Eusociality, characterized by reproductive division of labor, cooperative brood care, and multi-generational cohabitation, represents a pinnacle of complex social evolution, most notably manifested within the Hymenoptera order including bees, ants, and wasps. The molecular underpinnings underlying these sophisticated social structures remain an enigma, with noncoding RNAs (ncRNAs) emerging as crucial regulatory players. This article delves into the roles of ncRNAs in exerting epigenetic control during the development and maintenance of Hymenopteran eusociality. We consolidate current findings on various classes of ncRNAs, underscoring their influence on gene expression regulation pertinent to caste differentiation, developmental plasticity, and behavioral modulation. Evidence is explored supporting the hypothesis that ncRNAs contribute to epigenetic landscapes fostering eusocial traits through genomic regulation. They are likely to play an important role in eusociality “point of no return”. Critical analysis is provided on the functional insights garnered from ncRNA profiles correlated with caste-specific phenotypes, specifical for phylogenetic branches and transitional sociality models, drawing from comparative genomics and transcriptomics studies. Overall, ncRNA provides a missed understanding of both “genetic toolkit” and “unique genes” hypotheses of eusociality development. Moreover, it points to gaps in current knowledge, advocating for integrative approaches combining genomics, proteomics, and epigenetics to decipher the complexity of eusociality. Understanding the ncRNA contributions offers not only a window into the molecular intricacies of Hymenoptera sociality but also extends our comprehension of how complex biological systems evolve and function.

Despite global vaccination efforts, poliomyelitis continues to cause paralytic cases, highlighting the need for alternative therapeutic approaches. Nanobodies offer significant advantages over conventional antibodies due to their small size, stability, and low immunogenicity, yet few have been developed specifically against poliovirus. This study presents a fully computational pipeline for de novo design of nanobodies targeting Virus Protein 3 (VP3) of the Poliovirus I Sabin strain. Our integrated approach employed Ig-VAE for scaffold generation, ProteinMPNN and RFantibody for sequence design, tFold-Ab/Ag for structure prediction, multi-platform molecular docking (Rfantibody, Rosetta3, ClusPro2, ReplicaDock 2.0), molecular dynamics simulations, and humanization tools. The pipeline identified three humanized nanobodies (scFv-0389-304-6H, scFv-0389-459-5H, and scFv-0743-166-7/H) that demonstrated strong binding to VP3 with binding free energies of −37.66 ± 10.35, −40.11 ± 20.01, and −48.62 ± 11.21 kcal/mol, respectively. All designs exhibited favorable physicochemical properties and high solubility. Notably, nanobodies humanized prior to CDR-loop design (scFv-0743-166-7/H) showed superior stability, binding affinity, and structural similarity to experimentally validated nanobodies. This work demonstrates the feasibility of a fully computational approach for designing promising nanobodies against viral targets, providing an alternative to traditional methods with potential applications in drug design.

Equine piroplasmosis remains relevant in veterinary practice owing to the possibility of acute disease and latent carrier status, in which laboratory detection of the pathogen is difficult. The aim of the study was a pilot assessment of agreement between blood smear microscopy, local screening PCR and laboratory real-time PCR for the detection of Babesia spp. in horses of different clinical status. Fourteen animals were examined. All underwent clinical examination, microscopy of thin peripheral blood smears, screening PCR using a commercial kit for the detection of Babesia spp. DNA, and testing in an accredited veterinary laboratory, the results of which were used as the comparator method. The full protocol of the laboratory method was not disclosed, therefore it was used as a comparator rather than an absolute reference method. Clinical signs compatible with acute infestation were recorded in 3 of 14 animals, in which the pathogen was detected by microscopy and screening PCR. Laboratory PCR was positive in 10 of 14 horses, including clinically healthy animals negative by the routine methods. Positive percent agreement of microscopy and local screening PCR with the comparator was 30,0 % each, negative percent agreement was 100,0 and 75,0 %, respectively. Cohen kappa was 0,196 and 0,034, indicating slight agreement. Values are reported with 95 % confidence intervals calculated by the Wilson method. A negative result of the routine methods does not exclude Babesia spp. infestation in clinically healthy horses. The findings are preliminary and require verification in an expanded sample using a validated reference method.

Aim. To carry out in silico screening of interactions of synthetic glucocorticoids with TRPM8.Materials and methods. Information on the structure of the ligands was obtained from the PubChem chemical database in sdf format. The TRPM8 protein model was downloaded from the AlphaFold Protein Structure Database (AlpahaFold ID: AF-Q7Z2QW). Prediction of molecular cavities and coordinates of their centers was carried out on the PrankWeb web server. Modeling of molecular interactions was carried out using AutoDock (generation of 100 epochs) and MOE (generation of 300 poses) software.Results. The study revealed that the ligands formed stable complexes with TRPM8, but all of them, except for beclomethasone dipropionate, did not interact with the Tyr745 amino acid residue (the key binding site for channel activation). Thus, it can be assumed that glucocorticoids are most likely inhibitors of this ion channel. Of all glucocorticoids, special attention was paid to prednisolone, flunisolide, and budesonide, since the results of molecular docking of these molecules using AutoDock and MOE showed comparable data.Conclusion. The results obtained provide an insight into the therapeutic potential of these drugs in terms of their use in the treatment of cold-induced airway hyperresponsiveness and also expand the potential for their personalized use in the treatment of bronchial asthma and COPD.

The development of neurodegenerative diseases is associated with proper neuronal circuit formation, axonal guidance. The DCC receptor (deleted in colorectal cancer / colorectal cancer suppressor) and SHH (sonic hedgehog protein) are among the key regulators of axonal guidance.Aim. Interaction prediction of specific enhancer regions of DCC and SHH genes with respectively annotated transcription factors.Materials and methods. An in silico study was performed. The iEnhancer-2L and ES-ARCNN algorithms were selected to estimate enhancer sequence strength. The interaction between transcription factor and enhancer sequence was assessed using the molecular docking method. The enhancer sequence of DCC and SHH protein genes were taken from the NCBI open-source database in FASTA format. Ensembl database was used for enhancer mapping, GeneCards was used for screening and selection of potentially appropriate enhancers and transcription factors associated with these enhancers. The structures of transcription factors as well as their DNA-binding domains were taken from the UniProtKB/Swiss-prot database. An HDOCK scoring function was used as a metric for assessing the possibility of interaction of the target gene transcription factor with associated enhancer sequence.Results. The results showed that the interactions of transcription factor NANOG with the DCC gene enhancer sequence and the interaction of transcription factor CEBPA with the SHH gene enhancer sequence predicted by molecular docking method are potentially possible. The iEnhancer-2L and ES-ARCNN algorithms predicted the enhancer sequence of the SHH gene as strong one. The enhancer sequence of the DCC gene was estimated as strong in the iEnhancer-2L algorithm and as weak in ES-ARCNN. Binding of the DCC gene enhancer sequence to the transcription factor NANOG at 1–206 bp and 686–885 bp sites is the most probable, binding of the SHH gene enhancer sequence to the transcription factor CEBPA at 1–500 bp (HDOCK limitation of 500 bp) is possible.Conclusion. In silico techniques applied in this study demonstrated satisfactory results of predicting the interaction of the transcription factor with the enhancer sequence. Limitations of the current techniques is the lack of consideration of specific transcription factor binding sites. This drawback can be eliminated by implementing an ab initio molecular dynamics simulations into the present pipeline.