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Between c. 300 BC and AD 350, the Meroitic kingdom dominated the Middle Nile Valley; following its breakdown, it was replaced by a series of smaller successor polities. Explanation for this change centres on socio-political and economic instability. Here, the authors investigate the role of climate and environment using stable carbon and oxygen isotope analyses of human and faunal dental enamel from 13 cemeteries. The results show increasing [delta][sup.18]O values towards the end of the Meroitic kingdom and in the postMeroitic period, combined with less negative [delta][sup.13]C values. These trends suggest a shift towards more arid conditions associated with changes in agricultural practices and land use that may have contributed to the kingdom's dissolution. Keywords: Sudan, Upper Nubia, Meroitic kingdom, isotope analysis, climate change, collapse, Introduction Kush was one of several early states that formed along the Middle Nile, flourishing for centuries until its fall towards the end of the Meroitic period (c. 300 BC-AD [...]

The purpose of this study is to determine the factors that explain the capital structure of Ukrainian non-financial corporations. The study was carried out on a sample of 8525 Ukrainian large and medium-sized enterprises on the time horizon of 2014-2019, covering one economic cycle. Banks and non-bank financial institutions are excluded from the sample of enterprises, since the structure of their assets differs from that of commercial companies. To determine the impact of fundamental factors, the capital structure of companies is represented separately by three indicators: i) the level of current debt, ii) the level of long-term debt, and iii) the level of debt in general in the structure of liabilities of enterprises. The list of indicators that explain the capital structure of Ukrainian companies includes fundamental indicators – profitability, company size, asset structure, current liquidity, growth; and macroeconomic variables: GDP growth and consumer price index. The results of the study confirm that the conception of sequential actions best explains the principle by which Ukrainian companies form the structure of liabilities. According to the results of the modeling, the company’s factors demonstrate statistical significance, but do not explain the variation in the level of debt in terms of types of economic activity. Only the factors of profitability, asset structure and type of economic activity are statistically significant for all types of models. The sign of the influence of factors that determine the capital structure of Ukrainian companies corresponds to the results of studies of both developed countries and transition economies. Also, the impact of factors on the level of indebtedness of enterprises differs significantly depending on the maturity of obligations. This study can be further developed by updating the calculations and data that include the period of recent crises. This will allow us to check whether companies have changed their approaches to choosing a capital structure during the wartime.

Abstract This study provides comprehensive quantitative evidence suggesting that adaptations to extreme temperatures and pH imprint a discernible environmental component in the genomic signature of microbial extremophiles. Both supervised and unsupervised machine learning algorithms were used to analyze genomic signatures, each computed as the k-mer frequency vector of a 500 kbp DNA fragment arbitrarily selected to represent a genome. Computational experiments classified/clustered genomic signatures extracted from a curated dataset of $$\sim 700$$ ∼ 700 extremophile (temperature, pH) bacteria and archaea genomes, at multiple scales of analysis, $$1\le k \le 6$$ 1 ≤ k ≤ 6 . The supervised learning resulted in high accuracies for taxonomic classifications at $$2\le k \le 6$$ 2 ≤ k ≤ 6 , and medium to medium-high accuracies for environment category classifications of the same datasets at $$3\le k \le 6$$ 3 ≤ k ≤ 6 . For $$k=3$$ k = 3 , our findings were largely consistent with amino acid compositional biases and codon usage patterns in coding regions, previously attributed to extreme environment adaptations. The unsupervised learning of unlabelled sequences identified several exemplars of hyperthermophilic organisms with large similarities in their genomic signatures, in spite of belonging to different domains in the Tree of Life.

Author(s): Jolanta Soltysiak [sup.1] , Izabela Krzysko-Pieczka [sup.2] , Anna Gertig-Kolasa [sup.2] , Ewa Mularz [sup.2] , Bogda Skowronska [sup.2] , Danuta Ostalska-Nowicka [sup.1] , Jacek Zachwieja [sup.1] Author Affiliations: [...], Background Diabetic ketoacidosis (DKA) and hyperglycaemia without ketoacidosis are common acute complications of diabetes. Their association with acute kidney injury (AKI) and diabetic kidney disease (DKD) was studied. Methods The study group consisted of 197 children with type 1 diabetes with average diabetes duration of 8.08 ± 2.32 years. The medical history of the patients was retrospectively reviewed. The number of children with severe hyperglycaemia, DKA and AKI was assessed. The association with the risk of chronic kidney disease (CKD) was analysed. Results AKI was found in 14% of cases hospitalised for DKA and 8% of cases hospitalised for hyperglycaemia. Patients with AKI showed a significantly increased corrected sodium (141.23 ± 5.09 mmol/L, p = 0.035). Patients with AKI in DKA showed a significant increase in WBC (20.73 ± 8.71 x 10.sup.3/[micro]L, p = 0.0009). Follow-up analysis after a minimum of 5 years of diabetes revealed that a single episode of DKA was found in 63 patients and a single episode of AKI in 18 patients. Two or more episodes of DKA were found in 18 patients, and nine cases were complicated by AKI. These patients showed a significant increase in urinary albumin excretion (44.20 ± 64.21 mg/24 h), the highest values of eGFR and the worst glycaemic control. Conclusions Diabetic children can develop AKI in the course of DKA and hyperglycaemia without ketoacidosis, which is associated with volume depletion and reflected by corrected sodium concentration. AKI in DKA seems to be complicated by stress and inflammation activation. AKI and poor glycaemic control with repeated DKA episodes can magnify the risk of progression to DKD. Graphical abstract

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells' self-renewal capabilities and eventually leads to their exhaustion. Mechanistically, we demonstrate that targeting members of the Ifi20x/IFI16 family of cytosolic DNA sensors using the oligodeoxynucleotide A151, which comprises four repeats of the TTAGGG motif of the telomeric DNA, overcomes interferon signaling activation in telomere-dysfunctional hematopoietic stem cells and these cells' skewed differentiation towards the megakaryocytic lineage. This study challenges the historical hypothesis that telomere attrition limits the proliferative potential of hematopoietic stem cells by inducing apoptosis, autophagy, or senescence, and suggests that targeting IFI16 signaling axis might prevent hematopoietic stem cell functional decline in conditions affecting telomere maintenance.

This study presents an updated risk map of the Ukrainian financial sector – an analytical tool for identifying and monitoring the buildup and materialization of systemic risks. The risk map methodology that the National Bank of Ukraine used until 2021 has been revised to ensure that risk assessment is based on reliable quantitative indicators rather than expert judgements, as well as to extend the list of risks considered. The instrument allows the stability of the financial system to be assessed across key risks, such as macroeconomic risk, the credit risks of households and non-financial corporations, capital adequacy risk, profitability risk, liquidity risk, and foreign exchange risk. We introduce indicators that capture a wide range of economic and financial vulnerabilities and group them by risks. Each risk category contains from four to seven indicators that combine both actual data and expectations. Statistical checks show that the indicators clearly signal previous crisis episodes, as well as the buildup of vulnerabilities during the research period. We find that macroeconomic risk and foreign exchange risk have the best explanatory and predictive power, while the weaker performance of other risks could result from structural changes in the banking sector over the past decades that have affected the overall risk profile of the financial sector.

Background/Objectives: Traumatic craniomaxillofacial (CMF) injuries are associated with various symptoms/concerns that affect patients' quality of life. The assessment of outcomes from the patient perspective has been limited by the absence of patient-reported outcome (PRO) measures tailored to this patient population. To address this need, we employed a mixed methods, multi-step process to first identify the most important symptoms/concerns and then use this information to construct a PRO symptom battery. Methods: CMF clinicians and patients who had sustained traumatic CMF injuries participated in semi-structured interviews to elicit the symptoms/concerns considered the most important. The data were analyzed using an iterative coding procedure and symptom/concern frequency was tabulated. The findings were used to develop a conceptual model of the most important symptoms to include in a PRO battery. Existing items were modified as needed and new items were drafted to ensure adequate coverage of the symptoms. Results: The resulting AO CMF Injury Symptom Battery includes four modules specific to the injury site (oral, ocular, nasopharyngeal, ear) and five universal modules (pain/sensation, cognitive, cosmetic, psychosocial, and injury impact). Conclusions: The AO CMF Injury Symptom Battery offers promise for assessing symptoms only patients can report on in clinical research and practice. Ongoing research will examine the battery's psychometric properties. [ABSTRACT FROM AUTHOR]

The effects of the 4.2 kya climatic event on northern Mesopotamia have been the subject of significant scholarly debate, with the notion of a megadrought that forced local populations to migrate attracting particular attention. Here, the authors analyse stable carbon ([delta][sup.13]C) and nitrogen ([delta][sup.15]N) isotopes in human tooth and bone samples to assess trends in subsistence practice at three sites in Syria before, during and after the presumed megadrought event. Despite the proximity of the sites, isotopic differences between them are more significant than diachronic change. Combined with other archaeological evidence, these results indicate a continuity in subsistence patterns, with no indication of disruption associated with the 4.2 kya event. Keywords: Syria, Khabur Basin, stable isotopes, subsistence, drought, sustainability, The 4.2 kya event in northern Mesopotamia Among the eight identified North Atlantic ice-rafting events that are interpreted as periods of aridification in the Northern Hemisphere, the event that started [...]

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Fungi are nature’s recyclers, allowing for ecological nutrient cycling and, in turn, the continuation of life on Earth. Some fungi inhabit the human microbiome where they can provide health benefits, while others are opportunistic pathogens that can cause disease. Yeasts, members of the fungal kingdom, have been domesticated by humans for the production of beer, bread, and, recently, medicine and chemicals. Still, the great untapped potential exists within the diverse fungal kingdom. However, many yeasts are intractable, preventing their use in biotechnology or in the development of novel treatments for pathogenic fungi. Therefore, as a first step for the domestication of new fungi, an efficient DNA delivery method needs to be developed. Here, we report the creation of superior conjugative plasmids and demonstrate their transfer via conjugation from bacteria to 7 diverse yeast species including the emerging pathogen Candida auris. To create our superior plasmids, derivatives of the 57 kb conjugative plasmid pTA-Mob 2.0 were built using designed gene deletions and insertions, as well as some unintentional mutations. Specifically, a cluster mutation in the promoter of the conjugative gene traJ had the most significant effect on improving conjugation to yeasts. In addition, we created Golden Gate assembly-compatible plasmid derivatives that allow for the generation of custom plasmids to enable the rapid insertion of designer genetic cassettes. Finally, we demonstrated that designer conjugative plasmids harboring engineered restriction endonucleases can be used as a novel antifungal agent, with important applications for the development of next-generation antifungal therapeutics.