BACKGROUND: Presensitized patients with circulating donor-specific antibodies (DSAs) before transplantation are at risk for antibody-mediated rejection (AMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold AMR activity undetected by histology could be operating in some early biopsies. METHODS: Transcriptome of kidney allograft biopsies performed within the first month in presensitized patients (DSA+) who had received desensitization and did not develop active/probable AMR by histology (R-) was compared with biopsies showing active/probable AMR (R+/DSA+). As negative controls, biopsies without rejection by histology in patients without DSA at transplantation were used (R-/DSA-). RNA sequencing from biopsies selected from the biobank was used in cohort 1 (n = 32) and microarray, including the molecular microscope (Molecular Microscope Diagnostic System [MMDx]) algorithm, in recent cohort 2 (n = 30). RESULTS: The transcriptome of R-/DSA+ was similar to R+/DSA+ as these groups differed in 14 transcripts only. Contrarily, large differences were found between both DSA+ groups and negative controls. Fast gene set enrichment analyses showed upregulation of the immune system in both DSA+ groups (gene ontology terms: adaptive immune response, humoral immune response, antigen receptor-mediated signaling, and B-cell receptor signaling or complement activation) when compared with negative controls. MMDx assessment in cohort 2 classified 50% of R-/DSA+ samples as AMR and found no differences in AMR molecular scores between R+ and R- DSA+ groups. In imlifidase desensitization, MMDx series showed a gradual increase in AMR scores over time. CONCLUSIONS: Presensitized kidney transplant recipients exhibited frequent molecular calls of AMR in biopsy-based transcript diagnostics despite desensitization therapy and negative histology.
- Publication type
- Journal Article MeSH
Cancer immunotherapy is increasingly used in clinical practice, but its success rate is reduced by tumor escape from the immune system. This may be due to the genetic instability of tumor cells, which allows them to adapt to the immune response and leads to intratumoral immune heterogeneity. The study investigated spatial immune heterogeneity in the tumor microenvironment and its possible drivers in a mouse model of tumors induced by human papillomaviruses (HPV) following immunotherapy. Gene expression was determined by RNA sequencing and mutations by whole exome sequencing. A comparison of different tumor areas revealed heterogeneity in immune cell infiltration, gene expression, and mutation composition. While the mean numbers of mutations with every impact on gene expression or protein function were comparable in treated and control tumors, mutations with high or moderate impact were increased after immunotherapy. The genes mutated in treated tumors were significantly enriched in genes associated with ECM metabolism, degradation, and interactions, HPV infection and carcinogenesis, and immune processes such as antigen processing and presentation, Toll-like receptor signaling, and cytokine production. Gene expression analysis of DNA damage and repair factors revealed that immunotherapy upregulated Apobec1 and Apobec3 genes and downregulated genes related to homologous recombination and translesion synthesis. In conclusion, this study describes the intratumoral immune heterogeneity, that could lead to tumor immune escape, and suggests the potential mechanisms involved.
- MeSH
- Immunotherapy * methods MeSH
- Papillomavirus Infections immunology virology MeSH
- Humans MeSH
- Disease Models, Animal * MeSH
- Mutation * MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Tumor Microenvironment * immunology MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Exome Sequencing MeSH
- Tumor Escape genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: This study aims to explore the lasting effects of stress experienced by pregnant women during World War II (WWII) on body and head measurements of their adult daughters. METHODS: The research sample consists of 336 female university students born in Poland between 1925 and 1951. The data include body measurements and socioeconomic information (parental occupation and number of siblings) acquired from questionnaires collected between the 1950s and 1970s. Student's t-test, Mann-Whitney test and Analysis of Variance were used to analyze differences in body measurements between groups of women born before and during the war, as well as the possible influences of socioeconomic variables. RESULTS: The mean measurements of body height, symphysion height, and waist circumference were lower in women conceived and born during the war compared to those born in the pre-war period. In contrast, the mean measurements of biacromial (shoulder) width, trunk length, and three head dimensions were higher in women conceived and born during the war. Additionally, the number of siblings appeared to be a significant factor that may have influenced the body measurements of women in both groups. For instance, a higher number of living siblings, particularly sisters, was associated with reduced body dimensions, such as body height and waist circumference, while a greater number of deceased siblings was linked to an increase in certain body dimensions. CONCLUSION: The results suggest that war-related prenatal conditions may have influenced the postnatal growth and development of women conceived and born during the war. Notably, the direction of these changes varied, which indicates that the growth response to the war-related conditions was a complex adaptation, reflecting both positive and negative changes in different body parts, rather than a uniform pattern of growth suppression.
- MeSH
- World War II * MeSH
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Stress, Psychological MeSH
- Socioeconomic Factors MeSH
- Pregnancy MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Poland MeSH
Yeasts are unicellular fungi that occur in a wide range of ecological niches, where they perform numerous functions. Furthermore, these microorganisms are used in industrial processes, food production, and bioremediation. Understanding the physiological and adaptive characteristics of yeasts is of great importance from ecological, biotechnological, and industrial perspectives. In this context, we evaluated the abilities to assimilate and ferment different carbon sources, to produce extracellular hydrolytic enzymes, and to tolerate salt stress, heavy metal stress, and UV-C radiation of two isolates of Eremothecium coryli, isolated from Momordica indica fruits. The two isolates were molecularly identified based on sequencing of the 18S-ITS1-5.8S-ITS2 region. Our isolates were able to assimilate nine carbon sources (dextrose, galactose, mannose, cellobiose, lactose, maltose, sucrose, melezitose, and pectin) and ferment three (glucose, maltose, and sucrose). The highest values of cellular dry weight were observed in the sugars maltose, sucrose, and melezitose. We observed the presence of hyphae and pseudohyphae in all assimilated carbon sources. The two isolates were also capable of producing amylase, catalase, pectinase, and proteases, with the highest values of enzymatic activity found in amylase. Furthermore, the two isolates were able to grow in media supplemented with copper, iron, manganese, nickel, and zinc and to tolerate saline stress in media supplemented with 5% NaCl. However, we observed a decrease in CFU at higher concentrations of these metals and NaCl. We also observed morphological changes in the presence of metals, which include changes in cell shape and cellular dimorphisms. The isolates were sensitive to UV-C radiation in the shortest exposure time (1 min). Our findings reinforce the importance of endophytic yeasts for biotechnological and industrial applications and also help to understand how these microorganisms respond to environmental variations caused by human activities.
- MeSH
- Endophytes * isolation & purification genetics metabolism physiology classification radiation effects MeSH
- Fermentation MeSH
- Phylogeny MeSH
- Stress, Physiological * MeSH
- Carbohydrate Metabolism * MeSH
- Fruit * microbiology MeSH
- Saccharomycetales * isolation & purification genetics physiology metabolism radiation effects classification MeSH
- Metals, Heavy toxicity MeSH
- Ultraviolet Rays MeSH
- Publication type
- Journal Article MeSH
The isolation and study of fungi within specific contexts yield valuable insights into the intricate relationships between fungi and ecosystems. Unlike culture-independent approaches, cultivation methods are advantageous in this context because they provide standardized replicates, specific species isolation, and easy sampling. This study aimed to understand the ecological process using a microcosm system with pesticide concentrations similar to those found in the soil, in contrast to high doses, from the isolation of the enriched community. The atrazine concentrations used were 0.02 mg/kg (control treatment), 300 ng/kg (treatment 1), and 3000 ng/kg (treatment 2), using a 28-day microcosm system. Ultimately, the isolation resulted in 561 fungi classified into 76 morphospecies. The Ascomycota phylum was prevalent, with Purpureocillium, Aspergillus, and Trichoderma being consistently isolated, denoting robust and persistent genera. Diversity analyses showed that the control microcosms displayed more distinct fungal morphospecies, suggesting the influence of atrazine on fungal communities. Treatment 2 (higher atrazine concentration) showed a structure comparable to that of the control, whereas treatment 1 (lower atrazine concentration) differed significantly, indicating that atrazine concentration impacted community variance. Higher atrazine addition subtly altered ligninolytic fungal community dynamics, implying its potential for pesticide degradation. Finally, variations in atrazine concentrations triggered diverse community responses over time, shedding light on fungal resilience and adaptive strategies against pesticides.
- MeSH
- Atrazine * metabolism pharmacology MeSH
- Biodegradation, Environmental MeSH
- Phylogeny MeSH
- Herbicides * metabolism MeSH
- Fungi * classification isolation & purification metabolism drug effects genetics growth & development MeSH
- Soil Pollutants metabolism MeSH
- Mycobiome * drug effects MeSH
- Soil Microbiology MeSH
- Publication type
- Journal Article MeSH
Článek se zabývá definicí a kategorizací digitálních her. Nejprve analyzuje dosavadní dostupné definice a upozorňuje na jejich úskalí v přesnosti a následné použitelnosti pro vymezení pojmu digitální hra. V návaznosti na tuto analýzu si klade za cíl poskytnout přesnější a komplexnější definici digitálních her založenou na kompilaci předešlých teoretických tezí. Dále se článek věnuje problematice kategorizace digitálních her, upozorňuje na nejednoznačnost označování herních žánrů, která může vést k zavádějícím označením a neshodám v herní komunitě i mezi odborníky. Digitální hry často kombinují prvky několika žánrů, což činí jejich tradiční zařazení obtížným. V reakci na tuto situaci přináší článek návrh alternativní kategorizace se zaměřením na primární herní smyčku, díky čemuž reflektuje současné trendy v herním průmyslu a umožňuje flexibilnější rozdělení her podle jejich dominantních mechanismů. Základní kategorizaci pak doplňuje žánrovými kombinacemi, specifickými doplňkovými žánry, otevřeností herního světa, sociálními aspekty, platebními modely a perspektivami pohledu. Článek reaguje na aktuální společenskou a odbornou potřebu zpřehlednění terminologie v oblasti digitálních her, což je nezbytné nejen pro vědecké bádání, ale i pro preventivní intervence a efektivní pedagogickou praxi. Systematické vymezení pojmů a žánrových kategorií přispívá k lepší orientaci odborníků napříč různými oblastmi, umožňuje přesnější diagnostiku fenoménu nadměrného hraní a zvyšuje srozumitelnost komunikace mezi výzkumníky, terapeuty, odborníky v praxi a jejich klienty. Článek tak nabízí důležitý nástroj pro mezioborové porozumění a efektivní aplikaci poznatků v praxi. Závěrem studie zdůrazňuje nutnost průběžné revize definic i způsobů kategorizace digitálních her s ohledem na jejich nepřetržitý vývoj. Digitální hry se neustále proměňují a rozšiřují o nové prvky, a proto je důležité, aby i teoretické rámce reflektovaly tyto změny a umožňovaly přesnější uchopení tohoto dynamického fenoménu.
The article focuses on the definition and categorization of digital games. It first analyzes existing definitions and highlights their shortcomings in terms of accuracy and applicability for defining the concept of a digital game. Following this analysis, the paper aims to provide a more precise and comprehensive definition of digital games, based on a synthesis of previous theoretical approaches. The article further examines the challenges of categorizing digital games, emphasizing the ambiguity in labeling game genres, which can lead to misleading classifications and disagreements within both the gaming community and experts. Digital games frequently combine elements from multiple genres, making their traditional classification difficult. In response to this issue, the article proposes an alternative categorization approach centred on the primary gameplay loop, reflecting current trends in the gaming industry and enabling a more flexible classification of games based on their dominant mechanics. This core categorization is complemented by genre combinations, specific sub-genres, game world openness, social aspects, monetization models, and perspectives of gameplay. The article responds to the current social and professional need to clarify terminology in the field of digital games, which is essential not only for scientific research but also for preventive interventions and effective pedagogical practice. The systematic definition of terms and genre categories contributes to better orientation for experts across different fields, enables more accurate diagnosis of the phenomenon of excessive gaming, and increases the clarity of communication between researchers, therapists, practitioners, and their clients. The article thus offers an important tool for interdisciplinary understanding and the effective application of knowledge in practice. Finally, the article emphasizes the necessity of continuously revising the definitions and classification methods of digital games in light of their ongoing evolution. As digital games constantly change and incorporate new elements, it is crucial that theoretical frameworks adapt to these transformations, ensuring a more accurate understanding of this dynamic phenomenon.
The soil microbiota exhibits an important function in the ecosystem, and its response to climate change is of paramount importance for sustainable agroecosystems. The macronutrients, micronutrients, and additional constituents vital for the growth of plants are cycled biogeochemically under the regulation of the soil microbiome. Identifying and forecasting the effect of climate change on soil microbiomes and ecosystem services is the need of the hour to address one of the biggest global challenges of the present time. The impact of climate change on the structure and function of the soil microbiota is a major concern, explained by one or more sustainability factors around resilience, reluctance, and rework. However, the past research has revealed that microbial interventions have the potential to regenerate soils and improve crop resilience to climate change factors. The methods used therein include using soil microbes' innate capacity for carbon sequestration, rhizomediation, bio-fertilization, enzyme-mediated breakdown, phyto-stimulation, biocontrol of plant pathogens, antibiosis, inducing the antioxidative defense pathways, induced systemic resistance response (ISR), and releasing volatile organic compounds (VOCs) in the host plant. Microbial phytohormones have a major role in altering root shape in response to exposure to drought, salt, severe temperatures, and heavy metal toxicity and also have an impact on the metabolism of endogenous growth regulators in plant tissue. However, shelf life due to the short lifespan and storage time of microbial formulations is still a major challenge, and efforts should be made to evaluate their effectiveness in crop growth based on climate change. This review focuses on the influence of climate change on soil physico-chemical status, climate change adaptation by the soil microbiome, and its future implications.
A Mycobacterium smegmatis transcriptional regulator, MSMEG_5850, and its ortholog in M. tuberculosis, rv0775 were annotated as putative TetR Family Transcriptional Regulators. Our previous study revealed MSMEG_5850 is involved in global transcriptional regulation in M. smegmatis and the presence of gene product supported the survival of bacteria during nutritional starvation. Phylogenetic analysis showed that MSMEG_5850 diverged early in comparison to its counterparts in virulent strains. Therefore, the expression pattern of MSMEG_5850 and its counterpart, rv0775, was compared during various in-vitro growth and stress conditions. Expression of MSMEG_5850 was induced under different environmental stresses while no change in expression was observed under mid-exponential and stationary phases. No expression of rv0775 was observed under any stress condition tested, while the gene was expressed during the mid-exponential phase that declined in the stationary phase. The effect of MSMEG_5850 on the survival of M. smegmatis under stress conditions and growth pattern was studied using wild type, knockout, and supplemented strain. Deletion of MSMEG_5850 resulted in altered colony morphology, biofilm/pellicle formation, and growth pattern of M. smegmatis. The survival rate of wild-type MSMEG_5850 was higher in comparison to knockout under different environmental stresses. Overall, this study suggested the role of MSMEG_5850 in the growth and adaptation/survival of M. smegmatis under stress conditions.
- MeSH
- Bacterial Proteins * genetics metabolism MeSH
- Biofilms growth & development MeSH
- Phylogeny MeSH
- Stress, Physiological * MeSH
- Microbial Viability MeSH
- Mycobacterium smegmatis * genetics growth & development physiology metabolism MeSH
- Gene Expression Regulation, Bacterial MeSH
- Transcription Factors * genetics metabolism MeSH
- Publication type
- Journal Article MeSH
Závěrečná práce NCO NZO
1 svazek : tabulky, grafy ; 30 cm
- Keywords
- adaptační proces,
- MeSH
- Adaptation, Psychological MeSH
- Laboratories, Clinical organization & administration MeSH
- Laboratories, Hospital organization & administration MeSH
- Mentoring MeSH
- Helping Behavior MeSH
- Laboratory Personnel MeSH
- Surveys and Questionnaires MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Publication type
- závěrečné práce
Neural networks are responsible for processing sensory stimuli and driving the synaptic activity required for brain function and behavior. This computational capacity is expensive and requires a steady supply of energy and building blocks to operate. Importantly, the neural networks are composed of different cell populations, whose metabolic profiles differ between each other, thus endowing them with different metabolic capacities, such as, for example, the ability to synthesize specific metabolic precursors or variable proficiency to manage their metabolic waste. These marked differences likely prompted the emergence of diverse intercellular metabolic interactions, in which the shuttling and cycling of specific metabolites between brain cells allows the separation of workload and efficient control of energy demand and supply within the central nervous system. Nevertheless, our knowledge about brain bioenergetics and the specific metabolic adaptations of neural cells still warrants further studies. In this review, originated from the Fourth International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Schmerlenbach, Germany (2022), we describe and discuss the specific metabolic profiles of brain cells, the intercellular metabolic exchanges between these cells, and how these bioenergetic activities shape synaptic function and behavior. Furthermore, we discuss the potential role of faulty brain metabolic activity in the etiology and progression of Alzheimer's disease, Parkinson disease, and Amyotrophic lateral sclerosis. We foresee that a deeper understanding of neural networks metabolism will provide crucial insights into how higher-order brain functions emerge and reveal the roots of neuropathological conditions whose hallmarks include impaired brain metabolic function.
- MeSH
- Energy Metabolism * physiology MeSH
- Humans MeSH
- Metabolic Networks and Pathways * physiology MeSH
- Brain * metabolism MeSH
- Nerve Net * metabolism MeSH
- Neurons * metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
