DNA damage response of polyploid cancer cells and observed a similar impact on the cell cycle to that seen in ESC - overcoming G1/S, adapting DNA damage checkpoints, tolerating DNA damage, and coupling telomere erosion to accelerated cell senescence, favouring transition by mitotic slippage into the ploidy cycle (reversible polyploidy). Next, we revealed a positive correlation between cancer WGD and deregulation of CC assessed by bioinformatics on 11 primary cancer datasets (rho=0.83; p<0.01). As previously shown, the cancer cells undergoing mitotic slippage cast off telomere fragments with TERT, restore the telomeres by recombination and return their depolyploidised mitotic offspring to TERT-dependent telomere regulation. Through depolyploidisation and the CC \"death loop\" the telomeres and Hayflick limit count are thus again renewed. This mechanism along with similar inactivity of the CC in early embryos support a life-cycle (embryonic) concept of cancer. Competing Interest Statement The authors have declared no competing interest. Footnotes * A few misprints and reference manager errors have been corrected; one unappropriated reference was substituted and one new reference added.

Liver hepatocytes possess remarkable regenerative capabilities, yet severe damage may compromise this process. Liver progenitor (“oval”) cells exhibit the potential to differentiate into both hepatocytes and cholangiocytes, making them promising candidates for cell therapy. However, their mechanisms in liver regeneration are not clear. Here, on rat liver oval stem-like epithelial cells (WB-F344) a wound healing assay was performed. The scratched near-confluent monolayers (70% area removed) underwent the G1-arrest, bi-nucleation at 10-12 hours post-wounding, starting movement of epithelial to mesenchymal transition (EMT) cell portion into the wounded areas. Nanog nuclear upregulation, fragmentation, and transition as granules into cytoplasm and around, along with p16Ink4a nuclear intrusion from the cytoplasm, loss of epithelial markers, and YAP1/Hippo activation were seen near the wound edge. The replicative stress and proliferation boost followed, documented at 24 hours. Proliferation concluded at 40-48 hours, accomplished by reconstitution of epithelial tissue, the disappearance of Nanog granulation and p16Ink4a return to the cytoplasm, releasing excess. This investigation reveals novel regulatory facets in liver regeneration by oval cells. It accentuates the stemness-senescence bistable switch regulated by reciprocal nucleo-cytoplasmic transitions of opposite regulators, coordinated with Hippo-pathway switch, replicative stress, and boost, along with ploidy, EMT-MET and paracrine secretome circuits - enabling successfully resolving the massive injury. Bistable nuclear-cytoplasmic switch between stemness and senescence regulators in the wound healing process by oval liver cells: (1-2) Priming phase: (1) at the wound edge, (2) in the wound; (3) Proliferative phase, wound closure. Nanog – green; p16INK4A – red, EMT cell - with blue nucleus.

Modern research in physical training shows increasing interest in optimizing training methods, particularly regarding the use of basic strength exercises. Although these exercises are widely applied in sports practice, their complex impact on various physical qualities remains insufficiently explored. The purpose of this study is to assess the effectiveness of a training program incorporating basic strength exercises (squats, bench press, deadlift) on the development of physical qualities in students, compared to a traditional general physical training program. Materials and methods. The study involved 120 students over 24 weeks, divided into a control group (CG, n = 60) and an experimental group (EG, n = 60). The main evaluation methods were: determining the maximum strength in basic exercises and the Cooper test. Students in CG were engaged in physical education according to the traditional curriculum twice a week for 90 minutes. Students in EG also trained twice a week for 90 minutes, but the content of the training sessions was modified according to the type of sports training in strength athletics. The EG program was based on three basic strength exercises from this sport: back squats, bench press, and deadlift (classic version). Results. Students in EG demonstrated significantly greater (p < 0.001) gains in performance: maximum strength increased by 19-21%, aerobic endurance - by 17.3% versus 7-8% and 7.2% in the control group, respectively. The effect size of the training program modification was d = 1.24-2.12 for different tests. The results confirm the hypothesis about the advantage of a combined training method. Of particular interest is the identified transfer of training - improvement in aerobic performance during strength-oriented training, which is consistent with modern concepts of systemic adaptation of the body to various types of physical activity. Conclusions. Inclusion of basic strength exercises in the educational process leads to a comprehensive improvement in the physical qualities of students and can be recommended for optimizing physical education programs. A promising direction for further research is to study the effect of the proposed methodology on a long-term time interval.