生物学最新文献

Streptococcus suis is an important zoonotic pathogen that threatens human and pig health. During infection, the host can impose oxidative stress to resist pathogen invasion. Resistance to oxidative toxicity is an important factor for pathogens. Glutathione synthesis contributes to reactive oxygen species (ROS) detoxification in bacterial cells. Little is known about the roles of glutathione synthesis and transport in S. suis. In this study, we demonstrated that glutathione treatment increased oxidative stress tolerance in S. suis. GshAB and GshT were found in S. suis glutathione synthesis and import by bioinformatics. In vitro, inactivation of gshAB and gshT led to increased sensitivity to oxidative stress. Inactivation of gshT led to growth defects in the medium. The intracellular glutathione content of gshAB or gshT deletion mutants was lower than that of wild type (WT) strain. The phagocytic resistance of gshAB and gshT mutants was lower than that of the WT strain. Moreover, the virulence of gshAB and gshT deletion mutants was significantly lower than that of the WT strain in mouse survival and tissue loading experiments. In conclusion, these results revealed the functions of GshAB and GshT in the pathogenesis of S. suis. These findings enhance our understanding of bacterial virulence mechanisms and may provide a new avenue for therapeutic intervention aimed at curbing S. suis infections.

In all domains of life, Archaea, Eukarya and Bacteria, the unusual amino acid selenocysteine (Sec) is co-translationally incorporated into proteins by recoding a UGA stop codon to a sense codon. A secondary structure on the mRNA, the selenocysteine insertion sequence (SECIS), is required, but its position, secondary structure and binding partner(s) are not conserved across the tree of life. Thus far, the nature of archaeal SECIS elements has been derived mainly from sequence analyses. A recently developed in vivo reporter system was used to study the structure-function relationships of SECIS elements in Methanococcus maripaludis. Through targeted mutagenesis, we defined the minimal functional SECIS element, the parts of the SECIS where structure and not the identity of the bases are relevant for function, and identified two conserved -and invariant- adenines that are most likely to interact with the other factor(s) of the Sec recoding machinery. Finally, we demonstrated the functionality of SECIS elements in the 5`-untranslated region of the mRNA and identified a potential mechanism of SECIS repositioning in the vicinity of the UGA for efficient selenocysteine insertion.

The lack of a sufficient number of validated miRNA targets severely hampers the understanding of their biological function. Even for the well-studied miR-155-5p, there are only 239 experimentally validated targets out of 42,554 predicted targets. For a more complete assessment of the immune-related miR-155 targetome, we used an inverse correlation of time-resolved mRNA profiles and miR-155-5p expression of early CD4+ T cell activation to predict immune-related target genes. Using a high-throughput miRNA interaction reporter (HiTmIR) assay we examined 90 target genes and confirmed 80 genes as direct targets of miR-155-5p. Our study increases the current number of verified miR-155-5p targets approximately threefold and exemplifies a method for verifying miRNA targetomes as a prerequisite for the analysis of miRNA-regulated cellular networks.

This study aimed to identify differentially expressed non-coding RNAs (ncRNAs) associated with preterm birth (PTB) and determine biological pathways being influenced in the context of PTB. We processed cell-free RNA sequencing data and identified seventeen differentially expressed (DE) ncRNAs that could be involved in the onset of PTB. Per the validation via customized RT-qPCR, the recorded variations in expressions of eleven ncRNAs were concordant with the in-silico analyses. The results of this study provide insights into the role of DE ncRNAs and their impact on pregnancy-related biological pathways that could lead to PTB. Further studies are required to elucidate the precise mechanisms by which these DE ncRNAs contribute to adverse pregnancy outcomes (APOs) and their potential as diagnostic biomarkers.

The bipartite GAL4/UAS system is the most widely used method for targeted gene expression in Drosophila melanogaster and facilitates rapid in vivo genetic experimentation. Defining precise gene expression patterns for tissues and/or cell types under GAL4 control will continue to evolve to suit experimental needs. However, the precise spatial and temporal expression patterns for some commonly used muscle tissue promoters are still unclear. This missing information limits the precise timing of experiments during development. Here, we focus on three muscle-enriched GAL4 drivers (Mef2-GAL4, C57-GAL4 and G7-GAL4) to better inform selection of the most appropriate muscle promoter for experimental needs. Specifically, C57-GAL4 and G7-GAL4 turn on in the first or second instar larval stages, respectively, and can be used to bypass myogenesis for studies of muscle function after development.

Targeting ferroptosis, cell death caused by the iron-dependent accumulation of lipid peroxides, and disruption of the redox balance are promising strategies in cancer therapy owing to the physiological characteristics of cancer cells. However, the detection of ferroptosis using in vivo imaging remains challenging. We previously reported that redox maps showing the reduction power per unit time of implanted tumor tissues via non-invasive redox imaging using a novel, compact, and portable electron paramagnetic resonance imaging (EPRI) device could be compared with tumor tissue sections. This study aimed to apply the EPRI technique to the in vivo detection of ferroptosis. Notably, redox maps reflecting changes in the redox status of tumors induced by the ferroptosis-inducing agent imidazole ketone erastin (IKE) were compared with the immunohistochemical images of 4-hydroxynonenal (4-HNE) in tumor tissue sections. Our comparison revealed a negative correlation between the reducing power of tumor tissue and the number of 4-HNE-positive cells. Furthermore, the control and IKE-treated groups exhibited significantly different distributions on the correlation map. Therefore, redox imaging using EPRI may contribute to the non-invasive detection of ferroptosis in vivo.

Circular RNAs (circRNAs) are a unique class of covalently closed single-stranded RNA molecules that play diverse roles in normal physiology and pathology. Among the major types of circRNA, exon-intron circRNA (EIciRNA) distinguishes itself by its sequence composition and nuclear localization. Recent RNA-seq technologies and computational methods have facilitated the detection and characterization of EIciRNAs, with features like circRNA intron retention (CIR) and tissue-specificity being characterized. EIciRNAs have been identified to exert their functions via mechanisms such as regulating gene transcription, and the physiological relevance of EIciRNAs has been reported. Within this review, we present a summary of the current understanding of EIciRNAs, delving into their identification and molecular functions. Additionally, we emphasize factors regulating EIciRNA biogenesis and the physiological roles of EIciRNAs based on recent research. We also discuss the future challenges in EIciRNA exploration, underscoring the potential for novel functions and functional mechanisms of EIciRNAs for further investigation.

The aim of the present study was to assess sleep timing in Drosophila melanogaster at different ages, within the setting of an enforced schedule of varying light-dark stimuli, simulating light exposure variations between four typical office working days and one free day spent outside by a human, for a total of 30 days. Locomotor activity recording started when male flies were 3 days old. Flies exhibited a bimodal activity pattern, with a morning and an evening peak, and clear anticipation of the lights on and lights off transitions. From experimental day 10 (i.e. 12-day-old flies) onwards, a decrease in activity counts/increase in sleep amount were observed. On free days, a rise in activity counts and a reduction in sleep amount during the lights on interval was observed and was also present, albeit less obvious, on the subsequent working day during the lights off interval. A progressive delay in sleep onset was observed in the first days of the experiment, peaking on day 4 (i.e. 6-day-old flies), after which sleep onset timing gradually advanced. A delay in sleep offset was also observed for the first 13 days of the experiment, after which sleep offset stabilized. In conclusion, 'adolescent' flies exhibited changes in sleep timing that were reminiscent of those of human adolescents.