Communications Biology最新文献

The recently emerged clade Ib of mpox virus (MPXV) is spreading rapidly across Central and West Africa raising concerns about its potential virulence. Similar to clade IIb lineage B.1, which was responsible for the 2022 global outbreak, clade Ib exhibits sustained human-to-human transmission and a pattern of APOBEC3-associated genomic mutations. Here, we show that clade Ib displays enhanced long-range spreading in cell culture compared to clade IIb. Additionally, using the CAST mouse model, we show that clade Ib exhibits a higher level of virulence compared to the markedly attenuated clade IIb. Clade Ib leads to significant weight loss and high mortality in animals following both intraperitoneal and intranasal challenge. Histopathological analysis revealed more severe and extensive lung lesions in clade Ib-infected animals, accompanied by a broader distribution of viral antigens. Moreover, clade Ib, unlike IIb, disseminated efficiently to internal organs. These findings indicate that clade Ib MPXV has not undergone attenuation after human-to-human transmission to the extent observed in clade IIb and underscore the need for surveillance and preparedness against new emerging MPXV lineages.

Post-transcriptional RNA modifications can alter RNA structure, stability, localization, and function. Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional modification that converts adenosine nucleotides in RNA to inosine nucleotides, catalyzed by adenosine-deaminase-acting-on-RNA (ADAR) enzymes. Recent studies have shown that A-to-I RNA editing is required for cardiovascular development and homeostasis whilst aberrant RNA editing plays a role in cardiovascular diseases. This article provides an overview of A-to-I RNA editing events that have been implicated in cardiovascular biology and disease. It also discusses harnessing RNA editing for cardiovascular disease biomarker development and engineering RNA editing for cardiovascular disease treatment.

Dispersal is a fundamental ecological and evolutionary process, but identifying its determinants and predicting it across species remains a major challenge. Dispersal syndromes, which describe patterns of covariation among traits related to dispersal, are thought to capture general rules of dispersal evolution and its ecological consequences. Based on the most comprehensive empirical dispersal dataset available for European birds, we test how dispersal syndromes form and how well they predict dispersal across species. We found that distinct dispersal processes were governed by different trait combinations, with body mass consistently predicting overall dispersal, whereas flight efficiency was key for long-distance dispersal events. However, multi-trait dispersal syndromes performed poorly for phylogenetically distant species and were outperformed by models based on single mechanistic traits, especially body mass, life history, and, to a lesser extent, flight efficiency. Thus, single traits with clear mechanistic meaning predict avian dispersal ability better than complex syndromes. These findings highlight the complexity of avian dispersal and emphasize the need for refined mechanistic approaches to understand the constraints shaping dispersal evolution. Together, our study calls for broader empirical efforts and more mechanistic frameworks to uncover the evolutionary and ecological drivers of dispersal.

Parasitoid wasps are important biological control resources, yet their genetic manipulation has long been constrained by small body size and parasitization behavior, limiting their broader application in pest management. Here we report a chromosome-level genome assembly of the ectoparasitoid Gregopimpla kuwanae (322.87 Mb, 24 chromosomes), a relatively large species that parasitizes various lepidopteran pests. In the first part of this study, we established a foundational genomic resource and experimental platform by producing a high-quality genome and demonstrating the feasibility of functional genetics: RNA interference successfully silenced the cinnabar gene, while CRISPR/Cas9 editing generated vestigial knockout mutants, thus establishing G. kuwanae as a tractable system for gene manipulation. In the second part, we applied comparative genomics to identify lineage-specific gene-family expansions linked to parasitism, including venom-related genes, immune suppression factors, and detoxification enzymes (cytochrome P450s and UDP-glucosyltransferases), and we identified eight HGT candidates; one candidate (JSFChr12G01362) showed pre-feeding expression in females and caused increased adult mortality upon RNAi. Our study provides both the means and the candidates for mechanistic dissection of parasitoid adaptations, laying a foundation for the broader application of parasitoid wasps in sustainable biocontrol programs.

Skeletal muscle development is cornerstone of vertebrate locomotion, relies on the functionally distinct muscle fiber-type. Although the cellular dynamics in myogenesis have been extensively studied, the developmental origins and pathways governing fiber-type diversification remain unresolved. Furthermore, the evolutionary conservation of these mechanisms across vertebrates is poorly understood. Thus, we generate a comprehensive single-cell transcriptomic atlas of duck skeletal muscle across embryonic development to explore the trajectory from myogenic progenitors to myofiber. We identified a differentiation mechanism whereby slow-twitch type could transdifferentiate into the fast-twitch type, a process mediated by LEF1+(I) subtype. Comparative analysis of datasets across vertebrates (avian and mammalian) reveals that this fiber-type conversion program is phylogenetically conserved, suggesting homology in muscle adaptation mechanisms. Our study provides the transcription factors roadmap of vertebrate myofiber development, bridging gaps in developmental and evolutionary biology. These insights advance fundamental knowledge of tissue patterning and hold translational potential for regenerative medicine and agricultural biotechnology.

Aluminum toxicity in rodents is well documented to be used for inducing experimental models that mimic the clinical phenotypes of Alzheimer's disease (AD). Liraglutide is a well-known antidiabetic drug promising for modulating neurodegenerative conditions. Thus, investigating the ameliorative effects of Liraglutide on AD induced by aluminum chloride (AlCl₃), highlighting the role of lysophosphatidic acid (LPA)/ β-secretase 1 (BACE1), is promising. Male rats are subdivided into four groups. Except for the normal group, animals are subjected to daily administration of AlCl₃ (70 mg/kg, i.p.) for 45 days. Along with AlCl₃, Liraglutide (0.3 mg/kg twice daily, s.c.) and Donepezil (1 mg/kg daily, i.p.) therapy are administered in AlCl3 + Lira and AlCl₃ + Done groups, respectively. Liraglutide significantly ameliorates AlCl₃-induced anxiety, depression-like behaviors, and deficits in memory functions. Liraglutide therapy retains the histopathological structure of the brain, with antioxidant and anti-apoptotic abilities. Moreover, Liraglutide successfully decreases hippocampal levels of oxidized low-density lipoprotein (oxLDL), LPA, lysophosphatidic acid receptor 1 (LPAR1), and β-secretase 1 (BACE1) compared with the AlCl₃ group. Thus, liraglutide shows neuroprotective effects mediated by downregulation of the oxLDL/LPA/LPAR1/BACE1 pathway, which is studied for the first time to our knowledge.

Adoptive cell therapies (ACT) leverage tumor-immune interactions to cure cancer. Despite promising phase I/II clinical trials of chimeric-antigen-receptor natural killer (CAR-NK) cell therapies, molecular mechanisms and cellular properties required to achieve clinical benefits in broad cancer spectra remain underexplored. While in vitro and in vivo experiments are essential, they are expensive, laborious, and limited to targeted investigations. Here, we present ABMACT (Agent-Based Model for Adoptive Cell Therapy), an in silico approach employing agent-based models (ABM) to simulate the continuous course and dynamics of an evolving tumor-immune ecosystem, consisting of heterogeneous "virtual cells" created based on knowledge and omics data observed in experiments and patients. Applying ABMACT in multiple therapeutic contexts indicates that to achieve optimal ACT efficacy, it is key to enhance immune cellular proliferation, cytotoxicity, and serial killing capacity. With ABMACT, in silico trials can be performed systematically to inform ACT product development and predict optimal treatment strategies.

Pigs are vital to global agriculture, and infectious diseases cause significant economic losses. Leukocytes provide a critical window into the genetic regulation of pig immune traits. However, understanding of these mechanisms within specific immune cell types remains insufficient. Here, we integrate 11 immune traits and systematically map the regulatory landscapes of expression quantitative trait loci (eQTLs), splicing QTLs (sQTLs), and alternative polyadenylation QTLs (apaQTLs) in porcine peripheral blood mononuclear cells (PBMCs) and neutrophils to uncover cell type-specific patterns. These molecular QTLs (molQTLs) exhibit strong cell-type specificity and preferentially regulate genes involved in cross-cell communication that are linked to core immunity, thereby shaping immune phenotypes through intercellular networks. Furthermore, we identify 588 molQTLs that colocalize with genome-wide association study signals for phagocytic capacity. Among these, 60.3% of apaQTLs independently modulate immune traits, including the variant rs330263631. Experiments confirm that rs330263631 modulates mRNA stability and expression levels of the TXNDC15 by dynamically selecting polyadenylation sites and altering the length of the 3' untranslated region. This work systematically delineates the PBMC- and neutrophil-specific genetic architecture underlying immune regulation in pigs and provides a molecular foundation for deciphering the genetic mechanisms of porcine immune traits.

African swine fever (ASF) is a highly contagious viral disease caused by the African swine fever virus (ASFV), which primarily affects pigs. ASFV encodes a variety of proteins that contribute to immune evasion, with the mechanisms of immune escape being diverse, complex, and not yet fully understood. In this study, the MGF 505-3R protein of ASFV was identified as a potential inhibitor of the host's inflammatory response. We demonstrate that MGF 505-3R suppresses the host antiviral response by promoting the ubiquitin-mediated degradation of MyD88, with the amino acid region 89-277 being essential for this function. Notably, this region directly mediates the interaction with MyD88 and induces its ubiquitination. Furthermore, MGF 505-3R and its derived peptide significantly inhibit the production of type I (IFN-α/β) and type III (IFN-λ) interferons, in addition to impairing NF-κB activation by blocking p65 phosphorylation and nuclear translocation. The MGF 505-3R peptide effectively attenuates the host inflammatory storm, decreasing the expression of cytokines such as TNF-α and IL-1β, and alleviating DSS-induced colitis in male C57BL/6 mice. These findings highlight the dual role of MGF 505-3R in suppressing both inflammatory and interferon pathways, underscoring its potential as a therapeutic candidate for inflammatory diseases and a target for antiviral strategies.

Biofilms are microbial communities of aggregated cells encased in extracellular matrix that are a pressing healthcare concern. Since biofilms have complex metabolic dynamics, in this study a new approach for studying biofilm metabolism is developed that employs optical-photothermal infrared (O-PTIR) spectroscopy imaging combined with ¹³C stable isotope probing and cryosectioning to track the carbon metabolism of cells at different depths of the biofilm. This approach demonstrated that metabolic gradients can be visualised using O-PTIR imaging, revealing a core of cells with low metabolic activity at the centre of the biofilm, with outer regions showing significantly higher metabolic activity. By incorporating the heavy stable isotope of carbon into bacterial biomass, we monitored the metabolic activity of gentamicin-resistant Salmonella Typhimurium within the biofilm structure upon exposure to various antibiotics. O-PTIR imaging revealed altered metabolic responses at various depths of the biofilm, with variations that depend on the bacterial antibiotic susceptibility profile.