Food and other environmental factors affect gene expression and behaviour of animals. Differences in bacterial food affect the behaviour and longevity of Caenorhabditis elegans. However, no research has been carried out to investigate whether bacteria could utilize endogenous RNAs to affect C. elegans physiology. Here we show that two Escherichia coli endogenous noncoding RNAs, OxyS and DsrA, impact on the physiology of C. elegans. OxyS downregulates che-2, leading to impairment in C. elegans chemosensory behaviour and DsrA suppresses diacylglycerol lipase gene F42G9.6, leading to a decrease in longevity. We also examine some genes in the C. elegans RNA interference pathway for their possible involvement in the effects of OxyS and DsrA. Other bacteria, such as Bacillus mycoides, may also utilize its noncoding RNAs to interfere with gene expression in C. elegans. Our results demonstrate that E. coli noncoding RNAs can regulate gene expression and physiological conditions of C. elegans and indicate that noncoding RNAs might have interspecies ecological roles.

Summary Synapse elimination occurs in development, plasticity and disease conditions. Although the importance of synapse elimination has been documented in many studies, the molecular mechanisms underlying this process remain to be understood. Here, using the development of C. elegans RME neurons as a model, we have uncovered the function of the apoptosis pathway in synapse elimination. We find that the conserved apoptotic cell death (CED) pathway and axonal mitochondria are required for elimination of transiently formed clusters of presynaptic components in RME neurons. The function of the CED pathway needs the activation of the actin filament severing protein, GSNL-1. Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region, and that the cleaved active form of GSNL-1 promotes its actin severing ability. Our data suggest that activation of the cell death pathway contributes to selective elimination of synapses through disassembly of actin filament network.

Seahorses have a circum-global distribution in tropical to temperate coastal waters. Yet, seahorses show many adaptations for a sedentary, cryptic lifestyle: they require specific habitats, such as seagrass, kelp or coral reefs, lack pelvic and caudal fins, and give birth to directly developed offspring without pronounced pelagic larval stage, rendering long-range dispersal by conventional means inefficient. Here we investigate seahorses’ worldwide dispersal and biogeographic patterns based on a de novo genome assembly of Hippocampus erectus as well as 358 re-sequenced genomes from 21 species. Seahorses evolved in the late Oligocene and subsequent circum-global colonization routes are identified and linked to changing dynamics in ocean currents and paleo-temporal seaway openings. Furthermore, the genetic basis of the recurring “bony spines” adaptive phenotype is linked to independent substitutions in a key developmental gene. Analyses thus suggest that rafting via ocean currents compensates for poor dispersal and rapid adaptation facilitates colonizing new habitats.

Chondrichthyan (cartilaginous fish) occupies a key phylogenetic position and is important for investigating evolutionary processes of vertebrates. However, limited whole genomes impede our in-depth knowledge of important issues such as chromosome evolution and immunity. Here, we report the chromosome-level genome of white-spotted bamboo shark. Combing it with other shark genomes, we reconstructed 16 ancestral chromosomes of bamboo shark and illustrate a dynamic chromosome rearrangement process. We found that genes on 13 fast-evolving chromosomes can be enriched in immune-related pathways. And two chromosomes contain important genes that can be used to develop single-chain antibodies, which were shown to have high affinity to human disease markers by using enzyme-linked immunosorbent assay. We also found three bone formation-related genes were lost due to chromosome rearrangements. Our study highlights the importance of chromosome rearrangements, providing resources for understanding of cartilaginous fish diversification and potential application of single-chain antibodies.

The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.

Purpose: To identify whether ferroptosis-related genes play predictive roles in bladder cancer patients and to develop a ferroptosis-related gene signature to predict overall survival outcomes.Materials and Methods: We downloaded the mRNA expression files and clinical data of 256 bladder samples (188 bladder tumour and 68 nontumour samples) from the GEO database and 430 bladder samples (411 bladder tumour and 19 nontumour samples) from the TCGA database. A multigene signature based on prognostic ferroptosis-related genes was constructed by least absolute shrinkage and selection operator Cox regression analysis in the GEO cohort. The TCGA cohort was used to validate the ferroptosis-related gene signature. Next, functional enrichment analysis, including both Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses, was performed to elucidate the mechanism underlying the signature. The ssGSEA scores of 16 immune cells and 13 immune-related pathway activities between the high-risk and low-risk groups were also analysed in our study.Results: Thirty-three (67.3%) ferroptosis-related genes were differentially expressed between bladder tumour samples and nontumour samples in the GEO cohort. The intersection of prognostic ferroptosis-related genes and differentially expressed genes identified four prognostic targets, including ALOX5, FANCD2, HMGCR and FADS2. The least absolute shrinkage and selection operator Cox regression successfully built a 4-gene signature: risk score value = esum (each gene’s normalized expression * each gene’s coefficient). Univariate and multivariate Cox regression analyses were performed in both the GEO and TCGA cohorts to test the independent prognostic value of the 4-gene risk signature. Multivariate Cox regression analysis in the GEO cohort identified age (p < 0.001), grade (p = 0.129) and risk score (p = 0.016) as independent prognostic predictors for overall survival. Multivariate Cox regression analysis in the TCGA cohort also identified age (p = 0.002), stage (p < 0.001) and risk score (p = 0.006) as independent prognostic predictors for overall survival. The type II IFN response was determined to be significantly weakened in the high-risk group in both the GEO and TCGA cohorts.Conclusion: We successfully built a ferroptosis-related gene signature of significant predictive value for bladder cancer. These results suggest a novel research direction for targeted therapy of bladder cancer in the future.

Gap junctions are present in both vertebrates and invertebrates from nematodes to mammals. Although the importance of gap junctions has been documented in many biological processes, the molecular mechanisms underlying gap junction dynamics remain unclear. Here, using the C. elegans PLM neurons as a model, we show that UNC-44/ankyrin acts upstream of UNC-33/CRMP in regulation of a potential kinesin VAB-8 to control gap junction dynamics, and loss-of-function in the UNC-44/UNC-33/VAB-8 pathway suppresses the turnover of gap junction channels. Therefore, we first show a signal pathway including ankyrin, CRMP, and kinesin in regulating gap junctions.

Interstitial cystitis/bladder pain syndrome (IC/BPS) has a significant impact on quality of life, but the etiopathogenesis remains largely unknown. The bladder microenvironment of patients with IC/BPS to obtain biological evidence supporting diagnosis and novel therapy is systematically characterized. Single-cell RNA sequencing (scRNA-seq) and image mass cytometry (IMC) are applied to bladder biopsies of the IC/BPS cohort. A total of 42 distinct cell clusters are identified from different groups. The increased hyperactivated Th1-biased response, but not Th2-biased response, and decreased immunosuppressive Treg are elucidated in the bladder microenvironment of non-Hunner-type IC (NHIC)/Hunner-type IC (HIC). M2/M2-like macrophage extends in the HIC and M1-like macrophage extends in NHIC, all of which secrete a range of chemokines with different pattern. The pro-inflammatory mediators, TNF-𝜶, produced by tissue-resident macrophages and IL6, by the inflammatory fibroblasts are identified as key mediators of IC/BPS pathogenesis. Additionally, a regulatory network between different cell types is observed as a shift from structural cell communication in unaffected normal bladder to a Macrophage-Endothelial-dominated interactome in NHIC/HIC. The results demonstrate the high heterogeneity in NHIC/HIC, and provide an essential resource for diagnosis, and treatment of IC/BPS in the future by highlighting the importance of the microenvironment of bladder mucosa.