BMC Biology最新文献

Background: Endogenous secretory peptides (ESPs) play crucial roles in amphibian skin, yet their identification remains challenging in species lacking genomic data. This study developed an innovative pipeline integrating transcriptomics and peptidomics to identify ESPs in the skin of Odorrana grahami. This approach enhances endogenous secretory protein prediction accuracy by rescuing candidates erroneously discarded during SignalP-based screening. Such false negatives typically result from inaccurate annotation of N-terminal start sites within 5'-UTRs by protein prediction tools like TransDecoder.

Results: Our approach enhanced potential endogenous secretory protein identification rates by 61.6%, discovering 107 putative ESPs (16 validated at the protein level). Among these, 74 ESPs are newly reported in O. grahami (including 62 novel peptides). These ESPs span 14 known families (11 newly reported in O. grahami, 8 of which are first reported within the genus Odorrana). The frog skin active peptide (FSAP) family (n = 83)-comprising the largest subset of ESPs identified in this study-showed unexpected diversity between our studied individual and previously reported individuals within the population. Collectively, O. grahami (n = 226) and Odorrana andersonii (n = 205) currently hold the highest documented counts of FSAP family peptides in amphibians. Phylogenetic analysis delineated five FSAP clades (A-E) containing 18 clustered groups, with the hypervariable clade D harboring diverse non-AMPs and tachykinin-convergent peptides. GO and KEGG pathway analyses indicated that ESPs in O. grahami skin are predominantly immunity-related.

Conclusions: This study highlights underestimated FSAP family peptide diversity in Odorrana and provides an adaptable framework for ESP discovery across taxa.

Background: Genome spatial organization plays a fundamental role in biological function across all domains of life. While the principles of nuclear architecture have been well-characterized in animals and plants, their functional relevance in filamentous fungi remains largely uncharacterized. The wheat pathogen Zymoseptoria tritici presents a unique model for genome evolution, with a compartmentalized genome comprising conserved core and highly variable accessory chromosomes linked to genome plasticity. Here, we present the first 3D genome analysis of a eukaryotic organism with an extensive set of accessory chromosomes, revealing a hierarchical genome architecture integrating core and accessory regions.

Results: At the nuclear level, centromere clustering defines the global genome conformation. Accessory chromosomes are spatially segregated from core arms but maintain focal contacts with pericentromeric regions of core chromosomes, contributing to mitotic stability. At finer resolution, we identify homotypic interactions among heterochromatin-rich compartments and self-interacting domains demarcated by specific histone marks, gene expression profiles, and insulator-like sequence motifs. Notably, a subset of highly insulated, transposon-rich heterochromatic domains forms strong inter-domain interactions. Additionally, domains defined under axenic conditions with coordinated transcriptional activation during wheat infection suggest a link between 3D architecture and dynamic gene regulation.

Conclusions: Our study uncovers the multi-scale principles of nuclear organization in a major fungal plant pathogen and reveals how hierarchical nuclear architecture contributes to gene expression coordination and genome stability. These findings establish a conceptual framework for investigating 3D genome function and chromatin-mediated regulation in filamentous fungi and other eukaryotic microbes.

Background: Female Aedes aegypti mosquitoes utilize host blood to support egg maturation by digesting, absorbing, and metabolizing its components. Among these, amino acids are essential as both signaling molecules and building blocks for yolk proteins. While their overall importance is established, the individual dynamics and regulation of each amino acid remain insufficiently understood.

Results: We systematically profiled free and protein-bound amino acids in whole bodies, ovaries, and excreta over time after blood feeding, revealing distinct temporal dynamics across amino acids. Notably, tyrosine, enriched in yolk proteins, exhibited a biphasic pattern: a transient decrease between 6 and 9 h post blood meal, followed by accumulation during egg maturation. We also performed RNA-seq and found that amino acid metabolism is partially regulated by 20-hydroxyecdysone (20E), indicating hormonal control of amino acid homeostasis. Integrating RNA-seq analysis with amino acid profiling further suggested an adaptation to metabolic imbalance between host blood and ovaries. The early decrease in tyrosine was attributed to enzymatic degradation by 4-hydroxyphenylpyruvate dioxygenase (Hpd), whose expression is induced by 20E, a key hormone orchestrating post-blood-feeding gene expression and egg maturation. Pharmacological inhibition of Hpd caused tyrosine accumulation and increased lethality, indicating that tight regulation of tyrosine catabolism is essential for survival.

Conclusions: This study highlights the temporally coordinated metabolism of individual amino acids during mosquito reproduction. Our dataset serves as a valuable resource for understanding nutrient allocation with endocrine regulation, as well as a foundation for developing novel strategies to disrupt mosquito survival by targeting the metabolic enzymes.

Background: Animal personalities are characterized by within-individual consistency linked to among-individual variability. Personality expression is often dependent on major life history events such as mating and the onset of reproduction. Here, we hypothesized that in facultatively polyandrous animals, multiple mating increases the females' assets (i.e., residual reproductive value - RRV), due to direct and/or indirect benefits. Based on the predictions of the asset protection principle, higher RRV should promote behaviors that reduce the risk of fitness loss and hence mediate behavioral repeatability displayed in groups.

Methods: We tested our hypothesis in group-living predatory mites, Phytoseiulus persimilis. Predatory mite females were presented with one or two mates, and their postmating repeatability in activity and sociability was evaluated in groups composed of females of the same and mixed mating types.

Results: Mating frequency had little effect on activity patterns but pronounced effects on sociability traits. Polyandrous females were on average more sociable as well as more repeatable in sociability than monandrous females. These behavioral shifts reflect strategies to mitigate inter-individual conflicts within groups to enhance asset protection.

Conclusions: Our study suggests that the mating frequency can critically influence female personality expression after mating and highlights the importance of considering mate-related variables in animal personality research.

Background: While nuclear genome segregation is well characterized, mechanisms underlying mitochondrial partitioning remain partially obscure, even though its failure can cause developmental arrest or harmful mutations. This knowledge gap invokes the need for new, more suitable model systems to study such mechanisms. Doubly Uniparental Inheritance (DUI) of mitochondria in bivalves is a useful system for such studies. In DUI, sperm mitochondria in male embryos are actively transported across cell divisions to precursors of the germline, and this male-specific pattern depends on maternal factors stored in eggs. The presence of distinct mitochondrial segregation patterns in male and female embryos offers a unique opportunity to investigate the molecular bases of this process.

Results: Here, we leveraged this system by (1) performing RNA-Seq on eggs producing male-biased versus female-biased progenies in the Mediterranean mussel Mytilus galloprovincialis to identify factors involved in differential mitochondrial segregation; and (2) inferring signatures of convergent evolutionary rate across DUI bivalve genomes to separate segregation-specific factors from those involved in sex determination. We show that differentially transcribed genes across eggs that give rise to either male- or female-biased progeny are predominantly associated with mitochondrial dynamics, cytoskeletal organization, and vesicular trafficking. We also identified multiple long noncoding RNAs-many derived from transposable elements-that might have roles in the regulation of other maternally supplied factors that shepherd paternal mitochondria.

Conclusions: By overlaying clues from expression and sequence evolution, we delineate a conserved protein-protein interaction network of factors that mediate mitochondrial segregation. This study reveals general principles of organelle selection in animals and unveils the contribution of new factors.

Background: Evidence suggests a link between attention-deficit/hyperactivity disorder (ADHD) and the gut microbiome in humans. Dogs are a valuable model for ADHD research, as their gut microbiome more closely resembles the human gut microbiome in composition and functional overlap compared to rodent models. This study investigated potential associations between dogs' ADHD-related traits and gut microbiome composition/diversity. We assessed inattention, Hyperactivity, impulsivity, and related functional impairments of 164 family dogs using the validated Dog ADHD and Functional Rating Scale, and analysed bacterial 16S rRNA gene sequences from their faecal samples to assess the gut microbiome composition.

Results: Higher relative abundance of members of the family Prevotellaceae and genus Prevotella was associated with lower inattention and inattention-related functional impairment scores by both decision tree and Generalized Linear Model analyses. Hyperactivity, impulsivity, and related functional impairments were found to be moderated by age, suggesting that these traits are predominantly age-related and only secondarily influenced by microbiome composition. ADHD total score was negatively associated with Erysipelotrichaceae and positively associated with Alloprevotella. Dogs with higher functional impairment scores had lower alpha-diversity in their gut microbiome, probably indicating reduced microbial health.

Conclusions: This is the first study that found negative associations between inattention and the relative abundance of Prevotellaceae in dogs, which parallels findings in human studies. Our current correlational results in family dogs represent only the first step in gaining more insight into the interplay of gut microbiome and neurodevelopmental processes in non-human animals.

Background: Accurate prediction of drug-target interactions (DTIs) is essential for advancing drug discovery. Although numerous computational methods have been proposed, many exhibit limited generalization, particularly when dealing with unseen drugs or targets.

Results: To address this challenge, we introduce GPS-DTI, a deep learning framework designed to capture both local and global features of drugs and proteins, thereby enhancing predictive robustness. Specifically, GPS-DTI employs a graph isomorphism network with edge features (GINE)-based graph neural network, combined with a multi-head attention mechanism (MHAM), to effectively model the structural characteristics of drug molecules. For proteins, representations are derived from the pre-trained Evolutionary Scale Model (ESM-2) model and further refined through convolutional neural networks (CNNs), yielding rich feature embeddings. A cross-attention module integrates drug and protein features, uncovering biologically meaningful interactions and improving model interpretability.

Conclusions: Comprehensive benchmarking across in-domain and cross-domain DTI prediction tasks demonstrates that GPS-DTI outperforms existing methods, underscoring its strong generalization capability. Notably, the model achieves state-of-the-art performance on drug-target affinity (DTA) tasks and shows robust adaptability when evaluated on an independent Coronavirus Disease 2019 (COVID-19)-related test set. Furthermore, visualization of cross-attention maps offers interpretable insights into key molecular interactions, highlighting the potential of GPS-DTI in real-world drug discovery applications.

Background: The genetic basis of host resistance to viral infections is generally shaped by complex interactions between host genetic variations affecting antiviral immunity and the rapid evolutionary adaptability of viruses. In this study, we investigated two isogenic rainbow trout lines exhibiting extreme resistance or susceptibility to the rhabdovirus VHSV. We compared transcriptomes of the pronephros - a major lymphoid organ in fish - at steady state and following VHSV infection. By integrating bulk tissue RNA-seq with single-cell RNA-seq, we mapped the divergent transcriptomic responses of resistant and susceptible fish to specific immune cell types.

Results: At steady state, differences in antiviral pathways were minimal. However, VHSV triggered markedly distinct transcriptomic shifts between the lines. Both resistant and susceptible fish exhibited a broad transcriptional response enriched in core type I interferon (IFN) pathway genes. However, line-specific responses were enriched in genes induced by infection independently of type I IFN. In resistant fish, lymphocyte responses included type I IFN pathway, numerous transcription factors, and various cytokine receptors. In contrast, lymphocyte responses in susceptible fish involved only a limited set of type I IFN-induced genes. Monocytic cell responses also diverged: susceptible fish upregulated IFN-induced genes, while resistant fish showed increased expression of proinflammatory genes.

Conclusions: This study reveals the contribution of the core set of interferon-stimulated genes conserved across vertebrates to the response of different immune cells and the response of other genes in resistant and susceptible fish. It provides a comprehensive basis for evolutionary studies of resistance to viruses in vertebrates.

Background: In the in vitro expansion of mesenchymal stem cells (MSCs), replicative or stress-induced senescence poses a significant challenge, leading to the loss of their cellular properties and therapeutic functions. Currently, there is a lack of efficient strategies to address this issue.

Results: Here we presented a novel approach to combat cellular senescence and promote cell proliferation by coculturing human MSCs with human peripheral blood lymphocytes (PBLs). In a heterogeneous population of MSCs comprising both aged and nonaged cells, PBL effector cells, rather than their cytokines, exhibited a dual role. They selectively induced apoptosis in aged cells by facilitating p53 SUMOylation and activating the p53-dependent mitochondrial pathway, while simultaneously safeguarding younger cells against senescence and promoting cell proliferation by activating Serpinb2/NF-κB signaling. This resulted in a decrease in aged MSCs and an enrichment of rejuvenated MSCs. This process effectively reversed the senescence phenotype, leading to the remodeling of stemness characteristics and the enhancement of functionality within the MSC population. Furthermore, MSCs rejuvenated by PBLs presented an enhanced therapeutic efficacy and a favorable safety profile.

Conclusions: PBLs rejuvenate MSCs by promptly removing aged cells and enhancing the stemness and proliferative capacity of nonaged cells. This work provides an ideal method for obtaining substantial MSCs while meeting the quality requirements for stem cell therapy.