The tumor microenvironment (TME) is a complex, highly structured, and dynamic ecosystem that plays a pivotal role in the progression of both primary and metastatic tumors. Precise assessment of the dynamic spatiotemporal features of the TME is crucial for understanding cancer evolution and designing effective therapeutic strategies. Cancer is increasingly recognized as a systemic disease, influenced not only by the TME, but also by a multitude of systemic factors, including whole-body metabolism, gut microbiome, endocrine signaling, and circadian rhythm. In this review, we summarize the intrinsic, extrinsic, and systemic factors contributing to the formation of 'cold' tumors within the framework of the cancer-immunity cycle. Correspondingly, we discuss potential strategies for converting 'cold' tumors into 'hot' ones to enhance therapeutic efficacy.

• MeSH
• cirkadiánní rytmus MeSH
• lidé MeSH
• nádorové mikroprostředí * imunologie   MeSH
• nádory * patologie   terapie   MeSH
• střevní mikroflóra MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Across the tree of life, DNA damage response (DDR) proteins play a pivotal, yet dichotomous role in organismal development and evolution. Here, we present a comprehensive analysis of 432 DDR proteins encoded by 68 genomes, including that of Nucleospora cyclopteri, an intranuclear microsporidia sequenced in this study. We compared the DDR proteins encoded by these genomes to those of humans to uncover the DNA repair-ome across phylogenetically distant eukaryotes. We also performed further analyses to understand if organismal complexity and lifestyle play a role in the evolution of DDR protein length and conserved domain architecture. We observed that the genomes of extreme parasites such as Paramicrocytos, Giardia, Spironucleus, and certain microsporidian lineages encode the smallest eukaryotic repertoire of DDR proteins and that pathways involved in modulation of nucleotide pools and nucleotide excision repair are the most preserved DDR pathways in the eukaryotic genomes analysed here. We found that DDR and DNA repair proteins are consistently longer than housekeeping and metabolic proteins. This is likely due to the higher number of physical protein-protein interactions which DDR proteins are involved. We find that although DNA repair proteins are generally longer than housekeeping proteins, their functional domains occupy a relatively smaller footprint. Notably, this pattern holds true across diverse organisms and shows no dependence on either lifestyle or mitochondrial status. Finally, we observed that unicellular organisms harbour proteins that are tenfold longer than their human homologues, with the extra amino acids forming interdomain regions with a clearly novel albeit undetermined function.

• MeSH
• Eukaryota * genetika   MeSH
• fylogeneze MeSH
• lidé MeSH
• Microsporidia genetika   MeSH
• molekulární evoluce * MeSH
• oprava DNA * MeSH
• poškození DNA * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Background and Objectives: Aortic stenosis (AS) is a frequent valvular disease characterized by the obstruction of left ventricular outflow. The resulting hemodynamic and structural changes create an arrhythmogenic substrate, with sudden cardiac death (SCD) often caused by ventricular arrhythmias (VAs) being a feared complication. This review examines the relationship between severe AS and VA, detailing the epidemiology, pathophysiological mechanisms, risk factors, and management approaches prior to aortic valve replacement (AVR). Materials and Methods: We conducted a comprehensive narrative review of the historical and contemporary literature investigating ventricular arrhythmias in severe aortic stenosis. Literature searches were performed in PubMed, MEDLINE, and Scopus databases using keywords, including "aortic stenosis", "ventricular arrhythmia", "sudden cardiac death", and "aortic valve replacement". Both landmark historical studies and modern investigations utilizing advanced monitoring techniques were included to provide a complete evolution of the understanding. Results: The prevalence of ventricular ectopy and non-sustained ventricular tachycardia increases with AS severity and symptom onset. Left ventricular hypertrophy, myocardial fibrosis, altered electrophysiological properties, and ischemia create the arrhythmogenic substrate. Risk factors include the male sex, concomitant aortic regurgitation, elevated filling pressures, and syncope. Diagnostic approaches range from standard electrocardiography to continuous monitoring and advanced imaging. Management centers on timely valve intervention, with medical therapy serving primarily as a bridge to AVR. Conclusions: Ventricular arrhythmias represent a consequence of valvular pathology in severe AS rather than an independent entity. Their presence signals advanced disease and a heightened risk for adverse outcomes. Multidisciplinary management with vigilant monitoring and prompt surgical referral is essential. Understanding this relationship enables clinicians to better identify high-risk patients requiring urgent intervention before life-threatening arrhythmic events occur.

• MeSH
• aortální stenóza * komplikace   chirurgie   patofyziologie   MeSH
• chirurgická náhrada chlopně * metody   MeSH
• komorová tachykardie etiologie   MeSH
• lidé MeSH
• náhlá srdeční smrt etiologie   MeSH
• rizikové faktory MeSH
• srdeční arytmie * etiologie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Non-canonical (non-B) DNA structures-e.g. bent DNA, hairpins, G-quadruplexes (G4s), Z-DNA, etc.-which form at certain sequence motifs (e.g. A-phased repeats, inverted repeats, etc.), have emerged as important regulators of cellular processes and drivers of genome evolution. Yet, they have been understudied due to their repetitive nature and potentially inaccurate sequences generated with short-read technologies. Here we comprehensively characterize such motifs in the long-read telomere-to-telomere (T2T) genomes of human, bonobo, chimpanzee, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. Non-B DNA motifs are enriched at the genomic regions added to T2T assemblies and occupy 9%-15%, 9%-11%, and 12%-38% of autosomes and chromosomes X and Y, respectively. G4s and Z-DNA are enriched at promoters and enhancers, as well as at origins of replication. Repetitive sequences harbor more non-B DNA motifs than non-repetitive sequences, especially in the short arms of acrocentric chromosomes. Most centromeres and/or their flanking regions are enriched in at least one non-B DNA motif type, consistent with a potential role of non-B structures in determining centromeres. Our results highlight the uneven distribution of predicted non-B DNA structures across ape genomes and suggest their novel functions in previously inaccessible genomic regions.

• MeSH
• DNA * chemie   genetika   MeSH
• G-kvadruplexy MeSH
• genom lidský MeSH
• genom * MeSH
• Hominidae * genetika   MeSH
• lidé MeSH
• nukleotidové motivy MeSH
• Pan troglodytes genetika   MeSH
• repetitivní sekvence nukleových kyselin MeSH
• telomery * genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Enterovirus D68 (EV-D68) causes respiratory disease ranging from mild to severe and in rare cases a paralytic syndrome, called acute flaccid myelitis (AFM). Since the global EV-D68 outbreak in 2014, the virus has mainly circulated in biennial epidemic cycles with peaks detected during even years. However, following the COVID-19 pandemic, the seasonal pattern of EV-D68 has been characterized by large yearly upsurges. Here, we describe the circulation of EV-D68 in Europe in 2023 and track its genetic evolution. STUDY DESIGN: Data was compiled from members of the European Non-Polio Network (ENPEN). This included monthly data on the total number of EV samples tested, EV positive samples, EV-D68 positive samples and cases, and other EV positive samples detected in 2023. Information on sample types and surveillance system was recorded. Sequence data from the VP1 gene was used for phylogenetic and amino acid sequence analysis. RESULTS: EV was detected in 13,585 out of 203,622 diagnostic samples tested (6.7 %), of which 402 (3.0 %) were determined as EV-D68, representing 386 cases. EV-D68 infections peaked in October 2023 (136/386; 35.2 %). 267/386 (69.2 %) of EV-D68 cases were captured through clinical EV surveillance, almost all of which (202/204 of positive samples with sample type information) were detected in respiratory specimens. Phylogenetic analysis performed on 99 VP1 sequences revealed a distinct B3-derived lineage with a previously undescribed residue change, D554E, in Europe. CONCLUSIONS: The study documents sustained circulation of EV-D68 in Europe in 2023, the evolution of B3-derived lineages, and appearance of previously undescribed amino acid substitutions in Europe. This stresses the need for continuous EV-D68 surveillance and harmonization of EV-D68 detection practices towards better data comparability across countries.

• MeSH
• COVID-19 epidemiologie   MeSH
• enterovirové infekce * epidemiologie   virologie   MeSH
• fylogeneze MeSH
• lidé MeSH
• lidský enterovirus D * genetika   klasifikace   izolace a purifikace   MeSH
• molekulární evoluce MeSH
• substituce aminokyselin MeSH
• virové plášťové proteiny * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

Diplonemids are among the most abundant and species-rich protists in the oceans. Marine heterotrophic flagellates, including diplonemids, have been suggested to play important roles in global biogeochemical cycles. Diplonemids are also the sister taxon of kinetoplastids, home to trypanosomatid parasites of global health importance, and thus are informative about the evolution of kinetoplastid biology. However, the genomic and cellular complement that underpins diplonemids' highly successful lifestyle is underexplored. At the same time, our framework describing cellular processes may not be as broadly applicable as presumed, as it is largely derived from animal and fungal model organisms, a small subset of extant eukaryotic diversity. In addition to uniquely evolved machinery in animals and fungi, there exist components with sporadic (i.e., "patchy") distributions across other eukaryotes. A most intriguing subset are components ("jötnarlogs") stochastically present in a wide range of eukaryotes but lost in animal and/or fungal models. Such components are considered exotic curiosities but may be relevant to inferences about the complexity of the last eukaryotic common ancestor (LECA) and frameworks of modern cell biology. Here, we use comparative genomics and phylogenetics to comprehensively assess the membrane-trafficking system of diplonemids. They possess several proteins thought of as kinetoplastid specific, as well as an extensive set of patchy proteins, including jötnarlogs. Diplonemids apparently function with endomembrane machinery distinct from existing cell biological models but comparable with other free-living heterotrophic protists, highlighting the importance of including such exotic components when considering different models of ancient eukaryotic genomic complexity and the cell biology of non-opisthokont organisms.

• MeSH
• biologická evoluce MeSH
• fylogeneze MeSH
• Kinetoplastida * fyziologie   genetika   MeSH
• Publikační typ
• časopisecké články MeSH

Telomeres, essential for maintaining genomic stability, are typically preserved through the action of telomerase, a ribonucleoprotein complex that synthesizes telomeric DNA. One of its two core components, telomerase RNA (TR), serves as the template for this synthesis, and its evolution across different species is both complex and diverse. This review discusses recent advancements in understanding TR evolution, with a focus on plants (Viridiplantae). Utilizing novel bioinformatic tools and accumulating genomic and transcriptomic data, combined with corresponding experimental validation, researchers have begun to unravel the intricate pathways of TR evolution and telomere maintenance mechanisms. Contrary to previous beliefs, a monophyletic origin of TR has been demonstrated first in land plants and subsequently across the broader phylogenetic megagroup Diaphoretickes. Conversely, the discovery of plant-type TRs in insects challenges assumptions about the monophyletic origin of TRs in animals, suggesting evolutionary innovations coinciding with arthropod divergence. The review also highlights key challenges in TR identification and provides examples of how these have been addressed. Overall, this work underscores the importance of expanding beyond model organisms to comprehend the full complexity of telomerase evolution, with potential applications in agriculture and biotechnology.

• MeSH
• fylogeneze MeSH
• molekulární evoluce * MeSH
• RNA * genetika   metabolismus   MeSH
• rostliny genetika   MeSH
• telomerasa * genetika   metabolismus   MeSH
• telomery * metabolismus   genetika   MeSH
• Viridiplantae genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Taylorella equigenitalis is the causative agent of sexually transmitted contagious equine metritis. Infections manifest as cervicitis, vaginitis and endometritis and cause temporary infertility and miscarriages of mares. While previous studies have analyzed this organism for various parameters, the evolutionary dynamics of this pathogen, including the emergence of antibiotic resistance, remains unresolved. The aim of this study was to isolate contemporary strains, determine their genome sequences, evaluate their antibiotic resistance and compare them with other strains. We determined nine complete whole genome sequences of T. equigenitalis strains, mainly from samples collected from Kladruber horses in the Czech Republic. While T. equigenitalis strains from Kladruby isolated between 1982 and 2018 were inhibited by streptomycin, contemporary strains were found to be resistant to streptomycin, suggesting the recent emergence of this mutation. In addition, we used the collection dates of Kladruber horse strains to estimate the genome substitution rate, which resulted in a scaled mean evolutionary rate of 6.9×10-7 substitutions per site per year. Analysis with other available T. equigenitalis genome sequences (n = 18) revealed similarity of the Czech T. equigenitalis genomes with the Austrian T. equigenitalis genome, and molecular dating suggested a common ancestor of all analyzed T. equigenitalis strains from 1.5-2.6 thousand years ago, dating to the first centuries A.D. Our study revealed a recently emerged streptomycin resistance in T. equigenitalis strains from Kladruber horses, emphasizing the need for antibiotic surveillance and alternative treatments. Additionally, our findings provided insights into the pathogen's evolution rate, which is important for understanding its evolution and preparing preventive strategies.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální léková rezistence genetika   MeSH
• fylogeneze MeSH
• genom bakteriální * genetika   MeSH
• koně mikrobiologie   MeSH
• molekulární evoluce MeSH
• nemoci koní * mikrobiologie   MeSH
• sekvenování celého genomu * MeSH
• Taylorella equigenitalis * genetika   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Horizontal gene transfer (HGT) is a key driver in the evolution of bacterial genomes. The acquisition of genes mediated by HGT may enable bacteria to adapt to ever-changing environmental conditions. Long-term application of antibiotics in intensive agriculture is associated with the dissemination of antibiotic resistance genes among bacteria with the consequences causing public health concern. Commensal farm-animal-associated gut microbiota are considered the reservoir of the resistance genes. Therefore, in this study, we identified known and not-yet characterized mobilized genes originating from chicken and porcine fecal samples using our innovative pipeline followed by network analysis to provide appropriate visualization to support proper interpretation.

• MeSH
• antibakteriální látky MeSH
• Bacteria genetika   MeSH
• bakteriální geny MeSH
• genom bakteriální MeSH
• mikrobiota * MeSH
• prasata MeSH
• přenos genů horizontální * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• cytogenetika MeSH
• terminologie jako téma MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• cytologie, klinická cytologie
• genetika, lékařská genetika
• NLK Publikační typ
• kolektivní monografie