Open Biology最新文献

Can anastasis contribute to cancer recurrence? Anastasis is a cell recovery mechanism to spare dying cells after the initiation of the cell death process. Emerging studies interrogate anastasis as an unexpected escape tactic for cancer cells to evade cell death-inducing anti-cancer therapy, leading to recurrence. After anastasis, cancer cells display increased invasiveness and genomic instability, which could be associated with the common and fatal features of metastasis and drug resistance at the cancer recurrence. These studies open an encouraging new conceptual avenue for arresting cancer recurrence by targeting anastasis in cancer cells after conventional anti-cancer therapy. Here, we highlight recent findings towards unravelling pathological roles of anastasis in cancer recurrence, for the purpose of stimulating ideas and promoting the development of this new field of cancer research.

ASCL1 is a key member of the proneural basic helix-loop-helix (bHLH) transcription factor (TF) family and it plays diverse roles in nervous system development and maintenance. ASCL1 is also one of the most studied bHLH TFs in the field of somatic cell reprogramming, as it can reconfigure the chromatin of the cell of origin to impose a neuronal identity. However, the ability of ASCL1 to drive neuronal fate does not come without exceptions, as there are cell types that are refractory to ASCL1-mediated reprogramming, and there are developmental contexts where ASCL1 does not drive neurogenesis but supports the generation of other lineages. ASCL1 has also emerged as an important player in cancers like neuroblastoma and glioblastoma, underscoring the clinical need for a robust understanding of how ASCL1 controls cell identity. In this review, we revisit the foundational studies that established ASCL1 as a critical regulator of neuronal differentiation and incorporate recent advances in our understanding of ASCL1 post-translational regulation and transcriptional control. By integrating these perspectives, this review provides a comprehensive overview of the diverse roles of ASCL1 in development, reprogramming and cancer, offering insights into its molecular functions and therapeutic potential.

This study investigates the reproductive apparatus of Epilachna clandestina, focusing on its secondary spermatheca, first described as a 'seminal node' by Katakura et al. for the Asian Epilachninae. We corroborate their previous findings that highlight this organ as the primary sperm storage site, contrasting with a vestigial typical spermatheca that lacks significant functionality. The functional spermatheca is a dilated, secretory region of the common oviduct filled with sperm. It features a specialized epithelium containing class 3 secretory cells and is lined by a thin chitinous cuticle, indicating that it qualifies as a true spermatheca. This organ seems to optimize sperm storage and maintenance when compared to the vestigial spermatheca. Additionally, we emphasize the close association between sperm and epithelial structures as mechanisms for efficient sperm retention and dosage, which could quantitatively and qualitatively improve reproductive success. Our findings may contribute to a greater understanding of the evolutionary adaptations of reproductive structures in Epilachninae and raise questions regarding the evolutionary history of these organs within ladybirds.

The study of the neural tube (NT), the antecedent structure of the central nervous system, is challenging due to the inaccessibility of the embryo. Thus, our understanding of this crucial timepoint in development is limited. The use of organoid models in recent years has proven immensely beneficial in the field of embryology, allowing the direct study of in vitro models of early neural development. As organoids advance in complexity, the vascularization of brain organoids has become a point of interest due to its significant role in neural development. This raises the question of whether the vascularization of NT organoids is necessary to improve their accuracy. This review summarizes the role of vascularization both during and before NT formation and explores the effects of endothelial-derived factors on this process. While the data indicate that vascularization is essential for proper NT formation, this review also highlights a significant gap in our knowledge and the need to clarify these interactions in order to generate more accurate organoid models.

Kaiso (ZBTB33) is a transcription factor involved in mitotic clonal expansion and tumorigenesis in association with Adenomatous Polyposis Coli (APC) loss of heterozygosity. ENCODE data show strong overlap of the Kaiso promoter-binding site-encode-derived Kaiso-binding site (eKBS) and many other transcription factors, including BRCA1. Here we sought to determine whether BRCA1 is a component of the Kaiso enhanceosome that regulates gene transcription. Using proximal ligation assays, immunoprecipitation followed by mass spectrometry, luciferase assays and ChIP-seq experiments, we evaluated the association between BRCA1 and Kaiso. Kaiso nuclear extract immunoprecipitation experiments revealed that Kaiso associates strongly with genes involved in RNA splicing and processing. When Kaiso was not crosslinked to DNA, BRCA1 was not detected among Kaiso-binding proteins. However, overexpression of BRCA1 increased Kaiso-mediated gene transcription in luciferase assays in a Kaiso-dependent manner. Comparison of BRCA1 ChIP-seq and Kaiso ChIP-seq data from HCT116 cells revealed both BRCA1 and Kaiso commonly bind to the promoters of 379 genes. The most enriched term associated with these genes where BRCA1 and Kaiso bind their promoters is metabolism of RNA. Disease processes associated with these BRCA1/Kaiso gene promoters indicate that BRCA1 is functionally linked to a Kaiso-directed programme of RNAP2-mediated gene transcription and likely associated with colorectal cancer development and maintenance.

Enterohaemorrhagic Escherichia coli causes sporadic, and sometimes large-scale, food poisoning outbreaks, for which antibiotic treatment in humans is contraindicated. As an alternative form of therapy, previous studies developed the family of salicylidene acylhydrazide (SA) anti-virulence compounds. One target of the SA compounds is AdhE, an enzyme that converts acetyl-CoA to ethanol and vice versa. AdhE oligomerizes, forming helicoidal filaments, heterogeneous in length, called spirosomes. We show it is possible to only partially fractionate AdhE spirosomes because in vitro they oligomerize in the absence of stimuli, and that spirosome formation is necessary to regulate the direction of AdhE enzymatic reactions. We also show that the SA compound ME0054 binds and perturbs AdhE spirosomes, enhancing the conversion of ethanol to acetyl-CoA. This mechanistic understanding of how ME0054 impacts AdhE function will help in the development of SA compounds as novel anti-virulence inhibitors.

Sound sensitivity is a common sensory complaint for people with autism spectrum disorder (ASD). How and why sounds are perceived as overwhelming by affected people is unknown. To process sound information properly, the brain requires high activity and fast processing, as seen in areas like the medial nucleus of the trapezoid body (MNTB) of the auditory brainstem. Recent work has shown dysfunction in mitochondria in a genetic model of ASD, Fragile X Syndrome (FXS). Whether mitochondrial functions are also altered in sound-processing neurons has not been characterized yet. To address this question, we imaged MNTB in a mouse model of FXS. We stained MNTB brain slices from wild-type and FXS mice with two mitochondrial markers, TOMM20 and PMPCB, located on the outer mitochondrial membrane and in the matrix, respectively. Our imaging reveals significant sex-specific differences between genotypes. Colocalization analyses between TOMM20 and PMPCB show that the integrity of mitochondrial subcompartments is most disrupted in female FXS mice compared with female wild-type mice. We highlight a quantitative fluorescence microscopy pipeline to monitor mitochondrial functions in the MNTB from control or FXS mice and provide four complementary readouts, paving the way to understanding how cellular mechanisms important to sound encoding are altered in ASD.

Gene presence/absence variations (PAVs) have been considered as the important determinants of genome evolution and phenotypic diversity. However, studies on gene PAVs have been poorly documented, especially in fishes. In the present study, the pan-genome of rainbow trout was constructed based on 268 whole-genome re-sequencing accessions (4.38 Tb data). It recovered an additional 62 Mb sequences and 1288 protein-coding genes. Then, 9831 (22.77%) gene PAVs were genotyped across the 268 individuals. PAV-based PCA analysis, together with phylogenetic topology and STRUCTURE, revealed the clear separation among the different wild and selection populations. Additionally, a PAV-based genome-wide association study (GWAS) identified three candidate PAVs significantly associated with artificial selection. Meanwhile, fixation index analysis revealed 35 PAVs with significant frequency differences between wild and selection populations in Canada, while 15 candidate PAVs were detected between the populations in America. Their biological functions have been reported to participate in the regulation of growth performance and stress response. The present study deepens our understanding of widespread gene PAVs and facilitates the identification of key candidates that contribute to important traits.

The type III secretion system (T3SS) has traditionally been studied for its role in bacterial virulence. However, recent research emphasizes its dual role in beneficial interactions between bacteria and plants. This review examines the immunomodulatory functions of T3SS beyond pathogenicity and focuses on how T3SS effectors manipulate plant immune responses to promote symbioses. By comparing T3SS mechanisms in pathogenic and non-pathogenic bacteria, we aim to understand how this system enables beneficial microbes to colonize plants and improve plant growth and stress resilience. We also investigate the potential of T3SS to trigger induced systemic resistance in plants, a mechanism that could be utilized in agriculture to improve crop resistance to pathogens. The review concludes with an outlook on future research and emphasizes the need for comprehensive studies on T3SS effectors in non-pathogenic bacteria and their interactions with plant hosts.