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Pharmaceuticals (Basel, Switzerland) May 2024Previously, we analyzed 316 herbal extracts to evaluate their potential nematocidal properties in In this study, our attention was directed towards ., resulting in...
Previously, we analyzed 316 herbal extracts to evaluate their potential nematocidal properties in In this study, our attention was directed towards ., resulting in reduced survival and heightened larval arrest/lethality, alongside a noticeable decrease in DAPI-stained bivalent structures and disrupted meiotic progression, thus disrupting developmental processes. Notably, . extracts activated a DNA damage checkpoint response via the ATM/ATR and CHK-1 pathways, hindering germline development. LC-MS analysis revealed 13 compounds in the . extracts, including flavonoids, terpenoids, tanshinones, an analog of resveratrol, iridoids, carotenoids, fatty acids, and alkaloids. Of these, 10 are known for their antitumor activity, suggesting the potential of beyond traditional gardening, extending into pharmaceutical and therapeutic applications.
PubMed: 38794181
DOI: 10.3390/ph17050611 -
Journal of Fungi (Basel, Switzerland) May 2024, one of the conidiation center regulatory genes in many filamentous fungi, plays an important role in promoting asexual spores (conidia) maturation. Our recent research...
, one of the conidiation center regulatory genes in many filamentous fungi, plays an important role in promoting asexual spores (conidia) maturation. Our recent research has found that knocking out or overexpressing (a homolog of ) in M7 does not affect the development of its asexual spores like other fungi, but both repress the development of its sexual spores (ascospores). However, the mechanism remains unclear. In this study, the function of on sexual reproduction and secondary metabolism in M7 was confirmed by a complementary experiment. Moreover, the regulatory roles of in modulating the expression of genes involved in sexual reproduction, meiosis, and biosynthesis of pigment and citrinin were analyzed based on the transcriptional data. These results not only contribute to clarifying the regulation of the reproduction and secondary metabolism of spp., but also to enriching the regulation molecular mechanism of reproduction in filamentous fungi.
PubMed: 38786694
DOI: 10.3390/jof10050338 -
Cells May 2024Mammalian oocyte development depends on the temporally controlled translation of maternal transcripts, particularly in the coordination of meiotic and early embryonic...
Mammalian oocyte development depends on the temporally controlled translation of maternal transcripts, particularly in the coordination of meiotic and early embryonic development when transcription has ceased. The translation of mRNA is regulated by various RNA-binding proteins. We show that the absence of cytoplasmic polyadenylation element-binding protein 3 (CPEB3) negatively affects female reproductive fitness. CPEB3-depleted oocytes undergo meiosis normally but experience early embryonic arrest due to a disrupted transcriptome, leading to aberrant protein expression and the subsequent failure of embryonic transcription initiation. We found that CPEB3 stabilizes a subset of mRNAs with a significantly longer 3'UTR that is enriched in its distal region with cytoplasmic polyadenylation elements. Overall, our results suggest that CPEB3 is an important maternal factor that regulates the stability and translation of a subclass of mRNAs that are essential for the initiation of embryonic transcription and thus for embryonic development.
Topics: Oocytes; Animals; RNA-Binding Proteins; Female; Mice; Meiosis; RNA, Messenger; Embryonic Development; Gene Expression Regulation, Developmental; 3' Untranslated Regions; Polyadenylation; RNA Stability
PubMed: 38786074
DOI: 10.3390/cells13100850 -
Biology May 2024Sertoli cells (SCs) are essential to maintaining germ cell development. Metformin, the main pharmacologic treatment for pediatric type 2 diabetes, is administered to...
Sertoli cells (SCs) are essential to maintaining germ cell development. Metformin, the main pharmacologic treatment for pediatric type 2 diabetes, is administered to children during SC maturation. The present study aimed to analyze whether metformin affects SC energy metabolism and blood-testis barrier (BTB) integrity. Primary SC cultures were used for the in vitro studies. In vivo effects were studied in Sprague-Dawley rats treated with 200 mg/kg metformin from Pnd14 to Pnd30. Metformin decreased fatty acid oxidation and increased 3-hydroxybutyrate production in vitro. Moreover, it decreased the transepithelial electrical resistance across the monolayer and induced ZO-1 redistribution, suggesting an alteration of cell junctions. In vivo, a mild but significant increase in BTB permeability and ZO-1 expression was observed in the metformin group, without changes in testicular histology and meiosis progression. Additionally, adult rats that received metformin treatment during the juvenile period showed no alteration in BTB permeability or daily sperm production. In conclusion, metformin exposure may affect BTB permeability in juvenile rats, but this seems not to influence spermatogenesis progression. Considering the results obtained in adult animals, it is possible to speculate that metformin treatment during the juvenile period does not affect testicular function in adulthood.
PubMed: 38785812
DOI: 10.3390/biology13050330 -
Development (Cambridge, England) Jun 2024The RNA-binding protein cytoplasmic polyadenylation element binding 1 (CPEB1) plays a fundamental role in regulating mRNA translation in oocytes. However, the specifics...
The RNA-binding protein cytoplasmic polyadenylation element binding 1 (CPEB1) plays a fundamental role in regulating mRNA translation in oocytes. However, the specifics of how and which protein kinase cascades modulate CPEB1 activity are still controversial. Using genetic and pharmacological tools, and detailed time courses, we have re-evaluated the relationship between CPEB1 phosphorylation and translation activation during mouse oocyte maturation. We show that both the CDK1/MAPK and AURKA/PLK1 pathways converge on CPEB1 phosphorylation during prometaphase of meiosis I. Only inactivation of the CDK1/MAPK pathway disrupts translation, whereas inactivation of either pathway alone leads to CPEB1 stabilization. However, CPEB1 stabilization induced by inactivation of the AURKA/PLK1 pathway does not affect translation, indicating that destabilization and/or degradation is not linked to translational activation. The accumulation of endogenous CCNB1 protein closely recapitulates the translation data that use an exogenous template. These findings support the overarching hypothesis that the activation of translation during prometaphase in mouse oocytes relies on a CDK1/MAPK-dependent CPEB1 phosphorylation, and that translational activation precedes CPEB1 destabilization.
Topics: Animals; Oocytes; Meiosis; mRNA Cleavage and Polyadenylation Factors; Phosphorylation; Mice; Protein Biosynthesis; Female; CDC2 Protein Kinase; Transcription Factors; Aurora Kinase A; Cyclin B1; Cell Cycle Proteins; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Signal Transduction
PubMed: 38785133
DOI: 10.1242/dev.202712 -
Genome Biology and Evolution May 2024We have sequenced, assembled, and analyzed the nuclear and mitochondrial genomes and transcriptomes of Potamopyrgus estuarinus and Potamopyrgus kaitunuparaoa, two...
We have sequenced, assembled, and analyzed the nuclear and mitochondrial genomes and transcriptomes of Potamopyrgus estuarinus and Potamopyrgus kaitunuparaoa, two prosobranch snail species native to New Zealand that together span the continuum from estuary to freshwater. These two species are the closest known relatives of the freshwater species Potamopyrgus antipodarum-a model for studying the evolution of sex, host-parasite coevolution, and biological invasiveness-and thus provide key evolutionary context for understanding its unusual biology. The P. estuarinus and P. kaitunuparaoa genomes are very similar in size and overall gene content. Comparative analyses of genome content indicate that these two species harbor a near-identical set of genes involved in meiosis and sperm functions, including seven genes with meiosis-specific functions. These results are consistent with obligate sexual reproduction in these two species and provide a framework for future analyses of P. antipodarum-a species comprising both obligately sexual and obligately asexual lineages, each separately derived from a sexual ancestor. Genome-wide multigene phylogenetic analyses indicate that P. kaitunuparaoa is likely the closest relative to P. antipodarum. We nevertheless show that there has been considerable introgression between P. estuarinus and P. kaitunuparaoa. That introgression does not extend to the mitochondrial genome, which appears to serve as a barrier to hybridization between P. estuarinus and P. kaitunuparaoa. Nuclear-encoded genes whose products function in joint mitochondrial-nuclear enzyme complexes exhibit similar patterns of nonintrogression, indicating that incompatibilities between the mitochondrial and the nuclear genome may have prevented more extensive gene flow between these two species.
Topics: Animals; Snails; Phylogeny; New Zealand; Genetic Introgression; Evolution, Molecular; Genome, Mitochondrial; Genome
PubMed: 38776329
DOI: 10.1093/gbe/evae091 -
Frontiers in Microbiology 2024Mamiellophyceae are dominant marine algae in much of the ocean, the most prevalent genera belonging to the order Mamiellales: , and , whose genetics and global...
Mamiellophyceae are dominant marine algae in much of the ocean, the most prevalent genera belonging to the order Mamiellales: , and , whose genetics and global distributions have been extensively studied. Conversely, the genus , despite its potential ecological importance, remains relatively under-characterised. In this study, we isolated and characterised a novel species of Mamiellophyceae, , from subtropical coastal waters in the South China Sea. Morphologically, it resembles other species; however, a comparative analysis of the 18S and ITS2 marker genes revealed its genetic distinctiveness. Furthermore, we sequenced and assembled the first genome of , uncovering significant differences from previously studied Mamiellophyceae species. Notably, the genome lacked any detectable outlier chromosomes and exhibited numerous unique orthogroups. We explored gene groups associated with meiosis, scale and flagella formation, shedding light on species divergence, yet further investigation is warranted. To elucidate the biogeography of , we conducted a comprehensive analysis using global metagenomic read mapping to the newly sequenced genome. Our findings indicate this species exhibits a cosmopolitan distribution with a low-level prevalence worldwide. Understanding the intricate dynamics between Mamiellophyceae and the environment is crucial for comprehending their impact on the ocean ecosystem and accurately predicting their response to forthcoming environmental changes.
PubMed: 38774501
DOI: 10.3389/fmicb.2024.1358574 -
EMBO Reports Jun 2024Alpha, beta, and gamma tubulins are essential building blocks for all eukaryotic cells. The functions of the non-canonical tubulins, delta, epsilon, and zeta, however,...
Alpha, beta, and gamma tubulins are essential building blocks for all eukaryotic cells. The functions of the non-canonical tubulins, delta, epsilon, and zeta, however, remain poorly understood and their requirement in mammalian development untested. Herein we have used a spermatogenesis model to define epsilon tubulin (TUBE1) function in mice. We show that TUBE1 is essential for the function of multiple complex microtubule arrays, including the meiotic spindle, axoneme and manchette and in its absence, there is a dramatic loss of germ cells and male sterility. Moreover, we provide evidence for the interplay between TUBE1 and katanin-mediated microtubule severing, and for the sub-specialization of individual katanin paralogs in the regulation of specific microtubule arrays.
Topics: Animals; Male; Microtubules; Tubulin; Mice; Katanin; Spermatogenesis; Adenosine Triphosphatases; Germ Cells; Spindle Apparatus; Spermatozoa; Infertility, Male; Mice, Knockout; Axoneme
PubMed: 38773322
DOI: 10.1038/s44319-024-00159-w -
PLoS Genetics May 2024Molecular dissection of meiotic recombination in mammals, combined with population-genetic and comparative studies, have revealed a complex evolutionary dynamic...
Molecular dissection of meiotic recombination in mammals, combined with population-genetic and comparative studies, have revealed a complex evolutionary dynamic characterized by short-lived recombination hotspots. Hotspots are chromosome positions containing DNA sequences where the protein PRDM9 can bind and cause crossing-over. To explain these fast evolutionary dynamic, a so-called intra-genomic Red Queen model has been proposed, based on the interplay between two antagonistic forces: biased gene conversion, mediated by double-strand breaks, resulting in hotspot extinction (the hotspot conversion paradox), followed by positive selection favoring mutant PRDM9 alleles recognizing new sequence motifs. Although this model predicts many empirical observations, the exact causes of the positive selection acting on new PRDM9 alleles is still not well understood. In this direction, experiment on mouse hybrids have suggested that, in addition to targeting double strand breaks, PRDM9 has another role during meiosis. Specifically, PRDM9 symmetric binding (simultaneous binding at the same site on both homologues) would facilitate homology search and, as a result, the pairing of the homologues. Although discovered in hybrids, this second function of PRDM9 could also be involved in the evolutionary dynamic observed within populations. To address this point, here, we present a theoretical model of the evolutionary dynamic of meiotic recombination integrating current knowledge about the molecular function of PRDM9. Our modeling work gives important insights into the selective forces driving the turnover of recombination hotspots. Specifically, the reduced symmetrical binding of PRDM9 caused by the loss of high affinity binding sites induces a net positive selection eliciting new PRDM9 alleles recognizing new targets. The model also offers new insights about the influence of the gene dosage of PRDM9, which can paradoxically result in negative selection on new PRDM9 alleles entering the population, driving their eviction and thus reducing standing variation at this locus.
Topics: Histone-Lysine N-Methyltransferase; Meiosis; Animals; Evolution, Molecular; Mice; Gene Conversion; DNA Breaks, Double-Stranded; Alleles; Models, Genetic; Humans; Recombination, Genetic
PubMed: 38768268
DOI: 10.1371/journal.pgen.1011274 -
Zoological Research May 2024Meiosis is a highly complex process significantly influenced by transcriptional regulation. However, studies on the mechanisms that govern transcriptomic changes during...
Meiosis is a highly complex process significantly influenced by transcriptional regulation. However, studies on the mechanisms that govern transcriptomic changes during meiosis, especially in prophase I, are limited. Here, we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes. This event, conserved in mice, involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset. Furthermore, we identified 282 transcriptional regulators (TRs) that underwent activation or deactivation subsequent to this process. Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes, while secreted ENHO signals may alter metabolic patterns in these cells. Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia (NOA). This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.
Topics: Animals; Male; Mice; Meiosis; Humans; Cell Communication; Sertoli Cells; Testis; Spermatogenesis; Gene Expression Regulation; Azoospermia; Transcription, Genetic; RNA, Small Cytoplasmic; Single-Cell Gene Expression Analysis
PubMed: 38766744
DOI: 10.24272/j.issn.2095-8137.2023.414