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Reproductive abnormalities have been observed in fallow deer populations in Hungary. We supposed mycotoxin contamination to be one of the possible causes because multi-mycotoxin contamination is known to be dangerous even at low toxin levels, especially for young animals. We investigated the spatial pattern of mycotoxin occurrences and the relationship between maternal and fetal mycotoxin levels. A total of 72 fallow deer embryos and their mothers were sampled in seven forested regions in Hungary in the 2020/2021 hunting season. We analyzed Aflatoxin (AF), Zearalenone (ZEA), Fumonizin B1 (FB1), DON, and T2-toxin concentrations in maternal and fetal livers by ELISA. AF was present in 70% and 82%, ZEA in 41% and 96%, DON in 90% and 98%, T2-toxin in 96% and 85%, and FB1 in 84% and 3% of hind and fetus livers, respectively. All mycotoxins passed into the fetus, but only Fumonizin B1 rarely passed. The individual variability of mycotoxin levels was extremely high, but the spatial differences were moderate. We could not prove a relation between the maternal and fetal mycotoxin concentrations, but we found an accumulation of ZEA and DON in the fetuses. These results reflect the possible threats of mycotoxins to the population dynamics and reproduction of wild fallow deer.

Oncolytic virus (OV) therapy has emerged as a promising frontier in cancer treatment, especially for solid tumours. While immunotherapies like immune checkpoint inhibitors and CAR-T cells have demonstrated impressive results, their limitations in inducing complete tumour regression have spurred researchers to explore new approaches targeting tumours resistant to current immunotherapies. OVs, both natural and genetically engineered, selectively replicate within cancer cells, inducing their lysis while sparing normal tissues. Recent advancements in clinical research and genetic engineering have enabled the development of targeted viruses that modify the tumour microenvironment, triggering anti-tumour immune responses and exhibiting synergistic effects with other cancer therapies. Several OVs have been studied for breast cancer treatment, including adenovirus, protoparvovirus, vaccinia virus, reovirus, and herpes simplex virus type I (HSV-1). These viruses have been modified or engineered to enhance their tumour-selective replication, reduce toxicity, and improve oncolytic properties.Newer generations of OVs, such as Oncoviron and Delta-24-RGD adenovirus, exhibit heightened replication selectivity and enhanced anticancer effects, particularly in breast cancer models. Clinical trials have explored the efficacy and safety of various OVs in treating different cancers, including melanoma, nasopharyngeal carcinoma, head and neck cancer, and gynecologic malignancies. Notably, Talimogene laherparepvec (T-VEC) and Oncorine have. been approved for advanced melanoma and nasopharyngeal carcinoma, respectively. However, adverse effects have been reported in some cases, including flu-like symptoms and rare instances of severe complications such as fistula formation. Although no OV has been approved specifically for breast cancer treatment, ongoing preclinical clinical trials focus on four groups of viruses. While mild adverse effects like low-grade fever and nausea have been observed, the effectiveness of OV monotherapy in breast cancer remains insufficient. Combination strategies integrating OVs with chemotherapy, radiotherapy, or immunotherapy, show promise in improving therapeutic outcomes. Oncolytic virus therapy holds substantial potential in breast cancer treatment, demonstrating safety in trials. Multi-approach strategies combining OVs with conventional therapies exhibit more promising therapeutic effects than monotherapy, signalling a hopeful future for OV-based breast cancer treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chowaniec, Ślubowska, Mroczek, Borowczyk, Braszka, Dworacki, Dobosz and Wichtowski.)

The SGI1 family integrative mobilizable elements, which are efficient agents in distribution of multidrug resistance in Gammaproteobacteria, have a complex, parasitic relationship with their IncC conjugative helper plasmids. Besides exploiting the transfer apparatus, SGI1 also hijacks IncC plasmid control mechanisms to time its own excision, replication and expression of self-encoded T4SS components, which provides advantages for SGI1 over its helpers in conjugal transfer and stable maintenance. Furthermore, SGI1 destabilizes its helpers in an unknown, replication-dependent way when they are concomitantly present in the same host. Here we report how SGI1 exploits the helper plasmid partitioning system to displace the plasmid and simultaneously increase its own stability. We show that SGI1 carries two copies of sequences mimicking the parS sites of IncC plasmids. These parS-like elements bind the ParB protein encoded by the plasmid and increase SGI1 stability by utilizing the parABS system of the plasmid for its own partitioning, through which SGI1 also destabilizes the helper plasmid. Furthermore, SGI1 expresses a small protein, Sci, which significantly strengthens this plasmid-destabilizing effect, as well as SGI1 maintenance. The plasmid-induced replication of SGI1 results in an increased copy-number of parS-like sequences and Sci expression leading to strong incompatibility with the helper plasmid., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

COVID-19 disease is characterised by a wide range of symptoms that in most cases resemble flu or cold. Early detection of infections, monitoring of patients' conditions, and identification of patients with worsening symptoms became crucial during the peak of pandemic. The aim of this study was to assess and compare the performance of common early warning scores at the time of admission to an emergency department in predicting in-hospital mortality in patients with COVID-19. The study was based on a retrospective analysis of patients with SARS-CoV-2 infection admitted to an emergency department between March 2020 and April 2022. The prognostic value of early warning scores in predicting in-hospital mortality was assessed using the receiver operating characteristic (ROC) curve. Patients' median age was 59 years, and 52.33% were male. Among all the EWS we assessed, REMS had the highest overall accuracy (AUC 0.84 (0.83-0.85)) and the highest NPV (97.4%). REMS was the most accurate scoring system, characterised by the highest discriminative power and negative predictive value compared to the other analysed scoring systems. Incorporating these tools into clinical practice in a hospital emergency department could provide more effective assessment of mortality and, consequently, avoid delayed medical assistance.

There is an ongoing process in which mitochondrial sequences are being integrated into the nuclear genome. The importance of these sequences has already been revealed in cancer biology, forensic, phylogenetic studies and in the evolution of the eukaryotic genetic information. Human and numerous model organisms' genomes were described from those sequences point of view. Furthermore, recent studies were published on the patterns of these nuclear localised mitochondrial sequences in different taxa.However, the results of the previously released studies are difficult to compare due to the lack of standardised methods and/or using few numbers of genomes. Therefore, in this paper our primary goal is to establish a uniform mining pipeline to explore these nuclear localised mitochondrial sequences.Our results show that the frequency of several repetitive elements is higher in the flanking regions of these sequences than expected. A machine learning model reveals that the flanking regions' repetitive elements and different structural characteristics are highly influential during the integration process.In this paper, we introduce a general mining pipeline for all mammalian genomes. The workflow is publicly available and is believed to serve as a validated baseline for future research in this field. We confirm the widespread opinion, on - as to our current knowledge - the largest dataset, that structural circumstances and events corresponding to repetitive elements are highly significant. An accurate model has also been trained to predict these sequences and their corresponding flanking regions., (© 2024. The Author(s).)

Key Message: Barley AGO4 proteins complement expressional changes of epigenetically regulated genes in Arabidopsis ago4-3 mutant and show a distinct affinity for the 5' terminal nucleotide of small RNAs, demonstrating functional conservation and divergence. The function of Argonaute 4 (AGO4) in Arabidopsis thaliana has been extensively characterized; however, its role in monocots, which have large genomes abundantly supplemented with transposable elements (TEs), remains elusive. The study of barley AGO4 proteins can provide insights into the conserved aspects of RNA-directed DNA methylation (RdDM) and could also have further applications in the field of epigenetics or crop improvement. Bioinformatic analysis of RNA sequencing data identified two active AGO4 genes in barley, HvAGO4a and HvAGO4b. These genes function similar to AtAGO4 in an Arabidopsis heterologous complementation system, primarily binding to 24-nucleotide long small RNAs (sRNAs) and triggering methylation at specific target loci. Like AtAGO4, HvAGO4B exhibits a preference for binding sRNAs with 5' adenine residue, while also accepting 5' guanine, uracil, and cytosine residues. In contrast, HvAGO4A selectively binds only sRNAs with a 5' adenine residue. The diverse binding capacity of barley AGO4 proteins is reflected in TE-derived sRNAs and in their varying abundance. Both barley AGO4 proteins effectively restore the levels of extrachromosomal DNA and transcript abundancy of the heat-activated ONSEN retrotransposon to those observed in wild-type Arabidopsis plants. Our study provides insight into the distinct binding specificities and involvement in TE regulation of barley AGO4 proteins in Arabidopsis by heterologous complementation., (© 2024. The Author(s).)

The transporter associated with antigen processing (TAP) is a key player in the major histocompatibility class I-restricted antigen presentation and an attractive target for immune evasion by viruses. Bovine herpesvirus 1 impairs TAP-dependent antigenic peptide transport through a two-pronged mechanism in which binding of the UL49.5 gene product to TAP both inhibits peptide transport and triggers its proteasomal degradation. How UL49.5 promotes TAP degradation has, so far, remained unknown. Here, we use high-content siRNA and genome-wide CRISPR-Cas9 screening to identify CLR2 KLHDC3 as the E3 ligase responsible for UL49.5-triggered TAP disposal. We propose that the C terminus of UL49.5 mimics a C-end rule degron that recruits the E3 to TAP and engages the cullin-RING E3 ligase in endoplasmic reticulum-associated degradation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Chondrosarcoma, the second most common primary malignant bone tumor, originates from cartilaginous tissue and accounts for almost 20% of all primary bone tumors. The management of chondrosarcoma remains challenging due to its diverse clinical course and prognosis, which can range from benign to highly aggressive with a huge risk of metastasis. Emerging research has demonstrated the importance of microRNA (miRNA) dysregulation in the pathogenesis of chondrosarcoma. MiRNAs are small, noncoding RNA molecules that play an essential role in gene expression regulation by targeting specific messenger RNAs (mRNAs) for degradation or translational repression. This article provides an extensive review of current miRNA research in chondrosarcoma, focusing on diagnostic strategies, cell cycle regulation, drug resistance, biomarkers of progression, and stem cell phenotype. We will examine recent studies identifying differentially expressed miRNAs in chondrosarcoma compared to normal cartilage tissue, exploring their potential as diagnostic and prognostic biomarkers. Furthermore, we will discuss the role of miRNAs in regulating cell cycle progression and their potential as therapeutic targets to overcome drug resistance. We will also investigate the prospective utility of miRNAs as biomarkers of progression and their role in modulating the stem cell phenotype of chondrosarcoma cells. This article offers a comprehensive analysis of current miRNA research in chondrosarcoma, focusing on its potential as diagnostic and prognostic biomarkers, therapeutic targets, and regulators of disease progression. By integrating the latest discoveries in this field, we aim to contribute to the development of novel approaches to the prevention, diagnosis, and treatment of chondrosarcoma, ultimately enhancing patient outcomes.

Background: Interspecific hybridisation is a powerful tool for increasing genetic diversity in plant breeding programmes. Hexaploid wheat (Triticum aestivum, 2n = 42) × barley (Hordeum vulgare, 2n = 14) intergeneric hybrids can contribute to the transfer of agronomically useful traits by creating chromosome addition or translocation lines as well as full hybrids. Information on the karyotype of hybrid progenies possessing various combinations of wheat and barley chromosomes is thus essential for the subsequent breeding steps. Since the standard technique of chromosome in situ hybridisation is labour-intensive and requires specific skills. a routine, cost-efficient, and technically less demanding approach is beneficial both for research and breeding., Results: We developed a Multiplex Polymerase Chain Reaction (MPCR) method to identify individual wheat and barley chromosomes. Chromosome-specific primer pairs were designed based on the whole genome sequences of 'Chinese Spring' wheat and 'Golden Promise' barley as reference cultivars. A pool of potential primers was generated by applying a 20-nucleotide sliding window with consecutive one-nucleotide shifts on the reference genomes. After filtering for optimal primer properties and defined amplicon sizes to produce an ordered ladder-like pattern, the primer pool was manually curated and sorted into four MPCR primer sets for the wheat A, B, and D sub-genomes, and for the barley genome. The designed MPCR primer sets showed high chromosome specificity in silico for the genome sequences of all 18 wheat and barley cultivars tested. The MPCR primers proved experimentally also chromosome-specific for the reference cultivars as well as for 13 additional wheat and four barley genotypes. Analyses of 16 wheat × barley F1 hybrid plants demonstrated that the MPCR primer sets enable the fast and one-step detection of all wheat and barley chromosomes. Finally, the established genotyping system was fully corroborated with the standard genomic in situ hybridisation (GISH) technique., Conclusions: Wheat and barley chromosome-specific MPCR offers a fast, labour-friendly, and versatile alternative to molecular cytogenetic detection of individual chromosomes. This method is also suitable for the high-throughput analysis of distinct (sub)genomes, and, in contrast to GISH, can be performed with any tissue type. The designed primer sets proved to be highly chromosome-specific over a wide range of wheat and barley genotypes as well as in wheat × barley hybrids. The described primer design strategy can be extended to many species with precise genome sequence information., (© 2024. The Author(s).)

Environmentally sensitive sex determination may help organisms adapt to environmental change but also makes them vulnerable to anthropogenic stressors, with diverse consequences for population dynamics and evolution. The mechanisms translating environmental stimuli to sex are controversial: although several fish experiments supported the mediator role of glucocorticoid hormones, results on some reptiles challenged it. We tested this hypothesis in amphibians by investigating the effect of corticosterone on sex determination in agile frogs (Rana dalmatina). This species is liable to environmental sex reversal whereby genetic females develop into phenotypic males. After exposing tadpoles during sex determination to waterborne corticosterone, the proportion of genetic females with testes or ovotestes increased from 11% to up to 32% at 3 out of 4 concentrations. These differences were not statistically significant except for the group treated with 10 nM corticosterone, and there was no monotonous dose-effect relationship. These findings suggest that corticosterone is unlikely to mediate sex reversal in frogs. Unexpectedly, animals originating from urban habitats had higher sex-reversal and corticosterone-release rates, reduced body mass and development speed, and lower survival compared to individuals collected from woodland habitats. Thus, anthropogenic environments may affect both sex and fitness, and the underlying mechanisms may vary across ectothermic vertebrates., (© 2023 The Authors. Journal of Experimental Zoology Part A: Ecological and Integrative Physiology published by Wiley Periodicals LLC.)

Grain Width and Weight 2 (GW2) is an E3-ubiquitin ligase-encoding gene that negatively regulates the size and weight of the grain in cereal species. Therefore, disabling GW2 gene activity was suggested for enhancing crop productivity. We show here that CRISPR/Cas-mediated mutagenesis of the barley GW2.1 homologue results in the development of elongated grains and increased protein content. At the same time, GW2.1 loss of function induces a significant grain yield deficit caused by reduced spike numbers and low grain setting. We also show that the converse effect caused by GW2.1 absence on crop yield and protein content is largely independent of cultivation conditions. These findings indicate that the barley GW2.1 gene is necessary for the optimization between yield and grain traits. Altogether, our data show that the loss of GW2.1 gene activity in barley is associated with pleiotropic effects negatively affecting the development of generative organs and consequently the grain production. Our findings contribute to the better understanding of grain development and the utilisation of GW2.1 control in quantitative and qualitative genetic improvement of barley., Competing Interests: Declaration of Competing Interest All the authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Mutations of the SCN1A gene, which encodes the voltage-dependent Na + channel's α subunit, are associated with diverse epileptic syndromes ranging in severity, even intra-family, from febrile seizures to epileptic encephalopathy. The underlying cause of this variability is unknown, suggesting the involvement of additional factors. The aim of our study was to describe the properties of mutated channels and investigate genetic causes for clinical syndromes' variability in the family of five SCN1A gene p.Arg1596Cys mutation carriers. The analysis of additional genetic factors influencing SCN1A -associated phenotypes was conducted through exome sequencing (WES). To assess the impact of mutations, we used patch clamp analysis of mutated channels expressed in HEK cells and in vivo neural excitability studies (NESs). In cells expressing the mutant channel, sodium currents were reduced. NESs indicated increased excitability of peripheral motor neurons in mutation carriers. WES showed the absence of non-SCA1 pathogenic variants that could be causative of disease in the family. Variants of uncertain significance in three genes, as potential modifiers of the most severe phenotype, were identified. The p.Arg1596Cys substitution inhibits channel function, affecting steady-state inactivation kinetics. Its clinical manifestations involve not only epileptic symptoms but also increased excitability of peripheral motor fibers. The role of Nav1.1 in excitatory neurons cannot be ruled out as a significant factor of the clinical phenotype.

Interspecific hybridizations among sturgeon species are feasible and often bidirectional. The American paddlefish ( Polyodon spathula ) from Family Polyodontidae and sturgeon species from Family Acipenseridae were reported capable of hybridization, but viable hybrids have been described only in crosses with the American paddlefish as paternal parents. In the reciprocal cross, the hybrids were not viable however embryos start to develop and reach late gastrula and early neurula stages. The goal of this study was to examine the hybridization between the sterlet sturgeon ( Acipenser ruthenus ) and the American paddlefish. Hybrid and purebred crosses were produced by artificial fertilization. Viable hybrid offspring were harvested (three month old) and verified in the families produced by female sterlet crossing with male American paddlefish. In the reciprocal hybrid crosses with female American paddlefish and male sterlet, the embryos development did not pass over 120 h post fertilization, indicating the unidirectional hybridization between American paddlefish and sterlet. Chromosome counting showed for the same ploidy level of viable hybrid and parent species. Analysis of three microsatellite markers confirmed the unidirectional hybridization between the American paddlefish and the sterlet species. Overall, the inferred genetic cause suggests that unidirectional hybridization between American paddlefish and sterlet may be the case not only for these two species but likely also between American paddlefish and other sturgeon species., Competing Interests: The authors declare there are no competing interests., (©2024 Káldy et al.)

Incorporating the centromere-specific histone H3 protein CENH3 into the centromeric nucleosomes is indispensable for accurate centromere function and balanced chromosome segregation in most eukaryotes, including higher plants. In the cell nuclei of interspecific hybrids, divergent centromeric DNAs cohabit and lead the corresponding parental chromosomes through the mitotic and meiotic cell divisions. Depending on the transmission of the parental chromosomes carrying the CENH3-encoding genes, CENH3 proteins from one or both parents may be present in these hybrids. The incorporation of parental CENH3 proteins into the divergent centromeres and their role in the chromosome elimination process in interspecific hybrids is still poorly understood. Here, we produced wheat × barley F1 hybrids that carried different combinations of barley chromosomes with genes encoding for either one (αCENH3) or both barley CENH3 protein variants (α- and βCENH3). We generated specific antibodies distinguishing between the wheat CENH3 proteins and barley αCENH3 and applied them together with FISH probes to detect the precise pattern of parental CENH3 deposition into the wheat and barley centromeric nucleosomes. Analysis of somatic and meiotic nuclei of the wheat × barley hybrids revealed the plasticity of the maternal (wheat) CENH3 proteins to become incorporated into the paternal (barley) centromeric nucleosomes. However, no evidence for paternal CENH3 plasticity was detected in this study. The significance of the unilateral centromere plasticity and possible patterns of CENH3 incorporation into centromeres in interspecific hybrids are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Mihók, Polgári, Lenykó-Thegze, Makai, Fábián, Ali, Kis, Sepsi and Sági.)

The significance of heat stress in agriculture is ever-increasing with the progress of global climate changes. Due to a negative effect on the yield of staple crops, including wheat, the impairment of plant reproductive development triggered by high ambient temperature became a restraint in food production. Although the heat sensitivity of male meiosis and the following gamete development in wheat has long been recognized, a detailed structural characterization combined with a comprehensive gene expression analysis has not been done about this phenomenon. We demonstrate here that heat stress severely alters the cytoskeletal configuration, triggers the failure of meiotic division in wheat. Moreover, it changes the expression of genes related to gamete development in male meiocytes and the tapetum layer in a genotype-dependent manner. 'Ellvis', a heat-tolerant winter wheat cultivar, showed high spikelet fertility rate and only scarce structural aberrations upon exposure to high temperature. In addition, heat shock genes and genes involved in scavenging reactive oxygen species were significantly upregulated in 'Ellvis', and the expression of meiosis-specific and major developmental genes showed high stability in this cultivar. In the heat-sensitive 'Mv 17-09', however, genes participating in cytoskeletal fiber nucleation, the spindle assembly checkpoint genes, and tapetum-specific developmental regulators were downregulated. These alterations may be related to the decreased cytoskeleton content, frequent micronuclei formation, and the erroneous persistence of the tapetum layer observed in the sensitive genotype. Our results suggest that understanding the heat-sensitive regulation of these gene functions would be an essential contribution to the development of new, heat-tolerant cultivars., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fábián, Péntek, Soós and Sági.)

Soft tissue sarcomas (STS) originating from connective tissue rarely affect the lymph nodes. However, involvement of lymph nodes in STS is an important aspect of prognosis and treatment. Currently, there is no consensus on the diagnosis and management of lymph node metastases in STS. The key risk factor for nodal involvement is the histological subtype of sarcoma. Radiological and pathological evaluation seems to be the most effective method of assessing lymph nodes in these neoplasms. Thus, sentinel lymph node biopsy (SLNB), which has been shown to be valuable in the management of melanoma or breast cancer, may also be a beneficial diagnostic option in some high-risk STS subtypes. This review summarizes data on the risk factors and clinical characteristics of lymph node involvement in STS. Possible management and therapeutic options are also discussed.

The mitochondrial retrograde signaling (RTG) pathway of communication from mitochondria to the nucleus was first studied in yeast Saccharomyces cerevisiae. It rewires cellular metabolism according to the mitochondrial state by reprogramming nuclear gene expression in response to mitochondrial triggers. The main players involved in retrograde signaling are the Rtg1 and Rtg3 transcription factors, and a set of positive and negative regulators, including the Rtg2, Mks1, Lst8, and Bmh1/2 proteins. Retrograde regulation is integrated with other processes, including stress response, osmoregulation, and nutrient sensing through functional crosstalk with cellular pathways such as high osmolarity glycerol or target of rapamycin signaling. In this review, we summarize metabolic changes observed upon retrograde stimulation and analyze the progress made to uncover the mechanisms underlying the integration of regulatory circuits. Comparisons of the evolutionary adaptations of the retrograde pathway that have occurred in the different yeast groups can help to fully understand the process., (© 2023 International Union of Biochemistry and Molecular Biology.)

Metaviridae is a family of reverse-transcribing viruses, closely related to retroviruses; they exist within their host's DNA as transposable elements. Transposable element study requires the use of specialized tools, in part because of their repetitive nature. By combining data from transcript RNA-Seq, small RNA-Seq, and parallel analysis of RNA ends-Seq from grapevine somatic embryos, we set up a bioinformatics flowchart that could be able to assemble and identify transposable elements., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Yeast mitochondrial genes are expressed as polycistronic transcription units that contain RNAs from different classes and show great evolutionary variability. The promoters are simple, and transcriptional control is rudimentary. Posttranscriptional mechanisms involving RNA maturation, stability, and degradation are thus the main force shaping the transcriptome and determining the expression levels of individual genes. Primary transcripts are fragmented by tRNA excision by RNase P and tRNase Z, additional processing events occur at the dodecamer site at the 3' end of protein-coding sequences. groups I and II introns are excised in a self-splicing reaction that is supported by protein splicing factors encoded by the nuclear genes, or by the introns themselves. The 3'-to-5' exoribonucleolytic complex called mtEXO is the main RNA degradation activity involved in RNA turnover and processing, supported by an auxiliary 5'-to-3' exoribonuclease Pet127p. tRNAs and, to a lesser extent, rRNAs undergo several different base modifications. This complex gene expression system relies on the coordinated action of mitochondrial and nuclear genes and undergoes rapid evolution, contributing to speciation events. Moving beyond the classical model yeast Saccharomyces cerevisiae to other budding yeasts should provide important insights into the coevolution of both genomes that constitute the eukaryotic genetic system., (© 2023 International Union of Biochemistry and Molecular Biology.)

Conventional dendritic cells (cDCs) are innate immune cells that play a pivotal role in inducing antiviral adaptive immune responses due to their extraordinary ability to prime and polarize naïve T cells into different effector T helper (Th) subsets. The two major subpopulations of cDCs, cDC1 (CD8α + in mice and CD141 + in human) and cDC2 (CD11b + in mice and CD1c + in human), can preferentially polarize T cells toward a Th1 and Th2 phenotype, respectively. During infection with ectromelia virus (ECTV), an orthopoxvirus from the Poxviridae family, the timing and activation of an appropriate Th immune response contributes to the resistance (Th1) or susceptibility (Th2) of inbred mouse strains to the lethal form of mousepox. Due to the high plasticity and diverse properties of cDC subpopulations in regulating the quality of a specific immune response, in the present study we compared the ability of splenic cDC1 and cDC2 originating from different ECTV-infected mouse strains to mature, activate, and polarize the Th immune response during mousepox. Our results demonstrated that during early stages of mousepox, both cDC subsets from resistant C57BL/6 and susceptible BALB/c mice were activated upon in vivo ECTV infection. These cells exhibited elevated levels of surface MHC class I and II, and co-stimulatory molecules and showed enhanced potential to produce cytokines. However, both cDC subsets from BALB/c mice displayed a higher maturation status than that of their counterparts from C57BL/6 mice. Despite their higher activation status, cDC1 and cDC2 from susceptible mice produced low amounts of Th1-polarizing cytokines, including IL-12 and IFN-γ, and the ability of these cells to stimulate the proliferation and Th1 polarization of allogeneic CD4 + T cells was severely compromised. In contrast, both cDC subsets from resistant mice produced significant amounts of Th1-polarizing cytokines and demonstrated greater capability in differentiating allogeneic T cells into Th1 cells compared to cDCs from BALB/c mice. Collectively, our results indicate that in the early stages of mousepox, splenic cDC subpopulations from the resistant mouse strain can better elicit a Th1 cell-mediated response than the susceptible strain can, probably contributing to the induction of the protective immune responses necessary for the control of virus dissemination and for survival from ECTV challenge.

Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The aim of this study is to reveal how myenteric barrier disruption and subsequent neuronal injury affects gut motility in vivo in a murine colitis model. We induced colitis with dextran sulfate sodium (DSS), with the co-administration of liposome-encapsulated clodronate (L-clodronate) to simultaneously deplete blood monocytes contributing to macrophage infiltration in the inflamed muscularis of experimental mice. DSS-treated animals receiving concurrent L-clodronate injection showed significantly decreased blood monocyte numbers and colon muscularis macrophage (MM) density compared to DSS-treated control (DSS-vehicle). DSS-clodronate-treated mice exhibited significantly slower whole gut transit time than DSS-vehicle-treated animals and comparable to that of controls. Experiments with oral gavage-fed Evans-blue dye showed similar whole gut transit times in DSS-clodronate-treated mice as in control animals. Furthermore, qPCR-analysis and immunofluorescence on colon muscularis samples revealed that factors associated with neuroinflammation and neurodegeneration, including Bax1, Hdac4, IL-18, Casp8 and Hif1a are overexpressed after DSS-treatment, but not in the case of concurrent L-clodronate administration. Our findings highlight that MM-infiltration in the muscularis layer is responsible for colitis-associated dysmotility and enteric neuronal dysfunction along with the release of mediators associated with neurodegeneration in a murine experimental model., (© 2023. The Author(s).)

Leber hereditary optic neuropathy (LHON) is a rare disorder causing a sudden painless loss of visual acuity in one or both eyes, affecting young males in their second to third decade of life. The molecular background of the LHON is up to 90%, genetically defined by a point mutation in mitochondrial DNA. Recently, an autosomal recessive form of LHON (LHONAR1, arLHON) has been discovered, caused by biallelic variants in the DNAJC30 gene. This study provides the results of the DNAJC30 gene analysis in a large group of 46 Polish patients diagnosed with LHON, together with the clinical characterization of the disease. The c.152A>G (p.Tyr51Cys) substitution in the DNAJC30 gene was detected in all the patients as homozygote or compound heterozygote. Moreover, we identified one novel variant, c.293A>G, p.(Tyr98Cys), as well as two ultra-rare DNAJC30 variants: c.293A>C, p.(Tyr98Ser), identified to date only in one individual affected with LHONAR1, and c.130_131delTC (p.Ser44ValfsTer8), previously described only in two patients with Leigh syndrome. The patients presented here represent the largest group of subjects with DNAJC30 gene mutations described to date. Based on our data, the autosomal recessive form of LHON caused by DNAJC30 gene mutations is more frequent than the mitochondrial form in Polish patients. The results of our study suggest that Sanger sequencing of the single-exon DNAJC30 gene should be a method of choice applied to identify a molecular background of clinically confirmed LHON in Polish patients. This approach will help to reduce the costs of molecular testing.

The golden jackal (Canis aureus) is a reoccurring species in the centre of the Carpathian basin, in Hungary. In total, 31 golden jackal tissue samples were collected, from 8 white-coated, 2 black-coated and one mottled animal across Hungary. Sequences and fragment length polymorphisms were studied for white colour (MC1R), and for black coat colouration (CBD103). In each white animal, the most widespread mutation causing white fur colour in dogs in homozygous form was detected. Three animals were found to carry the mutation in heterozygous form. The two black golden jackals were heterozygous for the 3 bp deletion in CBD103 that mutation for black coat colouration in dogs, and one of them also carried the mutation causing white fur. None of the white animals showed signs of hybridization, but both the black and the mottled coloured individuals were found to be hybrids based on genetic testing. Kinship was found three times, twice between white animals, and once between a white animal and an agouti animal carrying the mutation of white coat. Our results confirm the findings that golden jackal-dog hybrids may occur without human intervention, and the detected mutation causing white fur colour in golden jackals could possibly be due to an early hybridization event., (© 2023. The Author(s).)

The host-produced nodule specific cysteine-rich (NCR) peptides control the terminal differentiation of endosymbiotic rhizobia in the nodules of IRLC legumes. Although the Medicago truncatula genome encodes about 700 NCR peptides, only few of them have been proven to be crucial for nitrogen-fixing symbiosis. In this study, we applied the CRISPR/Cas9 gene editing technology to generate knockout mutants of NCR genes for which no genetic or functional data were previously available. We have developed a workflow to analyse the mutation and the symbiotic phenotype of individual nodules formed on Agrobacterium rhizogenes-mediated transgenic hairy roots. The selected NCR genes were successfully edited by the CRISPR/Cas9 system and nodules formed on knockout hairy roots showed wild type phenotype indicating that peptides NCR068, NCR089, NCR128 and NCR161 are not essential for symbiosis between M. truncatula Jemalong and Sinorhizobium medicae WSM419. We regenerated stable mutants edited for the NCR068 from hairy roots obtained by A. rhizogenes-mediated transformation. The analysis of the symbiotic phenotype of stable ncr068 mutants showed that peptide NCR068 is not required for symbiosis with S. meliloti strains 2011 and FSM-MA either. Our study reports that gene editing can help to elicit the role of certain NCRs in symbiotic nitrogen fixation., (© 2023. The Author(s).)

The purpose of this study was to determine the effectiveness of a phytobiotic-prebiotic feed additive (PPFA, which contains a combination of chicory and extracts of carob pulp and fenugreek) in the diets of fattening pigs on growth indicators, carcass characteristics, and fecal microbiota. A total of 329 crossbred pigs were randomly divided into two dietary treatments, including a basal diet without additives as the control group and a basal diet supplemented with 1 kg/T PPFA as the trial group. The PPFA supplementation led to a significant increase in the body weight gain and average daily gain of the trial group compared to those of the control group after 70 days of feeding. Through the S-EUROP evaluation system, we also found that the fattening pigs fed PPFA significantly improved their carcass indicators. Furthermore, it was shown that PPFA regulated porcine intestinal microbiota, including promoting the growth of the beneficial commensal bacteria (i.e., Bifidobacterium and Lactobacillus ) while inhibiting some potential pathogen bacteria (i.e., Bacteroidaceae and Campylobacteraceae ). Our work revealed that the phytobiotic-prebiotic feed additive containing carob pulp, chicory, and fenugreek positively influences the intestinal microbiota, growth performance, and carcass traits in fattening swine.

Antiviral RNAi is the main protective measure employed by plants in the fight against viruses. The main steps of this process have been clarified in recent years, primarily relying on the extensive genetic resources of Arabidopsis thaliana. Our knowledge of viral diseases of crops, however, is still limited, mainly due to the fact that A. thaliana is a non-host for many agriculturally important viruses. In contrast, Nicotiana benthamiana has an unparalleled susceptibility to viruses and, since it belongs to the Solanaceae family, it is considered an adequate system for modeling infectious diseases of crops such as tomatoes. We used a series of N. benthamiana mutants created by genome editing to analyze the RNAi response elicited by the emerging tomato pathogen, pepino mosaic virus (PepMV). We uncovered hierarchical roles of several Argonaute proteins (AGOs) in anti-PepMV defense, with the predominant contribution of AGO2. Interestingly, the anti-PepMV activities of AGO1A, AGO5, and AGO10 only become apparent when AGO2 is mutated. Taken together, our results prove that hierarchical actions of several AGOs are needed for the plant to build effective anti-PepMV resistance. The genetic resources created here will be valuable assets for analyzing RNAi responses triggered by other agriculturally important pathogenic viruses., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Background: NOL12 5'-3' exoribonucleases, conserved among eukaryotes, play important roles in pre-rRNA processing, ribosome assembly and export. The most well-described yeast counterpart, Rrp17, is required for maturation of 5.8 and 25S rRNAs, whereas human hNOL12 is crucial for the separation of the large (LSU) and small (SSU) ribosome subunit rRNA precursors., Results: In this study we demonstrate that plant AtNOL12 is also involved in rRNA biogenesis, specifically in the processing of the LSU rRNA precursor, 27S pre-rRNA. Importantly, the absence of AtNOL12 alters the expression of many ribosomal protein and ribosome biogenesis genes. These changes could potentially exacerbate rRNA biogenesis defects, or, conversely, they might stem from the disturbed ribosome assembly caused by delayed pre-rRNA processing. Moreover, exposure of the nol12 mutant to stress factors, including heat and pathogen Pseudomonas syringae, enhances the observed molecular phenotypes, linking pre-rRNA processing to stress response pathways. The aberrant rRNA processing, dependent on AtNOL12, could impact ribosome function, as suggested by improved mutant resistance to ribosome-targeting antibiotics., Conclusion: Despite extensive studies, the pre-rRNA processing pathway in plants remains insufficiently characterized. Our investigation reveals the involvement of AtNOL12 in the maturation of rRNA precursors, correlating this process to stress response in Arabidopsis. These findings contribute to a more comprehensive understanding of plant ribosome biogenesis., (© 2023. The Author(s).)

RNA stability and quality control are integral parts of gene expression regulation. A key factor shaping eukaryotic transcriptomes, mainly via 3'-5' exoribonucleolytic trimming or degradation of diverse transcripts in nuclear and cytoplasmic compartments, is the RNA exosome. Precise exosome targeting to various RNA molecules requires strict collaboration with specialized auxiliary factors, which facilitate interactions with its substrates. The predominant class of cytoplasmic RNA targeted by the exosome are protein-coding transcripts, which are carefully scrutinized for errors during translation. Normal, functional mRNAs are turned over following protein synthesis by the exosome or by Xrn1 5'-3'-exonuclease, acting in concert with Dcp1/2 decapping complex. In turn, aberrant transcripts are eliminated by dedicated surveillance pathways, triggered whenever ribosome translocation is impaired. Cytoplasmic 3'-5' mRNA decay and surveillance are dependent on the tight cooperation between the exosome and its evolutionary conserved co-factor-the SKI (superkiller) complex (SKIc). Here, we summarize recent findings from structural, biochemical, and functional studies of SKIc roles in controlling cytoplasmic RNA metabolism, including links to various cellular processes. Mechanism of SKIc action is illuminated by presentation of its spatial structure and details of its interactions with exosome and ribosome. Furthermore, contribution of SKIc and exosome to various mRNA decay pathways, usually converging on recycling of ribosomal subunits, is delineated. A crucial physiological role of SKIc is emphasized by describing association between its dysfunction and devastating human disease-a trichohepatoenteric syndrome (THES). Eventually, we discuss SKIc functions in the regulation of antiviral defense systems, cell signaling and developmental transitions, emerging from interdisciplinary investigations. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes., (© 2023 Wiley Periodicals LLC.)

U7 snRNP is a multisubunit endonuclease required for 3' end processing of metazoan replication-dependent histone pre-mRNAs. In contrast to the spliceosomal snRNPs, U7 snRNP lacks the Sm subunits D1 and D2 and instead contains two related proteins, Lsm10 and Lsm11. The remaining five subunits of the U7 heptameric Sm ring, SmE, F, G, B, and D3, are shared with the spliceosomal snRNPs. The pathway that assembles the unique ring of U7 snRNP is unknown. Here, we show that a heterodimer of Lsm10 and Lsm11 tightly interacts with the methylosome, a complex of the arginine methyltransferase PRMT5, MEP50, and pICln known to methylate arginines in the carboxy-terminal regions of the Sm proteins B, D1, and D3 during the spliceosomal Sm ring assembly. Both biochemical and cryo-EM structural studies demonstrate that the interaction is mediated by PRMT5, which binds and methylates two arginine residues in the amino-terminal region of Lsm11. Surprisingly, PRMT5 also methylates an amino-terminal arginine in SmE, a subunit that does not undergo this type of modification during the biogenesis of the spliceosomal snRNPs. An intriguing possibility is that the unique methylation pattern of Lsm11 and SmE plays a vital role in the assembly of the U7 snRNP., (© 2023 Yang et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Symbiotic interactions between legumes and rhizobia lead to the development of root nodules and nitrogen fixation by differentiated bacteroids within nodules. Differentiation of the endosymbionts is reversible or terminal, determined by plant effectors. In inverted repeat lacking clade legumes, nodule-specific cysteine-rich (NCR) peptides control the terminal differentiation of bacteroids. Medicago truncatula contains ∼700 NCR-coding genes. However, the role of few NCR peptides has been demonstrated. Here, we report characterization of fast neutron 2106 (FN2106), a symbiotic nitrogen fixation defective (fix-) mutant of M. truncatula. Using a transcript-based approach, together with linkage and complementation tests, we showed that loss-of-function of NCR343 results in impaired bacteroid differentiation and/or maintenance and premature nodule senescence of the FN2106 mutant. NCR343 was specifically expressed in nodules. Subcellular localization studies showed that the functional NCR343-YFP fusion protein colocalizes with bacteroids in symbiosomes in infected nodule cells. Transcriptomic analyses identified senescence-, but not defense-related genes, as being significantly upregulated in ncr343 (FN2106) nodules. Taken together, results from our phenotypic and transcriptomic analyses of a loss-of-function ncr343 mutant demonstrate an essential role of NCR343 in bacteroid differentiation and/or maintenance required for symbiotic nitrogen fixation., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Roy N. Alcalay received consulting fees from Avrobio, Caraway, Ono Therapeutics, GSK, Merck, Sanofi, Janssen and grants from the Michael J. Fox Foundation, DOD, the Parkinson’s Disease Foundation, and the NIH. Melinda Barkhuizen received a PhD scholarship from the National Research Foundation of South Africa (grant numbers 89230 and 98217) and internal funding from the research center where the study was conducted (DST/NWU Preclinical Drug Development Platform, North-West University, South Africa); Ampath Pathology laboratories in South Africa donated services in the form of drawing participant blood for DNA extractions, Several neurologists in South Africa assisted the authors with identifying patients with Parkinson`s disease and referring them to the genotyping study; the North-West University, South Africa provided Ethical oversight and approval of the genotyping project. Vincenzo Bonifati received grants from Stichting Parkinson Fonds (Netherlands) and Alzheimer Nederland, he received honoraria from the International Parkinson and Movement Disorder Society (MDS), for lectures and as Chair of the International Congress Scientific Program Committee (2020-2021), and from Elsevier Ltd. as co-Editor in Chief of the journal Parkinsonism & Related Disorders (2018-current); he is unpaid member of the Stichting Parkinson Fonds (Netherlands). Kathrin Brockmann received grants from the German Federal Ministry of Education and Research (BMBF; PDStrat; FKZ 031L0137B) and from the German Center for Neurodegenerative Diseases (DZNE), consulting fees from Abbvie, Lundbeck, UCB, Zambon, Roche, and honoraria from Abbvie and UCB. Jordi Clarimon is full-time employee at Lundbeck A/S (Denmark). Mario Cornejo-Olivas has subcontracts with Cleveland Clinic and San Marcos Foundation for recruiting participants for the LARGE PD study in Peru. Jean-Christophe Corvol received grants from Sanofi and the Michael J. Fox Foundation, consulting fees from Biogen, UCB, Denali, Idorsia, Prevail therapeutics, Theranexus, and honoraria from Biogen. Joana Damásio received honoraria from Zambon Pharmaceuticals. Anna De Rosa received grants for ROPAD – the Rostock International Parkinson’s Disease Study, sponsored by Centogene and grants from Zambon and AIFA (Italian Agency of Drug), and she is member of the advisory board at BIAL. Joaquim Ferreira received grants from Fundação MSD (Portugal), Novartis, Medtronic, and Abbvie, and lecture fees from Lundbeck, Abbvie, BIAL, Biogen, Sunovion Pharmaceuticals, ONO, Affiris, and Zambon, payment for expert testimony from Novartis, and he participates in advisory boards of Lundbeck, Abbvie, BIAL, Affiris, Sunovion Pharmaceuticals, and Zambon; he is employed by CNS (Campus Néurologico Sénior) and the Medical Faculty of Lisbon. Emilia Gatto received consulting fees from Bago Argentina, honoraria from Bago Argentina,UCB, IPMDS, and Europharm, and participates in advisory boards of Bago Argentina and UCB. Nir Giladi received grants from the Michael J Fox Foundation, The National Parkinson Foundation, The European Union, The Israel Science Foundation Teva, NNE program, Biogen, Ionis, Sieratzki Family Foundation, and The Aufzien Academic Center in Tel-Aviv University; he holds royalties or licenses at Lysosomal Therapeutics (LTI); he received consulting fees from Sionara, NeuroDerm, Pharma2B, Denali, Neuron23, Sanofi-Genzyme, Biogen, and Abbvie; he received honoraria from Abbvie, Sanofi-Genzyme, and the Movement Disorder Society. Nobutaka Hattori received grants from the Japan Society for the Promotion of Science (JSPS; 18H04043, 21H04820, 19K22603), the Japan Agency for Medical Research and Development (AMED; JP20dm0307101, JP20dm0207070, JP20ek0109358, JP19ek0109393, JP19gm0710011, JP19km0405206), Health Labour Sciences Research Grant (20FC1049, H29-FC1-062, H29-FC1-033), and the Japan Science and Technology Agency (JPMJMS2024-5); he participates in advisory boards at Dai-Nippon Sumitomo Pharma, Takeda Pharmaceutical, Kyowa Kirin, TEIJIN PHARMA LIMITED, Novartis Pharma, Ono Pharmaceutical, Biogen Idec Japan, and Kissei Pharmaceutical; he receives consulting fees from Hisamitsu Pharma; he received honoraria from Dai-Nippon Sumitomo Pharma, Takeda Pharmaceutical, Kyowa Kirin, AbbVie GK, Nippon Boehringer Ingelheim, Otsuka Pharmaceutical, Novartis Pharma, Bristol-Myers Squibb, Ono Pharmaceutical, FP Pharmaceutical, Eisai, Kissei Pharmaceutical, Nihon Medi-physics, and Daiichi Sankyo; he received payment for expert testimony from Mitsubishi Tanabe Pharma; he received support for attending meeting from Takeda Pharmaceutical, and Kyowa Kirin; he has 17 patents planned or pending and 5 issued; he is Team Leader at the Neurodegenerative Disorders Collaborative Laboratory, RIKEN Center for Brain Science; he holds equity stock (8%) of PARKINSON Laboratories Co. Ltd., unrelated to the submitted work. Silvia Jesús has received grants from “Consejería de Salud y Familias” PI-0459-2018, “acción B Clínicos-Investigdores” B-0007-2019 and from the “instituto de Salud Carlos III” PI-18/01898; she received honoraria from Abbvie, Bial, Merz, UCB, Italfarmaco, Zambon and Server. Valtteri Kaasinen received grants from Turku University Foundation, Päivikki and Sakari Sohlberg Foundation, and the Finnish Cultural Foundation; he received consulting fees from Nordic Infucare, Abbvie, and Adamant Health; he received honoraria from Nordic Infucare and Abbvie; he received Support for attending meetings and/or travel from Nordic Infucare; he participates on a Data Safety Monitoring Board or Advisory Board at Nordic Infucare and Abbvie; he is board member of the Finnish Neurological Society. Christine Klein received royalties from Oxford University Press; she received consulting fees from Centogene and Retromer Therapeutics; she received payment or honoraria from Desitin Pharma; she received support to attend meetings from the Movement Disorder Society; she participates on a Data Safety Monitoring Board or Advisory Board at the Else Kroener Fresenius Foundation. Peter Klivenyi received honoraria from Abbvie and Medtronic. Vladimir Kostic received Grant 17590 from the Ministry of Education, Science and Technological Development of Serbia; he received honoraria from Novartis and Boehringer Ingelheim. Shen-Yang Lim received the following grants, (i) Stipend - Global Parkinson’s Genetics Program (GP2) Working Group Co-Lead Award, from the Michael J. Fox Foundation, (ii) Michael J. Fox Foundation (Grant 18305: "Identifying leucocyte and urine biomarkers in PD patients with LRRK2 G2385R variant"). George Mellick received grants from the National Health and Medical Research Foundation, Australia (APP1151854, APP1084560). Lukasz Milanowski received grants from the Polish National Agency for Academic Exchange Iwanowska’s Fellowship PPN/IWA/2018/1/00006/U/00001/01, the APDA, the Foundation for Polish Science (FNP) and the Haworth Family Professorship in Neurodegenerative Diseases Fund. Pablo mir received grants from the Spanish Ministry of Science and Innovation (RTC2019-007150-1), the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (ISCIII-FEDER, PI19/01576), and the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PE-0210-2018); he received payment or honoraria for lectures from Abbvie, Abbott, and Zambon; he received Support for attending meetings and travel from Abbvie. Shalini Padmanabhan is employed by the Michael J. Fox Foundation. Andreas Puschmann received grants from Region Skåne, Sweden, Skåne University Hospital, Sweden, The Swedish Parkinson Academy, The Swedish Parkinson Foundation (Parkinsonfonden), MultiPark – a strategic research environment at Lund University, and Bundy Academy, Sweden; he received honoraria from Elsevier (Associate editor for Parkinsonism and Related Disorders), from the International Parkinson and Movement Disorder Society (MDS), and from the International Association of Parkinsonism and Related Disorders; he received support for travels from the International Association of Parkinsonism and Related Disorders; he is board member of the International Association of Parkinsonism and Related Disorders. Mariana Spitz received funding from Centogene for the ROPAD study; she received support for travels from Roche. Justin Solle is employed by the Michel J. Fox Foundation. Oksana Suchowersky received grants from Roche and WaveLifeSciences; she holds royalties or licenses at UpToDate; she received consulting fees from Abbvie and Sunovion; she received honoraria from the World Parkinson Conference; she participates in advisory boards at Alexion; she is board member of the Parkinson Society Alberta. Pichet Termsarasab received book royalties from Elsevier and Springer Nature Switzerland; he received honoraria for manuscript writing from MedLink Neurology and for lectures from Viatris. Bart van de Warrenburg received grants from Radboudumc, ZonMW, Hersenstichting, Gossweiler Foundation, and the Michael J Fox Foundation; he holds royalties or licenses at BSL Springer Nature; he received consulting fees from uniQure; he received honoraria from UKM Medical Center Kuala Lumpur; he participates in Medical advisory board of patient organizations (unpaid); he is unpaid member of Steering committees or executive boards of various research consortia; he received a wearable sensor set by Brugling Fund/Hersenstichting. Caroline H. Williams-Gray collaborates with Astra-Zeneca on the microbiome in Parkinson’s disease; she received consultancy fees from Modus Outcomes and Evidera, Inc./GlaxoSmithKline; she received honoraria from Profile Pharma Limited. Eva-Juliane Vollstedt, Harutyun Madoev, Anna Aasly, Azlina Ahmad-Annuar, Bashayer Al-Mubarak, Victoria Alvarez, Ignacio Amorin, Grazia Annesi, David Arkadir, Soraya Bardien, Roger A. Barker, A. Nazli Basak, Agnita Boon, Laura Brighina, Andrea Carmine Belin, Jonathan Carr, Leonor Correia Guedes, David Crosiers, Parimal Das, Patricia de Carvalho Aguiar, Jolanta Dorszewska, Sibel Ertan, Rosangela Ferese, Gençer Genç, Pilar Gómez-Garre, Hasmet Hanagasi, Faycal Hentati, Dorota Hoffman-Zacharska, Sergey N. Illarioshkin, Joseph Jankovic, Anneke Kievit, Dariusz Koziorowski, Andrea A. Kühn, Anthony E. Lang, Chin-Hsien Lin, Katja Lohmann, Vladana Markovic, Mika Henrik Martikainen, Marcelo Merello, Özgür Öztop-Çakmak, Márcia Mattos Gonçalves Pimentel, Teeratorn Pulkes, Ekaterina Rogaeva, Esther M. Sammler, Maria Skaalum Petersen, Matej Skorvanek, Ai Huey Tan, Avner Thaler, Vitor Tumas, Enza Maria Valente, Ruey-Mei Wu, Baorong Zhang, and Alexander Zimprich report no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Vollstedt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In cereal breeding, in vitro androgenesis methods are frequently applied to achieve doubled haploid (DH) plants. The aim of this study was to determine the effects of genotype (three registered varieties and eight F 1 crossing combinations) and induction medium (W14mf and P4mf) on anther cultures (ACs) of triticale (× Triticosecale Wittmack). Androgenesis was induced in the treatment of each tested genotype, and the genotype significantly influenced the efficiency of AC, including in embryo-like structures (ELSs), albinos, green plantlets, and transplanted plantlets. The utilized medium also had a significant effect on the number of ELSs, albinos, and transplanted plantlets. Both media were suitable for AC in triticale DH plant production. The efficiency of AC was higher when using the P4mf medium (103.7 ELS/100 anthers, 19.7 green plantlets/100 anthers) than when using the W14mf medium (90.0 ELS/100 anthers, 17.0 green plantlets/100 anthers). However, the green plantlet regeneration efficiency of microspore-derived structures was 18.0% when using the W14mf medium, while this value was 15.9% in the case of ELSs induced with the P4mf medium. After nursery seed evaluation and propagation (DH 1 ), the genetic homogeneity of the offspring generation (DH 2 ) was tested using a molecular genetic method. Most of the tested DH lines showed homogeneity and were progressed into a breeding program after agronomic selection. Some DH lines showed inhomogeneity, which could be explained by the outcross inclination of triticale. We would like to call breeders' attention to the outcross character of triticale and emphasize the vigilant propagation and maintenance of the triticale DH lines in breeding programs. Due to the outcross nature of triticale, even in self-pollinated genotypes, breeders should focus on careful maintenance, along with isolation in the case of line propagations, in triticale breeding programs.

Clematis vitalba L. is a climbing shrub and a pioneer plant in abandoned orchards or vineyards that are widespread in temperate climate zones. In past years, several viruses infecting the Clematis species have been identified, including different ilarviruses. Prunus virus I (PrVI) is a recently described ilarvirus, which has been shown to infect sweet cherries and peaches in Greece. Moreover, its presence has been detected in ornamental Clematis in Russia. In the present work, we analyzed the virome of wildly growing C. vitalba plants from Hungary, Slovakia and Croatia showing different kinds of symptoms using high-throughput sequencing (HTS) of small RNAs or ribodepleted RNAs. Applying HTS enabled us to identify the presence of PrVI in C. vitalba , and the bioinformatic analyses were further validated with RT-PCR using PrVI-specific primers and Sanger dideoxy sequencing. Nearly full genome sequences of all three viral RNAs of one Hungarian, two Slovak and one Croatian isolate were determined. Their phylogenetic analysis showed high similarity to each other and to other PrVI isolates described from Central Europe. As the sampled plants were co-infected with other viruses, it is not possible to determine a direct correlation between the infection with PrVI and the observed symptoms. Analyses of different Prunus species in stock collection showed infection of several peach and sweet cherry varieties in Hungary. Our results expand the knowledge on the natural host range of PrVI and highlight the necessity to evaluate alternative plant hosts (even non- Prunus ) of PrVI and the role of the virus in the etiology of the potential diseases.

Anti-microbial peptides provide a powerful toolkit for combating multidrug resistance. Combating eukaryotic pathogens is complicated because the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria (EPB), symbionts of entomopathogenic-nematode species, release a series of non-ribosomal templated anti-microbial peptides. Some may be potential drug candidates. The ability of an entomopathogenic-nematode/entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product. This explains that those gene complexes that are responsible for the biosynthesis of different non-ribosomal templated anti-microbial protective peptides (including those that are potently capable of inactivating the protist mammalian pathogen Leishmania donovanii and the gallinaceous bird pathogen Histomonas meleagridis ) are co-regulated. Our approach is based on comparative anti-microbial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated anti-microbial peptides that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourage us to forecast that the recently discovered "easy-PACId" research strategy is suitable for constructing entomopathogenic-bacterium (EPB) strains producing and releasing single, harmless, non-ribosomal templated anti-microbial peptides with considerable drug, (probiotic)-candidate potential.

Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma with a poor prognosis. Although these tumors are sensitive to radiotherapy/chemotherapy, the standard treatment for localized MCS is only surgical resection, and there are no established treatment guidelines for patients with advanced and metastatic MCS. Due to the low incidence of MCS, the pathology of these tumors is still unknown, and other therapeutic options are lacking. Some studies show the potential role of the PDGF/PPI3K/AKT, PKC/RAF/MEK/ERK, and pRB pathways, and BCL2 overexpression in the pathogenesis of MCS. These findings provide an opportunity to use protein kinases and BCL2 inhibitors as potential therapy in MCS. In this review, we summarize the current knowledge about MCS diagnosis and treatment options. We show the immunological and molecular biomarkers used in the diagnosis of MCS. In addition, we discuss the known prognostic and predictive factors in MCS. Finally, we present the novel trends, including targeted therapies and ongoing clinical trials using protein kinase inhibitors and the death receptor 5 (DR5) agonist, which may be the focus of future MCS treatment studies.

Tomato brown rugose fruit virus (ToBRFV) is an emerging tobamovirus. It was first reported in 2015 in Jordan in greenhouse tomatoes and now threatens tomato and pepper crops around the world. ToBRFV is a stable and highly infectious virus that is easily transmitted by mechanical means and via seeds, which enables it to spread locally and over long distances. The ability of ToBRFV to infect tomato plants harboring the commonly deployed Tm resistance genes, as well as pepper plants harboring the L resistance alleles under certain conditions, limits the ability to prevent damage from the virus. The fruit production and quality of ToBRFV-infected tomato and pepper plants can be drastically affected, thus significantly impacting their market value. Herein, we review the current information and discuss the latest areas of research on this virus, which include its discovery and distribution, epidemiology, detection, and prevention and control measures, that could help mitigate the ToBRFV disease pandemic.

In the nodules of IRLC legumes, including Medicago truncatula, nitrogen-fixing rhizobia undergo terminal differentiation resulting in elongated and endoreduplicated bacteroids specialized for nitrogen fixation. This irreversible transition of rhizobia is mediated by host produced nodule-specific cysteine-rich (NCR) peptides, of which c. 700 are encoded in the M. truncatula genome but only few of them have been proved to be essential for nitrogen fixation. We carried out the characterization of the nodulation phenotype of three ineffective nitrogen-fixing M. truncatula mutants using confocal and electron microscopy, monitored the expression of defence and senescence-related marker genes, and analysed the bacteroid differentiation with flow cytometry. Genetic mapping combined with microarray- or transcriptome-based cloning was used to identify the impaired genes. Mtsym19 and Mtsym20 mutants are defective in the same peptide NCR-new35 and the lack of NCR343 is responsible for the ineffective symbiosis of NF-FN9363. We found that the expression of NCR-new35 is significantly lower and limited to the transition zone of the nodule compared with other crucial NCRs. The fluorescent protein-tagged version of NCR343 and NCR-new35 localized to the symbiotic compartment. Our discovery added two additional members to the group of NCR genes essential for nitrogen-fixing symbiosis in M. truncatula., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

The practice of artificial insemination for the long-tailed chinchilla has not been fully elaborated to date, and existing data available regarding their reproduction properties is contradictory. Until now, the collection of semen for chinchillas has been most-commonly obtained using electro-ejaculation methods exclusively. The primary objective of this study was the development of a manual technique for semen collection which meets all animal welfare requirements. An additional aim was to determine the basic spermatological parameters, such as motility, concentration, type and ratio of morphological abnormalities and live/dead cell ratio, under typical northern-hemisphere conditions, in Hungary. Over a 3 month period, a special massage technique was developed for the study, and using this method, the sperm parameters of 46 males were subsequently analyzed weekly for a period of one year. Approximately 66% of chinchillas responded positively to this technique, with the success rate of semen-collection attempts showing no variation between seasons. Average sperm concentration for the whole year was 935.17 million/ml using this method. Total cell motility was the highest in winter (90.3%), and the lowest in spring (84.3%). The proportion of live, intact cells were above 80% on average for the year, while the ratios of live, morphologically abnormal and dead cells were 6% and 14%, respectively. We found that midpiece abnormalities occurred in the highest proportion (0.95%-3.38%), while the head abnormalities showed the lowest ratio (0.01%-0.15%). Standard deviation among the parameters was relatively high, with the spring season proving to be the weakest in terms of sperm quality. This study has demonstrated that, semen can be successfully collected without the use of electro-ejaculation or anesthesia. Furthermore, although spermatological parameters do exhibit some fluctuation for the different times of the year, semen collected is nonetheless suitable for the purpose of artificial insemination of chinchillas at any time., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Babarczi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Energy efficiency is one of the fundamental athletic performance-affecting features of the cell and the organism as a whole. Mitochondrial DNA (mtDNA) variants and haplogroups have been linked to the successful practice of various sports, but despite numerous studies, understanding of the correlation is far from being comprehensive. In this study, the mtDNA sequence and copy number were determined for 99 outstanding Polish male athletes performing in power (n = 52) or endurance sports (n = 47) and 100 controls. The distribution of haplogroups, single nucleotide variant association, heteroplasmy, and mtDNA copy number were analyzed in the blood and saliva. We found no correlation between any haplogroup, single nucleotide variant, especially rare or non-synonymous ones, and athletic performance. Interestingly, heteroplasmy was less frequent in the study group, especially in endurance athletes. We observed a lower mtDNA copy number in both power and endurance athletes compared to controls. This could result from an inactivity of compensatory mechanisms activated by disadvantageous variants present in the general population and indicates a favorable genetic makeup of the athletes. The results emphasize a need for a more comprehensive analysis of the involvement of the mitochondrial genome in physical performance, combining nucleotide and copy number analysis in the context of nuclear gene variants.

Background: Though multicolour labelling methods allow the routine detection of a wide range of fluorescent (immuno)probe types in molecular cytogenetics, combined applications for the simultaneous in situ detection of proteins and nucleic acids are still sporadic in plant cell biology. A major bottleneck has been the availability of high-quality plant nuclei with a balance between preservation of 3D ultrastructure and maintaining immunoreactivity. The aim of this study was to develop a quick and reliable procedure to prepare plant nuclei suitable for various combinations of immunolabelling and fluorescence in situ hybridisation methods (immunoFISH-GISH)., Results: The mechanical removal of the cell wall and cytoplasm, instead of enzymatic degradation, resulted in a gentle, yet effective, cell permeabilisation. Rather than manually releasing the nuclei from the fixed tissues, the procedure involves in-solution cell handling throughout the fixation and the preparation steps as ended with pipetting the pure nuclei suspension onto microscope slides. The optimisation of several critical steps is described in detail. Finally, the procedure is shown to be compatible with immunolabelling, FISH and GISH as well as their simultaneous combinations., Conclusion: A simple plant cell nuclei preparation procedure was developed for combined immunolabelling-in situ hybridisation methods. The main and critical elements of the procedure are: a short period of fixation, incorporation of detergents to facilitate the fixation of tissues and the penetration of probes, tissue grinding to eliminate unwanted cell components, and an optimal buffer to handle nuclei. The procedure is time efficient and is easily transferable without prior expertise., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Arbuscular mycorrhizal (AM) fungi could mitigate individual drought and heat stress in host plants. However, there are still major gaps in our understanding of AM symbiosis response to the combined stresses. Here, we compared seven AM fungi, Rhizophagus irregularis, Funneliformis mosseae, Funneliformis geosporum, Funneliformis verruculosum, Funneliformis coronatum, Septoglomus deserticola, Septoglomus constrictum, distributed to many world regions in terms of their impacts on tomato endurance to combined drought and chronic heat as well as combined drought and heat shock. A multidisciplinary approach including morphometric, ecophysiological, biochemical, targeted metabolic (by ultrahigh-performance LC-MS), and molecular analyses was applied. The variation among AM fungi isolates in the enhancement in leaf water potential, stomatal conductance, photosynthetic activity, and maximal PSII photochemical efficiency, proline accumulation, antioxidant enzymes (POD, SOD, CAT), and lowered ROS markers (H 2 O 2 , MDA) in host plants under combined stresses were observed. S. constrictum inoculation could better enhanced the host plant physiology and biochemical parameters, while F. geosporum colonization less positively influenced the host plants than other treatments under both combined stresses. F. mosseae- and S. constrictum-associated plants showed the common AM-induced modifications and AM species-specific alterations in phytohormones (ABA, SA, JA, IAA), aquaporin (SlSIP1-2; SlTIP2-3; SlNIP2-1; SlPIP2-1) and abiotic stress-responsive genes (SlAREB1, SlLEA, SlHSP70, SlHSP90) in host plants under combined stresses. Altogether, mycorrhizal mitigation of the negative impacts of drought + prolonged heat and drought + acute heat, with the variation among different AM fungi isolates, depending on the specific combined stress and stress duration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Heterozygous carriers of pathogenic/likely pathogenic variants in autosomal recessive disorders seem to be asymptomatic. However, in recent years, an increasing number of case reports have suggested that mild and unspecific symptoms can occur in some heterozygotes, as symptomatic heterozygotes have been identified across different disease types, including neurological, neuromuscular, hematological, and pulmonary diseases. The symptoms are usually milder in heterozygotes than in biallelic variants and occur "later in life". The status of symptomatic heterozygotes as separate entities is often disputed, and alternative diagnoses are considered. Indeed, often only a thin line exists between dual, dominant, and recessive modes of inheritance and symptomatic heterozygosity. Interestingly, recent population studies have found global disease effects in heterozygous carriers of some genetic variants. What makes the few heterozygotes symptomatic, while the majority show no symptoms? The molecular basis of this phenomenon is still unknown. Possible explanations include undiscovered deep-splicing variants, genetic and environmental modifiers, digenic/oligogenic inheritance, skewed methylation patterns, and mutational burden. Symptomatic heterozygotes are rarely reported in the literature, mainly because most did not undergo the complete diagnostic procedure, so alternative diagnoses could not be conclusively excluded. However, despite the increasing accessibility to high-throughput technologies, there still seems to be a small group of patients with mild symptoms and just one variant of autosomes in biallelic diseases. Here, we present some examples, the current state of knowledge, and possible explanations for this phenomenon, and thus argue against the existing dominant/recessive classification.

MicroRNAs (miRNAs), small non-coding RNA molecules, regulate a wide range of critical biological processes, such as proliferation, cell cycle progression, differentiation, survival, and apoptosis, in many cell types. The regulatory functions of miRNAs in embryogenesis and stem cell properties have been extensively investigated since the early years of miRNA discovery. In this review, we will compare and discuss the impact of stem-cell-specific miRNA clusters on the maintenance and regulation of early embryonic development, pluripotency, and self-renewal of embryonic stem cells, particularly in vertebrates.

PEComa (PEC tumor; perivascular epithelioid cell tumors) is a rare group of tumors of mesenchymal origin composed of perivascular epithelioid cells (PEC) with features of melanotic and smooth muscle differentiation. In this article, we would like to present the current treatment options for this group of tumors. PEComas are classified as tumors of uncertain malignant potential because recurrences occur after radical treatment. The primary treatment is surgical resection with negative margins. Due to the different locations of the tumors, often the cooperation of multispecialty surgeons is required during the operations. In locally advanced cases, cytoreduction and HIPEC may be effective but still are an experimental treatment. For nonresectable PEComa chemotherapy, mTOR inhibitors and VEGFR inhibitors are used., Competing Interests: Prof. Dr. Piotr Rutkowski reports personal fees from BMS, MSD, Novartis, Merck, Pierre Fabre, Sanofi, Philogen, and Astra Zeneca, outside the submitted work. The authors report that they have no other conflicts of interest in this work., (© 2023 Czarnecka et al.)

Our aim was to compare the health and performance of ad libitum (ADLIB) and restrictedly fed Holstein Friesian heifer calves. Calves were selected to ADLIB (n = 13) and control (n = 13) groups randomly. The period of ADLIB feeding lasted for 3 weeks after colostrum supplementation. The calves in the control group received the same milk replacer, which was supplied according to the restrained feeding schedule of the farm. There was no difference between the two groups in weight, weight gain or movement activity, furthermore in the values of glucose, albumin, total protein, BHB, AST, oxidant and antioxidant status incl. dROM, PAT and OSI. The IL8 gene had higher levels (non significant, p > 0.05) of expression in the ADLIB group during the first 20 days of life, which indicates that ADLIB feeding might potentiate a stronger immune response to environmental stress. The IGF1 gene showed increased expression in the ADLIB fed group at almost all time points, however the difference was already detected on the first day of the study, indicating the importance of individual differences even within the same breed. During the first 10 days INS expression was higher in the restricted group, followed by a shift by day 20 and after, when the ADLIB group showed a higher relative expression level. The observed values describe a trend that, although not significant (p > 0.05), would seem to indicate that ADLIB feeding might potentiate a stronger immune response to environmental stress., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Some chemoattractants and leukocytes such as M1 and M2 macrophages are known to be involved in the development of glomerulosclerosis during diabetic nephropathy (DN). In the course of diabetes, an altered and defective cellular metabolism leads to the increase in adenosine levels, and thus to changes in the polarity (M1/M2) of macrophages. MRS1754, a selective antagonist of the A2B adenosine receptor (A2BAR), attenuated glomerulosclerosis and decreased macrophage-myofibroblast transition in DN rats. Therefore, we aimed to investigate the effect of MRS1754 on the glomerular expression/secretion of chemoattractants, the intraglomerular infiltration of leukocytes, and macrophage polarity in DN rats. Kidneys/glomeruli of non-diabetic, DN, and MRS1754-treated DN rats were processed for transcriptomic analysis, immunohistopathology, ELISA, and in vitro macrophage migration assays. The transcriptomic analysis identified an upregulation of transcripts and pathways related to the immune system in the glomeruli of DN rats, which was attenuated using MRS1754. The antagonism of the A2BAR decreased glomerular expression/secretion of chemoattractants (CCL2, CCL3, CCL6, and CCL21), the infiltration of macrophages, and their polarization to M2 in DN rats. The in vitro macrophages migration induced by conditioned-medium of DN glomeruli was significantly decreased using neutralizing antibodies against CCL2, CCL3, and CCL21. We concluded that the pharmacological blockade of the A2BAR decreases the transcriptional expression of genes/pathways related to the immune response, protein expression/secretion of chemoattractants, as well as the infiltration of macrophages and their polarization toward the M2 phenotype in the glomeruli of DN rats, suggesting a new mechanism implicated in the antifibrotic effect of MRS1754.

Keratinocytes of the mammalian skin provide not only mechanical protection for the tissues, but also transmit mechanical, chemical, and thermal stimuli from the external environment to the sensory nerve terminals. Sensory nerve fibers penetrate the epidermal basement membrane and function in the tight intercellular space among keratinocytes. Here we show that epidermal keratinocytes produce hydrogen peroxide upon the activation of the NADPH oxidase dual oxidase 1 (DUOX1). This enzyme can be activated by increasing cytosolic calcium levels. Using DUOX1 knockout animals as a model system we found an increased sensitivity towards certain noxious stimuli in DUOX1-deficient animals, which is not due to structural changes in the skin as evidenced by detailed immunohistochemical and electron-microscopic analysis of epidermal tissue. We show that DUOX1 is expressed in keratinocytes but not in the neural sensory pathway. The release of hydrogen peroxide by activated DUOX1 alters both the activity of neuronal TRPA1 and redox-sensitive potassium channels expressed in dorsal root ganglia primary sensory neurons. We describe hydrogen peroxide, produced by DUOX1 as a paracrine mediator of nociceptive signal transmission. Our results indicate that a novel, hitherto unknown redox mechanism modulates noxious sensory signals., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Messenger RNA uridylation is pervasive and conserved among eukaryotes, but the consequences of this modification for mRNA fate are still under debate. Utilising a simple model organism to study uridylation may facilitate efforts to understand the cellular function of this process. Here we demonstrate that uridylation can be detected using simple bioinformatics approach. We utilise it to unravel widespread transcript uridylation in fission yeast and demonstrate the contribution of both Cid1 and Cid16, the only two annotated terminal uridyltransferases (TUT-ases) in this yeast. To detect uridylation in transcriptome data, we used a RNA-sequencing (RNA-seq) library preparation protocol involving initial linker ligation to fragmented RNA-an approach borrowed from small RNA sequencing that was commonly used in older RNA-seq protocols. We next explored the data to detect uridylation marks. Our analysis show that uridylation in yeast is pervasive, similarly to the one in multicellular organisms. Importantly, our results confirm the role of the cytoplasmic uridyltransferase Cid1 as the primary uridylation catalyst. However, we also observed an auxiliary role of the second uridyltransferase, Cid16. Thus both fission yeast uridyltransferases are involved in mRNA uridylation. Intriguingly, we found no physiological phenotype of the single and double deletion mutants of cid1 and cid16 and only minimal impact of uridylation on steady-state mRNA levels. Our work establishes fission yeast as a potent model to study uridylation in a simple eukaryote, and we demonstrate that it is possible to detect uridylation marks in RNA-seq data without the need for specific methodologies., Competing Interests: the authors have declared that no competing interests exist., (Copyright: © 2023 Lipińska-Zubrycka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)